@article {pmid42926042,
year = {2026},
author = {Goodman, JS and Stanaway, IB and Krueger, MA and Lee, YJ and Vusse, LKV and Waghmare, A and Cheng, GS and Dadwal, S and Boeckh, M and Gharib, SA and Hill, JA and Morrell, ED},
title = {Transcriptional Signatures Associated with Etiology of Post-Hematopoietic Cell Transplant Lung Injury.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
pmid = {42926042},
issn = {2666-6367},
support = {R01 HL188754/HL/NHLBI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; K23 AI119133/AI/NIAID NIH HHS/United States ; R01 HL169265/HL/NHLBI NIH HHS/United States ; K24 HL093294/HL/NHLBI NIH HHS/United States ; P30 DK017047/DK/NIDDK NIH HHS/United States ; P30 DK089507/DK/NIDDK NIH HHS/United States ; K24 AI190345/AI/NIAID NIH HHS/United States ; },
abstract = {Allogeneic hematopoietic cell transplant (alloHCT) is a potentially curative therapy for many hematologic disorders but is frequently complicated by infectious and noninfectious pulmonary injury. Differentiating these etiologies is challenging in clinical practice, and it remains unclear whether response signatures can distinguish infectious from non-infectious lung injury following transplantation. We performed bulk RNA sequencing of whole-blood samples from 52 alloHCT recipients within 120 days of transplantation who developed lung injury due to bacterial, viral, or fungal pathogens as well as idiopathic pneumonia syndrome (IPS). We compared expression of genes and immune programs across etiologies of lung injury. Distinct transcriptional programs were observed across etiologies. Viral pneumonia showed enrichment of interferon and adaptive immune signaling pathways. Bacterial pneumonia demonstrated enrichment of innate immune and heme metabolism pathways. Fungal pneumonia exhibited the strongest enrichment of cellular proliferation pathways. IPS showed lower enrichment of immune signaling pathways than infectious etiologies. Transcriptomic responses differ between infectious and noninfectious lung injury following alloHCT. These findings highlight the potential utility of transcriptomic profiling to support diagnosis, guide therapeutic management, and risk-stratify patients following transplantation.},
}

@article {pmid42926108,
year = {2026},
author = {Kalinsky, K and Wander, SA and Hamilton, E and Graff, SL and Jeselsohn, R and Park, KH and Demirci, U and Martin, M and Layman, RM and Hurvitz, SA and Sammons, S and Kaufman, PA and Ravenberg, E and Amdur, S and Litchfield, LM and Bianchini, G},
title = {Overall survival from the phase III postMONARCH trial of abemaciclib plus fulvestrant versus placebo plus fulvestrant for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2026.10.1283},
pmid = {42926108},
issn = {1569-8041},
abstract = {BACKGROUND: The phase III postMONARCH trial demonstrated a statistically significant improvement in progression-free survival (PFS) with abemaciclib plus fulvestrant versus placebo plus fulvestrant in participants with HR+, HER2- advanced breast cancer (ABC) after disease progression on prior CDK4/6i plus endocrine therapy (ET). Here we report the prespecified final overall survival (OS) analysis.

PARTICIPANTS AND METHODS: Eligible patients had disease progression on a CDK4/6i plus aromatase inhibitor as initial therapy for ABC or recurrence on or after adjuvant CDK4/6i plus ET. Participants were randomly assigned 1:1 to receive abemaciclib plus fulvestrant or placebo plus fulvestrant. The final OS analysis was pre-specified at 200 OS events (HR boundary 0.753). Time-to-event analyses used the Kaplan-Meier method, and stratified Cox models were used to estimate the HR and 95% confidence intervals (CI).

RESULTS: A total of 368 participants were randomly assigned 1:1 to abemaciclib plus fulvestrant (n = 182) or placebo plus fulvestrant (n = 186). At data cutoff, median follow-up was approximately 37 months; 200 OS events were observed (90 [50%] vs 110 [59%]). Median OS was 32.1 months with abemaciclib plus fulvestrant versus 24.6 months with placebo plus fulvestrant (HR, 0.80 [95% CI, 0.60 to 1.06]; P = 0.11, boundary for significance not reached). OS differences were consistent across subgroups. Updated PFS was consistent with the primary analysis (HR, 0.78 [95% CI, 0.62 to 0.99]; nominal P = 0.039). Time to second progression and chemotherapy-free survival also favored abemaciclib plus fulvestrant. Safety was consistent with the established abemaciclib profile with no new signals identified.

CONCLUSION: Abemaciclib plus fulvestrant resulted in numerically longer median OS versus placebo plus fulvestrant, though statistical significance was not reached. The totality of evidence supports consideration of abemaciclib-based treatment for patients with HR+, HER2- ABC after disease progression on prior CDK4/6i plus ET.

