@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.},
}

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

@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.},
}

@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.},
}

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

@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.},
}

@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.},
}

@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.},
}

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

@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.},
}

@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.},
}

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

@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.},
}

@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},
}

@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.},
}

@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.},
}

@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.},
}

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

@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 .},
}

@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.},
}

@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.},
}

@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},
}

@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},
}

@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.},
}

@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.},
}

@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.},
}

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

@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.},
}

Algorithms
Computer Simulation
Humans
*Models, Statistical
Female
*Microbiota
*Metabolic Networks and Pathways
Stochastic Processes

@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.},
}

Humans
*Precision Medicine/methods
*Urinary Bladder Neoplasms/genetics/classification
Gene Expression Profiling/methods
Cell Line, Tumor
Transcriptome
Multiomics

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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},
}

@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.},
}

@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.},
}

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

@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.},
}

@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.},
}

@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.},
}

@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},
}

@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.},
}

@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.},
}

Humans
*Artificial Intelligence
*User-Computer Interface
*Virtual Reality

@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.},
}

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

@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},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

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

@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.},
}

@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.},
}

@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.},
}

@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.},
}

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

@article {pmid41782345,
year = {2026},
author = {Likasitwatanakul, P and Blinka, SM and Zarka, JG and Gebrael, G and Weg, E and Longoria, O and Moore, JA and Sharp, A and de Bono, J and Sternberg, CN and Agarwal, N and Swami, U and Orme, JJ and Schweizer, MT and Sloan, L and Hwang, JH and Antonarakis, ES},
title = {Molecular Landscape of Prostate Cancers with Clival Metastases.},
journal = {The oncologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/oncolo/oyag074},
pmid = {41782345},
issn = {1549-490X},
abstract = {BACKGROUND: Clival metastases are a rare and clinically aggressive manifestation of advanced prostate cancer, associated with cranial nerve palsy and poor survival. The molecular features of prostate cancers giving rise to clivus metastases remain unknown.

PATIENTS AND METHODS: We performed a multi-center retrospective study across six institutions, identifying prostate cancer patients with radiographically confirmed clival metastases and available next-generation sequencing (NGS) data. Baseline characteristics and clinical outcomes were collected. Genomic alterations from tissue- and/or blood-based assays were aggregated at the patient level and compared with a publicly available metastatic castration-resistant prostate cancer (mCRPC) cohort (SU2C/PCF).

RESULTS: Fifty-nine patients with clival metastases contributed 87 molecular assays. More than half of patients had Gleason grade group 5 cancer and presented with de novo metastatic (M1) disease. The median interval from initial prostate cancer diagnosis to clival metastasis was 71.4 months (95%CI 42.0-101.7), while median overall survival following clival involvement was only 15.3 months (95%CI 6.9-22.8). Compared with the SU2C/PCF mCRPC cohort, clival metastases showed significant enrichment of BRAF and CHEK2 alterations, as well as homologous recombination repair (HRR) with relative depletion of AR-related, PI3K pathway, and G2-M pathway alterations.

CONCLUSION: Prostate cancers giving rise to clival metastases exhibit a distinct molecular profile enriched for DNA damage-repair and RAF kinase alterations, suggesting unique metastatic biology and potential therapeutic vulnerabilities.},
}

@article {pmid41781474,
year = {2026},
author = {Naderi, E and Watt, GP and Knight, JA and Malone, KE and Lynch, CF and John, EM and Shu, X and Nguyen, TL and Oh, JH and Woods, M and Liang, X and Derkach, A and Pike, MC and Bernstein, JL},
title = {Evaluating mammographic density polygenic risk score for contralateral breast cancer risk prediction.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-42365-7},
pmid = {41781474},
issn = {2045-2322},
}

@article {pmid41780572,
year = {2026},
author = {DeBerg, HA and Baloh, CH and DeGottardi, Q and Hou, J and Johansson, A and Newell, E and Laidlaw, TM and Sanda, S and Shamji, M and Durham, S and Togias, A and Kwok, WW},
title = {Differential effects of subcutaneous and sublingual immunotherapy on Timothy grass-specific Th2 CD4[+] T cell subsets.},
journal = {The Journal of allergy and clinical immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaci.2026.02.026},
pmid = {41780572},
issn = {1097-6825},
abstract = {BACKGROUND: Allergen-specific CD4[+] T cells are a highly heterogenous population. Depletion of these cells has been proposed as essential to achieve allergen desensitization in allergen immunotherapy.

OBJECTIVE: The overall aim of this study was to characterize the heterogeneity of Timothy grass (Phleum pratense, Phl p) allergen-specific CD4[+] T cells and determine how the frequency and phenotype of these cells change in response to sublingual (SLIT) and subcutaneous immunotherapy (SCIT). Correlations between frequencies of these cells with Total Nasal Symptom Score (TNSS) and grass-specific serum immunoglobulin were also investigated.

METHODS: Mass cytometry with lanthanides-tagged pMHCII multimers and CD154 upregulation assays were used to examine changes in the frequency and phenotype of Phl p-specific CD4[+] T cells in longitudinal peripheral blood mononuclear cell samples from a randomized, double-blind, placebo-controlled trial of SLIT and SCIT. Supervised and unsupervised clustering was used for data analysis.

RESULTS: Phenotypes of Phl p-specific T cells were highly heterogenous but can be categorized into two major meta-clusters: CRTH2[Hi]CD27[Lo] and CRTH2[Lo]CD27[Hi] , each with distinct phenotypic profiles. Weak positive correlations between TNSS and frequencies of T cells within both subsets were observed. SCIT preferentially depleted CRTH2[Hi]CD27[Lo] cells whereas SLIT depleted CRTH2[Lo]CD27[Hi] cells. CRTH2[Hi]CD27[Lo] cell frequency correlated with Phl p-specific IgE and IgG4, but not IgA levels.

CONCLUSION: Unsupervised clustering revealed distinct subpopulations of allergen-specific T cells that were differentially targeted and depleted by SCIT and SLIT, suggesting that SCIT and SLIT act through overlapping but distinct immunological pathways.},
}

@article {pmid41780060,
year = {2026},
author = {Daodu, RO and Chang, J and Prescott, J and Reinert, K and Kühnert, D},
title = {Lassa Virus Live Tracking and Lineage Assignment: How Nextstrain Can Enhance Surveillance and Public Health in Africa and Beyond.},
journal = {Emerging microbes & infections},
volume = {},
number = {},
pages = {2640699},
doi = {10.1080/22221751.2026.2640699},
pmid = {41780060},
issn = {2222-1751},
abstract = {Lassa virus (LASV), a zoonotic, bi-segmented arenavirus endemic to West Africa, causes seasonal epidemics with substantial morbidity and mortality. Increasing frequency of exported cases emphasises the need for near real-time genomic surveillance to support outbreak response and clinical decision-making. We developed a suite of open-access resources on the Nextstrain and Nextclade platforms tailored to LASV. These include live phylogenetic and phylogeographic visualization, as well as Nextclade builds for rapid mutation detection and lineage assignment based on the L and S segments and the glycoprotein complex (GPC). A dedicated GPC phylogeny enables tracking of clinically relevant mutations, including immunologically relevant variants such as alanine at position 76 (A76), which is prevalent in lineage II and is implicated in reduced binding of monoclonal antibody 25.10C. The Nextclade tools distinguish LASV from other mammarenaviruses and assign lineages with Matthews correlation coefficients (all >85%). These tools are available at https://nextstrain.org/lassa for immediate use in surveillance, data annotation, outbreak response, and potentially support clinical decision-making in both endemic regions and exported-case scenarios. A key limitation is dependence on genomic data quality and recency. Although sampling-to-submission delays have decreased over the past 40 years, the average delay in the past five years remains ∼2 years. In many endemic LASV regions, challenges, such as limited resources, infrastructure, and previous experiences of stigmatization and political repercussions linked to outbreak reporting, restrict data sharing. The resulting disparities and delays may hinder comprehensive surveillance and timely response, with implications for global public health.},
}

@article {pmid41779867,
year = {2026},
author = {Dosey, A and Dadonaite, B and Gillespie, RA and Leaf, EM and Vukovich, MJ and McGowan, J and Grey, E and Muramatsu, H and Jun, RHJ and Pardi, N and Kanekiyo, M and Bloom, JD and King, NP},
title = {Stabilization of the H5 clade 2.3.4.4b hemagglutinin improves vaccine-elicited neutralizing antibody responses in mice.},
journal = {Science translational medicine},
volume = {18},
number = {839},
pages = {eaea8770},
doi = {10.1126/scitranslmed.aea8770},
pmid = {41779867},
issn = {1946-6242},
mesh = {Animals ; *Antibodies, Neutralizing/immunology ; *Influenza Vaccines/immunology ; *Hemagglutinin Glycoproteins, Influenza Virus/immunology/chemistry ; Mice ; Mutation/genetics ; Antibodies, Viral/immunology ; Female ; Humans ; Protein Stability ; Mice, Inbred BALB C ; Epitope Mapping ; Cryoelectron Microscopy ; },
abstract = {Transmission of highly pathogenic avian influenza from H5 clade 2.3.4.4b has expanded in recent years to infect large populations of birds and mammals, heightening the risk of a human pandemic. Influenza viruses that are adapted to transmission in birds and a variety of mammals tend to have a less stable hemagglutinin (HA) than seasonal influenza viruses, enabling membrane fusion at comparatively higher pH levels. Here, we combined five mutations in the H5 HA that increased its melting temperature and promoted stable closure of the HA trimer. Structural analysis by cryo-electron microscopy revealed that the stabilizing mutations create several new hydrophobic interactions while maintaining the local HA structure. We found that vaccinating mice with stabilized H5 HA immunogens resulted in higher hemagglutination inhibition and neutralization titers than nonstabilized comparators. Epitope mapping of vaccine-elicited polyclonal antibody responses using negative-stain electron microscopy and deep mutational scanning showed that site E on the side of the HA receptor binding domain was immunodominant across all groups; however, the stabilized immunogens shifted responses toward the receptor binding site, which elicited a higher proportion of neutralizing antibodies. Consistent with these findings, stabilized H5 HA immunogens delivered as messenger RNA-lipid nanoparticle (mRNA-LNP) vaccines protected mice against H5N1 challenge. These findings highlight that H5 HA-stabilizing mutations enhance the quality of antibody responses across different vaccine formats, underscoring their potential to improve pandemic preparedness vaccines targeting viruses from this widely circulating clade.},
}

Animals
*Antibodies, Neutralizing/immunology
*Influenza Vaccines/immunology
*Hemagglutinin Glycoproteins, Influenza Virus/immunology/chemistry
Mice
Mutation/genetics
Antibodies, Viral/immunology
Female
Humans
Protein Stability
Mice, Inbred BALB C
Epitope Mapping
Cryoelectron Microscopy

@article {pmid41757067,
year = {2026},
author = {Kikawa, C and Huddleston, J and Turner, SA and Loes, AN and Liu, J and Gang, S and Griffiths, T and Drapeau, EM and Cowling, BJ and Ho, F and Leung, NHL and Englund, JA and Lacombe, K and Watanabe, S and Hasegawa, H and Busch, M and Lanteri, M and Stone, M and Spencer, B and Neher, RA and Smith, DJ and Bedford, T and Hensley, SE and Bloom, JD},
title = {Near real-time data on the human neutralizing antibody landscape to influenza virus as of early 2026 to inform vaccine-strain selection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41757067},
issn = {2692-8205},
abstract = {Twice each year, a decision is made on whether to update the strains included in the seasonal influenza vaccine to better match the most recent circulating viral strains. To characterize the antigenic properties of current seasonal influenza A strains to inform the upcoming decision about which strains to include in the 2026-2027 Northern Hemisphere vaccine, here we perform high-throughput sequencing-based neutralization assays using a library of 57 H3N2 and 34 H1N1 influenza hemagglutinins reflecting the circulating diversity of strains in late 2025 to early 2026. We assay this library against 302 human sera collected in late 2025. The resulting data set encompasses 27,409 titers, and provides a near real-time portrait of the human neutralizing antibody landscape against influenza virus. We find that many human sera have lower titers against the K subclade of H3N2 and the D.3.1.1 subclade of H1N1; these subclades have recently become dominant among their respective subtypes. Our measurements also reveal variability in titers to different subvariants within the K subclade of H3N2, with titers especially low to subclade K strains with additional mutations in antigenic regions D and E. We make all our data and accompanying visualizations publicly available to enable their use in vaccine-strain selection and analyses of influenza evolution and immunity.},
}

