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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About: RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE
RJR: Recommended Bibliography 29 Mar 2026 at 01:50 Created:
Publications by FHCRC Researchers
The Fred Hutchinson Cancer Research Center began in 1975, with critical help from Washington State's U.S. Senator Warren Magnuson.
Fred Hutch quickly became the permanent home to Dr. E. Donnall Thomas, who had spent decades developing an innovative treatment for leukemia and other blood cancers. Thomas and his colleagues were working to cure cancer by transplanting human bone marrow after otherwise lethal doses of chemotherapy and radiation. At the Hutch, Thomas improved this treatment and readied it for widespread use. Since then, the pioneering procedure has saved hundreds of thousands of lives worldwide.
While improving bone marrow transplantation remains central to Fred Hutch's research, it is now only part of its efforts. The Hutch is home to five scientific divisions, three Nobel laureates and more than 2,700 faculty, who collectively have published more than 10,000 scientific papers, presented here as a full bibliography.
NOTE: From 1995 to 2009 I served as the Hutch's vice president for information technology — hence my interest in the organization. Although my role was in the admin division, if you dig through this bibliography, you will find a couple of papers with me as an author.
Created with PubMed® Query: ( fhcrc[Affiliation] OR "fred hutchinson"[Affiliation] OR "Fred Hutchinson Cancer Research"[Affiliation] OR "Fred Hutch"[affiliation] ) NOT pmcbook NOT ispreviousversion
Citations The Papers (from PubMed®)
RevDate: 2026-03-26
CmpDate: 2026-03-24
Temporal and geographic analyses of colorectal cancer screening during and after the COVID-19 pandemic in a federally qualified health center.
PloS one, 21(3):e0345248.
BACKGROUND: The COVID-19 pandemic caused reductions in cancer screening services. We assessed the pandemic's impact on colorectal cancer screening in a large diverse federally qualified health center (FQHC) in Los Angeles, CA.
METHODS: We used interrupted time series regression to estimate trends in monthly colorectal cancer screening rates for four relevant COVID-19 pandemic periods: pre-pandemic (March 2018 - February 2020); early-pandemic (March - December 2020); vaccine-era (January 2021- May 2023); and post-pandemic (June 2023 - May 2024). We plotted spatial distribution patterns of screening across census tracts.
RESULTS: Participants were 83,430 unique individuals (55% male; 80% Hispanic) ages 50-75. Average monthly colorectal cancer screening rates dropped from 9.3% pre-pandemic to 5.9% early-pandemic. Monthly screening rates in the vaccine era (7.5%) never returned to pre-pandemic levels and further declined in the post-pandemic era (6.7%; p trend = 0.09). Screening rates were consistently higher for males, ages 65-75, Hispanic individuals, and Spanish-preferring individuals in both pre-COVID (March 2018-Feb 2020) and post-COVID (July 2020-May 2024) periods. Increases in stool-based testing aligned with mailed outreach campaigns.
CONCLUSIONS: Monthly post-pandemic screening rates never reached pre-pandemic levels and declined from 2023 to 2024. Sharp increases in stool-based testing coincided with mailed outreach events, highlighting the importance of home-based screening methods during disruptive events.
IMPACT: Our findings can help shape healthcare response strategies to reduce screening delays in the context of future natural disasters.
Additional Links: PMID-41875138
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid41875138,
year = {2026},
author = {Coronado, GD and Dickerson, JF and Tsou, MH and Shivaprakash, N and Rosales, AG and Voelkel, JL and Whyte, MA and Shuster, E and Petrik, AF and Llavona-Ortiz, JY and Jenkins, CL and Rutter, CM and Escaron, AL},
title = {Temporal and geographic analyses of colorectal cancer screening during and after the COVID-19 pandemic in a federally qualified health center.},
journal = {PloS one},
volume = {21},
number = {3},
pages = {e0345248},
pmid = {41875138},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/virology ; Male ; *Colorectal Neoplasms/diagnosis/epidemiology ; Middle Aged ; Female ; Aged ; *Early Detection of Cancer/statistics & numerical data/trends ; SARS-CoV-2 ; Pandemics ; Los Angeles/epidemiology ; Mass Screening ; Interrupted Time Series Analysis ; },
abstract = {BACKGROUND: The COVID-19 pandemic caused reductions in cancer screening services. We assessed the pandemic's impact on colorectal cancer screening in a large diverse federally qualified health center (FQHC) in Los Angeles, CA.
METHODS: We used interrupted time series regression to estimate trends in monthly colorectal cancer screening rates for four relevant COVID-19 pandemic periods: pre-pandemic (March 2018 - February 2020); early-pandemic (March - December 2020); vaccine-era (January 2021- May 2023); and post-pandemic (June 2023 - May 2024). We plotted spatial distribution patterns of screening across census tracts.
RESULTS: Participants were 83,430 unique individuals (55% male; 80% Hispanic) ages 50-75. Average monthly colorectal cancer screening rates dropped from 9.3% pre-pandemic to 5.9% early-pandemic. Monthly screening rates in the vaccine era (7.5%) never returned to pre-pandemic levels and further declined in the post-pandemic era (6.7%; p trend = 0.09). Screening rates were consistently higher for males, ages 65-75, Hispanic individuals, and Spanish-preferring individuals in both pre-COVID (March 2018-Feb 2020) and post-COVID (July 2020-May 2024) periods. Increases in stool-based testing aligned with mailed outreach campaigns.
CONCLUSIONS: Monthly post-pandemic screening rates never reached pre-pandemic levels and declined from 2023 to 2024. Sharp increases in stool-based testing coincided with mailed outreach events, highlighting the importance of home-based screening methods during disruptive events.
IMPACT: Our findings can help shape healthcare response strategies to reduce screening delays in the context of future natural disasters.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*COVID-19/epidemiology/virology
Male
*Colorectal Neoplasms/diagnosis/epidemiology
Middle Aged
Female
Aged
*Early Detection of Cancer/statistics & numerical data/trends
SARS-CoV-2
Pandemics
Los Angeles/epidemiology
Mass Screening
Interrupted Time Series Analysis
RevDate: 2026-03-24
CmpDate: 2026-03-24
Development of a Culturally Adapted Smartphone App (IndigeQuit) Designed to Help American Indian and Alaska Native People Quit Commercial Cigarettes: User-Centered Mixed Methods Study.
JMIR formative research, 10:e88768 pii:v10i1e88768.
BACKGROUND: Due to the colonization of tobacco plants by European settlers and the subsequent intensive marketing of commercial tobacco products to American Indian and Alaska Native (AI/AN) communities in the United States, commercial cigarette smoking accounts for half of all deaths among AI/AN people. Limited awareness, access to treatment, and the absence of culturally relevant, effective smoking cessation interventions contribute to these high death rates.
OBJECTIVE: This study aims to culturally adapt iCanQuit, a smartphone smoking cessation app proven efficacious for the general population, for AI/AN people.
METHODS: A user-centered and community-based participatory research (CBPR) mixed methods approach was applied to culturally adapt iCanQuit for AI/AN people in collaboration with a community advisory board (CAB) of AI/AN individuals using a 3-step process. Step 1 identified ways to culturally adapt the iCanQuit for AI/AN people through 1-on-1 qualitative interviews with 8 prior iCanQuit AI/AN participants. Step 2 involved developing prototypes of cultural refinements identified in step 1 through regular biweekly meetings of the CAB, research, and app development teams. The prototypes were then evaluated with a separate group of 4 prior iCanQuit AI/AN participants through 1-on-1 qualitative interviews. Step 3 involved beta testing the app through a 6-day diary study followed by 1-on-1 qualitative interviews with a nationally recruited group of 7 AI/AN adults who smoke commercial cigarettes. The development work associated with step 3 was further informed by the CAB and the research and app development teams.
RESULTS: Key findings identified 5 cultural refinements that informed subsequent app development and testing: (1) stories featuring AI/AN adults and elders emphasizing culture, spirituality, family, and community; (2) honoring the Earth as a motivator for cessation; (3) a guide character representative of AI/AN people; (4) clear distinction between ceremonial and commercial tobacco use; and (5) use of earth tones in visual design. In Step 3, all 7 (100%) diary study participants rated the beta version of the app as excellent or good/meets expectations (5/7, 71%, and 2/7, 29%, respectively) and that it felt made for them. They suggested 6 modifications which were incorporated into the final version of the app: (1) include vaping frequently asked questions, (2) feature motivation icons more prominently, (3) increase notification frequency, (4) track today's cigarettes rather than yesterday's, (5) allow users to update how much they spend per pack of cigarettes; and (6) rename the medications tool to reflect the inclusion of AI/AN traditional healing modalities.
CONCLUSIONS: A user-centered and CBPR development process yielded IndigeQuit-one of the first known apps developed specifically to help AI/AN adults quit commercial cigarette smoking.
TRIAL REGISTRATION: ClinicalTrials.gov NCT06145763; https://clinicaltrials.gov/ct2/show/NCT06145763.
Additional Links: PMID-41875428
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid41875428,
year = {2026},
author = {Bricker, JB and Santiago-Torres, M and Sullivan, BM and Mull, KE and Clark, HW and Fogel, CA and Hwang, SB and Keith, AR and Kornacki, C and Afraid Of Lightning-Craddock, T and Martinez, SA and Seneca, DS and Stanford, CM and Terry, C and Wilcox, SL and Nelson, L and Henderson, PN},
title = {Development of a Culturally Adapted Smartphone App (IndigeQuit) Designed to Help American Indian and Alaska Native People Quit Commercial Cigarettes: User-Centered Mixed Methods Study.},
journal = {JMIR formative research},
volume = {10},
number = {},
pages = {e88768},
doi = {10.2196/88768},
pmid = {41875428},
issn = {2561-326X},
mesh = {Humans ; *Mobile Applications ; *Smoking Cessation/methods/ethnology/psychology ; Female ; Male ; Adult ; Middle Aged ; *Alaska Natives/psychology ; Community-Based Participatory Research ; Qualitative Research ; Smartphone ; United States ; *American Indian or Alaska Native/psychology ; User-Centered Design ; },
abstract = {BACKGROUND: Due to the colonization of tobacco plants by European settlers and the subsequent intensive marketing of commercial tobacco products to American Indian and Alaska Native (AI/AN) communities in the United States, commercial cigarette smoking accounts for half of all deaths among AI/AN people. Limited awareness, access to treatment, and the absence of culturally relevant, effective smoking cessation interventions contribute to these high death rates.
OBJECTIVE: This study aims to culturally adapt iCanQuit, a smartphone smoking cessation app proven efficacious for the general population, for AI/AN people.
METHODS: A user-centered and community-based participatory research (CBPR) mixed methods approach was applied to culturally adapt iCanQuit for AI/AN people in collaboration with a community advisory board (CAB) of AI/AN individuals using a 3-step process. Step 1 identified ways to culturally adapt the iCanQuit for AI/AN people through 1-on-1 qualitative interviews with 8 prior iCanQuit AI/AN participants. Step 2 involved developing prototypes of cultural refinements identified in step 1 through regular biweekly meetings of the CAB, research, and app development teams. The prototypes were then evaluated with a separate group of 4 prior iCanQuit AI/AN participants through 1-on-1 qualitative interviews. Step 3 involved beta testing the app through a 6-day diary study followed by 1-on-1 qualitative interviews with a nationally recruited group of 7 AI/AN adults who smoke commercial cigarettes. The development work associated with step 3 was further informed by the CAB and the research and app development teams.
RESULTS: Key findings identified 5 cultural refinements that informed subsequent app development and testing: (1) stories featuring AI/AN adults and elders emphasizing culture, spirituality, family, and community; (2) honoring the Earth as a motivator for cessation; (3) a guide character representative of AI/AN people; (4) clear distinction between ceremonial and commercial tobacco use; and (5) use of earth tones in visual design. In Step 3, all 7 (100%) diary study participants rated the beta version of the app as excellent or good/meets expectations (5/7, 71%, and 2/7, 29%, respectively) and that it felt made for them. They suggested 6 modifications which were incorporated into the final version of the app: (1) include vaping frequently asked questions, (2) feature motivation icons more prominently, (3) increase notification frequency, (4) track today's cigarettes rather than yesterday's, (5) allow users to update how much they spend per pack of cigarettes; and (6) rename the medications tool to reflect the inclusion of AI/AN traditional healing modalities.
CONCLUSIONS: A user-centered and CBPR development process yielded IndigeQuit-one of the first known apps developed specifically to help AI/AN adults quit commercial cigarette smoking.
TRIAL REGISTRATION: ClinicalTrials.gov NCT06145763; https://clinicaltrials.gov/ct2/show/NCT06145763.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Mobile Applications
*Smoking Cessation/methods/ethnology/psychology
Female
Male
Adult
Middle Aged
*Alaska Natives/psychology
Community-Based Participatory Research
Qualitative Research
Smartphone
United States
*American Indian or Alaska Native/psychology
User-Centered Design
RevDate: 2026-03-21
Prognostic Utility of ctDNA for Trimodality Therapy Outcomes in Muscle Invasive Bladder Cancer.
Clinical genitourinary cancer, 24(4):102524 pii:S1558-7673(26)00024-8 [Epub ahead of print].
Additional Links: PMID-41864146
Publisher:
PubMed:
Citation:
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@article {pmid41864146,
year = {2026},
author = {Raizenne, BL and Koshkin, VS and Zhu, A and Ben-David, R and Dufault, SM and Eraky, A and Friedlander, TW and Hong, JC and Wong, AC and Chou, J and Chu, C and Mar, N and Ma, TM and Sfakianos, JP and Porten, S and Seyedin, SN},
title = {Prognostic Utility of ctDNA for Trimodality Therapy Outcomes in Muscle Invasive Bladder Cancer.},
journal = {Clinical genitourinary cancer},
volume = {24},
number = {4},
pages = {102524},
doi = {10.1016/j.clgc.2026.102524},
pmid = {41864146},
issn = {1938-0682},
}
RevDate: 2026-03-21
Estimating the Effect of Finasteride on Kallikrein Marker Levels in Blood and the Use of Converted Markers in the Four-Kallikrein Model.
European urology focus pii:S2405-4569(26)00038-6 [Epub ahead of print].
BACKGROUND AND OBJECTIVE: Although the effects of 5-α-reductase inhibitors (5-ARIs) on prostate-specific antigen (PSA) have been well-studied, the effects on other kallikrein markers have not been firmly established. Accordingly, a statistical model based on blood measurements of four kallikreins-known commercially as the "4Kscore"-cannot be used for men taking 5-ARIs. We investigated how finasteride affects kallikrein markers and whether suitably adjusted marker levels could be used in the four-kallikrein model to accurately predict the prostate biopsy results.
METHODS: We analyzed 500 participants from the Prostate Cancer Prevention Trial (PCPT) with PSA ≤3 ng/ml before finasteride and who had marker measurements after 1 yr on finasteride. Conversion factors were generated from this cohort to estimate prefinasteride marker levels in a separate PCPT cohort of 459 men on finasteride biopsied for cause. Adjusted marker levels were entered into the prespecified 4K model and performance characteristics assessed for predicting high-grade prostate cancer on biopsy.
KEY FINDINGS AND LIMITATIONS: Finasteride use halved total PSA (β 0.51, 95% confidence interval 0.49, 0.54). human kallikrein 2 was also halved (β 0.50); free PSA and intact PSA were slightly more than halved (β 0.44 for both). Predictions from the 4K model using adjusted markers improved discrimination over adjusted total PSA alone (AUC 0.734 vs 0.595; p < 0.001). While this cohort underwent only sextant biopsy, the ProtecT model, created on 10-12 core biopsies was still well-calibrated at clinically important thresholds. In decision-curve analysis, the 4K model had the highest net benefit for risk thresholds of ≥7%.
The 4K model can be used to inform prostate biopsy decision-making in men taking 5-ARIs for at least 3 mo by incorporating adjusted kallikrein levels into the scoring algorithm.
Additional Links: PMID-41864782
Publisher:
PubMed:
Citation:
show bibtex listing
hide bibtex listing
@article {pmid41864782,
year = {2026},
author = {Vertosick, EA and Goodman, P and Tangen, CM and Till, C and Thompson, IM and Lucia, MS and Eastham, J and Lilja, H and Vickers, AJ},
title = {Estimating the Effect of Finasteride on Kallikrein Marker Levels in Blood and the Use of Converted Markers in the Four-Kallikrein Model.},
journal = {European urology focus},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.euf.2026.03.005},
pmid = {41864782},
issn = {2405-4569},
abstract = {BACKGROUND AND OBJECTIVE: Although the effects of 5-α-reductase inhibitors (5-ARIs) on prostate-specific antigen (PSA) have been well-studied, the effects on other kallikrein markers have not been firmly established. Accordingly, a statistical model based on blood measurements of four kallikreins-known commercially as the "4Kscore"-cannot be used for men taking 5-ARIs. We investigated how finasteride affects kallikrein markers and whether suitably adjusted marker levels could be used in the four-kallikrein model to accurately predict the prostate biopsy results.
METHODS: We analyzed 500 participants from the Prostate Cancer Prevention Trial (PCPT) with PSA ≤3 ng/ml before finasteride and who had marker measurements after 1 yr on finasteride. Conversion factors were generated from this cohort to estimate prefinasteride marker levels in a separate PCPT cohort of 459 men on finasteride biopsied for cause. Adjusted marker levels were entered into the prespecified 4K model and performance characteristics assessed for predicting high-grade prostate cancer on biopsy.
KEY FINDINGS AND LIMITATIONS: Finasteride use halved total PSA (β 0.51, 95% confidence interval 0.49, 0.54). human kallikrein 2 was also halved (β 0.50); free PSA and intact PSA were slightly more than halved (β 0.44 for both). Predictions from the 4K model using adjusted markers improved discrimination over adjusted total PSA alone (AUC 0.734 vs 0.595; p < 0.001). While this cohort underwent only sextant biopsy, the ProtecT model, created on 10-12 core biopsies was still well-calibrated at clinically important thresholds. In decision-curve analysis, the 4K model had the highest net benefit for risk thresholds of ≥7%.
The 4K model can be used to inform prostate biopsy decision-making in men taking 5-ARIs for at least 3 mo by incorporating adjusted kallikrein levels into the scoring algorithm.},
}
RevDate: 2026-03-22
DNA electroporation of HIV Env elicits robust T cell responses and memory B cell responses with muted serum antibody levels that can be boosted with recombinant protein.
Vaccine, 79:128487 pii:S0264-410X(26)00295-1 [Epub ahead of print].
Broadly neutralizing antibodies against the HIV envelope protein exhibit the potential to prevent HIV-1 acquisition, a concept demonstrated both in non-human primate (NHP) challenge models and in human clinical trials. The use of DNA for vaccination, in combination with IL-12 and delivered via intradermal (ID)-adaptive electroporation (EP), has resulted in excellent cellular and humoral immunogenicity. HVTN 304 (NCT05828095) is a first-in-human, phase 1 clinical trial that evaluated the safety and immunogenicity of a novel vaccination regimen of a synthetic DNA-encoded stabilized HIV-1 Env native-like trimer (sD-NLT-AB05) adjuvanted with IL-12 DNA, either alone or in combination with a recombinant protein HIV-1 Env (Trimer 4571) adjuvanted with 3M-052-AF/Alum as a boost, in 20 participants without HIV. The DNA vectors were delivered via ID EP. The regimen did not induce autologous neutralizing antibodies in serum. Binding antibodies to Env were induced in over half of the participants receiving DNA only and in all participants who received the Trimer 4571 boost; the magnitude was increased by the second protein boost. The DNA-induced antibodies were primarily directed to the Env base; some Trimer protein-induced antibodies were directed to other regions of Env and the base. Env-specific CD4+ T cells expressing IFN-γ and/or IL-2 were detected in all participants, with CD8+ T cells detected in up to 75% of participants. The CD4+ T cell response included cells expressing IL-21. This study demonstrates that the DNA modality, in combination with a closely related heterologous boost, may be another modality to enable iterative testing of new vaccine regimens for HIV-1, as it primes a B cell response and a CD8+ T cell response without inducing high titers of serum antibody.
Additional Links: PMID-41865485
Publisher:
PubMed:
Citation:
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@article {pmid41865485,
year = {2026},
author = {De Rosa, SC and Gravett, RM and Hahn, WO and Villaran, M and Huang, Y and Schmitzberger, L and Montefiori, D and Domin, E and Tomaras, GD and Heptinstall, J and Seaton, KE and Ferrari, G and Ozorowski, G and Ward, AB and Lee, WH and van der Maas, L and Polakowski, L and Frank, I and Tieu, HV and Kalams, SA and Garcia, NMG and Huang, J and Ghosh, S and Purwar, M and Kulp, D and Humeau, L and Kwong, PD and McElrath, MJ and Corey, L and Weiner, D and , },
title = {DNA electroporation of HIV Env elicits robust T cell responses and memory B cell responses with muted serum antibody levels that can be boosted with recombinant protein.},
journal = {Vaccine},
volume = {79},
number = {},
pages = {128487},
doi = {10.1016/j.vaccine.2026.128487},
pmid = {41865485},
issn = {1873-2518},
abstract = {Broadly neutralizing antibodies against the HIV envelope protein exhibit the potential to prevent HIV-1 acquisition, a concept demonstrated both in non-human primate (NHP) challenge models and in human clinical trials. The use of DNA for vaccination, in combination with IL-12 and delivered via intradermal (ID)-adaptive electroporation (EP), has resulted in excellent cellular and humoral immunogenicity. HVTN 304 (NCT05828095) is a first-in-human, phase 1 clinical trial that evaluated the safety and immunogenicity of a novel vaccination regimen of a synthetic DNA-encoded stabilized HIV-1 Env native-like trimer (sD-NLT-AB05) adjuvanted with IL-12 DNA, either alone or in combination with a recombinant protein HIV-1 Env (Trimer 4571) adjuvanted with 3M-052-AF/Alum as a boost, in 20 participants without HIV. The DNA vectors were delivered via ID EP. The regimen did not induce autologous neutralizing antibodies in serum. Binding antibodies to Env were induced in over half of the participants receiving DNA only and in all participants who received the Trimer 4571 boost; the magnitude was increased by the second protein boost. The DNA-induced antibodies were primarily directed to the Env base; some Trimer protein-induced antibodies were directed to other regions of Env and the base. Env-specific CD4+ T cells expressing IFN-γ and/or IL-2 were detected in all participants, with CD8+ T cells detected in up to 75% of participants. The CD4+ T cell response included cells expressing IL-21. This study demonstrates that the DNA modality, in combination with a closely related heterologous boost, may be another modality to enable iterative testing of new vaccine regimens for HIV-1, as it primes a B cell response and a CD8+ T cell response without inducing high titers of serum antibody.},
}
RevDate: 2026-03-26
Improving pharmacy-based HPV vaccine delivery through communication training: Findings from a pilot feasibility study.
Journal of the American Pharmacists Association : JAPhA pii:S1544-3191(26)00063-4 [Epub ahead of print].
BACKGROUND: HPV vaccination coverage among U.S. adolescents remains below national targets. Community pharmacies are highly accessible vaccination venues, but staff need to enhance practical skills to identify vaccine-eligible adolescents and communicate effectively with parents.
OBJECTIVES: To evaluate the acceptability and feasibility of a team-based HPV vaccine communication training for pharmacy staff.
METHODS: We used a single-group pre/post-test design in three community pharmacies in Washington state between December 2022-May 2023. The prerecorded online vaccine communication training integrated vaccine eligibility forecasting with 5A's counseling and Announcement Approach recommendation language. Pharmacy staff involved in adolescent immunizations completed baseline (n=18) and follow-up (n=13) online surveys assessing behavioral outcomes related to adolescent HPV vaccination before and after completing the training. Adolescent vaccination counts were audited for pre- (February-May 2022) and post-implementation (February-May 2023) periods.
RESULTS: The proportion of staff reporting strong HPV vaccine recommendations increased from 22% pre-implementation to 67% post-implementation (p=0.016). The proportion of staff recommending HPV vaccination starting at ages 9-12 increased from 33% to 50% for both female and male adolescents, though this was not statistically significant (p=0.324). Self-efficacy improved for personal interactions (mean 2.8 to 3.4; p=0.004), goal setting (2.7 to 3.5; p=0.004), and addressing hesitancy (2.6 to 3.3; p=0.010). Post-implementation, staff rated the acceptability (mean 4.1/5), appropriateness (4.0/5), and feasibility (4.1/5) of pharmacy-based HPV vaccination favorably. Vaccination audits showed increased HPV doses at one pharmacy (2 doses to 20 doses) and no change at the other pharmacy (1 dose to 1 dose). The third pharmacy did not administer any adolescent vaccinations during the post-implementation period.
CONCLUSION: A team-based HPV vaccine communication training was acceptable and feasible and improved staff-reported HPV recommendation behaviors, with heterogeneous short-term changes in HPV vaccination delivery. Larger multisite studies with longer observation periods are needed to evaluate effects on vaccination uptake.
Additional Links: PMID-41866129
Publisher:
PubMed:
Citation:
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@article {pmid41866129,
year = {2026},
author = {Shah, PD and Schwartz, J and Bacci, JL and Calo, WA and Ko, LK and Glascock, M and Li, L and Watabayashi, K},
title = {Improving pharmacy-based HPV vaccine delivery through communication training: Findings from a pilot feasibility study.},
journal = {Journal of the American Pharmacists Association : JAPhA},
volume = {},
number = {},
pages = {103078},
doi = {10.1016/j.japh.2026.103078},
pmid = {41866129},
issn = {1544-3450},
support = {P30 CA014089/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: HPV vaccination coverage among U.S. adolescents remains below national targets. Community pharmacies are highly accessible vaccination venues, but staff need to enhance practical skills to identify vaccine-eligible adolescents and communicate effectively with parents.
OBJECTIVES: To evaluate the acceptability and feasibility of a team-based HPV vaccine communication training for pharmacy staff.
METHODS: We used a single-group pre/post-test design in three community pharmacies in Washington state between December 2022-May 2023. The prerecorded online vaccine communication training integrated vaccine eligibility forecasting with 5A's counseling and Announcement Approach recommendation language. Pharmacy staff involved in adolescent immunizations completed baseline (n=18) and follow-up (n=13) online surveys assessing behavioral outcomes related to adolescent HPV vaccination before and after completing the training. Adolescent vaccination counts were audited for pre- (February-May 2022) and post-implementation (February-May 2023) periods.
RESULTS: The proportion of staff reporting strong HPV vaccine recommendations increased from 22% pre-implementation to 67% post-implementation (p=0.016). The proportion of staff recommending HPV vaccination starting at ages 9-12 increased from 33% to 50% for both female and male adolescents, though this was not statistically significant (p=0.324). Self-efficacy improved for personal interactions (mean 2.8 to 3.4; p=0.004), goal setting (2.7 to 3.5; p=0.004), and addressing hesitancy (2.6 to 3.3; p=0.010). Post-implementation, staff rated the acceptability (mean 4.1/5), appropriateness (4.0/5), and feasibility (4.1/5) of pharmacy-based HPV vaccination favorably. Vaccination audits showed increased HPV doses at one pharmacy (2 doses to 20 doses) and no change at the other pharmacy (1 dose to 1 dose). The third pharmacy did not administer any adolescent vaccinations during the post-implementation period.
CONCLUSION: A team-based HPV vaccine communication training was acceptable and feasible and improved staff-reported HPV recommendation behaviors, with heterogeneous short-term changes in HPV vaccination delivery. Larger multisite studies with longer observation periods are needed to evaluate effects on vaccination uptake.},
}
RevDate: 2026-03-24
CmpDate: 2026-03-23
Impact of age on outcomes after CD19 CAR T-cell therapy for large B-cell lymphomas.
Blood neoplasia, 3(2):100187.
Age may influence clinical outcomes after CD19-directed chimeric antigen receptor (CAR) T-cell (CAR-T) therapy. Real-world data on the survival and toxicity outcomes of older patients receiving CAR-T therapy are limited. We used data from the Center for International Blood and Marrow Transplant Research for adults with diffuse large B-cell lymphoma who received CAR-T therapy from May 2018 to June 2020. Cumulative incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were reported. Efficacy and safety outcomes were assessed using age as a continuous variable and among 4 age groups: 18 to 54, 55 to 64, 65 to 74, and ≥75 years. Nearly half (44%) of 1916 total recipients were aged ≥65 years. Patients received either axicabtagene ciloleucel (75%) or tisagenlecleucel (25%). Overall rates of CRS and ICANS were 75% and 43%, and severe rates of CRS and ICANS were 9% and 21%, respectively. For all patients, 12-month overall survival (OS), progression-free survival (PFS), and relapse rates were 62%, 42%, and 55%, respectively. As a continuous variable, older age did not affect OS, PFS, and CRS; however, the risk of ICANS increased with age (hazard ratio [HR], 1.03; P < .001). At age >64 years, risk for ICANS increases (HR, 1.65;95% confidence interval (CI), 1.33-2.1; P < .001). In a categorical analysis, the 65 to 74-year age group had lower relapse risk (HR, 0.77;95% CI, 0.64-0.93; P = .005) than younger patients. CD19 CAR-T therapy is effective for older adults, and older age does not worsen mortality. Older age is associated with higher ICANS risk and should guide patient selection.
Additional Links: PMID-41867486
PubMed:
Citation:
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@article {pmid41867486,
year = {2026},
author = {Mirza, AS and Hosing, C and Foss, F and Kim, S and Moskop, A and Oloyede, T and Abid, MB and Afrough, A and Ahmed, S and Badar, T and Barba, P and Bhatt, VR and Brown, VI and Dahiya, S and Deol, A and Epperla, N and Ganguly, S and Grover, NS and Hashmi, H and Hashmi, S and Hematti, P and Hildebrandt, GC and Hill, JM and Hossain, NM and Ibrahim, U and Johnson, PC and Kharfan-Dabaja, MA and Krem, MM and Lekakis, LJ and Maziarz, RT and Murthy, HS and Riedell, PA and Salas, MQ and Shouse, G and Strouse, C and Thakar, MS and Turtle, CJ and Woolfrey, A and Wudhikarn, K and Yared, JA and Pasquini, MC and Gowda, L},
title = {Impact of age on outcomes after CD19 CAR T-cell therapy for large B-cell lymphomas.},
journal = {Blood neoplasia},
volume = {3},
number = {2},
pages = {100187},
pmid = {41867486},
issn = {2950-3280},
support = {U24 CA076518/CA/NCI NIH HHS/United States ; },
abstract = {Age may influence clinical outcomes after CD19-directed chimeric antigen receptor (CAR) T-cell (CAR-T) therapy. Real-world data on the survival and toxicity outcomes of older patients receiving CAR-T therapy are limited. We used data from the Center for International Blood and Marrow Transplant Research for adults with diffuse large B-cell lymphoma who received CAR-T therapy from May 2018 to June 2020. Cumulative incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were reported. Efficacy and safety outcomes were assessed using age as a continuous variable and among 4 age groups: 18 to 54, 55 to 64, 65 to 74, and ≥75 years. Nearly half (44%) of 1916 total recipients were aged ≥65 years. Patients received either axicabtagene ciloleucel (75%) or tisagenlecleucel (25%). Overall rates of CRS and ICANS were 75% and 43%, and severe rates of CRS and ICANS were 9% and 21%, respectively. For all patients, 12-month overall survival (OS), progression-free survival (PFS), and relapse rates were 62%, 42%, and 55%, respectively. As a continuous variable, older age did not affect OS, PFS, and CRS; however, the risk of ICANS increased with age (hazard ratio [HR], 1.03; P < .001). At age >64 years, risk for ICANS increases (HR, 1.65;95% confidence interval (CI), 1.33-2.1; P < .001). In a categorical analysis, the 65 to 74-year age group had lower relapse risk (HR, 0.77;95% CI, 0.64-0.93; P = .005) than younger patients. CD19 CAR-T therapy is effective for older adults, and older age does not worsen mortality. Older age is associated with higher ICANS risk and should guide patient selection.},
}
RevDate: 2026-03-23
CmpDate: 2026-03-23
Discovery of genetic susceptibility variants in pediatric and adult ependymoma.
Neuro-oncology advances, 8(1):vdag004.
BACKGROUND: Ependymoma is a malignancy of the neuroepithelium-derived ependyma that lines the spinal cord and ventricles of the brain, occurring most frequently in young children and older adults. Genetic susceptibility to ependymoma has proven difficult to assess due to disease rarity.
METHODS: We performed genome-wide association studies (GWAS) of 478 ependymoma patients and 4,841 disease-free controls of European ancestry. Ependymoma patients consisted of 117 children (<18 years old) with whole-genome sequencing (WGS), 142 children with genotyping, and 219 adults (≥18 years old) with genotyping. Genotyped samples were imputed using the 1,000 Genomes Project as the reference panel and underwent quality control filtering. The GWAS was performed separately by age group and technology (genotyped or WGS). GWAS variants were considered significant at P < 5 × 10[-8].
RESULTS: Among pediatric subjects with WGS data, we identified a significant intronic variant in EDIL3 (rs149378, P = 1.9 × 10[-8]) and a nearly significant intronic variant in LHX4 (rs79008224, P = 7.2 × 10[-8]). In pediatric subjects with genotyped data, two significant intronic variants were detected: FAM149A (rs6852180, P = 1.8 × 10[-8]) and CYS1 (rs61052588, P = 3.0 × 10[-8]). Additionally, an intergenic variant near C1orf94 (rs1404350, P = 1.2 × 10[-14]) was highly significant. In genotyped adult subjects, a single variant was observed in KCNQ3 (rs79089725, P = 2.0 × 10[-8]).
CONCLUSION: Our analysis represents one of the most extensive ependymoma-specific GWAS conducted to date. Several significant intronic variants were harbored in genes associated with cancer and neurological disease. Future studies are needed to investigate the role of these age-specific alterations in ependymoma pathogenesis.
Additional Links: PMID-41869074
PubMed:
Citation:
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@article {pmid41869074,
year = {2026},
author = {Strauss, JD and Shetty, PB and Tsavachidis, S and Byun, J and Mack, SC and Xiangjun, X and Armstrong, TS and Gilbert, MR and , and Mirabello, L and Bhatia, S and Leisenring, WM and Morton, LM and Armstrong, GT and Foss-Skiftesvik, J and Hagen, CM and Bybjerg-Grauholm, J and , and Ghozal, M and Bonaventure, A and Clavel, J and Bondy, ML and , and Amos, CI and Hoang, TT and Scheurer, ME},
title = {Discovery of genetic susceptibility variants in pediatric and adult ependymoma.},
journal = {Neuro-oncology advances},
volume = {8},
number = {1},
pages = {vdag004},
pmid = {41869074},
issn = {2632-2498},
abstract = {BACKGROUND: Ependymoma is a malignancy of the neuroepithelium-derived ependyma that lines the spinal cord and ventricles of the brain, occurring most frequently in young children and older adults. Genetic susceptibility to ependymoma has proven difficult to assess due to disease rarity.
METHODS: We performed genome-wide association studies (GWAS) of 478 ependymoma patients and 4,841 disease-free controls of European ancestry. Ependymoma patients consisted of 117 children (<18 years old) with whole-genome sequencing (WGS), 142 children with genotyping, and 219 adults (≥18 years old) with genotyping. Genotyped samples were imputed using the 1,000 Genomes Project as the reference panel and underwent quality control filtering. The GWAS was performed separately by age group and technology (genotyped or WGS). GWAS variants were considered significant at P < 5 × 10[-8].
RESULTS: Among pediatric subjects with WGS data, we identified a significant intronic variant in EDIL3 (rs149378, P = 1.9 × 10[-8]) and a nearly significant intronic variant in LHX4 (rs79008224, P = 7.2 × 10[-8]). In pediatric subjects with genotyped data, two significant intronic variants were detected: FAM149A (rs6852180, P = 1.8 × 10[-8]) and CYS1 (rs61052588, P = 3.0 × 10[-8]). Additionally, an intergenic variant near C1orf94 (rs1404350, P = 1.2 × 10[-14]) was highly significant. In genotyped adult subjects, a single variant was observed in KCNQ3 (rs79089725, P = 2.0 × 10[-8]).
CONCLUSION: Our analysis represents one of the most extensive ependymoma-specific GWAS conducted to date. Several significant intronic variants were harbored in genes associated with cancer and neurological disease. Future studies are needed to investigate the role of these age-specific alterations in ependymoma pathogenesis.},
}
RevDate: 2026-03-23
Mucosal tenofovir 1% gel stimulates cell proliferation and type I/III interferon pathways.
Microbiology spectrum [Epub ahead of print].
UNLABELLED: Oral tenofovir is a key antiretroviral used for treatment and pre-exposure prophylaxis (PrEP) of human immunodeficiency virus (HIV). A gel form has been tested for vaginal and rectal PrEP. We have shown that 7 days of tenofovir 1% gel had broad-ranging effects on gene expression in the rectum, especially suppression of anti-inflammatory mediators and induction of cell proliferation. Similarly, oral PrEP induced type I/III interferon-stimulated genes in the gut. It is unknown how long these effects last and whether they occur in other relevant body compartments. We measured the transcriptomes and proteomes of tissue samples obtained before and after daily topical tenofovir 1% gel application for 14 days (Microbicide Trials Network [MTN]-014 trial, rectal and vaginal) or 56 days (MTN-017 trial, rectal). While many changes seen after 7 days diminish after 14 and 56 days, some remain, notably increases in cell proliferation- and type I/III interferon-related genes. Vaginal gel uniquely induces changes related to epithelial-mesenchymal transition and angiogenesis. Induction of type I/III interferon-related genes is the most consistent and persistent mucosal response to tenofovir, occurring after both oral and topical use and at all tested time points. Hypothetically, interferon induction could improve antiviral efficacy, but also contribute to an increased chronic disease burden in people with HIV.
IMPORTANCE: Analyzing gene expression data from three separate clinical trials, we find that the antiretroviral drug tenofovir, which belongs to the class of nucleotide analogue reverse transcriptase inhibitors, induces the type I/III interferon system of innate immunity in the mucosa. This effect occurs in the absence of HIV infection and manifests itself over various treatment durations and after both oral and topical drug delivery. Tenofovir and other related medications are important components of long-term antiretroviral treatment taken by people living with HIV. Therefore, this unexpected immunological effect might need to be considered as a potential contributor to comorbidities in people living with HIV, as well as an immunopharmacological co-factor when testing novel HIV cure interventions.
CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT01768962, NCT01687218, and NCT01232803.
Additional Links: PMID-41869811
Publisher:
PubMed:
Citation:
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@article {pmid41869811,
year = {2026},
author = {Hughes, SM and Calienes, FL and Levy, CN and Pandey, U and Gornalusse, GG and Cranston, RD and Lama, JR and Pickett, J and Brand, RM and Hendrix, CW and Marzinke, MA and Dai, JY and Balar, B and Justman, JE and Nair, G and Berard, AR and Birse, K and Noel-Romas, L and Mayer, KH and Stekler, JD and Mackelprang, R and Burgener, AD and McGowan, I and Cameron, CM and Cameron, MJ and Woodrow, KA and Hladik, F},
title = {Mucosal tenofovir 1% gel stimulates cell proliferation and type I/III interferon pathways.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0168025},
doi = {10.1128/spectrum.01680-25},
pmid = {41869811},
issn = {2165-0497},
abstract = {UNLABELLED: Oral tenofovir is a key antiretroviral used for treatment and pre-exposure prophylaxis (PrEP) of human immunodeficiency virus (HIV). A gel form has been tested for vaginal and rectal PrEP. We have shown that 7 days of tenofovir 1% gel had broad-ranging effects on gene expression in the rectum, especially suppression of anti-inflammatory mediators and induction of cell proliferation. Similarly, oral PrEP induced type I/III interferon-stimulated genes in the gut. It is unknown how long these effects last and whether they occur in other relevant body compartments. We measured the transcriptomes and proteomes of tissue samples obtained before and after daily topical tenofovir 1% gel application for 14 days (Microbicide Trials Network [MTN]-014 trial, rectal and vaginal) or 56 days (MTN-017 trial, rectal). While many changes seen after 7 days diminish after 14 and 56 days, some remain, notably increases in cell proliferation- and type I/III interferon-related genes. Vaginal gel uniquely induces changes related to epithelial-mesenchymal transition and angiogenesis. Induction of type I/III interferon-related genes is the most consistent and persistent mucosal response to tenofovir, occurring after both oral and topical use and at all tested time points. Hypothetically, interferon induction could improve antiviral efficacy, but also contribute to an increased chronic disease burden in people with HIV.
IMPORTANCE: Analyzing gene expression data from three separate clinical trials, we find that the antiretroviral drug tenofovir, which belongs to the class of nucleotide analogue reverse transcriptase inhibitors, induces the type I/III interferon system of innate immunity in the mucosa. This effect occurs in the absence of HIV infection and manifests itself over various treatment durations and after both oral and topical drug delivery. Tenofovir and other related medications are important components of long-term antiretroviral treatment taken by people living with HIV. Therefore, this unexpected immunological effect might need to be considered as a potential contributor to comorbidities in people living with HIV, as well as an immunopharmacological co-factor when testing novel HIV cure interventions.
CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT01768962, NCT01687218, and NCT01232803.},
}
RevDate: 2026-03-23
Reflections on FDA Draft Guidance on Bayesian Methods in Trials-Protecting Scientific Integrity and Evidentiary Standards.
JAMA pii:2847013 [Epub ahead of print].
Additional Links: PMID-41870422
Publisher:
PubMed:
Citation:
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@article {pmid41870422,
year = {2026},
author = {Evans, SR and Fleming, TR and Janes, H and Dodd, LE},
title = {Reflections on FDA Draft Guidance on Bayesian Methods in Trials-Protecting Scientific Integrity and Evidentiary Standards.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2026.4175},
pmid = {41870422},
issn = {1538-3598},
}
RevDate: 2026-03-23
CmpDate: 2026-03-23
Mobile Health App Attitudes and Adoption Among Oncology Providers: Cross-Sectional National Survey.
Journal of medical Internet research, 28:e85583 pii:v28i1e85583.
BACKGROUND: Mobile health (mHealth) apps can address health inequities and enhance access to care for individuals with immunocompromising conditions. Although hundreds of oncology apps exist, research on provider perspectives regarding their use in clinical care remains limited.
OBJECTIVE: This study aimed to describe oncology providers' recommended apps, mHealth attitudes and beliefs, and perceived barriers to and facilitators of mHealth adoption. Exploratory aims examined differences based on provider type (medical vs psychosocial), provider age (<45 vs ≥45 years old), and patient population (pediatric vs adult).
METHODS: We conducted a cross-sectional survey administered via REDCap (Research Electronic Data Capture) to oncology providers across the United States between June and November 2024. Data were summarized using descriptive statistics. Pearson's chi-square analyses examined exploratory group differences based on provider type, provider age, and patient age.
RESULTS: Of 188 respondents, the majority self-identified as female (150/188, 79.8%), White (161/188, 85.6%), and non-Hispanic/Latino (174/188, 92.6%). Nearly all providers (178/188, 94.7%) reported either recommending or using mHealth apps with their patients, with primary use for patient-provider communication (139/188, 73.9%). Providers perceived potential benefit across a broad spectrum of holistic care functions. Providers, on average, reported a growth mindset and confidence in their ability to learn mHealth tools and in its potential to improve care access. Key facilitators included alignment with patient needs, increased accessibility, and cost-effectiveness, while barriers included disparities in technology access, digital health literacy, and data security and privacy. Exploratory analyses showed some significant group differences by provider role, provider age, and patient age. Psychosocial providers were significantly more likely to recommend or use apps for pain management (χ[2]1=14.34, P<.001, φ=0.28), mental health (χ[2]1=50.54, P<.001, φ=0.53), and sleep health (χ[2]1=25.47, P<.001, φ= 0.38). Psychosocial providers also perceived higher benefit for sleep health apps (χ[2]1=6.40, P=.01, φ=0.19). Medical providers were significantly more likely to perceive medication management apps as potentially beneficial (χ[2]1=10.93, P<.001, φ=0.25). Older providers (16/88, 18.2%) and adult care providers (8/32, 25%) were significantly more likely to recommend or use disease management apps compared to younger providers (5/100, 5%; χ[2]1=8.20, P=.004, φ=0.21) and pediatric care providers (6/101, 5.9%; χ[2]2=9.22, P=.01, Cramer V=0.22), respectively. Pediatric care providers (83/101, 82.2%) were more likely to recommend or use medical team communication apps compared to adult care providers (15/32, 46.9%; χ[2]2=15.66, P<.001, Cramer V=0.29).
CONCLUSIONS: Our study underscores the opportunity to develop inclusive mHealth solutions tailored to the diverse needs of individuals across the cancer care continuum, including those in active treatment and survivorship care. Engaging diverse medical and psychosocial providers is essential to inform clinical integration of mHealth technologies in oncology care.