NCT05169567.},
}

@article {pmid42926404,
year = {2026},
author = {Jiang, C and Li, JJ},
title = {scStable: assessing scRNA-seq analysis stability under bulk-derived between-sample variation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42926404},
issn = {2692-8205},
support = {R01 HG014687/HG/NHGRI NIH HHS/United States ; R35 GM140888/GM/NIGMS NIH HHS/United States ; },
abstract = {Single-cell RNA sequencing (scRNA-seq) studies often profile only one or a few biological samples, limiting assessment of discovery stability under between-sample variation. We present scStable, a framework for assessing scRNA-seq analysis stability by generating synthetic samples that preserve cell-level heterogeneity from a single-sample reference while injecting bulk-derived between-sample variation. In gastric cancer data comprising 21 matched scRNA-seq and bulk RNA-seq profiles, scStable better recapitulates observed between-sample variation than ZINB-WaVE, subsampling, and Gaussian noise injection. Using synthetic samples, scStable enables stability-aware analysis, including prioritization of stable differentially expressed genes and selection of clustering methods and hyperparameters.},
}

@article {pmid42926483,
year = {2026},
author = {Chavan, A and Ries, R and Biswas, P and Farrar, JE and Meshinchi, S and Roy Choudhury, S},
title = {CBFA2T3-GLIS2 establishes transcriptionally permissive enhancer hypermethylation associated with venetoclax response in pediatric AML.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42926483},
issn = {2692-8205},
support = {P20 GM121293/GM/NIGMS NIH HHS/United States ; },
abstract = {CBFA2T3-GLIS2 (C/G) defines a high-risk pediatric AML subtype in which de novo enhancer rewiring sustains an aggressive leukemic transcriptional state. The early epigenomic mechanisms reinforcing this program and linking it to leukemic survival remain incompletely defined. Here, we identify enhancer-proximal hypermethylation as a noncanonical, transcription-permissive feature of C/G AML. Using primary C/G-positive AML samples and a developmentally relevant C/G-transformed cord blood hematopoietic stem/progenitor cell model, we integrated DNA methylation, chromatin state, fusion occupancy, and gene expression across early and leukemia-stage contexts. Early C/G-associated hypermethylated regions localized near H3K27ac/H3K4me1-marked active or primed cis-regulatory elements, were enriched for ERG/ETS-like motifs, and showed related architecture in leukemia-stage contexts. DNMT3B was prominently increased in C/G contexts, and its loss selectively altered methylation-associated gene expression without measurably changing global 5mC. Genetic DNMT3B loss increased venetoclax sensitivity in vitro, while pharmacologic DNMT3B inhibition with Nanaomycin-A similarly enhanced venetoclax response. During venetoclax treatment, DNMT3B-deficient xenografts showed reduced disease burden and prolonged survival. To assess whether this interaction extended to clinically used hypomethylating agents, azacitidine or decitabine plus venetoclax induced apoptosis-related transcriptional programs and mitochondrial depolarization. These findings identify hypermethylated active cis-regulatory elements as C/G-associated states linked to transcriptional dysregulation and venetoclax response.},
}

@article {pmid42926802,
year = {2026},
author = {Chankhunthod, AB and Sorenson-Graff, R and Mercoli, J and Ishida, T and Dozono, S and Wellington, R and Fong, Y and Hadland, B and Zhao, HG},
title = {Single-Cell Behavioromics Enables Fate Prediction of Individual Hematopoietic Stem Cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42926802},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 HL168110/HL/NHLBI NIH HHS/United States ; R01 HL179317/HL/NHLBI NIH HHS/United States ; U24 DK126127/DK/NIDDK NIH HHS/United States ; },
abstract = {Achieving near-single-cell precision in the prospective identification of long-term engrafting hematopoietic stem cells (LT-HSCs) remains challenging, likely because current static, point-in-time single-cell phenotyping technologies do not capture the dynamic nature of cell fate decisions. Here, we overcome this barrier by longitudinally tracking individual hematopoietic stem and progenitor cells (HSPCs) in ex vivo niche cultures using live imaging, coupled with downstream immunophenotyping, single-cell transcriptomics, and transplant assays. Deep learning analysis of live imaging data achieved 98.5% average precision in predicting serially-engrafting LT-HSC (serial-LT-HSC) identity from each cell's behaviorome (the totality of observed behaviors), outperforming currently available technologies. Serial-LT-HSCs exhibited lower motility among HSPC populations, which was associated with reduced Activin signaling activity and elevated expression of cell adhesion genes. Correspondingly, antagonizing Activin signaling by Inhibin-A treatment in ex vivo niche cultures suppressed HSPC motility while increasing the frequency of post-expansion serial-LT-HSCs, revealing a novel role for Activin signaling in HSPC behavior and fate determination. Collectively, this study establishes a broadly applicable framework that connects behavioromic analysis and single-cell transcriptomics to enable near-single-cell precision in predicting stem cell fate and uncover molecular mechanisms governing behavior-fate relationships.},
}

@article {pmid42927981,
year = {2026},
author = {Arthur, JA and Case, AA and Patel, JN and Broglio, K and Nerness, R and Kale, S and Dussault, N and Ellis, R and Del Fabbro, E and Reddy, A and Ho, J and Childers, JW and Halphen, JM and Robbins-Welty, GA and Jones, CA and Davis, M},
title = {Top Ten Tips Palliative Care Clinicians Should Know About Urine Drug Testing.},
journal = {Journal of palliative medicine},
volume = {},
number = {},
pages = {10966218261499025},
doi = {10.1177/10966218261499025},
pmid = {42927981},
issn = {1557-7740},
abstract = {Opioid therapy is a key component of palliative care delivery but may sometimes be associated with complications such as nonmedical opioid use (NMOU) behavior. Clinicians are encouraged to adopt risk-mitigation strategies to minimize NMOU while optimizing opioid prescribing practices. Urine drug testing (UDT) is usually implemented in palliative care (PC) settings to mitigate such risks, but its role is not well-defined. In this article, a group of PC specialists with specific clinical and research interests and expertise in UDT offers 10 tips regarding the current evidence surrounding UDT, its appropriate application, interpretation of results, and the utilization of test results within the PC context. The goal is to inform practicing PC clinicians regarding the use of UDT in routine opioid therapy.},
}