@article {pmid41727567,
year = {2026},
author = {Termini, C and Woodruff, K and Patel, D and Peplinski, J and Setiawan, N and Hagen, M and Meshinchi, S},
title = {HS6ST1 regulates acute myeloid leukemia chemotherapy resistance via TGF-β1 signaling.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {41727567},
issn = {2693-5015},
abstract = {Despite therapeutic advances, relapse remains the leading cause of death in patients with acute myeloid leukemia (AML). Growth factor signaling controls AML survival, proliferation, relapse, and chemotherapy resistance. Here, we studied heparan sulfate proteoglycans, a class of molecules that bind growth factors via their heparan sulfate chains to change their signaling ability. Heparan sulfate-growth factor interactions are controlled by the addition of sulfate groups catalyzed by heparan sulfotransferases, such as those encoded by HS2ST1 and HS6ST1. Using AML patient cohort analyses, we demonstrate that increased HS6ST1 expression is associated with worse survival and increased relapse risk for AML patients harboring KMT2A-rearrangements. Using cell line derived xenografts, we show that AML cells depleted of HS2ST1, but not HS6ST1, have increased bone marrow leukemic burden. Further, AML cells depleted of HS6ST1 are more sensitive to cytarabine than Control cells, suggesting that HS6ST1 regulates AML chemotherapy resistance. Heparan sulfate antagonism with surfen synergized with cytarabine to further support AML cell death compared to cytarabine alone. Mechanistically, we demonstrate that HS6ST1 depletion in AML cells reduces TGF-β1-mediated signaling, which diminishes cell survival upon cytarabine treatment. Together, our data show that HS6ST1 promotes AML cell chemotherapy resistance by supporting TGF-β1 signaling.},
}

@article {pmid41727151,
year = {2026},
author = {Simonich, CAL and McMahon, TE and Kampman, L and Chu, HY and Bloom, JD},
title = {Complete definition of how mutations affect antibodies used to prevent RSV.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41727151},
issn = {2692-8205},
abstract = {New antibodies targeting the F protein of respiratory syncytial virus (RSV) have substantially reduced infant hospitalizations. However, viral resistance is a concern: one antibody failed clinical trials due to emergence of a resistant strain, and sporadic resistance mutations to the most widely used antibody (nirsevimab) have been identified in breakthrough infections. Here we define how RSV F mutations affect antibody neutralization. We first provide a biophysical model of how the buffering effect of bivalent IgG binding combines with differences in monovalent Fab potency to explain why nirsevimab resistance mutations are more common in subtype B than subtype A RSV strains. We then perform pseudovirus deep mutational scanning to safely measure how nearly all mutations to F affect its cell entry function and neutralization by the IgG and Fab forms of nirsevimab, clesrovimab, and several other key antibodies. We use these measurements to enable real-time surveillance of RSV sequences for antibody resistance, and identify rare strains with sporadic resistance mutations. Overall, our work improves understanding of the mechanisms by which viral mutations impact antibody neutralization, enables monitoring for natural RSV strains resistant to antibodies of public-health importance, and can help guide development of future antibodies with resilience to viral escape.},
}

@article {pmid41726900,
year = {2026},
author = {Baraznenok, E and Hsieh, HC and Lan, L and Konnick, EQ and Figiel, S and Rao, SR and Woodcock, DJ and Mills, IG and Hamdy, F and Valk, JE and Carter, KT and Yu, M and Paulson, TG and Dintzis, S and Grady, WM and Liu, JTC},
title = {Assessing the effects of a 3D pathology tissue-processing workflow on downstream molecular analyses.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41726900},
issn = {2692-8205},
abstract = {Non-destructive 3D pathology methods have emerged in recent years with the potential to enhance standard 2D histopathology by greatly increasing the amount of tissue sampled by imaging and by providing volumetric morphological context. Another key advantage is that tissues remain intact, allowing re-embedding after imaging for potential long-term storage and future histological or molecular analyses. However, the impact of 3D pathology protocols on biomolecules - including DNA, RNA, and proteins - and their compatibility with downstream assays, has not been systematically evaluated. Here, we applied a previously optimized 3D pathology protocol - involving deparaffinization, fluorescent H&E-analog staining, optical clearing, and open-top light-sheet microscopy - to formalin-fixed paraffin-embedded (FFPE) specimens of breast, prostate, and head and neck cancer. Following the protocol, tissues were re-embedded in paraffin and compared with paired FFPE controls that did not undergo 3D pathology processing. DNA and RNA were extracted and subjected to quality assessments. Amplifiability was tested by PCR and reverse transcription quantitative PCR (RT-qPCR) of housekeeping genes. Although the results showed a slight decrease in the average yield and increased fragmentation of both DNA and RNA, amplifiability was largely preserved. Sanger sequencing of the PCR products confirmed accurate sequence determinations, while total RNA sequencing indicated that the global transcriptomic profile was largely unchanged. IHC staining of common biomarkers produced comparable signals, suggesting those proteins are well preserved after the 3D pathology workflow. These results demonstrate the feasibility of combining 3D pathology with downstream molecular applications.},
}

@article {pmid41659542,
year = {2026},
author = {Jiang, M and Hu, C and Hedouin, S and Latino, AA and Arimura, Y and Stergachis, AB and Biggins, S},
title = {Native yeast kinetochore structures identify an essential inner kinetochore interaction.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41659542},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R35 GM149357/GM/NIGMS NIH HHS/United States ; },
abstract = {Kinetochores must accurately assemble on centromeres every cell cycle for faithful chromosome segregation. Although a conserved centromeric histone variant is essential for inner kinetochore formation, the budding yeast centromeric DNA is a poor template for nucleosome formation in vitro, possibly due to a resistance to bend. To better understand how the yeast inner kinetochore is assembled, we developed a one-step protocol to purify de novo assembled native inner kinetochore subcomplexes for structural studies. We performed cryoelectron microscopy on the purified complexes and generated medium to high resolution density maps of four separate inner kinetochore complexes, two of which had not previously been visualized. We detected differences between native and previously reconstituted structures, suggesting that the de novo assembly assay generated intermediate assemblage states. A strong extra structural density, which corresponds to an Ndc10 trimerization domain, associated with centromeric DNA and a pair of CBF3 complexes to induce significant centromere bending. Its deposition on the CBF3-CEN complex is essential for kinetochore assembly and chromosome segregation. We propose that Ndc10 trimerization facilitates bending of the centromeric DNA, leading to assembly and stabilization of the centromeric nucleosome and inner kinetochore.},
}

@article {pmid26761518,
year = {2016},
author = {Jacobson, JM and Zheng, L and Wilson, CC and Tebas, P and Matining, RM and Egan, MA and Eldridge, J and Landay, AL and Clifford, DB and Luetkemeyer, AF and Tiu, J and Martinez, AL and Janik, J and Spitz, TA and Hural, J and McElrath, J and Frahm, N and , },
title = {The Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection.},
journal = {Journal of acquired immune deficiency syndromes (1999)},
volume = {71},
number = {2},
pages = {163-171},
pmid = {26761518},
issn = {1944-7884},
support = {UM1 AI069494/AI/NIAID NIH HHS/United States ; UM1 AI069503/AI/NIAID NIH HHS/United States ; AI069556/AI/NIAID NIH HHS/United States ; UM1 AI069501/AI/NIAID NIH HHS/United States ; 2UM1AI069511-08/AI/NIAID NIH HHS/United States ; UM1 AI069534-08/AI/NIAID NIH HHS/United States ; 2 UM1 AI068636-08/AI/NIAID NIH HHS/United States ; UM1 AI069424/AI/NIAID NIH HHS/United States ; 2UM1AI069432/AI/NIAID NIH HHS/United States ; UM1 AI069432/AI/NIAID NIH HHS/United States ; 2UM1AI069412-08/AI/NIAID NIH HHS/United States ; U01 AI069439/AI/NIAID NIH HHS/United States ; U01 AI069556/AI/NIAID NIH HHS/United States ; UM1 AI069534/AI/NIAID NIH HHS/United States ; UM1 AI069439/AI/NIAID NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; HHSN272200800062C/AI/NIAID NIH HHS/United States ; P30 AI045008/AI/NIAID NIH HHS/United States ; UM1 AI069412/AI/NIAID NIH HHS/United States ; UM1 AI068634/AI/NIAID NIH HHS/United States ; 2UM1AI069501/AI/NIAID NIH HHS/United States ; UM1 AI069496/AI/NIAID NIH HHS/United States ; UL1 RR024160/RR/NCRR NIH HHS/United States ; UM1 AI069556/AI/NIAID NIH HHS/United States ; U01 AI69439/AI/NIAID NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; UM1 AI106701/AI/NIAID NIH HHS/United States ; 5-P30-AI-045008-15/AI/NIAID NIH HHS/United States ; F32 AI080062/AI/NIAID NIH HHS/United States ; UM1 AI069511/AI/NIAID NIH HHS/United States ; 2 UM1 AI069503-08/AI/NIAID NIH HHS/United States ; UM1AI068636/AI/NIAID NIH HHS/United States ; UM1 AI068636/AI/NIAID NIH HHS/United States ; },
mesh = {AIDS Vaccines/administration & dosage/*immunology ; Adolescent ; Adult ; CD4-Positive T-Lymphocytes/immunology ; Cytokines/immunology ; Electroporation ; Female ; HIV Antigens/*immunology ; HIV Infections/*drug therapy/immunology ; HIV-1/genetics/*immunology ; Humans ; Interferon-gamma/immunology ; Interleukin-12/*immunology ; Interleukin-2/immunology ; Male ; Middle Aged ; Vaccines, DNA/administration & dosage/*immunology ; Young Adult ; },
abstract = {BACKGROUND: Therapeutic vaccination is being studied in eradication and "functional cure" strategies for HIV-1. The Profectus Biosciences multiantigen (MAG) HIV-1 DNA vaccine encodes HIV-1 Gag/Pol, Nef/Tat/Vif, and Envelope, and interleukin-12 (IL-12) and is delivered by electroporation combined with intramuscular injection (IM-EP).

METHODS: Sixty-two HIV-1-infected patients on antiretroviral therapy (plasma HIV-1 RNA levels ≤ 200 copies/mL; CD4(+) T-cell counts ≥ 500 cells/mm(3)) were randomly allocated 5:1 to receive vaccine or placebo. At weeks 0, 4, and 12, 4 consecutive cohorts received 3000 μg HIV MAG pDNA with 0, 50, 250, or 1000 μg of IL-12 pDNA by IM-EP. A fifth cohort received HIV MAG pDNA and 1000 μg of IL-12 pDNA by standard IM injection.

RESULTS: CD4(+) T cells expressing IL-2 in response to Gag and Pol and interferon-γ responses to Gag, Pol, and Env increased from baseline to week 14 in the low-dose (50-μg) IL-12 arm vs. placebo (P < 0.05; intracellular cytokine staining). The total increase in the IL-2-expressing CD4 T-cell responses to any antigen was also higher in the low-dose IL-12 arm vs. placebo (P = 0.04). Cytokine responses by CD8 T cells to HIV antigens were not increased in any vaccine arm relative to placebo.

