@article {pmid41363715,
year = {2025},
author = {Wassertheil-Smoller, S and Larson, JC and Xue, X and Greywoode, R and Bohm, M and Liu, L and Wallace, R and Wactawski-Wende, J and Haring, B and LaMonte, M},
title = {Low Diastolic Blood Pressure and Risk of Ischemic Colitis in the Women's Health Initiative Cohort.},
journal = {The American journal of gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ajg.0000000000003878},
pmid = {41363715},
issn = {1572-0241},
abstract = {OBJECTIVES: To identify risk and protective factors in older women for incidence of ischemic colitis (IC) and 30-day mortality.

METHODS: We conducted a prospective study of 100,825 women in the Women's Health Initiative, with average of 13.1 years follow-up and extensive phenotypic and outcomes data in diverse race and ethnic groups. Lasso Cox regression selected variables related to incidence of ischemic colitis from multiple domains (demographic, comorbidities, risk factors, biomarkers, psychosocial factors, dietary factors). Cox regressions modelled the selected variables to obtain adjusted hazard ratios and 95% confidence limits.

RESULTS: Incidence rate of IC was twice as high among those with history of cardiovascular disease (55.7 per 10,000 person-years (py)) compared to those with no such history (27.3 per 10,000 py). After adjustment for multiple covariates, higher risk was associated with diastolic blood pressure below 90mmHg, using two or more types of antihypertensive medication compared to none (aHR =1.62, 95%CI: 1.47, 1.78), having gastrointestinal symptoms (aHR = 1.31, 95%CI: 1.20, 1.42 highest versus lowest quartile). Higher fiber intake was associated with lower risk, (aHR per increase of 10 grams per day = 0.93, 95%CI: 0.89, 0.97) Black women had lower adjusted risk of IC than White women (aHR = 0.73, 95%CI: 0.63, 0.83). Post IC 30-day all-cause mortality was 10.6% sepsis was an important cause of death.

CONCLUSIONS: Incidence rate of IC in older women was twice as high in those with a history of cardiovascular disease and was associated with low diastolic blood pressure and multi-class antihypertensive treatment. Dietary fiber intake was associated with lower risk. Black women had lower risk of IC compared to White women.},
}

@article {pmid41363134,
year = {2025},
author = {Murphy, NR and Snidarich, M and Budak, JZ and Brown, MC and Weiner, BJ and Giustini, N and Caverly, TJ and Ross, K and DeCell, K and Crothers, K and Triplette, M},
title = {Tensions in Implementation: A Mixed-Methods Evaluation of a Lung Cancer Screening Shared Decision-Making Aid for People With HIV.},
journal = {Health promotion practice},
volume = {},
number = {},
pages = {15248399251388644},
doi = {10.1177/15248399251388644},
pmid = {41363134},
issn = {1552-6372},
abstract = {People with HIV (PWH) are at increased risk for lung cancer, but lung cancer screening (LCS) is understudied in this population. We previously adapted a shared decision-making (SDM) aid for PWH and demonstrated its efficacy in improving LCS knowledge. In this study, we conducted a mixed-methods evaluation of the implementation of this aid. Participants were LCS-eligible PWH. Forty participants reviewed HIV-adapted and individually tailored decision aids at SDM visits and completed pre-/post-visit surveys. Fifteen completed semi-structured interviews. Interviews were analyzed using thematic analysis guided by the Health Equity Implementation Framework and triangulated with surveys through joint displays. Participants generally approved of the SDM aid as it explained the risks and benefits of screening, but six key implementation tensions emerged: (1) Participants generally trusted clinician recommendations but highlighted how their lived experience with HIV informed some medical skepticism and desire for autonomy. (2) There was appreciation for HIV-focused material, but emphasis on individuality and the variable experiences of PWH. (3) Participants were interested and motivated regarding LCS but highlighted systemic barriers. (4) The aid improved comfort for many, but increased anxiety or confusion for others. (5) Some preferred SDM with their primary care clinician, while others prioritized the opinion of an LCS-focused clinician. (6) Several were motivated to quit smoking after SDM, while others were reassured to continue smoking by lower-than-expected risk estimates. This adapted decision aid was well-received, but interviews highlighted tensions in implementation. Iterative adaptation of the decision aid and communication strategies is needed to optimize SDM for PWH.},
}

@article {pmid41361127,
year = {2025},
author = {Zvolensky, MJ and Shepherd, JM and Bevers, LM and Redmond, BY and Garey, L and Jo, D and Asfar, T and Castillo-Avilés, R and Santiago-Torres, M and Bricker, JB},
title = {Quit behavior among Hispanic persons who smoke: evaluating differences in nicotine replacement therapy.},
journal = {Journal of behavioral medicine},
volume = {},
number = {},
pages = {},
pmid = {41361127},
issn = {1573-3521},
support = {U54MD015946/MD/NIMHD NIH HHS/United States ; },
abstract = {Hispanic individuals experience significant health disparities related to smoking. Research focused on the methods employed to quit smoking among the Hispanic population is needed to better understand how to increase engagement with evidence-based smoking cessation guidelines and mitigate smoking-related health disparities. The present investigation sought to: (1) document smoking cessation methods used in previous quit attempts, including Nicotine Replacement Therapy (NRT), and (2) test group differences (NRT use vs not) in smoking-related vulnerability processes (i.e., cigarette dependence, perceived barriers for smoking cessation, severity of problems when trying to quit, and number of prior failed quit attempts). Participants were recruited nationally throughout the United States via Qualtrics Panels and were 302 Hispanic adults (38.1% female, Mage = 35.70, SD = 8.63) who endorsed daily cigarette smoking and a prior quit attempt. Results indicated that the most common method of quitting was 'cold turkey' (65.6%), but other methods were also employed (e.g., gradual reduction of cigarettes, enlisting social support). Moreover, there was a substantial number (57.9%) who used NRT in the form of nicotine gum or patch. Additionally, across each of the criterion variables studied, those who had used NRT demonstrated greater cigarette dependence, perceived barriers for smoking cessation, severity of problems when trying to quit, and number of prior failed quit attempts when compared to persons with no such history of NRT use. Overall, these data suggest that history of NRT use may identify a subgroup of Hispanic persons in need of more intensive smoking cessation treatment.},
}

@article {pmid41360798,
year = {2025},
author = {Birukov, A and Lin, N and Mongiovi, J and Razquin, C and Wang, F and Semnani-Azad, Z and Tessier, AJ and Guasch-Ferré, M and Ley, SH and Manson, JE and Sinkey, RG and Haring, B and Shadyab, AH and Balasubramanian, R and Martínez-González, MA and Rexrode, KM and Hu, FB and Zhang, C and Zeleznik, OA and Sasamoto, N},
title = {Plasma metabolomic signature of breastfeeding and risk of cardiometabolic diseases.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-65977-5},
pmid = {41360798},
issn = {2041-1723},
support = {R03CA259659//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01CA49449//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL034594//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U01CA176726//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01CA67262//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {Breastfeeding is inversely associated with cardiometabolic disease incidence in prospective studies; however, the metabolic pathways underlying these associations remain largely unknown. Here, we derive a plasma metabolomic score of lifetime total duration of breastfeeding using elastic net regularized regression in Nurses' Health Studies (n = 4349) and replicate in the Women's Health Initiative (n = 2088). Data include 181 untargeted plasma metabolites profiled by liquid chromatography mass spectrometry using blood samples collected in mid-life, and self-reported lifetime total duration of breastfeeding. We then examine the associations between the metabolite-based breastfeeding score and risk of T2D and CVD using multivariable Cox regression models and replicated in two external cohorts. The metabolite-based breastfeeding score comprised of 5 metabolites (i.e., C54:2 triglyceride, C56:2 triglyceride, C56:3 triglyceride, cotinine, indole-3-propionate), which show a modest but statistically significant correlation with lifetime total duration of breastfeeding. The metabolite-based breastfeeding score significantly inversely associate with T2D incidence (HR = 0.76, 95%CI = 0.71-0.82) and with CVD incidence (HR = 0.88, 95%CI = 0.84-0.93) independent of T2D and CVD risk factors. We identify plasma metabolite profiles in mid-life associated with breastfeeding duration, which is also linked to CVD and T2D risk.},
}

@article {pmid41360064,
year = {2025},
author = {Sehn, LH and Hübel, K and Luminari, S and Scholz, CW and Salar, A and Paneesha, S and Wahlin, BE and Panayiotidis, P and Lee, HP and Jiménez-Ubieto, A and Sancho, JM and Kim, TM and Domingo Domenech, E and Kumode, T and Poh, C and Thieblemont, C and Deeren, D and de Wit, E and Arbushites, M and Vassallo, I and Trneny, M and , },
title = {Tafasitamab, lenalidomide, and rituximab in relapsed or refractory follicular lymphoma (inMIND): a global, phase 3, randomised controlled trial.},
journal = {Lancet (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1016/S0140-6736(25)01778-7},
pmid = {41360064},
issn = {1474-547X},
abstract = {BACKGROUND: Follicular lymphoma is characterised by episodes of remission and relapse, with patients requiring multiple lines of therapy. Lenalidomide plus rituximab is a commonly used immunotherapy combination in patients with relapsed or refractory follicular lymphoma. We aimed to assess the efficacy and safety of adding tafasitamab, a CD19-targeted Fc-enhanced monoclonal antibody, to lenalidomide and rituximab in this setting.

METHODS: This phase 3, double-blind, randomised, placebo-controlled trial (inMIND) was done in 210 centres (including community-based haematology clinics, major hospitals, and academic institutions) in North America, Europe, and the Asia-Pacific region. Adults with relapsed or refractory follicular lymphoma, who had received at least one previous line of systemic therapy, were eligible for enrolment and randomly assigned (1:1) to receive treatment with up to 12 cycles (28-day cycle length) of tafasitamab (12 mg/kg by intravenous infusion on days 1, 8, 15, and 22 of cycles 1-3 and days 1 and 15 of cycles 4-12) or placebo, both with lenalidomide (20 mg/day orally on days 1-21 of cycles 1-12) and rituximab (375 mg/m[2] by intravenous infusion on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2-5). Treatment assignment was achieved via an interactive voice or web response system; patients, investigators, and the funder were masked until the primary analysis. Study endpoints were investigator assessed unless otherwise specified. The primary endpoint was progression-free survival in the intention-to-treat population of all randomised patients; safety was assessed in all randomised patients who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov (NCT04680052) and EUDRA-CT (2020-004407-13) and is active but no longer enrolling.

FINDINGS: Between April 16, 2021, and Aug 10, 2023, a total of 817 patients were assessed for eligibility; 548 patients with relapsed or refractory follicular lymphoma were enrolled and randomly assigned to treatment with either tafasitamab (n=273) or placebo (n=275). 299 (55%) of all randomised patients were male and 249 (45%) were female. The addition of tafasitamab to lenalidomide and rituximab resulted in significantly lower risk of progression, relapse, or death versus placebo (median progression-free survival by investigator 22·4 months [95% CI 19·2 to not evaluable] in the tafasitamab group vs 13·9 months [11·5-16·4] in the placebo group; hazard ratio 0·43 [95% CI 0·32-0·58]; p<0·0001) in the planned primary analysis. Improvement in progression-free survival was confirmed by independent review committee. Adverse events were reported in 272 (99%) of 274 patients in the tafasitamab group and 270 (99%) of 272 patients in the placebo group. Most common adverse events occurring in either the tafasitamab group or placebo group were neutropenia (133 [49%] vs 123 [45%]) and diarrhoea (103 [38%] vs 77 [28%]). There were no deaths due to treatment-related adverse events in the tafasitamab group; two (1%) patients had fatal adverse events related to treatment in the placebo group.

INTERPRETATION: The addition of tafasitamab to lenalidomide and rituximab resulted in a statistically significant and clinically meaningful improvement in progression-free survival, with an acceptable safety profile in patients with relapsed or refractory follicular lymphoma. This combination represents a potential new standard-of-care treatment.

FUNDING: Incyte.},
}

@article {pmid41359796,
year = {2025},
author = {Leaf, RK and Mones, JV and Shenoy, T and Warsame, M and Beltrami-Moreira, M and Panch, S and Leavitt, AD and Zon, RL and Kendall, EK and Shahamatdar, S and Lim, TL and Cui, C and Jiang, D and Kaunfer, SA and Durai, L and Hoge, ST and Dias, JA and Sha, C and Holmes, A and Easton, N and Corley, E and Zhao, E and Li, X and Spelman, A and Amos, CB and Soebbing, DR and Shabih, M and Jamison, T and Liu, B and Hussein, G and Yadav, SK and Elsaid, MI and Owen, DH and Mera, A and Juras, PK and Suresh, A and Heskel, MJ and Huang, JJ and Glezerman, I and Go, RS and Reynolds, K and Al-Samkari, H and Kroll, MH and Leaf, DE},
title = {Immune thrombocytopenia in patients treated with immune checkpoint inhibitors.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025031449},
pmid = {41359796},
issn = {1528-0020},
abstract = {Immune checkpoint inhibitor-associated immune thrombocytopenia (ICI-ITP) has been described in case reports and small case series, but comprehensive data on its incidence, risk factors, clinical features, treatment, and outcomes are lacking. We reviewed medical records of all adults initiating ICI therapy between 2016-2023 at 29 U.S. hospitals across seven major cancer centers to identify cases of ICI-ITP. Multivariable logistic regression was used to identify risk factors, and Cox modeling was performed to assess the association between ICI-ITP, its severity, and mortality. Among 86,467 patients, ICI-ITP occurred in 214 (0.25%). Independent risk factors included lower baseline platelet count, combination ICI therapy, stage 4 cancer, and additional immune-related adverse events. ICI-ITP occurred at a median of 8 weeks (IQR, 4-18) after ICI initiation, with a median nadir platelet count of 41 x109/L (IQR, 17-64). Patients were treated with glucocorticoids (n=106, [49.5%]), immune globulin (n=39 [18.2%]), and thrombopoietin receptor agonists (n=29 [13.6%]). Recovery occurred in 161 patients (75.2%) at a median of 2.3 weeks (IQR, 1.0-5.3). Of 76 patients rechallenged with ICIs, 23 (30.3%) developed recurrent ICI-ITP. ICI-ITP and its severity were associated with higher all-cause mortality, with a nearly threefold increase in risk among patients with severe ICI-ITP compared with those without ICI-ITP (adjusted HR 2.96 [95% CI, 2.14-4.08]). These findings establish ICI-ITP as a rare but clinically significant complication of ICI therapy, provide the first large-scale description of its risk factors and clinical course, and underscore the importance of timely recognition and management.},
}

@article {pmid41358143,
year = {2025},
author = {Othus, M and Patel, SP and Chae, YK and Dietrich, E and Ahluwalia, MS and Kurzrock, R},
title = {Outcomes of Patients with Rare Cancers Treated with Combination Immune Checkpoint Inhibitors With and Without Prior anti-PD-1/L1 Exposure (NCI/SWOG S1609).},
journal = {JCO oncology advances},
volume = {2},
number = {1},
pages = {},
pmid = {41358143},
issn = {2994-9750},
support = {U10 CA180819/CA/NCI NIH HHS/United States ; U10 CA180888/CA/NCI NIH HHS/United States ; UG1 CA233198/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: There are limited data on response and survival outcomes for patients who receive the combination of anti-PD-1 and anti-CLTA-4 after prior failure of an anti-PD-1/L1, in particular among patients with less common cancers. We analyzed a unique trial resource, an NCI-sponsored basket trial for participants with rare solid tumors conducted by SWOG that was open at over 1,000 sites across the USA (S1609/DART). Participants received Ipilimumab (1mg/kg every six weeks) plus nivolumab (240 mg every two weeks) (both intravenously). The trial eligibility allowed prior exposure to anti-PD-1/L1, and our objective was to compare response and survival outcomes for patients with and without prior anti-PD-1/PDL-1.

METHODS: Logistic and Cox regression models were used to evaluate associations between prior anti-PD-1/PDL-1 exposure and the endpoints of clinical benefit rate (CBR) (includes stable disease of at least six months and objective response by RECISTv1.1), progression-free survival (PFS), and overall survival (OS).

RESULTS: CBR was not significantly different between those with and without prior anti-PD-1/L1 exposure, 26% in both groups. There were no significant differences in PFS and OS between patients with and without prior anti-PD-1/L1 exposure on either univariate and multivariable analysis (multivariable hazard ratio, 95% confidence interval and p-value: PFS: 1.18, 0.83-1.68, p=0.36; OS: 1.11, 0.76-1.63, p=0.58).

CONCLUSIONS: There were no statistically or clinically significant differences in outcomes with and without prior anti-PD-1/L1 exposure for patients with a variety of rare cancers treated with nivolumab and ipilimumab. Patients with prior anti-PD-1/L1 exposure should be eligible for clinical trials evaluating combination immunotherapy.},
}

@article {pmid41356727,
year = {2025},
author = {Mohty, M and Ye, Y and Banerjee, R},
title = {Skills, attitude and knowledge for early-career hematologists: a pragmatic, scientific framework.},
journal = {Clinical hematology international},
volume = {7},
number = {4},
pages = {37-40},
pmid = {41356727},
issn = {2590-0048},
}

@article {pmid41354605,
year = {2025},
author = {Cheng, HH and Callis, S and Yu, EY and Delacroix, SE and Sokolova, AO and Tangen, CM and Lerner, SP and Dorff, TB and Lin, DW},
title = {Clinical Trial in Progress: SWOG S2210, a Phase 2 Study of Neoadjuvant Carboplatin for Localized High-risk Prostate Cancer with Germline BRCA1/2 Mutations.},
journal = {European urology focus},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.euf.2025.11.011},
pmid = {41354605},
issn = {2405-4569},
abstract = {SWOG S2210 is a phase 2 trial testing the use of biomarker-guided neoadjuvant carboplatin, a safe and accessible chemotherapy agent, for patients with localized high-risk prostate cancer and inherited BRCA1/2 mutations. The endpoints are pathologic complete response rates and survival outcomes.},
}

@article {pmid41354273,
year = {2025},
author = {Merkel, EC and Gooley, T and Thakar, MS and Furlan, SN and Summers, C and Kirkey, DC and Hadland, B and Burroughs, LM and Carpenter, PA and Petrovic, A and Goshorn, R and Irwin, R and Bleakley, M and Cooper, T and Tarlock, K and Dahlberg, A},
title = {Post Hematopoietic Cell Transplantation Maintenance Therapy with Low-Dose Azacitidine in a Pediatric Population with High-Risk Myeloid Malignancies.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.12.003},
pmid = {41354273},
issn = {2666-6367},
abstract = {BACKGROUND: Patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with high-risk features undergoing hematopoietic cell transplantation (HCT) experience high rates of relapse. Hypomethylating agent azacitidine (AZA) has been explored as post-HCT maintenance therapy at low-doses to prevent relapse based on its potential for clinical efficacy and enhancing the graft-versus-leukemia effect.

OBJECTIVE: To better understand the feasibility, tolerability, and efficacy of post-HCT maintenance AZA in the pediatric population with high-risk myeloid malignancies who underwent allogeneic HCT.

STUDY DESIGN: A retrospective analysis was conducted of 24 pediatric patients (median age 12.4 years) with high-risk myeloid malignancies who received post-HCT AZA at a single institution. Descriptive measures were used to summarize participant characteristics. Point estimates of overall survival (OS) and relapse-free survival (RFS) were obtained using the method of Kaplan and Meier. Point estimates of relapse and non-relapse mortality were summarized using cumulative incidence estimates.

RESULTS: AZA began at a median of 81 days post-HCT. The AZA dose ranged between 32-50 mg/m[2] x 5 days and AZA continued for a median of 9 cycles. No significant myelosuppression or hospitalizations attributed to AZA were observed. Eighteen patients (75%) were diagnosed with grade II acute graft-versus-host disease (GVHD) before AZA initiation; 3 (16.7%) experienced ≤ grade II acute GVHD flares while tapering immunosuppressive treatment (IST) and receiving AZA. Of the 20 patients in remission at 1-year post-HCT, 18 (90%) had completed or were tapering IST. Six patients relapsed and the 3-year point estimate of relapse was 27%. There were 3 deaths due to relapsed disease. The 3-year point estimate of OS was 91% (one of the 3 deaths occurred beyond 3 years, at 3.2 years) and the 3-year estimate of RFS was 73%. The median follow-up among the 21 surviving patients was 29 months (range 12-80).

CONCLUSIONS: This is the largest reported pediatric cohort receiving post-HCT prophylaxis with AZA. Our findings suggest AZA is tolerable with limited toxicity post-HCT and can be administered to pediatric patients with myeloid malignancies as maintenance therapy. Outcomes were favorable warranting further study.},
}

@article {pmid41352870,
year = {2025},
author = {Nagana Gowda, GA and Zhu, W and Raftery, D},
title = {NMR-based metabolomics: Where are we now and where are we going?.},
journal = {Progress in nuclear magnetic resonance spectroscopy},
volume = {150-151},
number = {},
pages = {101564},
pmid = {41352870},
issn = {1873-3301},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; P30 AR074990/AR/NIAMS NIH HHS/United States ; R01 GM138465/GM/NIGMS NIH HHS/United States ; R01 CA119171/CA/NCI NIH HHS/United States ; P30 DK035816/DK/NIDDK NIH HHS/United States ; R01 GM131491/GM/NIGMS NIH HHS/United States ; },
mesh = {*Metabolomics/methods ; Humans ; Magnetic Resonance Spectroscopy/methods ; Mass Spectrometry/methods ; Biomarkers/analysis/metabolism ; Animals ; },
abstract = {The fast-growing field of metabolomics focuses on the analyses of complicated mixtures of small molecules present in biological samples. To date, metabolomics has provided a wealth of information on biological systems and impacted numerous areas of basic and life sciences. A major focus of metabolomics has been on biomedicine with the goal of biomarker discovery, drug discovery and improved mechanistic understanding of the pathogenesis of many human diseases. Analytical methods play a pivotal role in metabolomics, with the two most widely used platforms being nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Among their many complementary capabilities, NMR is generally more reproducible and quantitative, whereas MS is more sensitive. Recent technological advances in NMR have resulted in multifaceted developments, including improvements in sensitivity, resolution and speed, along with expanded metabolite identification and quantitation, which together provide exciting potential for future studies. In addition to NMR developments, the combination of NMR with MS provides numerous benefits that are becoming more evident over time. Hence, the metabolomics field has witnessed an increased number of studies and applications that combine NMR with MS in numerous areas, including new methods development for unknown identification, metabolite quantitation, disease biomarker discovery, mechanistic understanding of disease pathogenesis, and dietary risk factors of diseases among others. This report describes the current status of state-of-the-art methods in NMR-based metabolomics, along with recent advances and future prospects, with an emphasis on the benefits of combining NMR with MS.},
}

*Metabolomics/methods
Humans
Magnetic Resonance Spectroscopy/methods
Mass Spectrometry/methods
Biomarkers/analysis/metabolism
Animals

@article {pmid41351880,
year = {2025},
author = {Wang, K and Saniei, S and Poddar, N and Martinez, IG and Chao, C and Autar, S and Fiore, P and Carcamo, S and Sreenath, M and Peplinski, JH and Ries, RE and Mei, AH and Rahman, NA and Mekerishvili, L and Quijada-Álamo, M and Freed, G and Zhang, M and Lachman, K and Diaz, Z and Gonzalez, MM and Zhang, J and Pham, G and Filipescu, D and Berisa, M and Balestra, T and Wheeler, N and Reisz, JA and D'Alessandro, A and Puleston, DJ and Bernstein, E and Chipuk, JE and Wunderlich, M and Tasian, SK and Marcellino, BK and Glass, IA and , and Sturgeon, CM and Landau, DA and Chen, Z and Papapetrou, EP and Izzo, F and Meshinchi, S and Hasson, D and Wagenblast, E and , },
title = {Ontogeny Dictates Oncogenic Potential, Lineage Hierarchy, and Therapy Response in Pediatric Leukemia.},
journal = {Cancer discovery},
volume = {},
number = {},
pages = {OF1-OF30},
doi = {10.1158/2159-8290.CD-25-0556},
pmid = {41351880},
issn = {2159-8290},
support = {R01CA292503//National Institutes of Health (NIH)/ ; R01CA290681//National Institutes of Health (NIH)/ ; S10OD026880//National Institutes of Health (NIH)/ ; S10OD030463//National Institutes of Health (NIH)/ ; //CureSearch for Children's Cancer (CSCC)/ ; //Edward P. Evans Foundation/ ; V2024-015//V Foundation for Cancer Research (VFCR)/ ; //Pew Charitable Trusts (Pew)/ ; 77-23//Damon Runyon Cancer Research Foundation (DRCRF)/ ; 7039-25//Leukemia and Lymphoma Society (LLS)/ ; 22-25847//Alex's Lemonade Stand Foundation for Childhood Cancer (ALSF)/ ; //Rally Foundation (Rally)/ ; R24HD000836//National Institutes of Health (NIH)/ ; //Leukemia and Lymphoma Society (LLS)/ ; //Andrew McDonough B+ Foundation (AMBF)/ ; P30CA196521//National Institutes of Health (NIH)/ ; UL1TR004419//National Center for Advancing Translational Sciences (NCATS)/ ; },
abstract = {UNLABELLED: Accumulating evidence links pediatric cancers to prenatal transformation events, yet the influence of the developmental stage on oncogenesis remains elusive. We investigated how hematopoietic stem cell developmental stages affect leukemic transformation, disease progression, and therapy response using a novel, humanized model of NUP98::NSD1-driven pediatric acute myeloid leukemia that is particularly aggressive with WT1 comutations. Fetal-derived hematopoietic stem cells readily transform into leukemia, and WT1 mutations further enhance stemness and alter lineage hierarchy. In contrast, stem cells from later developmental stages become progressively resistant to transformation. Single-cell analyses revealed that fetal-origin leukemia stem cells exhibit greater quiescence and reliance on oxidative phosphorylation than their postnatal counterparts. These differences drive distinct therapeutic responses despite identical oncogenic mutations. In patients, onco-fetal transcriptional programs correlate with worse outcomes. By targeting key vulnerabilities of fetal-origin leukemia cells, we identified combination therapies that significantly reduce aggressiveness, highlighting the critical role of ontogeny in pediatric cancer treatment.