Additional Links: PMID-41871339
Publisher:
PubMed:
Citation:
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@article {pmid41871339,
year = {2026},
author = {Lau, N and Srinakarin, K and Hong, SJ and Aalfs, H and Roth, ME and Ingram, KM and Berkman, A and Chan, S and Patten, J and Iwata, W and Taylor, MR and Fann, JR and Chow, EJ and Palermo, TM},
title = {Mobile Health App Attitudes and Adoption Among Oncology Providers: Cross-Sectional National Survey.},
journal = {Journal of medical Internet research},
volume = {28},
number = {},
pages = {e85583},
doi = {10.2196/85583},
pmid = {41871339},
issn = {1438-8871},
mesh = {Humans ; Cross-Sectional Studies ; *Mobile Applications ; Female ; Male ; Middle Aged ; *Telemedicine ; Adult ; *Attitude of Health Personnel ; United States ; Surveys and Questionnaires ; *Medical Oncology ; *Health Personnel/psychology ; },
abstract = {BACKGROUND: Mobile health (mHealth) apps can address health inequities and enhance access to care for individuals with immunocompromising conditions. Although hundreds of oncology apps exist, research on provider perspectives regarding their use in clinical care remains limited.
OBJECTIVE: This study aimed to describe oncology providers' recommended apps, mHealth attitudes and beliefs, and perceived barriers to and facilitators of mHealth adoption. Exploratory aims examined differences based on provider type (medical vs psychosocial), provider age (<45 vs ≥45 years old), and patient population (pediatric vs adult).
METHODS: We conducted a cross-sectional survey administered via REDCap (Research Electronic Data Capture) to oncology providers across the United States between June and November 2024. Data were summarized using descriptive statistics. Pearson's chi-square analyses examined exploratory group differences based on provider type, provider age, and patient age.
RESULTS: Of 188 respondents, the majority self-identified as female (150/188, 79.8%), White (161/188, 85.6%), and non-Hispanic/Latino (174/188, 92.6%). Nearly all providers (178/188, 94.7%) reported either recommending or using mHealth apps with their patients, with primary use for patient-provider communication (139/188, 73.9%). Providers perceived potential benefit across a broad spectrum of holistic care functions. Providers, on average, reported a growth mindset and confidence in their ability to learn mHealth tools and in its potential to improve care access. Key facilitators included alignment with patient needs, increased accessibility, and cost-effectiveness, while barriers included disparities in technology access, digital health literacy, and data security and privacy. Exploratory analyses showed some significant group differences by provider role, provider age, and patient age. Psychosocial providers were significantly more likely to recommend or use apps for pain management (χ[2]1=14.34, P<.001, φ=0.28), mental health (χ[2]1=50.54, P<.001, φ=0.53), and sleep health (χ[2]1=25.47, P<.001, φ= 0.38). Psychosocial providers also perceived higher benefit for sleep health apps (χ[2]1=6.40, P=.01, φ=0.19). Medical providers were significantly more likely to perceive medication management apps as potentially beneficial (χ[2]1=10.93, P<.001, φ=0.25). Older providers (16/88, 18.2%) and adult care providers (8/32, 25%) were significantly more likely to recommend or use disease management apps compared to younger providers (5/100, 5%; χ[2]1=8.20, P=.004, φ=0.21) and pediatric care providers (6/101, 5.9%; χ[2]2=9.22, P=.01, Cramer V=0.22), respectively. Pediatric care providers (83/101, 82.2%) were more likely to recommend or use medical team communication apps compared to adult care providers (15/32, 46.9%; χ[2]2=15.66, P<.001, Cramer V=0.29).
CONCLUSIONS: Our study underscores the opportunity to develop inclusive mHealth solutions tailored to the diverse needs of individuals across the cancer care continuum, including those in active treatment and survivorship care. Engaging diverse medical and psychosocial providers is essential to inform clinical integration of mHealth technologies in oncology care.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
Cross-Sectional Studies
*Mobile Applications
Female
Male
Middle Aged
*Telemedicine
Adult
*Attitude of Health Personnel
United States
Surveys and Questionnaires
*Medical Oncology
*Health Personnel/psychology
RevDate: 2026-03-23
Homologous Recombination Deficiency and Genomic Alterations in Advanced Prostate Cancer: Insights for Precision Therapy.
The oncologist pii:8537917 [Epub ahead of print].
BACKGROUND: the homologous recombination deficiency signature (HRDsig) is emerging as a novel potential predictor of PARP-inhibitor (PARPi) response. We compared genomic alterations (GA) across BRCA2-loss, BRCA2 short variant-mutated (svmut), and BRCA2-wild type (wt) clinically advanced prostate carcinoma (CAPC) samples, combined with an assessment of HRDsig status to gain a better understanding of these biomarkers.
METHODS: Comprehensive genomic profiling (CGP) was performed on 22,061 CAPC cases to evaluate all classes of GA. Microsatellite instability (MSI) status, tumor mutational burden (TMB), genomic ancestry, were derived from sequencing data. HRDsig status was calculated using genome-wide copy number features. PD-L1 expression was assessed by IHC. Comparisons were performed using Fisher's exact test with Benjamini-Hochberg correction for false discovery.
RESULTS: Among 22,061 CAPC cases, 10.2% were HRDsig+. HRDsig+ and were enriched for BRCA2, RB1, MYC, RAD21, and AR alterations, while SPOP, MSI-high, high TMB, and MMR signatures were more frequent in HRDsig- cases. Across BRCA2-defined subgroups, 597(2.7%) were BRCA2-loss, 1,085(4.9%) BRCA2-svmut, and 20,379(92.4%) BRCA2-wt. Both BRCA2-loss and BRCA2-svmut were associated with higher GA burden and enrichment for RB1 alterations. BRCA2-loss cases displayed lower TMB-high incidence, while BRCA2-svmut showed higher MSI-high and TMB-high incidence. Most BRCA2 alterations were bi-allelic, with concurrent alterations in other HRR genes being rare.
CONCLUSIONS: BRCA2-loss CAPC displays a distinct genomic landscape, marked by robust HRD features, suggesting the potential of higher sensitivity to PARPi. These findings highlight the relevance of HRDsig, and routinely use of CGP in refining patient selection for PARPi and guiding the design of future clinical trials.
Additional Links: PMID-41871940
Publisher:
PubMed:
Citation:
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@article {pmid41871940,
year = {2026},
author = {Mercinelli, C and Pavlick, D and Agarwal, N and Spiess, PE and Li, R and Kamat, AM and Grivas, P and Gupta, S and Maiorano, BA and Tateo, V and Cigliola, A and Piacentini, M and Jacob, JM and Bratslavsky, G and Basnet, A and Ross, JS and Necchi, A},
title = {Homologous Recombination Deficiency and Genomic Alterations in Advanced Prostate Cancer: Insights for Precision Therapy.},
journal = {The oncologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/oncolo/oyag100},
pmid = {41871940},
issn = {1549-490X},
abstract = {BACKGROUND: the homologous recombination deficiency signature (HRDsig) is emerging as a novel potential predictor of PARP-inhibitor (PARPi) response. We compared genomic alterations (GA) across BRCA2-loss, BRCA2 short variant-mutated (svmut), and BRCA2-wild type (wt) clinically advanced prostate carcinoma (CAPC) samples, combined with an assessment of HRDsig status to gain a better understanding of these biomarkers.
METHODS: Comprehensive genomic profiling (CGP) was performed on 22,061 CAPC cases to evaluate all classes of GA. Microsatellite instability (MSI) status, tumor mutational burden (TMB), genomic ancestry, were derived from sequencing data. HRDsig status was calculated using genome-wide copy number features. PD-L1 expression was assessed by IHC. Comparisons were performed using Fisher's exact test with Benjamini-Hochberg correction for false discovery.
RESULTS: Among 22,061 CAPC cases, 10.2% were HRDsig+. HRDsig+ and were enriched for BRCA2, RB1, MYC, RAD21, and AR alterations, while SPOP, MSI-high, high TMB, and MMR signatures were more frequent in HRDsig- cases. Across BRCA2-defined subgroups, 597(2.7%) were BRCA2-loss, 1,085(4.9%) BRCA2-svmut, and 20,379(92.4%) BRCA2-wt. Both BRCA2-loss and BRCA2-svmut were associated with higher GA burden and enrichment for RB1 alterations. BRCA2-loss cases displayed lower TMB-high incidence, while BRCA2-svmut showed higher MSI-high and TMB-high incidence. Most BRCA2 alterations were bi-allelic, with concurrent alterations in other HRR genes being rare.
CONCLUSIONS: BRCA2-loss CAPC displays a distinct genomic landscape, marked by robust HRD features, suggesting the potential of higher sensitivity to PARPi. These findings highlight the relevance of HRDsig, and routinely use of CGP in refining patient selection for PARPi and guiding the design of future clinical trials.},
}
RevDate: 2026-03-20
CmpDate: 2026-03-20
Tolerance and Resistance to Targeted Therapy in NSCLC: Emerging Concepts and Strategies.
JTO clinical and research reports, 7(4):100944.
The discovery of EGFR mutations two decades ago launched an era of rapid development and clinical application of targeted therapies in NSCLC. Today, increasing numbers of targeted therapies against somatic aberrations involving nine different genes have become available for treating patients with lung cancer and have improved their outcomes. However, acquired resistance and tumor tolerance to these therapies remains one of the biggest challenges in lung cancer treatment today. Most, if not all, targeted therapies have limited durability, which we now recognize is due to both genetic and non-genetic mechanisms of resistance. The state of our current understanding of resistance and new approaches to prevent or overcome resistance were recently presented at the International Association for the Study of Lung Cancer Hot Topics Meeting. Here, we summarize and discuss the emerging concepts and new strategies for combating drug tolerance and resistance in targeted therapies, including our understanding of the role of genetics, drug-tolerant persister cells, tumor plasticity and lineage transformation, spatial and temporal heterogeneity, microenvironmental influence, and novel therapeutic approaches.
Additional Links: PMID-41858873
PubMed:
Citation:
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@article {pmid41858873,
year = {2026},
author = {Sanchez-Cespedes, M and Lockwood, WW and Suda, K and Gardner, EE and Mitsudomi, T and Politi, K and Rolfo, C and Sen, T and Sos, ML and Tammela, T and Wynes, MW and Tsao, MS and Berger, AH},
title = {Tolerance and Resistance to Targeted Therapy in NSCLC: Emerging Concepts and Strategies.},
journal = {JTO clinical and research reports},
volume = {7},
number = {4},
pages = {100944},
pmid = {41858873},
issn = {2666-3643},
abstract = {The discovery of EGFR mutations two decades ago launched an era of rapid development and clinical application of targeted therapies in NSCLC. Today, increasing numbers of targeted therapies against somatic aberrations involving nine different genes have become available for treating patients with lung cancer and have improved their outcomes. However, acquired resistance and tumor tolerance to these therapies remains one of the biggest challenges in lung cancer treatment today. Most, if not all, targeted therapies have limited durability, which we now recognize is due to both genetic and non-genetic mechanisms of resistance. The state of our current understanding of resistance and new approaches to prevent or overcome resistance were recently presented at the International Association for the Study of Lung Cancer Hot Topics Meeting. Here, we summarize and discuss the emerging concepts and new strategies for combating drug tolerance and resistance in targeted therapies, including our understanding of the role of genetics, drug-tolerant persister cells, tumor plasticity and lineage transformation, spatial and temporal heterogeneity, microenvironmental influence, and novel therapeutic approaches.},
}
RevDate: 2026-03-20
Response to Piscitello et al.
Journal of the National Cancer Institute pii:8529772 [Epub ahead of print].
Additional Links: PMID-41859811
Publisher:
PubMed:
Citation:
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@article {pmid41859811,
year = {2026},
author = {Coronado, GD and Rutter, C and Nascimento De Lima, P},
title = {Response to Piscitello et al.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djag075},
pmid = {41859811},
issn = {1460-2105},
}
RevDate: 2026-03-20
DXA-Derived Abdominal Adiposity and Obesity-Related Cancer Risk Among Postmenopausal Women in the Women's Health Initiative.
Obesity (Silver Spring, Md.) [Epub ahead of print].
OBJECTIVE: Obesity is associated with the risk of several cancers, yet conventional anthropometric measures do not distinguish the contributions of different compartments of abdominal adipose tissue. This study examined the relationship between visceral (VAT) and subcutaneous (SAT) abdominal adiposity and the incidence of 13 obesity-related cancers (ObRCs) in postmenopausal women.
METHODS: Data from 9950 postmenopausal participants in the Women's Health Initiative (WHI) dual-energy X-ray absorptiometry (DXA) cohort were analyzed. Abdominal VAT and SAT were quantified from DXA scans using validated imaging software. Fine and Gray competing-risks models estimated associations with ObRC incidence over 177,295 person-years of follow-up.
RESULTS: Higher abdominal VAT was significantly associated with higher ObRC risk, independently of BMI, waist circumference (WC), and other confounders. Each 100-cm[2] increase in VAT corresponded to a 32% higher risk, with a nearly twofold increase for women in the highest VAT quartile. SAT and the VAT/SAT ratio were also significantly associated with risk, though more modestly. Findings were consistent across BMI, WC, age, and race/ethnicity strata and in time-varying models.
CONCLUSIONS: Visceral adiposity has a strong, independent association with ObRC risk in postmenopausal women. Incorporating imaging-based body composition measures may improve cancer risk stratification and guide targeted prevention strategies.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00000611 https://clinicaltrials.gov/study/NCT00000611.
Additional Links: PMID-41860387
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PubMed:
Citation:
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@article {pmid41860387,
year = {2026},
author = {Blew, RM and Ziller, SG and Odegaard, AO and Caan, BJ and Chen, Z and Roe, DJ and Manson, JE and Rohan, TE and Felix, AS and Harris, HR and Luo, J and Lane, DS and Bea, JW},
title = {DXA-Derived Abdominal Adiposity and Obesity-Related Cancer Risk Among Postmenopausal Women in the Women's Health Initiative.},
journal = {Obesity (Silver Spring, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/oby.70168},
pmid = {41860387},
issn = {1930-739X},
support = {R01CA253302//National Cancer Institute at the National Institutes of Health/ ; R01CA253302-02S1//National Cancer Institute at the National Institutes of Health/ ; R25CA217725//National Cancer Institute at the National Institutes of Health/ ; P30CA023074//National Cancer Institute at the National Institutes of Health/ ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; R01AG055018//National Institute on Aging of the National Institutes of Health/ ; },
abstract = {OBJECTIVE: Obesity is associated with the risk of several cancers, yet conventional anthropometric measures do not distinguish the contributions of different compartments of abdominal adipose tissue. This study examined the relationship between visceral (VAT) and subcutaneous (SAT) abdominal adiposity and the incidence of 13 obesity-related cancers (ObRCs) in postmenopausal women.
METHODS: Data from 9950 postmenopausal participants in the Women's Health Initiative (WHI) dual-energy X-ray absorptiometry (DXA) cohort were analyzed. Abdominal VAT and SAT were quantified from DXA scans using validated imaging software. Fine and Gray competing-risks models estimated associations with ObRC incidence over 177,295 person-years of follow-up.
RESULTS: Higher abdominal VAT was significantly associated with higher ObRC risk, independently of BMI, waist circumference (WC), and other confounders. Each 100-cm[2] increase in VAT corresponded to a 32% higher risk, with a nearly twofold increase for women in the highest VAT quartile. SAT and the VAT/SAT ratio were also significantly associated with risk, though more modestly. Findings were consistent across BMI, WC, age, and race/ethnicity strata and in time-varying models.
CONCLUSIONS: Visceral adiposity has a strong, independent association with ObRC risk in postmenopausal women. Incorporating imaging-based body composition measures may improve cancer risk stratification and guide targeted prevention strategies.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00000611 https://clinicaltrials.gov/study/NCT00000611.},
}
RevDate: 2026-03-22
CmpDate: 2026-03-20
Superabundant microRNAs are transcribed from human rDNA spacer promoters insulated by CTCF.
Science advances, 12(12):eaec1451.
microRNAs are ~22-nucleotide RNAs processed from primary transcripts and exported from the nucleus to repress gene expression by base-pairing to mRNAs. Unexpectedly, we find that the highest levels of RNA polymerase II (Pol II) at human microRNA genes are within the ribosomal gene repeat arrays (rDNAs). Alignment of public nascent transcript data to the hs1 human genome assembly reveals a 50-nucleotide transcript for both miR-1275 and miR-6724, which exits from the nucleus with exceptional rapidity. We show that the miR-1275/miR-6724 transcription unit is closely flanked by CCCTC-binding factor (CTCF) within a <400-bp span of the rDNA spacer promoter. miR-1275/miR-6724 and microRNA precursors expressed from the 5' external transcribed spacer (5'ETS) are exported independently of known RNA processing activities and are detected in exosomes and as circulating cancer biomarkers. We propose that the rDNA spacer promoter and 5'ETS microRNA genes have evolved for general regulatory functions in recipient cells.
Additional Links: PMID-41860999
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Citation:
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@article {pmid41860999,
year = {2026},
author = {Henikoff, S and Henikoff, JG},
title = {Superabundant microRNAs are transcribed from human rDNA spacer promoters insulated by CTCF.},
journal = {Science advances},
volume = {12},
number = {12},
pages = {eaec1451},
pmid = {41860999},
issn = {2375-2548},
mesh = {Humans ; *MicroRNAs/genetics ; *Promoter Regions, Genetic ; *CCCTC-Binding Factor/metabolism/genetics ; *Transcription, Genetic ; RNA Polymerase II/metabolism/genetics ; *DNA, Ribosomal/genetics ; *DNA, Ribosomal Spacer/genetics ; },
abstract = {microRNAs are ~22-nucleotide RNAs processed from primary transcripts and exported from the nucleus to repress gene expression by base-pairing to mRNAs. Unexpectedly, we find that the highest levels of RNA polymerase II (Pol II) at human microRNA genes are within the ribosomal gene repeat arrays (rDNAs). Alignment of public nascent transcript data to the hs1 human genome assembly reveals a 50-nucleotide transcript for both miR-1275 and miR-6724, which exits from the nucleus with exceptional rapidity. We show that the miR-1275/miR-6724 transcription unit is closely flanked by CCCTC-binding factor (CTCF) within a <400-bp span of the rDNA spacer promoter. miR-1275/miR-6724 and microRNA precursors expressed from the 5' external transcribed spacer (5'ETS) are exported independently of known RNA processing activities and are detected in exosomes and as circulating cancer biomarkers. We propose that the rDNA spacer promoter and 5'ETS microRNA genes have evolved for general regulatory functions in recipient cells.},
}
MeSH Terms:
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Humans
*MicroRNAs/genetics
*Promoter Regions, Genetic
*CCCTC-Binding Factor/metabolism/genetics
*Transcription, Genetic
RNA Polymerase II/metabolism/genetics
*DNA, Ribosomal/genetics
*DNA, Ribosomal Spacer/genetics
RevDate: 2026-03-20
Evaluating eight smoking metrics for modelling survival in non-small cell lung cancer.
Cancer epidemiology, 102:103052 pii:S1877-7821(26)00067-6 [Epub ahead of print].
INTRODUCTION: Smoking is a strong modifiable prognostic factor for lung cancer survival. We compared eight smoking metrics to determine which metric best models the relationship between smoking exposure with overall survival (OS) and lung cancer-specific survival (LCSS). These metrics included cigarettes-per-day, smoking duration, pack-years, square-root pack-years, logcig-years, the comprehensive smoking index, age-of-initiation, and years-since-quit.
MATERIALS/METHODS: This retrospective, pooled analysis included 25 International Lung Cancer Consortium studies between June 1, 1983-December 31, 2019. The performance of smoking metrics for modelling OS was compared based on 1) strength and significance in adjusted Cox-proportional hazard models and 2) linearity based on the goodness-of-fit assuming the log-hazard varies linearly with each smoking metric (i.e. the hazard ratio is constant across different values of the smoking metric) compared to models using non-linear splines. This process was repeated across clinicodemographic subgroups and for LCSS.
RESULTS: In total, 28,702 lung cancer patients were included (median age 64 [IQR: 57-71]; 53% male). Logcig-years (log(cigarettes/day+1)·years-smoked) had the highest adjusted hazard ratio per standard deviation (aHR 1.11; 95% CI: 1.09-1.13) and best goodness-of-fit when modelled linearly. Square-root pack-years had a similar effect size (aHR 1.11; 95% CI: 1.09-1.13) and had a strong linear relationship on visual assessment of spline curves. In subgroup analyses, logcig-years had a large effect size and maintained a linear relationship regardless of age, sex, stage, and histology. For lung cancer-specific survival (LCSS), logcig-years again had the highest aHR (1.09; 95% CI: 1.05-1.12) and the best linear goodness-of-fit, while square-root pack-years demonstrated the most linear relationship on visual assessment.
DISCUSSION: Logcig-years best modelled the relationship between smoking exposure and OS as well as LCSS, and had consistent associations across clinicodemographic subgroups. Logcig-years should be considered in clinical and research applications for quantifying smoking exposure in lung cancer.
Additional Links: PMID-41861692
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PubMed:
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@article {pmid41861692,
year = {2026},
author = {Lam, AC and Li, Y and Brown, MC and Deng, Y and Hueniken, K and Leighl, NB and Shepherd, FA and Murison, K and Wang, Z and Kothari, J and Wenzlaff, AS and Liu, H and Kohno, T and Pesatori, AC and Harris, C and Ma, H and Dai, J and Barnett, MJ and Diver, R and Leal, LF and Fernandez-Tardon, G and Pérez-Ríos, M and Davies, MP and Holleczek, B and Brennan, P and Zaridze, D and Holcatova, I and Lissowska, J and Świątkowska, B and Mates, D and Savic, M and Brenner, H and Andrew, AS and Taylor, F and Field, JK and Ruano-Ravina, A and Shete, SS and Tardon, A and Wang, Y and Marchand, LL and Reis, RM and Schabath, MB and Neuhouser, ML and Shen, H and Landi, MT and Shiraishi, K and Zhang, J and Schwartz, AG and Tsao, MS and Christiani, DC and Yang, P and Hung, RJ and Xu, W and Liu, G},
title = {Evaluating eight smoking metrics for modelling survival in non-small cell lung cancer.},
journal = {Cancer epidemiology},
volume = {102},
number = {},
pages = {103052},
doi = {10.1016/j.canep.2026.103052},
pmid = {41861692},
issn = {1877-783X},
abstract = {INTRODUCTION: Smoking is a strong modifiable prognostic factor for lung cancer survival. We compared eight smoking metrics to determine which metric best models the relationship between smoking exposure with overall survival (OS) and lung cancer-specific survival (LCSS). These metrics included cigarettes-per-day, smoking duration, pack-years, square-root pack-years, logcig-years, the comprehensive smoking index, age-of-initiation, and years-since-quit.
MATERIALS/METHODS: This retrospective, pooled analysis included 25 International Lung Cancer Consortium studies between June 1, 1983-December 31, 2019. The performance of smoking metrics for modelling OS was compared based on 1) strength and significance in adjusted Cox-proportional hazard models and 2) linearity based on the goodness-of-fit assuming the log-hazard varies linearly with each smoking metric (i.e. the hazard ratio is constant across different values of the smoking metric) compared to models using non-linear splines. This process was repeated across clinicodemographic subgroups and for LCSS.
RESULTS: In total, 28,702 lung cancer patients were included (median age 64 [IQR: 57-71]; 53% male). Logcig-years (log(cigarettes/day+1)·years-smoked) had the highest adjusted hazard ratio per standard deviation (aHR 1.11; 95% CI: 1.09-1.13) and best goodness-of-fit when modelled linearly. Square-root pack-years had a similar effect size (aHR 1.11; 95% CI: 1.09-1.13) and had a strong linear relationship on visual assessment of spline curves. In subgroup analyses, logcig-years had a large effect size and maintained a linear relationship regardless of age, sex, stage, and histology. For lung cancer-specific survival (LCSS), logcig-years again had the highest aHR (1.09; 95% CI: 1.05-1.12) and the best linear goodness-of-fit, while square-root pack-years demonstrated the most linear relationship on visual assessment.
DISCUSSION: Logcig-years best modelled the relationship between smoking exposure and OS as well as LCSS, and had consistent associations across clinicodemographic subgroups. Logcig-years should be considered in clinical and research applications for quantifying smoking exposure in lung cancer.},
}
RevDate: 2026-03-21
The Safety and Efficacy of Commercial BCMA-Directed CAR T-Cell Therapy in Systemic AL Amyloidosis With Concurrent Myeloma.
Additional Links: PMID-41862775
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PubMed:
Citation:
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@article {pmid41862775,
year = {2026},
author = {Rees, MJ and Cassano, RC and Tan, M and Zolotov, E and Sidana, S and Dima, D and Kort, J and Afrough, A and Gaballa, M and Pasvolsky, O and Mikkilineni, L and Khouri, J and Raza, S and Zanwar, SS and Ferreri, CJ and Kumar, S and Khan, AM and Atrash, S and Portuguese, AJ and Rana, MS and Banerjee, R and Freeman, C and Blue, B and Patel, KK and Anderson, LD and Puglianini, OC and Shune, LO and Biran, N and Hansen, DK and Lin, Y},
title = {The Safety and Efficacy of Commercial BCMA-Directed CAR T-Cell Therapy in Systemic AL Amyloidosis With Concurrent Myeloma.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70294},
pmid = {41862775},
issn = {1096-8652},
}
RevDate: 2026-03-19
Real-World Evidence for Pembrolizumab Gemcitabine Vinorelbine and Liposomal Doxorubicin in Classical Hodgkin Lymphoma.
Blood advances pii:567288 [Epub ahead of print].
Additional Links: PMID-41855500
Publisher:
PubMed:
Citation:
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@article {pmid41855500,
year = {2026},
author = {Baek, G and Varma, G and Yamshon, S and van Besien, HJ and Bartlett, NL and Watkins, MP and Shah, HR and Baron, K and Merryman, RW and Falade, AS and Svoboda, J and Prischak, S and D'Angelo, CR and Lukowski, JD and Advani, RH and Yeung, AH and Rosenberg, MC and Voutsinas, JM and Di, M and Lynch, RC and Poh, C and Raghunathan, V and Shadman, M and Smith, SD and Till, BG and Ujjani, CS and Diefenbach, C and Gopal, AK},
title = {Real-World Evidence for Pembrolizumab Gemcitabine Vinorelbine and Liposomal Doxorubicin in Classical Hodgkin Lymphoma.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025018267},
pmid = {41855500},
issn = {2473-9537},
}
RevDate: 2026-03-22
BlotDx: A deep learning tool for Western blot-based diagnostics.
Journal of virological methods, 343:115385 pii:S0166-0934(26)00049-2 [Epub ahead of print].
BACKGROUND: Western blot (WB) is the gold standard for herpes simplex virus (HSV-1/HSV-2) serology but requires manual interpretation by trained laboratory personnel, which is time-consuming and variable. This study presents BlotDx, a deep learning tool to assist in HSV WB interpretation to improve efficiency and diagnostic consistency.
METHODS: BlotDx uses a two-stage approach: (1) instance segmentation or object detection to identify blots from input images, and (2) classification models to determine positive or negative serostatus for HSV-1 and HSV-2, excluding indeterminate results. We developed three classifiers that differ in how information flows between stages. The primary dataset consisted of 926 blot pairs derived from samples collected between 2016 and 2017 and photographed in 2018; and a second institutional validation dataset containing 185 blot pairs from samples collected between 2019 and 2024 and photographed in a different laboratory space in 2025.
RESULTS: Evaluated against the ground truth of expert human review by three independent technicians, BlotDx demonstrated high diagnostic accuracy by 5-fold cross validation in both the primary dataset (98.8% for HSV-1, 95% confidence interval (CI): 97.9%-99.3%; and 98.9% for HSV-2, 95% CI: 98.0%-99.4%), and in the institutional validation dataset (97.3% for HSV-1, 95% CI: 93.8%-98.8%; and 96.2% for HSV-2, 95% CI: 92.4%-98.1%).
CONCLUSIONS: This study highlights the utility of AI as a diagnostic assistant for image-based assays like HSV Western blots, with potential applications in other diseases. The proposed two-stage approach, combined with modern deep learning techniques is scalable and offers a step towards transforming traditional diagnostic workflows by reducing costs and increasing efficiency.
Additional Links: PMID-41856415
Publisher:
PubMed:
Citation:
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@article {pmid41856415,
year = {2026},
author = {Liu, L and Sathees, S and Sobel, A and Pepper, G and Greninger, AL and Jerome, KR and Fong, Y and Roychoudhury, P},
title = {BlotDx: A deep learning tool for Western blot-based diagnostics.},
journal = {Journal of virological methods},
volume = {343},
number = {},
pages = {115385},
doi = {10.1016/j.jviromet.2026.115385},
pmid = {41856415},
issn = {1879-0984},
abstract = {BACKGROUND: Western blot (WB) is the gold standard for herpes simplex virus (HSV-1/HSV-2) serology but requires manual interpretation by trained laboratory personnel, which is time-consuming and variable. This study presents BlotDx, a deep learning tool to assist in HSV WB interpretation to improve efficiency and diagnostic consistency.
METHODS: BlotDx uses a two-stage approach: (1) instance segmentation or object detection to identify blots from input images, and (2) classification models to determine positive or negative serostatus for HSV-1 and HSV-2, excluding indeterminate results. We developed three classifiers that differ in how information flows between stages. The primary dataset consisted of 926 blot pairs derived from samples collected between 2016 and 2017 and photographed in 2018; and a second institutional validation dataset containing 185 blot pairs from samples collected between 2019 and 2024 and photographed in a different laboratory space in 2025.
RESULTS: Evaluated against the ground truth of expert human review by three independent technicians, BlotDx demonstrated high diagnostic accuracy by 5-fold cross validation in both the primary dataset (98.8% for HSV-1, 95% confidence interval (CI): 97.9%-99.3%; and 98.9% for HSV-2, 95% CI: 98.0%-99.4%), and in the institutional validation dataset (97.3% for HSV-1, 95% CI: 93.8%-98.8%; and 96.2% for HSV-2, 95% CI: 92.4%-98.1%).
CONCLUSIONS: This study highlights the utility of AI as a diagnostic assistant for image-based assays like HSV Western blots, with potential applications in other diseases. The proposed two-stage approach, combined with modern deep learning techniques is scalable and offers a step towards transforming traditional diagnostic workflows by reducing costs and increasing efficiency.},
}
RevDate: 2026-03-19
The Role of Microenvironment in Bispecific Antibodies Treatment in Multiple Myeloma.
European journal of haematology [Epub ahead of print].
Multiple myeloma (MM) is a clonal plasma cell malignancy that remains largely incurable despite major therapeutic advances. T-cell-redirecting bispecific antibodies (BsAbs) and chimeric antigen receptor T (CAR-T) cells have recently emerged as highly effective therapies in relapsed/refractory MM, inducing deep responses even in heavily pretreated patients. However, disease relapse, limited durability of response, and treatment-related toxicities remain frequent, underscoring the need to better understand mechanisms of resistance. Accumulating evidence indicates that the tumor microenvironment (TME) plays a central role in shaping BsAb efficacy in MM. Immunosuppressive cellular components, including regulatory T-cells, myeloid-derived suppressor cells, and dysfunctional antigen-presenting cells, as well as inhibitory cytokines, hypoxia, and metabolic constraints within the TME, profoundly impair T-cell activation, expansion, and persistence following BsAb engagement. In addition, chronic CD3 stimulation within the TME may promote T-cell exhaustion, contributing to suboptimal responses and disease progression. This review focuses on the dynamic interplay between BsAbs and the MM TME, highlighting how microenvironment-driven immune suppression, antigen escape, and impaired T-cell fitness influence clinical outcomes. We further discuss emerging strategies designed to overcome these barriers, including rational combination approaches, immunomodulatory agents, and next-generation trispecific antibodies that enhance co-stimulation or dual-antigen targeting. Understanding and therapeutically modulating the TME represents a critical step toward improving the depth, durability, and safety of BsAb-based therapies in MM.
Additional Links: PMID-41856486
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@article {pmid41856486,
year = {2026},
author = {Barachini, S and Cassano Cassano, R and Ronca, F and Petrini, I and Galimberti, S and Buda, G},
title = {The Role of Microenvironment in Bispecific Antibodies Treatment in Multiple Myeloma.},
journal = {European journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ejh.70168},
pmid = {41856486},
issn = {1600-0609},
abstract = {Multiple myeloma (MM) is a clonal plasma cell malignancy that remains largely incurable despite major therapeutic advances. T-cell-redirecting bispecific antibodies (BsAbs) and chimeric antigen receptor T (CAR-T) cells have recently emerged as highly effective therapies in relapsed/refractory MM, inducing deep responses even in heavily pretreated patients. However, disease relapse, limited durability of response, and treatment-related toxicities remain frequent, underscoring the need to better understand mechanisms of resistance. Accumulating evidence indicates that the tumor microenvironment (TME) plays a central role in shaping BsAb efficacy in MM. Immunosuppressive cellular components, including regulatory T-cells, myeloid-derived suppressor cells, and dysfunctional antigen-presenting cells, as well as inhibitory cytokines, hypoxia, and metabolic constraints within the TME, profoundly impair T-cell activation, expansion, and persistence following BsAb engagement. In addition, chronic CD3 stimulation within the TME may promote T-cell exhaustion, contributing to suboptimal responses and disease progression. This review focuses on the dynamic interplay between BsAbs and the MM TME, highlighting how microenvironment-driven immune suppression, antigen escape, and impaired T-cell fitness influence clinical outcomes. We further discuss emerging strategies designed to overcome these barriers, including rational combination approaches, immunomodulatory agents, and next-generation trispecific antibodies that enhance co-stimulation or dual-antigen targeting. Understanding and therapeutically modulating the TME represents a critical step toward improving the depth, durability, and safety of BsAb-based therapies in MM.},
}
RevDate: 2026-03-19
Cost-Effectiveness Analysis of [177]Lu-PSMA-617 Versus Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer from a U.S. Health Care Perspective.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine pii:jnumed.125.271825 [Epub ahead of print].
The TheraP trial demonstrated that [177]Lu-PSMA-617 improved progression-free survival (PFS) compared with cabazitaxel, with no significant difference in overall survival (OS). However, [177]Lu-PSMA-617 was associated with fewer severe adverse events, better patient-reported outcomes, and lower health care utilization rates. In this study, we evaluated the impact of these benefits on the cost-effectiveness of [177]Lu-PSMA-617 versus cabazitaxel from a U.S. health care perspective. Methods: A partitioned survival model was developed to estimate lifetime costs and health outcomes associated with [177]Lu-PSMA-617 versus cabazitaxel over a 60-mo horizon. OS and PFS associated with[177]Lu-PSMA-617 were derived from a retrospective cohort, and relative treatment effects (hazard ratios [HRs]) from the TheraP trial were applied to generate outcomes for patients treated with cabazitaxel. Health state utilities, adverse-event disutilities, and costs were obtained from published sources. Outcomes included total costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio, and net monetary benefit at willingness-to-pay (WTP) thresholds up to $200,000/QALY. Results: In the base case analysis, [177]Lu-PSMA-617 was not cost-effective compared with cabazitaxel (incremental cost-effectiveness ratio, $358,990/QALY). Cost-effectiveness results were most sensitive to the OS HR, the per-cycle cost of [177]Lu-PSMA-617, and the per-cycle cost of cabazitaxel. [177]Lu-PSMA-617 would become cost-effective if the per-cycle treatment cost was $27,656 or if the OS HR improved to 0.76 at a WTP threshold of $200,000/QALY. Probabilistic analyses found that [177]Lu-PSMA-617 was cost-effective in 19.7% of iterations at a WTP threshold of $200,000/QALY, 4.7% at $100,000/QALY, and 2.2% at $50,000/QALY. Conclusion: Although [177]Lu-PSMA-617 was not cost-effective compared with cabazitaxel in the base case analysis, it may achieve cost-effectiveness under more favorable assumptions of survival benefit or reduced cost per cycle. Probabilistic analyses further highlighted substantial uncertainty, with a low likelihood of cost-effectiveness.
Additional Links: PMID-41856667
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PubMed:
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@article {pmid41856667,
year = {2026},
author = {Gogebakan, KC and Kunst, N and Ghodsi, A and Owens, L and Iravani, A and Etzioni, R},
title = {Cost-Effectiveness Analysis of [177]Lu-PSMA-617 Versus Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer from a U.S. Health Care Perspective.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.271825},
pmid = {41856667},
issn = {1535-5667},
abstract = {The TheraP trial demonstrated that [177]Lu-PSMA-617 improved progression-free survival (PFS) compared with cabazitaxel, with no significant difference in overall survival (OS). However, [177]Lu-PSMA-617 was associated with fewer severe adverse events, better patient-reported outcomes, and lower health care utilization rates. In this study, we evaluated the impact of these benefits on the cost-effectiveness of [177]Lu-PSMA-617 versus cabazitaxel from a U.S. health care perspective. Methods: A partitioned survival model was developed to estimate lifetime costs and health outcomes associated with [177]Lu-PSMA-617 versus cabazitaxel over a 60-mo horizon. OS and PFS associated with[177]Lu-PSMA-617 were derived from a retrospective cohort, and relative treatment effects (hazard ratios [HRs]) from the TheraP trial were applied to generate outcomes for patients treated with cabazitaxel. Health state utilities, adverse-event disutilities, and costs were obtained from published sources. Outcomes included total costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio, and net monetary benefit at willingness-to-pay (WTP) thresholds up to $200,000/QALY. Results: In the base case analysis, [177]Lu-PSMA-617 was not cost-effective compared with cabazitaxel (incremental cost-effectiveness ratio, $358,990/QALY). Cost-effectiveness results were most sensitive to the OS HR, the per-cycle cost of [177]Lu-PSMA-617, and the per-cycle cost of cabazitaxel. [177]Lu-PSMA-617 would become cost-effective if the per-cycle treatment cost was $27,656 or if the OS HR improved to 0.76 at a WTP threshold of $200,000/QALY. Probabilistic analyses found that [177]Lu-PSMA-617 was cost-effective in 19.7% of iterations at a WTP threshold of $200,000/QALY, 4.7% at $100,000/QALY, and 2.2% at $50,000/QALY. Conclusion: Although [177]Lu-PSMA-617 was not cost-effective compared with cabazitaxel in the base case analysis, it may achieve cost-effectiveness under more favorable assumptions of survival benefit or reduced cost per cycle. Probabilistic analyses further highlighted substantial uncertainty, with a low likelihood of cost-effectiveness.},
}
RevDate: 2026-03-19
Experimental immunologists in the era of artificial intelligence.
Trends in immunology pii:S1471-4906(26)00006-2 [Epub ahead of print].
While artificial intelligence (AI) is transforming biological science, its full potential in immunology has yet to be realized due to limited data and the need for extensive experimental validation. This review provides a practical guide for experimental immunologists to actively contribute to AI development, with a focus on applications for B- and T-cell receptors. It not only gives an overview of common AI techniques in immunology but also highlights the important role of high-throughput experimental methodologies. Overall, we believe that the synergy between AI and experimental innovation will be a crucial catalyst for advancing the field of immunology.
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@article {pmid41856883,
year = {2026},
author = {Wang, Y and Ouyang, WO and Wang, C and Nourmohammad, A and Liu, G and Wu, NC},
title = {Experimental immunologists in the era of artificial intelligence.},
journal = {Trends in immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.it.2026.01.003},
pmid = {41856883},
issn = {1471-4981},
abstract = {While artificial intelligence (AI) is transforming biological science, its full potential in immunology has yet to be realized due to limited data and the need for extensive experimental validation. This review provides a practical guide for experimental immunologists to actively contribute to AI development, with a focus on applications for B- and T-cell receptors. It not only gives an overview of common AI techniques in immunology but also highlights the important role of high-throughput experimental methodologies. Overall, we believe that the synergy between AI and experimental innovation will be a crucial catalyst for advancing the field of immunology.},
}
RevDate: 2026-03-18
CmpDate: 2026-03-19
Brain volume trajectories in young children are associated with polygenic scores for late-onset Alzheimer's disease risk.
Alzheimer's & dementia : the journal of the Alzheimer's Association, 22(3):e71279.
INTRODUCTION: Polygenic risk scores (PRSs) for Alzheimer's disease (AD) capture an individual's genetic susceptibility to AD. Although thoroughly studied in older populations, there exists a notable gap in comprehensively exploring the association of AD PRS with early brain development.
METHODS: We examined longitudinal brain magnetic resonance imaging (MRI) data from 348 typically developing children in the RESONANCE cohort. Proportional cerebrospinal fluid (pCSF), white matter (pWM), and gray matter (pGM) volumes were analyzed using functional concurrent regression and Riemannian functional principal component analysis. AD-PRS scores (AD25 and AD54) were computed using genome-wide data.
RESULTS: Higher AD PRS was significantly associated with reduced pCSF during early childhood (ages 2.5 to 5.5 years for AD54). Energy and distance-based tests revealed overall significant differences in brain volume trajectories between moderate and low AD54 risk groups.
DISCUSSION: These findings suggest that genetic risk for late-onset AD is linked to early neurodevelopmental patterns, indicating that AD vulnerability may originate during critical windows of early brain maturation.
Additional Links: PMID-41851041
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PubMed:
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@article {pmid41851041,
year = {2026},
author = {Kundu, P and Zhu, C and Huentelman, M and Deoni, SCL and Naymik, M and Taguinod, F and De Both, M and Lewis, CR and Müller, HG},
title = {Brain volume trajectories in young children are associated with polygenic scores for late-onset Alzheimer's disease risk.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71279},
doi = {10.1002/alz.71279},
pmid = {41851041},
issn = {1552-5279},
support = {DMS-2014626//National Science Foundation/ ; DMS-2310450//National Science Foundation/ ; },
mesh = {Humans ; *Alzheimer Disease/genetics/pathology/diagnostic imaging ; Magnetic Resonance Imaging ; Male ; Female ; *Brain/pathology/diagnostic imaging/growth & development ; Child, Preschool ; *Multifactorial Inheritance/genetics ; *Genetic Predisposition to Disease/genetics ; Longitudinal Studies ; Organ Size ; Gray Matter/diagnostic imaging/pathology ; Child ; Genome-Wide Association Study ; White Matter/pathology/diagnostic imaging ; Cohort Studies ; },
abstract = {INTRODUCTION: Polygenic risk scores (PRSs) for Alzheimer's disease (AD) capture an individual's genetic susceptibility to AD. Although thoroughly studied in older populations, there exists a notable gap in comprehensively exploring the association of AD PRS with early brain development.
METHODS: We examined longitudinal brain magnetic resonance imaging (MRI) data from 348 typically developing children in the RESONANCE cohort. Proportional cerebrospinal fluid (pCSF), white matter (pWM), and gray matter (pGM) volumes were analyzed using functional concurrent regression and Riemannian functional principal component analysis. AD-PRS scores (AD25 and AD54) were computed using genome-wide data.
RESULTS: Higher AD PRS was significantly associated with reduced pCSF during early childhood (ages 2.5 to 5.5 years for AD54). Energy and distance-based tests revealed overall significant differences in brain volume trajectories between moderate and low AD54 risk groups.
DISCUSSION: These findings suggest that genetic risk for late-onset AD is linked to early neurodevelopmental patterns, indicating that AD vulnerability may originate during critical windows of early brain maturation.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Alzheimer Disease/genetics/pathology/diagnostic imaging
Magnetic Resonance Imaging
Male
Female
*Brain/pathology/diagnostic imaging/growth & development
Child, Preschool
*Multifactorial Inheritance/genetics
*Genetic Predisposition to Disease/genetics
Longitudinal Studies
Organ Size
Gray Matter/diagnostic imaging/pathology
Child
Genome-Wide Association Study
White Matter/pathology/diagnostic imaging
Cohort Studies
RevDate: 2026-03-21
CmpDate: 2026-03-19
Participatory-informed preference optimization (PiPrO): A reinforcement learning simulation study.
PLOS digital health, 5(3):e0001294.
Artificial intelligence (AI) has transformative potential in public health, but its impact is limited by models that implicitly prioritize a single stakeholder perspective and do not make explicit and tunable trade-offs between community and clinician endorsement. To address this gap, we introduce Participatory-informed Preference Optimization (PiPrO), a large language model embedding-based calibration framework that generates a single clinical outcome prediction while explicitly accounting for differences between community and physician interpretations of the same scenario. PiPrO takes as input two embeddings derived from a large language model representing a community-facing context and a physician-facing context. It then applies a shared lightweight feedforward predictor to produce per-stakeholder scores which are then mixed using a single global mixing weight (alpha). Alpha controls how strongly the final prediction reflects the community versus physician responses and is learned using a policy-gradient update driven by an abundant but noisy community text and a sparse and biased physician text. PiPrO reliably learned stable alpha values and a consistent reward signal. Alpha shifts systematically toward physician weighting as community feedback becomes noisier and shifts toward community weighting as physician feedback becomes more biased. Our results suggest PiPrO's potential to produce more transparent, and context-sensitive AI-driven healthcare recommendations. Future research should validate this approach using real-world community inputs to ensure generalizability and practical impact.