CONCLUSIONS: HIV-1 MAG/low-dose IL-12 DNA vaccine delivered by IM-EP augmented CD4(+) but not CD8(+) T-cell responses to multiple HIV-1 antigens.},
}

AIDS Vaccines/administration & dosage/*immunology
Adolescent
Adult
CD4-Positive T-Lymphocytes/immunology
Cytokines/immunology
Electroporation
Female
HIV Antigens/*immunology
HIV Infections/*drug therapy/immunology
HIV-1/genetics/*immunology
Humans
Interferon-gamma/immunology
Interleukin-12/*immunology
Interleukin-2/immunology
Male
Middle Aged
Vaccines, DNA/administration & dosage/*immunology
Young Adult

@article {pmid41779832,
year = {2026},
author = {Rodriguez Chevez, HJ and Remington, AJ and Gray, MD and Alam, R and Gilmour, MW and Morningstar, C and Alencar, GF and Pulliam, T and McClure, EM and Singh, N and Urselli, F and Ouellette, S and Poljakov, K and Smythe, KS and Kulikauskas, RM and Robinson, KL and Moshiri, AS and Yeung, CCS and Lin, M and Shimp, KR and Schwartz, A and Macy, AM and Tooley, MR and Baker, ML and Carter, JJ and Hopwo, K and Singhi, N and Bakhtiari, J and Ruterbusch, M and Shasha, C and Iuliano, M and Mullen, LJ and DeBuysscher, BL and Veatch, JR and Koelle, DM and Galloway, DA and Nghiem, P and Taylor, JJ},
title = {Response of B cells specific for polyomavirus-derived oncoprotein is predictive of Merkel cell carcinoma tumor control.},
journal = {Cancer immunology research},
volume = {},
number = {},
pages = {},
doi = {10.1158/2326-6066.CIR-25-0950},
pmid = {41779832},
issn = {2326-6074},
abstract = {Merkel cell carcinomas (MCC) typically arise from clonal integration of the Merkel cell polyomavirus. Immunogenic viral oncoproteins then lead to tumorigenesis. Oncoprotein-specific T cells are essential for anti-MCC immunity, but it is unclear whether B cells promote tumor control. Here, we analyzed the frequency and phenotype of viral oncoprotein-specific and total B cells in blood samples from 47 patients with MCC and tumor samples from another 19 patients with MCC. The phenotype of blood B cells did not correlate with MCC patient outcomes. In contrast, all 11 patients with robust oncoprotein-specific antibody-secreting and/or germinal center B cells in tumors experienced long-term MCC control. In vitro, B cells engineered to be specific for viral oncoproteins increased the sensitivity of oncoprotein-specific CD4+ T cells by over 50-fold. Together, our findings suggest that cancer-specific B cells promote antitumor immunity via increased responses by T cells and that cancer-specific augmentation of B cells could be therapeutically relevant.},
}

@article {pmid41779777,
year = {2026},
author = {Ramsey, EL and Dobersch, S and Freie, B and Hong, NH and Wu, X and Kugel, S and Eisenman, RN and Carroll, PA},
title = {MondoA mediates transcriptional coordination between the MYC network and the integrated stress response in pancreatic cancer.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {10},
pages = {e2524659123},
doi = {10.1073/pnas.2524659123},
pmid = {41779777},
issn = {1091-6490},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R37 CA241472/CA/NCI NIH HHS/United States ; 465590102//DKFZ | Heidelberger Zentrum für Personalisierte Onkologie Deutsches Krebsforschungszentrum In Der Helmholtz-Gemeinschaft (DKFZ-HIPO)/ ; R35 CA231989/CA/NCI NIH HHS/United States ; PF-24-1196662-01-RMC//American Cancer Society (ACS)/ ; },
mesh = {Humans ; *Pancreatic Neoplasms/genetics/metabolism/pathology ; *Proto-Oncogene Proteins c-myc/genetics/metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; *Carcinoma, Pancreatic Ductal/genetics/metabolism/pathology ; Apoptosis/genetics ; Animals ; Activating Transcription Factor 4/genetics/metabolism ; Transcription, Genetic ; Mice ; *Stress, Physiological/genetics ; Cell Proliferation/genetics ; Gene Regulatory Networks ; *Transcription Factors/metabolism/genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism/genetics ; },
abstract = {MYC amplification contributes to poor survival and outcome in pancreatic ductal adenocarcinoma (PDAC). Here we show that in PDAC cell lines with amplified MYC, MondoA is required for viability, facilitating proliferation while suppressing apoptosis in vitro and in vivo. Transcriptional and genomic profiling demonstrates that loss of MondoA leads to altered expression of direct MondoA targets as well as MYC target genes and is accompanied by shifts in genomic occupancy of MYC, MNT, and the MondoA paralog ChREBP. This altered genomic binding by MYC network members is associated with transcriptional perturbation of multiple metabolic and stress pathways, as well as global changes in N6-methyladenosine modification (m[6]A) of messenger RNA (mRNA). MondoA inhibition disrupts coordination between MYC network members and the Integrated Stress Response (ISR), resulting in decreased translation of ATF4 mRNA, discordant gene regulation of shared targets of MYC and ATF4 and, ultimately, apoptosis. Reestablishing ATF4 protein expression rescues the diminished viability due to loss of MondoA expression or activity, providing direct evidence of a link between deregulated MYC and the transcriptional machinery of the ISR. Last, we find that small-molecule inhibition of MondoA is lethal in a subset of PDAC cell lines, including patient-derived organoids, suggesting that the ability to target MYC via chemical inhibition of MondoA transcriptional activity may have broad efficacy.},
}

Humans
*Pancreatic Neoplasms/genetics/metabolism/pathology
*Proto-Oncogene Proteins c-myc/genetics/metabolism
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
*Carcinoma, Pancreatic Ductal/genetics/metabolism/pathology
Apoptosis/genetics
Animals
Activating Transcription Factor 4/genetics/metabolism
Transcription, Genetic
Mice
*Stress, Physiological/genetics
Cell Proliferation/genetics
Gene Regulatory Networks
*Transcription Factors/metabolism/genetics
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism/genetics

@article {pmid41779000,
year = {2026},
author = {Yu, EY and Narayan, V and Esposito, G and Szmulewitz, R and Lu, Y and Lilly, MB and Calais, J and Bratslavsky, G and Menda, Y and Vasanawala, M and Pouliot, F and Laidley, D and Fleshner, N and Saad, F and Provost, JC and Teslenko, I and Rawat, NK and Ulaner, G},
title = {131I-LNTH-1095 Radioligand Therapy Plus Enzalutamide vs. Enzalutamide Alone in Men With PSMA-Avid Metastatic Castration-Resistant Prostate Cancer: A Phase 2 Study.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-25-4948},
pmid = {41779000},
issn = {1557-3265},
abstract = {PURPOSE: The phase 2 ARROW study was designed to evaluate radioligand therapy with 131I-LNTH-1095, an iodine-131-labeled small molecule targeting PSMA, in combination with enzalutamide in subjects with metastatic castration-resistant prostate cancer after progression on prior abiraterone therapy.

PATIENTS AND METHODS: Men ≥18 years with PSMA-positive prostate cancer (PSMA PET tracer uptake >1× liver SUVmean in all CT-measurable lesions) were randomized 2:1 to 131I-LNTH-1095 (4 cycles of 3.7 GBq/dose every 8 weeks)+enzalutamide (160 mg po qd) vs. enzalutamide alone. The primary endpoint was PSA50 response. Secondary endpoints included rPFS, ORR, OS, and safety.

RESULTS: Of 177 screened subjects, 120 were randomized (80: 131I-LNTH-1095+enzalutamide; 40: enzalutamide-monotherapy). PSA50 response was 62.9% (95% CI, 50.5-74.1) for 131I-LNTH-1095+enzalutamide vs. 31.3% (16.1-50.0) for enzalutamide alone (P=.003). Median rPFS was 14.0 months (95% CI: 8.64-18.20) for 131I-LNTH-1095+enzalutamide vs. 11.5 months (2.79-18.43) for enzalutamide alone (P=.10). Incidence of grade ≥3 treatment-emergent adverse events (TEAEs) was 65.8% for 131I-095+enzalutamide vs. 41.0% for enzalutamide-monotherapy; the most frequent TEAEs were fatigue (75.0 vs. 53.8%), nausea (59.2 vs. 33.3%), thrombocytopenia (51.3 vs. 0%), and decreased appetite (48.7 vs. 17.9%), respectively. Two deaths in the 131I-LNTH-1095+enzalutamide group were considered treatment-related. The study was not powered to detect rPFS and OS differences.

CONCLUSIONS: 131I-LNTH-1095+enzalutamide was associated with a statistically significant improvement in PSA50 response compared to enzalutamide alone despite a lower dosing schedule (4 cycles of 3.7 GBq/dose every 8 weeks) than the other approved PSMA RLT agents. Grade ≥3 adverse events were more frequent with combination therapy, particularly hematologic toxicity. NCT03939689.},
}

@article {pmid41777872,
year = {2025},
author = {Muno, BA and Haris, M and Zegeye, A and Behailu, R and Hassan, SA and Islam, JY and Smith, MD and Picou, B and Nnaji, C and Barnes-Balenciaga, J and Miller, M and Sawyer, S and McCullough, D and Mares, L and Burley Iii, U and Bijole, P and Haddock, IL and Hall, BW and Warren, M and Duncan, DT and Jacobs, SEW and Camacho-Rivera, M and Jaiswal, J and Patel, RC},
title = {Manifestations and Lived Experiences of Structural Racism for Racial and Ethnic Minority Communities Affected by HIV Across the United States.},
journal = {Health equity},
volume = {9},
number = {1},
pages = {474-490},
pmid = {41777872},
issn = {2473-1242},
abstract = {OBJECTIVE: To elucidate some of the manifestations of structural racism as a root cause of racialized inequities in HIV in the context of COVID-19, centered through the lens of community members with lived experiences.

METHODS: We partnered with eight community-based organizations to conduct focus group discussions structured around COVID-19 and HIV-related experiences. We utilized inductive coding and thematic analysis.

RESULTS: We conducted 10 focus group discussions (98 participants) across the United States between February and May 2023; 65% were ages 18-39, over 90% identified as Black, 39% were female, and 66% were cisgender. First, participants emphasized that structural racism intersects with other systems of oppression. Second, three main themes emerged as manifestations of structural racism: (1) lack of representation in state and federal decision-making levels, (2) differential access to resources, and (3) intergenerational mistrust and trauma.

CONCLUSION: The intersecting impact of the HIV epidemic and COVID-19 pandemic underscores the pervasive effects of structural racism that manifests in the United States.

HEALTH EQUITY IMPLICATIONS: More than ever, researchers must champion the experiences and needs of racial and ethnic minority communities to affect structural change.},
}

@article {pmid41776157,
year = {2026},
author = {Frouard, J and Telwatte, S and Luo, X and Gill, N and Thomas, R and Arneson, D and Roychoudhury, P and Butte, AJ and Wong, JK and Hoh, R and Deeks, SG and Lee, SA and Roan, NR and Yukl, SA},
title = {HIV-seq reveals gene expression differences between HIV-transcribing cells from viremic and suppressed people with HIV.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {41776157},
issn = {2041-1723},
support = {P01AI169606//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01DK120387//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI132128//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI147777//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01DK131526//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI183286//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R21AI170166//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; UM1AI164559//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; UM1AI164567//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; UM1AI164560//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30AI027763//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI183666//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI194343//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; BB19-SF-009/A135087//California HIV/AIDS Research Program (CHRP)/ ; },
abstract = {HIV-transcribing cells can perpetuate chronic inflammation in ART-suppressed people with HIV (PWH) and likely contribute to viral rebound after ART interruption. However, these cells are difficult to study using single-cell RNA-seq (scRNA-seq) due to their low frequency and low levels of HIV transcripts, which are usually not polyadenylated. By spiking in capture sequences targeting conserved regions of HIV during scRNA-seq - a new method we call "HIV-seq" - we detect double the mean number of HIV reads per cell from PWH. HIV RNA+ cells are enriched among T effector memory cells during both viremia and ART suppression but exhibit a cytotoxic signature during viremia only. In contrast, HIV-transcribing cells from ART-suppressed timepoints exhibit a distinct anti-inflammatory signature involving elevated TGF-β and diminished IFN signaling. These findings demonstrate that HIV-seq is a useful tool to better understand the mechanisms by which HIV-transcribing cells can persist during ART.},
}