SIGNIFICANCE: This study signifies the critical consequences of developmental timing in cancer initiation, revealing that identical driver mutations in fetal- versus postnatal-origin leukemias exhibit fundamentally distinct biology and treatment responses. Recognizing these developmental differences opens avenues for personalized therapeutic strategies, improving outcomes for pediatric patients with aggressive disease subtypes in leukemia.},
}

@article {pmid41351263,
year = {2025},
author = {Ferrier, K and Graff, M and Konigsberg, IR and Stanislawski, M and Highland, HM and Raffield, LM and Carson, AP and Boerwinkle, E and Norris, JM and Gignoux, CR and Hendricks, AE and Raghavan, S and North, KE and Young, KL and Justice, AE and Allison, MA and Budoff, MJ and Kasela, S and Aguet, F and Joseph, JJ and Kooperberg, C and Rich, SS and Rotter, JI and Lange, EM and Lange, LA},
title = {Epigenome-wide association study meta-analysis of BMI in African Americans.},
journal = {HGG advances},
volume = {},
number = {},
pages = {100552},
doi = {10.1016/j.xhgg.2025.100552},
pmid = {41351263},
issn = {2666-2477},
abstract = {Despite considerable advances in identifying risk factors for obesity, gaps remain in our understanding about its etiology. Genetic variants explain only a small portion of variation in obesity-related traits such as body mass index (BMI). Epigenetic regulation, which controls gene expression and is influenced by environmental and genetic factors, may account for additional variability in BMI. Epigenetic studies of BMI have largely been conducted in European ancestry populations, despite the disproportionate burden of obesity in African Americans (AAs). We conducted a sex-stratified BMI epigenome-wide association study (EWAS) meta-analysis in AA participants from the Jackson Heart Study (JHS, n=1604) and the Multi-Ethnic Study of Atherosclerosis (MESA, n=179) with Illumina EPIC (850k) array data. Linear regression models with methylation as the outcome and continuous BMI as the predictor were stratified by study and sex and meta-analyzed. We identified 208 methylation sites (CpGs, p< 8.72x10[-8]) significantly associated with BMI; 151 not been previously reported in literature. Replication was performed in a separate sample of AA participants with 450k array data, which lacks many CpGs present in the 850k array. Replication testing was possible for only 29 of the 151 CpGs; 19 were statistically significant (p<1.72×10[-3]). Sex-specific results showed 4 female-only and 3 male-only BMI-CpGs not identified in the sex-combined results. Differentially methylated region (DMR) analysis resulted in 66 DMRs, including several regions near genes previously implicated for obesity (e.g., SOCS3 and TGFB1). Further analyses showed enrichment of genes and traits related to the immune system and inflammation-related pathways (e.g., the IL-6/JAK/STAT pathway).},
}

@article {pmid41350402,
year = {2025},
author = {Robertson, AJ and Kerr, B and Feder, AF},
title = {Intracellular interactions shape antiviral resistance outcomes in poliovirus via eco-evolutionary feedback.},
journal = {Nature ecology & evolution},
volume = {},
number = {},
pages = {},
pmid = {41350402},
issn = {2397-334X},
support = {T32-GM136534-02//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 2142718//National Science Foundation (NSF)/ ; },
abstract = {Resistance evolution can undermine antiviral treatment. However, targeting antivirals to shared viral proteins could inhibit resistance evolution if susceptible viruses sensitize resistant ones during cellular coinfection. Pocapavir, a poliovirus capsid inhibitor, uses this sociovirological interference strategy. While susceptible viruses substantially suppress pocapavir resistance in cell culture, a pocapavir clinical trial found widespread resistance and limited clearance time improvements in treated participants. Here, to reconcile these findings, we present an intrahost eco-evolutionary model of pocapavir-treated poliovirus, which reproduces both in vitro interference and clinical resistance evolution. In the short term, high densities of susceptible viruses sensitize resistant ones, mirroring cell culture results. However, over multiple replication cycles, pocapavir's high potency collapses viral density, reducing coinfection and enabling resistance evolution, as observed clinically. Because resistance suppression relies on coinfection, enhancing susceptible virus survival could offer therapeutic advantages. Counterintuitively, we demonstrate that lessening antiviral potency can increase coinfection, limiting resistance while also maintaining low viral load. These findings suggest that antivirals relying on viral intracellular interactions must balance immediate neutralization with preserving future coinfection for sustained inhibition. Explicitly considering the eco-evolutionary feedback encompassing viral density, shared phenotypes and absolute fitness provides new insights for effective therapy design and illuminates viral evolutionary dynamics more broadly.},
}

@article {pmid41348987,
year = {2025},
author = {Kilari, D and Henderson, NC and Yamamoto, K and Yao, Y and Hwang, C and Barata, PC and Bilen, MA and Graham, L and Garje, R and Rothstein, S and Haider, S and Park, JJ and Raychaudhuri, R and Pilling, A and Chin, E and Koshkin, VS and Tripathi, A and Cackowski, FC and Nauseef, JT and Sokolova, A and Ayanambakkam, A and Zakharia, Y and Schweizer, MT and Armstrong, AJ and Dorff, TB and Reichert, ZR and McKay, RR},
title = {Impact of SPOP Mutations on Clinical Outcomes in Metastatic Prostate Cancer.},
journal = {JCO precision oncology},
volume = {9},
number = {},
pages = {e2500590},
doi = {10.1200/PO-25-00590},
pmid = {41348987},
issn = {2473-4284},
mesh = {Humans ; Male ; *Repressor Proteins/genetics ; *Prostatic Neoplasms/genetics/pathology/mortality/drug therapy ; Aged ; Middle Aged ; *Mutation ; *Nuclear Proteins/genetics ; Neoplasm Metastasis ; },
abstract = {PURPOSE: Previous studies suggest that SPOP mutations result in increased sensitivity to androgen receptor pathway inhibitors (ARPIs) but are limited by lack of granular data. We hypothesize that SPOP mutations are associated with improved outcomes across the spectrum of advanced prostate cancer (PC).

METHODS: Using the real-world clinicogenomic Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort database, we analyzed outcomes based on SPOP mutation status. The primary end point was overall survival (OS) from the diagnosis of metastatic disease. Secondary end points included real-world progression-free survival (PFS) and PSA90 response.

RESULTS: Among 2,097 patients with metastatic PC, 5.5% (N = 115) had SPOP-mutated tumors. Compared with SPOP wild-type, patients with SPOP mutations were older at diagnosis (median 65 v 63 years; P = .001) and had higher (≥8) Gleason sum (68% v 54%; P = .02), higher incidence of lung metastasis (17% v 6%; P = .001), and increased frequency of intraductal features (13% v 5%; P < .001). SPOP mutations were associated with improved PSA90 response with first ARPI exposure in the castrate-resistant setting (60% v 40.6%; OR, 2.20 [95% CI, 1.15 to 4.19]; P = .02) but not in the castrate-sensitive setting (78.9% v 71.5%; OR, 1.49 [95% CI, 0.66 to 3.37]; P = .43). Median PFS with first ARPI did not differ in SPOP-mutated versus wild-type group in both the castrate-sensitive (24.2 v 19.2 months; hazard ratio [HR], 0.80 [95% CI, 0.49 to 1.32]; P = .39) and castrate-resistant settings (15.0 v 12.4 months; HR, 0.81 [95% CI, 0.58 to 1.12]; P = .20). In multivariable analysis, SPOP mutations were associated with improved OS (HR, 0.65, P = .02).

CONCLUSION: SPOP mutations were associated with longer OS despite the presence of aggressive clinical features. The distinct clinical and molecular features of SPOP-mutated PC support its consideration as a unique molecular subtype with prognostic implications.},
}

Humans
Male
*Repressor Proteins/genetics
*Prostatic Neoplasms/genetics/pathology/mortality/drug therapy
Aged
Middle Aged
*Mutation
*Nuclear Proteins/genetics
Neoplasm Metastasis

@article {pmid41348052,
year = {2025},
author = {Dima, D and Banerjee, R and Hansen, DK},
title = {CAR T-cell therapy and bispecific antibodies in the management of multiple myeloma.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {324-333},
doi = {10.1182/hematology.2025000721},
pmid = {41348052},
issn = {1520-4383},
mesh = {Humans ; *Multiple Myeloma/therapy/immunology ; *Antibodies, Bispecific/therapeutic use ; *Immunotherapy, Adoptive/methods ; *Receptors, Chimeric Antigen/therapeutic use/immunology ; B-Cell Maturation Antigen/immunology ; },
abstract = {The introduction of CAR (chimeric antigen receptor) T-cell therapy and bispecific antibodies into clinical practice has revolutionized the treatment landscape of relapsed/refractory multiple myeloma (RRMM). Both modalities have shown impressive clinical efficacy with slightly different but overall manageable toxicity profiles. At present, two B-cell maturation antigen (BCMA)-targeted CAR T-cell therapies, idecabtagene vicleucel and ciltacabtagene autoleucel, are approved for standard use in the United States. There are currently 4 commercially approved bispecific antibodies: teclistamab, elranatamab, and linvoseltamab, which target BCMA, as well as talquetamab, which targets the GPRC5D antigen on the surface of plasma cells. In this review, we explore (a) the advantages and challenges of integrating CAR T-cell therapy earlier in the RRMM treatment course; (b) the safety and efficacy of bispecific antibodies and their evolving role in the current RRMM treatment paradigm; (c) practical considerations for both modalities, focusing on patient selection and supportive care strategies; and (d) recommendations for sequencing of T-cell redirecting therapies to maximize long-term outcomes.},
}

Humans
*Multiple Myeloma/therapy/immunology
*Antibodies, Bispecific/therapeutic use
*Immunotherapy, Adoptive/methods
*Receptors, Chimeric Antigen/therapeutic use/immunology
B-Cell Maturation Antigen/immunology

@article {pmid41348047,
year = {2025},
author = {Raychaudhuri, S and Cassaday, RD and Percival, MM},
title = {Peri-transplant conundrums: optimizing maintenance therapy using MRD-directed approaches.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {523-530},
doi = {10.1182/hematology.2025000745},
pmid = {41348047},
issn = {1520-4383},
mesh = {Humans ; Neoplasm, Residual ; *Hematopoietic Stem Cell Transplantation ; *Leukemia, Myeloid, Acute/therapy/genetics ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/genetics ; Antibodies, Bispecific/therapeutic use ; Sorafenib/therapeutic use ; Azacitidine/therapeutic use ; Aniline Compounds/therapeutic use ; *Maintenance Chemotherapy/methods ; Pyrazines ; },
abstract = {Improved understanding of the molecular underpinnings of acute leukemia has led to advances in the detection of very low levels of leukemia-specific abnormalities, known as measurable residual disease (MRD). The limit of detection for modern next-generation sequencing and polymerase chain reaction-based assays is as low as 10-6, allowing for quantitative and longitudinal monitoring in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In the period surrounding allogeneic hematopoietic cell transplantation (HCT), detectable MRD is clearly associated with poor outcomes, primarily due to an increased risk of morphologic relapse. In this review, we address the use of maintenance therapy for patients with acute leukemia, including those who are MRD-positive prior to and following HCT. Post-HCT azacitidine may have a role for MRD-positive AML. In AML with FLT3-internal tandem duplication mutation, post-HCT gilteritinib and sorafenib can be evidence-based strategies to target MRD. In ALL, blinatumomab is a powerful tool to eradicate MRD in patients with Philadelphia (Ph)-positive or Ph-negative ALL; tyrosine kinase inhibitors are indicated for post-HCT management of Ph+ ALL. Despite these advances, the optimal duration and type of intervention still remain unknown for many patients with acute leukemia who have peri-HCT MRD.},
}

Humans
Neoplasm, Residual
*Hematopoietic Stem Cell Transplantation
*Leukemia, Myeloid, Acute/therapy/genetics
*Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/genetics
Antibodies, Bispecific/therapeutic use
Sorafenib/therapeutic use
Azacitidine/therapeutic use
Aniline Compounds/therapeutic use
*Maintenance Chemotherapy/methods
Pyrazines

@article {pmid41348027,
year = {2025},
author = {Wang'ondu, RW and Loh, ML},
title = {Revisiting novel genomic classifiers in the era of immunotherapy for pediatric B-ALL.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {252-261},
doi = {10.1182/hematology.2025000712},
pmid = {41348027},
issn = {1520-4383},
mesh = {Humans ; Child ; *Immunotherapy/methods ; *Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy/genetics ; *Genomics ; Antibodies, Bispecific/therapeutic use ; Neoplasm, Residual ; Inotuzumab Ozogamicin/therapeutic use ; Algorithms ; Male ; },
abstract = {While recent improvements in survival for pediatric patients with newly diagnosed B-cell precursor acute lymphoblastic leukemia (B-ALL) have been attributed to risk stratification algorithms incorporating somatic genetics and early response dictating therapeutic intensity, recent antibody-based immunotherapeutic agents are changing the therapeutic landscape. Blinatumomab, inotuzumab ozogamicin, and chimeric antigen T-cell receptor therapies are approved by the US Food and Drug Administration for the treatment of relapsed and refractory B-ALL in children, and some have been incorporated into frontline therapies. Studies in both pediatric and adult patients have recently demonstrated superiority of adding blinatumomab to the consolidation phase of treatment in the frontline setting. Revisiting genomic classifiers of B-ALL in the era of antibody-based immunotherapeutic agents may be necessary to maximize the benefits of current risk stratification algorithms in combination with immunotherapy. Available data suggest the efficacy of these agents across genomic subtypes. Here we consider the impact of immunotherapeutic agents within the context of minimal residual disease and molecular classification-based risk stratification.},
}

Humans
Child
*Immunotherapy/methods
*Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy/genetics
*Genomics
Antibodies, Bispecific/therapeutic use
Neoplasm, Residual
Inotuzumab Ozogamicin/therapeutic use
Algorithms
Male

@article {pmid41348023,
year = {2025},
author = {Ali, N and Sandmaier, BM},
title = {New age HCT conditioning regimens: what works and why?.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {465-475},
doi = {10.1182/hematology.2025000738},
pmid = {41348023},
issn = {1520-4383},
mesh = {Humans ; *Transplantation Conditioning/methods ; *Hematopoietic Stem Cell Transplantation/methods ; Busulfan/analogs & derivatives/therapeutic use ; Radioimmunotherapy/methods ; },
abstract = {Conditioning regimens play an essential role in allogeneic transplantation by facilitating engraftment and eradicating malignancies. The landscape of conditioning regimens has undergone an evolution in the concept of intensity. Novel conditioning strategies aim to provide highly efficacious regimens with improved toxicity profiles. Integrating disease- specific chemotherapy and targeted agents into conditioning regimens provides enhanced disease elimination and relapse prevention. Agents like treosulfan provide safer conditioning with a favorable toxicity profile for patients with older age or medical comorbidities and can lower the incidence of long-term complications for younger patients. Additionally, methodologies for precise and targeted radiation delivery with minimal off-target effects are emerging. A promising development is radioimmunotherapy-based regimens that preferentially deplete hematopoietic cells and spare nonhematopoietic tissues. These advancements necessitate reexamination and harmonization of conditioning intensity stratification schemes for a more personalized and selective approach.},
}

Humans
*Transplantation Conditioning/methods
*Hematopoietic Stem Cell Transplantation/methods
Busulfan/analogs & derivatives/therapeutic use
Radioimmunotherapy/methods

@article {pmid40135838,
year = {2025},
author = {Iravani, A},
title = {Beyond the AJR: When Nonmetastatic Disease Is No Longer Nonmetastatic.},
journal = {AJR. American journal of roentgenology},
volume = {225},
number = {5},
pages = {e2532975},
doi = {10.2214/AJR.25.32975},
pmid = {40135838},
issn = {1546-3141},
}

@article {pmid41348020,
year = {2025},
author = {Pigazzi, M and Meshinchi, S and Locatelli, F},
title = {Using genomics to refine pediatric AML risk stratification.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {270-278},
doi = {10.1182/hematology.2025000714},
pmid = {41348020},
issn = {1520-4383},
mesh = {Humans ; *Leukemia, Myeloid, Acute/genetics/diagnosis/metabolism/therapy ; Nucleophosmin ; *Genomics/methods ; Child ; Mutation ; Risk Assessment ; Male ; Female ; },
abstract = {In the past 20 years, advances in genomic technologies have greatly improved our understanding of pediatric acute myeloid leukemia (AML). Today, cytogenetic tests can detect structural changes in approximately 75% of cases and remain a main tool for assessing risk. Recent technologies, such as next-generation sequencing, are revealing additional structural alterations (cryptic fusions) and mutations that often cooperate to influence disease biology and treatment response. This evolving genetic landscape has identified unique childhood subtypes of AML defined by specific fusions, such as NUP98::NSD1, CBFA2T3::GLIS2, and varied KMT2A rearrangements, which are linked to distinct clinical outcomes. Emerging data also point to the poor prognosis associated with certain subtypes of NPM1, like the NPM1-D isoform. Additionally, mutations in genes like WT1, DNMT3A, and TP53, the latter of which are rare in childhood AML, may influence patients' outcomes, particularly when occurring in combination. Targeted therapies, including FLT3, BCL2, and menin inhibitors, are beginning to reshape treatment, offering more personalized approaches. However, integrating these drugs effectively into the patient's treatment strategy remains challenging due to the genetic complexity and rarity of pediatric AML. Key issues ahead include identifying which genetic features truly affect outcomes, using this information to personalize therapy, predicting who will benefit from targeted drugs, and choosing the best markers to track disease response over time. Looking forward, collaborative efforts are urgently needed to validate pediatric-specific biomarkers, test novel drug combinations, and link genetic data to clinical outcomes to design trials and future treatment strategies.},
}

Humans
*Leukemia, Myeloid, Acute/genetics/diagnosis/metabolism/therapy
Nucleophosmin
*Genomics/methods
Child
Mutation
Risk Assessment
Male
Female

@article {pmid41347997,
year = {2025},
author = {Panch, SR and Raman, G and Bussel, JB},
title = {Refractory ITP: revisiting definitions, diagnostics, and management paradigms.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {312-323},
doi = {10.1182/hematology.2025000720},
pmid = {41347997},
issn = {1520-4383},
mesh = {Humans ; *Purpura, Thrombocytopenic, Idiopathic/diagnosis/therapy/physiopathology/blood ; Hemorrhage/therapy ; Platelet Count ; Disease Management ; },
abstract = {Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by decreased platelet counts and a variable propensity for bleeding. Significant strides have delineated the pathophysiologic mechanisms of ITP and led to new therapeutics. Despite these advances, 5% to 30% of patients persist with low platelet counts and/or ongoing bleeding. This review summarizes the current definitions and pathophysiology of refractory ITP, revisiting diagnostic realms and management strategies for these difficult-to-treat patients.},
}

Humans
*Purpura, Thrombocytopenic, Idiopathic/diagnosis/therapy/physiopathology/blood
Hemorrhage/therapy
Platelet Count
Disease Management

@article {pmid41347988,
year = {2025},
author = {Gupta, S and McNeer, J and O'Brien, M and Rau, R and Teachey, D},
title = {The challenge of deintensifying chemotherapy for children and adolescents with B-ALL in the immunotherapy era.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {229-235},
doi = {10.1182/hematology.2025000709},
pmid = {41347988},
issn = {1520-4383},
mesh = {Humans ; Adolescent ; Child ; *Immunotherapy/methods ; *Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy/drug therapy/immunology ; Female ; Male ; },
abstract = {Recent clinical trials have shown that the addition of immunotherapy has substantially improved cure rates for children and adolescents newly diagnosed with B-acute lymphoblastic leukemia. Most of these patients now have outcomes similar to those previously seen in only the most favorable subgroups. As such, efforts are underway to study whether the incorporation of immunotherapy can allow for elements of traditional toxic chemotherapy to be removed while maintaining excellent outcomes. In this article, we discuss important considerations for such studies, including those related to which patients are appropriate targets of deintensification efforts and which elements of therapy are or are not appropriate candidates for omission.},
}

Humans
Adolescent
Child
*Immunotherapy/methods
*Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy/drug therapy/immunology
Female
Male

@article {pmid41347976,
year = {2025},
author = {Cassaday, RD},
title = {Sanctuary sites and extramedullary relapses in the chemo-free world: insights from immunotherapies in B-ALL.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {245-251},
doi = {10.1182/hematology.2025000711},
pmid = {41347976},
issn = {1520-4383},
mesh = {Humans ; *Immunotherapy/methods ; *Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy/pathology/immunology ; Recurrence ; Tumor Microenvironment ; },
abstract = {When acute lymphoblastic leukemia (ALL) involves extramedullary sites, the appropriate pathologic term for this is lymphoblastic lymphoma. The biological mechanisms underpinning this process are not clear, but they are presumed to involve a multifactorial interplay between tumor cells and the microenvironment of the tissue in which they develop (eg, lymph nodes, thymus, leptomeninges). Importantly for clinicians, these factors may impair the efficacy of systemic therapy given to treat ALL. This gives rise to "sanctuary sites," so named because of the relative protection they provide to malignant blasts that may possess these characteristics. This has become increasingly relevant in the era of "chemotherapy-free" approaches for B-cell ALL, where the potency of antigen-targeted immunotherapies (eg, blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor-modified T cells) has been leveraged to reduce or eliminate the reliance on cytotoxic chemotherapy. Such approaches are appealing for their high response rates and favorable toxicity profiles compared to chemotherapy. However, extramedullary relapses have been observed with increased frequency: an outcome historically seen in around 10% of such cases, this can represent over 50% of relapses in some series. This review provides an overview of this emerging issue and what clinicians and investigators can do to address it.},
}

Humans
*Immunotherapy/methods
*Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy/pathology/immunology
Recurrence
Tumor Microenvironment

@article {pmid41346295,
year = {2025},
author = {Alexander, JL and Dávila Saldaña, BJ and Brazauskas, R and Dammalapati, SG and Griffith, LM and Shah, AJ and Shimano, KA and Ochs, HD and Bleesing, J and Ebens, CL and Kapadia, M and Bauchat, A and Kapoor, N and Oved, JH and Eissa, H and Lust, H and Keller, MD and Haines, H and Chandrakasan, S and Talano, JM and Rayes, A and Madden, LM and Shereck, EB and Miller, HK and Forbes Satter, LR and Martinez, CA and Rozmus, J and Bednarski, JJ and Yu, LC and Chellapandian, D and Aquino, VM and Knutsen, AP and Chong, H and Chopek, A and Gillio, AP and Joshi, A and Rangarajan, HG and Moore, TB and Andolina, JR and DeSantes, K and Vander Lugt, MT and Prockop, SE and Shyr, D and Sullivan, KE and Parikh, SH and Weinacht, KG and Torgerson, TR and Marsh, RA and Dvorak, CC and Chan, AY and Haddad, E and Heimall, J and Pulsipher, MA and Leiding, JW and Kohn, DB and Puck, JM and Notarangelo, LD and Rawlings, DJ and Cowan, MJ and Petrovic, A and Pai, SY and Burroughs, LM},
title = {Hematopoietic Cell Transplantation for Wiskott-Aldrich syndrome: A PIDTC Report.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017662},
pmid = {41346295},
issn = {2473-9537},
abstract = {Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to impact overall survival (OS). The influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium (PIDTC) from 1990-2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and 79.7%, respectively. Age ≥5 years, donor type, and a pre-HCT history of severe infection had a negative impact on OS and EFS, whereas pre-HCT autoimmunity had no impact. Reduced intensity regimens were associated with lower T cell and myeloid donor chimerism, particularly when non-busulfan-based regimens were used. Low myeloid donor chimerism was associated with lower platelet counts. Mixed chimerism was not consistently associated with post-HCT autoimmunity. Patients with class I (exon 1-2 missense and intron 5 hotspot variants) and class II variants (all others) had similar pre-HCT clinical symptom severity and no difference in OS, EFS or platelet recovery post-HCT. In conclusion, our study showed excellent long-term OS and EFS following HCT for WAS, highlighting the importance of early HCT, before the development of severe infections. We confirmed that HCT using busulfan-based conditioning was associated with improved donor chimerism and platelet recovery. This study was registered at www.clinicaltrials.gov as #NCT02064933.},
}

@article {pmid41279816,
year = {2025},
author = {Giorgi, EE and Gillespie, K and Domin, E and Fouda, G and Permar, SR and Montefiori, DC and Janes, H},
title = {Differences in neutralization susceptibility between clade C HIV viruses from breastmilk versus contemporaneous circulating viruses from sexually acquired infections.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279816},
issn = {2692-8205},
support = {INV-036842/GATES/Gates Foundation/United States ; INV-007368/GATES/Gates Foundation/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; R01 AI162245/AI/NIAID NIH HHS/United States ; P01 AI117915/AI/NIAID NIH HHS/United States ; },
abstract = {HIV viruses that establish infection possess phenotypic and genotypic characteristics that have been selected for and that differ across transmission routes, including their susceptibility to broadly neutralizing antibodies (bnAbs). While sexually transmitted viruses have been well characterized, studies of vertically transmitted viruses are sparse and from cohorts that are often small in size and more than a decade old. To investigate whether viruses transmitted vertically during lactation possess distinct neutralization profiles compared to viruses transmitted sexually, we compared the neutralization sensitivity of 25 clade C breastmilk viruses to that of 99 contemporaneous clade C viruses from sera of adults with sexual acquisition against three bnAbs in clinical development. Three out of 7 breastmilk donors (43%) had one or more viruses resistant to 2 or more bnAbs, compared to 8 out of 99 (8%) contemporaneous adult viruses (p=0.02). Breastmilk viruses were more resistant to PGT121 and VRC07.523 (median IC80 >50 compared to 1.16 for PGT121, and 12.75 vs. 0.38 for VRC07.523; p=0.013 and <0.001 respectively), and more breastmilk viruses than adult viruses were resistant to VRC07.523 (94% vs. 43%, p=0.001). Interestingly, the breastmilk viruses most resistant to VRC07.523 had on average one or more glycans in V3 compared to adult transmitted viruses (median 3 vs. 2 glycosylation sites, including flanking position 295; p=0.009), and the number of V3 glycans was negatively correlated with VRC07.523 sensitivity (p=0.007). These findings highlight potential differences in bnAb susceptibility of vertically transmitted viruses and emphasize the need to increase sequencing efforts and screening of infant viruses to better inform the efficacy of candidate bnAbs to prevent vertical transmission of HIV.},
}

@article {pmid41347212,
year = {2022},
author = {Ak, Ç and Chitsazan, AD and Gönen, M and Etzioni, R and Grossberg, AJ},
title = {Spatial prediction of COVID-19 pandemic dynamics in the United States.},
journal = {ISPRS international journal of geo-information},
volume = {11},
number = {9},
pages = {},
pmid = {41347212},
issn = {2220-9964},
support = {K08 CA245188/CA/NCI NIH HHS/United States ; },
abstract = {The impact of COVID-19 across the United States has been heterogeneous, with rapid spread and greater mortality in some areas compared with others. We used geographically-linked data to test the hypothesis that the risk for COVID-19 is defined by location and sought to define which demographic features are most closely associated with elevated COVID-19 spread and mortality. We leveraged geographically-restricted social, economic, political, and demographic information from US counties, to develop a computational framework using structured Gaussian processing to predict county-level case and death counts during the pandemic's initial and nationwide phases. After identifying the most predictive information sources by location, we applied an unsupervised clustering algorithm and topic modelling to identify groups of features most closely associated with COVID-19 spread. Our model successfully predicted COVID-19 case counts of unseen locations, after examining case counts and demographic information of neighboring locations, with overall Pearson's correlation coefficient and the proportion of variance explained of 0.96 and 0.84 during the initial phase and 0.95 and 0.87, respectively, during the nationwide phase. Aside from population metrics, presidential vote margin was the most consistently selected spatial feature in our COVID-19 prediction models. Urbanicity and 2020 presidential vote margins were more predictive than other demographic features. Models trained using death counts showed similar performance metrics. Topic modeling showed that counties with similar socioeconomic and demographic features tended to group together, and some of these grouped feature sets were associated with COVID-19 dynamics. Clustering of counties based on these feature groups found by topic modeling revealed groups of counties that experienced markedly different COVID-19 spread. We conclude that topic modeling can be used to group similar features and identify counties with similar features in epidemiologic research.},
}

@article {pmid41346251,
year = {2025},
author = {Hershman, DL and Till, C and Leblanc, M and Ramsey, S and Unger, JM},
title = {Development and validation of a risk prediction model for acute care use among older advanced cancer patients on clinical trials.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf342},
pmid = {41346251},
issn = {1460-2105},
abstract = {BACKGROUND: patients with advanced cancer are at risk for unplanned Emergency Department (ED) visits and hospital stays (HS). The purpose was to develop and validate a risk prediction model to identify patients at the highest risk for acute care use.