Additional Links: PMID-41855168
PubMed:
Citation:
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@article {pmid41855168,
year = {2026},
author = {Templin, T and Song, S and Fort, S and Sinnott-Armstrong, N},
title = {Participatory-informed preference optimization (PiPrO): A reinforcement learning simulation study.},
journal = {PLOS digital health},
volume = {5},
number = {3},
pages = {e0001294},
pmid = {41855168},
issn = {2767-3170},
abstract = {Artificial intelligence (AI) has transformative potential in public health, but its impact is limited by models that implicitly prioritize a single stakeholder perspective and do not make explicit and tunable trade-offs between community and clinician endorsement. To address this gap, we introduce Participatory-informed Preference Optimization (PiPrO), a large language model embedding-based calibration framework that generates a single clinical outcome prediction while explicitly accounting for differences between community and physician interpretations of the same scenario. PiPrO takes as input two embeddings derived from a large language model representing a community-facing context and a physician-facing context. It then applies a shared lightweight feedforward predictor to produce per-stakeholder scores which are then mixed using a single global mixing weight (alpha). Alpha controls how strongly the final prediction reflects the community versus physician responses and is learned using a policy-gradient update driven by an abundant but noisy community text and a sparse and biased physician text. PiPrO reliably learned stable alpha values and a consistent reward signal. Alpha shifts systematically toward physician weighting as community feedback becomes noisier and shifts toward community weighting as physician feedback becomes more biased. Our results suggest PiPrO's potential to produce more transparent, and context-sensitive AI-driven healthcare recommendations. Future research should validate this approach using real-world community inputs to ensure generalizability and practical impact.},
}
RevDate: 2026-03-23
CmpDate: 2026-03-23
Conditionally Site-Independent Neural Evolution of Antibody Sequences.
ArXiv.
Common deep learning approaches for antibody engineering focus on modeling the marginal distribution of sequences. By treating sequences as independent samples, however, these methods overlook affinity maturation as a rich and largely untapped source of information about the evolutionary process by which antibodies explore the underlying fitness landscape. In contrast, classical phylogenetic models explicitly represent evolutionary dynamics but lack the expressivity to capture complex epistatic interactions. We bridge this gap with CoSiNE, a continuous-time Markov chain parameterized by a deep neural network. Mathematically, we prove that CoSiNE provides a first-order approximation to the intractable sequential point mutation process, capturing epistatic effects with an error bound that is quadratic in branch length. Empirically, CoSiNE outperforms state-of-the-art language models in zero-shot variant effect prediction by explicitly disentangling selection from context-dependent somatic hypermutation. Finally, we introduce Guided Gillespie, a classifier-guided sampling scheme that steers CoSiNE at inference time, enabling efficient optimization of antibody binding affinity toward specific antigens.
Additional Links: PMID-41822160
PubMed:
Citation:
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@article {pmid41822160,
year = {2026},
author = {Lu, SZ and Vermani, A and Sanno, K and Lu, J and Matsen, FA and Jagota, M and Song, YS},
title = {Conditionally Site-Independent Neural Evolution of Antibody Sequences.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {41822160},
issn = {2331-8422},
abstract = {Common deep learning approaches for antibody engineering focus on modeling the marginal distribution of sequences. By treating sequences as independent samples, however, these methods overlook affinity maturation as a rich and largely untapped source of information about the evolutionary process by which antibodies explore the underlying fitness landscape. In contrast, classical phylogenetic models explicitly represent evolutionary dynamics but lack the expressivity to capture complex epistatic interactions. We bridge this gap with CoSiNE, a continuous-time Markov chain parameterized by a deep neural network. Mathematically, we prove that CoSiNE provides a first-order approximation to the intractable sequential point mutation process, capturing epistatic effects with an error bound that is quadratic in branch length. Empirically, CoSiNE outperforms state-of-the-art language models in zero-shot variant effect prediction by explicitly disentangling selection from context-dependent somatic hypermutation. Finally, we introduce Guided Gillespie, a classifier-guided sampling scheme that steers CoSiNE at inference time, enabling efficient optimization of antibody binding affinity toward specific antigens.},
}
RevDate: 2026-03-18
CmpDate: 2026-03-18
Real-world healthcare resource utilization and clinical outcomes among patients with relapsed/refractory multiple myeloma receiving ciltacabtagene autoleucel after four or more prior lines of therapy in inpatient versus outpatient settings.
Journal of medical economics, 29(1):871-884.
BACKGROUND: Ciltacabtagene autoleucel (cilta-cel) has demonstrated remarkable efficacy in relapsed or refractory multiple myeloma (RRMM). Outpatient (OP) administration of cilta-cel is increasingly used to improve access and reduce healthcare resource utilization (HCRU) compared to inpatient (IP) administration. We compared all-cause HCRU and clinical outcomes of IP versus OP administration of cilta-cel in patients with RRMM after ≥4 prior lines of therapy (LOT) in clinical practice.
METHODS: We identified adults receiving cilta-cel between 02/28/2022 and 06/30/2024 after ≥4 prior LOT using Komodo Research Database claims data and classified patients into cohorts by setting of administration (IP/OP). All-cause HCRU, treatment-free interval (TFI), overall survival (OS), and clinical events (e.g. cytokine release syndrome [CRS], immune effector cell-associated neurotoxicity syndrome [ICANS]) were assessed. Outcomes were compared using multivariate regression and reported as incidence rate ratios (IRR) with 95% confidence intervals (CI).
RESULTS: Among 242 patients, 148 (61.2%) received cilta-cel in IP and 94 (38.8%) in OP. Baseline characteristics were comparable between cohorts. Of patients in the OP cohort, 31.9% did not require an IP admission within 3 months post-infusion. During this period, the OP cohort had significantly fewer IP days per-patient-per-month (2.4 vs. 6.6; IRR [95% CI]: 0.37 [0.28; 0.48], p < 0.001) and more OP days (8.5 vs 5.4; IRR [95% CI]: 1.43 [1.26; 1.63], p < 0.001) than the IP cohort. From the fourth month post-infusion, no significant differences in HCRU were observed. Rates of CRS and ICANS, and long-term outcomes including 6 and 12 month TFI and OS were similar.
CONCLUSION: OP administration of cilta-cel yielded similar effectiveness and safety outcomes relative to IP administration, while significantly reducing IP resource use. These findings support the feasibility of OP administration of cilta-cel in treating RRMM patients and its potential to reduce the burden on the healthcare system.
Additional Links: PMID-41848013
Publisher:
PubMed:
Citation:
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@article {pmid41848013,
year = {2026},
author = {Janakiram, M and Fan, L and Ghosh, S and Alegria, V and Perciavalle, M and Emond, B and Maitland, J and Bixby, T and Nagar, SP and Qureshi, ZP and Dima, D},
title = {Real-world healthcare resource utilization and clinical outcomes among patients with relapsed/refractory multiple myeloma receiving ciltacabtagene autoleucel after four or more prior lines of therapy in inpatient versus outpatient settings.},
journal = {Journal of medical economics},
volume = {29},
number = {1},
pages = {871-884},
doi = {10.1080/13696998.2026.2640811},
pmid = {41848013},
issn = {1941-837X},
mesh = {Humans ; Male ; *Multiple Myeloma/drug therapy/therapy ; Female ; Middle Aged ; Aged ; *Patient Acceptance of Health Care/statistics & numerical data ; Adult ; Retrospective Studies ; *Immunotherapy, Adoptive/methods ; *Health Resources/statistics & numerical data/economics ; },
abstract = {BACKGROUND: Ciltacabtagene autoleucel (cilta-cel) has demonstrated remarkable efficacy in relapsed or refractory multiple myeloma (RRMM). Outpatient (OP) administration of cilta-cel is increasingly used to improve access and reduce healthcare resource utilization (HCRU) compared to inpatient (IP) administration. We compared all-cause HCRU and clinical outcomes of IP versus OP administration of cilta-cel in patients with RRMM after ≥4 prior lines of therapy (LOT) in clinical practice.
METHODS: We identified adults receiving cilta-cel between 02/28/2022 and 06/30/2024 after ≥4 prior LOT using Komodo Research Database claims data and classified patients into cohorts by setting of administration (IP/OP). All-cause HCRU, treatment-free interval (TFI), overall survival (OS), and clinical events (e.g. cytokine release syndrome [CRS], immune effector cell-associated neurotoxicity syndrome [ICANS]) were assessed. Outcomes were compared using multivariate regression and reported as incidence rate ratios (IRR) with 95% confidence intervals (CI).
RESULTS: Among 242 patients, 148 (61.2%) received cilta-cel in IP and 94 (38.8%) in OP. Baseline characteristics were comparable between cohorts. Of patients in the OP cohort, 31.9% did not require an IP admission within 3 months post-infusion. During this period, the OP cohort had significantly fewer IP days per-patient-per-month (2.4 vs. 6.6; IRR [95% CI]: 0.37 [0.28; 0.48], p < 0.001) and more OP days (8.5 vs 5.4; IRR [95% CI]: 1.43 [1.26; 1.63], p < 0.001) than the IP cohort. From the fourth month post-infusion, no significant differences in HCRU were observed. Rates of CRS and ICANS, and long-term outcomes including 6 and 12 month TFI and OS were similar.
CONCLUSION: OP administration of cilta-cel yielded similar effectiveness and safety outcomes relative to IP administration, while significantly reducing IP resource use. These findings support the feasibility of OP administration of cilta-cel in treating RRMM patients and its potential to reduce the burden on the healthcare system.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
Male
*Multiple Myeloma/drug therapy/therapy
Female
Middle Aged
Aged
*Patient Acceptance of Health Care/statistics & numerical data
Adult
Retrospective Studies
*Immunotherapy, Adoptive/methods
*Health Resources/statistics & numerical data/economics
RevDate: 2026-03-21
CmpDate: 2026-03-18
Vector Encoding of Phylogenetic Trees by Ordered Leaf Attachment.
Bulletin of mathematical biology, 88(4):.
As part of work to connect phylogenetics with machine learning, there has been considerable recent interest in vector encodings of phylogenetic trees. We present a simple new "ordered leaf attachment" (OLA) method for uniquely encoding a binary, rooted phylogenetic tree topology as an integer vector. OLA encoding and decoding take linear time in the number of leaf nodes, and the set of vectors corresponding to trees is a simply-described subset of integer sequences. The OLA encoding is unique compared to other existing encodings in having these properties. The integer vector encoding induces a distance on the set of trees, and we investigate this distance in relation to the NNI and SPR distances.
Additional Links: PMID-41848929
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@article {pmid41848929,
year = {2026},
author = {Richman, DH and Zhang, C and Matsen, FA},
title = {Vector Encoding of Phylogenetic Trees by Ordered Leaf Attachment.},
journal = {Bulletin of mathematical biology},
volume = {88},
number = {4},
pages = {},
pmid = {41848929},
issn = {1522-9602},
support = {AI162611/NH/NIH HHS/United States ; S10OD028685//Office of Research Infrastructure Programs, National Institutes of Health/ ; },
mesh = {*Phylogeny ; Mathematical Concepts ; *Models, Genetic ; Computational Biology ; Machine Learning ; Algorithms ; },
abstract = {As part of work to connect phylogenetics with machine learning, there has been considerable recent interest in vector encodings of phylogenetic trees. We present a simple new "ordered leaf attachment" (OLA) method for uniquely encoding a binary, rooted phylogenetic tree topology as an integer vector. OLA encoding and decoding take linear time in the number of leaf nodes, and the set of vectors corresponding to trees is a simply-described subset of integer sequences. The OLA encoding is unique compared to other existing encodings in having these properties. The integer vector encoding induces a distance on the set of trees, and we investigate this distance in relation to the NNI and SPR distances.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Phylogeny
Mathematical Concepts
*Models, Genetic
Computational Biology
Machine Learning
Algorithms
RevDate: 2026-03-18
Cocoa flavanol supplementation and prevention of cardiovascular disease: a novel analysis of the COSMOS randomized trial using "win ratio".
European journal of epidemiology [Epub ahead of print].
Cocoa flavanols may reduce cardiovascular disease (CVD) risk, yet large randomized trials remain inconclusive. The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) suggested a modest, nonsignificant benefit using Cox models, which do not account for event severity in composite outcomes. To address this, we applied generalized pairwise comparison (GPC), or "win ratio" (WR), to assess cocoa flavanols versus placebo on hierarchical CVD outcomes among healthy older US adults. This secondary analysis of COSMOS, a randomized, placebo-controlled, 2 × 2 factorial trial of cocoa extract and multivitamins for preventing CVD and cancer, included 21,442 adults (women ≥ 65, men ≥ 60 years) followed for a median of 3.6 years. The primary outcome was a hierarchical composite of total CVD, prioritizing: fatal CVD, non-fatal myocardial infarction (MI), non-fatal stroke, coronary revascularization, carotid surgery, peripheral artery surgery, and hospitalized unstable angina. Analyses followed the intention-to-treat principle. GPC estimated WRs and net treatment benefits (NTBs) for cocoa flavanols versus placebo. GPC analyses showed cocoa flavanol wins of 3.41% and placebo wins of 2.87%, yielding a reciprocal WR of 0.84 (95% CI 0.72-0.99) and negative NTBs of - 0.54% (- 1.04 to - 0.03), p = 0.037. Sensitivity analyses prioritizing stroke over MI produced similar findings. By contrast, Cox regression of the same composite yielded a nonsignificant hazard ratio of 0.90 (95% CI 0.79-1.03), suggesting standard time-to-first-event models underestimated benefit. GPC "WR" analyses showed cocoa flavanols significantly reduced CVD events by accounting for event severity in the composite CVD outcome, whereas Cox regression marginally missed these effects.
Additional Links: PMID-41849087
PubMed:
Citation:
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@article {pmid41849087,
year = {2026},
author = {Ogata, S and Manson, JE and Rist, PM and Hamaya, R and Aragaki, AK and Allison, M and Haring, B and Martin, LW and Nishimura, K and Clar, A and Sesso, HD and , },
title = {Cocoa flavanol supplementation and prevention of cardiovascular disease: a novel analysis of the COSMOS randomized trial using "win ratio".},
journal = {European journal of epidemiology},
volume = {},
number = {},
pages = {},
pmid = {41849087},
issn = {1573-7284},
support = {AG050657//National Institutes of Health, Bethesda/ ; AG071611//National Institutes of Health, Bethesda/ ; EY025623//National Institutes of Health, Bethesda/ ; HL157665//National Institutes of Health, Bethesda/ ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; JP22K17821//JSPS KAKENHI/ ; 25K02863//JSPS KAKENHI/ ; },
abstract = {Cocoa flavanols may reduce cardiovascular disease (CVD) risk, yet large randomized trials remain inconclusive. The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) suggested a modest, nonsignificant benefit using Cox models, which do not account for event severity in composite outcomes. To address this, we applied generalized pairwise comparison (GPC), or "win ratio" (WR), to assess cocoa flavanols versus placebo on hierarchical CVD outcomes among healthy older US adults. This secondary analysis of COSMOS, a randomized, placebo-controlled, 2 × 2 factorial trial of cocoa extract and multivitamins for preventing CVD and cancer, included 21,442 adults (women ≥ 65, men ≥ 60 years) followed for a median of 3.6 years. The primary outcome was a hierarchical composite of total CVD, prioritizing: fatal CVD, non-fatal myocardial infarction (MI), non-fatal stroke, coronary revascularization, carotid surgery, peripheral artery surgery, and hospitalized unstable angina. Analyses followed the intention-to-treat principle. GPC estimated WRs and net treatment benefits (NTBs) for cocoa flavanols versus placebo. GPC analyses showed cocoa flavanol wins of 3.41% and placebo wins of 2.87%, yielding a reciprocal WR of 0.84 (95% CI 0.72-0.99) and negative NTBs of - 0.54% (- 1.04 to - 0.03), p = 0.037. Sensitivity analyses prioritizing stroke over MI produced similar findings. By contrast, Cox regression of the same composite yielded a nonsignificant hazard ratio of 0.90 (95% CI 0.79-1.03), suggesting standard time-to-first-event models underestimated benefit. GPC "WR" analyses showed cocoa flavanols significantly reduced CVD events by accounting for event severity in the composite CVD outcome, whereas Cox regression marginally missed these effects.},
}
RevDate: 2026-03-20
CmpDate: 2026-03-18
Association between vaginal washing and group B Streptococcus colonization from periconception through the first trimester of pregnancy in a cohort of Kenyan women.
PloS one, 21(3):e0344736.
INTRODUCTION: Vaginal washing has been associated with adverse reproductive health outcomes including pelvic inflammatory disease, reduced fecundability, and HIV acquisition. This analysis tested the hypothesis that vaginal washing is associated with increased risk of group B streptococcus (GBS) colonization.
METHOD: Women planning pregnancies contributed monthly visits during which vaginal fluid specimens were collected and urine pregnancy testing was performed. In women who became pregnant, additional samples were collected at 9-12 weeks gestation. Broad-range 16S rRNA gene PCR with next generation sequencing (NGS) was performed to identify vaginal bacterial species. Generalized estimating equations with a log link, Poisson family, independent correlation structure and robust errors were used to generate prevalence ratios comparing the prevalence of GBS detection at vaginal washing visits versus non-vaginal washing visits.
RESULTS: The 189 women who became pregnant contributed 506 samples used in this analysis. Samples were collected at periconception 196 (38.9%), early first trimester 151 (29.8%), and late first trimester visits 159 (31.4%). The prevalence of GBS during the three time periods was 20/196 (10.2%), 11/151 (7.3%) and 2/159 (1.3%) respectively. Vaginal washing was practiced by 51/196 (26.0%), 27/151 (17.9%) and 32/159 (20.1%) participants during the three time periods. Compared to visits with no vaginal washing, there was no increased prevalence of GBS detection at visits where vaginal washing with water was reported (prevalence ratio [PR] 0.51, 95% confidence interval [CI] 0.16-1.62). However, the prevalence of GBS detection was nearly five-fold higher at visits when vaginal washing using water and soap was reported (PR 4.66, 95% CI 1.51, 14.33).
CONCLUSION: Vaginal washing with soap and water was associated with a nearly five-fold increase in GBS prevalence. Future studies should evaluate this association in later pregnancy and peripartum. Cessation or modification of vaginal washing practices could be a useful strategy for decreasing GBS colonization.
Additional Links: PMID-41849329
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Citation:
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@article {pmid41849329,
year = {2026},
author = {Jisuvei, CS and Kinuthia, J and Richardson, BA and Srinivasan, S and Lokken, EM and Mandaliya, K and Jaoko, W and Munch, M and Fiedler, TL and Fredricks, DN and McClelland, RS},
title = {Association between vaginal washing and group B Streptococcus colonization from periconception through the first trimester of pregnancy in a cohort of Kenyan women.},
journal = {PloS one},
volume = {21},
number = {3},
pages = {e0344736},
pmid = {41849329},
issn = {1932-6203},
mesh = {Humans ; Female ; Pregnancy ; Adult ; Kenya/epidemiology ; *Streptococcus agalactiae/isolation & purification/genetics ; Pregnancy Trimester, First ; *Streptococcal Infections/epidemiology/microbiology ; *Vagina/microbiology ; Young Adult ; *Vaginal Douching/adverse effects ; *Pregnancy Complications, Infectious/epidemiology/microbiology ; Prevalence ; Cohort Studies ; RNA, Ribosomal, 16S/genetics ; },
abstract = {INTRODUCTION: Vaginal washing has been associated with adverse reproductive health outcomes including pelvic inflammatory disease, reduced fecundability, and HIV acquisition. This analysis tested the hypothesis that vaginal washing is associated with increased risk of group B streptococcus (GBS) colonization.
METHOD: Women planning pregnancies contributed monthly visits during which vaginal fluid specimens were collected and urine pregnancy testing was performed. In women who became pregnant, additional samples were collected at 9-12 weeks gestation. Broad-range 16S rRNA gene PCR with next generation sequencing (NGS) was performed to identify vaginal bacterial species. Generalized estimating equations with a log link, Poisson family, independent correlation structure and robust errors were used to generate prevalence ratios comparing the prevalence of GBS detection at vaginal washing visits versus non-vaginal washing visits.
RESULTS: The 189 women who became pregnant contributed 506 samples used in this analysis. Samples were collected at periconception 196 (38.9%), early first trimester 151 (29.8%), and late first trimester visits 159 (31.4%). The prevalence of GBS during the three time periods was 20/196 (10.2%), 11/151 (7.3%) and 2/159 (1.3%) respectively. Vaginal washing was practiced by 51/196 (26.0%), 27/151 (17.9%) and 32/159 (20.1%) participants during the three time periods. Compared to visits with no vaginal washing, there was no increased prevalence of GBS detection at visits where vaginal washing with water was reported (prevalence ratio [PR] 0.51, 95% confidence interval [CI] 0.16-1.62). However, the prevalence of GBS detection was nearly five-fold higher at visits when vaginal washing using water and soap was reported (PR 4.66, 95% CI 1.51, 14.33).
CONCLUSION: Vaginal washing with soap and water was associated with a nearly five-fold increase in GBS prevalence. Future studies should evaluate this association in later pregnancy and peripartum. Cessation or modification of vaginal washing practices could be a useful strategy for decreasing GBS colonization.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
Female
Pregnancy
Adult
Kenya/epidemiology
*Streptococcus agalactiae/isolation & purification/genetics
Pregnancy Trimester, First
*Streptococcal Infections/epidemiology/microbiology
*Vagina/microbiology
Young Adult
*Vaginal Douching/adverse effects
*Pregnancy Complications, Infectious/epidemiology/microbiology
Prevalence
Cohort Studies
RNA, Ribosomal, 16S/genetics
RevDate: 2026-03-18
Clinical guideline for the diagnosis and treatment of fibrolamellar carcinoma.
Hepatology (Baltimore, Md.) [Epub ahead of print].
Additional Links: PMID-41849750
PubMed:
Citation:
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@article {pmid41849750,
year = {2026},
author = {O'Neill, AF and Zeme, EL and Abou-Alfa, GK and Baretti, M and Bondoc, AJ and Church, A and Ferrone, CR and Fitzgerald, M and Geller, JI and Gill, AE and Harris, WP and Kim, HB and Lee, SS and Liu, KX and Ortiz, MV and Rangaswami, A and Riehle, KJ and Rosenberg, AR and Torbenson, MS and Yarchoan, M and Gordan, JD},
title = {Clinical guideline for the diagnosis and treatment of fibrolamellar carcinoma.},
journal = {Hepatology (Baltimore, Md.)},
volume = {},
number = {},
pages = {},
pmid = {41849750},
issn = {1527-3350},
}
RevDate: 2026-03-18
Off-target reactivity in clinical monoclonal antibodies.
Structure (London, England : 1993) pii:S0969-2126(26)00054-7 [Epub ahead of print].
Biologics, including monoclonal antibodies (mAbs), are widely used therapeutics due to their high specificity, yet off-target interactions remain an underappreciated risk for safety and efficacy. To systematically assess antibody specificity, we applied rapid extracellular antigen profiling (REAP) to evaluate 174 FDA-approved and clinical-stage antibodies against 6,172 human extracellular proteins. We found a substantial burden of off-target reactivity, with 28% of antibodies exhibiting at least one off-target hit. Structural and biophysical analyses revealed that off-target binding arises from antibody intrinsic properties and epitope mimicry, either within related protein families or across structurally unrelated proteins. We further identified new off-target interactions of tanezumab and engineered its variable domains to eliminate off-target binding while preserving target affinity and developability. These findings highlight the prevalence of specific off-target reactivity in therapeutic antibodies and underscore the importance of evaluating specificity early in biologic drug development.
Additional Links: PMID-41850278
Publisher:
PubMed:
Citation:
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@article {pmid41850278,
year = {2026},
author = {Dai, Y and Brouillard, J and Jaycox, JR and Yeon, SM and Huck, JD and Yandamuri, SS and Zhong, Z and O'Connor, KC and Burnina, I and Henkel, C and LeMay, AK and Lilov, A and McGurk, E and Morrill, M and Parker, L and Sackett, T and Sandberg, C and Sivasubramanian, A and Geoghegan, JC and Ring, AM},
title = {Off-target reactivity in clinical monoclonal antibodies.},
journal = {Structure (London, England : 1993)},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.str.2026.02.012},
pmid = {41850278},
issn = {1878-4186},
abstract = {Biologics, including monoclonal antibodies (mAbs), are widely used therapeutics due to their high specificity, yet off-target interactions remain an underappreciated risk for safety and efficacy. To systematically assess antibody specificity, we applied rapid extracellular antigen profiling (REAP) to evaluate 174 FDA-approved and clinical-stage antibodies against 6,172 human extracellular proteins. We found a substantial burden of off-target reactivity, with 28% of antibodies exhibiting at least one off-target hit. Structural and biophysical analyses revealed that off-target binding arises from antibody intrinsic properties and epitope mimicry, either within related protein families or across structurally unrelated proteins. We further identified new off-target interactions of tanezumab and engineered its variable domains to eliminate off-target binding while preserving target affinity and developability. These findings highlight the prevalence of specific off-target reactivity in therapeutic antibodies and underscore the importance of evaluating specificity early in biologic drug development.},
}
RevDate: 2026-03-17
CmpDate: 2026-03-17
Characterizing the informativeness of pathogen genome sequence datasets about transmission between population groups.
Proceedings. Biological sciences, 293(2067):.
Pathogen genome analysis helps characterize transmission between population groups. The information carried by pathogen sequences comes from the accumulation of mutations within their genomes; thus, the pace at which mutations accumulate should determine the granularity of transmission processes that pathogen sequences can characterize. Here, we investigate how the complex interplay between mutation, transmission, population mixing and sampling impacts study power. First, we develop a conceptual probabilistic framework to quantify the ability of pairs of sequences in capturing between-group transmission history. This allows us to comprehensively explore the space of possible phylogeographic analyses by explicitly considering the pace at which mutations accumulate and the pace at which between-group transmission events occur. Using this framework, we identify a pathogen-intrinsic limit in the mixing scale at which their sequence data remain informative, with faster mutating pathogens enabling finer spatial characterization. Second, we perform a simulation study exploring a range of assumptions regarding sequencing intensity. The sample size further imposes a limit on the characterization of between-group transmission processes. This work highlights inherent horizons of resolvability for population mixing processes that depend on the interaction between evolution, transmission, mixing and sampling. Such considerations are important for the design of pathogen genomic studies.
Additional Links: PMID-41844245
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PubMed:
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@article {pmid41844245,
year = {2026},
author = {Tran-Kiem, C and Perofsky, AC and Lessler, J and Bedford, T},
title = {Characterizing the informativeness of pathogen genome sequence datasets about transmission between population groups.},
journal = {Proceedings. Biological sciences},
volume = {293},
number = {2067},
pages = {},
doi = {10.1098/rspb.2025.2983},
pmid = {41844245},
issn = {1471-2954},
support = {/TW/FIC NIH HHS/United States ; //EPSRC/ ; /CC/CDC HHS/United States ; /GATES/Gates Foundation/United States ; /HHMI/Howard Hughes Medical Institute/United States ; //National Institute of General Medical Sciences (NIH)/ ; },
mesh = {Mutation ; Phylogeography ; },
abstract = {Pathogen genome analysis helps characterize transmission between population groups. The information carried by pathogen sequences comes from the accumulation of mutations within their genomes; thus, the pace at which mutations accumulate should determine the granularity of transmission processes that pathogen sequences can characterize. Here, we investigate how the complex interplay between mutation, transmission, population mixing and sampling impacts study power. First, we develop a conceptual probabilistic framework to quantify the ability of pairs of sequences in capturing between-group transmission history. This allows us to comprehensively explore the space of possible phylogeographic analyses by explicitly considering the pace at which mutations accumulate and the pace at which between-group transmission events occur. Using this framework, we identify a pathogen-intrinsic limit in the mixing scale at which their sequence data remain informative, with faster mutating pathogens enabling finer spatial characterization. Second, we perform a simulation study exploring a range of assumptions regarding sequencing intensity. The sample size further imposes a limit on the characterization of between-group transmission processes. This work highlights inherent horizons of resolvability for population mixing processes that depend on the interaction between evolution, transmission, mixing and sampling. Such considerations are important for the design of pathogen genomic studies.},
}
MeSH Terms:
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Mutation
Phylogeography
RevDate: 2026-03-18
Phase 2 Study of Azacitidine plus Pembrolizumab as Second-Line Treatment in Patients with Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma.
The oncologist pii:8527013 [Epub ahead of print].
BACKGROUND: Epigenetic regulators represent a novel strategy to modulate the tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC). In preclinical models, DNA hypomethylating agents enhance cytotoxic T-cell infiltration, synergize with PD-1 blockade, and improve survival when combined with immune checkpoint blockade. This single-institution, phase II study evaluated the safety, efficacy, and biomarkers of azacitidine plus pembrolizumab in patients with previously treated PDAC.
METHODS: Patients with locally advanced or metastatic PDAC after one prior regimen received 50 mg/m2 subcutaneous azacitidine on days 1-5 of a 28-day cycle, starting week 1, and pembrolizumab 200 mg intravenously every 3 weeks starting week 3. Baseline and on-treatment blood and tumor was collected for exploratory biomarker analysis.
RESULTS: Thirty-six patients enrolled between October 2017 and September 2021 (median age: 62.5 years); 34 were evaluable for safety; 31 for efficacy. Treatment was generally well-tolerated, with Grade 1-2 fatigue and diarrhea most common AEs. Three patients (9.7%) had a partial response, and the disease control rate was 35.5%. Median progression-free and overall survival was 1.51 and 4.83 months, respectively. Exploratory analysis suggested higher baseline CD8+ T cells and lower tumor Ki-67 was associated with response, whereas low baseline CD8+ T cell and Granzyme B infiltration correlated with higher exponential tumor growth rate. PD-L1 and CD68 expression were not predictive of benefit.
CONCLUSION: Azacitidine plus pembrolizumab demonstrated limited clinical activity in second line, locally advanced or metastatic PDAC. Biomarker analysis suggests higher baseline CD8+ T-cell infiltration and lower proliferative index may identify patients more likely to benefit. (NCT03264404).
Additional Links: PMID-41844546
Publisher:
PubMed:
Citation:
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@article {pmid41844546,
year = {2026},
author = {Safyan, RA and White, RA and Gonda, TA and Lee, SM and Han, J and Kuriakose, N and Yamamoto, NK and Kugel, S and Jamison, JK and Manji, GA and Schwartz, GJ and Oberstein, PE and Bates, SE},
title = {Phase 2 Study of Azacitidine plus Pembrolizumab as Second-Line Treatment in Patients with Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma.},
journal = {The oncologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/oncolo/oyag091},
pmid = {41844546},
issn = {1549-490X},
abstract = {BACKGROUND: Epigenetic regulators represent a novel strategy to modulate the tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC). In preclinical models, DNA hypomethylating agents enhance cytotoxic T-cell infiltration, synergize with PD-1 blockade, and improve survival when combined with immune checkpoint blockade. This single-institution, phase II study evaluated the safety, efficacy, and biomarkers of azacitidine plus pembrolizumab in patients with previously treated PDAC.
METHODS: Patients with locally advanced or metastatic PDAC after one prior regimen received 50 mg/m2 subcutaneous azacitidine on days 1-5 of a 28-day cycle, starting week 1, and pembrolizumab 200 mg intravenously every 3 weeks starting week 3. Baseline and on-treatment blood and tumor was collected for exploratory biomarker analysis.
RESULTS: Thirty-six patients enrolled between October 2017 and September 2021 (median age: 62.5 years); 34 were evaluable for safety; 31 for efficacy. Treatment was generally well-tolerated, with Grade 1-2 fatigue and diarrhea most common AEs. Three patients (9.7%) had a partial response, and the disease control rate was 35.5%. Median progression-free and overall survival was 1.51 and 4.83 months, respectively. Exploratory analysis suggested higher baseline CD8+ T cells and lower tumor Ki-67 was associated with response, whereas low baseline CD8+ T cell and Granzyme B infiltration correlated with higher exponential tumor growth rate. PD-L1 and CD68 expression were not predictive of benefit.
CONCLUSION: Azacitidine plus pembrolizumab demonstrated limited clinical activity in second line, locally advanced or metastatic PDAC. Biomarker analysis suggests higher baseline CD8+ T-cell infiltration and lower proliferative index may identify patients more likely to benefit. (NCT03264404).},
}
RevDate: 2026-03-18
Comparable immunogenicity from murine blood collection methods in intranasal gonococcal vaccination with ACP and MtrE supports refinement of preclinical vaccine studies.
Scientific reports pii:10.1038/s41598-026-44505-5 [Epub ahead of print].
Additional Links: PMID-41845032
Publisher:
PubMed:
Citation:
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@article {pmid41845032,
year = {2026},
author = {Chanda, A and Song, Y and Nazir, J and Lin, C and Cheng, A and Sargent, J and Sikora, AE},
title = {Comparable immunogenicity from murine blood collection methods in intranasal gonococcal vaccination with ACP and MtrE supports refinement of preclinical vaccine studies.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-44505-5},
pmid = {41845032},
issn = {2045-2322},
support = {R01-AI117235//National Institute of Allergy and Infectious Diseases/ ; },
}
RevDate: 2026-03-18
Breaking Barriers to Completing Genetic Testing for Inherited Breast Cancer among At-Risk Black Women Using a Community-Based Participatory Research Approach.
HGG advances pii:S2666-2477(26)00031-X [Epub ahead of print].
National guidelines from the U.S. Preventive Services Task Force and the National Comprehensive Cancer Network recommend the use of family-health-history (FHH)-based risk assessment tools to guide genetic testing (GT) among women with an increased risk of inherited cancer and inform personalized cancer risk management. Prior research has focused on attitudes towards and decisions about initial uptake of GT in Black patients but little is known about the factors that impact the subsequent completion of GT after they have already provided consent. Using a community-based participatory research (CBPR) approach, we aimed to identify barriers and actionable strategies to improve GT completion offered through the Breast Health Assessment (BHA), an FHH screening tool administered at routine mammography visits. We conducted semi-structured interviews with 12 Black women who screened high-risk for inherited breast cancer and consented to GT through the BHA, but did not complete saliva sample collection. Thematic analysis revealed that lack of dedicated support throughout the BHA workflow emerged as a key obstacle to sample collection, whereas medical mistrust, shame, and limited knowledge were largely regarded as cultural barriers that had no impact on GT completion. Low utilization among participants reflected logistical challenges highlighting the need to evaluate multi-level implementation processes to better understand and address inequities in GT completion. Participants suggested implementing early educational outreach, culturally-relevant messaging, and interpersonal touchpoints to promote GT uptake. By applying a CBPR approach, we translated these findings into actionable, equity-focused strategies to improve GT completion within a population genetic screening program.
Additional Links: PMID-41846317
Publisher:
PubMed:
Citation:
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@article {pmid41846317,
year = {2026},
author = {Choi, SH and Ramesh, S and Reed, S and Menyah, G and Ganschow, P and Henderson, V and Dunnenberger, HM},
title = {Breaking Barriers to Completing Genetic Testing for Inherited Breast Cancer among At-Risk Black Women Using a Community-Based Participatory Research Approach.},
journal = {HGG advances},
volume = {},
number = {},
pages = {100591},
doi = {10.1016/j.xhgg.2026.100591},
pmid = {41846317},
issn = {2666-2477},
abstract = {National guidelines from the U.S. Preventive Services Task Force and the National Comprehensive Cancer Network recommend the use of family-health-history (FHH)-based risk assessment tools to guide genetic testing (GT) among women with an increased risk of inherited cancer and inform personalized cancer risk management. Prior research has focused on attitudes towards and decisions about initial uptake of GT in Black patients but little is known about the factors that impact the subsequent completion of GT after they have already provided consent. Using a community-based participatory research (CBPR) approach, we aimed to identify barriers and actionable strategies to improve GT completion offered through the Breast Health Assessment (BHA), an FHH screening tool administered at routine mammography visits. We conducted semi-structured interviews with 12 Black women who screened high-risk for inherited breast cancer and consented to GT through the BHA, but did not complete saliva sample collection. Thematic analysis revealed that lack of dedicated support throughout the BHA workflow emerged as a key obstacle to sample collection, whereas medical mistrust, shame, and limited knowledge were largely regarded as cultural barriers that had no impact on GT completion. Low utilization among participants reflected logistical challenges highlighting the need to evaluate multi-level implementation processes to better understand and address inequities in GT completion. Participants suggested implementing early educational outreach, culturally-relevant messaging, and interpersonal touchpoints to promote GT uptake. By applying a CBPR approach, we translated these findings into actionable, equity-focused strategies to improve GT completion within a population genetic screening program.},
}
RevDate: 2026-03-17
Preferred standard-of-care carfilzomib dosing in multiple myeloma: An international survey of haematologists/oncologists.
British journal of haematology [Epub ahead of print].
Additional Links: PMID-41841734
Publisher:
PubMed:
Citation:
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@article {pmid41841734,
year = {2026},
author = {Banerjee, R and Dong, S and McCaughan, G and Mehra, N and Wang, B and Sperling, AS and Cowan, AJ and Anderson, LD and Rajkumar, SV and Kaur, G},
title = {Preferred standard-of-care carfilzomib dosing in multiple myeloma: An international survey of haematologists/oncologists.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.70435},
pmid = {41841734},
issn = {1365-2141},
support = {UL1 TR002319/NH/NIH HHS/United States ; },
}
RevDate: 2026-03-18
CmpDate: 2026-03-16
Safety and Tolerability of Xanthohumol in Adults With Crohn's Disease: Results of a Triple-Masked, Randomized, Placebo-Controlled Phase 2 Trial.
Molecular nutrition & food research, 70(6):e70438.
Xanthohumol (XN), a flavonoid from hops (Humulus lupulus), exhibits mucosal anti-inflammatory, antioxidant, and microbiome-modulating effects, making it a candidate therapeutic for inflammatory bowel disease. We assessed the safety and tolerability of XN in adults with Crohn's disease (CD) over 8 weeks. In this randomized, triple-masked, placebo-controlled phase 2 trial, 20 adults with unremitted CD received either 24 mg/day XN or placebo for 8 weeks. Primary outcomes included clinical laboratory toxicology parameters, vital signs and adverse events (AEs). Disease activity was screened and assessed using the Crohn's Disease Activity Index (CDAI). XN was well tolerated, with adherence exceeding 95%. Neither halting nor stopping criteria were met, and all laboratory elevations were minor and transient in both groups. There were no attributable serious AEs in either group, and all moderate AEs were short-term and self-resolving. Between-group comparisons demonstrated differences for changes in BMI and gamma-glutamyltransferase (GGT), favoring XN: BMI: -0.67 (0.0, 1.3), p = 0.04 and GGT: -4.8 U/L, 95% CI 0.8-8.8, p = 0.02, which may reflect beneficial effects on hepatic and metabolic health in CD. XN at 24 mg/day was safe and well tolerated in adults with active CD, supporting further research in inflammatory bowel disease.
Additional Links: PMID-41834265
PubMed:
Citation:
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@article {pmid41834265,
year = {2026},
author = {Bradley, R and A Staab, C and E Jamieson, P and O Langley, B and O Metz, T and F Stevens, J},
title = {Safety and Tolerability of Xanthohumol in Adults With Crohn's Disease: Results of a Triple-Masked, Randomized, Placebo-Controlled Phase 2 Trial.},
journal = {Molecular nutrition & food research},
volume = {70},
number = {6},
pages = {e70438},
pmid = {41834265},
issn = {1613-4133},
support = {R01HL146549/HL/NHLBI NIH HHS/United States ; R01AT010271/AT/NCCIH NIH HHS/United States ; K24AT011568/AT/NCCIH NIH HHS/United States ; },
mesh = {Humans ; *Propiophenones/adverse effects/therapeutic use ; *Crohn Disease/drug therapy ; Adult ; Male ; Female ; *Flavonoids/adverse effects/therapeutic use ; Middle Aged ; Double-Blind Method ; Young Adult ; gamma-Glutamyltransferase/blood ; Body Mass Index ; Humulus/chemistry ; },
abstract = {Xanthohumol (XN), a flavonoid from hops (Humulus lupulus), exhibits mucosal anti-inflammatory, antioxidant, and microbiome-modulating effects, making it a candidate therapeutic for inflammatory bowel disease. We assessed the safety and tolerability of XN in adults with Crohn's disease (CD) over 8 weeks. In this randomized, triple-masked, placebo-controlled phase 2 trial, 20 adults with unremitted CD received either 24 mg/day XN or placebo for 8 weeks. Primary outcomes included clinical laboratory toxicology parameters, vital signs and adverse events (AEs). Disease activity was screened and assessed using the Crohn's Disease Activity Index (CDAI). XN was well tolerated, with adherence exceeding 95%. Neither halting nor stopping criteria were met, and all laboratory elevations were minor and transient in both groups. There were no attributable serious AEs in either group, and all moderate AEs were short-term and self-resolving. Between-group comparisons demonstrated differences for changes in BMI and gamma-glutamyltransferase (GGT), favoring XN: BMI: -0.67 (0.0, 1.3), p = 0.04 and GGT: -4.8 U/L, 95% CI 0.8-8.8, p = 0.02, which may reflect beneficial effects on hepatic and metabolic health in CD. XN at 24 mg/day was safe and well tolerated in adults with active CD, supporting further research in inflammatory bowel disease.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Propiophenones/adverse effects/therapeutic use
*Crohn Disease/drug therapy
Adult
Male
Female
*Flavonoids/adverse effects/therapeutic use
Middle Aged
Double-Blind Method
Young Adult
gamma-Glutamyltransferase/blood
Body Mass Index
Humulus/chemistry
RevDate: 2026-03-19
CmpDate: 2026-03-16
Smac mimetic combined with eCD4-Ig reverses latency without reducing SHIV reservoirs in rhesus macaques.
The Journal of clinical investigation, 136(6):.
Despite the success of antiretroviral therapy in controlling HIV replication, latent viral reservoirs persist, presenting a major barrier to a cure. Current treatment approaches that aim to reactivate latent virus and eliminate infected cells, termed "shock and kill," hold promise but have yet to demonstrate meaningful reservoir reduction in vivo. In this study, we explored combining ciapavir, a Smac mimetic latency-reversing agent, with adeno-associated virus-delivered (AAV-delivered) eCD4-Ig to treat antiretroviral therapy-suppressed, SHIV-infected rhesus macaques. We could demonstrate that a Smac mimetic can induce modest reactivation of the latent SHIV reservoir, as evidenced by transient increases in plasma viremia. However, while AAV-expressed eCD4-Ig conferred partial protection against intrarectal SHIV challenge in uninfected animals, neither eCD4-Ig nor ciapavir reduced the viral reservoir in SHIV-infected rhesus macaques, as determined by total SHIV DNA and a 5-target intact provirus detection assay. Animals treated with the combination showed no significant differences in viral rebound kinetics post-analytical treatment interruption compared with controls. Additionally, repeated ciapavir dosing resulted in adverse effects in some animals, suggesting potential toxicity with repeat administration. These findings highlight the challenges in reducing viral reservoirs using this shock-and-kill approach, particularly in SHIV-infected models, and suggest that further optimization of both latency-reversing agent and immune-mediated clearance strategies is required.