@article {pmid41775684,
year = {2026},
author = {Suarez-Carmona, M and Hampel, M and Zhang, XW and Pöchmann, A and Grauling-Halama, SA and Valous, NA and Charoentong, P and Ferber, D and Wissfeld, J and Höflich, A and Goriely, S and Detavernier, A and Azouz, A and Rongvaux, A and Zukunft, S and Fleming, I and Okun, JG and Baracos, V and Heikenwalder, M and Zitvogel, L and Xu, X and Xu, C and Volkmar, M and Schraivogel, D and Steinmetz, L and Hamanishi, J and Mandai, M and Gaida, M and Mokry, T and Nattenmüller, J and Sedlaczek, O and Monje, N and Schwab, R and Hasenburg, A and Mavratzas, A and Boger, RJ and Marmé, F and Schott, S and Halama, N},
title = {Harnessing lipid-driven immunometabolic pathways in omental metastases to enhance immunotherapy in patients with ovarian cancer.},
journal = {Signal transduction and targeted therapy},
volume = {11},
number = {1},
pages = {},
pmid = {41775684},
issn = {2059-3635},
support = {Zukunftsthema//Helmholtz Association/ ; ERDF 2022-2027 WAL IMAGIN SYST-IMM//Fédération Wallonie-Bruxelles (French Community of Belgium)/ ; 318346496//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; },
mesh = {Humans ; Female ; Animals ; Mice ; *Immunotherapy ; *Omentum/pathology/immunology ; *Ovarian Neoplasms/immunology/pathology/therapy/genetics ; Tumor Microenvironment/immunology/drug effects ; *Lipid Metabolism/immunology ; *Carcinoma, Ovarian Epithelial/immunology/pathology/therapy/genetics ; Tumor-Associated Macrophages/immunology ; Neoplasm Metastasis ; Signal Transduction ; },
abstract = {Immunotherapy with immune checkpoint blockade (ICB) in epithelial ovarian carcinoma (EOC) shows limited clinical benefit only for a small subset of patients. Overall response rates are low, so that overcoming immunotherapy resistance and improved stratification are key. In this study, we investigated the immunometabolic landscape of EOC with a focus on omental metastases, identifying lipid-laden macrophages as central elements for actionable therapeutic vulnerabilities and giving rise to biomarkers for improved patient stratification. Using patient-derived explants, we demonstrated a functional dichotomy inside the typically lipid-rich microenvironment of omental metastases: augmented maintenance of effector T cell function, while lipid uptake and processing by tumor-associated macrophages (TAMs) induces oxidative stress-dependent signaling programs, which drive macrophage dysfunction and immune suppression. Pharmacological modulation of lipid-driven signaling pathways through CCR5 inhibition (inflammation modulation through maraviroc) or blockade of the lipid scavenger receptor CD36 reprograms TAMs, restores T cell activity, and enhances antitumor immune responses within lipid-rich tumor niches. Mechanistically, studies in humanized mouse models reveal that maraviroc-mediated CCR5 inhibition induces transcriptional programs associated with immune activation in stressed, lipid-laden human TAMs. Consistent with these mechanistic insights, we demonstrated that the specific immunometabolic niche in omental metastases is clinically associated with responsiveness to ICB. We propose a non-invasive radiomics and machine-learning-based analysis of imaging data to assess omental involvement for patient stratification.},
}

Humans
Female
Animals
Mice
*Immunotherapy
*Omentum/pathology/immunology
*Ovarian Neoplasms/immunology/pathology/therapy/genetics
Tumor Microenvironment/immunology/drug effects
*Lipid Metabolism/immunology
*Carcinoma, Ovarian Epithelial/immunology/pathology/therapy/genetics
Tumor-Associated Macrophages/immunology
Neoplasm Metastasis
Signal Transduction

@article {pmid41775429,
year = {2026},
author = {Flores, TF and Tonorezos, ES and Bhatia, S and Brahmer, JR and Cappelli, LC and Cooper, M and Davies, M and Guild, S and Gunturu, K and Haanen, JBAG and Johnson, DB and Lacouture, ME and Leidner, R and Mitchell, S and Moledina, DG and Moslehi, J and Naidoo, J and Obeid, M and Postow, M and Puzanov, I and Reid, ME and Santomasso, BD and Schadendorf, D and Silk, AW and Sullivan, RJ and Walunas, T and Wang, Y and Ascierto, PA and Ernstoff, MS},
title = {Where is the data? Delayed and chronic irAE surveillance and management after cessation of ICIs: expert insights from SITC on survivorship care and the need for long-term data.},
journal = {Journal for immunotherapy of cancer},
volume = {14},
number = {3},
pages = {},
pmid = {41775429},
issn = {2051-1426},
abstract = {Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, offering durable responses and prolonged survival. However, these therapies also present unique challenges, particularly with the onset of immune-related adverse events (irAEs), which can manifest during treatment either acutely and/or become chronic or emerge long after treatment cessation. Delayed, chronic, and re-emergent irAEs often require tailored survivorship care, including coordination across multiple disciplines focused on oncology, specialty care, and primary care. Despite the increased usage of ICIs, there is limited longitudinal data guiding the surveillance, diagnosis, attribution, and management of irAEs after ICI treatment. To address these gaps, the Society for Immunotherapy of Cancer convened an Expert Panel to deliberate best practices and identify research opportunities for improving post-treatment care. This paper outlines these expert insights into irAE surveillance, coordination and continuity across care transitions and settings, and clinical management strategies. The paper also underscores the importance of clinicians' understanding of irAE onset patterns, multidisciplinary coordination, and the urgent need in the field for the development of a comprehensive irAE registry. By addressing these critical gaps, the oncology community can better support the growing population of ICI-treated cancer survivors, ensuring improved quality of life and care outcomes.},
}

@article {pmid41774708,
year = {2026},
author = {Hsieh, YP and O'Keefe, IP and Wang, Z and Sun, W and Yang, H and Vu, LM and Smalley, NE and Ernst, RK and Dandekar, AA and Malik, HS},
title = {Magnesium depletion by Candida albicans unleashes two unusual modes of colistin resistance in Pseudomonas aeruginosa with different fitness costs.},
journal = {PLoS biology},
volume = {24},
number = {3},
pages = {e3003673},
doi = {10.1371/journal.pbio.3003673},
pmid = {41774708},
issn = {1545-7885},
abstract = {Increasing bacterial resistance to colistin, a vital last-resort antibiotic, is an urgent challenge. Previous studies have shown that Mg2+ depletion enables Pseudomonas aeruginosa to become resistant to colistin. Here, we show that magnesium sequestration by Candida albicans also enables P. aeruginosa to evolve a nearly hundredfold higher level of colistin resistance through genetic changes in lipid A biosynthesis-modification pathways and a putative magnesium transporter. These mutations synergize with the Mg2+-sensing PhoPQ two-component signaling system to remodel lipid A structures of the bacterial outer membrane in previously uncharacterized ways. One predominant mutational pathway involves early mutations in htrB2, a non-essential gene involved in lipid A biosynthesis, which enhances resistance but compromises outer membrane integrity, resulting in fitness costs and increased susceptibility to other antibiotics. A second pathway achieves increased colistin resistance independently of htrB2 mutations without compromising membrane integrity. In both cases, reduced colistin binding to the bacterial membrane underlies resistance. Our findings reveal that Mg2+ scarcity triggers novel evolutionary trajectories, leading to extremely high colistin resistance in P. aeruginosa.},
}

@article {pmid41774517,
year = {2026},
author = {Crombie, JL and Ahmed, S and Frigault, MJ and Hunter, BD and Palomba, ML and Mirza, AS and Lunning, MA and Egini, O and Odstrcil Bobillo, MS and Kallam, A and Kambhampati Thiruvengadam, S and Lee, D and Dahiya, S and Hamadani, M and Herrera, AF and Lee, CJ and Patel, K and Patel, SS and Reagan, PM and Shadman, M and Bernasconi, D and Kim, S and Liu, FF and Roy, D and Pasquini, MC and Isufi, I},
title = {Real-world outcomes for lisocabtagene maraleucel in patients with relapsed or refractory large B-cell lymphoma.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025031733},
pmid = {41774517},
issn = {1528-0020},
abstract = {This study assessed real-world effectiveness and safety of lisocabtagene maraleucel (liso-cel) in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), including those with high-risk disease, secondary central nervous system (sCNS) involvement, comorbidities, and poor fitness, using data in the Center for International Blood and Marrow Transplant Research Registry from 5 Feb 2021 to 4 Feb 2025. Eligible patients (N=1116) received liso-cel and had ≥1 effectiveness and safety assessment after infusion, including 195 in the second-line setting, 71 with sCNS, and 257 with transformed LBCL. Median age was 71.1 years (range, 21.5‒91.2), with 72.3% ≥65 years. Within the overall population, 6.6% had Eastern Cooperative Oncology Group performance status of ≥2, 53.4% had ≥1 comorbidity, and median number of prior lines of therapy was 3 (range, 1‒16). Median study follow-up was 12.6 months (95% confidence interval [CI], 12.5‒12.8). Among effectiveness-evaluable patients (n=1109), objective response rate was 81.2% and complete response rate was 71.3%. Duration of response, progression-free survival, and overall survival rates (95% CI) at 12 months were 60.2% (56.4‒63.9), 51.2% (48.0‒54.4), and 67.6% (64.5‒70.6), respectively. Cytokine release syndrome was reported in 51.0% of patients, with grade ≥3 events in 2.5%. Immune effector cell-associated neurotoxicity syndrome was reported in 26.6% of patients, with grade ≥3 events in 9.2%. The 12-month nonrelapse mortality rate was 6.1% (95% CI, 4.6‒7.8). These real-world data reinforce the effectiveness and safety of liso-cel in this broad population of patients with R/R LBCL, including younger patients and those with high-risk disease features.},
}

@article {pmid41774512,
year = {2026},
author = {Becilli, M and Merli, P and Algeri, M and Del Bufalo, F and Pagliara, D and Bertaina, V and Agrati, C and Rosignoli, C and Cefalo, MG and Boccieri, E and Di Cecca, S and Iaffaldano, L and Lee, Y and De Angelis, B and Meshinchi, S and Quintarelli, C and Campana, D and Locatelli, F},
title = {Anti-CD7 fratricide-resistant chimeric antigen receptor T cells for relapsed/refractory acute myeloid leukemia.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025032299},
pmid = {41774512},
issn = {1528-0020},
abstract = {Autologous second-generation CD7-directed CAR T-cells, expressing an anti-CD7 protein expression blocker to prevent self-killing fratricide, were infused in three pediatric/young adult patients with relapsed/refractory CD7+ acute myeloid leukemia resulting in measurable residual disease negativity. The safety profile was favorable.},
}

@article {pmid41774321,
year = {2026},
author = {Chrostek, MR and Robinson, J and Krishnan, R and Yu, EY and Nordquist, LT and Vandross, AL and Salkeni, MA and Schehr, J and Mannino, M and Hintz, A and Caceres, J and Vatani, M and Emamekhoo, H and Nelson, P and Markey, C and Coates, E and Breitmeyer, J and Fong, L and De Bono, JS and Lang, JM and Zhao, SG},
title = {Phase I multi-center clinical and biomarker study of the dual-action androgen receptor inhibitor ONCT-534.},
journal = {Investigational new drugs},
volume = {},
number = {},
pages = {},
pmid = {41774321},
issn = {1573-0646},
support = {T32GM140935/GF/NIH HHS/United States ; P50CA269011/GF/NIH HHS/United States ; DP2 OD030734/GF/NIH HHS/United States ; },
abstract = {ONCT-534 is a dual-action androgen receptor inhibitor (DAARI) that combines AR antagonism and degradation via N-terminal domain binding, additionally targeting AR splice variants. In this study patients received ONCT-534 daily ranging from 40 to 1200 mg. The primary objectives were safety and dose-limiting toxicities (DLTs). Additional objectives included antitumor activity and AR signaling biomarkers. Adverse events (AEs) were assessed within the first 28 days for DLTs. Clinical activity was evaluated by PSA and radiographic progression per PCWG3 and RECIST v1.1. The trial was stopped early and not all patients were evaluated per protocol. Twenty-one patients received ONCT-534 across six doses. The most common AEs were anemia, back pain, and fatigue. While no DLTs were observed within 28 days, Grade 3/4 AEs occurred later in 9 patients (anemia most frequently). One patient discontinued due to treatment-related AE. No radiographic or PSA-based responses were observed; however, three patients showed PSA declines at week 4, with one achieving a PSA50 at time of study closure. Of 10 patients with baseline AR protein data, the median change was - 40.59% in AR protein levels at week 4. In the 300 mg cohort, 3 patients showed concordant decreases in AR protein and AR gene expression. Here, PSA levels correlated positively with AR target gene and AR gene expression. ONCT-534 had acceptable safety and demonstrated biological activity through AR protein degradation and AR signaling suppression in mCRPC patients. Although clinical responses weren't observed, these findings provide proof-of-concept for examining AR protein changes in patients receiving DAARIs.},
}

@article {pmid41771133,
year = {2026},
author = {Tosteson, ANA and Stout, NK and Su, YR and van Ravesteyn, NT and Lowry, KP and Abraham, L and Alagoz, O and DiFlorio-Alexander, R and de Koning, HJ and Hampton, JM and Henderson, L and Mandelblatt, JS and Onega, T and Schechter, CB and Sprague, BL and Stein, S and Trentham-Dietz, A and Miglioretti, DL and Kerlikowske, K and Lee, CI},
title = {Outcomes of Density-Targeted Supplemental Breast Magnetic Resonance Imaging Screening by Breast Cancer Risk: Long-Term Health and Economic Considerations.},
journal = {Annals of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.7326/ANNALS-25-00792},
pmid = {41771133},
issn = {1539-3704},
abstract = {BACKGROUND: Federally mandated breast density notifications motivate consideration of supplemental breast magnetic resonance imaging (MRI).

OBJECTIVE: To evaluate supplemental breast MRI strategies.

DESIGN: Simulation of women at average to 4 times higher-than-average relative risk (RR) for breast cancer incidence undergoing screening digital breast tomosynthesis (DBT) with or without supplemental MRI.