METHODS: We identified advanced cancer patients ≥65 years treated on SWOG trials from 1999-2014 using data linked to Medicare claims. The primary outcome was acute care use (ED visits or HS). A 60% random sample training set was used to identify candidate variables. An adverse risk model was built by summing adverse factors and creating high vs low-risk groups by splitting at the median. This risk model was tested in the 40% validation set.

RESULTS: Among N = 1397 patients from 6 trials, 839 comprised the training set. The proportion of patients with ≥1 HS/ED visit was 67.5%. Adverse risk factors were performance status (0 vs.≥1), coronary artery disease, hypertension, and liver disease. Patients with ≥2 factors (high-risk; 57.3%) vs. 0/1 risk factor (low-risk; 42.7%) were more likely to experience acute care (79.6% vs. 51.1%), corresponding to a > 3-fold increase in odds (OR = 3.38, 95%CI , 2.48-4.62). Results were similar in the test set, indicating successful validation. Among all patients, quartile-level proportions were 48.9% for zero risk factors vs. 84.0% for 3/4 risk factors. The C-statistic was 0.703.

CONCLUSIONS: A limited set of 4 variables predicted a threefold increased risk of acute care use in older patients with advanced cancer. Personalized interventions aimed at preventing acute care use could improve the quality of cancer care.},
}

@article {pmid41345384,
year = {2025},
author = {Shadman, M and Harper, JS and Bokun, A and Xu, C and Lin, P and Graf, G and Lu, X},
title = {Real-world treatment patterns and clinical outcomes among patients with diffuse large B-cell lymphoma in a US healthcare claims database.},
journal = {Blood cancer journal},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41408-025-01412-8},
pmid = {41345384},
issn = {2044-5385},
abstract = {Treatment options for diffuse large B-cell lymphoma (DLBCL) have expanded, but real-world data on treatment patterns and outcomes remain limited. This study examined real-world outcomes in DLBCL patients treated between 10/1/2015 and 6/30/2024. Patients were stratified by lines of therapy (LOT) and treatments (1L rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone [R-CHOP]; 2L stem cell transplant [SCT]; and chimeric antigen receptor T-cell [CAR T] therapy (any LOT). Variables were reported descriptively. Time-to-event outcomes were assessed using the Kaplan-Meier method. LOT data from 9875 patients were included. R-CHOP-based regimens were the most common 1L treatment (61.7%-67.3% in 2016-2023; 49.4% in 2024). Conventional chemoimmunotherapy use decreased in 2L (81.6% in 2016 to 41.9% in 2024) and 3L (47.6% in 2016 to 22.1% in 2024), while novel therapies increased (43.0% in 2L and 55.9% in 3L in 2024). Median overall survival declined across LOT (1L: 58.1 months; 2L: 30.0 months), as did median time to next treatment (1L: 36.1 months; 2L: 10.6 months). Twelve-month treatment failure rates were 36.0% after 1L, 51.8% after 2L, and 42.2% after CAR T. Among CAR T recipients, 93 received one of 36 distinct subsequent regimens, indicating no standard of care. These findings highlight the unmet needs in DLBCL.},
}

@article {pmid41344861,
year = {2025},
author = {Specht, JM and van Geel, JJL and Song, S and Liu, C and Hippe, DS and DiGregorio, NA and Brand, CJ and Linden, HM},
title = {The Role of Estrogen Receptor-Targeted PET with 16α-[18]F-Fluoro-17β-Estradiol in Predicting Response to Endocrine Therapies in Metastatic Breast Cancer: A Metaanalysis.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.270763},
pmid = {41344861},
issn = {1535-5667},
abstract = {[[18]F]16α-fluoro-17β-fluoroestradiol ([[18]F]FES) PET/CT imaging enables whole-body assessment of functional estrogen receptor (ER) expression in metastatic breast cancer (mBC). Identifying imaging biomarkers that predict endocrine therapy (ET) response remains a critical need in optimizing treatment selection. Our objective was to assess the predictive utility of [[18]F]FES PET/CT imaging in determining response to ET, with a focus on interlesional heterogeneity and individual patient outcomes. Methods: A systematic literature review and metaanalysis were conducted using 6 major databases through April 2024. Ten studies met inclusion criteria based on quantitative SUV reporting, use of FES PET/CT in mBC, and correlation with clinical outcomes. All patients had ER-positive mBC and received ET. Primary endpoints included progression-free survival (PFS) and response to ET. Patients were stratified by baseline [[18]F]FES PET/CT SUVmean or SUVmax thresholds (including 1.8) and by interlesional [[18]F]FES heterogeneity (presence of both [[18]F]FES-positive and [[18]F]FES-negative lesions). Results: Responders had a significantly higher baseline SUVmean than nonresponders (standardized mean difference, 0.91; 95% CI, 0.49-1.34; P < 0.001). Patients with a baseline SUVmax below 1.5 were significantly less likely to respond (odds ratio, 0.11; 95% CI, 0.02-0.72; P = 0.02). Across 5 studies, patients with heterogeneous [[18]F]FES uptake had a shorter median PFS (2.4-12.4 mo) than did those with all [[18]F]FES-positive lesions (14.6-23.6 mo), a statistically significant difference (ratio of median PFS, 0.25; 95% CI, 0.17-0.36; P < 0.001). In an individual-level analysis (n = 101), lesion-level [[18]F]FES-heterogeneous uptake was associated with a PFS of 5.5 versus 21.6 mo and a hazard ratio of 5.4 (95% CI, 3.2-9.4; P < 0.001). An [[18]F]FES SUVmax threshold of at least 1.8 was more prognostic of PFS than were higher SUVmax thresholds. Conclusion: [[18]F]FES PET/CT imaging provides prognostic insight beyond static ER testing by identifying functional heterogeneity in mBC. Lesion-level FES heterogeneity based on an SUVmax threshold of 1.8 may help stratify patients unlikely to benefit from ET, guiding more personalized treatment strategies.},
}

@article {pmid41344792,
year = {2026},
author = {, },
title = {Quantifying the fatal and non-fatal burden of disease associated with child growth failure, 2000-2023: a systematic analysis from the Global Burden of Disease Study 2023.},
journal = {The Lancet. Child & adolescent health},
volume = {10},
number = {1},
pages = {22-38},
pmid = {41344792},
issn = {2352-4650},
mesh = {Humans ; Child, Preschool ; *Global Burden of Disease/trends ; *Growth Disorders/epidemiology/mortality ; Infant ; Male ; Disability-Adjusted Life Years ; Female ; Thinness/epidemiology ; Prevalence ; Cost of Illness ; Child Mortality ; },
abstract = {BACKGROUND: Child growth failure (CGF), which includes underweight, wasting, and stunting, is among the factors most strongly associated with mortality and morbidity in children younger than 5 years worldwide. Poor height and bodyweight gain arise from a variety of biological and sociodemographic factors and are associated with increased vulnerability to infectious diseases. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to estimate CGF prevalence, the risk of infectious diseases associated with CGF, and the disease mortality, morbidity, and overall burden associated with CGF.

METHODS: In this analysis we estimated the all-cause and cause-specific (diarrhoea, lower respiratory tract infections, malaria, and measles) disability-adjusted life-years (DALYs) lost and mortality associated with stunting, wasting, underweight, and CGF in aggregate. We combined the burden associated with mild, moderate, and severe forms of CGF: stunting was defined as height-for-age Z scores (HAZ) less than -1, underweight was defined as weight-for-age Z scores (WAZ) less than -1, and wasting was defined as weight-for-height Z scores (WHZ) less than -1, according to WHO Child Growth Standards. Population-level continuous distributions of HAZ, WAZ, and WHZ were estimated for 2000 to 2023 using data from surveys, literature, and individual-level study data. The risk of incidence of, and mortality due to, diarrhoea, lower respiratory infections, malaria, and measles was separately estimated in a meta-regression framework from longitudinal cohort data for Z scores less than -1. Finally, fatal outcomes associated with these diseases were estimated with vital registration, verbal autopsy, and case-fatality data, while non-fatal outcomes were estimated with surveys as well as health-care utilisation and case reporting data. The exposure prevalence and relative risk estimates were from continuous distributions, allowing for direct assessment of the attributable fractions for mild, moderate, and severe stunting, underweight, wasting, and the combined impact of child growth failure within populations. All estimates were age-specific, sex-specific, geography-specific, and year-specific.

FINDINGS: We estimated that, in children younger than 5 years in 2023, CGF was associated with 79·4 million (95% uncertainty interval [UI] 47·0-106) DALYs lost and 880 000 (517 000-1 170 000) deaths. This represented 17·9% (10·6-23·8) of 444 million (434-457) total under-5 DALYs and 18·8% (11·1-25·0) of all 4·67 million (4·59-4·75) under-5 deaths. Compared to stunting (33·0 million [24·1-42·2] DALYs, 373 000 [272 000-477 000] deaths) and wasting (39·2 million [23·8-53·0] DALYs, 428 000 [256 000-583 000] deaths), childhood underweight was associated with the largest share of CGF-related disease burden: 52·2 million (21·9-75·1) DALYs and 573 000 (236 000-824 000) deaths in children younger than 5 years in 2023.

INTERPRETATION: CGF remains a leading factor associated with death and disability in children younger than 5 years, despite global attention and focused interventions to reduce the prevalence of associated CGF indicators. Our findings underscore the need for policies, strategies, and interventions that focus on all indicators of CGF to reduce its associated health burden.

FUNDING: Gates Foundation.},
}

Humans
Child, Preschool
*Global Burden of Disease/trends
*Growth Disorders/epidemiology/mortality
Infant
Male
Disability-Adjusted Life Years
Female
Thinness/epidemiology
Prevalence
Cost of Illness
Child Mortality

@article {pmid41344516,
year = {2025},
author = {Alongi, F and Cuccia, F and Kotecha, R and Campione, M and Louie, AV and Ma, L and Minniti, G and Tree, AC and Dahele, M and Lo, S and Af Rosenschold, PM and Suh, JH and Niyazi, M and Sheehan, J and Guckenberger, M and Sahgal, A},
title = {ESTRO-ISRS clinical practice recommendations for re-irradiation of spinal mestastases with Stereotactic body radiotherapy: delphi consensus supported by a systematic review and meta-analysis.},
journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology},
volume = {},
number = {},
pages = {111304},
doi = {10.1016/j.radonc.2025.111304},
pmid = {41344516},
issn = {1879-0887},
abstract = {BACKGROUND: Stereotactic body radiotherapy (SBRT) is an established treatment for previously unirradiated spinal metastases; however, the literature is limited with respect to SBRT as a re-irradiation salvage therapy. We performed a systematic review and meta-analysis as basis for joint ESTRO-ISRS clinical practice recommendations of salvage SBRT for spinal metastases.

METHODS: A systematic review and meta-analysis were performed using PRISMA methodology, including publications from January 2006 to September 2024, reporting on the clinical outcomes of ≥ 5 patients treated with spine SBRT re-irradiation (≥5 Gy per fraction) for vertebral metastases. These data served as basis for joint ESTRO-ISRS clinical practice recommendations.

RESULTS: After the initial article screen, 20 studies (5 prospective, 15 retrospective) met the inclusion criteria for analysis. A total of 1538 spine metastases were treated in 1284 patients. The median re-irradiation dose was 24 Gy in 2 fractions (range: 16-30 Gy in 1-5 fractions) after a median 30 Gy in 10 fractions of prior conventional radiotherapy. Vertebral compression fracture, nerve root damage, and myelopathy events were observed in a pooled proportion of 5.0 %, 5.6 %, and 1.7 %, respectively. With a median follow-up of 12 months, the pooled 1- and 2-year LC rates were 81 % (95 % CI: 77-86 %) and 70 % (95 % CI: 61-79 %), respectively. Despite the low level of evidence, a consensus was reached after the first round of voting for 11 practice recommendations, suggesting a substantial level of agreement among the experts.

CONCLUSIONS: Re-irradiation with SBRT for spine metastases following prior conventional radiation or SBRT was efficacious, safe, and is a recommended treatment option in appropriately selected patients. Joint practice recommendations are provided on behalf of ESTRO and ISRS to guide clinical practice.},
}

@article {pmid41343677,
year = {2025},
author = {Ersoy-Fazlioglu, B and Lingadahalli, S and Altintas, UB and Cingoz, A and Tekoglu, E and Lok Yu, IP and Dikbas, M and Missaghimamaghani, O and Yavuz, K and Adomat, H and Kulac, I and Morova, T and Xiao, K and Gleave, M and Fazli, L and Cejas, P and Cherkasov, A and Zwart, W and Haffner, MC and Long, HW and Collins, C and Bagci-Onder, T and Lack, NA},
title = {Distinct transcription factor interactions drive HOXB13 activity in different stages of prostate cancer.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {49},
pages = {e2500327122},
doi = {10.1073/pnas.2500327122},
pmid = {41343677},
issn = {1091-6490},
support = {PJT-173331//CIHR | Canadian Institutes of Health Research - Antimicrobial Resistance Research Initiative (AMR)/ ; NIH P50 CA097186//North Spore/ ; 221Z116//TUBITAK | Ulusal Metroloji Enstitüsü, Türkiye Bilimsel ve Teknolojik Araştirma Kurumu (TÜBİTAK UME)/ ; PDF//Prostate Cancer Fight Foundation (PCFF)/ ; },
mesh = {Male ; *Homeodomain Proteins/metabolism/genetics ; Humans ; *Prostatic Neoplasms/metabolism/pathology/genetics ; Receptors, Androgen/metabolism/genetics ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; *Transcription Factors/metabolism/genetics ; Animals ; Mice ; },
abstract = {HOXB13 is a lineage-specific transcription factor that plays a critical role in initiation and progression of prostate cancer (PCa). While most research has focused on the role of HOXB13 on androgen receptor (AR) activity, here we demonstrate that HOXB13 is frequently expressed in AR-negative tumors and is essential for the proliferation of both AR-positive and -negative PCa models. Strikingly, HOXB13 is remarkably selective and has almost no effect on nonprostatic tissues. Despite this common essentiality in PCa, HOXB13 activity is markedly different in AR-negative stem cell-like tumors, where interactions with the AP-1 change the HOXB13 cistrome and interactome. Yet despite these distinct activities, HOXB13 activity is commonly mediated by SMARCD2, a member of the mSWI/SNF chromatin remodeling complex. The HOXB13/SMARCD2 interaction alters chromatin accessibility at HOXB13-binding sites, causing increased proliferation in AR-negative PCa. Overall, this work demonstrates a distinct mechanism of action for HOXB13 and highlights its critical role in AR-negative castration-resistant PCa.},
}

Male
*Homeodomain Proteins/metabolism/genetics
Humans
*Prostatic Neoplasms/metabolism/pathology/genetics
Receptors, Androgen/metabolism/genetics
Cell Proliferation
Gene Expression Regulation, Neoplastic
Cell Line, Tumor
*Transcription Factors/metabolism/genetics
Animals
Mice

@article {pmid41343299,
year = {2025},
author = {Huddleston, J and Bedford, T},
title = {Timely vaccine strain selection and genomic surveillance improve evolutionary forecast accuracy of seasonal influenza A/H3N2.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {41343299},
issn = {2050-084X},
support = {R01 AI165821-01//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {*Influenza A Virus, H3N2 Subtype/genetics/immunology ; Humans ; *Influenza, Human/prevention & control/virology/epidemiology ; *Influenza Vaccines/immunology ; *Evolution, Molecular ; Seasons ; Forecasting ; COVID-19/prevention & control ; SARS-CoV-2 ; Genomics ; Pandemics ; },
abstract = {Evolutionary forecasting models inform seasonal influenza vaccine design by predicting which current genetic variants will dominate in the influenza season 12 months later. Forecasting models depend on hemagglutinin sequences from global public health networks to identify current genetic variants (clades) and estimate clade fitnesses. The lag between collection of a clinical sample and public availability of its sequence averages ∼3 months, complicating the 12-month forecasting problem by reducing our understanding of current clade frequencies. Despite continued methodological improvements to forecasting models, these constraints of a 12-month forecast horizon and 3-month submission lags impose an upper bound on any model's accuracy. The SARS-CoV-2 pandemic revealed that modern vaccine technology reduces forecast horizons to 6 months and expanded sequencing support reduces submission lags to 1 month on average. We quantified the potential effects of these public health policy changes on forecast accuracy for A/H3N2 populations. Reducing forecast horizons to 6 months reduced average absolute forecasting errors to 25% of the 12-month average, while reducing submission lags decreased uncertainty in current clade frequencies by 50%. These results show the potential to improve the accuracy of existing forecasting models through realistic changes to public health policy.},
}

*Influenza A Virus, H3N2 Subtype/genetics/immunology
Humans
*Influenza, Human/prevention & control/virology/epidemiology
*Influenza Vaccines/immunology
*Evolution, Molecular
Seasons
Forecasting
COVID-19/prevention & control
SARS-CoV-2
Genomics
Pandemics

@article {pmid41342729,
year = {2026},
author = {Perkins, RB and Wolf, AMD and Church, TR and Elkin, EB and Skates, SJ and Etzioni, RD and Guerra, CE and Herzig, A and Hoffman, RM and Oeffinger, KC and Raoof, S and Shih, YT and Walter, LC and Zeigler-Johnson, C and Manassaram-Baptiste, D and Smith, RA},
title = {Self-collected vaginal specimens for human papillomavirus testing and guidance on screening exit: An update to the American Cancer Society cervical cancer screening guideline.},
journal = {CA: a cancer journal for clinicians},
volume = {76},
number = {1},
pages = {e70041},
pmid = {41342729},
issn = {1542-4863},
mesh = {Humans ; Female ; *Uterine Cervical Neoplasms/diagnosis/virology ; *Papillomavirus Infections/diagnosis/virology ; *Early Detection of Cancer/methods/standards ; *Specimen Handling/methods/standards ; United States ; Adult ; Middle Aged ; *Vaginal Smears/methods ; Aged ; American Cancer Society ; *Papillomaviridae/isolation & purification ; Mass Screening/methods/standards ; Practice Guidelines as Topic ; Vagina/virology ; Human Papillomavirus Viruses ; },
abstract = {This update expands the 2020 American Cancer Society (ACS) cervical cancer screening guideline for average-risk women and individuals with a cervix who are at average risk, to include self-collection for human papillomavirus (HPV) testing and revised guidance for exiting cervical cancer screening. Self-collected vaginal specimens, a method of primary HPV testing, align with the ACS cervical cancer screening guideline. When clinician-collected cervical specimens are used for HPV testing, repeat screening is recommended every 5 years for those with a negative test. For self-collected vaginal specimens, the ACS endorses the following recommendations of the Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee (of which it is a member): (1) primary HPV screening using clinician-collected cervical specimens is preferred, and self-collected vaginal specimens are acceptable for average-risk individuals aged 25-65 years; and (2) repeat testing in 3 years is recommended after a negative result on a self-collected HPV screening test. These recommendations apply only to combinations of collection devices and HPV assays approved by the US Food and Drug Administration for HPV testing in a clinical setting or at home. The rationale notes that the use of self-collected vaginal specimens can overcome barriers to screening for many patients, but most patients who test HPV-positive will require extra follow-up steps, and data on long-term, real-world effectiveness are limited. For certain high-risk individuals, clinician-collected samples are still recommended. Furthermore, in response to high rates of cervical cancer among individuals older than 65 years and with poor implementation of current exiting screening criteria, ACS has amended the 2020 guideline to recommend HPV testing at ages 60 and 65 years, with the last HPV test at an age no younger than 65 years as a requisite to exiting screening. The revised recommendation states: To qualify for discontinuation of screening, the ACS recommends an average-risk woman or an individual with a cervix at average risk have negative primary HPV tests (preferred) or negative co-testing using HPV tests and cytology (acceptable) at ages 60 and 65 years. If primary HPV tests or co-testing are not available, three consecutive negative cytology (Papanicolaou) tests at the recommended screening interval with the last test at age 65 years are acceptable. If self-collected vaginal specimens are used for HPV testing, the 3-year testing interval should be followed. Additional screening exit stipulations relate to women at higher risk because of prior abnormal test results or current immune suppression.},
}

Humans
Female
*Uterine Cervical Neoplasms/diagnosis/virology
*Papillomavirus Infections/diagnosis/virology
*Early Detection of Cancer/methods/standards
*Specimen Handling/methods/standards
United States
Adult
Middle Aged
*Vaginal Smears/methods
Aged
American Cancer Society
*Papillomaviridae/isolation & purification
Mass Screening/methods/standards
Practice Guidelines as Topic
Vagina/virology
Human Papillomavirus Viruses

@article {pmid41340045,
year = {2025},
author = {Omame, A and Iyaniwura, SA and Ebenezer, A and Han, Q and Wang, X and Bragazzi, NL and Kong, JD and Woldegerima, WA},
title = {Pre-exposure vaccination in the high-risk population is crucial in controlling mpox resurgence in Canada.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-025-12172-y},
pmid = {41340045},
issn = {1471-2334},
abstract = {As mpox spread continues across several endemic and non-endemic countries around the world, vaccination has become an integral part of the global response to control the epidemic. Some vaccines have been recommended for use against mpox by the World Health Organization (WHO). As the roll-out of mpox vaccines continue across the globe, it is imperative to develop mathematical models to support public health officials and governments agencies in optimizing vaccination strategies to curtail the resurgence of mpox. In this article, we develop a compartmental mathematical model to investigate the impact of vaccination in controlling a potential mpox resurgence in Canada. The model categorizes individuals into high- and low-risk groups and incorporates pre-exposure vaccination in the high-risk group and post-exposure vaccination in the high- and low-risk groups. The vaccine-free version of the model was calibrated to the daily reported cases of mpox in Canada from April to October 2022, from which we estimated key model parameters, including the sexual and non-sexual transmission rates. Furthermore, we calibrated the full model to the daily reported cases of mpox in Canada in 2024, to estimate the current mpox vaccination rates in Canada. Our results highlight the importance of pre-exposure vaccination in the high-risk group on controlling a potential resurgence of mpox in Canada, and the minimal effects of post-exposure vaccination in the high- and low-risk groups on the outbreak. In addition, our model predicts the possibility of mpox becoming endemic in Canada, in the absence of pre-exposure vaccination in the high-risk group. Overall, our modeling result suggests that pre-exposure vaccination in the high-risk group is crucial in controlling mpox outbreak in Canada. Stepping up this vaccination is sufficient to avert a potential mpox resurgence in Canada.Clinical trial number Not applicable.},
}

@article {pmid41338864,
year = {2025},
author = {Scordo, M and Perales, MA and Mauguen, A and Lin, A and Kunvarjee, B and Paes Pena, M and Mcavoy, D and Nguyen, LK and Hogan, M and Chapman, N and Bieler, J and Cho, C and Gyurkocza, B and Harris, AC and Spitzer, B and O'Reilly, RJ and Jakubowski, AA and Lin, RJ and Papadopoulos, EB and Politikos, I and Ponce, DM and Shaffer, BC and Shah, GL and Tamari, R and Giralt, SA and Boelens, JJ and Curran, KJ},
title = {Model-based antithymocyte globulin dosing in ex vivo CD34+ selected allogeneic haematopoietic cell transplantation: a single-centre, single-arm, phase 2 study.},
journal = {The Lancet. Haematology},
volume = {12},
number = {12},
pages = {e956-e965},
doi = {10.1016/S2352-3026(25)00293-5},
pmid = {41338864},
issn = {2352-3026},
mesh = {Humans ; *Antilymphocyte Serum/administration & dosage/therapeutic use ; *Hematopoietic Stem Cell Transplantation/methods/adverse effects ; Male ; Female ; Middle Aged ; Adult ; Graft vs Host Disease/prevention & control/etiology ; *Antigens, CD34/metabolism ; *Transplantation Conditioning/methods ; Transplantation, Homologous ; *Hematologic Neoplasms/therapy/mortality ; Aged ; Melphalan/administration & dosage ; },
abstract = {BACKGROUND: Ex-vivo CD34+ selected allogeneic haematopoietic cell transplantation (HCT) provides favourable chronic graft-versus-host disease (GVHD)-free relapse-free survival but is limited by delayed immune reconstitution and early non-relapse mortality. High anti-thymocyte globulin (ATG) exposure after HCT has been associated with delayed CD4+ T-cell immune reconstitution, increased non-relapse mortality, and poor overall survival.

METHODS: We report the final analysis of a single-centre, phase 2 trial investigating pharmacokinetic model-based ATG (targeting <20 AU × d/mL post-HCT exposure) in participants of any age undergoing ex vivo CD34+ selected allogeneic HCT after myeloablative conditioning for haematological malignancies. Two myeloablative conditioning regimens were used at the discretion of the treating physician: the chemotherapy-based regimen (target cumulative exposure of 65 mg × h/L busulfan, 140 mg/m[2] melphalan, and 150 mg/m[2] fludarabine) and a high-dose total-body irradiation-based regimen (included total-body irradiation [1375 cGy], thiotepa [10 mg/kg], and cyclophosphamide [100 mg/kg]). The primary objective was an improvement in CD4+ immune reconstitution (>50 cells per μL at two consecutive timepoints by day +100) in at least 32% of the per protocol population. This study was registered with ClinicalTrials.gov (NCT04872595) and is completed.