@article {pmid42934071,
year = {2026},
author = {Gillessen, S and Turco, F and Davis, ID and Efstathiou, JA and Emmett, L and Fizazi, K and James, ND and Shore, N and Small, EJ and Smith, M and Sweeney, CJ and Tombal, BF and Walz, J and Zilli, T and Lin, HM and Pedrani, M and Puglisi, M and Achard, V and Agarwal, N and Aggarwal, R and Antonarakis, ES and Aparicio, A and Armstrong, AJ and Bastos, DA and Attard, G and Axcrona, K and Ayadi, M and Batra, A and Beltran, H and Bjartell, A and Blanchard, P and Bossaert, F and Bourlon, MT and Briers, E and Briganti, A and Buttigliero, C and Castellano, D and Castro, E and Cheng, HH and Chi, KN and Chiong, E and Clarke, N and Cornford, P and Dai, B and Santis, M and Deschamps, A and Duran, I and Ekeke, ON and El Nahas, TIH and Fanti, S and Fatiregun, OA and Fay, A and Fong, PC and Fonteyne, V and Fossati, N and Francolini, G and Freedland, S and Quiroga, MNG and George, DJ and Giannarini, G and Gleave, ME and Gravis, G and Greene, K and Hadaschik, B and Hakim, L and Halabi, S and Heidegger, I and Heinrich, D and Herrmann, K and Hofman, MS and Hong, SK and Hope, TA and Horvath, LG and Hussain, MHA and Jereczek-Fossa, BA and Jones, B and Jones, RJ and Joshua, AM and Kanesvaran, R and Keizman, D and Khauli, RB and Kristiansen, G and Lang, J and Loblaw, A and Loeb, S and Mahal, BA and Maluf, FC and Mateo, J and Matheson, D and Matikainen, MP and McDermott, R and McKay, RR and Mehra, N and Merseburger, AS and Michalski, J and Morgans, AK and Morris, MJ and Mrabti, H and Mukherji, D and Murphy, DG and Murthy, V and Mutambirwa, SBA and Nguyen, PL and O'Sullivan, JM and Oh, WK and Oprea-Lager, D and Ost, P and Padhani, AR and Paller, CJ and Pang, JS and Papatsoris, A and Parker, C and Patašius, A and Poon, DMC and Pritchard, CC and Rabah, DM and Rathkopf, D and Ryan, CJ and Rylance, A and Saad, F and Sade, JP and Samuels, A and Sandhu, S and Sartor, OA and Schaeffer, EM and Schmidt-Hegemann, NS and Seibert, TM and Sharifi, N and Skoneczna, IA and Sokolova, A and Spratt, DE and Srinivas, S and Suzuki, H and Taplin, ME and Karlsson, CT and Tilki, D and Uemura, H and Ürün, Y and van As, N and van den Bergh, R and Vapiwala, N and von Amsberg, G and Wei, Q and Yamoah, K and Ye, D and Yu, EY and Zapatero, A and Omlin, A},
title = {Management of Patients with High-risk Localised, Locally Advanced, and Biochemically Recurrent Prostate Cancer: Report from the 2026 Advanced Prostate Cancer Consensus Conference.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2026.09.027},
pmid = {42934071},
issn = {1873-7560},
abstract = {BACKGROUND: Innovations have improved outcomes in high-risk localised, locally advanced, and biochemically recurrent prostate cancer (PC), yet high-level evidence remains limited for many management decisions. The 2026 Advanced Prostate Cancer Consensus Conference (APCCC) surveyed an international panel on key clinical questions to complement evidence-based guidelines.

OBJECTIVE: Here we present the voting results for the questions on high-risk localised, locally advanced, and biochemically recurrent PC from APCCC 2026.

Before the conference, a multidisciplinary panel of 144 international PC experts used a modified Delphi process to develop 313 multiple-choice consensus questions, of which 134 covered high-risk localised and locally advanced PC, including prostate-specific antigen (PSA) persistence and PSA recurrence, and side effects of treatment. These questions were administered to the 133 voting panel members "panellists" via a web-based survey prior to the conference.

Consensus was defined a priori as ≥75% agreement, with strong consensus defined as ≥90% agreement. Overall, consensus was reached for 44 of the 134 questions (32.8%), with seven questions reaching a strong consensus. Results and limitations The voting results show varying degrees of consensus, as discussed in this article and as detailed in the Supplementary Material. An interactive heat map for the questions can be found at https://apccc.org/APCCC2026-votings-localised-and-locally-advanced-prostate-cancer/. These findings do not include a formal literature review or meta-analysis.