Additional Links: PMID-41837286
PubMed:
Citation:
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@article {pmid41837286,
year = {2026},
author = {Pache, L and Bui, JK and Klouser, LM and Fennessey, CM and Noyola, AC and Einhaus, T and Zhu, H and Stensland, L and Leguizamo, I and Koroma, AA and Teriete, P and Chang, WLW and Hyrien, O and Duggan, NN and Heimann, D and Pérez-Osorio, AC and Bar, KJ and Cosford, ND and Keele, BF and Hartigan-O'Connor, DJ and Farzan, M and Gardner, MR and Jerome, KR and Chanda, SK and Kiem, HP and Peterson, CW},
title = {Smac mimetic combined with eCD4-Ig reverses latency without reducing SHIV reservoirs in rhesus macaques.},
journal = {The Journal of clinical investigation},
volume = {136},
number = {6},
pages = {},
pmid = {41837286},
issn = {1558-8238},
mesh = {Animals ; Macaca mulatta ; *Simian Immunodeficiency Virus/physiology/drug effects/genetics ; *Simian Acquired Immunodeficiency Syndrome/drug therapy/virology/genetics ; *Virus Latency/drug effects ; Dependovirus/genetics ; Apoptosis Regulatory Proteins ; Viremia ; *Mitochondrial Proteins ; Humans ; },
abstract = {Despite the success of antiretroviral therapy in controlling HIV replication, latent viral reservoirs persist, presenting a major barrier to a cure. Current treatment approaches that aim to reactivate latent virus and eliminate infected cells, termed "shock and kill," hold promise but have yet to demonstrate meaningful reservoir reduction in vivo. In this study, we explored combining ciapavir, a Smac mimetic latency-reversing agent, with adeno-associated virus-delivered (AAV-delivered) eCD4-Ig to treat antiretroviral therapy-suppressed, SHIV-infected rhesus macaques. We could demonstrate that a Smac mimetic can induce modest reactivation of the latent SHIV reservoir, as evidenced by transient increases in plasma viremia. However, while AAV-expressed eCD4-Ig conferred partial protection against intrarectal SHIV challenge in uninfected animals, neither eCD4-Ig nor ciapavir reduced the viral reservoir in SHIV-infected rhesus macaques, as determined by total SHIV DNA and a 5-target intact provirus detection assay. Animals treated with the combination showed no significant differences in viral rebound kinetics post-analytical treatment interruption compared with controls. Additionally, repeated ciapavir dosing resulted in adverse effects in some animals, suggesting potential toxicity with repeat administration. These findings highlight the challenges in reducing viral reservoirs using this shock-and-kill approach, particularly in SHIV-infected models, and suggest that further optimization of both latency-reversing agent and immune-mediated clearance strategies is required.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
Macaca mulatta
*Simian Immunodeficiency Virus/physiology/drug effects/genetics
*Simian Acquired Immunodeficiency Syndrome/drug therapy/virology/genetics
*Virus Latency/drug effects
Dependovirus/genetics
Apoptosis Regulatory Proteins
Viremia
*Mitochondrial Proteins
Humans
RevDate: 2026-03-18
CmpDate: 2026-03-16
Contribution of Life-Course Socioeconomic Position to Later-Life Brain Volumes in US Hispanic/Latino Adults.
Neurology, 106(7):e214716.
BACKGROUND AND OBJECTIVES: Low life-course socioeconomic position (SEP) has been associated with worse cognitive function in older age. However, its association with brain structure remains unclear. We assessed whether SEP at 3 periods of the life-course and socioeconomic mobility are associated with later-life MRI-derived brain volumes.
METHODS: We used longitudinal data from the Hispanic Community Health Study/Study of Latinos and its Investigations of Neurocognitive Aging-MRI ancillary study. We determined childhood SEP using participant self-reports of their parent's educational attainment (
RESULTS: We included 2,400 adults aged 50-85 years. Higher childhood SEP (TGMV 0.13; 95% CI 0.02-0.24) and higher height residuals (TGMV 0.17; 95% CI 0.09-0.24) were associated with larger brain volumes. Similarly, higher adult SEP at visit 1 (TGMV 0.18; 95% CI 0.05-0.31) and visit 2 (TGMV 0.16; 95% CI 0.04-0.29), upward socioeconomic mobility, and stable high SEP were associated with larger brain volumes. Higher adult SEP at visit 2 (log-WMHV -0.16; 95% CI -0.29 to -0.02) and upward mobility were also associated with smaller log-WMHV.
DISCUSSION: This study highlights the contribution of higher life-course SEP to greater brain health as indexed by larger brain volumes in later life. Our results suggest that the effect of early-life socioeconomic disadvantages persists beyond socioeconomic conditions in adulthood.
Additional Links: PMID-41838964
PubMed:
Citation:
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@article {pmid41838964,
year = {2026},
author = {Filigrana, P and Moon, JY and Gallo, LC and González, HM and Lipton, RB and Tarraf, W and Kaplan, RC and Daviglus, ML and Testai, FD and Marquine, MJ and Cai, J and Perreira, KM and Stickel, AM and DeCarli, C and Isasi, CR},
title = {Contribution of Life-Course Socioeconomic Position to Later-Life Brain Volumes in US Hispanic/Latino Adults.},
journal = {Neurology},
volume = {106},
number = {7},
pages = {e214716},
pmid = {41838964},
issn = {1526-632X},
support = {N01 HC065236/HL/NHLBI NIH HHS/United States ; N01 HC065235/HL/NHLBI NIH HHS/United States ; RF1 AG054548/AG/NIA NIH HHS/United States ; N01 HC065234/HL/NHLBI NIH HHS/United States ; N01 HC065237/HL/NHLBI NIH HHS/United States ; R01 AG077639/AG/NIA NIH HHS/United States ; N01 HC065233/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; *Brain/diagnostic imaging/anatomy & histology ; Middle Aged ; Magnetic Resonance Imaging ; *Hispanic or Latino ; Aged ; Longitudinal Studies ; United States ; Organ Size ; *Social Class ; Aged, 80 and over ; Adult ; White ; },
abstract = {BACKGROUND AND OBJECTIVES: Low life-course socioeconomic position (SEP) has been associated with worse cognitive function in older age. However, its association with brain structure remains unclear. We assessed whether SEP at 3 periods of the life-course and socioeconomic mobility are associated with later-life MRI-derived brain volumes.
METHODS: We used longitudinal data from the Hispanic Community Health Study/Study of Latinos and its Investigations of Neurocognitive Aging-MRI ancillary study. We determined childhood SEP using participant self-reports of their parent's educational attainment (
RESULTS: We included 2,400 adults aged 50-85 years. Higher childhood SEP (TGMV 0.13; 95% CI 0.02-0.24) and higher height residuals (TGMV 0.17; 95% CI 0.09-0.24) were associated with larger brain volumes. Similarly, higher adult SEP at visit 1 (TGMV 0.18; 95% CI 0.05-0.31) and visit 2 (TGMV 0.16; 95% CI 0.04-0.29), upward socioeconomic mobility, and stable high SEP were associated with larger brain volumes. Higher adult SEP at visit 2 (log-WMHV -0.16; 95% CI -0.29 to -0.02) and upward mobility were also associated with smaller log-WMHV.
DISCUSSION: This study highlights the contribution of higher life-course SEP to greater brain health as indexed by larger brain volumes in later life. Our results suggest that the effect of early-life socioeconomic disadvantages persists beyond socioeconomic conditions in adulthood.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
Male
Female
*Brain/diagnostic imaging/anatomy & histology
Middle Aged
Magnetic Resonance Imaging
*Hispanic or Latino
Aged
Longitudinal Studies
United States
Organ Size
*Social Class
Aged, 80 and over
Adult
White
RevDate: 2026-03-17
Dynamics of phage-host interactions in Bacteroides fragilis resolved by single-cell transcriptomics.
Nature communications pii:10.1038/s41467-026-70381-8 [Epub ahead of print].
The interactions between lytic phages and their hosts are typically studied in bulk culture, which obscures cell-cell differences in infection susceptibility or expression of protective factors. Here, we use bacterial single-cell RNA sequencing to profile the transcriptomes of ~50,000 cells from cultures of a human pathobiont, Bacteroides fragilis, infected with a lytic bacteriophage. From a single sampling, we quantified the asynchronous progression of phage infection in individual bacterial cells and reconstructed the infection timeline, characterizing both host and phage transcriptomic changes as infection unfolded. Further, we discovered phenotypic subpopulations of bacteria that remained uninfected. Each cell's vulnerability to phage infection was influenced by expression of multiple genetic loci, most prominently phase-variable capsular polysaccharide (CPS) biosynthesis pathways and an operon predicted to encode fimbrial genes. These findings uncovered genome-wide phase variation and stochasticity that enable bacterial survival and re-growth without acquiring additional mutations. Overall, we establish bacterial single-cell RNA sequencing as a powerful platform for investigating the dynamics of host-phage interactions and revealing the roles of phase variation and stochasticity in bacterial defenses.
Additional Links: PMID-41839859
Publisher:
PubMed:
Citation:
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@article {pmid41839859,
year = {2026},
author = {Gupta, A and Morella, N and Sutormin, D and Li, N and Gaisser, K and Robertson, A and Ispolatov, Y and Seelig, G and Dey, N and Kuchina, A},
title = {Dynamics of phage-host interactions in Bacteroides fragilis resolved by single-cell transcriptomics.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-70381-8},
pmid = {41839859},
issn = {2041-1723},
support = {R35GM150994//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; DE-SC0023091//DOE | SC | Biological and Environmental Research (BER)/ ; DE-SC0023091//DOE | SC | Biological and Environmental Research (BER)/ ; Postdoctoral Fellowship//Washington Research Foundation (WRF)/ ; U54 CA274374/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {The interactions between lytic phages and their hosts are typically studied in bulk culture, which obscures cell-cell differences in infection susceptibility or expression of protective factors. Here, we use bacterial single-cell RNA sequencing to profile the transcriptomes of ~50,000 cells from cultures of a human pathobiont, Bacteroides fragilis, infected with a lytic bacteriophage. From a single sampling, we quantified the asynchronous progression of phage infection in individual bacterial cells and reconstructed the infection timeline, characterizing both host and phage transcriptomic changes as infection unfolded. Further, we discovered phenotypic subpopulations of bacteria that remained uninfected. Each cell's vulnerability to phage infection was influenced by expression of multiple genetic loci, most prominently phase-variable capsular polysaccharide (CPS) biosynthesis pathways and an operon predicted to encode fimbrial genes. These findings uncovered genome-wide phase variation and stochasticity that enable bacterial survival and re-growth without acquiring additional mutations. Overall, we establish bacterial single-cell RNA sequencing as a powerful platform for investigating the dynamics of host-phage interactions and revealing the roles of phase variation and stochasticity in bacterial defenses.},
}
RevDate: 2026-03-17
Chronic myeloid leukaemia: have basophils gone the way of the Dodo bird?.
Leukemia [Epub ahead of print].
Additional Links: PMID-41840226
PubMed:
Citation:
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@article {pmid41840226,
year = {2026},
author = {Turcsanyi, L and Zhang, XS and Kudelka, M and Kubikova, K and Radvansky, M and Yang, S and Kriegova, E and Juranova, J and Mayer, J and Klamova, H and Belohlavkova, P and Karas, M and Stejskal, L and Cmunt, E and Othus, M and Gale, RP and Jiang, Q and Faber, E},
title = {Chronic myeloid leukaemia: have basophils gone the way of the Dodo bird?.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {41840226},
issn = {1476-5551},
support = {IGA_LF_2025_014//Univerzita Palackého v Olomouci (Palacký University Olomouc)/ ; IGA_LF_2025_14//Univerzita Palackého v Olomouci (Palacký University Olomouc)/ ; IGA_LF_2025_05//Univerzita Palackého v Olomouci (Palacký University Olomouc)/ ; IGA_LF_2025_014//Univerzita Palackého v Olomouci (Palacký University Olomouc)/ ; MH CZ - DRO (FNOL, 00098892)//Ministerstvo Zdravotnictví Ceské Republiky (Ministry of Health of the Czech Republic)/ ; MH CZ - DRO (FNOL, 00098892)//Ministerstvo Zdravotnictví Ceské Republiky (Ministry of Health of the Czech Republic)/ ; MH CZ-DRO (FNOL 00098892)//Ministerstvo Zdravotnictví Ceské Republiky (Ministry of Health of the Czech Republic)/ ; MH CZ (FNOL, 00098892)//Ministerstvo Zdravotnictví Ceské Republiky (Ministry of Health of the Czech Republic)/ ; },
}
RevDate: 2026-03-18
CmpDate: 2026-03-14
Longitudinal Detection of Tumor-Specific Peptides in Cerebrospinal Fluid for Pediatric Brain Tumor Surveillance.
Cells, 15(5):.
Pediatric brain tumor survivors remain at high risk of recurrence, yet current surveillance strategies relying on neuroimaging and cerebrospinal fluid (CSF) cytology have limited sensitivity for early or minimal disease. Tumor-specific peptides (TSPs) derived from individual tumors represent a promising class of highly specific biomarkers for longitudinal disease monitoring through CSF-based proteomic analysis. In this study, tumor tissue and serial CSF samples from six pediatric brain tumor patients (five medulloblastomas and one atypical teratoid/rhabdoid tumor (ATRT)) were analyzed using an integrated proteogenomic workflow combining discovery and targeted mass spectrometry. TSPs were identified from resected tumor tissue and matched against shotgun CSF proteomic datasets to nominate candidate biomarkers. High-confidence peptides were synthesized as isotopically labeled standards and quantified longitudinally using targeted multiple reaction monitoring. Two TSP biomarkers derived from individualized pediatric brain tumors (one medulloblastoma and one ATRT) demonstrated robust detection in serial CSF samples and exhibited temporal concordance with radiographic disease course, declining with treatment response and increasing during disease progression. These findings establish the feasibility of detecting and longitudinally quantifying TSPs in CSF and support further investigation of individualized proteomic biomarkers for treatment response monitoring and disease surveillance in pediatric brain tumors.
Additional Links: PMID-41827907
PubMed:
Citation:
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@article {pmid41827907,
year = {2026},
author = {Chesney, KM and Whiteaker, JR and Hood, B and Zhou, M and Zhang, H and Rivero-Hinojosa, S and Paulovich, AG and Conrads, TP and Rood, BR},
title = {Longitudinal Detection of Tumor-Specific Peptides in Cerebrospinal Fluid for Pediatric Brain Tumor Surveillance.},
journal = {Cells},
volume = {15},
number = {5},
pages = {},
pmid = {41827907},
issn = {2073-4409},
support = {R50 CA211499/CA/NCI NIH HHS/United States ; U01 CA271407/CA/NCI NIH HHS/United States ; 44844//Lilabean/ ; 44568//Jeff Gordon/ ; },
mesh = {Humans ; *Brain Neoplasms/cerebrospinal fluid/diagnosis ; Child ; Male ; *Peptides/cerebrospinal fluid ; Female ; *Biomarkers, Tumor/cerebrospinal fluid ; Child, Preschool ; Medulloblastoma/cerebrospinal fluid ; Proteomics/methods ; Longitudinal Studies ; Adolescent ; Infant ; },
abstract = {Pediatric brain tumor survivors remain at high risk of recurrence, yet current surveillance strategies relying on neuroimaging and cerebrospinal fluid (CSF) cytology have limited sensitivity for early or minimal disease. Tumor-specific peptides (TSPs) derived from individual tumors represent a promising class of highly specific biomarkers for longitudinal disease monitoring through CSF-based proteomic analysis. In this study, tumor tissue and serial CSF samples from six pediatric brain tumor patients (five medulloblastomas and one atypical teratoid/rhabdoid tumor (ATRT)) were analyzed using an integrated proteogenomic workflow combining discovery and targeted mass spectrometry. TSPs were identified from resected tumor tissue and matched against shotgun CSF proteomic datasets to nominate candidate biomarkers. High-confidence peptides were synthesized as isotopically labeled standards and quantified longitudinally using targeted multiple reaction monitoring. Two TSP biomarkers derived from individualized pediatric brain tumors (one medulloblastoma and one ATRT) demonstrated robust detection in serial CSF samples and exhibited temporal concordance with radiographic disease course, declining with treatment response and increasing during disease progression. These findings establish the feasibility of detecting and longitudinally quantifying TSPs in CSF and support further investigation of individualized proteomic biomarkers for treatment response monitoring and disease surveillance in pediatric brain tumors.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Brain Neoplasms/cerebrospinal fluid/diagnosis
Child
Male
*Peptides/cerebrospinal fluid
Female
*Biomarkers, Tumor/cerebrospinal fluid
Child, Preschool
Medulloblastoma/cerebrospinal fluid
Proteomics/methods
Longitudinal Studies
Adolescent
Infant
RevDate: 2026-03-16
CmpDate: 2026-03-14
Characterization and Evaluation of CD24 and NPY as Biomarkers for Metastatic Castration-Resistant Prostate Cancer.
Diagnostics (Basel, Switzerland), 16(5):.
Background/Objectives: Prostate cancer is the most diagnosed and third most deadly cancer among men in Europe. Metastatic castration-resistant prostate cancer (mCRPC) is incurable and resistant to standard androgen ablation therapy. More biomarkers are needed to select patients for novel personalized treatments. Previous whole-genome RNA sequencing results indicated a possible role for cluster of differentiation 24 (CD24) and neuropeptide Y (NPY) as diagnostic or prognostic biomarkers in androgen receptor-positive (AR[+]) mCRPC. Methods: We analyzed tissue microarrays representing 127 primary prostate cancers (with matched adjacent benign prostatic glands) and 124 metastases (from 34 patients) using immunohistochemistry to detect CD24 or NPY. Results: CD24 was more highly expressed in primary prostate cancer than in adjacent benign tissue for nuclear (p: <0.001), cytoplasmic (p: <0.001), and membranous staining (p: <0.001), while NPY showed no difference. Average NPY scores were lower in prostate cancers that later recurred (geometric mean 17.6, 95% CI: 9.5-32.5) compared to those that did not (38.7, CI: 23.2-64.4; p: 0.044, d: 0.773). In mCRPC, CD24 was detectable in 76% of cores at the cell membrane and in 58% in the nucleus. NPY was detectable in the cytoplasm of 17%. Scores for NPY and nuclear (but not membranous) CD24 were higher in AR[+] mCRPC. In the RNA sequencing results, CD24 did not correlate with AR or kallikrein-related peptidase 3 (KLK3), while NPY positively correlated with AR (rs: 0.313; p: <0.004) and KLK3 (rs: 0.400; p: <0.004). NPY and CD24 scores did not correlate with neuroendocrine mCRPC markers. Nuclear and membranous CD24 showed differential expression by metastatic site. Conclusions: We did not find strong evidence to support the use of CD24 or NPY alone as clinical biomarkers. Membranous and nuclear CD24 were expressed in the majority of mCRPC specimens, while NPY expression was more limited. NPY and nuclear CD24 were more highly expressed in AR[+] mCRPC than AR[-] neuroendocrine disease, and nuclear CD24 displayed site-specific expression, suggesting a potential role for nuclear CD24 in promoting AR[+] mCRPC.
Additional Links: PMID-41827933
PubMed:
Citation:
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@article {pmid41827933,
year = {2026},
author = {McHenry, PR and Fakhruddin, N and Homer, K and Gil da Costa, RM and True, LD and Morrissey, C},
title = {Characterization and Evaluation of CD24 and NPY as Biomarkers for Metastatic Castration-Resistant Prostate Cancer.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {5},
pages = {},
pmid = {41827933},
issn = {2075-4418},
support = {PO1CA163227/GF/NIH HHS/United States ; },
abstract = {Background/Objectives: Prostate cancer is the most diagnosed and third most deadly cancer among men in Europe. Metastatic castration-resistant prostate cancer (mCRPC) is incurable and resistant to standard androgen ablation therapy. More biomarkers are needed to select patients for novel personalized treatments. Previous whole-genome RNA sequencing results indicated a possible role for cluster of differentiation 24 (CD24) and neuropeptide Y (NPY) as diagnostic or prognostic biomarkers in androgen receptor-positive (AR[+]) mCRPC. Methods: We analyzed tissue microarrays representing 127 primary prostate cancers (with matched adjacent benign prostatic glands) and 124 metastases (from 34 patients) using immunohistochemistry to detect CD24 or NPY. Results: CD24 was more highly expressed in primary prostate cancer than in adjacent benign tissue for nuclear (p: <0.001), cytoplasmic (p: <0.001), and membranous staining (p: <0.001), while NPY showed no difference. Average NPY scores were lower in prostate cancers that later recurred (geometric mean 17.6, 95% CI: 9.5-32.5) compared to those that did not (38.7, CI: 23.2-64.4; p: 0.044, d: 0.773). In mCRPC, CD24 was detectable in 76% of cores at the cell membrane and in 58% in the nucleus. NPY was detectable in the cytoplasm of 17%. Scores for NPY and nuclear (but not membranous) CD24 were higher in AR[+] mCRPC. In the RNA sequencing results, CD24 did not correlate with AR or kallikrein-related peptidase 3 (KLK3), while NPY positively correlated with AR (rs: 0.313; p: <0.004) and KLK3 (rs: 0.400; p: <0.004). NPY and CD24 scores did not correlate with neuroendocrine mCRPC markers. Nuclear and membranous CD24 showed differential expression by metastatic site. Conclusions: We did not find strong evidence to support the use of CD24 or NPY alone as clinical biomarkers. Membranous and nuclear CD24 were expressed in the majority of mCRPC specimens, while NPY expression was more limited. NPY and nuclear CD24 were more highly expressed in AR[+] mCRPC than AR[-] neuroendocrine disease, and nuclear CD24 displayed site-specific expression, suggesting a potential role for nuclear CD24 in promoting AR[+] mCRPC.},
}
RevDate: 2026-03-14
CmpDate: 2026-03-14
Perspectives and Practices in Pediatric to Adult Healthcare Transition in Kidney Transplantation: An American Society of Transplantation (AST) Member Survey.
Pediatric transplantation, 30(3):e70286.
BACKGROUND: Adolescent and young adult (AYA) kidney transplant recipients (KTR) are susceptible to risk-taking behaviors that peak during transfer from pediatric to adult healthcare, resulting in poorer outcomes. Professional guidelines support healthcare transition (HCT) practices to mitigate this risk; however, HCT perspectives and practices among providers, especially adult providers caring for KTR in the US, have not been widely studied.
METHODS: An online survey of American Society of Transplantation (AST) members was conducted targeting both adult providers (AP) and pediatric providers (PP).
RESULTS: The survey was completed by 135 respondents (predominantly US), including 61 PP and 74 AP. US respondents who disclosed their center ID represented 30% of all programs. Providers agreed that HCT was important (PP 97%, AP 94%) and a shared responsibility (PP 91% and AP 84%). Respondents to our survey frequently worked within transition programs (PP 70% vs. AP 48%), but the majority did not have a formal HCT policy to guide them (PP 43%, AP 21%). Multidisciplinary transition clinics were rare (PP 27%, AP 23%). Only 64% of PP included targeted HCT education either as part of a routine visit or a HCT session. Perceived barriers to providing HCT interventions were similar in both groups, including a lack of provider resources, outcomes tracking, provider communication, and patient/caregiver feedback.
CONCLUSION: Providers recognize the importance of HCT and the joint responsibility of PP and AP but have difficulty following best practices. A multipronged approach will be necessary to address barriers. Our survey reminds us of the gap that persists in providing AYAs with a seamless transfer from pediatric to adult care.
Additional Links: PMID-41830051
Publisher:
PubMed:
Citation:
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@article {pmid41830051,
year = {2026},
author = {Ong, SC and Kosmach-Park, B and Alomar, O and Woodside, K and Blosser, CD and Twombley, K and Basu, A and Herrera, N and Jittirat, A and Merzkani, M and George, R and Alhamad, T},
title = {Perspectives and Practices in Pediatric to Adult Healthcare Transition in Kidney Transplantation: An American Society of Transplantation (AST) Member Survey.},
journal = {Pediatric transplantation},
volume = {30},
number = {3},
pages = {e70286},
doi = {10.1111/petr.70286},
pmid = {41830051},
issn = {1399-3046},
mesh = {Humans ; *Kidney Transplantation ; *Transition to Adult Care ; Adolescent ; Adult ; United States ; Young Adult ; Male ; Surveys and Questionnaires ; Female ; Child ; Societies, Medical ; *Attitude of Health Personnel ; Middle Aged ; },
abstract = {BACKGROUND: Adolescent and young adult (AYA) kidney transplant recipients (KTR) are susceptible to risk-taking behaviors that peak during transfer from pediatric to adult healthcare, resulting in poorer outcomes. Professional guidelines support healthcare transition (HCT) practices to mitigate this risk; however, HCT perspectives and practices among providers, especially adult providers caring for KTR in the US, have not been widely studied.
METHODS: An online survey of American Society of Transplantation (AST) members was conducted targeting both adult providers (AP) and pediatric providers (PP).
RESULTS: The survey was completed by 135 respondents (predominantly US), including 61 PP and 74 AP. US respondents who disclosed their center ID represented 30% of all programs. Providers agreed that HCT was important (PP 97%, AP 94%) and a shared responsibility (PP 91% and AP 84%). Respondents to our survey frequently worked within transition programs (PP 70% vs. AP 48%), but the majority did not have a formal HCT policy to guide them (PP 43%, AP 21%). Multidisciplinary transition clinics were rare (PP 27%, AP 23%). Only 64% of PP included targeted HCT education either as part of a routine visit or a HCT session. Perceived barriers to providing HCT interventions were similar in both groups, including a lack of provider resources, outcomes tracking, provider communication, and patient/caregiver feedback.
CONCLUSION: Providers recognize the importance of HCT and the joint responsibility of PP and AP but have difficulty following best practices. A multipronged approach will be necessary to address barriers. Our survey reminds us of the gap that persists in providing AYAs with a seamless transfer from pediatric to adult care.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Kidney Transplantation
*Transition to Adult Care
Adolescent
Adult
United States
Young Adult
Male
Surveys and Questionnaires
Female
Child
Societies, Medical
*Attitude of Health Personnel
Middle Aged
RevDate: 2026-03-14
Phase II trial with nivolumab and sorafenib in HCC identified enrichment of immunosuppressive monocytes in patients with Child-Pugh B liver dysfunction.
JHEP reports : innovation in hepatology pii:S2589-5559(26)00088-1 [Epub ahead of print].
BACKGROUND AND AIMS: Immune checkpoint inhibition (ICI) and anti-angiogenic therapies are active in hepatocellular carcinoma (HCC), although patients with impaired hepatic function have worse outcomes.
METHODS: We conducted an open-label phase II clinical trial to assess the safety and efficacy of the multikinase inhibitor, sorafenib, combined with nivolumab, in patients with advanced HCC and varying liver function. In a Part 1 safety lead-in, we investigated the maximum-tolerated dose (MTD) of the combination in patients with Child-Pugh A or B7. In Part 2, we enrolled patients with Child-Pugh B7-9 HCC with the primary endpoint of grade >/=3 treatment-related adverse events (TRAE) incidence. Exploratory endpoints included immunologic biomarkers.
RESULTS: Overall, 25 patients were consented and 16 eligible patients enrolled. In Part 1, dose-limiting toxicity occurred in 1 of 6 patients in Dose Level -1, and 2 of 5 patients in Dose Level 1; Dose Level -1 was determined to be the MTD. In total, 69% of patients experienced a Grade >/=3 TRAE, with similar distribution for patients with Child-Pugh A and B (70%, 95% CI: 0.35, 0.93 vs 66.7%, 95% CI: 0.22, 0.96). The objective response rate was 6%; median overall survival was 12.99 months (Child-Pugh A: 15.26 and Child-Pugh B: 10.41). We found that patients with Child-Pugh B liver disease harbored more circulating suppressive CD14[+] monocytes at baseline.
CONCLUSIONS: While combination sorafenib and nivolumab demonstrated acceptable safety at the MTD in both Child-Pugh subgroups, the objective response rate was below the pre-specified threshold to be declared worthy of further exploration. A distinct immune cell profile in Child-Pugh B patients may define mechanisms of resistance and potential therapeutic targets in this population with unmet clinical need.
IMPACT AND IMPLICATIONS: This study addresses the critical need for effective therapies for patients with advanced hepatocellular carcinoma (HCC) and compromised liver function, a population historically excluded from many clinical trials. The findings suggest that while the combination of sorafenib and nivolumab demonstrated acceptable safety across different liver function subgroups, there was a low response rate overall. Importantly, the discovery of distinct immune profiles, particularly an increase in suppressive immune cells in patients with worse liver function, provides insights into potential mechanisms of resistance to immunotherapy. These results are crucial for understanding how we can improve the treatment of advanced HCC, especially in patients with impaired liver function.
GOV IDENTIFIER: NCT03439891.
Additional Links: PMID-41831609
Publisher:
PubMed:
Citation:
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@article {pmid41831609,
year = {2026},
author = {Keenan, BP and Fan, Z and Le, BK and Harris, Q and Chen, J and Clark, M and Lea, A and Zhang, L and Cheung, A and Lara, F and Gordan, JD and Bracci, P and Behr, SC and Fong, L and Venook, AP and Kim, EJ and Kelley, RK},
title = {Phase II trial with nivolumab and sorafenib in HCC identified enrichment of immunosuppressive monocytes in patients with Child-Pugh B liver dysfunction.},
journal = {JHEP reports : innovation in hepatology},
volume = {},
number = {},
pages = {101817},
doi = {10.1016/j.jhepr.2026.101817},
pmid = {41831609},
issn = {2589-5559},
abstract = {BACKGROUND AND AIMS: Immune checkpoint inhibition (ICI) and anti-angiogenic therapies are active in hepatocellular carcinoma (HCC), although patients with impaired hepatic function have worse outcomes.
METHODS: We conducted an open-label phase II clinical trial to assess the safety and efficacy of the multikinase inhibitor, sorafenib, combined with nivolumab, in patients with advanced HCC and varying liver function. In a Part 1 safety lead-in, we investigated the maximum-tolerated dose (MTD) of the combination in patients with Child-Pugh A or B7. In Part 2, we enrolled patients with Child-Pugh B7-9 HCC with the primary endpoint of grade >/=3 treatment-related adverse events (TRAE) incidence. Exploratory endpoints included immunologic biomarkers.
RESULTS: Overall, 25 patients were consented and 16 eligible patients enrolled. In Part 1, dose-limiting toxicity occurred in 1 of 6 patients in Dose Level -1, and 2 of 5 patients in Dose Level 1; Dose Level -1 was determined to be the MTD. In total, 69% of patients experienced a Grade >/=3 TRAE, with similar distribution for patients with Child-Pugh A and B (70%, 95% CI: 0.35, 0.93 vs 66.7%, 95% CI: 0.22, 0.96). The objective response rate was 6%; median overall survival was 12.99 months (Child-Pugh A: 15.26 and Child-Pugh B: 10.41). We found that patients with Child-Pugh B liver disease harbored more circulating suppressive CD14[+] monocytes at baseline.
CONCLUSIONS: While combination sorafenib and nivolumab demonstrated acceptable safety at the MTD in both Child-Pugh subgroups, the objective response rate was below the pre-specified threshold to be declared worthy of further exploration. A distinct immune cell profile in Child-Pugh B patients may define mechanisms of resistance and potential therapeutic targets in this population with unmet clinical need.
IMPACT AND IMPLICATIONS: This study addresses the critical need for effective therapies for patients with advanced hepatocellular carcinoma (HCC) and compromised liver function, a population historically excluded from many clinical trials. The findings suggest that while the combination of sorafenib and nivolumab demonstrated acceptable safety across different liver function subgroups, there was a low response rate overall. Importantly, the discovery of distinct immune profiles, particularly an increase in suppressive immune cells in patients with worse liver function, provides insights into potential mechanisms of resistance to immunotherapy. These results are crucial for understanding how we can improve the treatment of advanced HCC, especially in patients with impaired liver function.
GOV IDENTIFIER: NCT03439891.},
}
RevDate: 2026-03-15
Navigation activities in an organized colorectal cancer screening program improve follow-up colonoscopy completion.
Scientific reports pii:10.1038/s41598-026-44477-6 [Epub ahead of print].
Additional Links: PMID-41832336
Publisher:
PubMed:
Citation:
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@article {pmid41832336,
year = {2026},
author = {Kimura, A and Peck, A and Bell-Brown, A and Todd, K and Akinsoto, NO and Fang, V and Wood, J and Issaka, RB},
title = {Navigation activities in an organized colorectal cancer screening program improve follow-up colonoscopy completion.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-44477-6},
pmid = {41832336},
issn = {2045-2322},
support = {K08CA241296/CA/NCI NIH HHS/United States ; },
}
RevDate: 2026-03-15
In vitro and in vivo base editing of CCR5 in hematopoietic stem cells confers HIV-1 resistance.
Molecular therapy : the journal of the American Society of Gene Therapy pii:S1525-0016(26)00203-0 [Epub ahead of print].
Here we present an HIV gene therapy strategy by in vivo precision gene editing in hematopoietic stem cells (HSC). We successfully generated a panel of helper-dependent adenoviral vectors expressing all-in-one base editors (HDAd-BEs) targeting the CCR5 gene. In a HIV-permissive cell line, transduction with the HDAd-BE vector led to near complete target site editing, CCR5 knockout, and inhibition of HIV infection. In HSC-enriched human CD34[+] cells from mobilized donors or cord blood, we measured efficient precision base editing after HDAd-BE transduction and selection. Following in vitro T cell differentiation and HIV infection, we demonstrated that HIV genome titers were significantly lower with precision CCR5 base editing. Importantly, in a humanized mouse model, in vivo transduction with the HDAd-BE vector followed by selection resulted in ∼50% base editing at the CCR5 target site in bone marrow mononuclear cells, which conferred ∼12-fold lower HIV plasma titers than control animals after HIV challenge. No significant off-target editing and adverse effects associated with the treatment were observed. By targeting HSCs to precisely engineer HIV-resistant cells in vivo, our strategy represents an efficient, durable, and affordable approach to achieve a functional cure for HIV infection.
Additional Links: PMID-41832601
Publisher:
PubMed:
Citation:
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@article {pmid41832601,
year = {2026},
author = {Anderson, AK and Georgakopoulou, A and Kuhlmann, AS and Wang, H and Riker, A and Karuppusamy, KV and Radtke, S and Bui, JK and Kiem, HP and Lieber, A and Li, C},
title = {In vitro and in vivo base editing of CCR5 in hematopoietic stem cells confers HIV-1 resistance.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.03.018},
pmid = {41832601},
issn = {1525-0024},
abstract = {Here we present an HIV gene therapy strategy by in vivo precision gene editing in hematopoietic stem cells (HSC). We successfully generated a panel of helper-dependent adenoviral vectors expressing all-in-one base editors (HDAd-BEs) targeting the CCR5 gene. In a HIV-permissive cell line, transduction with the HDAd-BE vector led to near complete target site editing, CCR5 knockout, and inhibition of HIV infection. In HSC-enriched human CD34[+] cells from mobilized donors or cord blood, we measured efficient precision base editing after HDAd-BE transduction and selection. Following in vitro T cell differentiation and HIV infection, we demonstrated that HIV genome titers were significantly lower with precision CCR5 base editing. Importantly, in a humanized mouse model, in vivo transduction with the HDAd-BE vector followed by selection resulted in ∼50% base editing at the CCR5 target site in bone marrow mononuclear cells, which conferred ∼12-fold lower HIV plasma titers than control animals after HIV challenge. No significant off-target editing and adverse effects associated with the treatment were observed. By targeting HSCs to precisely engineer HIV-resistant cells in vivo, our strategy represents an efficient, durable, and affordable approach to achieve a functional cure for HIV infection.},
}
RevDate: 2026-03-12
CmpDate: 2026-03-12
Change in sleep duration following a cancer diagnosis.
Cancer causes & control : CCC, 37(4):.
INTRODUCTION: The objective of this study was to investigate how the experience of a cancer diagnosis impacts sleep duration among Cancer Prevention Study-3 (CPS-3) participants.
METHODS: CPS-3 is a prospective cohort of US adults aged 30-65 years. At baseline (2006-2013), 2015, and 2018, participants reported their average sleep duration during the prior year. Cancer incidence was determined via linkage to state registries. Participants who experienced a cancer diagnosis during study follow-up with complete sleep data prior to (pre-reference) and after cancer diagnosis (post-reference) were included. We matched individuals with a cancer diagnosis to participants without a cancer diagnosis during follow-up (1:4 ratio) based on age, sex, cohort entry year, and timepoint of sleep duration measures. Change in sleep duration was calculated as the difference between average sleep duration measurements at two survey timepoints (pre- and post-reference) (decrease, no change [ref], increase). We used multivariable multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between receiving a cancer diagnosis (exposure) and change in sleep duration (outcome) adjusted for demographic, lifestyle, and health factors.
RESULTS: Among the 20,210 included CPS-3 participants (4,042 cancer survivors), participants who received a cancer diagnosis had higher odds of increasing sleep duration (OR = 1.16, 95% CI 1.07, 1.27) compared to participants who did not receive a cancer diagnosis. Restricting to female participants with a diagnosis of any cancer and breast cancer only showed similar results.
CONCLUSION: The experience of a cancer diagnosis may contribute to increased sleep duration beyond expected age-related changes.
Additional Links: PMID-41817876
PubMed:
Citation:
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@article {pmid41817876,
year = {2026},
author = {Donzella, SM and Newton, CC and VoPham, T and Peoples, AR and Bodelon, C and Shams-White, MM and Patel, AV and Zhong, C and Phipps, AI},
title = {Change in sleep duration following a cancer diagnosis.},
journal = {Cancer causes & control : CCC},
volume = {37},
number = {4},
pages = {},
pmid = {41817876},
issn = {1573-7225},
mesh = {Humans ; Female ; Middle Aged ; Male ; *Neoplasms/diagnosis/epidemiology ; Adult ; Aged ; *Sleep/physiology ; Prospective Studies ; Follow-Up Studies ; United States/epidemiology ; Time Factors ; Incidence ; Registries ; Sleep Duration ; },
abstract = {INTRODUCTION: The objective of this study was to investigate how the experience of a cancer diagnosis impacts sleep duration among Cancer Prevention Study-3 (CPS-3) participants.
METHODS: CPS-3 is a prospective cohort of US adults aged 30-65 years. At baseline (2006-2013), 2015, and 2018, participants reported their average sleep duration during the prior year. Cancer incidence was determined via linkage to state registries. Participants who experienced a cancer diagnosis during study follow-up with complete sleep data prior to (pre-reference) and after cancer diagnosis (post-reference) were included. We matched individuals with a cancer diagnosis to participants without a cancer diagnosis during follow-up (1:4 ratio) based on age, sex, cohort entry year, and timepoint of sleep duration measures. Change in sleep duration was calculated as the difference between average sleep duration measurements at two survey timepoints (pre- and post-reference) (decrease, no change [ref], increase). We used multivariable multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between receiving a cancer diagnosis (exposure) and change in sleep duration (outcome) adjusted for demographic, lifestyle, and health factors.
RESULTS: Among the 20,210 included CPS-3 participants (4,042 cancer survivors), participants who received a cancer diagnosis had higher odds of increasing sleep duration (OR = 1.16, 95% CI 1.07, 1.27) compared to participants who did not receive a cancer diagnosis. Restricting to female participants with a diagnosis of any cancer and breast cancer only showed similar results.
CONCLUSION: The experience of a cancer diagnosis may contribute to increased sleep duration beyond expected age-related changes.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
Female
Middle Aged
Male
*Neoplasms/diagnosis/epidemiology
Adult
Aged
*Sleep/physiology
Prospective Studies
Follow-Up Studies
United States/epidemiology
Time Factors
Incidence
Registries
Sleep Duration
RevDate: 2026-03-12
Determinants of natural killer cell-mediated antibody dependent cellular cytotoxicity in SARS-CoV-2 antibodies.
PLoS pathogens, 22(3):e1014026 pii:PPATHOGENS-D-25-02145 [Epub ahead of print].
A growing body of evidence underscores the role of antibody-dependent cellular cytotoxicity (ADCC) in antiviral immunity. Yet, the mechanisms underlying the ability of certain antibodies (Abs) to mediate potent ADCC activity remain poorly characterized - in particular the contribution of features within the antigen-binding Fab region remains largely unexplored. In this study, we leveraged a collection of 142 SARS-CoV-2 monoclonal Abs to systematically dissect the determinants of ADCC activity. We analyzed their epitope domain target, binding characteristics, neutralization potency, somatic hypermutation (SHM) and CDR3 length to determine the contribution of these features to ADCC activity. We found that ADCC activity is primarily shaped by epitope target - particularly targeting of the S2 domain of the Spike glycoprotein. ADCC potency was not associated with the degree of SHM or neutralization. Notably, ADCC activity was not correlated with binding activity and moderate binding to antigen was sufficient for ADCC activity. By integrating these analyses, we provide a comprehensive framework for understanding the molecular and functional determinants of ADCC. Together, these findings offer novel insights into the mechanisms that underpin ADCC functions, with implications for vaccine design and therapeutic Abs development.
Additional Links: PMID-41818265
Publisher:
PubMed:
Citation:
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@article {pmid41818265,
year = {2026},
author = {Depierreux, DM and Ruiz, F and Lilly, M and Guenthoer, J and Chohan, V and Overbaugh, J},
title = {Determinants of natural killer cell-mediated antibody dependent cellular cytotoxicity in SARS-CoV-2 antibodies.},
journal = {PLoS pathogens},
volume = {22},
number = {3},
pages = {e1014026},
doi = {10.1371/journal.ppat.1014026},
pmid = {41818265},
issn = {1553-7374},
abstract = {A growing body of evidence underscores the role of antibody-dependent cellular cytotoxicity (ADCC) in antiviral immunity. Yet, the mechanisms underlying the ability of certain antibodies (Abs) to mediate potent ADCC activity remain poorly characterized - in particular the contribution of features within the antigen-binding Fab region remains largely unexplored. In this study, we leveraged a collection of 142 SARS-CoV-2 monoclonal Abs to systematically dissect the determinants of ADCC activity. We analyzed their epitope domain target, binding characteristics, neutralization potency, somatic hypermutation (SHM) and CDR3 length to determine the contribution of these features to ADCC activity. We found that ADCC activity is primarily shaped by epitope target - particularly targeting of the S2 domain of the Spike glycoprotein. ADCC potency was not associated with the degree of SHM or neutralization. Notably, ADCC activity was not correlated with binding activity and moderate binding to antigen was sufficient for ADCC activity. By integrating these analyses, we provide a comprehensive framework for understanding the molecular and functional determinants of ADCC. Together, these findings offer novel insights into the mechanisms that underpin ADCC functions, with implications for vaccine design and therapeutic Abs development.},
}
RevDate: 2026-03-15
CmpDate: 2026-03-12
Evaluation of mixed response in tumor size and survival in patients with rare cancers treated with dual checkpoint inhibitor therapy (DART SWOG S1609).
Journal for immunotherapy of cancer, 14(3):.
BACKGROUND: Mixed response, where different lesions within the same patient show discordant responses to treatment, remains poorly understood. To better understand the complex effects of mixed response on patient survival, we devised three different definitions of mixed response. This retrospective analysis provides the first evaluation of the association between mixed response and survival outcomes in patients with rare cancers treated with dual checkpoint blockade using ipilimumab plus nivolumab, based on data from 52 baskets in the DART SWOG S1609 trial.
METHODS: We included 438 patients with Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1-measurable disease and at least two target lesions, after exclusions for ineligibility, early death, or missing data. Overall survival (OS) and progression-free survival (PFS) were compared using log-rank tests and Cox regression, stratified by basket and using a day 65 landmark. A mixed response was evaluated using three definitions: Method 1-RECIST discordance across lesions; Method 2-presence of ≥1 lesion with >5 mm increase or ≥1 with >5 mm decrease; and Method 3-same as Method 2 but with a 1 mm cut-off.
RESULTS: Mixed response was significantly associated with worse OS and PFS using both Method 1 (OS: HR 1.80; PFS: HR 1.58) and Method 2 (OS: HR 1.55; PFS: HR 1.57) compared with "all SD/stable per lesion". Among patients classified as "SD by RECIST", those who exhibited a mixed per lesion response according to Method 1 had significantly worse OS (median 9.9 months (8.8-12.4)) than those with a non-mixed per lesion response (median 22.7 months (19.2-32.0)). Further stratification showed that any lesion increasing >5 mm was linked to worse outcomes (OS: HR >2.37, p<0.05).
CONCLUSIONS: Mixed response was significantly associated with worse survival outcomes in patients treated with dual immune checkpoint inhibitors, even among those with RECIST-defined stable disease. Our findings suggest that the "worst"-responding lesion drives prognosis, underscoring the limitations of RECIST in capturing clinically relevant heterogeneity. This study highlights the need to incorporate lesion-level assessment into immunotherapy decision-making and provides a foundation for guiding earlier transition to the next line therapies or other therapeutic options. Future studies integrating molecular biomarkers are warranted to refine response evaluation criteria and optimize immune checkpoint inhibitor-based strategies.
Additional Links: PMID-41819545
PubMed:
Citation:
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@article {pmid41819545,
year = {2026},
author = {Chae, YK and Othus, M and Lyu, J and Lee, S and Paik, S and Dietrich, E and Jung, CM and Chung, LI and Patel, S and Kurzrock, R},
title = {Evaluation of mixed response in tumor size and survival in patients with rare cancers treated with dual checkpoint inhibitor therapy (DART SWOG S1609).},
journal = {Journal for immunotherapy of cancer},
volume = {14},
number = {3},
pages = {},
pmid = {41819545},
issn = {2051-1426},
mesh = {Humans ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Male ; Female ; *Neoplasms/drug therapy/mortality/pathology ; Middle Aged ; Retrospective Studies ; Aged ; Nivolumab/therapeutic use/pharmacology ; Adult ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Ipilimumab/therapeutic use/pharmacology ; Response Evaluation Criteria in Solid Tumors ; *Rare Diseases/drug therapy/mortality ; Tumor Burden ; },
abstract = {BACKGROUND: Mixed response, where different lesions within the same patient show discordant responses to treatment, remains poorly understood. To better understand the complex effects of mixed response on patient survival, we devised three different definitions of mixed response. This retrospective analysis provides the first evaluation of the association between mixed response and survival outcomes in patients with rare cancers treated with dual checkpoint blockade using ipilimumab plus nivolumab, based on data from 52 baskets in the DART SWOG S1609 trial.