DATA SOURCES: Breast Cancer Surveillance Consortium and literature.

TARGET POPULATION: Women aged 40 years or older.

TIME HORIZON: Lifetime.

PERSPECTIVE: U.S. federal payer.

INTERVENTION: Screening with DBT with or without breast density-targeted MRI by starting age (40, 45, or 50 years) and interval (annual or biennial).

OUTCOME MEASURES: Breast cancer deaths averted, false-positive biopsy recommendations, harm-benefit ratios, and incremental cost-effectiveness ratios (ICERs).

RESULTS OF BASE-CASE ANALYSIS: Across all starting ages and intervals, DBT averted 7.4 to 10.5 breast cancer deaths per 1000 average-risk women screened and 23.2 to 33.6 per 1000 women with 4 times higher-than-average risk. Across all RR levels, DBT with supplemental MRI for women with extremely dense breasts (DBT+MRId) averted 0.1 to 0.8 additional breast cancer deaths and resulted in 22 to 186 additional false-positive biopsy recommendations. False-positive biopsies per breast cancer death averted for biennial DBT+MRId for women with 2 times higher-than-average risk were similar to those associated with DBT in average-risk women. For all risk groups, biennial DBT+MRId starting at age 50 years was more effective but less cost-effective than DBT starting at age 45 years.

The ICERs were sensitive to cancer risk, MRI costs, and false-positive biopsy rates.

LIMITATION: Subgroups considered risk and breast density only.

CONCLUSION: Supplemental MRI for women aged 40 years or older with extremely dense breasts and higher-than-average risk (RR ≥2.0) had harm-benefit ratios similar to biennial DBT alone and could be cost-effective if MRI costs and false-positive biopsy rates are reduced.

PRIMARY FUNDING SOURCE: National Cancer Institute.},
}

@article {pmid41771028,
year = {2026},
author = {Kamat, AM and Hensley, PJ and Maiorano, BA and Li, R and Psutka, SP and Mouw, KW and Horowitz, A and Gupta, S and Necchi, A},
title = {Bacillus Calmette-Guérin (BCG) and Beyond: Is Systemic Immunotherapy for BCG-Naïve Non-Muscle-Invasive Bladder Cancer Progress or Overreach?.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502670},
doi = {10.1200/JCO-25-02670},
pmid = {41771028},
issn = {1527-7755},
}

@article {pmid41770790,
year = {2026},
author = {Minnie, S and Ho, K and Boiko, JR and Adams, RC and Ensbey, KS and Nemychenkov, NS and Legg, SR and Schmidt, CR and Comstock, ML and Lyons, J and Sekiguchi, T and Koyama, M and Spencer, A and Green, DJ and Hill, GR},
title = {CSF-1R inhibition and lenalidomide synergize to promote myeloma control after autologous stem cell transplantation.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025030207},
pmid = {41770790},
issn = {1528-0020},
abstract = {Autologous stem cell transplantation (ASCT) with maintenance lenalidomide remains the mainstay of consolidation therapy for eligible multiple myeloma (MM) patients but preventing disease relapse remains a critical unmet need. Here we investigated whether immunosuppressive myeloid populations in bone marrow (BM) correlated with ASCT outcomes. We identified a subset of CD64+CD169+CD163+ macrophages that expressed CSF-1R, PD-L1, and CD155, and were expanded in patients who relapsed post-ASCT. Using a preclinical ASCT model with suboptimal endogenous anti-myeloma activity, we demonstrated that while neither CSF-1R inhibition nor lenalidomide monotherapy significantly improved outcomes, their combination synergistically attenuated disease progression and prolonged survival. Single-cell RNA sequencing revealed that lenalidomide expanded NK-like CD8+ T-cells but paradoxically also increased the frequency of Csf1r+ macrophages. Cell-cell communication analyses identified Csf1r+ macrophages as suppressors of these NK-like and effector-like exhausted (Tphex) CD8 T-cell populations through CD94/NKG2A and PD-L1/PD-1, respectively. CSF-1R blockade depleted these immunosuppressive macrophages, which correlated with decreased expression of inhibitory receptors and enhanced expression of activation markers in Tphex. Given the FDA approval of axatilimab for chronic GVHD, combining CSF-1R blockade with lenalidomide maintenance represents a readily testable strategy to improve progression-free survival after ASCT.},
}

@article {pmid41770651,
year = {2026},
author = {Abrams, HR and Loggers, ET and Wagner, MJ and Kim, EY and Schaub, SK and Roberts, JL and Brinkmann, E and Thompson, M and Moore, R and Johnson, R and Baroudi, M and Morin, N and Gooley, T and Cranmer, LD},
title = {A Phase 1 Study of Neoadjuvant Cabozantinib in Combination With Radiation Therapy for Sarcomas of the Extremities.},
journal = {American journal of clinical oncology},
volume = {},
number = {},
pages = {},
pmid = {41770651},
issn = {1537-453X},
abstract = {OBJECTIVES: Cabozantinib demonstrates activity in multiple soft tissue sarcoma (STS) subtypes, but use with concurrent radiation therapy (RT) has been limited by concern for risk of fistula or perforation. This phase 1 trial evaluated the safety of concurrent cabozantinib and RT as neoadjuvant therapy in patients with extremity STS.

METHODS: Adults with newly diagnosed localized extremity STS planned for neoadjuvant RT and surgical resection were eligible. Participants received radiation with 5000 to 5040 cGy with conventional fractionation and cabozantinib 40 mg or 60 mg daily. Patients were observed for dose-limiting toxicity (DLT) up to 28 days after completion of concurrent cabozantinib/RT. The primary objective was to identify a recommended phase 2 dose (RP2D) of cabozantinib for combination with RT, and secondary objectives included estimating rates of treatment-related adverse event (TRAE), margin positivity, and objective response.

RESULTS: Six patients were enrolled with histologic subtypes of undifferentiated pleomorphic sarcoma, myxofibrosarcoma, leiomyosarcoma, and myxoid liposarcoma. No DLT due to the combination of cabozantinib and radiation was observed, but 3/6 (50%) patients required dose-reduction due to TRAE of cabozantinib alone. No grade ≥3 toxicities were attributed to RT. The RP2D was cabozantinib 60 mg. Six (100%) patients demonstrated stable disease at 12 weeks, and 5 (83%) underwent R0 resection. Two (33%) patients experienced metastatic relapse, and 1 (17%) died without relapse; 3 (50%) patients survived without relapse by last contact. No local recurrences occurred.

CONCLUSIONS: In this phase 1 trial, concurrent cabozantinib/RT was feasible and demonstrated an acceptable safety profile for patients with extremity STS.},
}

@article {pmid41767406,
year = {2026},
author = {Haddox, HK and Abdel Aziz, O and Galloway, JG and Kent, J and Cooper, CR and Jennings-Shaffer, C and Dumm, W and Temple, SD and Bloom, JD and Matsen, FA},
title = {Clonal interference and changing selective pressures shape the escape of SARS-CoV-2 from hundreds of antibodies.},
journal = {Virus evolution},
volume = {12},
number = {1},
pages = {veaf104},
pmid = {41767406},
issn = {2057-1577},
abstract = {SARS-CoV-2 has evolved increased resistance to human polyclonal antibody responses. But, how it escaped individual monoclonal antibodies from these responses has not been thoroughly explored. Cao et al. used deep mutational scanning to identify mutations that allow SARS-CoV-2 to escape individual antibodies, doing so for hundreds of different antibodies. Here, we use these data to reconstruct how the virus escaped each antibody in nature. For each antibody, we predict how levels of escape changed in the global SARS-CoV-2 population over time. For many antibodies, these levels dramatically fluctuated due to escape mutations being displaced by clade-turnover events. We validate predicted patterns using pseudovirus neutralization data. Fitness effects estimated from natural sequences suggest that mutations are displaced due to clonal interference between clades and that the order in which mutations arose is shaped by changing selective pressures. Overall, this work suggests that SARS-CoV-2 evaded polyclonal responses via complex evolutionary dynamics.},
}

@article {pmid41726945,
year = {2026},
author = {Patton, RD and Netzley, A and Persse, TW and Nair, A and Galipeau, PC and Coleman, IM and Itagi, P and Chandra, P and Adil, M and Vashisth, M and Sayar, E and Hiatt, JB and Dumpit, R and Kollath, L and Demirci, RA and Ghodsi, A and Lam, HM and Morrissey, C and Iravani, A and Chen, DL and Hsieh, AC and MacPherson, D and Haffner, MC and Nelson, PS and Ha, G},
title = {Deep learning-based non-invasive profiling of tumor transcriptomes from cell-free DNA for precision oncology.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41726945},
issn = {2692-8205},
abstract = {Circulating tumor DNA (ctDNA) profiling from liquid biopsies is increasingly adopted as a minimally invasive solution for clinical cancer diagnostic applications. Current methods for inferring gene expression from ctDNA require specialized assays or ultra-deep, targeted sequencing, which preclude transcriptome-wide profiling at single-gene resolution. Herein we jointly introduce Triton, a tool for comprehensive fragmentomic and nucleosome profiling of cell-free DNA (cfDNA), and Proteus, a multi-modal deep learning framework for predicting single gene expression, using standard depth (~30-120x) whole genome sequencing of cfDNA. By synthesizing fragmentation and inferred nucleosome positioning patterns in the promoter and gene body from Triton, Proteus reproduced expression profiles using pure ctDNA from patient-derived xenografts (PDX) with an accuracy similar to RNA-Seq technical replicates. Applying Proteus to cfDNA from four patient cohorts with matched tumor RNA-Seq, we show that the model accurately predicted the expression of specific prognostic and phenotype markers and therapeutic targets. As an analog to RNA-Seq, we further confirmed the immediate applicability of Proteus to existing tools through accurate prediction of gene pathway enrichment scores. Our results demonstrate the potential clinical utility of Triton and Proteus as non-invasive tools for precision oncology applications such as cancer monitoring and therapeutic guidance.},
}

@article {pmid41763494,
year = {2026},
author = {Lee, S and Shu, X and Derkach, A and Reiner, AS and Liang, X and Woods, M and Concannon, P and Lynch, CF and Malone, KE and Knight, JA and John, EM and Deasy, JO and Bernstein, JL and Oh, JH},
title = {Integrating genomic and non-genomic data to stratify the risk of contralateral breast cancer after radiotherapy.},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2026.02.237},
pmid = {41763494},
issn = {1879-355X},
abstract = {PURPOSE: Women treated with radiation therapy (RT) for breast cancer have an increased risk of developing radiation-associated contralateral breast cancer (CBC). Predicting CBC events is challenging due to the complex interplay of genomic, treatment, personal, and clinical factors. This study investigated computational methods that integrate genome-wide single nucleotide polymorphisms (SNPs) and non-genomic data to develop a risk stratification model for developing CBC in women treated with RT for their first primary breast cancer.

METHODS: This study used a subset of the population-based WECARE Study that included 633 CBC cases and 1,253 individually matched unilateral breast cancer (UBC) controls who were treated with RT and had SNP data available from a genome-wide association study (GWAS). The study population was split into training, validation, and test sets for rigorous modeling and validation. Three data integration methods were compared in terms of their ability to stratify CBC risk: 1) Naive integration, 2) Sequential integration, and 3) Sequential iterative integration. A biological analysis of the final model was performed using gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) analysis with gene annotation information informed by the model.

RESULTS: The best-performing integration method was the sequential iterative integration equipped with the mixed effect random forest (MERF) algorithm. This approach achieved an area under the curve of 0.64 to stratify CBC risk in the test set, representing moderate predictive power. Calibration analysis showed good agreement between the lowest and highest risk bins stratified using sorted predicted values in the test set, resulting in an odds ratio of 3.27 for both predicted and observed CBC occurrence. GSEA and PPI analysis revealed that genes with high importance scores were associated with pathways relevant to lipid and fatty acid metabolism as well as breast cancer sensitivity to tamoxifen.