CONCLUSIONS: The voting results can help physicians and patients navigate controversial areas of clinical management for which evidence is scant or conflicting. The findings can also help funders and policymakers in prioritising areas for future research. Importantly, APCCC 2026 once again identified important gaps (areas of no consensus) that merit evaluation in specifically designed trials.},
}

@article {pmid42936961,
year = {2026},
author = {Owoyemi, I and Sprangers, B and Bregman, A and Ramos, E and Webber, A and Murakami, N and Michalski-McNeely, B and Gordon, E and Blosser, CD},
title = {Best clinical practice in kidney transplant and cancer clinics.},
journal = {Current opinion in nephrology and hypertension},
volume = {},
number = {},
pages = {},
doi = {10.1097/MNH.0000000000001233},
pmid = {42936961},
issn = {1473-6543},
abstract = {PURPOSE OF REVIEW: Transplant onconephrology is an evolving subspeciality within nephrology that focuses on the interaction between cancer and the kidney. The goal of this subspecialty is to provide optimal care for people with cancers who are risk or develop cancer-related kidney complications or nephrotoxicity from cancer therapeutics. This goal is accomplished through application of increasing knowledge about transplant nephrology and oncology.

RECENT FINDINGS: People with a history of malignancy who are evaluated for kidney transplant need careful risk assessment to inform candidacy, immunosuppression management and prevent post-transplant recurrence. Post-transplant malignancies occur frequently and are a leading cause of death in kidney transplant recipients. People with pre- and post-transplant cancers experience significant stressors and healthcare demands, and benefit from multidisciplinary clinical care to address their high-risk conditions.

SUMMARY: This review provides a comprehensive overview of the best practices of outpatient clinical care for the growing population of high-risk patients with cancer before and after kidney transplant based on clinical experience and available data.},
}

@article {pmid42937546,
year = {2026},
author = {Borad, MJ and Droz Dit Busset, M and Javle, MM and Shaib, WL and Personeni, N and Mody, K and Babiker, H and Bergamo, F and Harris, WP and Damjanov, N and Macarulla, T and Brandi, G and Masi, G and Abou-Alfa, GK and Halfdanarson, TR and Knox, J and Tam, VC and Bernat, M and Engelhardt, M and Friedmann, S and Häckl, M and McKernan, P and Saulay, M and Goff, LW and Hollebecque, A and Adeva, J and Jeffry Evans, TR and Bridgewater, J and Foerster, F and Kendall, SD and Roth, G and Cunningham, D and Vogel, A and Niger, M and Mahipal, A and Mazzaferro, V},
title = {A pivotal Phase 2 study of derazantinib for previously-treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 aberrations: FIDES-01.},
journal = {Hepatology (Baltimore, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/HEP.0000000000001902},
pmid = {42937546},
issn = {1527-3350},
abstract = {BACKGROUND AIMS: To evaluate safety and efficacy of FGFR1-3 kinase inhibitor derazantinib, in advanced intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions or rearrangements (FGFR2F), mutations (FGFR2M), or amplifications (FGFR2A), previously treated with chemotherapy.

APPROACH RESULTS: Open-label, non-controlled Phase 2 trial. Patients with advanced iCCA, ≥1 prior chemotherapy, and FGFR2F (Substudy 1) or FGFR2M/FGFRA (Substudy 2), received once-daily oral derazantinib 300 mg until disease progression, unacceptable toxicity, consent withdrawal or investigator decision to stop. Efficacy was assessed by central radiology review using RECIST v1.1. Primary endpoints were objective response rate (ORR; Substudy 1) and 3-month progression-free survival (PFS3; Substudy 2). Other endpoints were PFS, ORR (Substudy 2), disease control rate (DCR), duration of response (DOR), and overall survival (OS). In Substudy 1, ORR and DCR were 22.3% (23/103 partial responses) and 75.7%, respectively; median (95% CI) PFS was 8.1 (5.5,8.3) months, DOR was 6.5 (4.6,9.2) months, and OS was 17.2 (12.5,22.4) months. In Substudy 2, PFS3 was 63% (27/43), ORR was 9.3% (3 partial, 1 complete response), DCR was 69.8%, and OS was 11.9 (8.4,15.9) months. There were no Grade 4 or 5 drug-related events. FGFR inhibitor class-specific toxicities included drug-related hyperphosphataemia (38%, Grade 3: 3%) and dry eye (36%). Nail disorders (10%, any grade or causality), stomatitis (5%), retinal events (5%), and palmar-plantar erythrodysesthesia (1%) were infrequent.

CONCLUSIONS: In previously chemotherapy treated, FGFR-inhibitor-naïve patients with iCCA harboring FGFR2 fusions, mutations, or amplifications, derazantinib showed clinically meaningful efficacy with durable objective responses, and a manageable safety profile.},
}