METHODS: We included 438 patients with Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1-measurable disease and at least two target lesions, after exclusions for ineligibility, early death, or missing data. Overall survival (OS) and progression-free survival (PFS) were compared using log-rank tests and Cox regression, stratified by basket and using a day 65 landmark. A mixed response was evaluated using three definitions: Method 1-RECIST discordance across lesions; Method 2-presence of ≥1 lesion with >5 mm increase or ≥1 with >5 mm decrease; and Method 3-same as Method 2 but with a 1 mm cut-off.
RESULTS: Mixed response was significantly associated with worse OS and PFS using both Method 1 (OS: HR 1.80; PFS: HR 1.58) and Method 2 (OS: HR 1.55; PFS: HR 1.57) compared with "all SD/stable per lesion". Among patients classified as "SD by RECIST", those who exhibited a mixed per lesion response according to Method 1 had significantly worse OS (median 9.9 months (8.8-12.4)) than those with a non-mixed per lesion response (median 22.7 months (19.2-32.0)). Further stratification showed that any lesion increasing >5 mm was linked to worse outcomes (OS: HR >2.37, p<0.05).
CONCLUSIONS: Mixed response was significantly associated with worse survival outcomes in patients treated with dual immune checkpoint inhibitors, even among those with RECIST-defined stable disease. Our findings suggest that the "worst"-responding lesion drives prognosis, underscoring the limitations of RECIST in capturing clinically relevant heterogeneity. This study highlights the need to incorporate lesion-level assessment into immunotherapy decision-making and provides a foundation for guiding earlier transition to the next line therapies or other therapeutic options. Future studies integrating molecular biomarkers are warranted to refine response evaluation criteria and optimize immune checkpoint inhibitor-based strategies.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
Male
Female
*Neoplasms/drug therapy/mortality/pathology
Middle Aged
Retrospective Studies
Aged
Nivolumab/therapeutic use/pharmacology
Adult
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Ipilimumab/therapeutic use/pharmacology
Response Evaluation Criteria in Solid Tumors
*Rare Diseases/drug therapy/mortality
Tumor Burden
RevDate: 2026-03-12
Prognostic Value of Cycle 1 SPECT SUVmean in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with [177]Lu-PSMA-617.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine pii:jnumed.125.271593 [Epub ahead of print].
This study aimed to determine whether SPECT SUVmean measured after the first cycle of [177]Lu-PSMA-617 is associated with oncologic outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: This retrospective study included 192 consecutive patients with mCRPC treated with [177]Lu-PSMA-617 who underwent SPECT 24 h after cycle 1. Associations of total tumor SPECT SUVmean with a decline of 50% or more from baseline in prostate-specific antigen (PSA) levels (PSA50), PSA progression-free survival (PSA-PFS), and overall survival (OS) were evaluated using logistic and Cox regression adjusted for prostate-specific membrane antigen PET SUVmean and scan interval. Results: Higher SPECT SUVmean quartiles were independently associated with greater odds of PSA50 response (odds ratios of 4.45, 10.2, and 17.1 for quartiles 2 (Q2), 3 (Q3), and 4 (Q4), respectively (P < 0.05 for all), longer PSA-PFS (hazard ratios of 0.52, 0.29, and 0.17 for Q2-Q4, respectively; P < 0.05 for all), and longer OS (hazard ratios of 1.03, 0.82, and 0.42 for Q2-Q4, respectively; P < 0.05 for Q4 only). Conclusion: SPECT SUVmean measured after the first cycle of [177]Lu-PSMA-617 in patients with mCRPC was prognostic for PSA50 and PSA-PFS, independent of the prostate-specific membrane antigen PET SUVmean, whereas its association with OS was limited and observed only in the highest quartile.
Additional Links: PMID-41819830
Publisher:
PubMed:
Citation:
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@article {pmid41819830,
year = {2026},
author = {Ghodsi, A and Demirci, RA and Gulati, R and Nelson, PS and Raychaudhuri, R and Cheng, HH and Sunkara, R and Khan, H and Rios, RN and Hsieh, A and Grivas, P and Montgomery, B and Yezefski, TA and Yu, EY and Schweizer, MT and Chen, DL and Iravani, A},
title = {Prognostic Value of Cycle 1 SPECT SUVmean in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with [177]Lu-PSMA-617.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.271593},
pmid = {41819830},
issn = {1535-5667},
abstract = {This study aimed to determine whether SPECT SUVmean measured after the first cycle of [177]Lu-PSMA-617 is associated with oncologic outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: This retrospective study included 192 consecutive patients with mCRPC treated with [177]Lu-PSMA-617 who underwent SPECT 24 h after cycle 1. Associations of total tumor SPECT SUVmean with a decline of 50% or more from baseline in prostate-specific antigen (PSA) levels (PSA50), PSA progression-free survival (PSA-PFS), and overall survival (OS) were evaluated using logistic and Cox regression adjusted for prostate-specific membrane antigen PET SUVmean and scan interval. Results: Higher SPECT SUVmean quartiles were independently associated with greater odds of PSA50 response (odds ratios of 4.45, 10.2, and 17.1 for quartiles 2 (Q2), 3 (Q3), and 4 (Q4), respectively (P < 0.05 for all), longer PSA-PFS (hazard ratios of 0.52, 0.29, and 0.17 for Q2-Q4, respectively; P < 0.05 for all), and longer OS (hazard ratios of 1.03, 0.82, and 0.42 for Q2-Q4, respectively; P < 0.05 for Q4 only). Conclusion: SPECT SUVmean measured after the first cycle of [177]Lu-PSMA-617 in patients with mCRPC was prognostic for PSA50 and PSA-PFS, independent of the prostate-specific membrane antigen PET SUVmean, whereas its association with OS was limited and observed only in the highest quartile.},
}
RevDate: 2026-03-12
RNA polymerase II: the elephant in the room.
Trends in genetics : TIG pii:S0168-9525(26)00008-9 [Epub ahead of print].
How genes respond to external signals is poorly understood, with transcription factors and histones proposed as mediators of signals to RNA polymerase II (Pol II). However, recent work shows that Pol II is the direct target of more than 100 protein kinases, a previously underappreciated mechanism for generating epigenetic complexity.
Additional Links: PMID-41820080
Publisher:
PubMed:
Citation:
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@article {pmid41820080,
year = {2026},
author = {Henikoff, S and Hahn, S},
title = {RNA polymerase II: the elephant in the room.},
journal = {Trends in genetics : TIG},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tig.2026.01.008},
pmid = {41820080},
issn = {0168-9525},
abstract = {How genes respond to external signals is poorly understood, with transcription factors and histones proposed as mediators of signals to RNA polymerase II (Pol II). However, recent work shows that Pol II is the direct target of more than 100 protein kinases, a previously underappreciated mechanism for generating epigenetic complexity.},
}
RevDate: 2026-03-16
CmpDate: 2026-03-13
"Give me the sense that I matter:" Queer women's recommendations for an ideal cervical cancer screening exam and pathways to screening equity.
Women's health (London, England), 22:17455057261428108.
BACKGROUND: Cervical cancer screening is a powerful tool in the prevention, early detection, and diagnosis of precancers and cancer. There is mounting evidence, however, demonstrating that Queer cisgender women experience disparities in cervical cancer screening access and uptake compared to their heterosexual counterparts. To close gaps in screening, Queer women's voices and visions must foreground recommendations aimed at remedying screening inequities.
OBJECTIVES: This study aims to explore perceptions on an ideal cervical cancer screening exam among a racially and ethnically diverse group of Queer women.
DESIGN: This qualitative interview study is led in partnership with a multidisciplinary community steering committee. Our work is grounded in the Reproductive Justice Framework.
METHODS: We held in-depth interviews with 19 Queer women to understand their recommendations for improving cervical cancer screening experiences for their community. Data from these interviews were analyzed through thematic analysis.
RESULTS: We identified five themes around creating an ideal cervical cancer screening experience among Queer women: (1) community outreach and education, (2) cues of affirmation and safety, (3) Queer patient navigation and advocacy, (4) Queer-affirming and knowledgeable providers, and (5) trauma-informed care.
CONCLUSION: Engaging Queer women in developing solutions to address screening disparities is a missing link in cervical cancer prevention and the advancement of reproductive health equity. We share actionable strategies at the healthcare professional, community, and organizational levels to support healthcare systems in translating Queer women's visions into practice. Our findings also inform medical organizations, expert panels, and health authorities on patient-defined strategies and pathways to remedying screening inequity.
Additional Links: PMID-41821238
PubMed:
Citation:
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@article {pmid41821238,
year = {2026},
author = {Williams, DM and Reilly, S and Lord, T and Ayers, K and Kissiah-Grove, S and Robinson, M and Fong, L and Angel, J},
title = {"Give me the sense that I matter:" Queer women's recommendations for an ideal cervical cancer screening exam and pathways to screening equity.},
journal = {Women's health (London, England)},
volume = {22},
number = {},
pages = {17455057261428108},
pmid = {41821238},
issn = {1745-5065},
mesh = {Humans ; Female ; Young Adult ; Adult ; Middle Aged ; *Uterine Cervical Neoplasms/diagnosis/prevention & control ; *Early Detection of Cancer/psychology ; *Sexual and Gender Minorities/psychology ; *Healthcare Disparities ; *Patient Acceptance of Health Care/psychology ; Qualitative Research ; Interviews as Topic ; Professional-Patient Relations ; },
abstract = {BACKGROUND: Cervical cancer screening is a powerful tool in the prevention, early detection, and diagnosis of precancers and cancer. There is mounting evidence, however, demonstrating that Queer cisgender women experience disparities in cervical cancer screening access and uptake compared to their heterosexual counterparts. To close gaps in screening, Queer women's voices and visions must foreground recommendations aimed at remedying screening inequities.
OBJECTIVES: This study aims to explore perceptions on an ideal cervical cancer screening exam among a racially and ethnically diverse group of Queer women.
DESIGN: This qualitative interview study is led in partnership with a multidisciplinary community steering committee. Our work is grounded in the Reproductive Justice Framework.
METHODS: We held in-depth interviews with 19 Queer women to understand their recommendations for improving cervical cancer screening experiences for their community. Data from these interviews were analyzed through thematic analysis.
RESULTS: We identified five themes around creating an ideal cervical cancer screening experience among Queer women: (1) community outreach and education, (2) cues of affirmation and safety, (3) Queer patient navigation and advocacy, (4) Queer-affirming and knowledgeable providers, and (5) trauma-informed care.
CONCLUSION: Engaging Queer women in developing solutions to address screening disparities is a missing link in cervical cancer prevention and the advancement of reproductive health equity. We share actionable strategies at the healthcare professional, community, and organizational levels to support healthcare systems in translating Queer women's visions into practice. Our findings also inform medical organizations, expert panels, and health authorities on patient-defined strategies and pathways to remedying screening inequity.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
Female
Young Adult
Adult
Middle Aged
*Uterine Cervical Neoplasms/diagnosis/prevention & control
*Early Detection of Cancer/psychology
*Sexual and Gender Minorities/psychology
*Healthcare Disparities
*Patient Acceptance of Health Care/psychology
Qualitative Research
Interviews as Topic
Professional-Patient Relations
RevDate: 2026-03-17
Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.
Molecular therapy : the journal of the American Society of Gene Therapy pii:S1525-0016(26)00192-9 [Epub ahead of print].
Gamma delta (γδ) T cells are defined by their unique ability to recognize a limited repertoire of non-peptide, non-MHC-associated antigens on transformed and pathogen-infected cells. In addition to their inability to mediate GvHD, γδ T cells exhibit properties distinct from other lymphocyte subsets, prompting significant interest in their development as an off-the-shelf cellular immunotherapeutic. However, their low abundance in circulation, heterogeneity, limited methods for ex vivo expansion, and under-developed methodologies for genetic modification have hindered basic study and clinical application of γδ T cells. Here, we implement a feeder-free, scalable approach for ex vivo manufacture of polyclonal, non-virally modified, gene edited chimeric antigen receptor (CAR)-γδ T cells for therapeutic application. Engineered CAR-γδ T cells demonstrate robust functionality in vitro and in vivo. Longitudinal in vivo pharmacokinetic profiling of adoptively transferred polyclonal CAR-γδ T cells uncover subset-specific responses to IL-15 cytokine armoring and multiplex base editing. Our results present a robust platform for genetic modification of polyclonal CAR-γδ T cells and present unique opportunities to further define synergy and the contribution of discrete, engineered CAR-γδ T cell subsets to therapeutic efficacy in vivo.
Additional Links: PMID-41821313
Publisher:
PubMed:
Citation:
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@article {pmid41821313,
year = {2026},
author = {Bridge, J and Johnson, MJ and Kar, B and Kim, J and Wenthe, S and Krueger, J and Wick, B and Kluesner, MG and Crane, AT and Bell, J and von Dissen, L and Stelljes, E and Skeate, JG and Moriarity, BS and Webber, BR},
title = {Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.03.007},
pmid = {41821313},
issn = {1525-0024},
abstract = {Gamma delta (γδ) T cells are defined by their unique ability to recognize a limited repertoire of non-peptide, non-MHC-associated antigens on transformed and pathogen-infected cells. In addition to their inability to mediate GvHD, γδ T cells exhibit properties distinct from other lymphocyte subsets, prompting significant interest in their development as an off-the-shelf cellular immunotherapeutic. However, their low abundance in circulation, heterogeneity, limited methods for ex vivo expansion, and under-developed methodologies for genetic modification have hindered basic study and clinical application of γδ T cells. Here, we implement a feeder-free, scalable approach for ex vivo manufacture of polyclonal, non-virally modified, gene edited chimeric antigen receptor (CAR)-γδ T cells for therapeutic application. Engineered CAR-γδ T cells demonstrate robust functionality in vitro and in vivo. Longitudinal in vivo pharmacokinetic profiling of adoptively transferred polyclonal CAR-γδ T cells uncover subset-specific responses to IL-15 cytokine armoring and multiplex base editing. Our results present a robust platform for genetic modification of polyclonal CAR-γδ T cells and present unique opportunities to further define synergy and the contribution of discrete, engineered CAR-γδ T cell subsets to therapeutic efficacy in vivo.},
}
RevDate: 2026-03-13
CmpDate: 2026-03-13
Early rise in nasal secretory IgA associated with shorter duration of SARS-CoV-2 virus shedding in an acute infection cohort.
Frontiers in immunology, 17:1722585.
INTRODUCTION: Understanding the role of mucosal immune responses in preventing coronavirus replication is essential for the development of broad-spectrum therapeutics and vaccines capable of interrupting transmission. Investigating the relationship between mucosal antibodies and viral shedding may provide critical insights into protective mechanisms against SARS-CoV-2 and inform strategies for enhancing mucosal immunity.
METHODS: In a subset of the larger CoVPN 5001 cohort, 143 participants from the US, Mexico, and South America were characterized as either short (<7 days), intermediate (7-21 days), or prolonged (>21 days) virus shedders based on RT-qPCR measurements over the first month of acute SARS-CoV-2 infection. We measured systemic circulating serum IgA and secretory IgA (SIgA) in serially collected nasal lavage fluids to 15 SARS-CoV-2 antigens, including spike variants, receptor binding domain (RBD), and N-terminal Domain (NTD) and evaluated the relationship between antibody titers and duration of viral shedding using multivariate and binary logistic regression modeling. We also assessed antibody responses to RBD proteins of endemic alpha and beta coronaviruses to compare variations in antibody kinetics throughout the course of infection.
RESULTS: We found that increased serum IgA and mucosal secretory IgA antibody titers during the earliest phase of acute infection were associated with decreased viral shedding duration, with nasal IgA responses to the spike NTD being the strongest factor associated with viral shedding (adjusted p<0.1). In contrast, antibody titers against endemic human coronaviruses remained stable throughout the course of infection, consistent with a specific role for newly elicited SARS-CoV-2 antibodies in virus control.
DISCUSSION: These findings demonstrate that early rises in serum and mucosal IgA titers are associated with reduced duration of viral shedding. Notably, nasal secretory IgA responses targeting the spike N-terminal domain were most strongly associated with shorter shedding, suggesting a potentially protective role for SARS-CoV-2-specific nasal IgA during acute SARS-CoV-2 infection. These results highlight the importance of mucosal immunity for limiting viral transmission and shedding, offering future insights for pan-coronavirus therapeutics and vaccine development aimed for enhancing SARS-COV-2 mucosal antibody responses.
Additional Links: PMID-41822483
PubMed:
Citation:
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@article {pmid41822483,
year = {2026},
author = {Brackett, C and Zhang, L and Do, BTN and Baral, S and Fisher, LH and Hahn, WO and Carnacchi, AJ and Hilliard, S and Li, SS and Premkumar, L and Greninger, AL and Hyrien, O and Seaton, KE and Tomaras, GD},
title = {Early rise in nasal secretory IgA associated with shorter duration of SARS-CoV-2 virus shedding in an acute infection cohort.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1722585},
pmid = {41822483},
issn = {1664-3224},
mesh = {Humans ; *Virus Shedding/immunology ; *COVID-19/immunology/virology ; *SARS-CoV-2/immunology/physiology ; *Immunoglobulin A, Secretory/immunology/blood ; Male ; Female ; *Antibodies, Viral/immunology/blood ; Adult ; Middle Aged ; Immunity, Mucosal ; Cohort Studies ; Spike Glycoprotein, Coronavirus/immunology ; *Nasal Mucosa/immunology ; Nasal Lavage Fluid/immunology ; },
abstract = {INTRODUCTION: Understanding the role of mucosal immune responses in preventing coronavirus replication is essential for the development of broad-spectrum therapeutics and vaccines capable of interrupting transmission. Investigating the relationship between mucosal antibodies and viral shedding may provide critical insights into protective mechanisms against SARS-CoV-2 and inform strategies for enhancing mucosal immunity.
METHODS: In a subset of the larger CoVPN 5001 cohort, 143 participants from the US, Mexico, and South America were characterized as either short (<7 days), intermediate (7-21 days), or prolonged (>21 days) virus shedders based on RT-qPCR measurements over the first month of acute SARS-CoV-2 infection. We measured systemic circulating serum IgA and secretory IgA (SIgA) in serially collected nasal lavage fluids to 15 SARS-CoV-2 antigens, including spike variants, receptor binding domain (RBD), and N-terminal Domain (NTD) and evaluated the relationship between antibody titers and duration of viral shedding using multivariate and binary logistic regression modeling. We also assessed antibody responses to RBD proteins of endemic alpha and beta coronaviruses to compare variations in antibody kinetics throughout the course of infection.
RESULTS: We found that increased serum IgA and mucosal secretory IgA antibody titers during the earliest phase of acute infection were associated with decreased viral shedding duration, with nasal IgA responses to the spike NTD being the strongest factor associated with viral shedding (adjusted p<0.1). In contrast, antibody titers against endemic human coronaviruses remained stable throughout the course of infection, consistent with a specific role for newly elicited SARS-CoV-2 antibodies in virus control.
DISCUSSION: These findings demonstrate that early rises in serum and mucosal IgA titers are associated with reduced duration of viral shedding. Notably, nasal secretory IgA responses targeting the spike N-terminal domain were most strongly associated with shorter shedding, suggesting a potentially protective role for SARS-CoV-2-specific nasal IgA during acute SARS-CoV-2 infection. These results highlight the importance of mucosal immunity for limiting viral transmission and shedding, offering future insights for pan-coronavirus therapeutics and vaccine development aimed for enhancing SARS-COV-2 mucosal antibody responses.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Virus Shedding/immunology
*COVID-19/immunology/virology
*SARS-CoV-2/immunology/physiology
*Immunoglobulin A, Secretory/immunology/blood
Male
Female
*Antibodies, Viral/immunology/blood
Adult
Middle Aged
Immunity, Mucosal
Cohort Studies
Spike Glycoprotein, Coronavirus/immunology
*Nasal Mucosa/immunology
Nasal Lavage Fluid/immunology
RevDate: 2026-03-13
Estimating the Carbon Footprint of External Beam Radiotherapy: Should This Be a Concern for LMICs?.
Journal of medical imaging and radiation oncology [Epub ahead of print].
PURPOSE: This study aims to estimate the carbon footprint associated with external beam radiotherapy in a low- and middle-income country (LMIC) context, specifically at the Uganda Cancer Institute (UCI), and to evaluate whether sustainability should be a priority alongside treatment access in such radiation therapy settings.
METHODOLOGY: A carbon footprint analysis was conducted for patients treated for locally advanced cervical cancer at UCI between 2023 and 2024. The assessment included emissions from three key components: (1) patient travel to and from the facility, (2) pre-treatment imaging using CT and 2D simulation and (3) energy consumption by three Varian TrueBeam linear accelerators during treatment and idle times. Emission estimates were calculated using activity data and standard global warming potential (GWP) conversion factors.
RESULTS: Patient travel emerged as a major contributor to carbon emissions due to the centralisation of services in Kampala and the lack of regional treatment centres. Energy use from LINACs and imaging contributed less significantly, owing in part to Uganda's low-carbon electricity grid powered largely by hydropower. CT scans generated approximately 0.105 kg CO2 per scan, and LINAC operations added modest emissions depending on usage patterns and machine idle time.
CONCLUSION: While radiotherapy-related emissions in LMICs like Uganda are relatively modest compared to high-income countries, they are non-negligible and expected to rise with growing access to cancer care. Incorporating sustainability considerations into the future planning of radiotherapy infrastructure and service expansion is both feasible and necessary. Carbon-conscious planning should be integrated into decisions around siting and radiotherapy expansion to promote environmentally responsible cancer care in LMICs.
Additional Links: PMID-41826235
Publisher:
PubMed:
Citation:
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@article {pmid41826235,
year = {2026},
author = {Yorke, AA and Ignatius, K and Schreiner, JL and Kron, T},
title = {Estimating the Carbon Footprint of External Beam Radiotherapy: Should This Be a Concern for LMICs?.},
journal = {Journal of medical imaging and radiation oncology},
volume = {},
number = {},
pages = {},
doi = {10.1111/1754-9485.70083},
pmid = {41826235},
issn = {1754-9485},
abstract = {PURPOSE: This study aims to estimate the carbon footprint associated with external beam radiotherapy in a low- and middle-income country (LMIC) context, specifically at the Uganda Cancer Institute (UCI), and to evaluate whether sustainability should be a priority alongside treatment access in such radiation therapy settings.
METHODOLOGY: A carbon footprint analysis was conducted for patients treated for locally advanced cervical cancer at UCI between 2023 and 2024. The assessment included emissions from three key components: (1) patient travel to and from the facility, (2) pre-treatment imaging using CT and 2D simulation and (3) energy consumption by three Varian TrueBeam linear accelerators during treatment and idle times. Emission estimates were calculated using activity data and standard global warming potential (GWP) conversion factors.
RESULTS: Patient travel emerged as a major contributor to carbon emissions due to the centralisation of services in Kampala and the lack of regional treatment centres. Energy use from LINACs and imaging contributed less significantly, owing in part to Uganda's low-carbon electricity grid powered largely by hydropower. CT scans generated approximately 0.105 kg CO2 per scan, and LINAC operations added modest emissions depending on usage patterns and machine idle time.
CONCLUSION: While radiotherapy-related emissions in LMICs like Uganda are relatively modest compared to high-income countries, they are non-negligible and expected to rise with growing access to cancer care. Incorporating sustainability considerations into the future planning of radiotherapy infrastructure and service expansion is both feasible and necessary. Carbon-conscious planning should be integrated into decisions around siting and radiotherapy expansion to promote environmentally responsible cancer care in LMICs.},
}
RevDate: 2026-03-14
Author Correction: Age-related epithelial defects limit thymic function and regeneration.
Additional Links: PMID-41826733
Publisher:
PubMed:
Citation:
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@article {pmid41826733,
year = {2026},
author = {Kousa, AI and Jahn, L and Zhao, K and Flores, AE and Acenas, D and Lederer, E and Argyropoulos, KV and Lemarquis, AL and Granadier, D and Cooper, K and D'Andrea, M and Sheridan, JM and Tsai, J and Sikkema, L and Lazrak, A and Nichols, K and Lee, N and Ghale, R and Malard, F and Andrlova, H and Velardi, E and Youssef, S and Burgos da Silva, M and Docampo, M and Sharma, R and Mazutis, L and Wimmer, VC and Rogers, KL and DeWolf, S and Gipson, B and Gomes, ALC and Setty, M and Pe'er, D and Hale, L and Manley, NR and Gray, DHD and van den Brink, MRM and Dudakov, JA},
title = {Author Correction: Age-related epithelial defects limit thymic function and regeneration.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41590-026-02489-4},
pmid = {41826733},
issn = {1529-2916},
}
RevDate: 2026-03-17
A National Survey of Medical Physicists: Part 2-Assessing Work Effort and Perceived Challenges and Satisfaction in HDR Brachytherapy.
International journal of radiation oncology, biology, physics pii:S0360-3016(26)00402-5 [Epub ahead of print].
PURPOSE: To collect national data from medical physicists on work effort, challenges, and job satisfaction in high-dose rate (HDR) brachytherapy (BT) as a function of procedure complexity.
METHODS AND MATERIALS: A survey was administered in cooperation with IROC-Houston. Question topics included demographics, practice patterns, caseload, procedure complexity, relative time and effort required for simple and complex cases, and challenges/satisfaction associated with HDR BT.
RESULTS: Of 429 completed responses, 365 performed HDR BT. The most commonly treated anatomic sites were gynecologic, prostate, and skin, with 56% of respondents' clinics performing interstitial procedures. Respondents indicated that the median time and intensity ratios of a single-channel HDR BT, relative to a weekly chart check (CPT77336), were 5 and 3, respectively, implying a work ratio of 15. When comparing the most complex procedure with a single-channel treatment, the median time and intensity ratios reported were both 5, implying a work ratio of 25. The time and intensity ratios scaled with increasing complexity for gyne procedures (ie, 1, 2-3, and ≥4 channels). Most respondents reported that it was more stressful to cover HDR BT versus external beam radiation therapy (EBRT) (82%) and to switch between services (73%). Job satisfaction was impacted most positively by direct patient contact and the experience level of authorized users, but most negatively by increased stress compared with other services and maintaining skill levels due to infrequent cases. Only the subset of respondents at clinics treating complex gyne with a high caseload (≥25 patients/y) indicated that staff allocation was inadequate or that a colleague had left their position due to HDR BT.
CONCLUSIONS: The results show a relationship between work effort and procedure complexity, which is currently not addressed in national staffing recommendations. To sustain a workforce capable of supporting HDR brachytherapy into the future, professional societies/leaders must recognize the stress and intensity of complex cases and adjust staffing recommendations accordingly.
Additional Links: PMID-41722658
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@article {pmid41722658,
year = {2026},
author = {Al-Hallaq, HA and Zoberi, JE and Tran, A and Kim, H and Lowenstein, JR and Meyer, J},
title = {A National Survey of Medical Physicists: Part 2-Assessing Work Effort and Perceived Challenges and Satisfaction in HDR Brachytherapy.},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2026.02.229},
pmid = {41722658},
issn = {1879-355X},
abstract = {PURPOSE: To collect national data from medical physicists on work effort, challenges, and job satisfaction in high-dose rate (HDR) brachytherapy (BT) as a function of procedure complexity.
METHODS AND MATERIALS: A survey was administered in cooperation with IROC-Houston. Question topics included demographics, practice patterns, caseload, procedure complexity, relative time and effort required for simple and complex cases, and challenges/satisfaction associated with HDR BT.
RESULTS: Of 429 completed responses, 365 performed HDR BT. The most commonly treated anatomic sites were gynecologic, prostate, and skin, with 56% of respondents' clinics performing interstitial procedures. Respondents indicated that the median time and intensity ratios of a single-channel HDR BT, relative to a weekly chart check (CPT77336), were 5 and 3, respectively, implying a work ratio of 15. When comparing the most complex procedure with a single-channel treatment, the median time and intensity ratios reported were both 5, implying a work ratio of 25. The time and intensity ratios scaled with increasing complexity for gyne procedures (ie, 1, 2-3, and ≥4 channels). Most respondents reported that it was more stressful to cover HDR BT versus external beam radiation therapy (EBRT) (82%) and to switch between services (73%). Job satisfaction was impacted most positively by direct patient contact and the experience level of authorized users, but most negatively by increased stress compared with other services and maintaining skill levels due to infrequent cases. Only the subset of respondents at clinics treating complex gyne with a high caseload (≥25 patients/y) indicated that staff allocation was inadequate or that a colleague had left their position due to HDR BT.
CONCLUSIONS: The results show a relationship between work effort and procedure complexity, which is currently not addressed in national staffing recommendations. To sustain a workforce capable of supporting HDR brachytherapy into the future, professional societies/leaders must recognize the stress and intensity of complex cases and adjust staffing recommendations accordingly.},
}
RevDate: 2026-03-12
Management of chronic myeloid leukemia with tyrosine kinase inhibitors: adverse events, toxicities and therapy dosing.
Haematologica [Epub ahead of print].
Targeted therapies have made near normal life span an attainable goal for many patients with chronic phase (CP) chronic myeloid leukemia (CML). Most patients require years of therapy and not everyone may be able to discontinue treatment permanently without CML recurrence. BCR::ABL1 targeted tyrosine kinase inhibitors (TKIs) including ATP binding site and allosteric inhibitors that bind to the myristoyl pocket are associated with treatment-emergent adverse events (TEAEs) that may compromise quality of life and well-being. Although alternative treatment options exist, side effects may persist, or new ones occur after a therapy switch. Using a case-based approach, this review examines the incidence of non-hematologic and hematologic TEAEs with specific therapies, provides guidance on AE management, and describes the impact of therapy dose reduction on efficacy and tolerability.
Additional Links: PMID-41816837
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@article {pmid41816837,
year = {2026},
author = {Oehler, VG and Berman, E and Huang, IJ},
title = {Management of chronic myeloid leukemia with tyrosine kinase inhibitors: adverse events, toxicities and therapy dosing.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2025.288334},
pmid = {41816837},
issn = {1592-8721},
abstract = {Targeted therapies have made near normal life span an attainable goal for many patients with chronic phase (CP) chronic myeloid leukemia (CML). Most patients require years of therapy and not everyone may be able to discontinue treatment permanently without CML recurrence. BCR::ABL1 targeted tyrosine kinase inhibitors (TKIs) including ATP binding site and allosteric inhibitors that bind to the myristoyl pocket are associated with treatment-emergent adverse events (TEAEs) that may compromise quality of life and well-being. Although alternative treatment options exist, side effects may persist, or new ones occur after a therapy switch. Using a case-based approach, this review examines the incidence of non-hematologic and hematologic TEAEs with specific therapies, provides guidance on AE management, and describes the impact of therapy dose reduction on efficacy and tolerability.},
}
RevDate: 2026-03-13
CmpDate: 2026-03-12
APOE and plasma AD biomarkers: The role of genetic ancestry in Hispanics/Latinos.
Alzheimer's & dementia : the journal of the Alzheimer's Association, 22(3):e71213.
BACKGROUND: Apolipoprotein E (APOE) alleles are well-established genetic risk factors for Alzheimer's disease (AD), but their effects on AD biomarkers (amyloid beta [Aβ]42/40, phosphorylated tau [p-tau]181, neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]) may vary across populations due to ancestry-, age-, and sex-related differences. We hypothesized that these effects vary across Hispanic/Latino background groups with distinct ancestral admixture.
METHODS: We analyzed ε2 and ε4 allele associations with AD biomarkers using survey-weighted linear regression models, adjusting for demographic covariates. Secondary analyses examined genetic analysis group- and ancestry-specific effects.
RESULTS: ε4 was associated with lower Aβ42/40 and higher p-tau181and GFAP levels, but not with NfL, suggesting its role in Aβ and tau deposition and neuroinflammation. ε4 associations were stronger in those with higher European and lower African ancestry.
DISCUSSION: These findings expand on prior studies suggesting that genetic ancestry modifies APOE-associated AD risk in Hispanic/Latino populations and highlight the importance of capturing ancestry-based heterogeneity in AD biomarker research.
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@article {pmid41816965,
year = {2026},
author = {Cheung, C and Anita, NZ and Filigrana, P and Fornage, M and Gonzalez, KA and Gallo, LC and Isasi, CR and Kaplan, RC and Li, X and Márquez, F and Parada, H and Perreira, KM and Ramos, AR and Rundek, T and Tarraf, W and Testai, FD and DeCarli, C and González, HM and Sofer, T},
title = {APOE and plasma AD biomarkers: The role of genetic ancestry in Hispanics/Latinos.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71213},
doi = {10.1002/alz.71213},
pmid = {41816965},
issn = {1552-5279},
support = {R01 AG048642/AG/NIA NIH HHS/United States ; R01 AG080598/AG/NIA NIH HHS/United States ; R01AG075758//National Institute on Aging (NIA)/ ; R01 AG075758/AG/NIA NIH HHS/United States ; R56AG048642//National Institute on Aging (NIA)/ ; R01AG048642//National Institute on Aging (NIA)/ ; },
mesh = {Humans ; *Hispanic or Latino/genetics ; Female ; Male ; *Alzheimer Disease/genetics/blood/ethnology ; Biomarkers/blood ; tau Proteins/blood ; Aged ; Amyloid beta-Peptides/blood ; *Apolipoproteins E/genetics ; Glial Fibrillary Acidic Protein/blood ; Neurofilament Proteins/blood ; Middle Aged ; Aged, 80 and over ; Apolipoprotein E4/genetics ; Peptide Fragments/blood ; White ; },
abstract = {BACKGROUND: Apolipoprotein E (APOE) alleles are well-established genetic risk factors for Alzheimer's disease (AD), but their effects on AD biomarkers (amyloid beta [Aβ]42/40, phosphorylated tau [p-tau]181, neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]) may vary across populations due to ancestry-, age-, and sex-related differences. We hypothesized that these effects vary across Hispanic/Latino background groups with distinct ancestral admixture.
METHODS: We analyzed ε2 and ε4 allele associations with AD biomarkers using survey-weighted linear regression models, adjusting for demographic covariates. Secondary analyses examined genetic analysis group- and ancestry-specific effects.
RESULTS: ε4 was associated with lower Aβ42/40 and higher p-tau181and GFAP levels, but not with NfL, suggesting its role in Aβ and tau deposition and neuroinflammation. ε4 associations were stronger in those with higher European and lower African ancestry.
DISCUSSION: These findings expand on prior studies suggesting that genetic ancestry modifies APOE-associated AD risk in Hispanic/Latino populations and highlight the importance of capturing ancestry-based heterogeneity in AD biomarker research.},
}
MeSH Terms:
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Humans
*Hispanic or Latino/genetics
Female
Male
*Alzheimer Disease/genetics/blood/ethnology
Biomarkers/blood
tau Proteins/blood
Aged
Amyloid beta-Peptides/blood
*Apolipoproteins E/genetics
Glial Fibrillary Acidic Protein/blood
Neurofilament Proteins/blood
Middle Aged
Aged, 80 and over
Apolipoprotein E4/genetics
Peptide Fragments/blood
White
RevDate: 2026-03-12
Reading the "T" Leaves: Predicting Outcomes with Bispecific Antibodies in Multiple Myeloma.
Blood cancer discovery pii:775215 [Epub ahead of print].
In this issue of Blood Cancer Discovery, Frenking and colleagues demonstrate the prognostic potential of three risk score models to predict hematotoxicity, infections, response rates, and survival following bispecific T-cell engager (TCE) therapy in multiple myeloma. These risk score models, which the authors validated using retrospective real-world data from 278 patients, can easily be calculated using routine blood testing and offer the potential to improve the efficacy and safety of TCE therapy. See related article by Frenking et al., p. XX .
Additional Links: PMID-41817149
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@article {pmid41817149,
year = {2026},
author = {Banerjee, R and Dhodapkar, MV},
title = {Reading the "T" Leaves: Predicting Outcomes with Bispecific Antibodies in Multiple Myeloma.},
journal = {Blood cancer discovery},
volume = {},
number = {},
pages = {OF1-OF3},
doi = {10.1158/2643-3230.BCD-26-0041},
pmid = {41817149},
issn = {2643-3249},
abstract = {In this issue of Blood Cancer Discovery, Frenking and colleagues demonstrate the prognostic potential of three risk score models to predict hematotoxicity, infections, response rates, and survival following bispecific T-cell engager (TCE) therapy in multiple myeloma. These risk score models, which the authors validated using retrospective real-world data from 278 patients, can easily be calculated using routine blood testing and offer the potential to improve the efficacy and safety of TCE therapy. See related article by Frenking et al., p. XX .},
}
RevDate: 2026-03-12
Molecular Characterization of KLK2 RNA Expression in Prostate Cancer.
Clinical cancer research : an official journal of the American Association for Cancer Research pii:775238 [Epub ahead of print].
PURPOSE: KLK2 is an androgen-regulated gene critical in prostate cancer biology with multiple KLK2-targeted therapies in clinical development. We investigated KLK2 RNA expression patterns and associations with molecular features to provide context for emerging KLK2-targeted treatments.
EXPERIMENTAL DESIGN: DNA/RNA next-generation sequencing was performed on 7,078 prostate cancer specimens. KLK2-high/low RNA expression was defined as ≥75th/<25th percentiles (transcripts per million, TPM). KLK2 expression was evaluated across histologic subtypes, disease states, and metastatic sites, with correlative analyses of genomic alterations, RNA signatures, and clinical outcomes.
RESULTS: KLK2 gene expression varied significantly by histology, with highest levels in adenocarcinoma (8.79 log2[TPM+1]) and minimal expression in histologic neuroendocrine prostate cancer (0.33 log2[TPM+1]). Expression was significantly higher in androgen deprivation therapy (ADT)/androgen receptor pathway inhibitor (ARPI)-sensitive versus ADT/ARPI-exposed tumors (8.97 vs. 8.38 log2[TPM+1], q<0.001). Localized tumors demonstrated higher expression than lymph node (8.93 vs. 8.76 log2[TPM+1]) or distant metastases (8.23 log2[TPM+1]), with visceral metastases showing the lowest levels. In the overall cohort, KLK2 expression correlated positively with androgen receptor signaling (r=0.25-0.47) and negatively with neuroendocrine signaling. High KLK2 expression was associated with significantly improved overall survival (93.9 vs. 74.4 months, hazard ratio 0.68, p<0.001) in the total cohort, with similar patterns in patients with ADT/ARPI-sensitive and ADT/ARPI-exposed disease.
CONCLUSIONS: This large-scale clinico-genomic analysis reveals distinct KLK2 expression patterns across prostate cancer histologies, tumor sites, and clinical states. These findings provide a molecular framework understanding KLK2 as a therapeutic target in prostate cancer.
Additional Links: PMID-41817312
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PubMed:
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@article {pmid41817312,
year = {2026},
author = {McKay, RR and Nazari, SS and Elliott, A and Smith, N and Barata, P and Kilari, D and Garje, R and Haffner, MC and Morrissey, C and Rupnow, BA and Basu, S and Drake, C and Rose, B and Bagrodia, A and Agarwal, N and Antonarakis, ES and Beltran, H},
title = {Molecular Characterization of KLK2 RNA Expression in Prostate Cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-25-4293},
pmid = {41817312},
issn = {1557-3265},
abstract = {PURPOSE: KLK2 is an androgen-regulated gene critical in prostate cancer biology with multiple KLK2-targeted therapies in clinical development. We investigated KLK2 RNA expression patterns and associations with molecular features to provide context for emerging KLK2-targeted treatments.
EXPERIMENTAL DESIGN: DNA/RNA next-generation sequencing was performed on 7,078 prostate cancer specimens. KLK2-high/low RNA expression was defined as ≥75th/<25th percentiles (transcripts per million, TPM). KLK2 expression was evaluated across histologic subtypes, disease states, and metastatic sites, with correlative analyses of genomic alterations, RNA signatures, and clinical outcomes.
RESULTS: KLK2 gene expression varied significantly by histology, with highest levels in adenocarcinoma (8.79 log2[TPM+1]) and minimal expression in histologic neuroendocrine prostate cancer (0.33 log2[TPM+1]). Expression was significantly higher in androgen deprivation therapy (ADT)/androgen receptor pathway inhibitor (ARPI)-sensitive versus ADT/ARPI-exposed tumors (8.97 vs. 8.38 log2[TPM+1], q<0.001). Localized tumors demonstrated higher expression than lymph node (8.93 vs. 8.76 log2[TPM+1]) or distant metastases (8.23 log2[TPM+1]), with visceral metastases showing the lowest levels. In the overall cohort, KLK2 expression correlated positively with androgen receptor signaling (r=0.25-0.47) and negatively with neuroendocrine signaling. High KLK2 expression was associated with significantly improved overall survival (93.9 vs. 74.4 months, hazard ratio 0.68, p<0.001) in the total cohort, with similar patterns in patients with ADT/ARPI-sensitive and ADT/ARPI-exposed disease.
CONCLUSIONS: This large-scale clinico-genomic analysis reveals distinct KLK2 expression patterns across prostate cancer histologies, tumor sites, and clinical states. These findings provide a molecular framework understanding KLK2 as a therapeutic target in prostate cancer.},
}
RevDate: 2026-03-13
Inference on function-valued parameters using a restricted score test.
Journal of the Royal Statistical Society. Series B, Statistical methodology [Epub ahead of print].
It is often of interest to make inference on an unknown function that is a local parameter of the data-generating mechanism, such as a density or regression function. Such estimands can typically only be estimated at a slower-than-parametric rate in nonparametric and semiparametric models, and performing calibrated inference can be challenging. In many cases, these estimands can be expressed as the minimizer of a population risk functional. Here, we propose a general framework that leverages such representation and provides a nonparametric extension of the score test for inference on an infinite-dimensional risk minimizer. We demonstrate that our framework is applicable in a wide variety of problems. As both analytic and computational examples, we describe how to use our general approach for inference on a mean regression function under (i) nonparametric and (ii) partially additive models, and evaluate the operating characteristics of the resulting procedures via simulations. Assessment of effect heterogeneity, inference on density functions, and conditional independence testing are discussed as additional examples.
Additional Links: PMID-41808921
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@article {pmid41808921,
year = {2026},
author = {Hudson, A and Carone, M and Shojaie, A},
title = {Inference on function-valued parameters using a restricted score test.},
journal = {Journal of the Royal Statistical Society. Series B, Statistical methodology},
volume = {},
number = {},
pages = {},
pmid = {41808921},
issn = {1467-9868},
support = {R01 GM114029/GM/NIGMS NIH HHS/United States ; R01 GM133848/GM/NIGMS NIH HHS/United States ; R01 HL137808/HL/NHLBI NIH HHS/United States ; RF1 AG090462/AG/NIA NIH HHS/United States ; },
abstract = {It is often of interest to make inference on an unknown function that is a local parameter of the data-generating mechanism, such as a density or regression function. Such estimands can typically only be estimated at a slower-than-parametric rate in nonparametric and semiparametric models, and performing calibrated inference can be challenging. In many cases, these estimands can be expressed as the minimizer of a population risk functional. Here, we propose a general framework that leverages such representation and provides a nonparametric extension of the score test for inference on an infinite-dimensional risk minimizer. We demonstrate that our framework is applicable in a wide variety of problems. As both analytic and computational examples, we describe how to use our general approach for inference on a mean regression function under (i) nonparametric and (ii) partially additive models, and evaluate the operating characteristics of the resulting procedures via simulations. Assessment of effect heterogeneity, inference on density functions, and conditional independence testing are discussed as additional examples.},
}
RevDate: 2026-03-11
Reply to: Methodologic Considerations for Subsequent Colorectal Cancer in Survivors of Childhood Cancer.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [Epub ahead of print].
Additional Links: PMID-41812087
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PubMed:
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@article {pmid41812087,
year = {2026},
author = {Owens, CA and Ludmir, EB and Liu, Q and Qiu, W and Gupta, AC and Smith, SA and Rigaud, B and Brock, KK and Bates, JE and Meyers, TG and Paulino, AC and Peterson, CB and Kry, SF and Teepen, JC and Ronckers, CM and Neglia, JP and Leisenring, WM and Oeffinger, KC and Nathan, PC and Turcotte, LM and Hodgson, DC and Hudson, MM and Robison, LL and Moskowitz, CS and Armstrong, GT and Henderson, TO and Yasui, Y and Howell, RM},
title = {Reply to: Methodologic Considerations for Subsequent Colorectal Cancer in Survivors of Childhood Cancer.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2600051},
doi = {10.1200/JCO-26-00051},
pmid = {41812087},
issn = {1527-7755},
}
RevDate: 2026-03-12
Context dependency is essential for predicting intrahost evolution.
Nature ecology & evolution, 10(3):389-391.