FINDINGS: Between June 14, 2021, and Nov 28, 2023, we enrolled 59 participants with haematological malignancies. Among evaluable participants (n=56), the median age was 55 years (IQR 30-63), 34 (61%) were male, 22 (39%) were female, 44 (79%) had myeloid malignancies, and 44 (79%) had received chemotherapy-only myeloablative conditioning. The median estimated ATG exposure after HCT was 10 AU × d/mL (IQR 9-11). CD4+ immune reconstitution was reached in 39 (70%) of 56 participants, meeting the study's primary endpoint. The most common grade 3 or worse adverse events were infections (103 [40%] of 259 events) and oral or gastrointestinal events (44 [17%] of 259 events). Grade 5 adverse events occurred in three participants including secondary graft failure (n=1) and multi-organ failure (n=2), with a total of four treatment-related deaths among participants.

INTERPRETATION: These results demonstrate that model-based ATG dosing promotes robust CD4+ immune reconstitution after ex vivo CD34+ selected allogeneic HCT, underscoring the potential of pharmacokinetically guided ATG as a strategy to optimise immune recovery in myeloablative, calcineurin inhibitor-free transplantation for haematological malignancies.

FUNDING: US National Cancer Institute, Memorial Sloan Kettering Cancer Center.},
}

Humans
*Antilymphocyte Serum/administration & dosage/therapeutic use
*Hematopoietic Stem Cell Transplantation/methods/adverse effects
Male
Female
Middle Aged
Adult
Graft vs Host Disease/prevention & control/etiology
*Antigens, CD34/metabolism
*Transplantation Conditioning/methods
Transplantation, Homologous
*Hematologic Neoplasms/therapy/mortality
Aged
Melphalan/administration & dosage

@article {pmid41338709,
year = {2025},
author = {Pandey, S and Anderson, N and Snidarich, M and Tsosie, U and Omernik, B and Brown, MC and Crothers, K and Walsh, C and Budak, JZ and Brooks, E and Echo-Hawk, A and Triplette, M},
title = {Common Determinants of Lung Cancer Screening Uptake in Three High-Risk and Underserved Communities.},
journal = {Journal of the American College of Radiology : JACR},
volume = {22},
number = {12},
pages = {1552-1566},
doi = {10.1016/j.jacr.2025.08.018},
pmid = {41338709},
issn = {1558-349X},
mesh = {Humans ; *Lung Neoplasms/diagnostic imaging/diagnosis ; Male ; Female ; *Early Detection of Cancer/statistics & numerical data ; Focus Groups ; Middle Aged ; Qualitative Research ; United States ; Aged ; *Vulnerable Populations ; Medically Underserved Area ; Adult ; Healthcare Disparities ; },
abstract = {OBJECTIVE: Though lung cancer screening (LCS) has significant mortality benefits and has been recommended by the US Preventive Services Task Force since 2013, uptake has been low, especially in most underserved populations. The objective of this study was to harmonize qualitative data from three parallel studies focused on communities with historically high rates of tobacco use and who face lung cancer disparities-people with human immunodeficiency virus; individuals that identify as lesbian, gay, bisexual, transgender, queer or questioning, and others; and urban-dwelling American Indian or Alaska Native individuals-to understand common barriers and facilitators to LCS to inform clinical programming.

METHODS: This qualitative study re-analyzed deidentified focus group transcripts from three recently conducted qualitative studies performed in partnership with these communities. Participants were all eligible, or near eligible, for LCS by US Preventive Services Task Force 2021 criteria. Transcripts were analyzed using inductive thematic analysis, with final themes mapped to the Health Equity Implementation Framework.

RESULTS: A total of 26 focus groups or interviews were analyzed, including a total of 109 participants (people with human immunodeficiency virus, n = 43; individuals that identify as lesbian, gay, bisexual, transgender, queer or questioning, and others, n = 21; American Indian or Alaska Native, n = 45). Fifteen themes emerged that represented common determinants of LCS behavior across the domains of the Health Equity Implementation Framework. Themes demonstrated broad interest in LCS and preventive health care but multilevel barriers to LCS engagement and completion. Participants endorsed facilitators such as community engagement, patient-provider information sharing, and patient navigation to enhance LCS uptake.

DISCUSSION: Despite several barriers to screening that contribute to low uptake, there are facilitators that could be used through multilevel interventions to support LCS in underserved high-risk populations.},
}

Humans
*Lung Neoplasms/diagnostic imaging/diagnosis
Male
Female
*Early Detection of Cancer/statistics & numerical data
Focus Groups
Middle Aged
Qualitative Research
United States
Aged
*Vulnerable Populations
Medically Underserved Area
Adult
Healthcare Disparities

@article {pmid41338220,
year = {2025},
author = {Shao, Y and Tran, Q and Feng, Y and Kolekar, P and Liu, Y and Liang, Z and Fan, L and McBride, A and Jones, T and Cameron, A and Mulder, H and Ji, L and Huang, BJ and Klco, JM and Meshinchi, S and Zhang, J and Carroll, WL and Loh, ML and Easton, J and Brown, PA and Ma, X},
title = {Analysis of error profiles of indels and structural variants in deep-sequencing data.},
journal = {Cell genomics},
volume = {},
number = {},
pages = {101082},
doi = {10.1016/j.xgen.2025.101082},
pmid = {41338220},
issn = {2666-979X},
abstract = {Despite extensive studies of the error profiles of SNVs, those of insertions/deletions (indels)/structural variants (SVs) remain elusive. Using ultra-deep sequencing, we show that the error rates of indel/SVs are >100-fold lower than those of SNVs, although repeat indels have high error rates of 1%. We validated this pattern in a cohort of 103 patients with relapsed B cell acute lymphoblastic leukemia (B-ALL). We analyzed repeat indels in 339 cancer driver genes and demonstrated that the number of repeat units is highly predictive of the error rate. We then analyzed minimal residual disease samples from 72 patients with relapsed B-ALL and demonstrated that our approach had positive detections in 61% of cases, outperforming clinical flow cytometry (51% detection). Overall, we established indel and SV error profiles in deep next-generation sequencing (NGS) data, enabling superior tumor detection at very low burdens, which has a significant impact on the clinical diagnosis and monitoring of human cancers and other diseases.},
}

@article {pmid41338217,
year = {2025},
author = {Li, Q and Song, Q and Chen, Z and Choi, J and Moreno, V and Ping, J and Wen, W and Li, C and Shu, X and Yan, J and Shu, XO and Cai, Q and Long, J and Huyghe, JR and Pai, R and Gruber, SB and Yang, Y and Casey, G and Wang, X and Toriola, AT and Li, L and Singh, B and Lau, KS and Zhou, L and Zhang, Z and Wu, C and Peters, U and Zheng, W and Long, Q and Yin, Z and Guo, X},
title = {Large-scale integration of omics and electronic health records to identify potential risk protein biomarkers and therapeutic drugs for cancer prevention.},
journal = {American journal of human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajhg.2025.11.008},
pmid = {41338217},
issn = {1537-6605},
abstract = {Identifying risk protein targets and their therapeutic drugs is crucial for effective cancer prevention. Here, we conduct integrative and fine-mapping analyses of large genome-wide association studies data for breast, colorectal, lung, ovarian, pancreatic, and prostate cancers and characterize 710 lead variants independently associated with cancer risk. Through mapping protein quantitative trait loci (pQTLs) for these variants using plasma proteomics data from over 75,000 participants, we identify 365 proteins associated with cancer risk. Subsequent colocalization analysis identifies 101 proteins, including 74 not reported in previous studies. We further characterize 36 potential druggable proteins for cancers or other disease indications. Analyzing >3.5 million electronic health records, we conducted analyses of emulated trials for 11 drugs across 290 comparisons and identified three drugs significantly associated with reduced colorectal cancer risk: caffeine vs. paroxetine (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.41-0.64), haloperidol vs. prochlorperazine (HR, 0.47; 95% CI, 0.33-0.68), and trazodone hydrochloride vs. paroxetine (HR, 0.49; 95% CI, 0.38-0.63). Conversely, caffeine was associated with increased cancer risk in comparison with finasteride (colorectal cancer) and fluoxetine (breast cancer). Meta-analysis identified six drugs significantly associated with cancer risk, including acetazolamide, which was associated with reduced colorectal cancer risk (HR, 0.79; 95% CI, 0.72-0.87). This study identifies previously unreported protein biomarkers and candidate drug targets across six major cancer types and highlights several approved drugs with potential chemopreventive effects.},
}

@article {pmid41337691,
year = {2025},
author = {Necchi, A and Guerrero-Ramos, F and Crispen, PL and Herrera-Imbroda, B and Garje, R and Szabados, B and Peyton, CC and Pradere, B and Ku, JH and Shore, N and Bögemann, M and Preston, MA and Xylinas, E and Sanchez de Llano, C and Gong, C and Hasan, M and Urtishak, K and Battaglia, S and Stitou, H and Bhanvadia, S and Sweiti, H and Psutka, SP},
title = {Gemcitabine intravesical system plus cetrelimab or cetrelimab alone as neoadjuvant therapy in patients with MIBC: primary analysis and biomarker results of SunRISe-4.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {101200JCO2502382},
doi = {10.1200/JCO-25-02382},
pmid = {41337691},
issn = {1527-7755},
abstract = {PURPOSE: Standard of care for muscle-invasive bladder cancer (MIBC) is radical cystectomy (RC) with neoadjuvant cisplatin-based chemotherapy (NAC). However, many patients are ineligible for or refuse cisplatin. SunRISe-4 (NCT04919512) is an open-label, multicenter, parallel-cohort phase II study assessing neoadjuvant gemcitabine intravesical system (TAR-200) plus cetrelimab or cetrelimab monotherapy in patients with MIBC.

PATIENTS AND METHODS: Adults with ECOG performance status 0-1, cT2-T4a N0M0, ineligible/refusing NAC, and planned for RC were randomized 5:3, stratified by TURBT completeness (residual tumor ≤3 cm permitted) and T stage, to receive TAR-200 plus cetrelimab (Cohort 1 [C1]) or cetrelimab monotherapy (C2). The primary endpoint was pathologic complete response (pCR) at RC. Secondary endpoints included recurrence-free survival (RFS) and safety. Exploratory endpoints included pathological overall response (pOR; ≤ypT1N0) and circulating and urinary tumor DNA (ct/utDNA) molecular residual disease. Side-by-side descriptive efficacy summary was planned.

RESULTS: At May 9, 2025, data cutoff, 159 patients were treated; 88 in C1 and 46 in C2 underwent RC. pCR, pOR, and 1-year RFS rates were 38%, 53%, and 77%, respectively, in C1 and28%, 44%, and 64% in C2. pCR rates were consistent across subgroups. No new safety signals were observed. Across cohorts, utDNA- status before RC (week 12) and utDNA clearance correlated with pCR (P<10[-5] and <10[-3], respectively). ctDNA- status at baseline and week 12 was associated with longer RFS compared with ctDNA+ status at the same timepoint (P=.04 and .01, respectively).

CONCLUSIONS: TAR-200 plus cetrelimab provided higher pCR, pOR, and 1-year RFS rates compared with cetrelimab monotherapy, supporting further investigation of the neoadjuvant combination in MIBC. utDNA and ctDNA MRD results support further investigation as biomarkers for residual local and non-local disease, respectively.},
}

@article {pmid41337582,
year = {2025},
author = {Dighe, K and Colak, O and Moitra, P and Alafeef, M and Skrodzki, D and Aditya, T and Saha, P and Gunaseelan, N and Hural, J and Pinto, C and Pan, D},
title = {Distinguishing active HIV-1 infection from vaccine-induced seropositivity in HIV vaccine trial participants.},
journal = {Science advances},
volume = {11},
number = {49},
pages = {eadz5639},
pmid = {41337582},
issn = {2375-2548},
mesh = {Humans ; *AIDS Vaccines/immunology/adverse effects ; *HIV-1/immunology ; *HIV Infections/diagnosis/immunology/blood/virology/prevention & control ; HIV Antibodies/immunology/blood ; ROC Curve ; HIV Core Protein p24/immunology ; RNA, Viral/blood ; *HIV Seropositivity/diagnosis/immunology ; Male ; Sensitivity and Specificity ; Female ; },
abstract = {Vaccine-induced seropositivity (VISP) causes antibodies produced by HIV-1 vaccines to react with standard serological tests, complicating diagnosis and leading to false positives. To distinguish VISP from true HIV infections, we developed a rapid, multiplexed companion electrochemical assay that integrates a three-dimensional-printed device with screen-printed electrodes coated with antigen, antibody, and methylene blue-labeled antisense oligonucleotide probes. The test delivers quantitative results within 5 minutes with calculated analytical limits of detection of 5.88 picograms per milliliter for p24 antigen, 10.96 picograms per milliliter for anti-p24 antibody, and 1259 copies per milliliter for HIV-1 RNA, with minimal cross-reactivity. Clinical testing with 104 plasma samples obtained from vaccinated/unvaccinated, HIV-positive/negative individuals demonstrated 95% sensitivity and 98% specificity in distinguishing active HIV-1 infection from VISP cases. Receiver operating characteristic analysis produced area under the curve values of 0.9888 for HIV-1 RNA, 0.9705 for anti-p24 antibody, and 0.9356 for p24 antigen. These findings highlight the potential to reduce false-positive results caused by VISP by integrating this diagnostic test in clinical trials and large-scale vaccination programs.},
}

Humans
*AIDS Vaccines/immunology/adverse effects
*HIV-1/immunology
*HIV Infections/diagnosis/immunology/blood/virology/prevention & control
HIV Antibodies/immunology/blood
ROC Curve
HIV Core Protein p24/immunology
RNA, Viral/blood
*HIV Seropositivity/diagnosis/immunology
Male
Sensitivity and Specificity
Female

@article {pmid41335420,
year = {2025},
author = {Zhao, LP and Papadopoulos, GK and Skyler, JS and Parikh, HM and Kwok, WW and Lybrand, TP and Bondinas, GP and Moustakas, AK and Wang, R and Pyo, CW and Nelson, WC and Geraghty, DE and Lernmark, Å},
title = {Profiling Associations Between IGHG-FCGR Ligand-Receptor Interactions and Disease Progression From Stage 1 and 2 to Stage 3 Type 1 Diabetes.},
journal = {Diabetes},
volume = {},
number = {},
pages = {},
doi = {10.2337/db25-0610},
pmid = {41335420},
issn = {1939-327X},
support = {R01 DK132406/DK/NIDDK NIH HHS/United States ; },
abstract = {UNLABELLED: The primary objective of this study was to investigate whether ligand-receptor interactions (LRIs) between IGHG and FCGR gene products are associated with progression to type 1 diabetes (T1D). Using two completed clinical trials (DPT-1 and TN07), we applied next-generation targeted sequencing to genotype IGHG and FCGR genes in a cohort of 1,214 individuals and assessed LRI associations with disease progression. A Cox regression model was used to quantify LRI associations. IGHG or FCGR alone was found to have weak and sporadic associations with progression. Multiple LRIs between IGHG and FCGR gene products were found to be associated with progression, especially LRIs of IGHG2 with multiple FCGR receptors that accelerate progression and those of IGHG4 with multiple FCGR receptors (some overlapping) that delay progression. Furthermore, as several crystal structures of FcγRs complexed with distinct IgG molecules are known, application of this knowledge here was hampered by the absence of any information on the subclass distribution of each of the several T1D-related autoantibodies. It cannot be excluded that their respective state of glycosylation may influence binding affinity to various FcγRs and the function of thus-formed complexes. Our findings suggest that LRIs of the IGHG and FCGR gene products probably influence progression, shedding new insights into some of the immunological mechanisms involved in progression to T1D. Our findings potentially facilitate the search for new immunotherapeutic treatment through intervening at key steps in the progression.

ARTICLE HIGHLIGHTS: This study investigated ligand-receptor interactions (LRIs) between IGHG and FCGR gene products in type 1 diabetes progression. Genes of 1,214 participants from the DPT-1 and TN07 trials were sequenced using next-generation targeted sequencing technology, and LRI associations with the progression time to type 1 diabetes were analyzed using Cox regression modeling. Weak associations were found for IGHG or FCGR variants individually, but multiple LRIs significantly impacted progression. Several IGHG2-FCGR interactions accelerated progression, while a few other IGHG4-FCGR interactions delayed it. The results may provide insights into certain immunogenetic mechanisms of T1D and suggest therapeutic potential of targeting specific LRIs.},
}

@article {pmid41335170,
year = {2025},
author = {Le, H and Baek, G and Huang, I and Siu, C and Shadman, M},
title = {The Evolving Therapeutic Landscape of Richter Transformation.},
journal = {Current hematologic malignancy reports},
volume = {20},
number = {1},
pages = {21},
pmid = {41335170},
issn = {1558-822X},
mesh = {Humans ; *Leukemia, Lymphocytic, Chronic, B-Cell/therapy/pathology ; Immunotherapy/methods ; Molecular Targeted Therapy ; Protein Kinase Inhibitors/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Lymphoma, Large B-Cell, Diffuse/therapy/pathology ; },
abstract = {PURPOSE OF REVIEW: Richter transformation (RT), the progression of chronic lymphocytic leukemia (CLL) to aggressive lymphomas, poses a significant therapeutic challenge with historically poor outcomes. Chemoimmunotherapy (CIT) regimens have demonstrated limited efficacy with short durations of response. This review aims to evaluate the evolving treatment landscape for RT, with a focus on recent advances in targeted therapies, immunotherapies, and cellular therapies that are redefining the current and future standards of care.

RECENT FINDINGS: The treatment paradigm for RT is rapidly shifting away from cytotoxic chemotherapy. The combination of the B-cell lymphoma 2 inhibitor venetoclax with CIT has emerged as a new first-line benchmark with promising response rates and overall survival. Covalent Bruton tyrosine kinase (BTK) inhibitors had modest activity as monotherapy but showed improved responses when given with an immune checkpoint inhibitor. Pirtobrutinib has demonstrated responses even in heavily pretreated patients. Furthermore, advancement in immunotherapy has expanded treatment options for this patient population with bispecific T-cell engagers achieving high response rates and chimeric antigen receptor T-cell therapy providing deep, durable responses and favorable median overall survival in the relapsed/refractory (R/R) setting. The therapeutic landscape for RT has broadened with the introduction of targeted agents and immunotherapy. Venetoclax-based regimens represent a new standard for chemotherapy-eligible patients, allowing for a more effective bridge to potentially curative consolidation with transplantation. For R/R disease, novel BTK inhibitors, bispecific antibodies, and cellular therapies are demonstrating substantial efficacy. Ongoing trials investigating combinations of these agents are poised to further transform RT management.},
}

Humans
*Leukemia, Lymphocytic, Chronic, B-Cell/therapy/pathology
Immunotherapy/methods
Molecular Targeted Therapy
Protein Kinase Inhibitors/therapeutic use
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
*Lymphoma, Large B-Cell, Diffuse/therapy/pathology

@article {pmid41335105,
year = {2025},
author = {Irinyi, L and Mintzes, B and Warning, J and Collie, L and Rush, A and Turtle, CJ and Byrne, JA},
title = {Long-Term Follow-Up of Patients Receiving Cell and Gene Therapy Products.},
journal = {Human gene therapy},
volume = {},
number = {},
pages = {},
doi = {10.1177/10430342251403439},
pmid = {41335105},
issn = {1557-7422},
abstract = {Cell and gene therapies present unique challenges for long-term follow-up as they may lead to adverse events that could emerge years after treatment. Long-term follow-up helps identify potential delayed adverse events, such as oncogenesis or immunogenicity, which might not manifest immediately after treatment. Current regulatory guidelines emphasize a risk-based approach, recommending follow-up durations based on the therapy's mechanism of action between 5 and 15 years. To facilitate long-term monitoring, regulatory authorities recommend the establishment of long-term follow-up protocols, often involving patient registries and supported by real-world data sources to systematically capture and track data from treated patients. These long-term follow-ups are instrumental in both post-approval safety studies and reimbursement decisions, where payers may link payments to treatment outcomes. As the field of cell and gene therapy evolves, regulatory frameworks continue to adapt, balancing the need for comprehensive long-term follow-up with the feasibility of implementation to ensure that therapies are adequately monitored, ensuring patient safety and therapeutic effectiveness over time. However, maintaining patient engagement over extended periods, ensuring high-quality data collection, and addressing privacy concerns present significant challenges. Innovative solutions such as decentralized data collection, digital health technologies, and data linkage with electronic health records aim to alleviate patient burden and improve data reliability.},
}

@article {pmid41282799,
year = {2025},
author = {Ellis, AL and Stauss, M and Tiburcio, PB and Emmen, IE and Edlefsen, PT and Kosmider, E and Barlow, S and Goss, M and Temte, JL and Stachler, E and McMahon, K and Sabeti, P and O'Connor, DH and O'Connor, SL},
title = {Adaptation of the multiplexed CRISPR-Cas13 CARMEN RVP assay for longitudinal detection of respiratory pathogens from air samples.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282799},
abstract = {Air sampling is a non-invasive alternative to individual testing for respiratory pathogens. Alternative methods to the "gold standard" quantitative RT-PCR (qRT-PCR) are required to enable higher throughput, lower cost, and more multiplexed detection of pathogens. The multiplexed CRISPR-Cas13 CARMEN Respiratory Viral Panel (RVP) was described previously for high-throughput detection of nine respiratory pathogens from nasal swab samples. Here, we modified and optimized the CARMEN RVP assay to overcome the unique challenges of air samples, including low biomass and environmental inhibitors. We monitored for SARS-CoV-2 and influenza A (Flu A) via qRT-PCR in air samples from 15 schools within Dane County, Wisconsin (USA) during the 2023-2024 school year. SARS-CoV-2 was detectable throughout the entire sampling period, while Flu A detection was seasonal from November 2023 to March 2024. We then analyzed a subset of samples from seven schools using an optimized CARMEN RVP assay for air surveillance (RVP_air) and compared results to qRT-PCR. The RVP_air assay detected several additional pathogens beyond our primary targets. The frequencies and patterns of SARS-CoV-2 positivity, but not Flu A, were similar between qRT-PCR and RVP_air across the 2023-2024 sampling period. We developed a secondary panel (RVP_air_flu) to better detect both H1N1 and H3N2 subtypes. Finally, we compared air sample results to clinical nasal swabs collected from the same school district. For several pathogens (SARS-CoV-2, HCoV-OC43, Flu A), positive air detections coincided with positive nasal swabs. These findings demonstrate that the RVP_air assay can effectively detect airborne pathogens from infected individuals within indoor spaces.},
}

@article {pmid41282795,
year = {2025},
author = {Wu, X and Kim, A and Breeze, CE and O'Mara, TA and Ramachandran, D and Dörk, T and Koutros, S and Rothman, N and Prokunina-Olsson, L and Mancuso, N and Lindström, S and Kraft, P},
title = {Prioritizing context-specific genetic risk mechanisms in 11 solid cancers.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282795},
abstract = {BACKGROUND: While genome-wide association studies (GWAS) have identified hundreds of cancer-associated genetic variants, the specific biological contexts where these variants exert their effects remain largely unknown. We aimed to prioritize context-specific genetic risk mechanisms for 11 solid cancers at both genome-wide and single-variant resolutions.

METHODS: We integrated cancer GWAS summary statistics from European ancestry samples (avg. n cases=47,856) with ~1,500 context-specific annotations representing candidate cis-regulatory elements. For genome-wide analysis, we applied CT-FM, a method that leverages heritability enrichment estimates and an annotation correlation matrix to select likely disease-relevant biological contexts. After identifying putative causal SNPs (PIP≥0.5) via functionally informed fine-mapping, we used CT-FM-SNP to identify relevant contexts for individual variants. A combined SNP-to-gene framework was applied to construct putative {regulatory SNP-context-gene-cancer}
quadruplets.

RESULTS: Stratified LD score regression analysis identified 52 annotations with significant heritability enrichment (Bonferroni-corrected P≤0.05). CT-FM prioritized four high-confidence (PIP≥0.5) biological contexts: mammary luminal epithelial cells for breast cancer, a prostate cancer epithelial cell line (VCaP) for prostate cancer, and bulk tumor tissue contexts for colorectal and renal cancers. Variant-level analysis of hundreds of putatively causal SNPs corroborated these findings and identified additional high-confidence contexts for other malignancies, including estrogen receptor-negative breast cancer and bladder cancer. A total of 489 putative regulatory quadruplets were constructed, proposing specific molecular mechanisms underlying the observed GWAS signals.

CONCLUSION: These findings advance our understanding of genetic susceptibility to different cancers. Future work in larger, more diverse GWAS, coupled with more comprehensive annotation atlases, is essential to expand upon and validate our results.},
}

@article {pmid41279922,
year = {2025},
author = {Mihalas, AB and Mitchell, K and Arora, S and O'Connor, SA and Patel, AP and Plaisier, CL and Paddison, PJ},
title = {Characterization of quiescent subpopulations and proliferative compartments in glioblastoma.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279922},
issn = {2692-8205},
abstract = {Glioblastoma (GBM) quiescent (Q) cell populations are hypothesized to contain cancer stem-like cells (CSC) that drive tumor growth, cellular heterogeneity, and recurrence. However, GBM tumors do not neatly resolve into developmental hierarchies and Q stem-like activities are difficult to assess. Here, we evaluated tumor Q subpopulations in patient-derived GBM xenograft tumors using live cell reporters, DNA label retention assays, and single cell genomics. Compared to adult neural stems cells (NSCs), GBM Q populations contain hybrid transcriptional states composed of networks found in both dormant and activated adult NSCs, resulting in constitutive expression of key Q egress transcription factors and their targets (e.g., AP-1 and CCND1/2). As a result, even the longest Q-residing cells (~12 days) in xenograft tumors continuously cycle and fail to enter dormant Q states. We provide evidence and hypothesize that transient Q states in primary tumors arise as part of distinct proliferative compartments rather than deterministic developmental hierarchies driven by CSC activity. We further speculate that increases in basal translation rates drive Q instability in GBM tumors.},
}

@article {pmid41334909,
year = {2025},
author = {Walter, M and Haick, AK and Massa, PA and Klouser, LM and Stensland, L and Santo, TK and Xie, H and Jerome, KR},
title = {Herpes simplex virus 1 strain 17+ with R2 mutation in UL37 has residual retrograde transport.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0195925},
doi = {10.1128/spectrum.01959-25},
pmid = {41334909},
issn = {2165-0497},
abstract = {UNLABELLED: Herpes simplex virus 1 (HSV-1) causes lifelong recurrent infections. Following primary infection of the oral or genital mucosa, HSV-1 travels retrogradely through axons and establishes latency in the cell body of ganglionic neurons of the peripheral nervous system. Periodic reactivation in neurons and anterograde transport of virions back to peripheral regions cause oral or genital ulcerations. Many host and viral factors implicated in retrograde and anterograde transport of HSV-1 have been identified. In particular, studies reported that introducing five amino acid substitutions in the R2 region of the viral tegument protein UL37 was sufficient to completely eliminate retrograde transport of HSV-1 strain F. Here, we introduced the same R2 mutations in the highly neurovirulent HSV-1 strain 17+. We show that this R2[17] virus is highly attenuated in mice and acts as a potent vaccine that protects mice against acute HSV-1 infection. However, we report that the R2[17] virus has residual retrograde transport. We show that R2[17] can establish latency in mouse models of ocular and vaginal infection and reactivate. These results contradict published evidence and show that the R2 mutation is not sufficient to fully prevent retrograde transport of HSV-1.