@article {pmid42944053,
year = {2026},
author = {Zhang, J and Murray, J and Mu, W and Venugopal, S and Yim, E and Einhaus, T and Radtke, S and Peterson, CW and Kiem, HP and An, DS},
title = {Evaluation of Anti-HIV-1 HSPC-Based Gene Therapy with Negative Selection Marker in Pigtail Macaques.},
journal = {Viruses},
volume = {18},
number = {10},
pages = {},
pmid = {42944053},
issn = {1999-4915},
support = {P51 OD010425//Washington National Biomedical Research Center/ ; P30 CA015704//Fred Hutchinson/University of Washington/Seattle Children's Cancer Consortium/ ; //James B. Pendleton Charitable Trust/ ; U42 OD011123/OD/NIH HHS/United States ; AI152501//National Institute of Allergy and Infectious Diseases/ ; U19 AI149504/AI/NIAID NIH HHS/United States ; //McCarthy Family Foundation/ ; U19 AI149504//National Institute of Allergy and Infectious Diseases/ ; U54 DK106829/DK/NIDDK NIH HHS/United States ; P51 OD010425/OD/NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P30 AI152501/AI/NIAID NIH HHS/United States ; U42 OD011123//Washington National Biomedical Research Center/ ; },
mesh = {Animals ; Macaca nemestrina ; *Genetic Therapy/methods ; Genetic Vectors ; *Hematopoietic Stem Cells/virology/metabolism ; *HIV-1/genetics ; *HIV Infections/therapy/virology ; Lentivirus/genetics ; *Hematopoietic Stem Cell Transplantation/methods ; Gene Therapy Agents ; Receptors, CCR5/genetics ; Viral Load ; Humans ; Recombinant Fusion Proteins ; },
abstract = {Despite significant medical progress, HIV-1 remains a critical global health crisis. While combination antiretroviral therapy (cART) effectively suppresses viremia, it is not curative due to the persistence of latent viral reservoirs. Autologous hematopoietic stem and progenitor cell (HSPC) gene therapy offers a promising avenue toward sustained, drug-free remission. In this study, we investigated the feasibility and safety of a multifunctional "defend and attack" HSPC gene therapy strategy in the pigtail macaque (Macaca nemestrina) model. The species-optimized lentiviral vector, PM-MNDU-anti-HIV-1-huEGFRt, carries four therapeutic payloads: a pigtail macaque-specific CCR5 shRNA (PM-CCR5sh1005), a CD4-based chimeric antigen receptor (D1D2CAR), a C46 fusion inhibitor peptide, and a truncated human epidermal growth factor receptor (huEGFRt) serving as a cell-surface tracking marker and anti-EGFR antibody Cetuximab (CTX)-mediated negative selection marker. Following busulfan conditioning, autologous transplantation of vector-modified HSPCs in two pigtail macaques resulted in safe hematopoietic recovery. Both animals achieved sustained, multilineage gene marking in peripheral blood and lymphoid tissues without adverse effects. In one animal, upon Simian-Human Immunodeficiency Virus (SHIV) challenge, vector-modified cells underwent robust, antigen-driven multilineage expansion across both lymphoid and myeloid compartments, which contracted during cART-induced viral suppression and rapidly rebounded following treatment interruption. Administration of CTX demonstrated partial, transient reduction in huEGFRt[+] cells, accompanied with a reciprocal increase in plasma viral load. These findings support the feasibility of evaluating a multi-pronged anti-HIV HSPC gene therapy strategy with a negative selection marker in a non-human primate (NHP) model.},
}

Animals
Macaca nemestrina
*Genetic Therapy/methods
Genetic Vectors
*Hematopoietic Stem Cells/virology/metabolism
*HIV-1/genetics
*HIV Infections/therapy/virology
Lentivirus/genetics
*Hematopoietic Stem Cell Transplantation/methods
Gene Therapy Agents
Receptors, CCR5/genetics
Viral Load
Humans
Recombinant Fusion Proteins

@article {pmid42944564,
year = {2026},
author = {Cornelisse, E and Kousa, D and Menz, BD and Murphy-Reuter, B and Shahnam, A and Chin-Yee, B and Calabro, R and Li, LX and Ramsey, I and Abuhelwa, AY and Logan, JM and Ng, HS and Aravinthan, M and Goonan, J and Carthew, H and Molyneux, P and Tang, J and Hitchen, N and Hong, M and Gandhi, J and Fontanarosa, S and Scarfo, NL and Daniel, K and Marotti, SB and Mariadas, J and van Diermen, B and Susai Manickam, DJ and Ruanglertboon, W and Postma, D and McCradden, MD and Reddy, S and Bacchi, S and Mangoni, AA and McKinnon, RA and Kichenadasse, G and Lyman, GH and Kuderer, NM and Sorich, MJ and Rowland, A and Hopkins, AM},
title = {Development and Pilot Evaluation of a Standardized and Accessible Rubric (OMNI) for Assessing Generative AI in Health Care Contexts: Four-Stage Mixed Methods Study.},
journal = {Journal of medical Internet research},
volume = {28},
number = {},
pages = {e100531},
pmid = {42944564},
issn = {1438-8871},
mesh = {Pilot Projects ; Generative Artificial Intelligence ; Humans ; *Delivery of Health Care ; *Artificial Intelligence ; },
abstract = {BACKGROUND: The rapid adoption of generative AI in the community and health care necessitates reliable, human-led evaluation.

OBJECTIVE: This study aimed to develop a standardized rubric to support health care professionals, administrators, and researchers in evaluating generative AI outputs in health contexts.

METHODS: A rubric was developed through a 4-stage mixed methods study: literature synthesis, expert refinement, pilot application, and post-pilot feedback. The rubric was informed by 69 publications and refined through iterative feedback from a multidisciplinary expert panel (n=23). The pilot rubric was applied to 4 health care scenarios: responses to health-related Reddit questions, generation of health-related images and videos, responses to health professional continuing education questions, and automated physician-to-physician clinical documentation generation. Via these scenarios, 15 clinicians (medical practitioners, pharmacists, and medical oncologists) evaluated 250 input-output pairs using domain-level ratings and qualitative comments. The evaluated outputs included 200 AI-generated responses across the 4 health care scenarios and 50 physician-tagged replies in the health-related Reddit questions scenario.