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@article {pmid41813924,
year = {2026},
author = {Feder, AF and DeWitt, WS},
title = {Context dependency is essential for predicting intrahost evolution.},
journal = {Nature ecology & evolution},
volume = {10},
number = {3},
pages = {389-391},
pmid = {41813924},
issn = {2397-334X},
}
RevDate: 2026-03-10
The Pathologic Response Evaluation and Detection in Circulating Tumor-DNA Study: Ultrasensitive Circulating Tumor-DNA Assessment of Breast Cancer Minimal Residual Disease.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [Epub ahead of print].
PURPOSE: Patients with stage II/III human epidermal growth factor receptor 2 (HER2)-positive or triple-negative breast cancer (TNBC) frequently receive neoadjuvant therapy (NAT). Although pathologic complete response (pCR) correlates with improved outcomes, many non-pCR patients have long-term survival. Circulating tumor-DNA (ctDNA) minimal residual disease (MRD) assessment may provide additional or superior risk stratification.
METHODS: Pathologic Response Evaluation and Detection in Circulating Tumor-DNA is a prospective, multicenter study evaluating ctDNA as a biomarker of treatment response using a tumor-informed, ultrasensitive (<100 parts per million) assay. The primary objective was to determine whether the negative predictive value (NPV) of post-NAT ctDNA for pCR was ≥90%. A prespecified secondary objective for the TNBC cohort was to assess associations between ctDNA and 5-year invasive disease-free survival (IDFS). ctDNA was evaluated at baseline, after NAT before surgery, and after surgery.
RESULTS: Of 227 enrolled patients, 220 were evaluable for pCR (48% HER2-positive; 52% TNBC) and 91 patients (41%) had pCR. The primary objective was not met. Although all patients with pCR were ctDNA-negative after NAT, 40% of non-pCR patients were also ctDNA-negative (NPV, 60% [95% CI, 0.50 to 0.69]). However, the prespecified secondary objective was met. Detectable ctDNA after NAT was prognostic for recurrence (hazard ratio [HR], 8.9 [95% CI, 2.4 to 33]; P = .001), independent of pCR. Additionally, detectable ctDNA after surgery identified patients at extremely high recurrence risk (HR, 128 [95% CI, 15 to 1,083]; P < .001), while ctDNA-negative patients after surgery had 94% 5-year IDFS.
CONCLUSION: In HER2-positive breast cancer and TNBC, ctDNA after NAT does not discriminate pCR from non-pCR. However, ctDNA provides markedly superior prognostic stratification, identifying patients with exceptional outcomes and those at extreme risk. These findings support ctDNA-guided therapeutic de-escalation and escalation strategies.
Additional Links: PMID-41805422
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PubMed:
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@article {pmid41805422,
year = {2026},
author = {Hunter, NB and Parsons, HA and Cope, L and Canzoniero, JV and Navarro, FCP and El-Refai, S and Anampa, JD and Sparano, JA and Rimawi, M and Storniolo, AM and Mainor, C and Nanda, R and DeMichele, A and Gupta, GP and Stringer-Reasor, EJ and Lynce, F and Cobain, EF and Puhalla, S and Jankowitz, R and Rexer, B and Mayer, I and Hwang, ES and Blackwell, K and El Ayass, W and Lee, Y and Tweed, C and Wilkinson, M and Pennisi, A and Sun, B and Wright, P and Gralow, JR and Chen, R and Boyle, SM and Stearns, V and Wolff, AC and Park, BH},
title = {The Pathologic Response Evaluation and Detection in Circulating Tumor-DNA Study: Ultrasensitive Circulating Tumor-DNA Assessment of Breast Cancer Minimal Residual Disease.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502934},
doi = {10.1200/JCO-25-02934},
pmid = {41805422},
issn = {1527-7755},
abstract = {PURPOSE: Patients with stage II/III human epidermal growth factor receptor 2 (HER2)-positive or triple-negative breast cancer (TNBC) frequently receive neoadjuvant therapy (NAT). Although pathologic complete response (pCR) correlates with improved outcomes, many non-pCR patients have long-term survival. Circulating tumor-DNA (ctDNA) minimal residual disease (MRD) assessment may provide additional or superior risk stratification.
METHODS: Pathologic Response Evaluation and Detection in Circulating Tumor-DNA is a prospective, multicenter study evaluating ctDNA as a biomarker of treatment response using a tumor-informed, ultrasensitive (<100 parts per million) assay. The primary objective was to determine whether the negative predictive value (NPV) of post-NAT ctDNA for pCR was ≥90%. A prespecified secondary objective for the TNBC cohort was to assess associations between ctDNA and 5-year invasive disease-free survival (IDFS). ctDNA was evaluated at baseline, after NAT before surgery, and after surgery.
RESULTS: Of 227 enrolled patients, 220 were evaluable for pCR (48% HER2-positive; 52% TNBC) and 91 patients (41%) had pCR. The primary objective was not met. Although all patients with pCR were ctDNA-negative after NAT, 40% of non-pCR patients were also ctDNA-negative (NPV, 60% [95% CI, 0.50 to 0.69]). However, the prespecified secondary objective was met. Detectable ctDNA after NAT was prognostic for recurrence (hazard ratio [HR], 8.9 [95% CI, 2.4 to 33]; P = .001), independent of pCR. Additionally, detectable ctDNA after surgery identified patients at extremely high recurrence risk (HR, 128 [95% CI, 15 to 1,083]; P < .001), while ctDNA-negative patients after surgery had 94% 5-year IDFS.
CONCLUSION: In HER2-positive breast cancer and TNBC, ctDNA after NAT does not discriminate pCR from non-pCR. However, ctDNA provides markedly superior prognostic stratification, identifying patients with exceptional outcomes and those at extreme risk. These findings support ctDNA-guided therapeutic de-escalation and escalation strategies.},
}
RevDate: 2026-03-11
Structural basis for antibody cross-neutralization of Dengue and Zika viruses.
Communications biology pii:10.1038/s42003-026-09805-6 [Epub ahead of print].
Safe and effective vaccines against co-circulating mosquito-borne orthoflaviviruses such as Zika virus (ZikV) and the four serotypes of Dengue virus (DenV1-4) must elicit broadly neutralizing antibodies (bnAbs) to prevent the risk of enhancement of infection by non-neutralizing antibodies. We recently discovered new orthoflavivirus-directed bnAbs, including F25.S02, which neutralizes DenV1-4 and ZikV with comparable or superior potency to the previously characterized E dimer epitope (EDE) bnAbs. Here, we used cryoEM and X-ray crystallography to understand the basis of cross-neutralization of F25.S02 at the molecular level. We obtained a ~ 4.2 Å cryoEM structure of F25.S02 Fab bound to a stabilized DenV3 soluble E protein dimer and a 2.3 Å crystal structure of F25.S02 Fab bound to ZikV soluble E protein dimer. Like previously described EDE1 bnAbs, the structural epitope of F25.S02 is at the E dimer interface, encompassing predominantly conserved regions in domain II, including the fusion loop. However, unlike EDE1 bnAbs, F25.S02 binding is almost entirely dependent on the heavy chain and is shifted slightly away from the dimer symmetry axis. Our findings emphasize the importance of this cross-neutralizing site of vulnerability for DenV and ZikV that can facilitate rational design of vaccines and therapeutics.
Additional Links: PMID-41807764
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@article {pmid41807764,
year = {2026},
author = {Hurlburt, NK and Lubow, J and Goo, L and Pancera, M},
title = {Structural basis for antibody cross-neutralization of Dengue and Zika viruses.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-09805-6},
pmid = {41807764},
issn = {2399-3642},
abstract = {Safe and effective vaccines against co-circulating mosquito-borne orthoflaviviruses such as Zika virus (ZikV) and the four serotypes of Dengue virus (DenV1-4) must elicit broadly neutralizing antibodies (bnAbs) to prevent the risk of enhancement of infection by non-neutralizing antibodies. We recently discovered new orthoflavivirus-directed bnAbs, including F25.S02, which neutralizes DenV1-4 and ZikV with comparable or superior potency to the previously characterized E dimer epitope (EDE) bnAbs. Here, we used cryoEM and X-ray crystallography to understand the basis of cross-neutralization of F25.S02 at the molecular level. We obtained a ~ 4.2 Å cryoEM structure of F25.S02 Fab bound to a stabilized DenV3 soluble E protein dimer and a 2.3 Å crystal structure of F25.S02 Fab bound to ZikV soluble E protein dimer. Like previously described EDE1 bnAbs, the structural epitope of F25.S02 is at the E dimer interface, encompassing predominantly conserved regions in domain II, including the fusion loop. However, unlike EDE1 bnAbs, F25.S02 binding is almost entirely dependent on the heavy chain and is shifted slightly away from the dimer symmetry axis. Our findings emphasize the importance of this cross-neutralizing site of vulnerability for DenV and ZikV that can facilitate rational design of vaccines and therapeutics.},
}
RevDate: 2026-03-13
CmpDate: 2026-03-11
Phenotypically similar but functionally distinct NK cell populations within the human maternal-fetal interface.
ImmunoHorizons, 10(3):.
Natural killer (NK) cell function within tissues extends beyond exerting cytotoxicity, encompassing a range of functions that are just starting to become fully elucidated. In the context of human placentation, NK cells play a key role in enabling initial placentation, which is associated with the acquisition of tolerance-like properties. If and to which extent NK cells maintain these tolerance-like properties over the course of human pregnancy is still poorly understood. We asked if NK cells isolated from the decidual-placental interface of full-term human pregnancies are able to exert effector function. We observed a significant and striking lack in the ability of NK cells isolated from the decidual-placental interface (DPI) to produce interferon-g (IFN-γ) in response to the activating cytokines interleukin (IL)-12, IL-15, and IL-18. In contrast, NK cells from the decidua retained their responsiveness to cytokine-mediated activation. Notably, CD103+CD69+ tissue-resident NK cells were present in both DPI and decidua, yet exhibited distinct effector function from one another. Using high-parameter flow cytometry and single-cell sequencing, we found that this functional discrepancy was not directly predictable based on their cell surface phenotype or cell transcript. Together, our findings reveal the presence of distinct functional resident NK cell populations in 2 anatomically adjacent tissues at healthy full-term pregnancies.
Additional Links: PMID-41808348
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@article {pmid41808348,
year = {2026},
author = {Frutoso, M and DeJong, CS and Shree, R and McCartney, SA and Prlic, M},
title = {Phenotypically similar but functionally distinct NK cell populations within the human maternal-fetal interface.},
journal = {ImmunoHorizons},
volume = {10},
number = {3},
pages = {},
pmid = {41808348},
issn = {2573-7732},
support = {1R01AI179712/NH/NIH HHS/United States ; R21AI144677/NH/NIH HHS/United States ; },
mesh = {Humans ; *Killer Cells, Natural/immunology/metabolism ; Female ; Pregnancy ; *Decidua/immunology/cytology ; *Placenta/immunology/cytology ; Cytokines/metabolism ; Interferon-gamma/metabolism ; Placentation/immunology ; Lymphocyte Activation ; Phenotype ; Flow Cytometry ; },
abstract = {Natural killer (NK) cell function within tissues extends beyond exerting cytotoxicity, encompassing a range of functions that are just starting to become fully elucidated. In the context of human placentation, NK cells play a key role in enabling initial placentation, which is associated with the acquisition of tolerance-like properties. If and to which extent NK cells maintain these tolerance-like properties over the course of human pregnancy is still poorly understood. We asked if NK cells isolated from the decidual-placental interface of full-term human pregnancies are able to exert effector function. We observed a significant and striking lack in the ability of NK cells isolated from the decidual-placental interface (DPI) to produce interferon-g (IFN-γ) in response to the activating cytokines interleukin (IL)-12, IL-15, and IL-18. In contrast, NK cells from the decidua retained their responsiveness to cytokine-mediated activation. Notably, CD103+CD69+ tissue-resident NK cells were present in both DPI and decidua, yet exhibited distinct effector function from one another. Using high-parameter flow cytometry and single-cell sequencing, we found that this functional discrepancy was not directly predictable based on their cell surface phenotype or cell transcript. Together, our findings reveal the presence of distinct functional resident NK cell populations in 2 anatomically adjacent tissues at healthy full-term pregnancies.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Killer Cells, Natural/immunology/metabolism
Female
Pregnancy
*Decidua/immunology/cytology
*Placenta/immunology/cytology
Cytokines/metabolism
Interferon-gamma/metabolism
Placentation/immunology
Lymphocyte Activation
Phenotype
Flow Cytometry
RevDate: 2026-03-10
CmpDate: 2026-03-10
Inference for microbe-metabolite association networks using a latent graph model.
Biometrics, 82(1):.
Correlation networks are commonly used to infer associations between microbes and metabolites. The resulting $p$-values are then corrected for multiple comparisons using existing methods such as the Benjamini & Hochberg (BH) procedure to control the false discovery rate (FDR). However, most existing methods for FDR control assume the $p$-values are weakly dependent. Consequently, they can have low power in recovering microbe-metabolite association networks that exhibit important topological features, such as the presence of densely associated modules. We propose a novel inference procedure that is both powerful for detecting significant associations in the microbe-metabolite network and capable of controlling the FDR. Power enhancement is achieved by modeling latent structures in the form of a bipartite stochastic block model. We develop a variational expectation-maximization (EM) algorithm to estimate the model parameters and incorporate the learned graph in the testing procedure. In addition to FDR control, this procedure provides a clustering of microbes and metabolites into modules, which is useful for interpretation. We demonstrate the merit of the proposed method in simulations and an application to bacterial vaginosis.
Additional Links: PMID-41804865
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PubMed:
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@article {pmid41804865,
year = {2026},
author = {Ma, J},
title = {Inference for microbe-metabolite association networks using a latent graph model.},
journal = {Biometrics},
volume = {82},
number = {1},
pages = {},
doi = {10.1093/biomtc/ujag042},
pmid = {41804865},
issn = {1541-0420},
support = {R01 GM145772/GF/NIH HHS/United States ; },
mesh = {Algorithms ; Computer Simulation ; Humans ; *Models, Statistical ; Female ; *Microbiota ; *Metabolic Networks and Pathways ; Stochastic Processes ; },
abstract = {Correlation networks are commonly used to infer associations between microbes and metabolites. The resulting $p$-values are then corrected for multiple comparisons using existing methods such as the Benjamini & Hochberg (BH) procedure to control the false discovery rate (FDR). However, most existing methods for FDR control assume the $p$-values are weakly dependent. Consequently, they can have low power in recovering microbe-metabolite association networks that exhibit important topological features, such as the presence of densely associated modules. We propose a novel inference procedure that is both powerful for detecting significant associations in the microbe-metabolite network and capable of controlling the FDR. Power enhancement is achieved by modeling latent structures in the form of a bipartite stochastic block model. We develop a variational expectation-maximization (EM) algorithm to estimate the model parameters and incorporate the learned graph in the testing procedure. In addition to FDR control, this procedure provides a clustering of microbes and metabolites into modules, which is useful for interpretation. We demonstrate the merit of the proposed method in simulations and an application to bacterial vaginosis.},
}
MeSH Terms:
show MeSH Terms
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Algorithms
Computer Simulation
Humans
*Models, Statistical
Female
*Microbiota
*Metabolic Networks and Pathways
Stochastic Processes
RevDate: 2026-03-12
CmpDate: 2026-03-10
Multi-omic profiling defines three distinct molecular subtypes of urothelial carcinoma with implications for precision therapy.
Clinical and translational medicine, 16(3):e70638.
BACKGROUND: Urothelial carcinoma (UC) is a biologically heterogeneous disease, and current molecular classifications have limited integration into clinical decision-making. To further pursue precision oncology efforts in UC, we developed a molecular classification framework applicable to transcriptomic and proteomic data from non-muscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC) and urothelial cancer cell lines.
METHODS: Using a whole-transcriptome self-organised map and regularised semi-supervised clustering of 4439 bulk NMIBC and MIBC transcriptomes and proteomes, and 33 UC cell lines, we identified three molecular UC clusters. Making use of both in silico and in vitro approaches, we selected promising treatment approaches for each cluster.
RESULTS: The three developed clusters displayed distinct signatures of mRNA, proteins, biological processes, metabolism and essential driver genes. They also differed in prognosis and machine learning-predicted treatment vulnerabilities and resistance. High-risk, stroma-rich Cluster #1 cancers were predicted to respond to selected cytotoxic drugs, ferroptosis inducers and PARP inhibitors. For the aggressive, fast-proliferating, immune-infiltrated Cluster #2 tumours with basal/squamous differentiation, cytotoxic agents and EGFR/ERBB- and MEK/ERK-targeting therapies were proposed. Cluster #3 cancers of predominantly luminal papillary phenotype with scarce stroma and immune infiltration were enriched with NMIBC and low-risk malignancies. For patients with Cluster #3 tumours, selected epigenetic drugs or EGFR/FGFR inhibitors may represent attractive treatment options.
CONCLUSIONS: Our novel molecular taxonomy holds promise as a practical framework for patient risk stratification and clinical trials in UC. Our molecular classification scheme may facilitate personalised transcriptome- and proteome-based risk assessment and clinical trial design for the development of various therapeutics.
KEY POINTS: We developed three UC clusters, applicable for MIBC and NMIBC, which were validated using transcriptomic- and proteomic datasets. Publically available UC cell lines were assigned to the clusters, to have in vitro models representing each cluster. The clusters differ in molecular and biological signatures, with distinct prognostic and therapeutic characteristics.
Additional Links: PMID-41804750
PubMed:
Citation:
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@article {pmid41804750,
year = {2026},
author = {van Creij, NCH and Tymoszuk, P and Handle, F and Seeber, A and Sellemond, T and Martowicz, A and Comperat, E and Wafa, H and Ormanns, S and Günther, M and Parson, W and Noeparast, M and Santer, FR and Subiela, JD and Grivas, P and Li, R and Culig, Z and Pichler, R},
title = {Multi-omic profiling defines three distinct molecular subtypes of urothelial carcinoma with implications for precision therapy.},
journal = {Clinical and translational medicine},
volume = {16},
number = {3},
pages = {e70638},
pmid = {41804750},
issn = {2001-1326},
mesh = {Humans ; *Precision Medicine/methods ; *Urinary Bladder Neoplasms/genetics/classification ; Gene Expression Profiling/methods ; Cell Line, Tumor ; Transcriptome ; Multiomics ; },
abstract = {BACKGROUND: Urothelial carcinoma (UC) is a biologically heterogeneous disease, and current molecular classifications have limited integration into clinical decision-making. To further pursue precision oncology efforts in UC, we developed a molecular classification framework applicable to transcriptomic and proteomic data from non-muscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC) and urothelial cancer cell lines.
METHODS: Using a whole-transcriptome self-organised map and regularised semi-supervised clustering of 4439 bulk NMIBC and MIBC transcriptomes and proteomes, and 33 UC cell lines, we identified three molecular UC clusters. Making use of both in silico and in vitro approaches, we selected promising treatment approaches for each cluster.
RESULTS: The three developed clusters displayed distinct signatures of mRNA, proteins, biological processes, metabolism and essential driver genes. They also differed in prognosis and machine learning-predicted treatment vulnerabilities and resistance. High-risk, stroma-rich Cluster #1 cancers were predicted to respond to selected cytotoxic drugs, ferroptosis inducers and PARP inhibitors. For the aggressive, fast-proliferating, immune-infiltrated Cluster #2 tumours with basal/squamous differentiation, cytotoxic agents and EGFR/ERBB- and MEK/ERK-targeting therapies were proposed. Cluster #3 cancers of predominantly luminal papillary phenotype with scarce stroma and immune infiltration were enriched with NMIBC and low-risk malignancies. For patients with Cluster #3 tumours, selected epigenetic drugs or EGFR/FGFR inhibitors may represent attractive treatment options.
CONCLUSIONS: Our novel molecular taxonomy holds promise as a practical framework for patient risk stratification and clinical trials in UC. Our molecular classification scheme may facilitate personalised transcriptome- and proteome-based risk assessment and clinical trial design for the development of various therapeutics.
KEY POINTS: We developed three UC clusters, applicable for MIBC and NMIBC, which were validated using transcriptomic- and proteomic datasets. Publically available UC cell lines were assigned to the clusters, to have in vitro models representing each cluster. The clusters differ in molecular and biological signatures, with distinct prognostic and therapeutic characteristics.},
}
MeSH Terms:
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Humans
*Precision Medicine/methods
*Urinary Bladder Neoplasms/genetics/classification
Gene Expression Profiling/methods
Cell Line, Tumor
Transcriptome
Multiomics
RevDate: 2026-03-10
IFN-gene signatures in B cells following influenza A and B virus infection and influenza vaccination.
EMBO molecular medicine [Epub ahead of print].
Influenza viruses continue to cause a substantial global disease burden. Despite influenza vaccination, some individuals succumb to life-threatening influenza or death. Yet our understanding of immune features elicited by vaccination and influenza A and B virus (IAV, IBV) infection is limited. To define molecular signatures of influenza-specific B-cells, we performed scRNA-sequencing of influenza-specific B-cells in vaccinees and hospitalized IAV/IBV-infected patients using HA-probes. We observed increased interferon-stimulated gene signatures (IF44L, IFITM1 and XAF1), in total B-cells from IBV-patients, but not at 1-month following patients' recovery or in IAV-patients or vaccinees. Phenotypic differentiation and isotype class-switching of HA-specific B-cells were observed following vaccination, with clonal sharing between memory and atypical B-cell phenotypes. In-vitro influenza virus infection experiments showed IBVs having higher infectivity of human PBMCs, including B-cells, and reduced B-cell proliferation compared to IAV, potentially associated with antiproliferative effect of IFITM1. We provide key insights into B-cell immunity towards IBV and IAV infections and vaccination, which will inform rational vaccine design and therapeutic strategies aimed at eliciting robust HA-specific B-cell responses, while minimizing adverse effects caused by natural infection.
Additional Links: PMID-41803327
PubMed:
Citation:
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@article {pmid41803327,
year = {2026},
author = {Zhang, W and Allen, EK and Li, S and Tarasova, I and Farrukee, R and Kedzierski, L and Gilbertson, B and McQuilten, HA and Habel, JR and Allen, LF and Rockman, S and Londrigan, SL and Kent, SJ and Wheatley, AK and Trubiano, JA and Kotsimbos, TC and Cheng, AC and Schroeder, J and Crawford, JC and Thomas, PG and Kedzierska, K and Nguyen, THO},
title = {IFN-gene signatures in B cells following influenza A and B virus infection and influenza vaccination.},
journal = {EMBO molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {41803327},
issn = {1757-4684},
support = {2033783//DHAC | National Health and Medical Research Council (NHMRC)/ ; 1194036//DHAC | National Health and Medical Research Council (NHMRC)/ ; 2016491//DHAC | National Health and Medical Research Council (NHMRC)/ ; 2026762//DHAC | National Health and Medical Research Council (NHMRC)/ ; 2012463//DHAC | National Health and Medical Research Council (NHMRC)/ ; 2038242//DHAC | National Health and Medical Research Council (NHMRC)/ ; T11-712/19-N//Theme-based Research Scheme of the Research Grants Council of the Hong Kong Special Administrative Region (HKSAR), China/ ; 1U01AI144616-01//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; HHS-NIH-NIAID-BAA2018//HHS | National Institutes of Health (NIH)/ ; },
abstract = {Influenza viruses continue to cause a substantial global disease burden. Despite influenza vaccination, some individuals succumb to life-threatening influenza or death. Yet our understanding of immune features elicited by vaccination and influenza A and B virus (IAV, IBV) infection is limited. To define molecular signatures of influenza-specific B-cells, we performed scRNA-sequencing of influenza-specific B-cells in vaccinees and hospitalized IAV/IBV-infected patients using HA-probes. We observed increased interferon-stimulated gene signatures (IF44L, IFITM1 and XAF1), in total B-cells from IBV-patients, but not at 1-month following patients' recovery or in IAV-patients or vaccinees. Phenotypic differentiation and isotype class-switching of HA-specific B-cells were observed following vaccination, with clonal sharing between memory and atypical B-cell phenotypes. In-vitro influenza virus infection experiments showed IBVs having higher infectivity of human PBMCs, including B-cells, and reduced B-cell proliferation compared to IAV, potentially associated with antiproliferative effect of IFITM1. We provide key insights into B-cell immunity towards IBV and IAV infections and vaccination, which will inform rational vaccine design and therapeutic strategies aimed at eliciting robust HA-specific B-cell responses, while minimizing adverse effects caused by natural infection.},
}
RevDate: 2026-03-09
Tooth loss and oral health-related quality of life in a sub-cohort within the Chronic Graft-versus-Host Disease Consortium.
Transplantation and cellular therapy pii:S2666-6367(26)00186-7 [Epub ahead of print].
BACKGROUND: Chronic graft-versus-host-disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation (alloHCT) that frequently affects the oral cavity with manifestations of oral mucosal inflammation, salivary gland hypofunction, and trismus. However, the long-term consequences of oral cGVHD on oral health outcomes are not defined.
OBJECTIVE: This report assesses long-term tooth loss and oral health-related quality of life (OHRQL) measures in patients who have received alloHCT.
STUDY DESIGN: Participants were evaluated at an initial post-transplant dental visit which consisted of dental and periodontal examination, oral mucosal examination, and panoramic radiographs. The National Institutes of Health (NIH) Modified Oral Mucosa Rating Scale (OMRS) and World Health Organization (WHO) Oral Health Assessment for Adults were used for diagnosis and grading of oral cGVHD and dental status. Pre-transplant dental records were available and utilized to calculate tooth loss data. Participants also completed the Oral Health Impact Profile-14 (OHIP-14) questionnaire, the NIH mouth sensitivity score, the Lee Symptom Scale (oral cavity items), and the shortened summated Xerostomia Inventory (XI).
RESULTS: This study enrolled 70 participants at a median of 8.8 years after alloHCT (range 6.7-11.8 years); 19 (27.1%) had no past oral cGVHD, 22 (31.4%) had past but no current oral cGVHD, and 29 (41.4%) had current oral cGVHD. Patients with current oral cGVHD had a mean tooth loss of 2.3, patients with past but no current oral cGVHD had a mean tooth loss of 1.0, and patients with no past oral cGVHD had a mean tooth loss of 2.1 (p=0.54, ANOVA). The mean overall OHIP-14 scores for the current, past but no current, and no past oral cGVHD groups were 13.6, 6.3, and 6.3, respectively (p=0.02, ANOVA). Oral cGVHD significantly impacted various aspects related to eating and meal choices.
CONCLUSIONS: The rate of tooth loss was not definitively different based on past/current oral cGVHD status. Further efforts at mitigating the adverse impacts of oral cGVHD on nutrition and oral-health-related quality of life has the potential to improve the lives of alloHCT recipients.
Additional Links: PMID-41802602
Publisher:
PubMed:
Citation:
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@article {pmid41802602,
year = {2026},
author = {Treister, NS and Liang, L and Lee, SJ and Cutler, C and Gooley, TA and Hujoel, P and Gbujie, D and Oh, UY and Bennett-Johnson, L and Hagstrom, MK and Rothen, M and Lloid, M and Dean, D and Sroussi, H},
title = {Tooth loss and oral health-related quality of life in a sub-cohort within the Chronic Graft-versus-Host Disease Consortium.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2026.03.004},
pmid = {41802602},
issn = {2666-6367},
abstract = {BACKGROUND: Chronic graft-versus-host-disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation (alloHCT) that frequently affects the oral cavity with manifestations of oral mucosal inflammation, salivary gland hypofunction, and trismus. However, the long-term consequences of oral cGVHD on oral health outcomes are not defined.
OBJECTIVE: This report assesses long-term tooth loss and oral health-related quality of life (OHRQL) measures in patients who have received alloHCT.
STUDY DESIGN: Participants were evaluated at an initial post-transplant dental visit which consisted of dental and periodontal examination, oral mucosal examination, and panoramic radiographs. The National Institutes of Health (NIH) Modified Oral Mucosa Rating Scale (OMRS) and World Health Organization (WHO) Oral Health Assessment for Adults were used for diagnosis and grading of oral cGVHD and dental status. Pre-transplant dental records were available and utilized to calculate tooth loss data. Participants also completed the Oral Health Impact Profile-14 (OHIP-14) questionnaire, the NIH mouth sensitivity score, the Lee Symptom Scale (oral cavity items), and the shortened summated Xerostomia Inventory (XI).
RESULTS: This study enrolled 70 participants at a median of 8.8 years after alloHCT (range 6.7-11.8 years); 19 (27.1%) had no past oral cGVHD, 22 (31.4%) had past but no current oral cGVHD, and 29 (41.4%) had current oral cGVHD. Patients with current oral cGVHD had a mean tooth loss of 2.3, patients with past but no current oral cGVHD had a mean tooth loss of 1.0, and patients with no past oral cGVHD had a mean tooth loss of 2.1 (p=0.54, ANOVA). The mean overall OHIP-14 scores for the current, past but no current, and no past oral cGVHD groups were 13.6, 6.3, and 6.3, respectively (p=0.02, ANOVA). Oral cGVHD significantly impacted various aspects related to eating and meal choices.
CONCLUSIONS: The rate of tooth loss was not definitively different based on past/current oral cGVHD status. Further efforts at mitigating the adverse impacts of oral cGVHD on nutrition and oral-health-related quality of life has the potential to improve the lives of alloHCT recipients.},
}
RevDate: 2026-03-09
VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor-Positive/HER2-/PIK3CA Wild-Type Advanced Breast Cancer.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [Epub ahead of print].
PURPOSE: Gedatolisib potently targets all four class I PI3K isoforms and mTORC1 and mTORC2 to comprehensively block the PI3K/AKT/mTOR pathway and has shown compelling activity in early clinical trials with palbociclib and fulvestrant.
METHODS: This phase III randomized trial (VIKTORIA-1; ClinicalTrials.gov identifier: NCT05501886) evaluated the efficacy of gedatolisib-based therapy, comparing gedatolisib, palbociclib, and fulvestrant (gedatolisib triplet) and gedatolisib plus fulvestrant (gedatolisib doublet) with fulvestrant monotherapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HER2-), PIK3CA wild-type (WT) advanced breast cancer. Eligible patients had disease progression during or after CDK4/6 inhibitor and aromatase inhibitor treatment. Comparison of progression-free survival as assessed by blinded independent central review for gedatolisib triplet versus fulvestrant and gedatolisib doublet versus fulvestrant was the primary objective.
RESULTS: A total of 392 patients were randomly assigned 1:1:1. The median study follow-up was 10.1 months. The median progression-free survival was 9.3 months in the gedatolisib-triplet group, 2.0 months in the fulvestrant group (hazard ratio [HR] for progression or death, 0.24 [95% CI, 0.17 to 0.35]; P < .001), and 7.4 months in the gedatolisib-doublet group (HR, 0.33 [95% CI, 0.24 to 0.48]; P < .001 v fulvestrant). Grade ≥3 treatment-related adverse events (TRAEs) reported in the gedatolisib-triplet and gedatolisib-doublet groups, respectively, included neutropenia (62.3%, 0.8%), stomatitis (19.2%, 12.3%), rash (4.6%, 5.4%), hyperglycemia (2.3%, 2.3%), and diarrhea (1.5%, 0.8%). Study treatment discontinuation because of TRAEs was reported in 2.3% (triplet) and 3.1% (doublet) of patients.
CONCLUSION: The addition of gedatolisib to fulvestrant, with or without palbociclib, significantly reduced the risk of disease progression or death in patients with hormone receptor-positive/HER2-, PIK3CA WT advanced breast cancer.
Additional Links: PMID-41802242
Publisher:
PubMed:
Citation:
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@article {pmid41802242,
year = {2026},
author = {Hurvitz, SA and Layman, RM and Curigliano, G and André, F and Cristofanilli, M and Kim, SB and Martínez Rodríguez, JL and Nadal, JC and Kim, GM and Lo, L and Remolina-Bonilla, YA and Rosselli, G and Emile, G and Korbenfeld, E and Puig, JM and Wesolowski, R and Martin, M and Ring, A and Han, HS and Giordano, A and Mutka, SC and Moss, K and Suzuki, S and Sullivan, B and Gorbatchevsky, I and Pistilli, B and , },
title = {VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor-Positive/HER2-/PIK3CA Wild-Type Advanced Breast Cancer.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502643},
doi = {10.1200/JCO-25-02643},
pmid = {41802242},
issn = {1527-7755},
abstract = {PURPOSE: Gedatolisib potently targets all four class I PI3K isoforms and mTORC1 and mTORC2 to comprehensively block the PI3K/AKT/mTOR pathway and has shown compelling activity in early clinical trials with palbociclib and fulvestrant.
METHODS: This phase III randomized trial (VIKTORIA-1; ClinicalTrials.gov identifier: NCT05501886) evaluated the efficacy of gedatolisib-based therapy, comparing gedatolisib, palbociclib, and fulvestrant (gedatolisib triplet) and gedatolisib plus fulvestrant (gedatolisib doublet) with fulvestrant monotherapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HER2-), PIK3CA wild-type (WT) advanced breast cancer. Eligible patients had disease progression during or after CDK4/6 inhibitor and aromatase inhibitor treatment. Comparison of progression-free survival as assessed by blinded independent central review for gedatolisib triplet versus fulvestrant and gedatolisib doublet versus fulvestrant was the primary objective.
RESULTS: A total of 392 patients were randomly assigned 1:1:1. The median study follow-up was 10.1 months. The median progression-free survival was 9.3 months in the gedatolisib-triplet group, 2.0 months in the fulvestrant group (hazard ratio [HR] for progression or death, 0.24 [95% CI, 0.17 to 0.35]; P < .001), and 7.4 months in the gedatolisib-doublet group (HR, 0.33 [95% CI, 0.24 to 0.48]; P < .001 v fulvestrant). Grade ≥3 treatment-related adverse events (TRAEs) reported in the gedatolisib-triplet and gedatolisib-doublet groups, respectively, included neutropenia (62.3%, 0.8%), stomatitis (19.2%, 12.3%), rash (4.6%, 5.4%), hyperglycemia (2.3%, 2.3%), and diarrhea (1.5%, 0.8%). Study treatment discontinuation because of TRAEs was reported in 2.3% (triplet) and 3.1% (doublet) of patients.
CONCLUSION: The addition of gedatolisib to fulvestrant, with or without palbociclib, significantly reduced the risk of disease progression or death in patients with hormone receptor-positive/HER2-, PIK3CA WT advanced breast cancer.},
}
RevDate: 2026-03-09
Oral preexposure prophylaxis use and the risk of bacterial sexually transmitted infections and HIV among African women: A prospective observational cohort study.
PLoS medicine, 23(3):e1004962 pii:PMEDICINE-D-25-00319 [Epub ahead of print].
BACKGROUND: Oral preexposure prophylaxis (PrEP) effectively reduces HIV incidence when used with sufficient adherence, but does not protect against bacterial sexually transmitted infections (STIs). Several studies have documented high rates of bacterial STIs among individuals initiating and using PrEP. We evaluated the association between PrEP use and the risk of STI among African women accessing family planning clinics.
METHODS AND FINDINGS: We conducted a prospective cohort study nested within a large pragmatic stepped-wedge cluster randomized trial of PrEP delivery in Kenyan family planning clinics, with participant enrollment from June 18, 2021, to May 18, 2023, and follow-up through February 02, 2024 (ClinicalTrials.gov: NCT04666792). The study population included sexually active HIV-negative women aged ≥15 years at elevated HIV risk per Kenyan PrEP guidelines. Participants were offered standard-of-care oral PrEP with the option to decline and followed quarterly for 12 months with assessments of HIV status, sexual behavior, and PrEP use. Urine samples were batch tested for Neissseria gonorrhoeae and Chlamydia trachomatis using the GeneXpert CT/NG real-time polymerase chain reaction nucleic acid amplification test assay. The primary exposure was self-reported PrEP initiation and PrEP use consistency through 6 months, categorized as never used PrEP, inconsistently on PrEP, or consistently on PrEP. Multivariable modified Poisson generalized estimating equation (GEE) models with robust standard errors were used to estimate associations between PrEP use and incident STI; clinic-level intracluster correlation coefficients were negligible. The secondary outcomes were incident HIV infection and sexual behaviors, which included condomless sex at last sex, sex with any new partners in the past 3 months, and multiple sex partners. HIV testing was performed at each scheduled visit, at enrollment, and 1, 3, 6, 9, and 12 months following the Kenya national HIV testing algorithm, using Determine HIV-1/2 and Fast Response test kits. All models for the primary outcome were adjusted for baseline covariates determined apriori as potential confounders, which included age, STI diagnosis at enrollment, any contraceptive use, number of sexual partners (categorized as any more than one sexual partner), education status, marital status, last partner HIV status, any transactional sex in 3 months pre-enrollment, and clinic site. Among 650 women enrolled, 60.0% (389) initiated PrEP at baseline and 14.6% (38/261) initiated post-enrollment. Median age was 26 years (IQR 23-30), 40% (262/650) were aged ≤24 years, and 67% (436/648) did not know their primary partner's HIV status. At baseline, 11% (74/650) had an STI, including 9.9% (23/232) of consistent PrEP users, 9.2% (13/141) of inconsistent users, and 14.0% (38/277) of women who declined PrEP. During follow-up, 19.1% (114/597) had at least one STI diagnosis, with similar risk among women who initiated PrEP at baseline compared with those who declined (19.2% [68/354] versus 18.9% [46/244]; aRR 1.11, 95% CI 0.76-1.61; p = 0.580). Compared with non-PrEP users (12.7% [25/195]), STI risk was 6.0% (12/200) among consistent PrEP users (aRR 0.56, 95% CI 0.27-1.19; p = 0.130) and 16.5% (17/103) among inconsistent users (aRR 1.43, 95% CI 0.73-2.77; p = 0.290). Chlamydia accounted for 87.7% (100/114) of STI diagnoses. STI risk was higher among women aged ≤24 years (aRR 1.47, 95% CI 1.04-2.07; p = 0.029) and those with a baseline STI (aRR 2.96, 95% CI 2.12-4.14; p < 0.001). Four HIV infections occurred over 594 person-years (incidence 0.67, 95% CI 0.18-1.72 per 100 person-years), including three among women who declined PrEP (incidence 1.25, 95% CI 0.26-3.66 per 100 person-years). The main study limitation was oral PrEP use was assessed based on client self-report and not objectively through drug levels testing.
CONCLUSIONS: In this prospective cohort study among African women at elevated risk for HIV, 60% initiated PrEP at baseline and 14.6% (38/261) post-enrollment. PrEP use was not associated with increased risk for STI diagnosis through one year of follow-up. HIV incidence was low overall, consistent with expanded PrEP availability in similar populations.
Additional Links: PMID-41802176
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@article {pmid41802176,
year = {2026},
author = {Mukasa, D and Kinuthia, J and Meisner, A and Matemo, D and Schaafsma, T and Morton, J and Wandera, C and Budiawan, E and Kemuto, V and Irine, C and Odhiambo, S and Bii, M and Oduor, B and Achieng, E and Oyombra, T and Ukah, UV and Mugwanya, KK and , },
title = {Oral preexposure prophylaxis use and the risk of bacterial sexually transmitted infections and HIV among African women: A prospective observational cohort study.},
journal = {PLoS medicine},
volume = {23},
number = {3},
pages = {e1004962},
doi = {10.1371/journal.pmed.1004962},
pmid = {41802176},
issn = {1549-1676},
abstract = {BACKGROUND: Oral preexposure prophylaxis (PrEP) effectively reduces HIV incidence when used with sufficient adherence, but does not protect against bacterial sexually transmitted infections (STIs). Several studies have documented high rates of bacterial STIs among individuals initiating and using PrEP. We evaluated the association between PrEP use and the risk of STI among African women accessing family planning clinics.
METHODS AND FINDINGS: We conducted a prospective cohort study nested within a large pragmatic stepped-wedge cluster randomized trial of PrEP delivery in Kenyan family planning clinics, with participant enrollment from June 18, 2021, to May 18, 2023, and follow-up through February 02, 2024 (ClinicalTrials.gov: NCT04666792). The study population included sexually active HIV-negative women aged ≥15 years at elevated HIV risk per Kenyan PrEP guidelines. Participants were offered standard-of-care oral PrEP with the option to decline and followed quarterly for 12 months with assessments of HIV status, sexual behavior, and PrEP use. Urine samples were batch tested for Neissseria gonorrhoeae and Chlamydia trachomatis using the GeneXpert CT/NG real-time polymerase chain reaction nucleic acid amplification test assay. The primary exposure was self-reported PrEP initiation and PrEP use consistency through 6 months, categorized as never used PrEP, inconsistently on PrEP, or consistently on PrEP. Multivariable modified Poisson generalized estimating equation (GEE) models with robust standard errors were used to estimate associations between PrEP use and incident STI; clinic-level intracluster correlation coefficients were negligible. The secondary outcomes were incident HIV infection and sexual behaviors, which included condomless sex at last sex, sex with any new partners in the past 3 months, and multiple sex partners. HIV testing was performed at each scheduled visit, at enrollment, and 1, 3, 6, 9, and 12 months following the Kenya national HIV testing algorithm, using Determine HIV-1/2 and Fast Response test kits. All models for the primary outcome were adjusted for baseline covariates determined apriori as potential confounders, which included age, STI diagnosis at enrollment, any contraceptive use, number of sexual partners (categorized as any more than one sexual partner), education status, marital status, last partner HIV status, any transactional sex in 3 months pre-enrollment, and clinic site. Among 650 women enrolled, 60.0% (389) initiated PrEP at baseline and 14.6% (38/261) initiated post-enrollment. Median age was 26 years (IQR 23-30), 40% (262/650) were aged ≤24 years, and 67% (436/648) did not know their primary partner's HIV status. At baseline, 11% (74/650) had an STI, including 9.9% (23/232) of consistent PrEP users, 9.2% (13/141) of inconsistent users, and 14.0% (38/277) of women who declined PrEP. During follow-up, 19.1% (114/597) had at least one STI diagnosis, with similar risk among women who initiated PrEP at baseline compared with those who declined (19.2% [68/354] versus 18.9% [46/244]; aRR 1.11, 95% CI 0.76-1.61; p = 0.580). Compared with non-PrEP users (12.7% [25/195]), STI risk was 6.0% (12/200) among consistent PrEP users (aRR 0.56, 95% CI 0.27-1.19; p = 0.130) and 16.5% (17/103) among inconsistent users (aRR 1.43, 95% CI 0.73-2.77; p = 0.290). Chlamydia accounted for 87.7% (100/114) of STI diagnoses. STI risk was higher among women aged ≤24 years (aRR 1.47, 95% CI 1.04-2.07; p = 0.029) and those with a baseline STI (aRR 2.96, 95% CI 2.12-4.14; p < 0.001). Four HIV infections occurred over 594 person-years (incidence 0.67, 95% CI 0.18-1.72 per 100 person-years), including three among women who declined PrEP (incidence 1.25, 95% CI 0.26-3.66 per 100 person-years). The main study limitation was oral PrEP use was assessed based on client self-report and not objectively through drug levels testing.
CONCLUSIONS: In this prospective cohort study among African women at elevated risk for HIV, 60% initiated PrEP at baseline and 14.6% (38/261) post-enrollment. PrEP use was not associated with increased risk for STI diagnosis through one year of follow-up. HIV incidence was low overall, consistent with expanded PrEP availability in similar populations.},
}
RevDate: 2026-03-10
CmpDate: 2026-03-09
Tumor inflammation-associated neurotoxicity in children with diffuse intrinsic pontine glioma receiving B7-H3-targeting CAR T cells on BrainChild-03.
Neuro-oncology practice, 13(1):105-111.
BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy is a promising treatment for central nervous system (CNS) tumors like diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG). Unlike systemic administration, locoregional CAR T therapy may result in tumor inflammation-associated neurotoxicity (TIAN), which was recently defined. This study retrospectively applies TIAN criteria to patients with DIPG/pontine DMG treated with intraventricular B7-H3 CAR T cells in the BrainChild-03 (BC-03) trial (NCT04185038).
METHODS: A retrospective analysis of DIPG/pontine DMG patients treated with locoregional B7-H3 CAR T cells in BC-03 was conducted. Neurological symptoms, headache, fever, hydrocephalus, and inflammatory markers were extracted from case reports and medical records. TIAN was classified as type 1 (mechanical damage) or type 2 (electrophysiologic dysfunction), and symptom patterns, resolution, imaging findings, and management were analyzed.
RESULTS: Among 21 patients (ages 2-22) receiving ≥1 infusion, 16 (76%) met TIAN criteria at least once. TIAN occurred in 49 of 152 infusions (32%), mostly grade 1 (n = 34) or grade 2 (n = 14), with one grade 3 event. Common symptoms included headache with fever (51%) and neurologic changes with headache (31%). In most patients, Type 1 vs Type 2 TIAN could not be defined; however, 1 patient required CSF diversion (type 1 TIAN), and 13 had worsening preexisting deficits (type 2). Median symptom resolution was <24 h (range: 0-33).