IMPORTANCE: Herpes simplex virus 1 (HSV-1) is a ubiquitous pathogen without a cure or vaccine. HSV-1 travels through nerves between the oral and genital mucosa and the peripheral nervous system, where it establishes lifelong latency. Studies reported that introducing five amino acid substitutions in the R2 region of the viral tegument protein UL37 was sufficient to completely eliminate the retrograde transport of HSV-1 strain F from the mucosa to the nervous system. Here, we present contradictory findings. We report that an HSV-1 virus from strain 17+ with the same R2 mutation has residual retrograde transport. This shows that the R2 mutation is not sufficient to fully prevent the retrograde transport of HSV-1 in all settings. This finding may be particularly relevant for assessing the safety of prospective live-attenuated vaccines that include the R2 mutation.},
}

@article {pmid41334748,
year = {2025},
author = {Fitzgerald, L and Ghosh, S and Khan, W and Bokun, A and Lax, A and Mu, F and Cook, EE and Chen, J and Chen, G and Wu, E and Lin, Y and Shi, L and Qureshi, ZP and Graf, SA},
title = {Real-world overall survival comparison between first-line Bruton tyrosine kinase inhibitors in treating chronic lymphocytic leukemia/small lymphocytic lymphoma: An analysis of Veterans Health Administration data.},
journal = {Journal of managed care & specialty pharmacy},
volume = {},
number = {},
pages = {1-15},
doi = {10.18553/jmcp.2025.25169},
pmid = {41334748},
issn = {2376-1032},
abstract = {BACKGROUND: Three covalent Bruton's tyrosine kinase inhibitors (BTKis) are approved first-line (1L) treatments for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). However, limited real-world data, especially in veterans, evaluate long-term outcomes associated with the different BTKis.

OBJECTIVE: To describe and compare real-world overall survival (rwOS) among patients with CLL/SLL treated with BTKis in the Veterans Health Administration electronic medical record database.

METHODS: This was a retrospective cohort study of patients with CLL/SLL who initiated 1L monotherapy of ibrutinib, acalabrutinib, or zanubrutinib between November 2019 and September 2023. Patients were grouped into 3 cohorts based on the BTKi initiated: (1) ibrutinib, (2) acalabrutinib, or (3) acalabrutinib or zanubrutinib (given small sample initiating zanubrutinib). Key inclusion criteria were 1L monotherapy treatment with a BTKi, at least 2 diagnoses of CLL/SLL, and continuous enrollment at least 12 months prior to and at least 28 days after the initiation of the BTKi. rwOS comparing the BTKi cohorts was analyzed using Kaplan-Meier methodology and adjusted Cox proportional hazards models. Sensitivity analyses adjusting for different sets of covariates were conducted.

RESULTS: The study included samples of 1,059, 504, and 612 patients treated with ibrutinib, acalabrutinib, and acalabrutinib or zanubrutinib (108 received zanubrutinib), respectively. Median rwOS was not reached in any cohort. In the main analysis comparing the ibrutinib and acalabrutinib cohorts, after adjustment for baseline characteristics, treatment with acalabrutinib was associated with an increased risk of death compared with ibrutinib (hazard ratio [HR], 1.33; 95% CI, 1.01-1.76; P = 0.042). In the main analysis comparing the ibrutinib and acalabrutinib or zanubrutinib cohorts, the adjusted risk of death was numerically higher for acalabrutinib- or zanubrutinib-treated patients compared with ibrutinib (HR, 1.32; 95% CI, 1.00-1.74; P = 0.050). For both comparisons, sensitivity analyses indicated similar trends in rwOS.

CONCLUSIONS: As new therapies emerge, this study highlights the comparative effectiveness of BTKis in the real world, potentially informing current clinical practice.},
}

@article {pmid41334110,
year = {2026},
author = {Kim, Y and Yang, G and Oh, J and Gwak, SY and Kim, KH and Lee, J and Kim, JS and Lee, CG and Cho, J and Ky, B and Yoon, HI and Grassberger, C},
title = {Consolidation ICIs Alter cardiac subregion radiosensitivity in NSCLC patients treated with Chemo-Radiotherapy.},
journal = {Clinical and translational radiation oncology},
volume = {56},
number = {},
pages = {101069},
pmid = {41334110},
issn = {2405-6308},
abstract = {PURPOSE: he addition of immune checkpoint inhibitor (ICI) as consolidation therapy after chemoradiation (CRT) has improved survival rates in non-small cell lung cancer (NSCLC) patients. However, the cardiotoxicity of CRT combined with ICI remains underexplored. This study assesses if ICI exposure alters the critical cardiac subregion linked to radiation-induced heart disease (RIHD) following CRT.

METHODS: We conducted a retrospective analysis of 321 locally advanced NSCLC patients treated with definitive CRT from August 2008 to December 2019, including 67 who received consolidation ICI. Cardiac contours include the entire heart, chambers, major coronary arteries, and conduction nodes. The primary endpoint was RIHD, defined as a major adverse cardiac event and atrial fibrillation. We used Fine-Gray analysis to investigate associations between RIHD and mean doses to cardiac subregions.

RESULTS: In total, 53 patients (18.4 %) developed RIHD, with no significant difference between CRT and CRT + ICI groups. Doses to cardiac subregions were similar between the groups. In the CRT group, multivariable analysis shows that dose to the base of the heart, especially the sinoatrial node (SAN), correlated with increased RIHD risk (HR = 1.02 per 1 Gy, 95 %CI [1.01-1.03], p < 0.001). In the CRT + IO group, the left ventricle (LV) dose was a significant predictor (1.06 [1.06-1.1], p = 0.006).

CONCLUSIONS: Doses to the SAN and the base of the heart correlate with RIHD in CRT patients, while doses to LV in CRT + ICI patients. While the 2-6 % increased risk per Gy seems modest, it is clinically significant as the subregions, being small structures, can potentially be completely spared with a carefully optimized plan.},
}

@article {pmid41333983,
year = {2025},
author = {Hong, G and Walsh, J and Koshy, A and Hsu, JY and O'Dea, AL and Vesely, EM and Memon, W and Dezube, RH and Goss, CH and Goss, LB and Greene, A and Gross, JE and Wilson, A and Nichols, DP and Zhang, SX and Cramer, RA},
title = {Home sputum collection for Aspergillus fumigatus detection in adults with cystic fibrosis.},
journal = {ERJ open research},
volume = {11},
number = {6},
pages = {},
pmid = {41333983},
issn = {2312-0541},
abstract = {BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) has impacted the ability for people with cystic fibrosis (PwCF) to spontaneously expectorate sputum, leading to lower respiratory sampling rates and infection detection challenges. Home sampling may permit a potential strategy for fungal detection in PwCF.

METHODS: We conducted a prospective decentralised cohort study of PwCF to test the feasibility of home sputum collection and ambient temperature transport for Aspergillus fumigatus (Af) detection. Participants collected and shipped weekly sputum samples from home to the laboratory for fungal culture and completed electronic questionnaires. Descriptive statistics were calculated for patient factors, sputum characteristics and Af-positive cultures. We used a generalised estimating equations model to determine the association between highly effective modulator therapy (HEMT) and sputum volume.

RESULTS: We enrolled 76 adults with cystic fibrosis (CF) with a median (interquartile range) forced expiratory volume in 1 s (FEV1) % predicted of 72.5% (53.8-86.3). 60 (79%) were on ETI and 44 (58%) had a history of Aspergillus. 70 (92%) successfully collected and shipped three or more sputum samples. Of 284 samples received, 83% arrived within one day. Sputum collection was reported as easy in 83 (29%) and somewhat easy in 114 (40%) collection events. Sputum volume from PwCF on HEMT was 36% lower than those not on HEMT (36%, 95% CI 3-58; p=0.03), adjusting for covariates. Af was detected in 205 (73%) of home sputum samples.

CONCLUSION: Home sputum collection is feasible in adults with CF. Af was detected in remotely collected sputum samples. Further work to assess the validity of home sputum samples in PwCF is necessary to determine the value of remote specimens in clinical and research settings.},
}

@article {pmid41330919,
year = {2025},
author = {Lai, M and Kim, K and Zheng, Y and Castellani, CA and Ratliff, SM and Wang, M and Liu, X and Haessler, J and Huan, T and Bonsu, K and Newcomb, C and McKessy, K and Bielak, LF and Zhao, W and Joehanes, R and Ma, J and Guo, X and Manson, JE and Grove, ML and Bressler, J and Taylor, KD and Lappalainen, T and Kasela, S and Blackwell, TW and Lake, NJ and Faul, JD and Ferrier, KR and Ekker, SC and Hou, L and Kooperberg, C and Reiner, AP and Zhang, K and Peyser, PA and Fornage, M and Boerwinkle, E and Raffield, LM and Carson, AP and Rich, SS and Liu, Y and Levy, D and Rotter, JI and Smith, JA and Arking, DE and Liu, C and , },
title = {Epigenome-wide association study of nuclear DNA methylation in relation to mitochondrial heteroplasmy.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-65845-2},
pmid = {41330919},
issn = {2041-1723},
abstract = {We analyze 10,986 participants (mean age 77; 63% women; 54% non-White) across seven U.S. cohorts to study the relationship between mitochondrial DNA (mtDNA) heteroplasmy and nuclear DNA methylation. We identify 597 CpGs associated with heteroplasmy burden, generally showing lower methylation. These CpGs are enriched in dynamically regulated island shores and depleted in CpG islands, indicating involvement in context-specific rather than constitutive gene regulation. In HEK293T cells, we introduce a truncating mtDNA mutation (MT-COX3, mt.9979) and observe a positive correlation between variant allele fraction and methylation at cg04569152, supporting a direct mtDNA-nDNA epigenetic link. Many heteroplasmy-associated CpGs overlap with known methylation-trait associations for metabolic and behavioral traits. Composite CpG scores predict all-cause mortality and incident CVD, with one-unit increases associated with 1.27-fold and 1.12-fold higher hazards, respectively. These findings suggest an mtDNA-nDNA epigenetic connection in aging and disease, though its direction and mechanisms remain to be studied.},
}

@article {pmid41330717,
year = {2025},
author = {Park, YH and Cortes, J and Modi, S and Hurvitz, SA and Bianchini, G and Iwata, H and Shitara, K and Siena, S and Goto, Y and Ku, GY and Powell, CA and Swain, SM and Arunachalam, M and Janek, M and Cheng, Y and Chu, C and Verma, P and Kuptsova-Clarkson, N and Mathias, E and Goodman, E and Rugo, HS},
title = {Characterization of the Safety Profile of Trastuzumab Deruxtecan by Dose: A Pooled Analysis Across DESTINY Studies.},
journal = {The oncologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/oncolo/oyaf396},
pmid = {41330717},
issn = {1549-490X},
abstract = {BACKGROUND: Trastuzumab deruxtecan (T-DXd), an approved human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate, may cause treatment-emergent adverse events (TEAEs), most commonly gastrointestinal and hematologic TEAEs. This pooled analysis evaluated TEAEs across two doses of T-DXd in patients with different cancers to support safe and effective real-world use.

PATIENTS AND METHODS: Data were pooled from nine phase I-III clinical trials (DS8201-A-J101; DESTINY-Breast01/02/03/04; DESTINY-Lung01/02; DESTINY-Gastric01/02) of T-DXd 5.4 or 6.4 mg/kg every 3 weeks in patients (N = 1678) with metastatic breast, gastric, or lung cancer with varying HER2 expression or HER2 mutation status. Nausea, vomiting, neutropenia, fatigue, and interstitial lung disease (ILD) were evaluated for time to onset and dose-related outcomes. Antiemetic analysis was limited before a 2020 protocol change recommending prophylaxis.

RESULTS: Common TEAEs (in ≥ 20%) were fatigue, nausea, vomiting, neutropenia, anemia, and thrombocytopenia; mostly grade 1 or 2. TEAEs leading to dose reduction, drug interruption, and discontinuation with T-DXd were 22.6%, 42.8%, and 17.7% (5.4 mg/kg), and 29.7%, 47.6%, and 16.6% (6.4 mg/kg), respectively. Neutropenia, nausea, and fatigue occurred in 34.6%, 74.6%, and 56.5% of patients (5.4 mg/kg) and 49.3%, 65.5%, and 52.8% (6.4 mg/kg). Adjudicated drug-related ILD occurred in 12.0% and 10.9%, respectively.

CONCLUSION: Gastrointestinal and hematologic TEAEs were most common, with nausea, neutropenia, and fatigue most commonly reported. ILD/pneumonitis occurred in ∼11%-12% of patients, with severe cases infrequent. Most TEAEs were low grade, though dose modifications highlight the need for proactive TEAE management, particularly in older patients and those with renal impairment.},
}

@article {pmid41329166,
year = {2026},
author = {Arends, T and Bennett, SR and Tapscott, SJ},
title = {DUX4-induced HSATII RNA accumulation drives protein aggregation, impacting RNA processing pathways.},
journal = {The Journal of cell biology},
volume = {225},
number = {2},
pages = {},
doi = {10.1083/jcb.202501129},
pmid = {41329166},
issn = {1540-8140},
support = {R01AR045203/NH/NIH HHS/United States ; P30 CA015704/NH/NIH HHS/United States ; K99AR081926/NH/NIH HHS/United States ; /AR/NIAMS NIH HHS/United States ; T32CA009657/CA/NCI NIH HHS/United States ; //Fred Hutch/ ; //University of Washington/ ; //Seattle Children's Cancer Consortium/ ; },
mesh = {Humans ; *Homeodomain Proteins/metabolism/genetics ; *Muscular Dystrophy, Facioscapulohumeral/genetics/metabolism/pathology ; *RNA Processing, Post-Transcriptional ; *RNA, Satellite/genetics/metabolism ; Ribonucleoproteins/metabolism/genetics ; *Protein Aggregates ; Animals ; RNA Splicing ; Mice ; },
abstract = {RNA-driven protein aggregation leads to cellular dysregulation and contributes to the development of diseases and tumorigenesis. Here, we show that double homeobox 4 (DUX4), an early embryonic transcription factor and causative gene of facioscapulohumeral muscular dystrophy (FSHD), induces the accumulation of stable intranuclear RNAs, including nucleolar RNA and human satellite II (HSATII) RNA that drive protein aggregation in muscle cells. Specifically, HSATII RNA sequesters RNA methylation factors. HSATII-YBX-1 ribonucleoprotein (RNP) complex formation is mediated by HSATII double-stranded RNA and RNA methylase NSUN2 activity. Aberrant HSATII-RNP complexes affect RNA processing pathways, including RNA splicing. Differential splicing of genes mediated by HSATII-RNP complexes is associated with pathways known to be dysregulated by DUX4 expression. These findings highlight the broader influence of DUX4 on nuclear RNA dynamics and suggest that HSATII RNA could be a critical mediator of RNA processing regulation. Understanding the impact of HSATII-RNP formation on RNA processing provides insight into the molecular mechanisms underlying FSHD.},
}

Humans
*Homeodomain Proteins/metabolism/genetics
*Muscular Dystrophy, Facioscapulohumeral/genetics/metabolism/pathology
*RNA Processing, Post-Transcriptional
*RNA, Satellite/genetics/metabolism
Ribonucleoproteins/metabolism/genetics
*Protein Aggregates
Animals
RNA Splicing
Mice

@article {pmid41282907,
year = {2025},
author = {Reed, JC and Downs, C and McAllister, K and Mauer, C and McClurkan, CL and Wilson, D and Holzhauer, K and Dickerson, JA and Cannon, CA and Babu, TM and Golden, MR and Koelle, DM and Greninger, AL},
title = {Differentiating Mpox Infection and Vaccination Using a Validated Multiplex Orthopoxvirus IgG Serology Assay.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282907},
abstract = {The resurgence of monkeypox virus (MPXV) outbreaks has increased demand for validated serological assays to assess exposure and immunity. Cross-reactivity among orthopoxivuses, stemming from high sequence conservation, complicates distinguishing antibody responses from natural MPXV infection versus vaccination or other orthopoxvirus exposures. We validated the Meso Scale Discovery (MSD) V-PLEX Orthopoxvirus Panel 1 (IgG) Kit, which quantifies antibody levels to five MPXV antigens and their vaccina virus (VACV) orthologs, following Good Clinical Laboratory Practice (GCLP) guidelines. We assessed assay performance using serum from 26 individuals with prior mpox, 52 JYNNEOS vaccine recipients, and 179 unexposed controls. The assay reliably detected antibody responses in all exposed cohorts with peak levels observed 2-months post-vaccination. Antibody levels to specific antigens also correlated with Modified Vaccinia Ankara (MVA) neutralization titer, particularly for MPXV B6R/VACV B5R, MPXV E8L/VACV D8L, and MPXV M1R/VACV L1. Receiver operating characteristic (ROC) analysis showed that some individual antigens achieved high sensitivity and specificity for exposure detection (AUC > 0.96 for VACV D8L, MPXV B6R, VACV B5R); however, individual antigens performed poorly in distinguishing infection from vaccination. In contrast, antibody level ratios between some MPXV and VACV orthologs effectively differentiated MPXV infection from vaccinia vaccination with high sensitivity and specificity (e.g. MPXV A35R/VACV A33R ortholog ratio, AUC = 0.97, sensitivity = 0.97, specificity = 0.96). Our findings validate the MSD assay for clinical research and serosurveillance to assess MPXV immunity and support the utility of ortholog pair ratio analysis as a strategy to discriminate vaccinated and infected individuals.},
}

@article {pmid41328526,
year = {2025},
author = {Zhang, X and Vasan, S and Zheng, C and Prentice, RL and Navarro, SL and Tinker, L and Raftery, D and Gowda, GAN and Van Horn, L and Sun, Y and Tabung, FK and Pan, K and Lampe, JW and Neuhouser, ML},
title = {Calibrated Dietary Patterns and Cancer Risk in the Women's Health Initiative Cohorts.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwaf259},
pmid = {41328526},
issn = {1476-6256},
abstract = {We developed calibration equations using metabolomics from fasting blood and 24-hour urine for Healthy Eating Index 2010 (HEI-2010) and Alternative Healthy Eating Index 2010 (AHEI-2010) to address measurement error from self-reported diet. We examined associations between metabolomic-calibrated dietary patterns and cancer risk in the Women's Health Initiative (WHI, n=108,522). Metabolomic signatures were created from a WHI Feeding (n=153;2010-2014) and WHI Observational Study (n=450;2006-2009). Dietary patterns were regressed on metabolites using the feeding study food intake records. Metabolomic-based dietary patterns were estimated from 24-hour dietary recalls, FFQ and 4DFR in the Observational Study using a stepwise approach. Cox regression estimated cancer risk of metabolomic-calibrated dietary patterns with a median follow-up of 15.8 years. Adjusted R2 for HEI-2010 and AHEI-2010 calibration equations were 57.5% and 48.8% for FFQ, 61.6% and 62.6% for 4DFR, and 52.5% and 53.2% for dietary recalls. Without calibration, a 20% increment in HEI-2010 was associated with lower risk of colorectal (HR=0.94, 95% CI=0.90-0.99), lung (HR=0.90, 95% CI=0.86-0.94), bladder (HR=0.86, 95% CI=0.75-0.99), and total invasive cancers (HR=0.98, 95% CI=0.96-0.99). With metabolomic calibration, higher HEI-2010 was associated with lower risk of lung (HR=0.79, 95% CI=0.71-0.88) and total invasive cancers (HR=0.96, 95% CI=0.92-1.00). Metabolomic-calibrated dietary patterns might mitigate measurement errors and strengthen diet-cancer associations.},
}

@article {pmid41326929,
year = {2025},
author = {Hinkel, RE and Kalima, M and Msadabwe, SC and Mwaba, CK and Ng'uni, FC and Fisa, R and Tambatamba, BC and Chuba, A and Trejo, MJ and Lishimpi, K and Soliman, AS},
title = {False-Positive Screening, Over-Referral, and Length of time between Cervical Cancer Early Detection and Confirmed Diagnosis Over Nine Years in Lusaka, Zambia.},
journal = {Journal of epidemiology and global health},
volume = {},
number = {},
pages = {},
doi = {10.1007/s44197-025-00478-8},
pmid = {41326929},
issn = {2210-6014},
abstract = {PURPOSE: While Zambia has an efficient program for early detection of cervical cancer, most cases are diagnosed at advanced stages. This study examined the time between suspecting cancers at screening clinics and histopathologic confirmation of cervical cancer in the Lusaka Province of Zambia.

METHODS: This study included the records of 3,483 women with suspected cancerous lesions identified by visual inspection of the cervix (VIA) who were referred from Lusaka Province screening facilities from 2014 to 2022. The study linked screening records with corresponding histopathologic results of the lesions after examination at the University Teaching Hospital. Variables abstracted from the medical records included age, human immunodeficiency virus (HIV) status, district of residence and referral clinic, and dates of referral and confirmed diagnosis.

RESULTS: False-positive VIA results constituted about 90% of all referrals. Women living with HIV (WLWH) had longer wait times between screening referrals and receipt of histopathologic results, most notably women coming from rural settings (median of 146 days) compared to urban settings (median of 69 days) (p < 0.05). Among women diagnosed with low-grade intraepithelial lesions, WLWH had a 63% higher risk of confirmed cancer diagnosis (CI: 1.16, 2.29) than women not living with HIV. For high-grade intraepithelial lesions, the adjusted HR showed WLWH having a 17% (CI: 0.89, 1.53) higher risk of confirmed cancer diagnosis compared to women not living with HIV.

CONCLUSION: The high rate of false-positives and long wait times call for expanded service infrastructure, particularly in rural settings, and continuing provider education/training to optimize screening sensitivity and shorten wait times in the Lusaka Province. Such measures may reduce the overload on the existing histopathology infrastructure and may provide lessons for other limited-resource countries facing similar cancer control and prevention challenges.},
}

@article {pmid41326736,
year = {2025},
author = {Peluso, MJ and Sandel, DA and Deitchman, AN and Kim, SJ and Dalhuisen, T and Tummala, HP and Tibúrcio, R and Zemelko, L and Borgo, GM and Singh, SS and Schwartz, K and Deswal, M and Williams, MC and Hoh, R and Shimoda, M and Narpala, S and Serebryannyy, L and Khalili, M and Vendrame, E and SenGupta, D and Whitmore, LS and Tisoncik-Go, J and Gale, M and Koup, RA and Mullins, JI and Felber, BK and Pavlakis, GN and Reeves, JD and Petropoulos, CJ and Glidden, DV and Spitzer, MH and Gama, L and Caskey, M and Nussenzweig, MC and Chew, KW and Henrich, TJ and Yukl, SA and Cohn, LB and Deeks, SG and Rutishauser, RL},
title = {Correlates of HIV-1 control after combination immunotherapy.},
journal = {Nature},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41586-025-09929-5},
pmid = {41326736},
issn = {1476-4687},
abstract = {The identification of therapeutic strategies to induce sustained antiretroviral therapy (ART)-free control of HIV infection is a major priority.[1] Combination immunotherapy including HIV vaccination, immune stimulation/latency reversal, and passive transfer of broadly neutralizing antibodies (bNAbs) has shown promise in non-human primate models,[2-6] but few studies have translated such approaches into people. We performed a single-arm, proof-of-concept study in ten people with HIV on ART combining the following three approaches: (1) therapeutic vaccination with an HIV/Gag conserved element (CE)-targeted DNA+IL-12 prime/MVA boost regimen followed by (2) administration of two bNAbs (10-1074, VRC07-523LS) and a toll-like receptor 9 agonist (lefitolimod) during ART suppression, followed by (3) repeat bNAb administration at the time of ART interruption (NCT04357821). Seven of the ten participants exhibited post-intervention control after stopping ART, independent of residual bNAb plasma levels. Robust expansion of activated CD8+ T cells early in response to rebounding virus correlated with lower median viral load following peak viremia off ART. These data suggest that combination immunotherapy approaches might prove effective to induce sustained control of HIV by slowing rebound and improving CD8+ T cell responses, and that these approaches should continue to be optimized.},
}

@article {pmid41326734,
year = {2025},
author = {Gaebler, C and Kor, S and Allers, K and Perotti, M and Mwangi, D and Meixenberger, K and Hanke, K and Trenkner, T and Kraus, T and Sha, Y and Arentowicz, C and Odidika, S and Grahn, N and Scheck, R and Perkins, N and Pardons, M and Igbokwe, V and Corman, V and Burmeister, T and Blau, O and Sürücü, G and Pruß, A and Schneider, CG and Klausen, G and Sauter, J and Klein, F and Sander, LE and Hofmann, J and Vuong, L and Bullinger, L and Penter, L and Gruell, H and Reeves, DB and Schommers, P and Hoelzemer, A and Obermeier, M and Blau, IW and Schneider, T and Penack, O},
title = {Sustained HIV-1 remission after heterozygous CCR5Δ32 stem cell transplantation.},
journal = {Nature},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41586-025-09893-0},
pmid = {41326734},
issn = {1476-4687},
abstract = {HIV cure is exceptionally rare, documented in only six cases among the estimated 88 million individuals who have acquired HIV since the epidemic's onset[1-6]. Successful cures, including the pioneering Berlin patient, are limited to individuals receiving allogeneic stem cell transplants (allo-SCT) for hematological cancers. HIV resistance from stem cell donors with the rare homozygous CCR5 Δ32 mutation was long considered the main mechanism for HIV remission without antiretroviral therapy (ART), but recent reports highlight CCR5-independent mechanisms as important contributors to HIV cure[6-8]. Here, we provide new evidence for this conceptual shift, reporting exceptionally long, treatment-free HIV remission following allo-SCT with functionally active CCR5. A heterozygous CCR5 wild-type/Δ32 male living with HIV received allo-SCT from an HLA-matched unrelated heterozygous CCR5 wild-type/Δ32 donor as treatment for acute myeloid leukemia. Three years after allo-SCT, the patient discontinued ART. To date, HIV remission has been sustained for over six years with undetectable plasma HIV RNA. Reservoir analysis revealed intact proviral HIV before transplantation, but no replication-competent virus in blood or intestinal tissues after allo-SCT. Declining or absent HIV-specific antibody and T cell responses support the absence of viral activity. High antibody-dependent cellular cytotoxicity (ADCC) activity at the time of transplantation may have contributed to HIV reservoir clearance. These results demonstrate that CCR5Δ32-mediated HIV resistance is not essential for durable remission, underscoring the importance of effective viral reservoir reductions in HIV cure strategies.},
}

@article {pmid41326606,
year = {2025},
author = {Yu, TC and Kikawa, C and Dadonaite, B and Loes, AN and Englund, JA and Bloom, JD},
title = {Pleiotropic mutational effects on function and stability constrain the antigenic evolution of influenza haemagglutinin.},
journal = {Nature ecology & evolution},
volume = {},
number = {},
pages = {},
pmid = {41326606},
issn = {2397-334X},
support = {R01AI165821//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; 75N93021C00015/AI/NIAID NIH HHS/United States ; T32GM007270//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; DGE-2140004//National Science Foundation (NSF)/ ; },
abstract = {The evolution of human influenza virus haemagglutinin (HA) involves simultaneous selection to acquire antigenic mutations that escape population immunity while preserving protein function and stability. Epistasis shapes this evolution, as an antigenic mutation that is deleterious in one genetic background may become tolerated in another. However, the extent to which epistasis can alleviate pleiotropic conflicts between immune escape and protein function/stability is unclear. Here we measure how all amino acid mutations in the HA of a recent human H3N2 influenza strain affect its cell entry function, acid stability and neutralization by human serum antibodies. We find that epistasis has entrenched certain mutations so that reverting to the ancestral amino acid identity in earlier strains is no longer tolerated. Epistasis has also enabled the emergence of antigenic mutations that were detrimental to the cell entry function of HA in earlier strains. However, epistasis appears insufficient to overcome the pleiotropic costs of antigenic mutations that impair the stability of HA, explaining why some mutations that strongly escape human antibodies never fix in nature. Our results refine our understanding of the mutational constraints that shape recent H3N2 influenza evolution: epistasis can enable antigenic change, but pleiotropic effects can restrict its trajectory.},
}

@article {pmid41325870,
year = {2025},
author = {Khouderchah, C and Lynch, RC and Holmberg, LA},
title = {Impact of Post-Autologous Peripheral Blood Stem Cell Transplant (ASCT)- Granulocyte Colony Stimulating Factor (G-CSF) on Toxicity Profiles in Hodgkin Lymphoma (HL) Patients Receiving Pre-ASCT Immune Checkpoint Inhibitors (ICI).},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.11.035},
pmid = {41325870},
issn = {2666-6367},
}

@article {pmid41325737,
year = {2025},
author = {Rillamas-Sun, E and Huang, Y and Langley, BO and Donzella, SM and Cobos, S and Guthrie, KA and Davidson, NE and Di, C and Greenlee, H},
title = {Comparisons of Physical Activity and Sedentary Behavior Measurements From the ActiGraph, International Physical Activity Questionnaire, and Fitbit in Women With History of Breast Cancer.},
journal = {Journal of physical activity & health},
volume = {},
number = {},
pages = {1-9},
doi = {10.1123/jpah.2025-0009},
pmid = {41325737},
issn = {1543-5474},
abstract = {BACKGROUND: Self-reported and wearable device derived data on physical activity (PA) differ in burden, transparency, and validity, underscoring the need for comparison in cancer survivorship research. Physical activity and sedentary behavior measured from the ActiGraph, International Physical Activity Questionnaire (IPAQ), and Fitbit Inspire device in women with early-stage breast cancer were compared.