CONCLUSION: The MERF approach demonstrated the potential for integrating high-dimensional genomic and low-dimensional non-genomic data to stratify CBC risk.},
}

@article {pmid41763313,
year = {2026},
author = {Kirtane, K and Kalos, M and Billups, R and Chapuis, AG and Coutinho, V and Feldman, SA and Gastman, B and Haanen, J and Hanley, PJ and Hegde, P and Hopewell, EL and Levine, BL and Locke, FL and Maus, MV and Nair, NV and Nathenson, M and Perales, MA and Rivière, I and Sikder, D and Tendler, C and Yee, C and Luke, J and O'Cearbhaill, RE},
title = {Advancing Cell Therapies for Solid Tumors: A Pathway to Overcome Biological, Operational, and Regulatory Hurdles.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2026.02.054},
pmid = {41763313},
issn = {2666-6367},
abstract = {Cellular therapies have revolutionized the treatment of hematologic malignancies and are now emerging as potentially promising interventions for solid tumors. While considerable learnings can be leveraged from hematologic applications to inform the development of cell therapies in solid tumors, a number of biological and operational challenges-such as target-antigen heterogeneity; off-tumor target-mediated toxicity; immunosuppressive microenvironment; limited trafficking and persistence; tissue accessibility; and significantly larger patient populations-necessitate innovative clinical, manufacturing, regulatory, and operational strategies to deliver effective cell therapies for solid tumors. This white paper, informed by the 2025 Summit on Advancing Cell Therapy for Solid Tumors-co-sponsored by American Society for Transplantation and Cellular Therapy (ASTCT) and Society for Immunotherapy of Cancer (SITC)-proposes a framework for cellular therapy development in solid tumors, with an emphasis on logistical, operational, and regulatory considerations unique to this setting. The paper lays out an innovative, collaborative operational model to leverage collective experience and knowledge; emphasize standardization; invest in both prospective and retrospective banking of materials; engage in regulatory data-driven recalibration; engage payers before therapy begins; and establish regional manufacturing hubs and tailored accreditation pathways to support scalability and quality assurance. Operational innovations that can streamline access include hub-and-spoke clinical networks-where a central specialized facility is connected to smaller, more accessible locations-as well as early patient referrals. To safely implement new therapies, it is essential for providers to undergo enhanced training to manage cellular therapy-specific and delayed toxicities. Regulatory recalibrations-including streamlined evaluation of long-term follow-up requirements and proactive payer engagement for comprehensive reimbursement-are equally vital. Finally, cell therapy experts must lead cross-disciplinary education to ensure equitable and safe access as indications for cellular therapy expand across solid-tumor types, autoimmune diseases, and other disease types. Collaborative efforts across clinical, operational, regulatory, and policy initiatives are vital in order to unlock the full potential of cellular therapy for diverse patient populations.},
}

@article {pmid41763306,
year = {2026},
author = {Rosenthal, KJ and Felix-Sanchez, P and Forbush, K and Rhoads, N and Kang, M and Vicente, JJ and Smith, FD and Wordeman, L and Ong, SE and Cheung, KJ and Scott, JD},
title = {AKAP2 is required for assembly of cytoskeletal signaling complexes that promote growth and metastasis of triple-negative breast cancer.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111329},
doi = {10.1016/j.jbc.2026.111329},
pmid = {41763306},
issn = {1083-351X},
abstract = {A Kinase Anchoring Proteins (AKAPs) that coordinate spatiotemporal signaling are increasingly implicated in cancer. Elevated AKAP2 protein correlates with an invasive phenotype in triple-negative breast cancer cell lines. A combination of biochemical, cellular, and omics approaches show that AKAP2 cytoskeleton and focal adhesion associated scaffolds contribute to the progression of basal-like triple-negative breast cancer. Proximity proteomics identifies AKAP2 as an element of focal adhesions in MDA-MB-231 cells. Molecular and immunofluorescent microscopy studies demonstrate that AKAP2 indirectly constrains focal adhesion kinase (FAK). Gene silencing of AKAP2 not only decreases FAK levels but also attenuates the phosphorylation of the cell motility adapter protein paxillin on Tyr118. Cell-derived xenograft studies in mice establish that AKAP2 is required for triple-negative breast cancer growth and metastasis, phenotypes that are linked to FAK action. These findings discover a new role for focal adhesion-associated AKAP2 in triple-negative breast cancer pathology.},
}

@article {pmid41761831,
year = {2026},
author = {Boeckh, M and Corey, L},
title = {Cytomegalovirus and Aging-How Can the Field Move Forward?.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag099},
pmid = {41761831},
issn = {1537-6613},
}

@article {pmid41760865,
year = {2026},
author = {Mandrik, O and Thomas, C and Bessey, A and Brennan, A and Carvalho, AL and Castilla-Rodríguez, I and Doroshenko, O and Hill, H and Kunst, N and Nagy, B and Payne, K and Pollard, D and Ramsey, SD and Roitberg, F and Shinkins, B and Smitht, RA and Howard, T and Whyte, S},
title = {Ten Recommendations for Modelling Cost Effectiveness of Screening: Perspectives of an International Stakeholder Group.},
journal = {PharmacoEconomics},
volume = {},
number = {},
pages = {},
pmid = {41760865},
issn = {1179-2027},
support = {189350//University of Sheffield/ ; },
abstract = {Modelling the cost effectiveness of screening interventions presents unique challenges. These relate to a lack of knowledge about underlying health states and disease progression in the absence of screening, added costs arising from incidental findings, screening recall and follow-up diagnostics, imperfect uptake, potential harms to otherwise healthy people, and impacts on resource capacity and equity. No specific but generalisable advice currently exists to help guide health economic modellers working in this area. There is a need for tailored recommendations beyond the widely used, health economic modelling frameworks. We aimed to develop a set of recommendations for modelling the cost effectiveness of screening programmes. In our iterative process, we first drafted a conceptual document outlining key issues requiring recommendations. This framework was then expanded based on additional themes identified through a survey of screening modelling experts. Next, the draft recommendations were shared with a broader international expert group, which included modellers, health economists and policy specialists. Finally, the core concepts were refined and agreed upon during a virtual stakeholder meeting. A set of ten recommendations and a checklist are presented. The document provides guidance on critical methodological requirements for modelling screening interventions. These guidelines are intended to help health economic modellers and screening policy makers working to evaluate screening interventions across a wide range of diseases and jurisdictions with clarity, rigour and consistency.},
}

@article {pmid41760378,
year = {2026},
author = {Cook, AJ and Wellman, RD and Marsh, T and Tiwari, RC and Nguyen, MD and Russek-Cohen, E and Peng, Y and Nelson, JC},
title = {Estimating Risk Differences Using Large Healthcare Data Networks for Medical Product Post-Market Safety Outcomes in a Distributed Data Setting and Allowing for Active Post-Market Surveillance.},
journal = {Statistics in medicine},
volume = {45},
number = {6-7},
pages = {e70440},
doi = {10.1002/sim.70440},
pmid = {41760378},
issn = {1097-0258},
support = {HHSF223200910006I/FD/FDA HHS/United States ; 75D30122D15428/CC/CDC HHS/United States ; },
abstract = {Risk differences allow decision makers to easily estimate the excess safety risk associated with a medical product relative to the potential benefits. However, in post-market observational surveillance studies that actively monitor (e.g., sequentially over time) for safety risk of new medical products, available methods target a relative measure (e.g., odds ratio and relative risk), which can be especially unstable in the rare event setting. These studies are typically conducted within distributed healthcare networks (e.g., Food and Drug Administration [FDA] Sentinel and Centers for Disease Control [CDC] Vaccine Safety Datalink) with patient-level data protected behind firewalls, but sharing of aggregate, deidentified data for centralized analyses. We propose an inverse probability of treatment weighting (IPTW) method that uses site-specific propensity scores to estimate site-specific risk differences that are combined to create an overall stratified risk difference estimate. This method is tailored to the rare event setting and requires minimal data sharing. The stratified IPTW approach is then extended to the active post-market surveillance setting by incorporating group sequential monitoring boundaries using a novel permutation approach. A simulation study is conducted to evaluate the performance of the new methods relative to two centralized analysis approaches, and the methods are applied to a safety surveillance study comparing the risk of febrile seizure between two vaccines using FDA Sentinel Data from three healthcare organizations.},
}

@article {pmid41758981,
year = {2026},
author = {Gill, H and Palandri, F and Ross, DM and Göthert, JR and Cochrane, T and Larsen, SR and Halpern, AB and Shortt, J and Rossetti, JM and Liang, J and Marchetti, M and Wilson, AJ and Innes, AJ and Hanna, M and Vianelli, N and Stevenson, WS and Vannucchi, AM and Kleppe, M and Flynn, J and Natsoulis, G and Harrison, CN and Rienhoff, HY},
title = {Phase 2 study of the lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat for essential thrombocythemia.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017575},
pmid = {41758981},
issn = {2473-9537},
abstract = {Novel treatments that can improve disease course of essential thrombocythemia (ET) are needed. In this phase 2 trial, participants with ET who required cytoreduction and had inadequate response to or were intolerant of ≥1 standard therapy received bomedemstat at a starting dose of 0.6 mg/kg per day, titrated to achieve a target platelet count (200-400×109/L). Primary end points were safety and response, defined as a platelet count ≤400×109/L without new thromboembolic events. Seventy-three participants received bomedemstat. At 24 weeks, 49 of 64 evaluable participants (77%) had a response. Durable reductions in platelet count (≤400×109/L for ≥12 weeks) were observed in 52 of 72 participants (72%). Durable reduction in white blood cell count (<10×109/L for ≥12 weeks) was observed in 61 of 72 participants (85%); of 10 participants with elevated white blood cell count at baseline, 9 had normal white blood cell count (<10×109/L) at week 24. Hemoglobin levels remained stable. After 24 weeks of treatment, a decrease in variant allele frequency of CALR, JAK2, or MPL was observed in 39 of 46 (85%) evaluable participants. By week 24, 2 of 73 participants (3%) had experienced ≥1 thrombotic event and 15 of 73 (21%) experienced ≥1 hemorrhagic event. During overall treatment period, grade 3 or 4 adverse events (AEs) occurred in 34 of 73 participants (47%). AEs led to temporary treatment interruption in 29 participants (40%) and permanent discontinuation in 11 (15%). No participants died due to AEs. Bomedemstat had clinically relevant activity and manageable safety in participants with ET. Registration: NCT04254978 (Study of Bomedemstat in Participants With Essential Thrombocythemia [IMG-7289-CTP-201/MK-3543-003]).},
}

@article {pmid41758580,
year = {2026},
author = {Cai, Y and Surapaneni, A and Vasconcelos, AG and Johnson, M and Hsu, L and Sun, W and Kooperberg, C and Yu, B and Yeo, WJ and Auer, PL and Grams, ME and Franceschini, N and Raffield, LM and Reiner, AP},
title = {Alterations of Plasma Metabolites Associated with Sickle Cell Trait.},
journal = {Clinical journal of the American Society of Nephrology : CJASN},
volume = {},
number = {},
pages = {},
doi = {10.2215/CJN.0000001015},
pmid = {41758580},
issn = {1555-905X},
abstract = {BACKGROUND: Sickle cell trait (SCT) is the heterozygous carrier state for sickle cell disease (SCD) and is common among individuals of African ancestry. While SCT is a known risk factor for chronic kidney disease and end-stage kidney disease (ESKD), the mechanisms underlying this phenotypic association have not been fully characterized. We utilized metabolomic profiling to gain insight into the pathobiology of SCT.

METHODS: We used a nontargeted metabolomics approach (Metabolon Global Discovery Panel) to measure baseline plasma levels of 851 metabolites in 986 older Black or African American women with SCT (mean age 61 ± 7 years) compared to 998 age- and race-matched controls without SCT from the prospective Women's Health Initiative (WHI) study. Age-adjusted linear regression was used to assess the association between metabolite levels and SCT. Replication was performed in an independent sample of 1,070 African American men and women (including 70 with SCT) from the Atherosclerosis Risk in Communities (ARIC) study.

RESULTS: In age-adjusted models, 69 metabolites were significantly associated with SCT in WHI after correction for multiple testing. Many of the SCT-associated metabolites are markers of kidney glomerular filtration (eGFR) and/or related to oxidative stress metabolic pathways known to be altered in SCD homozygotes. Of the 64 SCT-associated metabolites available for replication, 25 or 39% were replicated in the ARIC study. Inclusion of SCT-associated metabolites was associated with significantly better risk prediction of incident ESKD in WHI among SCT individuals compared with a baseline model adjusted for age + estimated glomerular filtration rate (eGFR).