RESULTS: The final rubric, OMNI, comprised 10 evaluation domains (Accuracy, Safety, Recognizes Uncertainty, Completeness, Communicates Clearly, Empathetic, Context Aware, Referencing, Follows Instructions, and Avoids Coerciveness) assessed on 4-point Likert scales, supported by detailed instructional and example materials. Via the 4 pilot scenarios, assessors generated 9600 domain-level ratings and 4010 qualitative comments. The mean pairwise agreement for the 4-point Likert groups ranged from 30.8% to 53.4%, increasing to 59.3% to 79.6% when collapsed into broad agreement categories; Gwet's AC2 ranged from 0.49 to 0.80. OMNI differentiated strengths and weaknesses between models within scenarios, while recurrent limitations in Referencing, Recognizes Uncertainty, Completeness, Empathetic, and Accuracy were identified across scenarios. Multimodal image and video outputs had the highest occurrence of negative rating domains. Assessors reported OMNI was usable and indicated they would reuse it.

CONCLUSIONS: OMNI is a standardized, accessible rubric for expert-led evaluation of generative AI outputs in health contexts. Pilot application demonstrated that OMNI could differentiate AI performance across models and domains while generating structured feedback. Further work is needed to assess its applicability to purpose-built health AI tools, agentic systems, and organizational evaluation settings.},
}

Pilot Projects
Generative Artificial Intelligence
Humans
*Delivery of Health Care
*Artificial Intelligence

@article {pmid41779378,
year = {2026},
author = {Lam, DL and Rahbar, H},
title = {Strengthening the Case for Personalized Breast Cancer Screening Approaches.},
journal = {AJR. American journal of roentgenology},
volume = {227},
number = {4},
pages = {e2634789},
doi = {10.2214/AJR.26.34789},
pmid = {41779378},
issn = {1546-3141},
}

@article {pmid42918760,
year = {2026},
author = {Afrough, A and Pasvolsky, O and Portuguese, AJ and Zanwar, S and Gaballa, MR and Sannareddy, A and Dima, D and Goel, U and Ali, HM and Julian, K and De Menezes Silva Corraes, A and Janakiram, M and Goldsmith, S and Davis, JA and Green, K and Biran, N and Fogel, L and Zolotov, E and Herr, MM and Hassan, H and Shune, L and Kort, J and Ye, C and Bal, S and Costa, LJ and Joiner, L and Al Hadidi, S and Khan, AM and Raza, S and Anwer, F and Khouri, J and Banerjee, R and Cassano Cassano, R and Sidana, S and Rana, MS and Mikkilineni, L and Hosoya, H and Atrash, S and Ferreri, C and Varga, C and Sborov, DW and Midha, S and Nadeem, O and Grajales-Cruz, A and Baz, R and Blue, B and Freeman, C and Locke, FL and Patel, KK and Lin, Y and Kumar, SK and Hansen, DK and Anderson, LD and Voorhees, PM and Castaneda-Puglianini, O},
title = {Impact of extramedullary plasmacytoma on outcomes in patients with relapsed refractory multiple myeloma treated with talquetamab: U.S. Myeloma Immunotherapy Consortium.},
journal = {Blood cancer journal},
volume = {16},
number = {1},
pages = {},
pmid = {42918760},
issn = {2044-5385},
support = {R01 CA281756/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Multiple Myeloma/drug therapy/pathology/mortality ; Female ; Male ; *Plasmacytoma/drug therapy/mortality/pathology ; Middle Aged ; Aged ; *Antibodies, Bispecific/therapeutic use ; Immunotherapy/methods ; Adult ; Aged, 80 and over ; Treatment Outcome ; Neoplasm Recurrence, Local/drug therapy ; Prognosis ; },
abstract = {Talquetamab, a GPRC5D-targeting bispecific antibody, shows promising activity in relapsed-refractory multiple myeloma. However, real-world outcomes in patients with extramedullary disease (EMD) remain poorly described. We studied 360 patients treated with talquetamab at 15 U.S. centers by Dec 2024. Soft tissue plasmacytomas (STP) were classified as EMD (not contiguous with bone) or paraskeletal disease (PSD; contiguous with bone). If both were present, patients were assigned to the EMD category. Of those, 97 (27%) had EMD, 22 (6%) had PSD, and 241 (67%) had No-STP. Median follow-up was 12.8 months. Overall response rates were 68% in EMD, 63% in PSD, and 65% in No-STP (p = 0.8). Median progression-free survival was 4.3, 4.5, and 7.8 months, respectively (p = 0.009), and median overall survival was 10.3 months, 13.0 months, and not reached (p = 0.070). These findings demonstrate that EMD and PSD are associated with preserved response rates but shorter PFS and OS with talquetamab. While systemic markers of tumor burden and inflammation-particularly lactate dehydrogenase (LDH) and ferritin-emerged as independent predictors of inferior PFS, elevated LDH also retained independent prognostic significance for OS. While EMD was associated with shorter PFS and OS on univariate analysis, it did not retain independent prognostic significance on multivariable analysis, suggesting that inferior outcomes are driven by aggressive disease biology rather than by lesion anatomy alone. These findings are hypothesis-generating and require prospective validation. Talquetamab retains clinical utility in this high-risk population with EMD, though outcomes are suboptimal with a need for further refinement of treatment approaches.},
}