METHODS: Breast cancer survivors participating in a lifestyle intervention trial concurrently provided ActiGraph and IPAQ data at baseline and 6 months. Fitbit devices were used for PA self-monitoring after randomization and data were available at follow-up only. Comparisons of PA measurements were estimated via Pearson correlation coefficients and visualized using Bland-Altman plots. Prevalence of meeting moderate to vigorous PA guidelines of ≥150 minutes per week were also calculated.

RESULTS: At baseline (n = 73), mean vigorous PA was 2 and 5 minutes per day for ActiGraph and IPAQ, respectively (r = .22, P = .06), while mean sedentary hours per day were 11.4 and 6.2 for ActiGraph and IPAQ, respectively (r = .29, P = .01). Correlations between ActiGraph and IPAQ at 6-month follow-up (n = 50) were not statistically significant. Six-month comparisons of PA measures between ActiGraph and Fitbit (n = 30) were higher than those between IPAQ and Fitbit (n = 30). Prevalence of meeting moderate to vigorous PA guidelines at baseline was 40% for ActiGraph and 59% for IPAQ (P = .01). At 6 months, proportions meeting moderate to vigorous PA guidelines were 50%, 73%, and 67% for ActiGraph, IPAQ, and Fitbit, respectively.

CONCLUSION: Correlations of PA comparing self-report from IPAQ and activity devices from ActiGraph and Fitbit were weak. Strengths and limitations of PA measurement methods should be weighed accordingly in studies of lifestyle interventions for breast cancer survivors.},
}

@article {pmid41325571,
year = {2025},
author = {Tomasini, P and Wang, Y and Li, Y and Felip, E and Wu, L and Cui, J and Besse, B and Spira, AI and Neal, JW and Goto, K and Baik, CS and Marmarelis, ME and Ichihara, E and Zhang, Y and Lee, JS and Lee, SH and Yang, JC and Michels, S and Anastasiou, Z and Curtin, JC and Lyu, X and Mahoney, J and Demirdjian, L and Meyer, CS and Zhang, Y and Leconte, I and Lorenzini, P and Knoblauch, RE and Trani, L and Baig, M and Bauml, JM and Cho, BC and , },
title = {Amivantamab Plus Lazertinib in Atypical EGFR-Mutated Advanced Non-Small Cell Lung Cancer: Results From CHRYSALIS-2.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2402835},
doi = {10.1200/JCO-24-02835},
pmid = {41325571},
issn = {1527-7755},
abstract = {PURPOSE: For patients with advanced non-small cell lung cancer (NSCLC) harboring atypical epidermal growth factor receptor (EGFR) mutations (eg, S768I, L861Q, G719X), efficacy of current treatment options is limited.

PATIENTS AND METHODS: CHRYSALIS-2 Cohort C enrolled participants with NSCLC harboring atypical EGFR mutations (G719X, S768I, L861Q, etc) and ≤2 previous lines of therapy. Participants were treatment-naïve or previously received first- or second-generation EGFR tyrosine kinase inhibitors. Coexisting exon 20 insertions, exon 19 deletions, or exon 21 L858R mutations were exclusionary. Participants received 1,050 mg (1,400 mg if ≥80 kg) intravenous amivantamab once weekly for the first 4 weeks and then once every 2 weeks plus 240 mg oral lazertinib once daily. The primary end point was investigator-assessed objective response rate (ORR).

RESULTS: As of January 12, 2024, 105 participants received amivantamab-lazertinib. Most common atypical mutations were G719X (56%), L861X (26%), and S768I (23%), including single and compound mutations. In the overall population (median follow-up: 16.1 months), the ORR was 52% (95% CI, 42 to 62). The median duration of response (mDoR) was 14.1 months (95% CI, 9.5 to 26.2). The median progression-free survival (mPFS) was 11.1 months (95% CI, 7.8 to 17.8); median overall survival (mOS) was not estimable (NE; 95% CI, 22.8 to NE). Adverse events were consistent with previous studies and primarily grade 1 and 2. Among treatment-naïve participants, the ORR was 57% (95% CI, 42 to 71). The mPFS was 19.5 months (95% CI, 11.2 to NE), the mDoR was 20.7 months (95% CI, 9.9 to NE), and mOS was NE (95% CI, 26.3 to NE). Solitary or compound EGFR mutations had no major impact on ORR. The ORR in participants with P-loop and αC-helix compressing, classical-like, and T790M-like mutations was 45% (n = 38), 64% (n = 14), and 67% (n = 3), respectively.

CONCLUSION: In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals.},
}

@article {pmid41325480,
year = {2025},
author = {Johnson, MM and Sung, K and Haddox, HK and Vora, AA and Araki, T and Victora, GD and Song, YS and Fukuyama, J and Matsen Iv, FA},
title = {Nucleotide context models outperform protein language models for predicting antibody affinity maturation.},
journal = {PLoS computational biology},
volume = {21},
number = {12},
pages = {e1013758},
doi = {10.1371/journal.pcbi.1013758},
pmid = {41325480},
issn = {1553-7358},
abstract = {Antibodies play a crucial role in adaptive immunity. They develop as B cell receptors (BCRs): membrane-bound forms of antibodies that are expressed on the surfaces of B cells. BCRs are refined through affinity maturation, a process of somatic hypermutation (SHM) and natural selection, to improve binding to an antigen. Computational models of affinity maturation have developed from two main perspectives: molecular evolution and language modeling. The molecular evolution perspective focuses on nucleotide sequence context to describe mutation and selection; the language modeling perspective involves learning patterns from large data sets of protein sequences. In this paper, we compared models from both perspectives on their ability to predict the course of antibody affinity maturation along phylogenetic trees of BCR sequences. This included models of SHM, models of SHM combined with an estimate of selection, and protein language models. We evaluated these models for large human BCR repertoire data sets, as well as an antigen-specific mouse experiment with a pre-rearranged cognate naive antibody. We demonstrated that precise modeling of SHM, which requires the nucleotide context, provides a substantial amount of predictive power for predicting the course of affinity maturation. Notably, a simple nucleotide-based convolutional neural network modeling SHM outperformed state-of-the-art protein language models, including one trained exclusively on antibody sequences. Furthermore, incorporating estimates of selection based on a custom deep mutational scanning experiment brought only modest improvement in predictive power. To support further research, we introduce EPAM (Evaluating Predictions of Affinity Maturation), a benchmarking framework to integrate evolutionary principles with advances in language modeling, offering a road map for understanding antibody evolution and improving predictive models.},
}

@article {pmid41325432,
year = {2025},
author = {Müller, NF and Wick, RR and Judd, LM and Williamson, DA and Bedford, T and Howden, BP and Duchêne, S and Ingle, DJ},
title = {Quantifying plasmid movement in drug-resistant Shigella species using phylodynamic inference.},
journal = {PLoS pathogens},
volume = {21},
number = {12},
pages = {e1013621},
doi = {10.1371/journal.ppat.1013621},
pmid = {41325432},
issn = {1553-7374},
abstract = {The 'silent pandemic' of antimicrobial resistance (AMR) represents a significant global public health threat. AMR genes in bacteria are often carried on mobile elements, such as plasmids. The horizontal movement of plasmids allows AMR genes and resistance to key therapeutics to disseminate in a population. However, the quantification of the movement of plasmids remains challenging with existing computational approaches. Here, we introduce a novel method that allows us to reconstruct and quantify the movement of plasmids in bacterial populations over time. To do so, we model chromosomal and plasmid DNA co-evolution using a joint coalescent and plasmid transfer process in a Bayesian phylogenetic network approach. This approach reconstructs differences in the evolutionary history of plasmids and chromosomes to reconstruct instances where plasmids likely move between bacterial lineages while accounting for parameter uncertainty. We apply this new approach to a five-year dataset of Shigella, exploring the plasmid transfer rates of five different plasmids with different AMR and virulence profiles. In doing so, we reconstruct the co-evolution of the large Shigella virulence plasmid with the chromosome DNA. We quantify higher plasmid transfer rates of three small plasmids that move between lineages of Shigella sonnei. Finally, we determine the recent dissemination of a multidrug-resistant plasmid between S. sonnei and S. flexneri lineages in multiple independent events and through steady growth in prevalence since 2010. This approach has a strong potential to improve our understanding of the evolutionary dynamics of AMR-carrying plasmids as they are introduced, circulate, and are maintained in bacterial populations.},
}

@article {pmid41325059,
year = {2025},
author = {Zhang, Y and Walker, RW and Kaplan, RC and Qi, Q},
title = {Added sugars, gut microbiota, and host health.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2592431},
doi = {10.1080/19490976.2025.2592431},
pmid = {41325059},
issn = {1949-0984},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Animals ; Bacteria/classification/metabolism/genetics/isolation & purification ; *Dietary Sugars/adverse effects/metabolism ; Fatty Acids, Volatile/metabolism ; Obesity/microbiology ; },
abstract = {Excessive intake of added sugars is a global public health concern, given its established links with cardiometabolic disease and other chronic conditions. Emerging evidence suggests that the gut microbiota might mediate the harms of high sugar intake. In this review, we summarize evidence from animal and human studies regarding the impact of added sugar intake on gut microbiota diversity and composition, and discuss potential mechanisms linking sugar-induced microbial changes to health outcomes. Added sugars, including glucose, fructose, and sucrose, can alter gut microbial diversity, enrich sugar-utilizing taxa, and deplete short-chain fatty acid-producing bacteria. These microbial changes may impair gut barrier integrity, increase luminal oxygen and alternative electron acceptors under inflammatory conditions, reduce short-chain fatty acid production, alter bile acid and amino acid metabolism, and promote translocation of endotoxin across the gut barrier into the bloodstream. Collectively, these pathways may link added sugar intake to irritable bowel syndrome, obesity, liver steatosis, diabetes, and cardiovascular diseases. However, inconsistent results on alterations in the gut microbiota related to added sugar intake were observed across studies, which may be due to differences in sugar dose and form (liquid vs. solid), as well as population variation in background diet, host genetics, and gut microbial ecology. Future research should focus on mechanistic investigations, characterization of inter-individual variability in response to added sugar intake, and clinical studies to assess whether dietary or therapeutic interventions can reverse sugar-induced gut microbial changes and improve host health outcomes.},
}

Humans
*Gastrointestinal Microbiome/drug effects
Animals
Bacteria/classification/metabolism/genetics/isolation & purification
*Dietary Sugars/adverse effects/metabolism
Fatty Acids, Volatile/metabolism
Obesity/microbiology

@article {pmid41324589,
year = {2025},
author = {Murray, JD and Einhaus, TK and Radtke, S and Bar, KJ and Peterson, CW and Kiem, HP},
title = {Engraftment of gene-edited hematopoietic stem cells after antibody-drug conjugate conditioning in nonhuman primates.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017838},
pmid = {41324589},
issn = {2473-9537},
abstract = {Hematopoietic stem cell (HSC) gene therapies provide lifelong benefit in numerous hematological diseases and disorders, but safety and toxicity remain a critical barrier for routine application. In the setting of immunodeficiency syndromes and infectious diseases such as human immunodeficiency virus (HIV) infection, conditioning regimens may exacerbate immune dysfunction, blunting or impairing overall efficacy. Here, we conduct a head-to-head comparison of two novel antibody drug conjugates (ADC) with a pyrrolobenzodiazepine (PDB) payload for autologous transplantation in rhesus macaques: ADCs targeting either CD117 or CD45 and benchmarked against the clinical standard busulfan. We quantified extent of myeloablation and immunosuppression, time to hematopoietic recovery, long-term engraftment of CCR5 CRISPR-edited autologous HSC, and resistance to infection when challenged with increasing concentrations of an HIV-like virus. Both ADCs enabled engraftment of CRISPR-edited HSCs, although with lower levels of long-term editing compared to busulfan. We observed myeloablation with similar times to hematopoietic recovery and preserved lymphocyte counts with all three conditioning regimens, but neither ADC conditioning nor busulfan enabled sufficient CCR5 editing for viral immunity. While these results only apply to the specific ADC conditioning protocols tested here, they are a step towards developing targeted strategies to engraft cells with therapeutic edits and highlight the need for further refinement of antibody-based selection.},
}

@article {pmid41324575,
year = {2025},
author = {Coronado, GD and Hoffman, RM and Llavona-Ortiz, J and Rutter, CM},
title = {The Centers for Medicare and Medicaid Services and others misunderstand stool testing for colorectal cancer.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf341},
pmid = {41324575},
issn = {1460-2105},
abstract = {The May 2021 Centers for Medicare and Medicaid Services (CMS) coverage determination allowed reimbursement for blood-based biomarker tests and other tests for colorectal cancer (CRC) screening that meet minimum 74% sensitivity and 90% specificity thresholds. However, these performance benchmarks fail to account for the importance of detecting precancerous lesions and the impact of the recommended testing interval on the effectiveness of screening. We review the limitations of the CMS criteria, summarize supporting evidence for stool-based testing and colonoscopy as effective and cost-efficient screening modalities, and offer recommendations to strengthen CMS coverage decisions to better align with public health goals in CRC prevention.},
}

@article {pmid41324241,
year = {2025},
author = {Sadowska-Klasa, A and Lim, FY and Xie, H and Zamora, D and Stevens-Ayers, T and Leisenring, WM and Edmison, BC and De Rosa, SC and Mielcarek, M and Boeckh, M},
title = {New Insights Into Factors Shaping CMV-Specific T-Cell Polyfunctionality After Hematopoietic Cell Transplantation.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70152},
pmid = {41324241},
issn = {1096-8652},
support = {//Fred Hutchinson Cancer Research Center/ ; //Gdański Uniwersytet Medyczny/ ; CA15704/NH/NIH HHS/United States ; K23AI163343/NH/NIH HHS/United States ; },
abstract = {Polyfunctional cytomegalovirus (CMV)-specific T cells are critical for antiviral immunity in allogeneic hematopoietic cell transplantation (HCT) recipients. However, gaps remain in managing refractory CMV and optimizing virus-specific cellular therapy (VST). We conducted a comparative analysis of how timing and dosing of immunosuppressive agents, including post-transplant cyclophosphamide (PT-Cy), corticosteroids, mycophenolate mofetil (MMF), and calcineurin inhibitors (CNIs), shape CMV-specific T-cell polyfunctionality. CD4[+] and CD8[+] T-cell responses (IFN-γ plus ≥ 1 functional marker) were assessed following pp65 stimulation within 100 days post-HCT in the pre- and post-letermovir era. Among 243 patients, 31% exhibited polyfunctional CD4[+] and CD8[+] responses. PT-Cy did not significantly impair T-cell functionality. Cyclosporine was associated with higher frequencies of polyfunctional T cells compared to tacrolimus, even at concentrations above the therapeutic range. Intermediate (≥ 0.5 mg/kg) and high-dose (≥ 1 mg/kg) corticosteroids, especially within 2-4 weeks before testing, significantly suppressed T-cell responses, though rapid tapering preserved function. Prolonged administration of MMF (≥ 2000 mg) diminished T-cell polyfunctionality. These findings provide novel insights into the importance of timing and dosing of the immunosuppressive effects of PT-Cy, corticosteroids, MMF and CNIs on CMV-specific immunity. Adjusting immunosuppression in specific time windows may improve the management of refractory CMV infections and optimize VST in HCT recipients.},
}

@article {pmid41279560,
year = {2025},
author = {Sohn, MH and Dubocanin, D and Vollger, MR and Kwon, Y and Minkina, A and Munson, KM and Hart, SF and Ranchalis, JE and Parmalee, NL and Sedeño-Cortés, AE and Ou, J and Au, NY and Bohaczuk, S and Carroll, B and Frazar, CD and Harvey, WT and Hoekzema, K and Huang, MF and Jacques, CN and Jensen, DM and Kolar, JT and Lee, R and Lin, J and Loy, K and Mack, T and Mao, Y and Pham, MM and Ryke, E and Smith, JD and Sutherlin, L and Swanson, EG and Weiss, JM and Wg, SA and Carvalho, C and Coorens, TH and Harris, K and Wei, CL and Eichler, EE and Altemose, N and Bennett, JT and Stergachis, AB},
title = {A telomere-to-telomere map of somatic mutation burden and functional impact in cancer.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279560},
issn = {2692-8205},
abstract = {Oncogenesis involves widespread genetic and epigenetic alterations, yet the full spectrum of somatic variation genome-wide remains unresolved. We generated a near-telomere-to-telomere (T2T) diploid assembly of a donor paired with deep short- and long-read sequencing of their melanoma. This revealed that 16% of somatic variants occur in sequences absent from GRCh38, with satellite repeats acting as hotspots for UV-induced damage due to sequence-intrinsic mutability and inefficient repair. Centromere kinetochore domains emerged as focal sites of structural, genetic, and epigenetic variation, leading to remodeling of centromere kinetochore binding domains during tumor evolution. Single-molecule telomere reconstructions uncovered cycles of attrition, deletion, and telomerase-mediated extension that shape cancer telomeres. Finally, diploid chromatin maps exposed that copy number alterations and epimutations, rather than point mutations, predominate in rewiring cancer regulatory programs. These findings define the full landscape of a cancer's somatic variation and their functional impact, establishing a blueprint for T2T studies of mosaicism.},
}

@article {pmid41323215,
year = {2025},
author = {Bobić, M and Bushe, DH and Lee, H and Winey, BA and Efstathiou, JA and Paganetti, H and Pursley, J and Peters, N and Nenoff, L},
title = {Comparison of cone beam computed tomography post-processing methods for online adaptive proton therapy of prostate cancer.},
journal = {Physics and imaging in radiation oncology},
volume = {36},
number = {},
pages = {100858},
pmid = {41323215},
issn = {2405-6316},
abstract = {BACKGROUND AND PURPOSE: Although cone beam computed tomography (CBCT) enables online adaptive radiotherapy, its CT number accuracy may be insufficient for online adaptive proton therapy (OAPT). We compared proton dose distributions calculated directly on CBCT with calculations using additional CBCT image-processing methods in prostate cancer.

MATERIALS AND METHODS: Retrospective proton plans were created for 10 prostate patients originally treated with 5-fraction online adaptive photon radiotherapy using CBCT. These plans were forward-calculated on each CBCT with four different approaches: (1) the clinical CBCT with a dedicated CT number calibration, (2) CBCT with histogram correction, (3) CT deformed to the CBCT, and (4) deformed CT with an air-cavity correction. Additionally, adaptive treatment using an OAPT workflow was simulated for each fraction and compared among the four CBCT-based methods. Dose-volume histograms (DVH) and related parameters were compared between the four methods for both non-adaptive and online adaptive treatment simulations.

RESULTS: Proton dose distributions were comparable across all CBCT-based strategies, with median differences of up to 1% for all DVH metrics compared to a reference method. Larger differences were observed for doses calculated directly on the CBCT for patient geometries deviating from the CBCT-specific calibration. Despite these differences, all four methods indicated the dosimetric benefits of OAPT over non-adaptive treatment.

CONCLUSION: An advanced CBCT system enables proton dose calculations performed directly on the CBCT, demonstrating sufficient accuracy for integration into an OAPT workflow. Additional CBCT-based post-processing techniques are recommended to maximize the dosimetric benefit of plan adaptation in all patient populations.},
}

@article {pmid41323153,
year = {2025},
author = {Ojee, E and Odiyo, J and Adhiambo, J and Mabele, E and Omondi, V and Begnel, ER and Chohan, BH and Kinuthia, J and Gantt, S and Lehman, DA and Aluvaala, J and Were, F and Were, V and Wamalwa, D and Slyker, J},
title = {A cost analysis of postpartum home visit programming in Kenya: estimates to aid policymakers.},
journal = {Frontiers in health services},
volume = {5},
number = {},
pages = {1644078},
pmid = {41323153},
issn = {2813-0146},
abstract = {INTRODUCTION: The World Health Organization (WHO) and UNICEF recommend at least two postnatal home visits by a health provider within the first two weeks of life to improve newborn survival. Kenya's Universal Health Coverage (UHC) initiative includes a home-visit strategy to advance Sustainable Development Goal (SDG) 3.2, which targets reducing neonatal mortality to below 12 per 1,000 live births. We estimated the costs of starting a postnatal home-visit program in a level three health facility in Kenya, based on recommendations from Kenya's Ministry of Health policymakers.

METHODS: An ingredients-based costing method was used to determine the actual costs of home visits incurred during a research project conducted in 2019, and to estimate program costs from the government's perspective as the payer. Per-visit costs were calculated for three staffing approaches: Community Health Promoter (CHP), Registered Nurse (RN), and a Combined model where two providers (RN + CHP) visited each home together.

RESULTS: Staff salaries and transportation costs were the main drivers of recurrent program expenses. The CHP approach had the lowest total cost at $27,302 ($24.46 per visit), followed by the RN-only approach at $36.45 per visit, while the Combined model (RN+CHP) was the most expensive at $52.10 per visit. Discussions with policymakers noted that the RN+CHP approach was least feasible and scalable. They proposed an alternative "Hybrid" model in line with current programs being scaled up: weekly RN visits during the first month of life (neonatal period), and quarterly CHP visits thereafter.