CONCLUSIONS: We identified and replicated metabolites associated with SCT, many of which are related to eGFR and/or pathways altered in SCD (e.g., oxidative stress, membrane remodeling). These results suggest that plasma metabolomic profiling may be useful in ESKD risk stratification for individuals with SCT, meriting validation in larger cohorts.},
}

@article {pmid41752282,
year = {2026},
author = {Amissah, CM and Crump, AA and Fu, YH and Khadka, S and Contreras, J and Jones, SMW and Reeve, BB and Villalonga-Olives, E},
title = {Developing an Index to Measure Structural Racism: Methodological Process, Challenges, and Considerations.},
journal = {International journal of environmental research and public health},
volume = {23},
number = {2},
pages = {},
pmid = {41752282},
issn = {1660-4601},
support = {R01MD019029//National Institute of Health/ ; },
abstract = {Access to valid and reliable measures of structural racism is essential for addressing health inequities, yet few validated ecological-level indices exist for assessing structural racism affecting Black and Hispanic populations in the United States. Guided by the National Institute on Minority Health and Health Disparities framework, our interdisciplinary team undertook the development of an ecological-level structural racism index. In the process, we encountered substantive methodological and data-related challenges that warrant explicit documentation. This paper describes the methodological process used to identify and select indicators of structural racism, including a modified Delphi consensus process involving social epidemiologists, health inequality researchers, community members, economic inequality specialists, and psychometricians. We outline a five-step approach for extracting and harmonizing geographic-level data from publicly available sources and discuss key challenges encountered, including limited availability of granular geographic data, insufficient data documentation guidelines, inconsistent reporting frequencies, and difficulties in adapting publicly available datasets for structural racism measurement. Rather than presenting a finalized index, this paper serves as a methodological guide and cautionary account for researchers seeking to develop ecological measures of structural racism, emphasizing the importance of transparency, adaptability, and rigorous data selection in advancing public health equity research.},
}

@article {pmid41749842,
year = {2026},
author = {Chakrabarti, S and Cohen, SA and Tin, A and Dangl, A and Chung, KY and Tejani, MA and Fakih, MG and Chandana, SR and Donahue, CA and George, V and Malla, M and Aushev, VN and George, GV and Ortiz, JB and Herter, WK and Nagarajan, A and Weinberg, BA and Sharma, VR and Botta, GP and Cho, M and Azzi, G and Kasi, A and Dayyani, F and Hanna, DL and Somer, BG and Malhotra, M and Sharma, S and Jurdi, A and Liu, MC and Landmann, RG and Dasari, A},
title = {Utility of Circulating Tumor DNA to Assess Tumor Response in Patients with Locally Advanced Rectal Cancer Undergoing Neoadjuvant Therapy.},
journal = {Cancers},
volume = {18},
number = {4},
pages = {},
pmid = {41749842},
issn = {2072-6694},
abstract = {BACKGROUND: Circulating tumor (ct)DNA is a prognostic biomarker in gastrointestinal malignancies. In rectal cancer, its utility to inform perioperative management and predict recurrence, particularly in patients undergoing non-operative management (NOM), remains unclear. Studies are needed to clarify how post-neoadjuvant therapy (NAT) and post-surgical ctDNA status correlate with clinical outcomes in localized rectal cancer.

METHODS: We retrospectively analyzed ctDNA data from 220 patients with rectal cancer using a personalized tumor-informed assay (Signatera™, Natera, Inc., Austin, TX, USA). Of these, 148 (67.3%) underwent NAT followed by surgery, and 72 (32.7%) underwent NAT followed by NOM. We assessed associations between post-NAT ctDNA status and survival outcomes. In the surgical cohort, we examined associations between post-operative ctDNA status and clinical response, pathological response, survival outcomes, and NAR scores.

RESULTS: In the surgical cohort, ctDNA positivity at the post-operative MRD timepoint was a strong predictor of recurrence, with an 88.3% relapse rate compared to 11.5% in ctDNA-negative patients (p < 0.001). Among the 64 NOM patients with post-NAT ctDNA, 21.9% (14/64) were ctDNA-positive, of whom 100% (14/14) relapsed (92.9% local-only), 13 relapsed by the time of data cut-off, and one relapsed 8 months after the cut-off. Only 10% (5/50) of the ctDNA-negative NOM patients experienced local recurrence (p < 0.0001). ctDNA positivity post-NAT was associated with inferior DFS (p = 0.003).

CONCLUSION: ctDNA was a strong predictor of recurrence in rectal cancer, including in NOM settings. In NOM patients, ctDNA detected local recurrences, highlighting its potential to guide post-NAT surveillance and treatment.},
}

@article {pmid41748788,
year = {2026},
author = {Montano-Campos, JF and Adair, JE and Basu, A and Kyeyune, RB and Bayigga, L and Kityo-Mutuluuza, C and Hansen, R},
title = {Cost-effectiveness of gene therapy for sickle cell disease in Uganda: tailoring high-income evidence to Uganda's context.},
journal = {Gene therapy},
volume = {},
number = {},
pages = {},
pmid = {41748788},
issn = {1476-5462},
support = {P51OD010425//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U42OD011123//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI167009//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI158728//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; INV002613//Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)/ ; INV03398//Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)/ ; },
abstract = {Blood stem cell gene therapy to treat hemoglobinopathies is beginning to transform health for small numbers of patients in the U.S. and Europe, where these conditions qualify as rare diseases. Yet hemoglobinopathies are common globally, disproportionately affecting low- and middle-income countries (LMICs), creating an ethical imperative to ensure access where disease burden is greatest. Gene therapy could have blockbuster drug potential if distributable to these regions, but cost is a major barrier. Cost-effectiveness analysis (CEA) models are seldom adapted to low-income settings, where limited data and resources constrain efforts to contextualize high-income evidence. Here, we present a novel framework to evaluate high-income country authorized gene therapies in LMIC contexts. Uganda, where sickle cell disease (SCD) imposes a major burden and no curative therapies are available, is the test case. We evaluate cost-effectiveness of gene therapy for adolescents and adults with SCD in Uganda, adapting U.S. evidence to local economic conditions. Using a three-state Markov model to estimate lifetime costs of standard-of-care in Uganda, two U.S.-based CEA models were adapted using scaling factors and applied to two authorized gene therapies for SCD, Lyfgenia™ (lovo-cel) and Casgevy® (exa-cel), assuming biologically consistent efficacy across populations. Incremental cost-effectiveness ratios (ICERs) were calculated from healthcare and societal perspectives, with internationally accepted gross domestic product-based thresholds. This study demonstrates that Casgevy could be cost-effective in Uganda at a scaled cost when societal benefits are considered. This framework enables CEAs for emerging therapies where local clinical trial data are limited, supporting local decision-makers, global funders, and manufacturers in advancing equitable access to transformative therapies in LMICs.},
}

@article {pmid41748695,
year = {2026},
author = {Jutzi, JS and Crosse, E and Kim, CJ and van Gasteren, B and Laurore, C and Rolles, B and Kramer, F and Tishena, A and Rocha, AV and Wazir, M and Weeks, LD and How, J and Stahl, M and Luskin, MR and Lindsley, RC and Pozdnyakova, O and Rai, S and Graubert, TA and Bradley, RK and Mullally, A and Marneth, AE},
title = {Mutant SRSF2-associated impaired erythropoiesis is defined by increased mTORC1 signaling due to FYN missplicing.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {41748695},
issn = {1476-5551},
support = {W81XWH-20-1-0904//U.S. Department of Defense (United States Department of Defense)/ ; W81XWH2110909//U.S. Department of Defense (United States Department of Defense)/ ; Hypatia//Radboud Universitair Medisch Centrum (Radboudumc)/ ; 70114570//Deutsche Krebshilfe (German Cancer Aid)/ ; R01HL131835//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; I15-0026//Starr Foundation/ ; },
abstract = {Somatic mutations in RNA splicing regulators, including the serine/arginine-rich protein SRSF2, are frequently observed in myeloid malignancies. Using mouse models and primary human samples, we investigated the impact of SRSF2 mutations on erythropoiesis. We found reduced erythropoiesis in Srsf2[P95H] versus wild-type mice upon stress-induced erythropoiesis and identified that SRSF2 mutations correlate with reduced hemoglobin in JAK2-mutant patients with myeloproliferative neoplasms (MPN). Consistent with this, Jak2[V617F]-Srsf2[P95H] versus Jak2[V617F] mice displayed reduced red blood cell counts and erythroid precursor frequencies. RNA-sequencing on erythroid precursors showed reduced expression of heme metabolism and mitotic spindle-related genes, and increased expression of mTORC1 signaling in Srsf2[P95H] versus wild-type cells. RNA splicing analyses on the same cells and on human patient samples identified aberrant FYN splicing in SRSF2[mut] cells, with increased aberrant FYNB over normal FYNT transcripts. FYNB, but not FYNT, expression resulted in reduced erythroid differentiation and increased phosphorylation of mTORC1 downstream target S6. Additionally, increased S6 phosphorylation was confirmed in primary Srsf2[P95H] erythroid cells. mTORC1 pathway inhibition using rapamycin normalized FYNB- and Srsf2[P95H]-induced impaired erythropoiesis and significantly increased erythroid colony formation of SRSF2-mutant myelodysplastic neoplasm (MDS) bone marrow cells. Our data reveal targetable molecular mechanisms of impaired erythropoiesis in SRSF2-mutant cells.},
}

@article {pmid41747891,
year = {2026},
author = {Booth, A and Hillman, S and Laumann, K and Zhao, YQ and LeBlanc, M and Chansky, K and Giri, S and Dill, J and Johnson, J and Kelley, K and Martin, L and Osarogiagbon, RU and Morris, MJ and Chiang, AC and Kozono, DE and Blanke, CD and Galanis, E and Gray, JE and Stinchcombe, TE and Aljumaily, R and Morgensztern, D and Mandrekar, SJ},
title = {PROSPECT-LUNG: A National Clinical Trials Network Trial Advancing Pragmatic Innovation in Cancer Clinical Trials.},
journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer},
volume = {},
number = {},
pages = {103650},
doi = {10.1016/j.jtho.2026.103650},
pmid = {41747891},
issn = {1556-1380},
abstract = {PURPOSE: Clinical trial designs marked by extensive data collection, restrictive eligibility, and lengthy protocols create inefficiencies, increase costs, and hinder accrual. These are further compounded by staffing shortages and operational burdens. By incorporating pragmatic features including simplified eligibility criteria, streamlined protocol, and data collection, the PROSPECT-Lung trial paves the way forward as a model for enhancing clinical trial efficiency and feasibility, while maintaining scientific rigor.

PATIENTS AND METHODS: PROSPECT-Lung (CTIU2317-A082304-S2402) is a pragmatic, phase III, open-label, randomized trial comparing 3-year real-world event-free survival and overall survival using approved perioperative and adjuvant immunotherapy-based treatment strategies in patients with resectable non-small cell lung cancer. Protocol length and data collection elements were compared with Alliance A081801, Integration of Immunotherapy into Adjuvant Therapy for Resected NSCLC: ALCHEMIST CHEMO-IO (ClinicalTrials.gov Identifier: NCT04267848), a phase III trial in the same disease setting, to quantify streamlining efforts.

RESULTS: Relative to A081801, PROSPECT-Lung achieved major reductions in trial complexity. Protocol length decreased from 88 to 30 pages (65%), and data fields per patient were reduced from 2523 to 438 (82.6%), driven by streamlined summary versus cycle-by-cycle data collection. These efficiencies translate to estimated site workload reductions from 210 hours per patient in A081801 to 36.5 hours in PROSPECT-Lung. At full accrual, this equates to more than 190,000 hours saved in chart review, data entry, documentation, and quality control.

CONCLUSION: By broadening eligibility and streamlining logistics, PROSPECT-Lung reduces burden for patients, investigators, and sites while preserving scientific integrity. This pragmatic approach, when appropriate and possible, provides a replicable model for future cancer trials, promoting efficiency, accessibility, and real-world relevance.},
}

@article {pmid41747248,
year = {2026},
author = {Kelly, MM and Dempsey, A and Ameral, V and Petrakis, BA and Reilly, ED and Quigley, K and Bricker, JB and Heffner, JL},
title = {Web-Based Acceptance and Commitment Therapy Tobacco Cessation Program for Veterans With Mental Health Disorders: Adaptation and Usability Testing.},
journal = {JMIR formative research},
volume = {10},
number = {},
pages = {e75394},
doi = {10.2196/75394},
pmid = {41747248},
issn = {2561-326X},
abstract = {BACKGROUND: US veterans with mental health disorders have high rates of smoking and low rates of smoking cessation.

OBJECTIVE: This study aims to focus on an adaptation of a web-based acceptance and commitment therapy (ACT) tobacco cessation intervention (Vet WebQuit) for veterans with mental health disorders who use tobacco and used a qualitative approach to test its usability (n=16).

METHODS: Participants were asked to walk through the site during laboratory-based usability testing and "think aloud" about the features of the intervention. A trained facilitator used semistructured interview questions to assess participants' experiences with Vet WebQuit and obtain feedback on their impressions of the site. Qualitative analyses identified themes regarding participants' experiences with the intervention, usability concerns, and recommendations for improving Vet WebQuit.