Humans
*Multiple Myeloma/drug therapy/pathology/mortality
Female
Male
*Plasmacytoma/drug therapy/mortality/pathology
Middle Aged
Aged
*Antibodies, Bispecific/therapeutic use
Immunotherapy/methods
Adult
Aged, 80 and over
Treatment Outcome
Neoplasm Recurrence, Local/drug therapy
Prognosis

@article {pmid42920068,
year = {2026},
author = {Walsh, C and Anderson, N and Tsosie, U and Omernik, B and Long, S and Echo-Hawk, A and Baker, L and Begay, A and Rusk, AM and Parker, M and Louie, T and Fonseca, GA and Triplette, M},
title = {A Study of Multidisciplinary Perspectives on Lung Cancer Prevention Care for American Indian/Alaska Native People.},
journal = {Journal of racial and ethnic health disparities},
volume = {},
number = {},
pages = {},
pmid = {42920068},
issn = {2196-8837},
support = {Bristol Myers Squibb Foundation//Bristol Myers Squibb Foundation/ ; },
abstract = {BACKGROUND: Lung cancer is the leading cause of cancer-related death among American Indian/Alaska Native (AI/AN) people. Lung cancer screening (LCS) remains underutilized among AI/AN people. Multi-disciplinary perspectives can help to inform lung cancer prevention care for this population.

METHODS: We conducted a mixed-methods study with healthcare providers and researchers who intersect with AI/AN care. Participants completed an electronic questionnaire and qualitative interviews about their role(s), perceptions of commercial tobacco use and cessation services, and LCS in AI/AN communities. Survey data were analyzed descriptively. Interview transcripts were analyzed using applied thematic analysis, with final themes organized by Consolidated Framework for Implementation Research domains.

RESULTS: Multi-disciplinary care providers (n = 21) reported significant gaps in awareness of and access to tobacco cessation and LCS in AI/AN communities. Key themes include tailoring lung health resources to AI/AN cultures and improving access to and awareness of LCS. Ideal programming centers culture and family and applies Indigenous methodologies to optimize resource development.

CONCLUSION: Study findings support culturally tailored resources and barrier directed supports to enhance commercial tobacco cessation and LCS in marginalized communities. By working collaboratively within and across disciplines, healthcare systems, and Tribal communities, we can optimize care to promote lung cancer prevention in AI/AN communities.},
}

@article {pmid42921838,
year = {2026},
author = {Yi, JC and Paras, G and Barnett, MJ and Henrikson, NB and Panattoni, LE and Lowry, D and Lydum, R and Jones, SMW},
title = {Moderating Role of Social Support Between Financial Hardship and Quality of Life in Breast Cancer Survivors.},
journal = {Psycho-oncology},
volume = {35},
number = {10},
pages = {},
doi = {10.1002/pon.70636},
pmid = {42921838},
issn = {1099-1611},
support = {#135634//American Cancer Society/ ; },
mesh = {Humans ; Female ; *Social Support ; *Quality of Life/psychology ; *Breast Neoplasms/psychology/economics ; Cross-Sectional Studies ; Middle Aged ; *Financial Stress/psychology ; Adult ; Adaptation, Psychological ; *Cancer Survivors/psychology ; Aged ; Mental Health ; Surveys and Questionnaires ; Depression/psychology ; Anxiety/psychology ; },
abstract = {OBJECTIVE: Financial hardship is common for cancer survivors. Little is known about the relationships between financial hardship, social support (emotional, informational and instrumental) and quality of life and mental health.

METHODS: Cross-sectional, secondary analyses of survey data from breast cancer survivors that included financial hardship, social support and quality of life. The survivors needed to be diagnosed within 2 years prior to approach and were part of a cancer registry. The patient reported measures included a financial hardship measure our team developed for cancer survivors, the FACT-G7, PROMIS mental health and social support and the Cancer and Treatment Distress scale. Interaction terms were computed to test for moderation. Separate hierarchical regressions assessed how much if any variance was accounted for in these moderation analyses.

RESULTS: A total of 598 breast cancer survivors completed the survey. Participants were predominantly over age 40 (97%), 98% female and 83% White. The correlations between financial hardship, mental health, quality of life and social support were in the moderate range. There were no significant associations with emotional or informational social support. However, instrumental social support moderated the relationships between financial coping and quality of life, financial depression and mental health and financial anxiety and mental health.

CONCLUSIONS: Instrumental social support moderated the relationships between financial hardship and quality of life and mental health outcomes but emotional and informational social support did not. For financial hardship, it may be useful to increase instrumental social support.},
}

Humans
Female
*Social Support
*Quality of Life/psychology
*Breast Neoplasms/psychology/economics
Cross-Sectional Studies
Middle Aged
*Financial Stress/psychology
Adult
Adaptation, Psychological
*Cancer Survivors/psychology
Aged
Mental Health
Surveys and Questionnaires
Depression/psychology
Anxiety/psychology