DISCUSSION: This study presents a costing tool and generalizable formula that policymakers can use to estimate program costs based on different facility characteristics and staffing needs. The findings can support Kenya's efforts to scale up postnatal home-visit programs to improve maternal and newborn health outcomes within the UHC framework.},
}

@article {pmid41321622,
year = {2025},
author = {Nukaya, M and Carney, PR and Cafferty, C and Zahed, K and Yun, I and Al-Adra, DP and Kazim, NA and Farghli, AR and Chan, M and Stram, A and Kratz, JD and Berres, ME and Yen, A and Gujral, TS and Sethupathy, P and Bradfield, CA and Ronnekleiv-Kelly, SM},
title = {CDK7 is a novel therapeutic target in fibrolamellar carcinoma.},
journal = {iScience},
volume = {28},
number = {12},
pages = {113925},
pmid = {41321622},
issn = {2589-0042},
abstract = {Fibrolamellar Carcinoma (FLC) is a rare and deadly cancer that arises in young, otherwise healthy patients. For patients that cannot be treated with surgery, only 30%-45% survive to 5 years with current treatment options. These poor survival odds highlight the need for new therapeutic targets. Using patient samples, we identified that abnormal function of cyclin-dependent kinase 7 (CDK7) is a key component of pathways that are essential for FLC cancer cell identity and survival. Consequently, drug inhibitors of CDK7 suppressed these abnormal pathways and also caused cancer cell death in a dose-dependent manner. This held true in several patient-derived models of FLC. We then found that inhibition of CDK7 can combine with other drug candidates to increase the therapeutic response in FLC cells. Taken together, this suggests CDK7 is a promising target for future treatment in human FLC.},
}

@article {pmid41321225,
year = {2025},
author = {Sekeres, MA and Mattison, RJ and Artz, AS and Baer, MR and Chua, CC and Demichelis-Gomez, R and Egan, PC and Fletcher, L and Foucar, CE and Garcia, JS and Gilberto, L and Gómez-De León, A and Lancet, JE and Loh, KP and Malcovati, L and Marini, BL and Platzbecker, U and Sorror, ML and Tinsley-Vance, S and Treitz, J and Oliveros, MJ and Ibrahim, S and Roldan, Y and Guyatt, GH and Brignardello-Petersen, R},
title = {American Society of Hematology 2025 guidelines for treating newly diagnosed acute myeloid leukemia in older adults.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017934},
pmid = {41321225},
issn = {2473-9537},
abstract = {Older adults with acute myeloid leukemia (AML) represent a cancer population in whom disease-based risk factors, comorbidities, patient goals, and treatment risks and benefits influence treatment recommendations. These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians and other health professionals in their decisions about management of AML in older adults. ASH formed a multidisciplinary guideline panel, including patient representatives, that minimized bias from conflicts of interest. Clarity Research Group at McMaster University supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including Evidence-to-Decision frameworks, to assess evidence and make recommendations. The panel agreed on 9 critical clinical recommendations for managing AML in older adults, mirroring real-time practitioner-patient conversations: the decision to pursue antileukemic treatment vs. best supportive management; traditional induction and post-remission therapy vs. hypomethylating agent or low-dose cytarabine, or combinations with venetoclax; the role and duration of post-remission therapy; combinations with venetoclax vs. monotherapy; the use of targeted therapy, including IDH and FLT3 inhibitors, in appropriate patients; the role of hematopoietic stem cell transplantation in non-favorable prognosis AML; and the role of transfusion support for patients no longer receiving antileukemic therapy. Key recommendations of these guidelines include treatment over best supportive care; venetoclax-based regimens over monotherapies; and incorporation of FLT3 inhibitors into traditional induction and post-remission therapy.},
}

@article {pmid41279611,
year = {2025},
author = {Mullins, JI and Deng, W and Giorgi, EE and Magaret, CA and Rolland, M and Bhattacharya, T and Westfall, DH and Yssel, AEJ and Bumgarner, RE and Murrell, B and Ndung'u, T and Robb, ML and Rossenkhan, R and Edlefsen, PT and Dong, KL and Chen, L and Gwashu-Nyangiri, A and Zhao, H and Thebus, R and Sawe, F and Nitayaphan, S and York, T and Matten, D and Murrell, H and Pankow, AP and Juraska, M and Ludwig, J and Hural, J and Cohen, MS and Corey, L and McElrath, MJ and Gilbert, PB and Williamson, C},
title = {Long-Read Deep Sequencing Reveals High Rates of Multilineage Transmission and Rapid Viral Population Changes in Acute HIV Infection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279611},
issn = {2692-8205},
abstract = {Understanding the selective forces acting upon HIV early in infection is crucial to design prevention strategies. By leveraging deep sequencing and the short diagnostic intervals of the FRESH and RV217 cohorts (median 4 days) between the last-negative and first-positive RNA tests, we captured a precise and early snapshot of acute HIV infection. The frequency of multiple transmitted viruses of 38% in these as well as placebo recipients from the AMP trials was higher than previously published, with the true frequency likely to be higher. The relative abundance of lineages fluctuated substantially over time in two-thirds of the multilineage infections, generating uncertainty in identifying the specific viruses that were transmitted and founding the infection. Viral populations exhibited diversity and selection on the Gag and Env proteins at the earliest times examined, with sites inferred to be undergoing negative selection most evident. These data may help explain vaccination failures and provide new targets for prevention.},
}

@article {pmid41279479,
year = {2025},
author = {Larsen, BB and Harari, S and Gen, R and Stewart, C and Veesler, D and Bloom, JD},
title = {Functional and antigenic constraints on the Nipah virus fusion protein.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279479},
issn = {2692-8205},
abstract = {Nipah virus is a highly pathogenic virus in the family Paramyxoviridae that utilizes two distinct surface glycoproteins to infect cells. The receptor-binding protein (RBP) binds host receptors whereas the fusion protein (F) merges viral and host membranes. Here, we use non-replicative pseudoviruses to safely measure the effects of all F single amino-acid residue mutations on its cell entry function and neutralization by monoclonal antibodies. We compare mutational tolerance in F with previous experimental measurements for RBP and show that F is much more functionally constrained than the RBP. We also identify mutationally intolerant sites on the F trimer surface and core that are critical for proper function, and describe mutations that are candidates for stabilizing F in the prefusion conformation for vaccine design. We quantify how F mutations affect neutralization by six monoclonal antibodies, and show that the magnitude of mutational effects on neutralization varies among antibodies. Our measurements of mutational effects on Nipah virus F predict the ability of the antibodies to neutralize the related Hendra virus. Overall, our work defines the functional and antigenic constraints on the F protein from an important zoonotic virus.},
}

@article {pmid41320687,
year = {2025},
author = {Mileto, A and Inoue, A and Mohammadinejad, P and Coveler, AL and Lee, YS and Leng, S and Johnson, MP and Sun, Y and Thomas, JV and Yeh, BM and Bruining, DH and Fletcher, JG},
title = {Prospective pilot evaluation of dark borosilicate oral contrast media for the evaluation of the stomach and small bowel using CT.},
journal = {Abdominal radiology (New York)},
volume = {},
number = {},
pages = {},
pmid = {41320687},
issn = {2366-0058},
support = {R44 DK103495/DK/NIDDK NIH HHS/United States ; },
abstract = {PURPOSE: To evaluate the feasibility of use of dark borosilicate oral contrast media (DBOCM) in abdominopelvic CT in comparison with conventional oral contrast media (COCM) in a multi-institutional setting.

METHODS: Patients with known or suspected inflammatory bowel disease (IBD) (Site A) or suspected peritoneal carcinomatosis (Site B), who had undergone initial standard-of-care CT using COCM (positive, n = 10; neutral n = 22), underwent research CT with DBOCM. Attenuation differences between bowel wall and lumen using COCM and DBOCM were measured. Three radiologists independently examined all examinations with COCM and DBOCM. Patient tolerance and safety were recorded. Bowel wall visualization, distention, distended bowel length, and radiologist preference for bowel visualization were rated. Imaging findings using both oral contrast media were recorded, and a final consensus evaluation was performed to evaluate whether additional findings detected with DBOCM were visible with COCM.

RESULTS: Thirty-two patients (IBD, n = 15; suspected peritoneal carcinomatosis, n = 17) were included. No severe adverse effects were seen with DBOCM. Compared to COCM, DBOCM yielded significantly higher attenuation differences between bowel wall and lumen (P < .001). Bowel wall visualization, distention, and distended bowel length was significantly higher from the stomach to the ileum using DBOCM (P < .001). DBOCM was preferred by each reader over COCM for all intestinal segments, but significance was not achieved in pooled results. Additional imaging findings were found in seven patients (22% [7/32]; 95% CI 9-40%) using DBOCM.

CONCLUSION: Compared to COCM, DBOCM yielded improved bowel wall visualization and distention, also revealing additional imaging findings.},
}

@article {pmid41320342,
year = {2025},
author = {Crown, J and Stroyakovskii, D and Yardley, DA and Huang, CS and Fasching, PA and Bardia, A and Chia, S and Im, SA and Martin, M and Xu, B and Barrios, CH and Untch, M and Moroose, R and Hurvitz, SA and Hortobagyi, GN and Slamon, DJ and Visco, F and Spera, G and Zarate, JP and Halligan, D and Li, Z and Loi, S},
title = {Adjuvant ribociclib plus nonsteroidal aromatase inhibitor therapy in patients with HR-positive/HER2-negative early breast cancer: 5-year follow-up of NATALEE efficacy outcomes and updated overall survival.},
journal = {ESMO open},
volume = {10},
number = {11},
pages = {105858},
doi = {10.1016/j.esmoop.2025.105858},
pmid = {41320342},
issn = {2059-7029},
mesh = {Humans ; *Aminopyridines/therapeutic use/administration & dosage ; *Purines/therapeutic use/administration & dosage ; Female ; *Aromatase Inhibitors/therapeutic use/administration & dosage ; *Breast Neoplasms/drug therapy/mortality/pathology ; Middle Aged ; Male ; Follow-Up Studies ; Receptor, ErbB-2/metabolism ; Aged ; Adult ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Treatment Outcome ; Chemotherapy, Adjuvant/methods ; Receptors, Progesterone/metabolism ; Receptors, Estrogen/metabolism ; Letrozole/administration & dosage/therapeutic use ; },
abstract = {BACKGROUND: At the primary efficacy analysis of the NATALEE phase III trial, ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) demonstrated a statistically significant improvement in invasive disease-free survival (iDFS) versus NSAI alone in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC). Continued follow-up of efficacy outcomes is important in assessing the durability of treatment benefit. We report 5-year estimates of efficacy outcomes, including an udpated analysis of overall survival (OS).

PATIENTS AND METHODS: Eligible patients included pre/postmenopausal women and men with HR-positive/HER2-negative EBC and anatomic stage IIA (N1 or N0 with high-risk factors), IIB, or III disease. Patients were randomized 1 : 1 to ribociclib 400 mg/day (3 weeks on/1 week off for 3 years) + NSAI (letrozole 2.5 mg/day or anastrozole 1 mg/day for 5 years) or NSAI alone. Premenopausal women and men received goserelin. The primary endpoint was iDFS, and secondary/exploratory endpoints included distant disease-free survival, recurrence-free survival, distant recurrence-free survival, and OS.

RESULTS: With a median iDFS follow-up of 55.4 months, ribociclib + NSAI demonstrated persistent iDFS benefit versus NSAI alone [hazard ratio 0.716, 95% confidence interval (CI) 0.618-0.829, nominal one-sided log-rank P < 0.0001]. Absolute iDFS improvement between treatment arms increased from the 3- (Δ2.7%) to the 5-year (Δ4.5%) time points. Persistent benefit over time was also observed across subgroups [including N0 patients (hazard ratio 0.606, 95% CI 0.372-0.986)] and secondary/exploratory endpoints. As OS continues to mature, numerical improvement in favor of ribociclib was observed (hazard ratio 0.800, 95% CI 0.637-1.003, nominal one-sided log-rank P = 0.026).

CONCLUSIONS: This prespecified 5-year follow-up of efficacy outcomes from NATALEE demonstrated that ribociclib + NSAI continued to reduce the risk of recurrence beyond the 3-year treatment window, supporting its use as adjuvant therapy in patients with HR-positive/HER2-negative EBC. An ongoing positive trend for improved OS in favor of ribociclib + NSAI was observed.},
}

Humans
*Aminopyridines/therapeutic use/administration & dosage
*Purines/therapeutic use/administration & dosage
Female
*Aromatase Inhibitors/therapeutic use/administration & dosage
*Breast Neoplasms/drug therapy/mortality/pathology
Middle Aged
Male
Follow-Up Studies
Receptor, ErbB-2/metabolism
Aged
Adult
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Treatment Outcome
Chemotherapy, Adjuvant/methods
Receptors, Progesterone/metabolism
Receptors, Estrogen/metabolism
Letrozole/administration & dosage/therapeutic use

@article {pmid41319224,
year = {2024},
author = {Chen, Z and Heng, S and Tapley, A and De Rosa, S and Zhang, B},
title = {Determining vaccine responders in the presence of baseline immunity using single-cell assays and paired control samples.},
journal = {Biostatistics (Oxford, England)},
volume = {26},
number = {1},
pages = {},
doi = {10.1093/biostatistics/kxaf045},
pmid = {41319224},
issn = {1468-4357},
mesh = {Humans ; *Single-Cell Analysis/methods ; *Immunogenicity, Vaccine/immunology ; *COVID-19 Vaccines/immunology ; B-Lymphocytes/immunology ; COVID-19/prevention & control/immunology ; Cytokines/immunology ; Vaccination ; Immunity, Cellular ; },
abstract = {A key objective in vaccine studies is to evaluate vaccine-induced immunogenicity and determine whether participants have mounted a response to the vaccine. Cellular immune responses are essential for assessing vaccine-induced immunogenicity, and single-cell assays, such as intracellular cytokine staining (ICS) and B-cell phenotyping (BCP), are commonly employed to profile individual immune cell phenotypes and the cytokines they produce after stimulation. In this article, we introduce a novel statistical framework for identifying vaccine responders using ICS data collected before and after vaccination. This framework incorporates paired control data to account for potential unintended variations between assay runs, such as batch effects, that could lead to misclassification of participants as vaccine responders or non-responders. To formally integrate paired control data for accounting for assay variation across different time points (ie before and after vaccination), our proposed framework calculates and reports two $ P $-values, both adjusting for paired control data but in distinct ways: (i) the maximally adjusted $ P $-value, which applies the most conservative adjustment to the unadjusted $ P $-value, ensuring validity over all plausible batch effects consistent with the paired control samples' data, and (ii) the minimally adjusted $ P $-value, which imposes only the minimal adjustment to the unadjusted $ P $-value, such that the adjusted $ P $-value cannot be falsified by the paired control samples' data. Minimally and maximally adjusted $ P $-values offer a balanced approach to managing Type I error rates and statistical power in the presence of batch effects. We apply this framework to analyze ICS data collected at baseline and 4 wks post-vaccination from the COVID-19 Prevention Network (CoVPN) 3008 study. Our analysis helps address two clinical questions: (i) which participants exhibited evidence of an incident Omicron infection between baseline and 4 wks after receiving the final dose of the primary vaccination series, and (ii) which participants showed vaccine-induced T cell responses against the Omicron BA.4/5 Spike protein.},
}

Humans
*Single-Cell Analysis/methods
*Immunogenicity, Vaccine/immunology
*COVID-19 Vaccines/immunology
B-Lymphocytes/immunology
COVID-19/prevention & control/immunology
Cytokines/immunology
Vaccination
Immunity, Cellular

@article {pmid41315206,
year = {2025},
author = {Afrough, A and Dima, D and Razzo, B and Goel, U and Sannareddy, A and Pasvolsky, O and Vazquez-Martinez, MA and Ferreri, CJ and Banerjee, R and Khouri, J and Davis, JA and Gaballa, MR and Lieberman-Cribbin, A and Rana, MS and Julian, K and Anwer, F and Shune, L and DeJarnette, S and Grajales-Cruz, AF and Ouchveridze, E and De Avila, G and Susanibar-Adaniya, SP and Portuguese, AJ and Schrum, D and Eberwein, E and Hosoya, H and Mikkilineni, L and Kaur, G and McGuirk, JP and Rossi, A and Herr, MM and Castaneda, O and Locke, FL and Raza, S and Lin, Y and Atrash, S and Sborov, DW and Voorhees, PM and Richard, S and Garfall, AL and Sidana, S and Patel, KK and Hansen, DK and Cowan, AJ and Anderson, LD and Lee, HC},
title = {The impact of extramedullary and paraskeletal plasmacytomas on treatment outcomes in multiple myeloma treated with teclistamab: U.S. Myeloma Immunotherapy Consortium real-world experience.},
journal = {Blood cancer journal},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41408-025-01414-6},
pmid = {41315206},
issn = {2044-5385},
abstract = {Teclistamab, a bispecific antibody targeting B-cell maturation antigen (BCMA), is effective in relapsed or refractory multiple myeloma (RRMM), but its impact on patients with soft tissue plasmacytomas is unclear. We studied 385 RRMM patients treated with teclistamab at 13 U.S. centers through September 2023, with follow-up to April 2024. Soft tissue plasmacytomas were classified as true extramedullary disease (EMD; not contiguous with bone) or paraskeletal plasmacytomas (PSK; contiguous with bone). Patients with the simultaneous presence of both were classified as true-EMD, reflecting its adverse prognosis. Of those, 109 (28%) had true EMD, 33 (9%) had PSK, and 243 (63%) had no soft tissue plasmacytoma (No-STP). Median follow-up was 9.9 months. Overall response rates were 38% in true-EMD, 54.1% in PSK, and 62.4% in No-STP (p < 0.001). Median progression-free survival (PFS) was 1.4 months in true-EMD, 6.51 months in PSK, and 8.95 months in No-STP (p < 0.0001). Median overall survival (OS) was 9.54 months for true EMD, 13.1 months for PSK, and not reached in No-STP (p = 0.00012). In multivariable analysis, true-EMD was independently associated with inferior PFS and OS, while PSK showed numerically lower outcomes. These findings highlight the need for tailored strategies in patients with soft tissue plasmacytomas, particularly those with true-EMD.},
}

@article {pmid41314741,
year = {2025},
author = {Buchbinder, SP and Spinosa Guzman, S and Sanchez, J and Willems, W and Stieh, DJ and van Duijn, J and van Rosmalen, MGM and Hendriks, J and Nijs, S and Lavreys, L and Paez, CA and Grinzstejn, B and Hutter, J and Mann, P and Sierra Madero, JG and Cahn, P and Castagna, A and Truyers, C and Roels, S and Gilbert, PB and Carone, M and Luedtke, A and Corey, L and Pau, MG and Tomaka, F and , },
title = {Efficacy and safety of a mosaic HIV-1 vaccine regimen in men who have sex with men and transgender individuals (HVTN 706/HPX3002/Mosaico): a global, randomised, double-blind, placebo-controlled, phase 3 trial.},
journal = {The lancet. HIV},
volume = {12},
number = {12},
pages = {e823-e835},
doi = {10.1016/S2352-3018(25)00195-X},
pmid = {41314741},
issn = {2352-3018},
mesh = {Humans ; Male ; *HIV Infections/prevention & control/immunology ; Adult ; *AIDS Vaccines/administration & dosage/immunology/adverse effects ; Double-Blind Method ; *HIV-1/immunology ; *Transgender Persons ; Middle Aged ; *Homosexuality, Male ; Young Adult ; Vaccine Efficacy ; Female ; },
abstract = {BACKGROUND: There is a high unmet need for effective HIV prevention options, including vaccines, for individuals at high risk of HIV acquisition who choose not to use pre-exposure prophylaxis or other prevention strategies. This study evaluated the efficacy and safety of an HIV-1 vaccine regimen consisting of tetravalent mosaic adenovirus serotype 26-based vaccine (Ad26.Mos4.HIV) and bivalent clade C glycoprotein (gp) 140-mosaic gp140 vaccine, in a population with high seroincidence.

METHODS: This randomised, double-blind, phase 3 trial enrolled adult cisgender men and transgender individuals without HIV from 52 academic medical centres, health departments, and community-based clinics in Latin America, Europe, and the USA. Participants were randomly assigned (1:1) by use of a centrally prepared, computer-generated randomisation schedule to receive intramuscular injections of vaccine or saline placebo in stratified permuted blocks. Study participants, study site personnel (except for those with primary responsibility for study vaccine preparation and dispensing), and investigators were masked from vaccine allocation. The vaccine regimen consisted of Ad26.Mos4.HIV administered at months 0 and 3 followed by Ad26.Mos4.HIV administered concurrently with aluminium phosphate-adjuvanted clade C gp140-mosaic gp140 at months 6 and 12. The primary endpoint was vaccine efficacy in preventing HIV-1 acquisition between months 7 and 24 or between months 7 and 30 in the per-protocol population, which included all randomly assigned participants who received at least one study vaccination and who had not been diagnosed with HIV-1 4 weeks after the third vaccination, had received all planned vaccinations at the first three vaccination visits within the respective visit windows, and had no major protocol deviations linked to incorrect product administration. Safety outcomes were assessed in all randomised participants who received at least one study vaccination. The trial is registered with ClinicalTrials.gov (NCT03964415) and is complete.

FINDINGS: Between Nov 4, 2019, and Aug 13, 2021, 3900 participants were enrolled and randomly assigned; 3887 received at least one study vaccination (1942 assigned to vaccine, 1945 to placebo). 3870 (99·6%) of 3887 participants were assigned male at birth, seven (0·2%) were assigned female, and one participant's sex at birth was undifferentiated; 3557 (91·5%) participants identified as male gender, 48 (1·2%) as female gender, and 278 (7·2%) as transgender or non-binary. The per-protocol population included 1525 participants in the vaccine group and 1494 in the placebo group. From month 7 to month 24 in the per-protocol population, HIV-1 incidence per 100 person-years was 3·63 (95% CI 2·77 to 4·67) in the vaccine group and 3·35 (2·53 to 4·36) in the placebo group, with an estimated vaccine efficacy (months 7-24) of -0·7% (95% CI -50·9 to 32·8; p=0·97). Vaccine efficacy (months 7-30) was -149·1% (-737·7 to 26·0; p=0·14). Most solicited local and systemic adverse events were mild or moderate and short-lived. Medically attended adverse events occurred in 999 (51·4%) of 1942 participants given vaccine and 1002 (51·5%) of 1945 participants given placebo; serious adverse events occurred in 82 (4·2%) of 1942 participants given vaccine and 77 (4·0%) of 1945 participants given placebo. No fatal adverse events considered related to the study vaccine occurred. Adverse events of special interest (thrombotic events or thrombocytopenia) occurred in four participants with vaccine and two with placebo; none had thrombosis with thrombocytopenia syndrome.

INTERPRETATION: The lack of efficacy in this and other HIV vaccine trials points to the importance of current efforts to develop vaccines that generate broadly neutralising antibodies.

FUNDING: Johnson & Johnson; HIV Vaccine Trials Network; Division of AIDS, a division of National Institute of Allergy and Infectious Diseases; and US Army Medical Materiel Development Activity, a subordinate command of the US Army Medical Research and Development Command.},
}

Humans
Male
*HIV Infections/prevention & control/immunology
Adult
*AIDS Vaccines/administration & dosage/immunology/adverse effects
Double-Blind Method
*HIV-1/immunology
*Transgender Persons
Middle Aged
*Homosexuality, Male
Young Adult
Vaccine Efficacy
Female

@article {pmid41314597,
year = {2025},
author = {Mosher, CE and Shinn, EH and Addington, EL and Wu, W and Bricker, JB and Helft, PR and Turk, AA and Vater, LB and Masood, A and Jalal, SI and Loehrer, PJ and Champion, VL and Johns, SA},
title = {Protocol of a randomized trial of acceptance and commitment therapy for patient fatigue interference and caregiver burden in advanced gastrointestinal cancer.},
journal = {Contemporary clinical trials},
volume = {},
number = {},
pages = {108168},
doi = {10.1016/j.cct.2025.108168},
pmid = {41314597},
issn = {1559-2030},
abstract = {Fatigue's interference with activities, mood, and cognition is one of the most prevalent and distressing problems of patients with advanced gastrointestinal cancer. As fatigue interferes with patient functioning, family caregivers often report feeling burdened by increasing demands. Evidence-based interventions for patient fatigue interference and caregiver burden are lacking in advanced gastrointestinal cancer. In a pilot trial, telephone-based Acceptance and Commitment Therapy (ACT) showed potential for reducing patient fatigue interference and caregiver burden in this population. The current Phase II trial seeks to determine the efficacy of this intervention for patients with advanced gastrointestinal cancer and moderate-to-severe fatigue interference and their family caregivers with significant caregiving burden. In this trial, 244 dyads are randomly assigned to either the ACT intervention or an education/support control. Participants in both conditions attend six weekly 50-min telephone sessions, four of which involve both dyad members, and a 30-min booster session. The primary aim is to test the effects of telephone-delivered ACT on patient fatigue interference and caregiver burden. Secondary outcomes include patient sleep interference and patient and caregiver engagement in daily activities and quality of life. Outcomes are assessed at baseline, 2 weeks post-intervention, and 3 months post-intervention. This trial also examines whether increased psychological flexibility, defined as mindful acceptance of present experiences, including challenges, while pursuing actions aligned with personal values, mediates ACT's effects on primary outcomes. Our ability to demonstrate ACT's efficacy will support its adoption in cancer care. Findings will also inform future ACT trials for dyads coping with other serious illnesses. Trial Registration ID: NCT06532877.},
}

@article {pmid41313144,
year = {2025},
author = {Anderson, BO and Li, CI},
title = {Lobular carcinoma and endocrine biology: Lessons learned and future directions.},
journal = {Cancer},
volume = {131},
number = {23},
pages = {e70194},
doi = {10.1002/cncr.70194},
pmid = {41313144},
issn = {1097-0142},
}

@article {pmid41310247,
year = {2025},
author = {Alves, IM and Termini, CM},
title = {Blocking ferroptosis to expand human HSCs.},
journal = {Nature cell biology},
volume = {},
number = {},
pages = {},
pmid = {41310247},
issn = {1476-4679},
support = {1K01DK126989-01A1//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; 23CDA1039196//American Heart Association (American Heart Association, Inc.)/ ; SPK-08-25//Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation)/ ; },
}

@article {pmid41310100,
year = {2025},
author = {Hernandez, LE and Smitherman, AB and Santacroce, SJ and Liu, Y and Roy, MM and Ross, WL and Armstrong, H and Appel, B and Casillas, J and Hurtado-de-Mendoza, A and Demedis, J and Horwitz, LI and Mendoza, JA and Kadan-Lottick, NS},
title = {Childhood cancer survivors and their caregivers are amenable to survivorship surveillance with community-based primary care providers.},
journal = {Journal of cancer survivorship : research and practice},
volume = {},
number = {},
pages = {},
pmid = {41310100},
issn = {1932-2267},
abstract = {PURPOSE: A minority of childhood cancer survivors (CCS) receive post-therapy survivorship surveillance at their oncology center (OC) within 5 years of diagnosis. Primary care providers (PCPs) could be a promising alternative. We determined CCS' preferences for the site of surveillance, associated factors, and rationale.

METHODS: CCS diagnosed with cancer at < 21 years at one of four participating hospitals, 2-4 years post-therapy, and English- or Spanish-speaking (or their caregivers if CCS < 18 years) indicated their preference and reasons for site of survivorship surveillance (OC vs. PCP vs. no preference) at baseline prior to randomization into the BRIDGES trial (NCT05448560). Multivariable logistic regression models estimated prevalence ratios for site preference and examined associations with patient characteristics. Qualitative methods examined reasons for preference.

RESULTS: Of 235 participants, 92% (n = 214; 48% female, 36% Hispanic, 46% public insurance, median age 12 years at enrollment) indicated their preference. The majority (63%) were amenable to PCP-based surveillance (21% preferred PCP, 42% no preference). Preference for OC was associated with identifying as non-Hispanic "other" (Black, Asian, multi-racial) vs. non-Hispanic White (PR 4.7, p = 0.005, 95% CI 1.68, 13.84) and older age (PR 1.1/year, p = 0.02, 95% CI 1.01, 1.15), but not insurance or area-level social determinants of health (SDoH) indices. Reasons for preference comprised two themes: practical (facts, logistics) and psychological (emotions, beliefs). OCs were preferred for psychological reasons (46/60; 77%); PCPs were preferred for practical reasons (25/35; 74%).

CONCLUSIONS: Among diverse CCS, most were amenable to PCP-based survivorship surveillance, independent of SDoH factors.