RESULTS: Overall, veterans found that the Vet WebQuit layout was simple and easy to navigate and use. Veterans reported that several features of the program were useful, including the quit plan, identification of triggers, content that targets mental health concerns (eg, dealing with anger), information on the health effects of smoking, tools for managing triggers (eg, urge surfing), and involving others in their quit plan. Veterans reported that particular features of the ACT approach for tobacco cessation were appealing to them, including the distinction between internal and external smoking triggers, the inclusion of the serenity prayer, and mindfulness exercises, which they could use as a tool reduce the intensity of cravings. Veterans reported wanting more information on the health aspects of smoking (ie, effects on breathing and lung capacity) as a way to motivate them to quit smoking. In addition, they suggested targeting specific mental health concerns that serve as triggers for smoking, including nightmares, boredom, and social isolation.

CONCLUSIONS: Overall, results from this project identified important elements of ACT digital tobacco cessation interventions for veterans with mental health disorders.},
}

@article {pmid41747197,
year = {2026},
author = {Sharp, J and Strati, P and Bhatta, S and Huang, JJ and Thomas, CJ and Elghawy, O and Reef, D and Gorzewski, AM and Wang, JS and Shouse, G and Reinert, C and Teferra, A and Toro Velez, E and Pelcovits, A and Ollila, TA and Clark, WB and Yazbeck, V and Maakaron, JE and Kamdar, M and Fitzgerald, LA and Danilov, AV and Karmali, R and Grover, NS and Barta, SK and Voorhees, TJ and Chen, AI and Shadman, M and Ahmed, S and Epperla, N},
title = {Real-World Outcomes and Toxicities of CAR-T in Relapsed/Refractory Follicular Lymphoma: A Multicenter Cohort Study.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025019115},
pmid = {41747197},
issn = {2473-9537},
abstract = {Chimeric antigen receptor T-cell (CAR-T) therapy revolutionized treatment of relapsed/refractory (R/R) follicular lymphoma (FL). Real-world efficacy and toxicity data are needed as clinical trial populations are often not representative. Hence, we conducted a multi-center retrospective study of patients with R/R FL undergoing commercial CAR-T with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) between 2021 and 2024. Endpoints included measures of efficacy (overall response rate [ORR], complete response rate [CRR], progression-free survival [PFS], and overall survival [OS]) and toxicity (rates of cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS]). Among 136 patients, 100 (74%) received axi-cel and 36 (26%) received tisa-cel. Axi-cel patients were younger (median age 60 vs 68 years, p=0.001) and received bendamustine lymphodepletion less often (9% vs 33%, p<0.001). Median follow up was 14.4 months (range 0.8 - 72.0 months). In the unweighted analysis, axi-cel was associated with higher ORR (96% vs 80%, p=0.007), CRR (88% vs 71%, p=0.024), and longer median PFS (30.5 months vs 11.9 months, p=0.021) compared with tisa-cel. Median OS did not differ significantly between the two products (not reached vs 23.6 months, p=0.061). Rates of CRS were comparable (75% vs 75%, p=0.99), whereas ICANS occurred more frequently with axi-cel (42% vs 17%, p=0.008). After inverse probability of treatment weighting, efficacy outcomes were largely similar between axi-cel and tisa-cel, however, axi-cel remained associated with significantly higher toxicity. In real-world settings, both axi-cel and tisa-cel demonstrated efficacy in patients with R/R FL, although PFS was inferior to that reported in clinical trials.},
}

@article {pmid41746780,
year = {2026},
author = {Shaffer, BC and Lee, SJ and Perales, MA},
title = {How I Treat: Selection of Hematopoietic Cell Donors in the Era of Post-Transplant Cyclophosphamide.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025030823},
pmid = {41746780},
issn = {1528-0020},
abstract = {Selection of a hematopoietic progenitor cell donor for allogeneic hematopoietic cell transplantation (allo HCT) is essential for treatment planning; however, the parameters that define an "optimal" donor in the modern era are not well defined. Historically, donor-recipient human leukocyte antigen (HLA) mismatching correlated strongly with risk for graft versus host disease (GVHD) and reduced survival. For this reason, donor selection was typically hierarchical: HLA matched related and unrelated donors were evaluated first, followed by HLA mismatched donors (or deferral of HCT altogether) in patients lacking an HLA matched donor. The advent of post-transplant cyclophosphamide (PTCy)-based GVHD prevention has changed this paradigm. Survival outcomes following HLA-mismatched donor HCT with PTCy, including from related haploidentical or HLA-mismatched unrelated donors, are not different than HLA matched donor recipients in recent clinical trials and retrospective studies. These encouraging results present a new challenge: In the PTCy era, how should donors be prioritized among the many potential sources available? Herein we review HLA and non-HLA parameters that inform donor selection and discuss approaches to increase donor availability. Case vignettes focusing on concepts that may be adapted to heterogenous clinical scenarios are presented.},
}

@article {pmid41746629,
year = {2026},
author = {Shadman, M and LeBlanc, M and Rimsza, L and Leonard, JP and Smith, SM and Li, H and Friedberg, JW},
title = {Treatment of Follicular Lymphoma With CHOP and Anti-CD20 Therapy: 15-Year Follow-Up of the SWOG S0016 Trial.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
pmid = {41746629},
issn = {2374-2445},
abstract = {IMPORTANCE: Follicular lymphoma (FL) has historically been regarded as incurable, with patients experiencing late relapses after initial chemoimmunotherapy treatment.

OBJECTIVE: To provide 15-year follow-up data from the SWOG S0016 trial that evaluated the potential for long-term remission and cure following chemoimmunotherapy with cyclophosphamide, hydroxydaunorubicin/doxorubicin, oncovin, and prednisone/prednisolone (CHOP)-based regimens.

This multicenter, intergroup study was conducted at academic and community practice locations throughout the US and enrolled patients with untreated, advanced-stage FL. Cure modeling, which involves estimating the proportion of patients cured of the disease, was conducted by incorporating background mortality rates to estimate the proportion of patients cured of FL during the S0016 trial. Patients were enrolled between May 2001 and October 2008 and followed up for a median (IQR) of 15.5 (13.6-16.9) years. The 15-year analysis was conducted in June 2025.

INTERVENTIONS: Patients were randomized to receive either rituximab plus CHOP (R-CHOP) or CHOP followed by radioimmunotherapy (CHOP-RIT).

MAIN OUTCOMES: The main outcomes were 15-year progression free survival (PFS) and overall survival (OS). Secondary outcomes included cure modeling.

RESULTS: A total of 531 eligible patients (242 female patients [46%]; median [IQR] age, 53 [45-61] years) were included in the final analysis (267 [50%] received R-CHOP and 264 [50%] CHOP-RIT). The overall 15-year OS was 70%, with no significant difference between treatment arms, and the 15-year PFS was 40% (95% CI, 36.0%-44.7%). CHOP-RIT demonstrated superior 15-year PFS (47% vs 34%; P = .004) compared with R-CHOP. Cure modeling estimated an overall cure rate of 42%, with the highest cure rates observed in patients with low Follicular Lymphoma International Prognostic Index scores and normal β2 microglobulin levels. The rate of relapse declined substantially over time, from 6.8% during the first 5 years to 0.6% between 15 to 20 years.

CONCLUSIONS AND RELEVANCE: The results of this secondary analysis suggest that a subset of patients with advanced-stage FL can achieve cure with CHOP-based chemoimmunotherapy, as relapse rates decline over time. This finding represents a paradigm shift in the understanding of and approach to FL, with implications for initial patient discussions and future research strategies.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00006721.},
}

@article {pmid41746611,
year = {2026},
author = {Andrasik, M and Broder, G and Louis, K and Baepanye, K and Kamel, L and Davis, A and Segura, P and Makhubalo, B and Leon Rhandomy, MR and Soler, J and Certo, SK and Gonzalez, R and Dawit, W and Reinstein, S and Shipman, CE and Seyama, L and Sanchez Sarmiento, H and Mpongo, NC and Swann, E and Morar, NS},
title = {Building Trust and Engaging Communities for HIV Prevention Research Globally.},
journal = {AIDS education and prevention : official publication of the International Society for AIDS Education},
volume = {38},
number = {1},
pages = {1-17},
doi = {10.1521/aeap.2026.38.1.1},
pmid = {41746611},
issn = {1943-2755},
abstract = {The HIV Vaccine Trials Network (HVTN) is the largest publicly funded international collaboration facilitating the evaluation of vaccines to prevent HIV and TB. Central to the HVTN's success is the reliance on robust community engagement methods, ensuring community participation and facilitating community awareness and knowledge of research. Community engagement is a dynamic process that requires active participation from all stakeholders to ensure success. The HVTN and its global Clinical Research Sites (CRSs) located in Africa, Latin America, and North America are known as the Network. We describe relationships across the Network, specific staff roles and responsibilities, and the myriad activities undertaken to ensure optimal community engagement. Key activities include involving active Community Advisory Boards (CABs), using community consultations, and having trained Community Engagement staff at each CRS. Operating with robust community engagement has resulted in rapid enrollment and high retention of diverse participant populations across Network studies.},
}

@article {pmid41744883,
year = {2026},
author = {Bea, JW and Ziller, SG and Decker, D and Roe, DJ and Odegaard, AO and Ochs-Balcom, HM and Lima, SM and Caan, B and Wactawski-Wende, J and Pichardo, MS and Harris, H and Chen, Z},
title = {DXA-Derived Visceral and Subcutaneous Adipose Tissue and Postmenopausal Breast Cancer Mortality.},
journal = {Current oncology (Toronto, Ont.)},
volume = {33},
number = {2},
pages = {},
pmid = {41744883},
issn = {1718-7729},
support = {R01CA253302//National Cancer Institute at the National Institutes of Health/ ; },
abstract = {BACKGROUND: Elevated abdominal adipose tissue at time of diagnosis is associated with breast cancer mortality. We sought to understand the association between abdominal adipose tissue (subcutaneous, SAT and visceral, VAT) assessed via dual-energy X-ray absorptiometry (DXA) and breast cancer mortality in the prevention setting.

METHODS: Women enrolled in the Women's Health Initiative study with baseline whole-body DXA scans were included in the study (n = 9767). Causes of death were adjudicated up to 27 years of follow-up. Competing risk models were used to examine independent associations between baseline VAT, SAT, per 100 cm[2], and breast cancer-specific deaths; findings were reported as sub-hazard ratios (SHR) and confidence intervals (CI). Time-varying analyses additionally included DXA at years 3 and 6. Covariates included demographic, lifestyle, and tumor factors.

RESULTS: Baseline VAT and SAT ranged from undetectable to 616.25 cm[2] and 55.26-952.46 cm[2], respectively. There were 738 incident breast cancer cases post-enrollment, and 87 breast cancer-related deaths. Median age at diagnosis was 62 years. In adjusted models, higher baseline VAT and SAT were significantly associated with higher risk breast cancer mortality (49% and 40%, respectively); time-varying models were similar.

CONCLUSIONS: Higher VAT and SAT were similarly associated with breast cancer mortality in this group of postmenopausal women.},
}

@article {pmid41744290,
year = {2026},
author = {Armstrong, AJ and Morris, MJ and Abida, W and Aggarwal, RR and Antonarakis, ES and Attard, G and Beltran, H and Bryce, A and Carducci, MA and Cheng, HH and Chen, DL and Chi, KN and Childs, DS and Dahut, W and Emmett, L and Fizazi, K and Gafita, A and George, DJ and Hermann, K and Hofman, MS and Hope, T and Hussain, M and Kelly, WK and Kessler, E and Kuo, PH and Lang, J and Liu, G and Marshall, CH and Morgans, AK and McKay, RR and Nanus, D and Nelson, P and Paller, C and Reichert, ZR and Ryan, CJ and Sartor, AO and Schöder, H and Schwartz, LH and Sharifi, N and Stadler, WM and Stein, M and Sternberg, CN and Szmulewitz, RZ and Tagawa, ST and Sokolova, AO and Wyatt, AW and Yamoah, K and Yu, EY and Halabi, S and Scher, HI and , },
title = {Trial Design and Objectives for Patients With Prostate Cancer: Recommendations From the Prostate Cancer Working Group 4.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502834},
doi = {10.1200/JCO-25-02834},
pmid = {41744290},
issn = {1527-7755},
abstract = {PURPOSE: The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer.

METHODS: We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer.

RESULTS: PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)-defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework.

CONCLUSION: PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator-naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.},
}