CONCLUSIONS: TIAN was common within this cohort but mostly low-grade and transient. Refining its classification and understanding its clinical impact will aid safety assessments and trial comparisons for CNS-directed CAR T therapies.
Additional Links: PMID-41798119
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@article {pmid41798119,
year = {2026},
author = {Ronsley, R and Choe, M and Wright, J and Seidel, K and Lee, A and Wendler, J and Annesley, C and Jensen, MC and Park, JR and Vitanza, NA and Gust, J},
title = {Tumor inflammation-associated neurotoxicity in children with diffuse intrinsic pontine glioma receiving B7-H3-targeting CAR T cells on BrainChild-03.},
journal = {Neuro-oncology practice},
volume = {13},
number = {1},
pages = {105-111},
pmid = {41798119},
issn = {2054-2577},
support = {R37 CA289981/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy is a promising treatment for central nervous system (CNS) tumors like diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG). Unlike systemic administration, locoregional CAR T therapy may result in tumor inflammation-associated neurotoxicity (TIAN), which was recently defined. This study retrospectively applies TIAN criteria to patients with DIPG/pontine DMG treated with intraventricular B7-H3 CAR T cells in the BrainChild-03 (BC-03) trial (NCT04185038).
METHODS: A retrospective analysis of DIPG/pontine DMG patients treated with locoregional B7-H3 CAR T cells in BC-03 was conducted. Neurological symptoms, headache, fever, hydrocephalus, and inflammatory markers were extracted from case reports and medical records. TIAN was classified as type 1 (mechanical damage) or type 2 (electrophysiologic dysfunction), and symptom patterns, resolution, imaging findings, and management were analyzed.
RESULTS: Among 21 patients (ages 2-22) receiving ≥1 infusion, 16 (76%) met TIAN criteria at least once. TIAN occurred in 49 of 152 infusions (32%), mostly grade 1 (n = 34) or grade 2 (n = 14), with one grade 3 event. Common symptoms included headache with fever (51%) and neurologic changes with headache (31%). In most patients, Type 1 vs Type 2 TIAN could not be defined; however, 1 patient required CSF diversion (type 1 TIAN), and 13 had worsening preexisting deficits (type 2). Median symptom resolution was <24 h (range: 0-33).
CONCLUSIONS: TIAN was common within this cohort but mostly low-grade and transient. Refining its classification and understanding its clinical impact will aid safety assessments and trial comparisons for CNS-directed CAR T therapies.},
}
RevDate: 2026-03-09
Fusariosis in Patients With Hematologic Malignancies in the Era of Antifungal Prophylaxis.
Transplant infectious disease : an official journal of the Transplantation Society [Epub ahead of print].
BACKGROUND: Invasive fusariosis (IF) is an uncommon but frequently fatal infection among patients with hematologic malignancies (HM). Despite widespread mould-active prophylaxis, breakthrough infections and treatment failures may occur. We aim to describe the clinical epidemiology, diagnostic approaches, antifungal management strategies, and outcomes of IF in the era of routine antifungal prophylaxis.
METHODS: We conducted a retrospective study of all cancer patients diagnosed with IF at a tertiary cancer center that met probable/proven criteria for IF from 2015 to 2024. We collected data on demographics, oncologic history, diagnostics, therapy, and outcomes.
RESULTS: Twenty-two patients met criteria for proven IF. Most had acute myeloid leukemia (73%), and many underwent prior hematopoietic cell transplant (36%); nearly all were neutropenic (96%, median:48 days). Skin was the most common clinical site of infection (68%), followed by sino-pulmonary involvement (41%); fungemia occurred in 32%. Fever (77%) and skin nodules (64%) were frequent, while serum galactomannan was uniformly negative. Most common species complex was Fusarium fujikuroi. In our cohort, 82% occurred during antifungal prophylaxis, most often posaconazole. Minimum inhibitory concentrations were high for azoles and lower for amphotericin B and terbinafine. Antifungal regimens ranged from monotherapy to triple therapy. Overall mortality was 68%, of which 45% of deaths were attributed to IF. Mortality did not differ by antifungal regimen, species complexes, or presence of fungemia.
CONCLUSIONS: IF remains a life-threatening infection in patients with HM, often presenting as disseminated disease, despite prophylaxis. High azole MICs and the observed diversity of antifungal regimens highlight the ongoing uncertainty regarding optimal treatment and the need for prospective studies to define the role of combination therapy.
Additional Links: PMID-41797392
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@article {pmid41797392,
year = {2026},
author = {Vega, P and Bhattacharyya, P and Lieberman, JA and Kuczmarski, TM and Yoke, LH and So, LM and Smith, HZ and Lengermann, R and Cohen, S and Fredricks, DN and Pergam, SA},
title = {Fusariosis in Patients With Hematologic Malignancies in the Era of Antifungal Prophylaxis.},
journal = {Transplant infectious disease : an official journal of the Transplantation Society},
volume = {},
number = {},
pages = {e70203},
doi = {10.1111/tid.70203},
pmid = {41797392},
issn = {1399-3062},
support = {T32AI118690//National Institute of Allergy and Infectious Diseases of the National Institutes of Health/ ; P30-CA015704//National Cancer Institute Cancer Center/ ; },
abstract = {BACKGROUND: Invasive fusariosis (IF) is an uncommon but frequently fatal infection among patients with hematologic malignancies (HM). Despite widespread mould-active prophylaxis, breakthrough infections and treatment failures may occur. We aim to describe the clinical epidemiology, diagnostic approaches, antifungal management strategies, and outcomes of IF in the era of routine antifungal prophylaxis.
METHODS: We conducted a retrospective study of all cancer patients diagnosed with IF at a tertiary cancer center that met probable/proven criteria for IF from 2015 to 2024. We collected data on demographics, oncologic history, diagnostics, therapy, and outcomes.
RESULTS: Twenty-two patients met criteria for proven IF. Most had acute myeloid leukemia (73%), and many underwent prior hematopoietic cell transplant (36%); nearly all were neutropenic (96%, median:48 days). Skin was the most common clinical site of infection (68%), followed by sino-pulmonary involvement (41%); fungemia occurred in 32%. Fever (77%) and skin nodules (64%) were frequent, while serum galactomannan was uniformly negative. Most common species complex was Fusarium fujikuroi. In our cohort, 82% occurred during antifungal prophylaxis, most often posaconazole. Minimum inhibitory concentrations were high for azoles and lower for amphotericin B and terbinafine. Antifungal regimens ranged from monotherapy to triple therapy. Overall mortality was 68%, of which 45% of deaths were attributed to IF. Mortality did not differ by antifungal regimen, species complexes, or presence of fungemia.
CONCLUSIONS: IF remains a life-threatening infection in patients with HM, often presenting as disseminated disease, despite prophylaxis. High azole MICs and the observed diversity of antifungal regimens highlight the ongoing uncertainty regarding optimal treatment and the need for prospective studies to define the role of combination therapy.},
}
RevDate: 2026-03-09
Epidemiology of Cancer-Associated Venous Thromboembolism Across the United States.
American journal of hematology [Epub ahead of print].
Prior epidemiological studies on cancer-associated venous thromboembolism (VTE) were limited by homogenous patient populations. We leverage Cosmos, a collaborative dataset of Epic electronic health record systems, to conduct an updated evaluation of cancer-associated VTE in the United States (US). Cosmos includes patients from all 50 states, and the dataset is representative of the US census in terms of age, race, ethnicity, and insurance coverage. We included patients in the US with a new cancer diagnosis between 2018 and 2023. We computed the cumulative incidence of VTE at 6 and 12 months after the diagnosis date and used Cox regression to identify risk factors and examine the association between VTE type within the first year and mortality. We identified 1 628 626 patients, with a cumulative incidence of VTE at 6 months of 2.7% and at 12 months of 3.7%. Major risk factors included prior VTE, cancer type, advanced stage, and chemotherapy-based treatment regimens. The occurrence of VTE within the first year of cancer diagnosis was independently associated with increased mortality.
Additional Links: PMID-41796432
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PubMed:
Citation:
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@article {pmid41796432,
year = {2026},
author = {Lam, BD and Ryu, J and Jafari, O and Kim, RB and Ma, S and Ranjan, M and Jiang, JY and Li, A},
title = {Epidemiology of Cancer-Associated Venous Thromboembolism Across the United States.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70271},
pmid = {41796432},
issn = {1096-8652},
abstract = {Prior epidemiological studies on cancer-associated venous thromboembolism (VTE) were limited by homogenous patient populations. We leverage Cosmos, a collaborative dataset of Epic electronic health record systems, to conduct an updated evaluation of cancer-associated VTE in the United States (US). Cosmos includes patients from all 50 states, and the dataset is representative of the US census in terms of age, race, ethnicity, and insurance coverage. We included patients in the US with a new cancer diagnosis between 2018 and 2023. We computed the cumulative incidence of VTE at 6 and 12 months after the diagnosis date and used Cox regression to identify risk factors and examine the association between VTE type within the first year and mortality. We identified 1 628 626 patients, with a cumulative incidence of VTE at 6 months of 2.7% and at 12 months of 3.7%. Major risk factors included prior VTE, cancer type, advanced stage, and chemotherapy-based treatment regimens. The occurrence of VTE within the first year of cancer diagnosis was independently associated with increased mortality.},
}
RevDate: 2026-03-11
CmpDate: 2026-03-10
Efficacy and safety of ruxolitinib for graft-versus-host disease prophylaxis in patients with aplastic anemia undergoing PBSC-only allogeneic stem cell transplantation: a prospective phase II study.
Experimental hematology & oncology, 15(1):.
BACKGROUND: While peripheral blood hematopoietic stem cell transplantation (PB-HSCT) supports rapid engraftment and reduces graft failure risk in aplastic anemia (AA) patients, it compromised higher risk of acute graft-versus-host disease (aGVHD), highlighting the need for more effective prophylactic strategies. This phase II clinical trial was designed to assess the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, as part of GVHD prophylaxis regimen following PB-HSCT.
METHODS: This open-label, single-arm, Phase II clinical trial (ClinicalTrials.gov: NCT05914714) enrolled patients with AA between June 2023 and December 2024. Ruxolitinib was initiated at the start of conditioning and continued for 3 months post-transplant at a dose of 5 mg twice daily. A historical control cohort receiving standard GVHD prophylaxis between January 2019 and May 2023 was included for comparison. To address baseline imbalances, propensity score-based inverse probability of treatment weighting (IPTW) was applied. The primary objective was the incidence of aGVHD six months after HSCT. Secondary endpoints included one-year overall survival (OS) and GVHD-free, failure-free survival (GFFS). Immune reconstitution-including T cells, B cells, NK cells-and levels of pro-inflammatory cytokines were also evaluated to explore potential mechanisms.
RESULTS: A total of 82 patients were enrolled (ruxolitinib group n = 46, historical control cohort n = 36). Comparative analysis showed that ruxolitinib significantly reduced the cumulative incidence of grade II-IV aGVHD (HR 0.24; p = 0.004) and severe aGVHD (0% vs 15.8%; p = 0.008) compared with the control group. At a median follow-up of 417 days (range: 112-725), the ruxolitinib group demonstrated significantly superior 1-year GFFS (91.6% vs. 72.1%; HR 0.23, weighted log-rank p = 0.012). Notably, the ruxolitinib group not only exhibited more rapid recovery of CD4 + Tregs at 3 months post-HSCT. Notably, but also suppressed proinflammatory cytokine levels during engraftment.
CONCLUSIONS: The peri-transplantation addition of ruxolitinib to the standard GVHD prophylaxis regimen in PB-HSCT for AA patients has shown to be a safe and effective approach to reducing both the incidence of aGVHD, while improving patient outcomes. Our study suggests that ruxolitinib may offer a promising strategy for improving survival and immune recovery. Trial registration clinicaltrials.gov identifier: NCT05914714.
Additional Links: PMID-41796372
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@article {pmid41796372,
year = {2026},
author = {Zhang, X and Pan, L and Zhao, Y and Ma, R and Zhang, L and Zhang, Y and Li, G and Zhai, W and Ma, Q and Pang, A and Yang, D and Feng, S and Zhang, P and He, Y and Qin, G and Jiang, E and Han, M},
title = {Efficacy and safety of ruxolitinib for graft-versus-host disease prophylaxis in patients with aplastic anemia undergoing PBSC-only allogeneic stem cell transplantation: a prospective phase II study.},
journal = {Experimental hematology & oncology},
volume = {15},
number = {1},
pages = {},
pmid = {41796372},
issn = {2162-3619},
support = {3332021055//Fundamental Research Funds for the Central Universities/ ; 82100225//National Natural Science Foundation of China/ ; 82070192//National Natural Science Foundation of China/ ; 2023ZD0502400//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; 2023YFC2508900//National Key R&D Program of China/ ; 2023-I2M-2-007//CAMS Innovation Fund for Medical Sciences/ ; 23JCZXJC00220//Tianjin Natural Science Foundation/ ; },
abstract = {BACKGROUND: While peripheral blood hematopoietic stem cell transplantation (PB-HSCT) supports rapid engraftment and reduces graft failure risk in aplastic anemia (AA) patients, it compromised higher risk of acute graft-versus-host disease (aGVHD), highlighting the need for more effective prophylactic strategies. This phase II clinical trial was designed to assess the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, as part of GVHD prophylaxis regimen following PB-HSCT.
METHODS: This open-label, single-arm, Phase II clinical trial (ClinicalTrials.gov: NCT05914714) enrolled patients with AA between June 2023 and December 2024. Ruxolitinib was initiated at the start of conditioning and continued for 3 months post-transplant at a dose of 5 mg twice daily. A historical control cohort receiving standard GVHD prophylaxis between January 2019 and May 2023 was included for comparison. To address baseline imbalances, propensity score-based inverse probability of treatment weighting (IPTW) was applied. The primary objective was the incidence of aGVHD six months after HSCT. Secondary endpoints included one-year overall survival (OS) and GVHD-free, failure-free survival (GFFS). Immune reconstitution-including T cells, B cells, NK cells-and levels of pro-inflammatory cytokines were also evaluated to explore potential mechanisms.
RESULTS: A total of 82 patients were enrolled (ruxolitinib group n = 46, historical control cohort n = 36). Comparative analysis showed that ruxolitinib significantly reduced the cumulative incidence of grade II-IV aGVHD (HR 0.24; p = 0.004) and severe aGVHD (0% vs 15.8%; p = 0.008) compared with the control group. At a median follow-up of 417 days (range: 112-725), the ruxolitinib group demonstrated significantly superior 1-year GFFS (91.6% vs. 72.1%; HR 0.23, weighted log-rank p = 0.012). Notably, the ruxolitinib group not only exhibited more rapid recovery of CD4 + Tregs at 3 months post-HSCT. Notably, but also suppressed proinflammatory cytokine levels during engraftment.
CONCLUSIONS: The peri-transplantation addition of ruxolitinib to the standard GVHD prophylaxis regimen in PB-HSCT for AA patients has shown to be a safe and effective approach to reducing both the incidence of aGVHD, while improving patient outcomes. Our study suggests that ruxolitinib may offer a promising strategy for improving survival and immune recovery. Trial registration clinicaltrials.gov identifier: NCT05914714.},
}
RevDate: 2026-03-08
Chronic exercise training intensity, immune cells, and cancer outcomes: a scoping review.
JNCI cancer spectrum pii:8510733 [Epub ahead of print].
BACKGROUND: Exercise has emerged as a potent, non-pharmacological intervention to enhance immune function in patients with cancer. The effects of exercise are likely influenced by patients' oncologic characteristics, such as cancer treatment, and intervention variables, such as exercise intensity, which can lead to heterogeneous outcomes. This scoping review aims to identify patterns, trends, and gaps in the literature regarding the relationship between chronic exercise training intensity and immune cell parameters in the context of treatment status.
METHODS: Reports were retrieved from PubMed, MEDLINE, and CINAHL. Eligible reports were controlled clinical trials of an exercise training intervention with more than one exercise session, included an objectively defined exercise intensity, and reported cellular immune outcomes.
RESULTS: 21 articles (15 randomized controlled trials) were included. Results suggest a dose-response effect of intensity, where vigorous-intensity exercise (reported in 6 studies) elicited beneficial immunomodulation, such as enhanced natural killer cell cytotoxicity. Light-to-moderate and moderate-intensity exercise (reported in 8 studies) resulted in no significant immunological changes in 5 studies, particularly for patients undergoing active treatment. Comparisons across studies were difficult due to heterogeneity in patients' clinical characteristics, intervention details, and immune parameters. Few reported cancer clinical outcomes such as disease progression, and none directly examined the relationships between immune and clinical endpoints.
CONCLUSIONS: While direct comparisons of exercise intensities are lacking, these results suggest that vigorous exercise training may exert greater immune modulation than low-to-moderate intensity exercise training. Rigorously designed trials are needed to confirm these findings and establish the role of exercise in oncologic care.
Additional Links: PMID-41795834
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@article {pmid41795834,
year = {2026},
author = {Kang, DW and Courneya, KS and Swartz, MC and Maleki Vareki, S and Gordon, NB and Cesar Rosa Neto, J and Simpson, RJ and Baker, KS and Schadler, KL and Lavoy, EC},
title = {Chronic exercise training intensity, immune cells, and cancer outcomes: a scoping review.},
journal = {JNCI cancer spectrum},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncics/pkag021},
pmid = {41795834},
issn = {2515-5091},
abstract = {BACKGROUND: Exercise has emerged as a potent, non-pharmacological intervention to enhance immune function in patients with cancer. The effects of exercise are likely influenced by patients' oncologic characteristics, such as cancer treatment, and intervention variables, such as exercise intensity, which can lead to heterogeneous outcomes. This scoping review aims to identify patterns, trends, and gaps in the literature regarding the relationship between chronic exercise training intensity and immune cell parameters in the context of treatment status.
METHODS: Reports were retrieved from PubMed, MEDLINE, and CINAHL. Eligible reports were controlled clinical trials of an exercise training intervention with more than one exercise session, included an objectively defined exercise intensity, and reported cellular immune outcomes.
RESULTS: 21 articles (15 randomized controlled trials) were included. Results suggest a dose-response effect of intensity, where vigorous-intensity exercise (reported in 6 studies) elicited beneficial immunomodulation, such as enhanced natural killer cell cytotoxicity. Light-to-moderate and moderate-intensity exercise (reported in 8 studies) resulted in no significant immunological changes in 5 studies, particularly for patients undergoing active treatment. Comparisons across studies were difficult due to heterogeneity in patients' clinical characteristics, intervention details, and immune parameters. Few reported cancer clinical outcomes such as disease progression, and none directly examined the relationships between immune and clinical endpoints.
CONCLUSIONS: While direct comparisons of exercise intensities are lacking, these results suggest that vigorous exercise training may exert greater immune modulation than low-to-moderate intensity exercise training. Rigorously designed trials are needed to confirm these findings and establish the role of exercise in oncologic care.},
}
RevDate: 2026-03-07
Understanding the cervicovaginal immune response to Lactobacillus crispatus CTV-05.
Additional Links: PMID-41794050
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PubMed:
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@article {pmid41794050,
year = {2027},
author = {Sabo, MC and Shah, JA and Lund, JM and McClelland, RS},
title = {Understanding the cervicovaginal immune response to Lactobacillus crispatus CTV-05.},
journal = {The Lancet. Microbe},
volume = {},
number = {},
pages = {101377},
doi = {10.1016/j.lanmic.2026.101377},
pmid = {41794050},
issn = {2666-5247},
}
RevDate: 2026-03-07
Racial and ethnic differences in the impact of air pollution on the risk of Alzheimer's disease and related dementias in the Multiethnic Cohort Study.
Environment international, 209:110169 pii:S0160-4120(26)00127-3 [Epub ahead of print].
BACKGROUND AND OBJECTIVES: Meta-analysis results, based largely among Whites, suggested that fine particulate matter (PM2.5) exposure increases the risk of clinical dementia. This study investigated the association of air pollution and incidence of Alzheimer's disease and related dementias (ADRD) by race and ethnicity.
METHODS: We investigated incidence of AD (n = 4,010) and other dementia (n = 4,971) among 44,954 California Multiethnic Cohort (MEC) participants (28% African American, 14% Japanese American, 44% Latino, 14% White adults) who were enrolled in the fee-for-service component of Medicare (2001-2016). We used Cox proportional hazards regression to examine associations between exposure to PM, airport-related ultrafine particles (aUFP) and gaseous pollutants and incidence of AD, other dementia, and ADRD in a minimally- and fully-adjusted model, considering 12 established ADRD risk factors. We conducted stratified analyses to examine associations by sex, and race/ethnicity.
RESULTS: ADRD incidence was associated with PM2.5 (per 2 µg/m[3]), airport-related UFP (aUFP, per 4400 particles/cm[3]) and nitrogen dioxide (NO2, per 10 µg/m[3]) with hazard ratios (HRs, 95%CI), respectively, of 1.04 (1.02-1.06), 1.03 (1.01-1.05) and 1.09 (1.06-1.12). The AD-associations with PM2.5 and NO2, were stronger than the corresponding associations with other dementia (Pheterogeneity ≤ 0.003). Similar patterns of results were observed by sex and across race and ethnicity. Statistically significant findings for ADRD with PM2.5, aUFP and NO2 were observed among African American (respective HRs 1.03, 1.04, 1.09), and Latino and White participants for NO2 (HR 1.10, 1.08). Results in all and African American participants remained statistically significant in fully-adjusted models. Although the effect of PM2.5 was diluted in a co-pollutant with NO2, both PM2.5 and aUFP were significantly associated with ADRD incidence in a co-pollutant model, and NO2 and aUFP (but not PM2.5) remained associated in a multipollutant model. We did not observe consistent modifying effects for any of the 12 established ADRD risk factors.
CONCLUSIONS: In this multiethnic population, incidence of ADRD increased with exposures to PM2.5, aUFP, and NO2 in all subjects and this pattern was most prominent among African American adults. These results emphasize that ADRD prevention should include not only individual-level factors but also population-wide policies and regulation to curb air pollution.
Additional Links: PMID-41793956
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PubMed:
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@article {pmid41793956,
year = {2026},
author = {Wu, AH and Wu, J and Tseng, C and Darst, BF and Park, SY and Stram, DO and Larson, T and Fruin, S and Setiawan, VW and Yu, X and Wilkens, LR and Hu, H and Haiman, C and Ritz, B and Crimmins, EM and Lim, U and Cheng, I and Marchand, LL},
title = {Racial and ethnic differences in the impact of air pollution on the risk of Alzheimer's disease and related dementias in the Multiethnic Cohort Study.},
journal = {Environment international},
volume = {209},
number = {},
pages = {110169},
doi = {10.1016/j.envint.2026.110169},
pmid = {41793956},
issn = {1873-6750},
abstract = {BACKGROUND AND OBJECTIVES: Meta-analysis results, based largely among Whites, suggested that fine particulate matter (PM2.5) exposure increases the risk of clinical dementia. This study investigated the association of air pollution and incidence of Alzheimer's disease and related dementias (ADRD) by race and ethnicity.
METHODS: We investigated incidence of AD (n = 4,010) and other dementia (n = 4,971) among 44,954 California Multiethnic Cohort (MEC) participants (28% African American, 14% Japanese American, 44% Latino, 14% White adults) who were enrolled in the fee-for-service component of Medicare (2001-2016). We used Cox proportional hazards regression to examine associations between exposure to PM, airport-related ultrafine particles (aUFP) and gaseous pollutants and incidence of AD, other dementia, and ADRD in a minimally- and fully-adjusted model, considering 12 established ADRD risk factors. We conducted stratified analyses to examine associations by sex, and race/ethnicity.
RESULTS: ADRD incidence was associated with PM2.5 (per 2 µg/m[3]), airport-related UFP (aUFP, per 4400 particles/cm[3]) and nitrogen dioxide (NO2, per 10 µg/m[3]) with hazard ratios (HRs, 95%CI), respectively, of 1.04 (1.02-1.06), 1.03 (1.01-1.05) and 1.09 (1.06-1.12). The AD-associations with PM2.5 and NO2, were stronger than the corresponding associations with other dementia (Pheterogeneity ≤ 0.003). Similar patterns of results were observed by sex and across race and ethnicity. Statistically significant findings for ADRD with PM2.5, aUFP and NO2 were observed among African American (respective HRs 1.03, 1.04, 1.09), and Latino and White participants for NO2 (HR 1.10, 1.08). Results in all and African American participants remained statistically significant in fully-adjusted models. Although the effect of PM2.5 was diluted in a co-pollutant with NO2, both PM2.5 and aUFP were significantly associated with ADRD incidence in a co-pollutant model, and NO2 and aUFP (but not PM2.5) remained associated in a multipollutant model. We did not observe consistent modifying effects for any of the 12 established ADRD risk factors.
CONCLUSIONS: In this multiethnic population, incidence of ADRD increased with exposures to PM2.5, aUFP, and NO2 in all subjects and this pattern was most prominent among African American adults. These results emphasize that ADRD prevention should include not only individual-level factors but also population-wide policies and regulation to curb air pollution.},
}
RevDate: 2026-03-07
CmpDate: 2026-03-07
Codesigning COVID-19 booster promotion materials in online workshops with long-term care staff: a process evaluation.
Health education research, 41(2):.
When engaging communities in vaccine promotion efforts, it is critical to understand who has availability and interest in participating, and how participants experience the process. Guided by the Reach, Effectiveness, Adoption, Implementation, Maintenance framework, we evaluated an online codesign process with long-term care center staff to design coronavirus disease (COVID-19) booster promotion materials for their colleagues. Twenty-six staff joined codesign teams organized by self-identified race to culturally tailor materials during a cluster-randomized controlled trial with 40 centers in two US states. Data sources included surveys; interviews; screening, enrollment, and attendance data; fidelity assessment; codesigned materials; and focus groups. We report summary statistics and thematic analyses. We found that time constraints could impede enrollment. Most codesigners enjoyed collaborating and identified their individual contributions. Many linked having shared characteristics with their teammates (e.g. race, gender, age) to a feeling of connection. A few reported feeling motivated to engage in booster promotion. The process resulted in messages aligned with known psychological antecedents of vaccination. Considering recruitment challenges and limited participation of direct care staff, organizers should consider shorter codesign processes. Organizing teams based on shared characteristics could promote comfort. Community input should inform codesign structure and team composition to achieve optimum enrollment and engagement.
Additional Links: PMID-41793312
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PubMed:
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@article {pmid41793312,
year = {2026},
author = {Arthur, KC and Wilson, KB and Berry, B and Binion, B and Becker, M and Derus, A and Diop, SL and Gachuiri, M and Green, BB and Koné, A and Licitra, J and Liou, C and McCracken, CE and Nisotel, LE and Owens, SE and Piccorelli, AV and Ramsey, S and Schwartz, LB and Senturia, K and Svoboda, J and Volney, J and Williamson, BD and Hsu, C},
title = {Codesigning COVID-19 booster promotion materials in online workshops with long-term care staff: a process evaluation.},
journal = {Health education research},
volume = {41},
number = {2},
pages = {},
doi = {10.1093/her/cyag004},
pmid = {41793312},
issn = {1465-3648},
support = {COVID-2021C2-13168/PCORI/Patient-Centered Outcomes Research Institute/United States ; },
mesh = {Humans ; *COVID-19/prevention & control ; Female ; Male ; SARS-CoV-2 ; *COVID-19 Vaccines/administration & dosage ; United States ; *Long-Term Care ; *Health Promotion/methods ; Middle Aged ; Adult ; *Health Personnel/education ; *Immunization, Secondary ; Focus Groups ; },
abstract = {When engaging communities in vaccine promotion efforts, it is critical to understand who has availability and interest in participating, and how participants experience the process. Guided by the Reach, Effectiveness, Adoption, Implementation, Maintenance framework, we evaluated an online codesign process with long-term care center staff to design coronavirus disease (COVID-19) booster promotion materials for their colleagues. Twenty-six staff joined codesign teams organized by self-identified race to culturally tailor materials during a cluster-randomized controlled trial with 40 centers in two US states. Data sources included surveys; interviews; screening, enrollment, and attendance data; fidelity assessment; codesigned materials; and focus groups. We report summary statistics and thematic analyses. We found that time constraints could impede enrollment. Most codesigners enjoyed collaborating and identified their individual contributions. Many linked having shared characteristics with their teammates (e.g. race, gender, age) to a feeling of connection. A few reported feeling motivated to engage in booster promotion. The process resulted in messages aligned with known psychological antecedents of vaccination. Considering recruitment challenges and limited participation of direct care staff, organizers should consider shorter codesign processes. Organizing teams based on shared characteristics could promote comfort. Community input should inform codesign structure and team composition to achieve optimum enrollment and engagement.},
}
MeSH Terms:
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hide MeSH Terms
Humans
*COVID-19/prevention & control
Female
Male
SARS-CoV-2
*COVID-19 Vaccines/administration & dosage
United States
*Long-Term Care
*Health Promotion/methods
Middle Aged
Adult
*Health Personnel/education
*Immunization, Secondary
Focus Groups
RevDate: 2026-03-06
Associations of genetically predicted interleukin-6 and tumor necrosis factor signaling pathways with mortality among persons with colorectal cancer: a two-sample Mendelian randomization.
BMC medicine pii:10.1186/s12916-026-04736-9 [Epub ahead of print].
BACKGROUND: Despite significant progress in identifying risk factors for colorectal cancer (CRC), factors influencing survival in people with CRC remain less understood. Pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) have been implicated in cancer progression and may influence CRC outcomes. We investigated associations between genetically predicted levels of IL-6 and TNF-α signaling pathways and mortality in people with CRC.
METHODS: We conducted a two-sample Mendelian randomization (MR) analysis using cis-acting single nucleotide polymorphisms (SNPs) associated with soluble IL-6 receptor alpha (sIL6-RA) and IL-6 signal transducer gp130 (IL6ST), representing IL-6 signaling, and with TNF-α, and its soluble receptors (sTNF-R1, sTNF-R2). SNPs were obtained separately from two large genome-wide association studies (GWAS): deCODE and UK Biobank (UKB). The outcome was CRC-specific mortality among 16,964 CRC cases (4010 deaths) in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Analyses were stratified by tumor site and stage. The inverse variance weighted (IVW) method, incorporating a correlation matrix for dependent SNPs, was used for primary analyses. Because literature links TNF-α to CRC incidence, we additionally performed a simulation study to evaluate the potential impact of collider bias resulting from restricting analyses to CRC cases.
RESULTS: Genetically predicted sIL6-RA was weakly positively associated with CRC-specific mortality (deCODE-SNPs (n = 13) HR per 1 SD increase: 1.06; 95% CI: 1.00-1.12; UKB-SNPs (n = 11) HR: 1.09; 95% CI: 1.02-1.17). Genetically proxied IL6ST levels showed no association with CRC-specific mortality in the overall sample (deCODE-SNPs (n = 19) HR: 1.04; 95% CI: 0.90-1.21; UKB-SNPs (n = 9) HR: 1.11; 95% CI: 0.87-2.42), while higher IL6ST levels were associated with increased mortality among patients with stage 2/3 disease (deCODE-SNPs (n = 19) HR: 1.45; 95% CI: 1.10-1.91; UKB-SNPs (n = 9) HR: 1.87; 95% CI: 1.22-2.89). No associations were observed for TNF-α, sTNF-R1, or sTNF-R2. Findings for all exposures were consistent across both GWAS datasets. Simulation analyses for TNF-α indicated collider bias was present but limited in magnitude.
CONCLUSIONS: Our findings suggest that IL-6 signaling may play a role in CRC progression although of limited magnitude, whereas TNF-related pathways appear less relevant for prognosis.
Additional Links: PMID-41792766
Publisher:
PubMed:
Citation:
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@article {pmid41792766,
year = {2026},
author = {Bouka, M and Nimptsch, K and Pham, TT and Bouras, E and Kanellopoulou, A and Phipps, AI and Van Guelpen, B and Brenner, H and Li, L and Le Marchand, L and Tsilidis, KK and Pischon, T},
title = {Associations of genetically predicted interleukin-6 and tumor necrosis factor signaling pathways with mortality among persons with colorectal cancer: a two-sample Mendelian randomization.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04736-9},
pmid = {41792766},
issn = {1741-7015},
abstract = {BACKGROUND: Despite significant progress in identifying risk factors for colorectal cancer (CRC), factors influencing survival in people with CRC remain less understood. Pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) have been implicated in cancer progression and may influence CRC outcomes. We investigated associations between genetically predicted levels of IL-6 and TNF-α signaling pathways and mortality in people with CRC.
METHODS: We conducted a two-sample Mendelian randomization (MR) analysis using cis-acting single nucleotide polymorphisms (SNPs) associated with soluble IL-6 receptor alpha (sIL6-RA) and IL-6 signal transducer gp130 (IL6ST), representing IL-6 signaling, and with TNF-α, and its soluble receptors (sTNF-R1, sTNF-R2). SNPs were obtained separately from two large genome-wide association studies (GWAS): deCODE and UK Biobank (UKB). The outcome was CRC-specific mortality among 16,964 CRC cases (4010 deaths) in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Analyses were stratified by tumor site and stage. The inverse variance weighted (IVW) method, incorporating a correlation matrix for dependent SNPs, was used for primary analyses. Because literature links TNF-α to CRC incidence, we additionally performed a simulation study to evaluate the potential impact of collider bias resulting from restricting analyses to CRC cases.
RESULTS: Genetically predicted sIL6-RA was weakly positively associated with CRC-specific mortality (deCODE-SNPs (n = 13) HR per 1 SD increase: 1.06; 95% CI: 1.00-1.12; UKB-SNPs (n = 11) HR: 1.09; 95% CI: 1.02-1.17). Genetically proxied IL6ST levels showed no association with CRC-specific mortality in the overall sample (deCODE-SNPs (n = 19) HR: 1.04; 95% CI: 0.90-1.21; UKB-SNPs (n = 9) HR: 1.11; 95% CI: 0.87-2.42), while higher IL6ST levels were associated with increased mortality among patients with stage 2/3 disease (deCODE-SNPs (n = 19) HR: 1.45; 95% CI: 1.10-1.91; UKB-SNPs (n = 9) HR: 1.87; 95% CI: 1.22-2.89). No associations were observed for TNF-α, sTNF-R1, or sTNF-R2. Findings for all exposures were consistent across both GWAS datasets. Simulation analyses for TNF-α indicated collider bias was present but limited in magnitude.
CONCLUSIONS: Our findings suggest that IL-6 signaling may play a role in CRC progression although of limited magnitude, whereas TNF-related pathways appear less relevant for prognosis.},
}
RevDate: 2026-03-06
Impact of Genetic Predisposition to Obesity on Long-Term Maintenance of Modest Weight Loss in Postmenopausal Women.
Obesity (Silver Spring, Md.) [Epub ahead of print].
OBJECTIVE: Long-term weight regain limits the population-level benefits of obesity interventions. We tested whether the polygenic risk score of BMI (PRSBMI) modifies weight trajectories following modest weight loss.
METHODS: The analytic sample included 9897 postmenopausal women from the Women's Health Initiative Dietary Modification Trial (6132 European American; 3749 African American). PRSBMI was derived from a trans-ancestry GWAS of ~2 million participants. Longitudinal weight change (7 years) was modeled using weighted GEE.
RESULTS: In European Americans, the PRSBMI × randomization × time interactions approached significance at the 95th percentile (p = 0.052) and 85th percentile (p = 0.07). No interaction was observed in African Americans. In analyses restricted to European Americans who lost ≥ 5% of initial weight by year 1 (20%; n = 1273), women in the ≥ 95th percentile of PRSBMI regained nearly twice as much per year as those with average risk (0.94 vs. 0.48 kg/year, p = 0.0016).
CONCLUSIONS: A high PRSBMI was associated with faster weight regain following modest weight loss in European American women. While further validation is required in a diverse population, these results suggest the potential for genetics to inform targeted strategies for sustaining long-term weight management.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005.
Additional Links: PMID-41792585
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PubMed:
Citation:
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@article {pmid41792585,
year = {2026},
author = {Lee, HH and Avery, CL and Graff, M and Kim, D and Arias, J and Van Horn, L and Kooperberg, C and North, KE},
title = {Impact of Genetic Predisposition to Obesity on Long-Term Maintenance of Modest Weight Loss in Postmenopausal Women.},
journal = {Obesity (Silver Spring, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/oby.70175},
pmid = {41792585},
issn = {1930-739X},
support = {75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D000//National Heart, Lung, and Blood Institute, National Institutes/ ; T32HL129982//National Heart, Lung, and Blood Institute, National Institutes/ ; /NH/NIH HHS/United States ; //U.S. Department of Health and Human Services/ ; /NH/NIH HHS/United States ; //U.S. Department of Health and Human Services/ ; //Intramural Research Program/ ; /CP/NCI NIH HHS/United States ; /CA/NCI NIH HHS/United States ; /NH/NIH HHS/United States ; },
abstract = {OBJECTIVE: Long-term weight regain limits the population-level benefits of obesity interventions. We tested whether the polygenic risk score of BMI (PRSBMI) modifies weight trajectories following modest weight loss.
METHODS: The analytic sample included 9897 postmenopausal women from the Women's Health Initiative Dietary Modification Trial (6132 European American; 3749 African American). PRSBMI was derived from a trans-ancestry GWAS of ~2 million participants. Longitudinal weight change (7 years) was modeled using weighted GEE.
RESULTS: In European Americans, the PRSBMI × randomization × time interactions approached significance at the 95th percentile (p = 0.052) and 85th percentile (p = 0.07). No interaction was observed in African Americans. In analyses restricted to European Americans who lost ≥ 5% of initial weight by year 1 (20%; n = 1273), women in the ≥ 95th percentile of PRSBMI regained nearly twice as much per year as those with average risk (0.94 vs. 0.48 kg/year, p = 0.0016).
CONCLUSIONS: A high PRSBMI was associated with faster weight regain following modest weight loss in European American women. While further validation is required in a diverse population, these results suggest the potential for genetics to inform targeted strategies for sustaining long-term weight management.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005.},
}
RevDate: 2026-03-06
Comparative analysis of RADS classification systems for solitary bone lesions: malignancy risk stratification performance and clinical utility.
European radiology [Epub ahead of print].
OBJECTIVE: To compare the malignancy risk stratification performance and inter-reader reliability of four Reporting and Data System (RADS) algorithms for solitary bone lesions: CT Bone-RADS, MRI Bone-RADS, Osseous Tumor (OT)-RADS, and Bone Tumor Imaging (BTI)-RADS.
MATERIALS AND METHODS: This retrospective analysis included patients with solitary bone lesions who underwent both CT and MRI between March 2005 and September 2021. Three radiologists independently categorized each lesion using CT Bone-RADS (1-4), MRI Bone-RADS (1-4), OT-RADS (2-5), and BTI-RADS (1-4). Categories were dichotomized into high- versus low-risk for malignancy. Diagnostic performance metrics and area under the receiver operating characteristic curve (AUC) were calculated for each reader as well as for a consensus interpretation generated using a majority-vote method. The reference standard was either histopathologic confirmation or imaging surveillance. Inter-reader reliability was assessed using Gwet's AC1 statistic.
RESULTS: A total of 207 patients (mean age, 49 ± 18 years; 111 men and 96 women) were included. Consensus malignancy risk stratification performance (AUC; sensitivity/specificity/positive predictive value/negative predictive value/accuracy, %) was as follows: CT Bone-RADS (0.52; 95/9/43/73/44), MRI Bone-RADS (0.60; 98/12/44/88/47), OT-RADS (0.91; 93/71/69/94/80), and BTI-RADS (0.89; 98/39/53/96/63). Inter-reader reliability (AC1) was excellent for CT Bone-RADS (0.978), MRI Bone-RADS (0.931), and BTI-RADS (0.822), and moderate for OT-RADS (0.585).
CONCLUSION: Among the evaluated bone tumor-RADS, OT-RADS demonstrated the most balanced diagnostic performance with moderate inter-reader reliability. CT Bone-RADS, MRI Bone-RADS, and BTI-RADS showed excellent inter-reader reliability.
KEY POINTS: Question Evaluation of solitary bone lesions is important but often challenging. This study compared four bone tumor-RADS algorithms to determine which provides the best malignancy risk stratification. Findings Among the four RADS algorithms, OT-RADS demonstrated the most balanced overall diagnostic performance in consensus analysis, while CT Bone-RADS, MRI Bone-RADS, and BTI-RADS showed excellent inter-reader reliability. Clinical relevance Knowledge of each RADS system's performance characteristics helps clinicians apply these algorithms appropriately to optimize the assessment of solitary bone lesions.
Additional Links: PMID-41792574
PubMed:
Citation:
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@article {pmid41792574,
year = {2026},
author = {Azhideh, A and Haseli, S and Park, C and Lee, H and Kim, HS and Mirghaderi, P and Chalian, M},
title = {Comparative analysis of RADS classification systems for solitary bone lesions: malignancy risk stratification performance and clinical utility.},
journal = {European radiology},
volume = {},
number = {},
pages = {},
pmid = {41792574},
issn = {1432-1084},
abstract = {OBJECTIVE: To compare the malignancy risk stratification performance and inter-reader reliability of four Reporting and Data System (RADS) algorithms for solitary bone lesions: CT Bone-RADS, MRI Bone-RADS, Osseous Tumor (OT)-RADS, and Bone Tumor Imaging (BTI)-RADS.
MATERIALS AND METHODS: This retrospective analysis included patients with solitary bone lesions who underwent both CT and MRI between March 2005 and September 2021. Three radiologists independently categorized each lesion using CT Bone-RADS (1-4), MRI Bone-RADS (1-4), OT-RADS (2-5), and BTI-RADS (1-4). Categories were dichotomized into high- versus low-risk for malignancy. Diagnostic performance metrics and area under the receiver operating characteristic curve (AUC) were calculated for each reader as well as for a consensus interpretation generated using a majority-vote method. The reference standard was either histopathologic confirmation or imaging surveillance. Inter-reader reliability was assessed using Gwet's AC1 statistic.
RESULTS: A total of 207 patients (mean age, 49 ± 18 years; 111 men and 96 women) were included. Consensus malignancy risk stratification performance (AUC; sensitivity/specificity/positive predictive value/negative predictive value/accuracy, %) was as follows: CT Bone-RADS (0.52; 95/9/43/73/44), MRI Bone-RADS (0.60; 98/12/44/88/47), OT-RADS (0.91; 93/71/69/94/80), and BTI-RADS (0.89; 98/39/53/96/63). Inter-reader reliability (AC1) was excellent for CT Bone-RADS (0.978), MRI Bone-RADS (0.931), and BTI-RADS (0.822), and moderate for OT-RADS (0.585).
CONCLUSION: Among the evaluated bone tumor-RADS, OT-RADS demonstrated the most balanced diagnostic performance with moderate inter-reader reliability. CT Bone-RADS, MRI Bone-RADS, and BTI-RADS showed excellent inter-reader reliability.
KEY POINTS: Question Evaluation of solitary bone lesions is important but often challenging. This study compared four bone tumor-RADS algorithms to determine which provides the best malignancy risk stratification. Findings Among the four RADS algorithms, OT-RADS demonstrated the most balanced overall diagnostic performance in consensus analysis, while CT Bone-RADS, MRI Bone-RADS, and BTI-RADS showed excellent inter-reader reliability. Clinical relevance Knowledge of each RADS system's performance characteristics helps clinicians apply these algorithms appropriately to optimize the assessment of solitary bone lesions.},
}
RevDate: 2026-03-06
Is it "time to eliminate" time to elimination of symptoms as a primary trial endpoint for respiratory virus targeting drugs?.
The Journal of infectious diseases pii:8509492 [Epub ahead of print].
Additional Links: PMID-41791419
Publisher:
PubMed:
Citation:
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@article {pmid41791419,
year = {2026},
author = {Schiffer, JT and Esmaeili, S and Owens, K and Boeckh, M and Waghmare, A},
title = {Is it "time to eliminate" time to elimination of symptoms as a primary trial endpoint for respiratory virus targeting drugs?.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag148},
pmid = {41791419},
issn = {1537-6613},
}
RevDate: 2026-03-12
CmpDate: 2026-03-12
Mapping the specificity of H3N2 strain-specific and cross-reactive human neutralizing antibodies elicited by the 2025-2026 influenza vaccine.
medRxiv : the preprint server for health sciences.