Survivorship surveillance by PCPs may be a useful alternative for CCS.},
}

@article {pmid41309676,
year = {2025},
author = {Yu, Z and Vromman, A and Nguyen, NQH and Schuermans, A and Li, L and Rentz, T and Nakao, T and Vellarikkal, SK and Uddin, MM and Niroula, A and Griffin, G and Honigberg, MC and Lin, AE and Gibson, CJ and Katz, DH and Tahir, UA and Fang, S and Dron, JS and Pan, M and Haidermota, S and Ganesh, S and Antoine, T and Weinstock, J and Austin, TR and Vasan, RS and Peloso, GM and Hornsby, W and Ganz, P and Manson, JE and Haring, B and Kooperberg, C and Reiner, AP and Bis, JC and Psaty, BM and Min, YI and Correa, A and Lange, LA and Post, WS and Rotter, JI and Rich, SS and Wilson, JG and Ebert, BL and Yu, B and Ballantyne, CM and Coresh, J and Sankaran, VG and Bick, AG and Jaiswal, S and Gerszten, RE and , and Libby, P and Gupta, RM and Natarajan, P},
title = {Human plasma proteomic profile of clonal hematopoiesis.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-66755-z},
pmid = {41309676},
issn = {2041-1723},
support = {R01HL142711, R01HL127564, R01HL148050, R01HL151283, R01HL148565, R01HL135242, and R01HL151152//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL173028, R01HL148565//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; K08HL161445//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 1R01 HL159081, R01 HL153499//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL148565//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 1R01HL134892 and 1R01HL163099-01//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; K99HL165024//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01DK125782//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; 5U01DK108809//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; TNE-18CVD04//Fondation Leducq/ ; TNE-18CVD04//Fondation Leducq/ ; Paul and Phyllis Fireman Endowed Chair in Vascular Medicine//Massachusetts General Hospital (MGH)/ ; R00HG012956//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; Harold M. English Fellowship Fund//Harvard Medical School/ ; KAW 2020.0239//Science for Life Laboratory (SciLifeLab)/ ; R01 MH104964 and R01 MH123451//U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/ ; 24RGRSG1275749, 25SFRNCCKMS1443062, 25SFRNPCKMS1463898//American Heart Association (American Heart Association, Inc.)/ ; Burroughs Wellcome Foundation Career Award for Medical Scientists//Burroughs Wellcome Fund (BWF)/ ; },
abstract = {Plasma proteomic profiles associated with subclinical somatic mutations in blood cells may offer insights into downstream clinical consequences. Here we explore these patterns in clonal hematopoiesis of indeterminate potential (CHIP), which is linked to several cancer and non-cancer outcomes, including coronary artery disease (CAD). Among 61,833 participants (3881 with CHIP) from TOPMed and UK Biobank (UKB) with blood-based DNA sequencing and proteomic measurements (1,148 proteins by SomaScan in TOPMed and 2917 proteins by Olink in UKB), we identify 32 and 345 proteins from TOPMed and UKB, respectively, associated with CHIP and most prevalent driver genes (DNMT3A, TET2, and ASXL1). These associations show substantial heterogeneity by driver genes, sex, and race, and were enriched for immune response and inflammation pathways. Mendelian randomization in humans, coupled with ELISA in hematopoietic Tet2-/- vs wild-type mice validation, disentangle causal proteomic perturbations from TET2 CHIP. Lastly, we identify plasma proteins shared between CHIP and CAD.},
}

@article {pmid41308682,
year = {2025},
author = {Necchi, A and Stitou, H and Bhanvadia, S and Psutka, SP},
title = {SunRISe-4 perioperative safety and TURBT stratification - Authors' reply.},
journal = {The Lancet. Oncology},
volume = {26},
number = {12},
pages = {e621},
doi = {10.1016/S1470-2045(25)00671-0},
pmid = {41308682},
issn = {1474-5488},
}

@article {pmid41308477,
year = {2025},
author = {Hoggard, NK and Elshafae, SM and Daniels, NA and Young, JA and Premanandan, C and Echols, JB and Chandrashekar, DS and Hildreth, BE and Haffner, MC and Rosol, TJ},
title = {Comparative histologic survey and transcriptomic investigation into canine prostate carcinoma.},
journal = {Research in veterinary science},
volume = {198},
number = {},
pages = {105981},
doi = {10.1016/j.rvsc.2025.105981},
pmid = {41308477},
issn = {1532-2661},
abstract = {Dogs share features in prostate gland anatomy, physiology, and pathology with men. However, human and canine prostate carcinoma (PC) have histologic and molecular differences. Particularly, the histogenesis of canine PC (cPC) is unclear. This study investigated the origin of cPC using histopathology and transcriptomics with comparison to men. Prostate glands retrospectively and prospectively collected from 445 dogs (approximately 95 % autopsy samples) were surveyed for early carcinomas and preneoplastic lesions, particularly high-grade prostatic intraepithelial neoplasia (HGPIN) due to its role in the pathogenesis of PC in men. Lineage gene signatures defining prostate luminal epithelium and urothelium were identified for inter- and intraspecies RNA-sequencing comparisons, including between cPC and canine urinary bladder urothelial carcinoma (UC). Postmortem prostate lesion frequencies were similar to previously reported canine studies. Intraductal/intra-acinar growth (31/35; 88.6 %) was common in representative samples of cPC. Prostate epithelial changes consistent with HGPIN in men were not observed. Proliferative lesions and early carcinomas were rare (7/445; 1.6 %). Patterns in prostate and urothelium marker gene expression signatures differed between human and canine PC. Compared to non-neoplastic prostate gland, cPC had significantly decreased prostate-specific and increased urothelium gene signatures. The results suggest many cases diagnosed as cPC are UC or have urothelial differentiation and thus differ from PC in men, with important implications for canine tumor classification and translational studies.},
}

@article {pmid41308080,
year = {2025},
author = {Gee-Rodriguez, K and Yun, J and Duong, A and Indorf, A},
title = {Comparing relative dose intensity of weekly nab-paclitaxel regimens in early breast cancer: A retrospective study at a large academic outpatient cancer center.},
journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners},
volume = {},
number = {},
pages = {10781552251399901},
doi = {10.1177/10781552251399901},
pmid = {41308080},
issn = {1477-092X},
abstract = {IntroductionNational guidelines for breast cancer support substitution with nab-paclitaxel for paclitaxel or docetaxel due to medical necessity.[1] This study aimed to assess for correlation between weekly nab-paclitaxel dose and relative dose intensity (RDI) amongst early breast cancer patients.MethodsThis single-center, retrospective cohort study included adult patients with early breast cancer who switched from weekly paclitaxel to nab-paclitaxel after hypersensitivity reaction. The primary outcome of RDI was assessed in patients receiving nab-paclitaxel 80 mg/m[2] (NB80) or 100 mg/m[2] (NB100) intravenously (IV) weekly. Secondary outcomes included adverse effects, incidence of nab-paclitaxel alterations, and growth factor (GCSF) administration for secondary prophylaxis.ResultsAmongst 26 patients, the median age was 43 years (range 33 to 71), with the majority (54%) having stage II or later disease. Median RDI with NB80 was 91% (range 69 to 100%) versus 86% (55 to 100%) with NB100. Fifty percent of all patients underwent dose reductions. Dose delays occurred in a higher proportion of patients on 50% with NB80 vs 33% with NB100. Early nab-paclitaxel discontinuations occurred more on NB100 (33% vs 10%). Incidence of chemotherapy-induced peripheral neuropathy (CIPN) was 80% vs 83% with NB80 and NB100, respectively, while grade 2 CIPN was more common on NB100 (50% vs 35%). A lower rate of neutropenia resulted from NB80 (60 vs 67% with NB100).ConclusionNab-paclitaxel dosed at 80 mg/m[2] IV weekly, after switching due to paclitaxel hypersensitivity, may promote improved RDI and safety compared to nab-paclitaxel 100 mg/m[2] weekly amongst early breast cancer patients.},
}

@article {pmid41308031,
year = {2025},
author = {Gardner, JA and Nusapan, R and Tan, J and Levy, B and Tang, G and Fang, M and Velagaleti, GV and Cao, Y and Astbury, C and Mixon, JC and J Souers, R and Peterson, JF and Zou, YS},
title = {Current and Future Utilization of Optical Genome Mapping: Insights From the 2024 College of American Pathologists Supplemental Questionnaire.},
journal = {Archives of pathology & laboratory medicine},
volume = {},
number = {},
pages = {},
doi = {10.5858/arpa.2025-0472-CP},
pmid = {41308031},
issn = {1543-2165},
abstract = {CONTEXT.—: Optical genome mapping (OGM) represents a promising cytogenomic technology that detects structural variants, including fusions, rearrangements, copy number variants, and loss of heterozygosity, in a single assay. Unlike karyotyping, fluorescence in situ hybridization, or chromosomal microarray, OGM leverages long-molecule imaging to map the whole genome with high resolution. This positions OGM as a novel tool for constitutional and somatic/cancer genomics. However, its current and planned utilization in clinical and research settings remains unknown, necessitating further investigation.

OBJECTIVE.—: To investigate the current utilization of OGM in clinical and research laboratories, assess its applications, and evaluate future utilization strategies.

DESIGN.—: In 2024, a supplemental questionnaire was incorporated into 6 College of American Pathologists proficiency testing programs to evaluate OGM's utilization.

RESULTS.—: Of 921 returned questionnaires, 712 were analyzed after duplicates were removed. Sixty-seven (9.4%) currently offered OGM testing: 5.2% (37) for research only, 1.8% (13) for only clinical use, and 2.4% (17) for both. Future adoption plans showed 7.6% (53 of 700 laboratories) and 7.9% (55 of 700 laboratories) aiming to implement OGM clinically within 12 and 24 months, respectively. The most common applications included hematologic malignancies and constitutional/germline postnatal disorders, followed by prenatal testing. International laboratories demonstrated statistically higher utilization rates than domestic laboratories (P = .001).

CONCLUSIONS.—: This first survey on OGM clinical utilization reveals its status as a niche technology, with 67 laboratories currently using it. Its primary clinical applications are in constitutional/germline analysis and hematologic malignancies. Although international laboratories led in 2024, 108 laboratories (domestic and international) plan clinical adoption within 24 months, signaling OGM's potential for broader integration.},
}

@article {pmid41307621,
year = {2025},
author = {Lopez, K and Silva, M and Briant, KJ and Fox, B and Dee, C and Ceballos, RM and Thompson, B},
title = {Involving Latinas in Understanding Barriers, Facilitators, and Appropriate Outreach for Mammography in Tacoma, Washington, USA.},
journal = {Journal of community health},
volume = {},
number = {},
pages = {},
pmid = {41307621},
issn = {1573-3610},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {Breast cancer screening rates are lower for Hispanic females (Latinas) than their non-Hispanic White counterparts. This discrepancy is partly due to health disparities, such as limited access to care, inability to take time off work, lack of health insurance, and cultural and emotional barriers. In response to a health department request, the Carol Milgard Breast Center conducted a qualitative assessment, as part of a community grant pilot award from Fred Hutchinson Cancer Center, to better understand the barriers and facilitators influencing Latinas' participation in mammography screening. The objective was to identify key characteristics of an intervention aimed at encouraging mammogram uptake among Latinas. Forty women were recruited and consented to participate in structured interviews, which included questions on their perceptions of mammography. The interviews explored structural barriers (e.g., lack of insurance), cultural issues (e.g., prioritizing family over individual health), and emotional concerns (e.g., fear of embarrassment). By detailing lessons learned and community identified outreach strategies, this work advances the evidence base on community engagement with Latinas for cancer education and outreach. Findings underscore the need for linguistically and culturally tailored resources, trusted messengers, and outreach approaches that meet Latinas where they are. The identified strategies can inform interventions to improve mammography uptake in similar communities and guide larger-scale implementation efforts.},
}

@article {pmid41307276,
year = {2025},
author = {Robins, LI and Gafken, P and Lin, C and Jones, L and Hooper, SE},
title = {Dissecting HOCl Action in Chronic Wound Biofilms: Proteomic Insights From a Host-Relevant Model of Pseudomonas aeruginosa.},
journal = {MicrobiologyOpen},
volume = {14},
number = {6},
pages = {e70181},
pmid = {41307276},
issn = {2045-8827},
support = {//The authors received no specific funding for this work./ ; },
mesh = {*Pseudomonas aeruginosa/drug effects/physiology ; *Biofilms/drug effects/growth & development ; *Hypochlorous Acid/pharmacology/metabolism ; Proteomics ; *Proteome/analysis ; *Bacterial Proteins/analysis/metabolism ; Microbial Viability/drug effects ; Pseudomonas Infections/microbiology ; Humans ; },
abstract = {Pseudomonas aeruginosa is found in 48%-52% of chronic wound biofilms, where its resistance to antimicrobials and host immunity presents a major clinical challenge. Although hypochlorous acid (HOCl) is known to be an effective antimicrobial, its mechanism of action remains unclear because standard experimental conditions often produce a mixture of HOCl and hypochlorite (OCl[-]), making it difficult to isolate the effects of HOCl. Here, we use proteomic profiling to investigate the effects of a pure, stable HOCl gel on P. aeruginosa biofilms in a physiologically relevant chronic wound model. We applied HOCl gel (5.7 mM, pH 6) to mature P. aeruginosa biofilms established in a wound-mimicking flow model. Proteins were analyzed using tandem mass tag (TMT)-based quantitative proteomics, identifying 1,878 proteins. HOCl treatment significantly reduced biofilm viability and altered the abundance of 330 proteins. We observed substantial depletion of proteins involved in biosynthesis, virulence, antibiotic resistance, and biofilm formation, alongside enrichment of stress response proteins. These findings indicate a shift toward survival phenotypes and weakened pathogenicity. Our data reveal that HOCl disrupts multiple pathways essential for P. aeruginosa survival and virulence. Crucially, our experimental design eliminates confounding factors that can lead to unintentional testing of mixed HOCl and OCl[-] species, allowing us to assess the specific effects of HOCl. These findings call for a re-evaluation of HOCl research methodologies and reiterate the importance of realistic infection models in antimicrobial testing.},
}

*Pseudomonas aeruginosa/drug effects/physiology
*Biofilms/drug effects/growth & development
*Hypochlorous Acid/pharmacology/metabolism
Proteomics
*Proteome/analysis
*Bacterial Proteins/analysis/metabolism
Microbial Viability/drug effects
Pseudomonas Infections/microbiology
Humans

@article {pmid41281241,
year = {2025},
author = {Ukogu, OA and Montague, Z and Altan-Bonnet, G and Nourmohammad, A},
title = {Design principles of the cytotoxic CD8[+] T-cell response.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {41281241},
issn = {2331-8422},
support = {R35 GM142795/GM/NIGMS NIH HHS/United States ; ZIA BC012007/ImNIH/Intramural NIH HHS/United States ; },
abstract = {Cytotoxic T lymphocytes eliminate infected or malignant cells, safeguarding surrounding tissues. Although experimental and systems-immunology studies have cataloged many molecular and cellular actors involved in an immune response, the design principles governing how the speed and magnitude of T-cell responses emerge from cellular decision-making remain elusive. Here, we recast the T-cell response as a feedback-controlled program, wherein the rates of activation, proliferation, differentiation and death are regulated through antigenic, pro- and anti-inflammatory cues. By exploring a broad class of feedback-controller designs as potential immune programs, we demonstrate how the speed and magnitude of T-cell responses emerge from optimizing signal-feedback to protect against diverse infection settings. We recover an inherent trade-off: infection clearance at the cost of immunopathology. We show how this trade-off is encoded into the logic of T-cell responses by hierarchical sensitivity to different immune signals. Notably, we find that designs that balance harm from acute infections and autoimmunity produce immune responses consistent with experimentally observed patterns of T-cell effector expansion in mice. Extending our model to immune-based T-cell therapies for cancer tumors, we identify a trade-off between the affinity for tumor antigens ("quality") and the abundance ("quantity") of infused T-cells necessary for effective treatment. Finally, we show how therapeutic efficacy can be improved by targeted genetic perturbations to T-cells. Our findings offer a unified control-logic for cytotoxic T-cell responses and point to specific regulatory programs that can be engineered for more robust T-cell therapies.},
}

@article {pmid41279420,
year = {2025},
author = {Matsen, FA and Dumm, W and Sung, K and Johnson, MM and Rich, D and Starr, T and Song, YS and Fukuyama, J and Haddox, HK},
title = {Separating selection from mutation in antibody language models.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279420},
issn = {2692-8205},
support = {R01 AI146028/AI/NIAID NIH HHS/United States ; DP2 AI177890/AI/NIAID NIH HHS/United States ; R56 HG013117/HG/NHGRI NIH HHS/United States ; R01 HG013117/HG/NHGRI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; },
abstract = {Antibodies are encoded by nucleotide sequences that are generated by V(D)J recombination and evolve according to mutation and selection processes. Existing antibody language models, however, focus exclusively on antibodies as strings of amino acids and are fitted using standard language modeling objectives such as masked or autoregressive prediction. In this paper, we first show that fitting models using this objective implicitly incorporates nucleotide-level mutation processes as part of the protein language model, which degrades performance when predicting effects of mutations on functional properties of antibodies. To address this limitation, we devise a new framework: a Deep Amino acid Selection Model (DASM) that learns the selection effects of amino-acid mutations while explicitly factoring out the nucleotide-level mutation process. By fitting selection as a separate term from the mutation process, the DASM exclusively quantifies functional effects: effects that change some aspect of the function of the antibody. This factorization leads to substantially improved performance on standard functional benchmarks. Moreover, our model is an order of magnitude smaller and multiple orders of magnitude faster to evaluate than existing approaches, as well as being readily interpretable.},
}

@article {pmid41042379,
year = {2025},
author = {Bharadwaj, MC and Holt, SK and Iyer, HS and Lee, JR and Wolff, EM and Rebbeck, TR and Gore, JL and Nyame, YA},
title = {The Legacy of Chattel Slavery and Its Association with Prostate Cancer Incidences in the Southeastern United States.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {34},
number = {12},
pages = {2186-2193},
pmid = {41042379},
issn = {1538-7755},
support = {P50 CA097186/CA/NCI NIH HHS/United States ; CDMRP W81XWH211053//U.S. Department of Defense (DOD)/ ; P50 CA097186-17//National Cancer Institute (NCI)/ ; FY23-POP-02//Andy Hill CARE Fund (CARE)/ ; //Zhu Family Center for Global Cancer Prevention/ ; },
mesh = {Humans ; Male ; *Prostatic Neoplasms/epidemiology ; Incidence ; Southeastern United States/epidemiology ; *Enslavement/history/statistics & numerical data ; Black or African American/statistics & numerical data ; Middle Aged ; Health Status Disparities ; Aged ; White People/statistics & numerical data ; Socioeconomic Factors ; History, 19th Century ; White ; },
abstract = {BACKGROUND: Present-day disparities in prostate cancer outcomes are a direct result of major historical events, such as chattel slavery. Few studies have evaluated the association between the legacy of historical racism and prostate cancer, a disease with a wide health disparity globally. In this study, we assess the relationship between county-level historical chattel slavery in 1860 and prostate cancer incidences in 2018 among Black and White individuals.

METHODS: Prostate cancer incidences, socioeconomic variables, and 1860 slave data were all obtained from publicly available datasets. Our primary exposure was county-level density of enslaved people in 1860. Our primary dependent variable was prostate cancer incidence per 100,000. We used Poisson log-linear regression models to estimate the difference in county-level cancer counts per 10% increase in enslaved individuals in a county, adjusting for age and numerous social determinants of health.

RESULTS: County-level density of enslaved people correlated with various present-day social determinants of health. In our multivariable adjusted model, increased county-level enslaved populations in 1860 were independently associated with a significant increase in 2018 county-level prostate cancer incidences for both White and Black individuals.

CONCLUSIONS: Our results indicate that the presence of county-level chattel slavery was significantly associated with poorer present-day social determinants of health and increased prostate cancer incidences, regardless of race.

IMPACT: Addressing health inequities requires the acknowledgment of the role historical chattel slavery plays in health disparities affecting marginalized and low socioeconomic communities in America.},
}

Humans
Male
*Prostatic Neoplasms/epidemiology
Incidence
Southeastern United States/epidemiology
*Enslavement/history/statistics & numerical data
Black or African American/statistics & numerical data
Middle Aged
Health Status Disparities
Aged
White People/statistics & numerical data
Socioeconomic Factors
History, 19th Century
White

@article {pmid40779552,
year = {2025},
author = {Ahmed, S and DiPersio, J and Essell, J and Diefenbach, C and Perales, MA and Castilla-Llorente, C and Dahiya, S and Liu, Y and Xu, H and Fanton, C and Chaudhry, S and Lee, ZH and Marcondes, AMQ and Tagliaferri, MA and Zalevsky, J and Miklos, D and Turtle, CJ and McGuirk, J},
title = {NKTR-255 enhances complete response following CD19 CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma.},
journal = {Blood advances},
volume = {9},
number = {23},
pages = {6092-6095},
doi = {10.1182/bloodadvances.2025016423},
pmid = {40779552},
issn = {2473-9537},
}

@article {pmid41305628,
year = {2025},
author = {Garfias-Avila, N and Wang, CY and Lampe, JW and Mendoza, JA and Tapsoba, JD and Alcalá, NJ and Levy, L and Neuhouser, ML},
title = {Implications for Dietary Guideline Policy of a Cultural Adaptation of the US Dietary Guidelines for Women of Mexican Descent: A Pilot Study.},
journal = {Nutrients},
volume = {17},
number = {22},
pages = {},
pmid = {41305628},
issn = {2072-6643},
support = {1P50CA148143-16S1/NH/NIH HHS/United States ; },
mesh = {Humans ; Female ; Pilot Projects ; Adult ; *Nutrition Policy ; Middle Aged ; *Mexican Americans ; *Diet, Healthy/ethnology ; United States ; Diet ; Biomarkers/blood ; White ; },
abstract = {Background/Objectives: This study aims to evaluate whether the Dietary Guidelines for Americans (DGA) are effective for maintaining a healthy diet among Mexican-descent populations in the US or if a more culturally tailored policy approach is warranted. Methods: As a first outcome, 20 healthy women of Mexican descent from the Seattle area participated in a pilot randomized controlled trial. They were randomly assigned (10 participants each) to either a group receiving instruction on the standard 2015 DGA or a group receiving an adaptation of the DGA focused on traditional Mexican cuisine and culture. In this 12-week study (with follow-ups at 3 and 6 months), participants' acceptability of the cultural adaptation of the DGA was compared with that of the standard DGA with end-of-study surveys. Ten blood-based metabolic biomarkers were assessed at baseline and 3 months. Dietary changes at 3 months were assessed with a Food Frequency Questionnaire (FFQ) that was translated into Spanish but not culturally adapted. The secondary outcome was dietary change at 6 months. Results: The primary findings at 3 months showed that serum free fatty acids were reduced for the standard DGA arm. Carbohydrate consumption was reduced in the standard DGA arm only. The end-of-study survey results suggested that both interventions were well received by participants. Conclusions: The preliminary findings from this small sample size suggest that depending on a person's priorities, either intervention could be offered, with each arm showing slightly different dietary and biomarker outcomes.},
}

Humans
Female
Pilot Projects
Adult
*Nutrition Policy
Middle Aged
*Mexican Americans
*Diet, Healthy/ethnology
United States
Diet
Biomarkers/blood
White

@article {pmid41305521,
year = {2025},
author = {Swan, DA and Krantz, EM and Byrne, CM and Okuku, F and Nankoma, J and Mutyaba, I and Phipps, W and Schiffer, JT},
title = {Human Herpes Virus-8 Oral Shedding Heterogeneity Is Due to Varying Rates of Reactivation from Latency and Immune Containment.},
journal = {Viruses},
volume = {17},
number = {11},
pages = {},
pmid = {41305521},
issn = {1999-4915},
support = {5R01CA239593-25/NH/NIH HHS/United States ; },
mesh = {Humans ; *Virus Shedding ; *Herpesvirus 8, Human/physiology/immunology ; *Virus Latency ; *Virus Activation ; Viral Load ; Uganda/epidemiology ; Longitudinal Studies ; *Herpesviridae Infections/virology/immunology ; Male ; HIV Infections/virology/complications/immunology ; Female ; Adult ; *Mouth Mucosa/virology ; Sarcoma, Kaposi/virology/immunology ; Models, Theoretical ; },
abstract = {Human herpesvirus-8 (HHV-8) is a gamma herpesvirus linked to the development of Kaposi sarcoma (KS). KS is more common in persons living with HIV (PLWH), but endemic KS in HIV-negative individuals is also common in sub-Saharan Africa. HHV-8 shedding occurs in the oral mucosa and is likely responsible for transmission. The mechanistic drivers of different HHV-8 shedding patterns in infected individuals are unknown. We applied stochastic mathematical models to a longitudinal study of HHV-8 oral shedding in 295 individuals in Uganda who were monitored daily with oral swabs. Participants were divided into four groups based on whether they were HIV-negative or -positive, as well as KS-negative or -positive. In all groups, we observed a wide variance of shedding patterns, including no shedding, brief episodic low viral load shedding, prolonged episodic medium viral load shedding, and persistent high viral load shedding. Our model closely replicates patterns in individual data and attributes higher shedding rates to increased rates of viral reactivation and lower median viral load values to more rapid and effective engagement of cytolytic immune responses. Our model provides a framework for understanding different shedding patterns observed in individuals with HHV-8 infection.},
}

Humans
*Virus Shedding
*Herpesvirus 8, Human/physiology/immunology
*Virus Latency
*Virus Activation
Viral Load
Uganda/epidemiology
Longitudinal Studies
*Herpesviridae Infections/virology/immunology
Male
HIV Infections/virology/complications/immunology
Female
Adult
*Mouth Mucosa/virology
Sarcoma, Kaposi/virology/immunology
Models, Theoretical

@article {pmid41301877,
year = {2025},
author = {Bastin, N and Mezzanotte-Sharpe, J and Alvarez, R and Partridge, SC and Dintzis, SM and Stanton, SE and Gadi, VK and Kennedy, LC},
title = {Exploratory Analysis of the Impact of a Single Dose of Trastuzumab on the Immune Microenvironment in HER2-Positive Early-Stage Breast Cancer.},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
pmid = {41301877},
issn = {2227-9059},
support = {1P30CA015704-20/NH/NIH HHS/United States ; 1R01CA248192-20/NH/NIH HHS/United States ; N/A//Safeway Foundation/ ; 1T32CA009515-20/NH/NIH HHS/United States ; Hayden Family Foundation Young Investigator Award//ASCO/CCF/ ; 2T32CA217834-07/NH/NIH HHS/United States ; 5K12CA090625-25/NH/NIH HHS/United States ; },
abstract = {Background: How the tumor microenvironment (TME) influences treatment response in HER2+ breast cancer following HER2-directed therapy is crucial for individualizing therapies and is currently understudied. The purpose of this exploratory analysis was to elucidate changes in the TME following treatment with trastuzumab. Methods: Fourteen HER2+ early-stage breast cancer patients underwent tissue biopsies before and after a dose of trastuzumab. Samples were evaluated for stromal tumor-infiltrating lymphocytes (TILs) and RNA-based cell and gene expression signatures. Tumor inflammation signature scores were generated to measure whether an adaptive immune response developed to trastuzumab within the tumor. Patients were also stratified as immune responders or non-responders based on changes in TILs. Results: Of the 14 enrolled patients, 13 had samples available for analysis, and 7 had an immune response as assessed by changes in TILs compared to 6 non-responders. Trastuzumab treatment decreased PD-L1 and TGF-Beta signatures and increased CTLA4 gene signatures, although results were not statistically significant, and increased DUSP1 expression. In the TIL responder group, there was increased expression of dendritic cells as well as MARCO expression. Conclusions: These findings, although exploratory in nature, highlight trastuzumab's ability to induce an immune response and suggest that some patients may be more primed to mount an immune response following treatment than others. Patients without a robust response in TILs may benefit from additional agents to favorably modulate the TME for optimized responses to HER2-directed therapy, an area of research which warrants further study.},
}