An H3N2 variant, named subclade K, continues to circulate widely during the 2025-2026 influenza season. This virus possesses a hemagglutinin (HA) protein that has eleven substitutions relative to the HA of the Northern Hemisphere 2025-2026 H3N2 vaccine strain. Many of these substitutions are in epitopes in well-characterized HA antigenic sites. Despite this, interim vaccine effectiveness studies indicate that the 2025-2026 influenza vaccine provides moderate protection against H3N2 subclade K infection. We previously reported that many individuals who received the 2025-2026 influenza vaccine produced antibodies that inhibit H3N2 subclade K virus cellular attachment. Here, we show these individuals also produced antibodies that neutralize H3N2 subclade K virus infection, and we observed a strong correlation between hemagglutination-inhibition titers and neutralizing antibody titers. We completed additional specificity studies using samples from individuals who did or did not have antibodies that cross-reacted to H3N2 subclade K viruses. Using high-throughput neutralization assays, we determined that antibodies that bound to the vaccine strain but not H3N2 subclade K viruses typically targeted antigenic site B of HA. Conversely, we found that cross-reactive neutralizing antibodies elicited by vaccination commonly targeted antigenic site A, D, and E of HA that are conserved between the vaccine strain and H3N2 subclade K viruses. Additional electron microscopy-based polyclonal epitope mapping studies confirmed that cross-reactive antibodies elicited by vaccination typically target epitopes on the side of HA. Together, our studies provide an immunological explanation of why the 2025-2026 influenza vaccine was partially effective against antigenically advance H3N2 subclade K viruses. Our data suggest that vaccine strains for subsequent seasons need to be carefully considered, since subclade K viruses have already started to acquire additional substitutions in HA antigenic sites targeted by cross-reactive antibodies.
Additional Links: PMID-41757210
PubMed:
Citation:
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@article {pmid41757210,
year = {2026},
author = {Liu, J and Gang, S and Kikawa, C and Rodriguez, AJ and Li, SH and Ye, N and Griffiths, T and Drapeau, EM and Atkinson, RK and Loes, AN and Collman, RG and Ferguson, JA and Han, J and Ward, AB and Bloom, JD and Hensley, SE},
title = {Mapping the specificity of H3N2 strain-specific and cross-reactive human neutralizing antibodies elicited by the 2025-2026 influenza vaccine.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41757210},
abstract = {An H3N2 variant, named subclade K, continues to circulate widely during the 2025-2026 influenza season. This virus possesses a hemagglutinin (HA) protein that has eleven substitutions relative to the HA of the Northern Hemisphere 2025-2026 H3N2 vaccine strain. Many of these substitutions are in epitopes in well-characterized HA antigenic sites. Despite this, interim vaccine effectiveness studies indicate that the 2025-2026 influenza vaccine provides moderate protection against H3N2 subclade K infection. We previously reported that many individuals who received the 2025-2026 influenza vaccine produced antibodies that inhibit H3N2 subclade K virus cellular attachment. Here, we show these individuals also produced antibodies that neutralize H3N2 subclade K virus infection, and we observed a strong correlation between hemagglutination-inhibition titers and neutralizing antibody titers. We completed additional specificity studies using samples from individuals who did or did not have antibodies that cross-reacted to H3N2 subclade K viruses. Using high-throughput neutralization assays, we determined that antibodies that bound to the vaccine strain but not H3N2 subclade K viruses typically targeted antigenic site B of HA. Conversely, we found that cross-reactive neutralizing antibodies elicited by vaccination commonly targeted antigenic site A, D, and E of HA that are conserved between the vaccine strain and H3N2 subclade K viruses. Additional electron microscopy-based polyclonal epitope mapping studies confirmed that cross-reactive antibodies elicited by vaccination typically target epitopes on the side of HA. Together, our studies provide an immunological explanation of why the 2025-2026 influenza vaccine was partially effective against antigenically advance H3N2 subclade K viruses. Our data suggest that vaccine strains for subsequent seasons need to be carefully considered, since subclade K viruses have already started to acquire additional substitutions in HA antigenic sites targeted by cross-reactive antibodies.},
}
RevDate: 2026-03-07
CmpDate: 2026-03-07
Exploring Feature Priorities and User Needs in Developing Virtual Study Assistants.
JMIR formative research, 10:e86945 pii:v10i1e86945.
This formative research explored health science researchers' perspectives on the development of an artificial intelligence-based virtual study assistant and identified 8 potential features and their priorities.
Additional Links: PMID-41791098
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@article {pmid41791098,
year = {2026},
author = {Tsai, CS and Lee, H and Szewczyk, W and Palmer, JK and Putnam, S and Munson, SA and Heffner, JL and Vasbinder, A and Paullada, A and Yuwen, W and Reding, KW},
title = {Exploring Feature Priorities and User Needs in Developing Virtual Study Assistants.},
journal = {JMIR formative research},
volume = {10},
number = {},
pages = {e86945},
doi = {10.2196/86945},
pmid = {41791098},
issn = {2561-326X},
mesh = {Humans ; *Artificial Intelligence ; *User-Computer Interface ; *Virtual Reality ; },
abstract = {This formative research explored health science researchers' perspectives on the development of an artificial intelligence-based virtual study assistant and identified 8 potential features and their priorities.},
}
MeSH Terms:
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Humans
*Artificial Intelligence
*User-Computer Interface
*Virtual Reality
RevDate: 2026-03-06
CmpDate: 2026-03-07
Modulating AP-1 enables CAR T cells to establish an intratumoral stemlike reservoir and overcomes resistance to PD-1 blockade.
Science immunology, 11(117):eadw7685.
Chimeric antigen receptor T (CAR T) cell therapy has shown limited synergy with immune checkpoint inhibitors, but the mechanisms underlying resistance remain unclear. Stemlike T cells coexpressing programmed cell death protein 1 (PD-1) and T cell factor 1 (TCF1) mediate responses to PD-1-PD-L1 (programmed death ligand 1) blockade and are maintained by major histocompatibility complex (MHC)-dependent interactions with dendritic cells in lymphoid tissues. Because CAR T cells recognize intact antigen rather than peptide-MHC, their activation is restricted to tumors, potentially limiting maintenance of this critical subset. In murine models of lung cancer, CAR T cells down-regulated TCF1, became exhausted, and were not enhanced by PD-L1 blockade. Overexpression of the transcription factor c-Jun increased intratumoral PD-1[+]TCF1[+] CAR T cells but did not prevent exhaustion, given that PD-1 induced posttranscriptional c-Jun down-regulation. PD-L1 blockade restored c-Jun levels, markedly increased CAR T cells, and enabled near-complete tumor clearance, revealing a mechanism by which MHC-independent CAR T cells can be engineered to overcome resistance to PD-1-PD-L1 blockade.
Additional Links: PMID-41790934
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@article {pmid41790934,
year = {2026},
author = {Snyder, AJ and Garrison, SM and Kluesner, MG and Nutt, WS and Shasha, C and Ho, T and Marsh, SA and Linde, M and Wu, F and Meyer, L and Wilhelm, AR and Ortiz-Espinosa, S and Zepeda, V and Bingham, E and Malik, H and Mak, SR and Gad, E and Bhise, SS and Fan, E and Sarvothama, M and Wang, X and Potluri, S and Long, A and Elz, A and Ghajar, CM and Furlan, SN and Newell, EW and Srivastava, S},
title = {Modulating AP-1 enables CAR T cells to establish an intratumoral stemlike reservoir and overcomes resistance to PD-1 blockade.},
journal = {Science immunology},
volume = {11},
number = {117},
pages = {eadw7685},
doi = {10.1126/sciimmunol.adw7685},
pmid = {41790934},
issn = {2470-9468},
mesh = {Animals ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology ; Mice ; *Immunotherapy, Adoptive/methods ; *Receptors, Chimeric Antigen/immunology ; *Transcription Factor AP-1/immunology/metabolism ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; *Lung Neoplasms/immunology/therapy ; Drug Resistance, Neoplasm/immunology ; B7-H1 Antigen/immunology/antagonists & inhibitors ; Mice, Inbred C57BL ; Cell Line, Tumor ; },
abstract = {Chimeric antigen receptor T (CAR T) cell therapy has shown limited synergy with immune checkpoint inhibitors, but the mechanisms underlying resistance remain unclear. Stemlike T cells coexpressing programmed cell death protein 1 (PD-1) and T cell factor 1 (TCF1) mediate responses to PD-1-PD-L1 (programmed death ligand 1) blockade and are maintained by major histocompatibility complex (MHC)-dependent interactions with dendritic cells in lymphoid tissues. Because CAR T cells recognize intact antigen rather than peptide-MHC, their activation is restricted to tumors, potentially limiting maintenance of this critical subset. In murine models of lung cancer, CAR T cells down-regulated TCF1, became exhausted, and were not enhanced by PD-L1 blockade. Overexpression of the transcription factor c-Jun increased intratumoral PD-1[+]TCF1[+] CAR T cells but did not prevent exhaustion, given that PD-1 induced posttranscriptional c-Jun down-regulation. PD-L1 blockade restored c-Jun levels, markedly increased CAR T cells, and enabled near-complete tumor clearance, revealing a mechanism by which MHC-independent CAR T cells can be engineered to overcome resistance to PD-1-PD-L1 blockade.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology
Mice
*Immunotherapy, Adoptive/methods
*Receptors, Chimeric Antigen/immunology
*Transcription Factor AP-1/immunology/metabolism
Humans
Immune Checkpoint Inhibitors/pharmacology
*Lung Neoplasms/immunology/therapy
Drug Resistance, Neoplasm/immunology
B7-H1 Antigen/immunology/antagonists & inhibitors
Mice, Inbred C57BL
Cell Line, Tumor
RevDate: 2026-03-05
Correction: Regulation of metabolic adaptation and leukemia progression by MUSASHI2-DEPTOR-KIF11 axis.
Additional Links: PMID-41787068
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PubMed:
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@article {pmid41787068,
year = {2026},
author = {Setiawan, T and Muhammad, JA and Julianto, NM and Wirawan, LM and Jun, N and Sari, IN and Oehler, VG and Kim, DW and Kwon, HY},
title = {Correction: Regulation of metabolic adaptation and leukemia progression by MUSASHI2-DEPTOR-KIF11 axis.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41375-026-02909-2},
pmid = {41787068},
issn = {1476-5551},
}
RevDate: 2026-03-05
Key Updates on the Version 9 AJCC/UICC Staging System for Salivary Gland Carcinoma.
Annals of surgical oncology [Epub ahead of print].
BACKGROUND: Multiple studies have identified limitations in the nodal (N) category definitions of the eighth-edition tumor-node-metastasis classifi cation (TNM8) for major salivary gland carcinoma (SGC). Minor SGCs have traditionally been staged according to site of origin despite distinct biology and patterns of spread, and the feasibility of a unified staging system for both major and minor SGCs had not been systematically evaluated. These shortcomings prompted a comprehensive reassessment of SGC staging.
METHOD: A multidisciplinary international expert panel, in collaboration with the American Joint Committee on Cancer (AJCC) Head and Neck Core Group, developed and validated a refined TNM classification for SGC. The proposed system was subsequently adopted by both the AJCC and the Union for International Cancer Control (UICC).
RESULTS: The ninth edition (TNM9) introduces the first unified SGC-specific staging system applicable to both major and minor SGCs. Key revisions include: (1) exclusion of extremely rare or non-salivary-origin histologies (e.g., squamous cell carcinoma, neuroendocrine carcinoma, and basosquamous carcinoma); (2) integration of major and minor SGCs into a single staging framework, with clarification of T3-T4 definitions to ensure applicability across both groups; (3) simplified N categorization based on lymph node count and extranodal extension (ENE): N0 (no nodal disease), N1 (1-3 nodes without ENE), and N2 (3 nodes or any ENE); and (4) restriction of stage IV exclusively to M1 disease, allowing future refinement of metastatic subcategories. Clinical TNM (cTNM) applies the same criteria as pathologic TNM (pTNM), incorporating radiologic assessment of abnormal lymph node count and imaging-detected ENE (iENE).
CONCLUSIONS: By establishing a unified, biologically relevant staging system with improved prognostic discrimination, TNM9 enhances clinical applicability and promotes more consistent management of both major and minor salivary gland carcinomas.
Additional Links: PMID-41787039
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@article {pmid41787039,
year = {2026},
author = {Huang, SH and Seethala, RR and Patel, SG and O'Sullivan, B and Lydiatt, W and Ho, AS and Hosni, A and Vander Poorten, V and Glastonbury, CM and Bishop, J and Beadle, B and Ha, P and Kakarala, K and Rodriguez, CP and Ganly, I},
title = {Key Updates on the Version 9 AJCC/UICC Staging System for Salivary Gland Carcinoma.},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
pmid = {41787039},
issn = {1534-4681},
abstract = {BACKGROUND: Multiple studies have identified limitations in the nodal (N) category definitions of the eighth-edition tumor-node-metastasis classifi cation (TNM8) for major salivary gland carcinoma (SGC). Minor SGCs have traditionally been staged according to site of origin despite distinct biology and patterns of spread, and the feasibility of a unified staging system for both major and minor SGCs had not been systematically evaluated. These shortcomings prompted a comprehensive reassessment of SGC staging.
METHOD: A multidisciplinary international expert panel, in collaboration with the American Joint Committee on Cancer (AJCC) Head and Neck Core Group, developed and validated a refined TNM classification for SGC. The proposed system was subsequently adopted by both the AJCC and the Union for International Cancer Control (UICC).
RESULTS: The ninth edition (TNM9) introduces the first unified SGC-specific staging system applicable to both major and minor SGCs. Key revisions include: (1) exclusion of extremely rare or non-salivary-origin histologies (e.g., squamous cell carcinoma, neuroendocrine carcinoma, and basosquamous carcinoma); (2) integration of major and minor SGCs into a single staging framework, with clarification of T3-T4 definitions to ensure applicability across both groups; (3) simplified N categorization based on lymph node count and extranodal extension (ENE): N0 (no nodal disease), N1 (1-3 nodes without ENE), and N2 (3 nodes or any ENE); and (4) restriction of stage IV exclusively to M1 disease, allowing future refinement of metastatic subcategories. Clinical TNM (cTNM) applies the same criteria as pathologic TNM (pTNM), incorporating radiologic assessment of abnormal lymph node count and imaging-detected ENE (iENE).
CONCLUSIONS: By establishing a unified, biologically relevant staging system with improved prognostic discrimination, TNM9 enhances clinical applicability and promotes more consistent management of both major and minor salivary gland carcinomas.},
}
RevDate: 2026-03-11
CmpDate: 2026-03-11
Differential effects of two common GVHD prophylaxis regimens on the gut microbiome: Results from the BMT CTN 1801 study.
bioRxiv : the preprint server for biology.
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for many hematological malignancies, but graft-versus-host disease (GVHD) is a common complication. Low gut microbiome diversity is associated with higher GVHD risk and shorter survival in multiple studies. Recently, the BMT CTN 1703 clinical trial demonstrated superiority of a GVHD-prophylaxis regimen including post-transplant cyclophosphamide (PTCy) compared to the standard prophylaxis (tacrolimus and methotrexate, Tac/MTX) in terms of GVHD-free, relapse-free survival at one year among reduced intensity conditioning allo-HCT recipients. However, the effect of PTCy on the gut microbiome and its association with clinical outcome have not been described. Here, we report on a companion randomized clinical controlled trial (BMT CTN 1801), which collected 2575 longitudinal stool samples from 304 study participants. Samples were obtained up to weekly up to day 84 post allo-HCT and at less frequent intervals thereafter, up to 2 years. Microbiome diversity and absolute microbial load were lower in the PTCy group compared to the Tac/MTX group on days 14-28 post-HCT. However, diversity at the timepoint closest to neutrophil engraftment was not significantly associated with non-relapse mortality after one year or other clinical outcomes, contrary to expectations from previous studies. Microbial domination events, when a single species exceeds 30% relative abundance, were comparable across treatment arms and reflected both pathogen blooms as well as less severe disruptions of the microbial community. Clostridium scindens and secondary bile acid metabolism pathways were less prevalent in the PTCy arm than in the Tac/MTX arm post-HCT, yet presence of secondary bile acid metabolism pathways was associated with a lower risk of chronic GVHD. Given that PTCy was associated with a greater disruption of the microbiome as measured by diversity, absolute microbial abundance, and bile acid metabolism capability, but better clinical outcomes overall, these data suggest that the importance of the microbiome in modulating the host immune systems after allo-HCT is specific to different types of GVHD prophylaxis.
Additional Links: PMID-41756883
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Citation:
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@article {pmid41756883,
year = {2026},
author = {Wirbel, J and Saber, W and Martens, MJ and Peled, JU and Andermann, TM and Fei, T and Brooks, EF and Doyle, B and Pincus, NB and Jenq, RR and Bar, M and Bolaños-Meade, J and Bratrude, B and Chhabra, S and Choi, SW and Clark, W and Das, S and Elmariah, H and Gooptu, M and Holtan, SG and Jones, RJ and Levine, JE and Logan, BR and Al Malki, MM and Murthy, HS and Rashidi, A and Rezvani, AR and Riches, ML and Runaas, L and Sandhu, K and Spahn, A and Sung, AD and van den Brink, MRM and Horowitz, MM and Hamadani, M and Kean, LS and Perales, MA and Bhatt, AS},
title = {Differential effects of two common GVHD prophylaxis regimens on the gut microbiome: Results from the BMT CTN 1801 study.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41756883},
issn = {2692-8205},
abstract = {Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for many hematological malignancies, but graft-versus-host disease (GVHD) is a common complication. Low gut microbiome diversity is associated with higher GVHD risk and shorter survival in multiple studies. Recently, the BMT CTN 1703 clinical trial demonstrated superiority of a GVHD-prophylaxis regimen including post-transplant cyclophosphamide (PTCy) compared to the standard prophylaxis (tacrolimus and methotrexate, Tac/MTX) in terms of GVHD-free, relapse-free survival at one year among reduced intensity conditioning allo-HCT recipients. However, the effect of PTCy on the gut microbiome and its association with clinical outcome have not been described. Here, we report on a companion randomized clinical controlled trial (BMT CTN 1801), which collected 2575 longitudinal stool samples from 304 study participants. Samples were obtained up to weekly up to day 84 post allo-HCT and at less frequent intervals thereafter, up to 2 years. Microbiome diversity and absolute microbial load were lower in the PTCy group compared to the Tac/MTX group on days 14-28 post-HCT. However, diversity at the timepoint closest to neutrophil engraftment was not significantly associated with non-relapse mortality after one year or other clinical outcomes, contrary to expectations from previous studies. Microbial domination events, when a single species exceeds 30% relative abundance, were comparable across treatment arms and reflected both pathogen blooms as well as less severe disruptions of the microbial community. Clostridium scindens and secondary bile acid metabolism pathways were less prevalent in the PTCy arm than in the Tac/MTX arm post-HCT, yet presence of secondary bile acid metabolism pathways was associated with a lower risk of chronic GVHD. Given that PTCy was associated with a greater disruption of the microbiome as measured by diversity, absolute microbial abundance, and bile acid metabolism capability, but better clinical outcomes overall, these data suggest that the importance of the microbiome in modulating the host immune systems after allo-HCT is specific to different types of GVHD prophylaxis.},
}
RevDate: 2026-03-11
CmpDate: 2026-03-11
CaptureBody - an anti-CD45 × anti-IgG bispecific antibody enables accurate unmixing for spectral flow cytometry.
bioRxiv : the preprint server for biology.
Accurate spectral unmixing is a critical step for flow cytometry data analysis and requires a single stain control for every fluorescent parameter used in an experiment. Currently, compensation particles are often used for making single stain controls when a target protein is of low abundance or a cell type is of low frequency. However, compensation particles introduce incongruencies in emission spectra compared to cells resulting in spectral unmixing or compensation errors. To enable the use of cells regardless of the abundance of target proteins or immune cell type, we generated a bispecific antibody that links a human anti-CD45 and mouse anti-IgG variable region. We refer to this new bispecific tool as CaptureBody (CB) and highlight the benefits of its final nanobody-based design. We provide all sequences and methods necessary for the in-house expression of a CaptureBody to disseminate their use for spectral flow cytometry experiments.
Additional Links: PMID-41756882
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@article {pmid41756882,
year = {2026},
author = {Zambidis, AE and Siddaramaiah, LK and Konecny, AJ and Gray, M and Prlic, M},
title = {CaptureBody - an anti-CD45 × anti-IgG bispecific antibody enables accurate unmixing for spectral flow cytometry.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41756882},
issn = {2692-8205},
abstract = {Accurate spectral unmixing is a critical step for flow cytometry data analysis and requires a single stain control for every fluorescent parameter used in an experiment. Currently, compensation particles are often used for making single stain controls when a target protein is of low abundance or a cell type is of low frequency. However, compensation particles introduce incongruencies in emission spectra compared to cells resulting in spectral unmixing or compensation errors. To enable the use of cells regardless of the abundance of target proteins or immune cell type, we generated a bispecific antibody that links a human anti-CD45 and mouse anti-IgG variable region. We refer to this new bispecific tool as CaptureBody (CB) and highlight the benefits of its final nanobody-based design. We provide all sequences and methods necessary for the in-house expression of a CaptureBody to disseminate their use for spectral flow cytometry experiments.},
}
RevDate: 2026-03-05
Population-level cancer trends among solid organ transplant recipients in the United States during 1995-2021.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons pii:S1600-6135(26)00122-X [Epub ahead of print].
Solid organ transplant recipients (SOTRs) experience elevated cancer risk from immunosuppression and underlying medical conditions. Medical management has improved over time, and SOTRs are living longer. We used registry data covering 693,718 SOTRs in the United States (US) to evaluate population-level cancer trends during 1995-2021. Compared with SOTRs in 1995-2003, those in 2013-2021 were living at older ages and were followed at a longer time since their transplant. Based on 65,081 cancers, cancer incidence in SOTRs was higher during 2013-2021 than 1995-2003 (unadjusted incidence rate ratio [IRR] 1.29, 95% confidence interval [95%CI] 1.26-1.32). However, cancer incidence was lower in 2013-2021 after adjustment for age (IRR 0.93, 95%CI 0.91-0.95) and multivariable adjustment (0.93, 0.90-0.96). Results for the six most common cancer types showed varying trends during 1995-2021. Overall cancer incidence was higher in SOTRs than in the US general population during 1995-2021 and, most recently, in 2013-2021 (standardized incidence ratio 1.66, 95%CI 1.64-1.67). In conclusion, after accounting for age, there was an encouraging decline in cancer incidence among US SOTRs during 1995-2021. However, incidence remained elevated compared with the general population in 2013-2021. Measures are needed to reduce the cancer burden as SOTRs live longer after transplantation and the population ages.
Additional Links: PMID-41786253
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PubMed:
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@article {pmid41786253,
year = {2026},
author = {Engels, EA and Castenson, D and Luo, Q and Shiels, MS and Israni, A and Li, J and Madeleine, MM and Pawlish, K and Ramirez Aguilar, D and Zeng, Y and Pfieffer, RM},
title = {Population-level cancer trends among solid organ transplant recipients in the United States during 1995-2021.},
journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajt.2026.02.036},
pmid = {41786253},
issn = {1600-6143},
abstract = {Solid organ transplant recipients (SOTRs) experience elevated cancer risk from immunosuppression and underlying medical conditions. Medical management has improved over time, and SOTRs are living longer. We used registry data covering 693,718 SOTRs in the United States (US) to evaluate population-level cancer trends during 1995-2021. Compared with SOTRs in 1995-2003, those in 2013-2021 were living at older ages and were followed at a longer time since their transplant. Based on 65,081 cancers, cancer incidence in SOTRs was higher during 2013-2021 than 1995-2003 (unadjusted incidence rate ratio [IRR] 1.29, 95% confidence interval [95%CI] 1.26-1.32). However, cancer incidence was lower in 2013-2021 after adjustment for age (IRR 0.93, 95%CI 0.91-0.95) and multivariable adjustment (0.93, 0.90-0.96). Results for the six most common cancer types showed varying trends during 1995-2021. Overall cancer incidence was higher in SOTRs than in the US general population during 1995-2021 and, most recently, in 2013-2021 (standardized incidence ratio 1.66, 95%CI 1.64-1.67). In conclusion, after accounting for age, there was an encouraging decline in cancer incidence among US SOTRs during 1995-2021. However, incidence remained elevated compared with the general population in 2013-2021. Measures are needed to reduce the cancer burden as SOTRs live longer after transplantation and the population ages.},
}
RevDate: 2026-03-07
CmpDate: 2026-03-07
Cardiac radiosensitivity in the era of thoracic chemoradiotherapy and immunotherapy: a scoping review.
The Lancet. Oncology, 27(3):e130-e140.
Concurrent chemoradiotherapy followed by immune checkpoint inhibitor (ICI) consolidation is now the standard of care for unresectable stage III non-small-cell lung cancer (NSCLC) and is increasingly applied to other thoracic malignancies. Although survival outcomes have improved, concerns about cardiac toxicity have emerged, as both chemoradiotherapy and ICIs are independently cardiotoxic and their combined effects remain unclear. This scoping review first examines chemoradiotherapy-associated and ICI-associated cardiac toxicity separately, and then evaluates their convergence in combined chemoradiotherapy and ICI therapy. For this examination and evaluation, we draw on ten clinical studies, two reviews, and five preclinical reports that together address six key questions: (1) does ICI add cardiac risks to chemoradiotherapy, (2) does previous radiotherapy increase cardiac risks with ICI, (3) does ICI alter the radiosensitivity of cardiac subregions, (4) how should cardiac endpoints be defined, (5) can molecular or pharmacological interventions mitigate toxicity, and (6) what are the major risk factors and management strategies? We also highlight four major gaps: extension beyond NSCLC, long-term survivorship, the potential of advanced radiotherapy techniques, and the interplay between lymphopenia and cardiotoxicity. The convergence of chemoradiotherapy and ICIs represents a new cardiac risk profile. Addressing these questions through larger, long-term studies is essential to balance oncological efficacy with cardiovascular safety.
Additional Links: PMID-41785903
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PubMed:
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@article {pmid41785903,
year = {2026},
author = {Kim, Y and Bates, JE and Yoon, HI and Grassberger, C},
title = {Cardiac radiosensitivity in the era of thoracic chemoradiotherapy and immunotherapy: a scoping review.},
journal = {The Lancet. Oncology},
volume = {27},
number = {3},
pages = {e130-e140},
doi = {10.1016/S1470-2045(25)00651-5},
pmid = {41785903},
issn = {1474-5488},
mesh = {Humans ; *Chemoradiotherapy/adverse effects ; *Immune Checkpoint Inhibitors/adverse effects ; *Cardiotoxicity/etiology ; *Immunotherapy/adverse effects ; *Lung Neoplasms/therapy/pathology ; *Carcinoma, Non-Small-Cell Lung/therapy/pathology ; *Radiation Tolerance/drug effects ; *Heart/radiation effects/drug effects ; *Thoracic Neoplasms/therapy ; Risk Factors ; },
abstract = {Concurrent chemoradiotherapy followed by immune checkpoint inhibitor (ICI) consolidation is now the standard of care for unresectable stage III non-small-cell lung cancer (NSCLC) and is increasingly applied to other thoracic malignancies. Although survival outcomes have improved, concerns about cardiac toxicity have emerged, as both chemoradiotherapy and ICIs are independently cardiotoxic and their combined effects remain unclear. This scoping review first examines chemoradiotherapy-associated and ICI-associated cardiac toxicity separately, and then evaluates their convergence in combined chemoradiotherapy and ICI therapy. For this examination and evaluation, we draw on ten clinical studies, two reviews, and five preclinical reports that together address six key questions: (1) does ICI add cardiac risks to chemoradiotherapy, (2) does previous radiotherapy increase cardiac risks with ICI, (3) does ICI alter the radiosensitivity of cardiac subregions, (4) how should cardiac endpoints be defined, (5) can molecular or pharmacological interventions mitigate toxicity, and (6) what are the major risk factors and management strategies? We also highlight four major gaps: extension beyond NSCLC, long-term survivorship, the potential of advanced radiotherapy techniques, and the interplay between lymphopenia and cardiotoxicity. The convergence of chemoradiotherapy and ICIs represents a new cardiac risk profile. Addressing these questions through larger, long-term studies is essential to balance oncological efficacy with cardiovascular safety.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Chemoradiotherapy/adverse effects
*Immune Checkpoint Inhibitors/adverse effects
*Cardiotoxicity/etiology
*Immunotherapy/adverse effects
*Lung Neoplasms/therapy/pathology
*Carcinoma, Non-Small-Cell Lung/therapy/pathology
*Radiation Tolerance/drug effects
*Heart/radiation effects/drug effects
*Thoracic Neoplasms/therapy
Risk Factors
RevDate: 2026-03-05
Financial Hardship Before Diagnosis: Influence on Late-Stage Cancer Presentation and the Role of Screening.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [Epub ahead of print].
PURPOSE: This study investigates the relationship between prediagnosis financial hardship (FH) and cancer stage, and the mediating role of cancer screening in breast cancer.
METHODS: This case-control study used linked, deidentified records from adult cancer patients diagnosed with stage I to IV solid tumors (2014-2017) from the Western Washington SEER registry, along with credit report data from TransUnion and health care claims, encompassing various cancers. FH was defined as at least one record of collections, charge-offs, delinquent mortgage payments, tax liens, foreclosures, repossessions, or bankruptcies within 2 years before diagnosis. We used multivariable log-binomial regression to assess the association between FH and late-stage diagnosis (stages III and IV) overall and by cancer screening category, and mediation analysis to evaluate the role of screening mammography in breast cancer.
RESULTS: Among 50,148 patients with cancer (mean age 64 years, 52% female, 85% non-Hispanic White), 30% experienced FH before diagnosis, which was associated with a 14% higher probability of late-stage diagnosis (adjusted risk ratio [aRR], 1.14 [95% CI, 1.11 to 1.17]). This association was stronger for cancers with organized screening (aRR, 1.25 [95% CI, 1.21 to 1.29]) and those detectable by physical examinations (aRR, 1.44 [95% CI, 1.31 to 1.59]), but not for cancers without these protocols (aRR, 1.00 [95% CI, 0.94 to 1.07]), with variations among individual sites. Among patients with breast cancer, 70% of the increased risk of late-stage diagnosis was attributable to the nonreceipt of screening.
CONCLUSION: FH significantly affects cancer stage at diagnosis, especially for cancers with organized screening and physical examinations. In breast cancer, this association is largely attributed to lack of screening. These findings underscore FH as an important social determinant of health and the need for targeted interventions to improve screening access.
Additional Links: PMID-41785446
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PubMed:
Citation:
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@article {pmid41785446,
year = {2026},
author = {Khor, S and Yu, K and Fedorenko, CR and Ramsey, S and Rivers, Z and Kreizenbeck, K and Khan, HM and Li, L and Kestner, ST and Kwendakwema, CN and Shankaran, V},
title = {Financial Hardship Before Diagnosis: Influence on Late-Stage Cancer Presentation and the Role of Screening.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2501360},
doi = {10.1200/JCO-25-01360},
pmid = {41785446},
issn = {1527-7755},
abstract = {PURPOSE: This study investigates the relationship between prediagnosis financial hardship (FH) and cancer stage, and the mediating role of cancer screening in breast cancer.
METHODS: This case-control study used linked, deidentified records from adult cancer patients diagnosed with stage I to IV solid tumors (2014-2017) from the Western Washington SEER registry, along with credit report data from TransUnion and health care claims, encompassing various cancers. FH was defined as at least one record of collections, charge-offs, delinquent mortgage payments, tax liens, foreclosures, repossessions, or bankruptcies within 2 years before diagnosis. We used multivariable log-binomial regression to assess the association between FH and late-stage diagnosis (stages III and IV) overall and by cancer screening category, and mediation analysis to evaluate the role of screening mammography in breast cancer.
RESULTS: Among 50,148 patients with cancer (mean age 64 years, 52% female, 85% non-Hispanic White), 30% experienced FH before diagnosis, which was associated with a 14% higher probability of late-stage diagnosis (adjusted risk ratio [aRR], 1.14 [95% CI, 1.11 to 1.17]). This association was stronger for cancers with organized screening (aRR, 1.25 [95% CI, 1.21 to 1.29]) and those detectable by physical examinations (aRR, 1.44 [95% CI, 1.31 to 1.59]), but not for cancers without these protocols (aRR, 1.00 [95% CI, 0.94 to 1.07]), with variations among individual sites. Among patients with breast cancer, 70% of the increased risk of late-stage diagnosis was attributable to the nonreceipt of screening.
CONCLUSION: FH significantly affects cancer stage at diagnosis, especially for cancers with organized screening and physical examinations. In breast cancer, this association is largely attributed to lack of screening. These findings underscore FH as an important social determinant of health and the need for targeted interventions to improve screening access.},
}
RevDate: 2026-03-05
Nonmyeloablative Conditioning Combined with Anti-CD117 Antibody Briquilimab in Older Adults with High-Risk AML and MDS.
Blood pii:566932 [Epub ahead of print].
Briquilimab is a monoclonal antibody inhibiting stem cell factor (SCF) binding to CD117 (c-Kit). Based on preclinical data demonstrating the antibody clears hematopoietic stem and progenitor cells (HSPC) and myeloid malignant cells, we conducted a phase 1 trial examining briquilimab plus non-myeloablative fludarabine (flu) and total body irradiation (TBI) as conditioning for older adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing matched donor allogeneic hematopoietic cell transplantation (HCT). Briquilimab was infused 10-14 days before transplant day (TD) 0; fludarabine 30mg/m2 and TBI 2-3 Gy were administered on TD -4 to -2 and TD0, respectively. Graft-versus-host disease prophylaxis consisted of tacrolimus, sirolimus, and mycophenolate mofetil. Thirty-two patients enrolled (n=13 AML in complete remission [CR], n=3 AML in relapse, n=16 MDS). Median age was 70 years and most had detectable measurable residual disease at screening. There were no briquilimab infusion reactions, dose limiting toxicities, or primary graft failure events; briquilimab clearance was predictable across patients. Among the AML in CR cohort, 1-year EFS was 69.2% (95% CI, 37.3, 87.2); 1-year OS was 75% (95% CI, 40.8, 91.2). Among the MDS cohort, 1-year EFS was 53.8% (26.8, 74.8); 1-year OS was 76.4% (42.7, 91.8). One of 3 AML patients in relapse experienced a transient response. Marrow samples obtained before and after briquilimab and prior to flu/TBI demonstrated AML/MDS HSPC depletion (mean 62.4±22.7%) with resultant 3-fold increase in serum SCF. In summary, we demonstrate the feasibility, safety, and proof of concept of CD117 targeting with briquilimab as HCT conditioning for AML/MDS. The trial is registered at clinicaltrials.gov; using identifier: NCT04429191.
Additional Links: PMID-41785374
Publisher:
PubMed:
Citation:
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hide bibtex listing
@article {pmid41785374,
year = {2026},
author = {Muffly, LS and Lee, CJ and Gandhi, A and Varma, A and Scott, BL and Patel, SS and Shiraz, P and Youn, M and Yanagiba, C and Arulprakasam, J and Le, A and Kwon, HS and Long-Boyle, JR and Shizuru, JA and Pang, W and Artz, AS},
title = {Nonmyeloablative Conditioning Combined with Anti-CD117 Antibody Briquilimab in Older Adults with High-Risk AML and MDS.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025031858},
pmid = {41785374},
issn = {1528-0020},
abstract = {Briquilimab is a monoclonal antibody inhibiting stem cell factor (SCF) binding to CD117 (c-Kit). Based on preclinical data demonstrating the antibody clears hematopoietic stem and progenitor cells (HSPC) and myeloid malignant cells, we conducted a phase 1 trial examining briquilimab plus non-myeloablative fludarabine (flu) and total body irradiation (TBI) as conditioning for older adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing matched donor allogeneic hematopoietic cell transplantation (HCT). Briquilimab was infused 10-14 days before transplant day (TD) 0; fludarabine 30mg/m2 and TBI 2-3 Gy were administered on TD -4 to -2 and TD0, respectively. Graft-versus-host disease prophylaxis consisted of tacrolimus, sirolimus, and mycophenolate mofetil. Thirty-two patients enrolled (n=13 AML in complete remission [CR], n=3 AML in relapse, n=16 MDS). Median age was 70 years and most had detectable measurable residual disease at screening. There were no briquilimab infusion reactions, dose limiting toxicities, or primary graft failure events; briquilimab clearance was predictable across patients. Among the AML in CR cohort, 1-year EFS was 69.2% (95% CI, 37.3, 87.2); 1-year OS was 75% (95% CI, 40.8, 91.2). Among the MDS cohort, 1-year EFS was 53.8% (26.8, 74.8); 1-year OS was 76.4% (42.7, 91.8). One of 3 AML patients in relapse experienced a transient response. Marrow samples obtained before and after briquilimab and prior to flu/TBI demonstrated AML/MDS HSPC depletion (mean 62.4±22.7%) with resultant 3-fold increase in serum SCF. In summary, we demonstrate the feasibility, safety, and proof of concept of CD117 targeting with briquilimab as HCT conditioning for AML/MDS. The trial is registered at clinicaltrials.gov; using identifier: NCT04429191.},
}
RevDate: 2026-03-05
Proteogenomic features define subtypes of mantle cell lymphoma.
Blood advances pii:566936 [Epub ahead of print].
Mantle cell lymphoma (MCL) is a biologically heterogeneous B-cell malignancy. While genomics and transcriptomics have delineated parts of the MCL disease spectrum, the proteomics remains largely unexplored. Here, we conducted a comprehensive proteogenomic analysis integrating genomics, transcriptomics, and proteomics on peripheral blood samples from 27 MCL patients and 4 healthy donors to investigate the translational and post-translational dimensions of MCL. Our study identified 1,296 downregulated and 468 upregulated proteins in MCL cells. The splicing pathways were significantly upregulated at both the mRNA and protein levels, suggesting a critical role for aberrant RNA splicing in MCL pathogenesis. Integration of proteomic data with genetic aberrations revealed IGHV mutational status and CCND1 mutation are associated with distinctive transcriptomic and proteomic profiles, which correspond to significant differences in clinical outcomes. A multi-omics molecular stratification model incorporating proteomic data showed superior predictive power for patient survival compared to single-omics models (concordance index 0.83 vs. 0.74). This study provides the first comprehensive proteogenomic profile of MCL, offering novel insights into its molecular mechanisms and clinical behavior. The identification of molecular subtypes and prognostic protein signatures underscores the potential of proteomics to guide precision medicine strategies for MCL.
Additional Links: PMID-41785305
Publisher:
PubMed:
Citation:
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hide bibtex listing
@article {pmid41785305,
year = {2026},
author = {Yan, Y and Chen, W and Ge, X and Sun, J and Yu, L and Garcia-Mansfield, K and Zhang, X and Yu, Y and Xiong, W and Zou, D and An, G and Jia, Z and Pirrotte, P and Li, JJ and Yu, Z and Hao, M and Qiu, L and Qi, J and Wang, L and Yi, S},
title = {Proteogenomic features define subtypes of mantle cell lymphoma.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025018701},
pmid = {41785305},
issn = {2473-9537},
abstract = {Mantle cell lymphoma (MCL) is a biologically heterogeneous B-cell malignancy. While genomics and transcriptomics have delineated parts of the MCL disease spectrum, the proteomics remains largely unexplored. Here, we conducted a comprehensive proteogenomic analysis integrating genomics, transcriptomics, and proteomics on peripheral blood samples from 27 MCL patients and 4 healthy donors to investigate the translational and post-translational dimensions of MCL. Our study identified 1,296 downregulated and 468 upregulated proteins in MCL cells. The splicing pathways were significantly upregulated at both the mRNA and protein levels, suggesting a critical role for aberrant RNA splicing in MCL pathogenesis. Integration of proteomic data with genetic aberrations revealed IGHV mutational status and CCND1 mutation are associated with distinctive transcriptomic and proteomic profiles, which correspond to significant differences in clinical outcomes. A multi-omics molecular stratification model incorporating proteomic data showed superior predictive power for patient survival compared to single-omics models (concordance index 0.83 vs. 0.74). This study provides the first comprehensive proteogenomic profile of MCL, offering novel insights into its molecular mechanisms and clinical behavior. The identification of molecular subtypes and prognostic protein signatures underscores the potential of proteomics to guide precision medicine strategies for MCL.},
}
RevDate: 2026-03-06
CmpDate: 2026-03-06
Imprecision in tuberculosis infection outcomes: implications for non-inferiority vaccine trials.
International journal of epidemiology, 55(2):.
BACKGROUND: Randomized trials comparing new vaccines against tuberculosis for use in neonates and infants, for whom Bacille Calmette-Guérin vaccination is established practice, are using tuberculosis infection as the primary endpoint in a non-inferiority design. Markers of tuberculosis infection have imperfect sensitivity and specificity. Flaws in the non-inferiority trial design typically bias towards non-inferiority, which may result in falsely declaring non-inferiority.
METHODS: We conducted a statistical simulation study to assess the impact of imperfect markers of tuberculosis infection on the interpretation of tuberculosis vaccine trials testing a non-inferiority hypothesis of an infection primary outcome in a two-arm randomized comparison. Data were generated in three 2-year cumulative risk of tuberculosis infection scenarios (2%, 5%, and 8%). The specificity of tests of tuberculosis infection was assumed to range from 100% to 85%, while the sensitivity was assumed to range from 100% to 64%. Log-binomial regression was used to estimate the relative risk of tuberculosis infection.
RESULTS: With 100% sensitivity and specificity, type I error and power were both approximately equal to the expected values (2.5% and 80%, respectively) in all three cumulative tuberculosis risk scenarios. With modest deviations from perfect sensitivity and specificity (95% for both), the risk of falsely declaring non-inferiority was 96.8%, 53.2%, and 27.8% in the 2%, 5%, and 8% cumulative tuberculosis risk infection scenarios, respectively.
DISCUSSION: Tuberculosis vaccine non-inferiority trials using an infection primary outcome must be designed and interpreted accounting for the specificity of the tools used to measure infection, otherwise they risk declaring non-inferiority by default.
Additional Links: PMID-41782488
Publisher:
PubMed:
Citation:
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@article {pmid41782488,
year = {2026},
author = {Grint, DJ and White, RG and Churchyard, G and Fiore-Gartland, A and Rangaka, M and Garcia-Basteiro, AL and Cobelens, F},
title = {Imprecision in tuberculosis infection outcomes: implications for non-inferiority vaccine trials.},
journal = {International journal of epidemiology},
volume = {55},
number = {2},
pages = {},
doi = {10.1093/ije/dyag034},
pmid = {41782488},
issn = {1464-3685},
mesh = {Humans ; *Tuberculosis/prevention & control ; *Tuberculosis Vaccines ; Sensitivity and Specificity ; *BCG Vaccine ; *Equivalence Trials as Topic ; Infant ; Computer Simulation ; *Randomized Controlled Trials as Topic ; Biomarkers ; Research Design ; Infant, Newborn ; },
abstract = {BACKGROUND: Randomized trials comparing new vaccines against tuberculosis for use in neonates and infants, for whom Bacille Calmette-Guérin vaccination is established practice, are using tuberculosis infection as the primary endpoint in a non-inferiority design. Markers of tuberculosis infection have imperfect sensitivity and specificity. Flaws in the non-inferiority trial design typically bias towards non-inferiority, which may result in falsely declaring non-inferiority.
METHODS: We conducted a statistical simulation study to assess the impact of imperfect markers of tuberculosis infection on the interpretation of tuberculosis vaccine trials testing a non-inferiority hypothesis of an infection primary outcome in a two-arm randomized comparison. Data were generated in three 2-year cumulative risk of tuberculosis infection scenarios (2%, 5%, and 8%). The specificity of tests of tuberculosis infection was assumed to range from 100% to 85%, while the sensitivity was assumed to range from 100% to 64%. Log-binomial regression was used to estimate the relative risk of tuberculosis infection.
RESULTS: With 100% sensitivity and specificity, type I error and power were both approximately equal to the expected values (2.5% and 80%, respectively) in all three cumulative tuberculosis risk scenarios. With modest deviations from perfect sensitivity and specificity (95% for both), the risk of falsely declaring non-inferiority was 96.8%, 53.2%, and 27.8% in the 2%, 5%, and 8% cumulative tuberculosis risk infection scenarios, respectively.
DISCUSSION: Tuberculosis vaccine non-inferiority trials using an infection primary outcome must be designed and interpreted accounting for the specificity of the tools used to measure infection, otherwise they risk declaring non-inferiority by default.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Tuberculosis/prevention & control
*Tuberculosis Vaccines
Sensitivity and Specificity
*BCG Vaccine
*Equivalence Trials as Topic
Infant
Computer Simulation
*Randomized Controlled Trials as Topic
Biomarkers
Research Design
Infant, Newborn
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RJR Experience and Expertise
Researcher
Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.
Educator
Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.
Administrator
Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.
Technologist
Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.
Publisher
While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.
Speaker
Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.
Facilitator
Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.
Designer
Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.
RJR Picks from Around the Web (updated 11 MAY 2018 )
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Fossils of miniature humans (hobbits) discovered in Indonesia
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Dinosaur tail, complete with feathers, found preserved in amber.
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Mysterious fast radio burst (FRB) detected in the distant universe.
Big Data & Informatics
Big Data: Buzzword or Big Deal?
Hacking the genome: Identifying anonymized human subjects using publicly available data.