@article {pmid42922546,
year = {2026},
author = {Arora, S and Suresh, R and Holland, N and Glatzer, G and Jensen, M and Konnick, EQ and Pritchard, CC and Li, Y and Parsons, HA and Hurvitz, SA and Holland, EC},
title = {A pan-cohort transcriptional landscape of breast cancer maps subtype and microenvironmental programs.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42922546},
issn = {2692-8205},
support = {R35 CA253119/CA/NCI NIH HHS/United States ; },
abstract = {Breast cancer comprises heterogeneous transcriptional states that are incompletely captured by discrete clinical or molecular subtype labels. To visualize this heterogeneity in a unified framework, we integrated bulk RNA-seq data from 2,284 patient samples across 13 studies using 18,089 protein coding genes, a harmonized processing pipeline, batch correction, consensus clustering and PaCMAP dimensionality reduction to construct an interactive breast cancer transcriptional landscape. Consensus clustering identified five major regions, which were annotated using PAM50 scores calculated for each sample: Luminal A, Luminal B, HER2-enriched, and two basal-associated clusters. The basal clusters separated into an immune-rich region marked by T cell-inflamed, tumor-associated macrophages (TAM), and low-purity signatures, and a cell-cycle-driven region enriched for proliferation and DNA replication programs. Overlay of marker genes, pathways, kinases, neuronal-like signaling programs, cancer associated fibroblasts (CAF) states, and TAM programs revealed spatially organized subtype biology and microenvironmental heterogeneity. Finally, projection of therapy-associated resistance signatures identified landscape regions linked to predicted resistance to HER2-targeted therapy and hormone receptor-directed endocrine therapies. By enabling interactive exploration of transcriptional states, marker genes, pathways, and therapeutic response programs, this resource provides a community framework for biomarker discovery in breast cancer.},
}

@article {pmid42922682,
year = {2026},
author = {Brusselmans, M and Baele, G and Hong, SL and Gao, J and Suchard, MA and Rambaut, A and Carvalho, LM},
title = {An adaptive time-tree transition kernel for Bayesian phylogenetic inference.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {42922682},
issn = {2331-8422},
support = {R01 AI153044/AI/NIAID NIH HHS/United States ; R01 AI162611/AI/NIAID NIH HHS/United States ; U19 AI135995/AI/NIAID NIH HHS/United States ; },
abstract = {Bayesian phylogenetic and phylodynamic analyses can be very time-consuming, owing to the combination of complex models that are used to estimate key parameters from increasingly large genomic data sets and their associated metadata. The use of high-performance computer hardware can - to a certain extent - alleviate the computational burden and markedly decrease the time to results. Still, even converging to the posterior can be a lengthy endeavour, with the burn-in aspect of such analyses potentially taking days or even weeks for large data sets. One of the key aspects that hampers performance in Bayesian phylogenetic inference is the efficiency with which tree topology proposals explore tree space. We here propose a novel adaptive tree transition kernel, which we call 'subTreeLeap' (STL), which involves modifying the phylogeny by walking along patristic distance paths in the tree according to an adaptable radius parameter. STL is a general proposal, which can be used with contemporaneous or time-calibrated sequence data, being particularly suited to the latter due to respecting temporal precedence constraints. We carefully assess its impact on convergence and statistical mixing of the exploration of posterior tree space, by comparison to replicate "golden runs" obtained from lengthy analyses of empirical data under standard tree transition kernels. We find that STL successfully explores the same posterior tree space as standard kernels, but often does so in a more efficient manner. We discuss limitations as well as future potential improvements to STL that could substantially increase the speed at which Bayesian phylogenetic inferences are obtained.},
}

@article {pmid42922902,
year = {2026},
author = {Park, MS and Crotty, E and Prall, T and Zalusky, MP and Stevens, J and Paulson, V and Ronsley, R and Galbraith, K and Goffena, J and Storz, SH and Anderson, ZB and Miller, AL and Snyder, M and Cole, B and Leary, S and Lockwood, T and Miller, D},
title = {Concordance of rapid whole genome and targeted long read sequencing of pediatric brain tumors with standard clinical testing.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {42922902},
issn = {2693-5015},
support = {DP5 OD033357/OD/NIH HHS/United States ; },
abstract = {BACKGROUND: The 2021 WHO classification of central nervous system tumors requires integrated molecular testing for accurate diagnosis and risk stratification. Current clinical workflows typically require separate assays for single nucleotide variants (SNVs), copy number variants (CNVs), structural variants (SVs), and DNA methylation profiling, leading to diagnostic delays of weeks to months and substantial tissue consumption. Long-read sequencing (LRS) offers the potential to deliver all required molecular data from a single assay with dramatically reduced turnaround time.

METHODS: We evaluated 23 pediatric brain tumor samples, representing 10 different tumor types, using LRS on the Oxford Nanopore Technologies (ONT) platform, performing whole-genome sequencing (wgLRS; n=9), adaptive sampling (AS; n=20), or both (n=6). Using a streamlined protocol with an approximately 60-minute sample preparation time, we compared LRS-derived variant calls and methylation-based tumor classification against clinical testing results.

RESULTS: Both wgLRS and AS showed high concordance with clinical testing across all variant classes. SNVs and indels were detected with high sensitivity above 15% allele fraction (42 of 51 clinically reported variants), and a somatic-optimized caller recovered four additional driver mutations missed by the standard germline pipeline. CNV profiles showed strong agreement with clinical testing, and 5 of 6 clinically reported gene fusions were identified. Methylation classification was concordant with clinical diagnosis in 18 of 22 (82%) evaluable tumors after only 10 minutes of sequencing using Sturgeon alone, increasing to 19 of 22 (86%) within one hour of sequencing using three real-time classifiers. Adding MNP-Flex, which draws on an expanded 184-class reference, resolved one additional tumor for an overall methylation concordance of 20 of 22 (91%). All discordances were attributable to differences in sampled tissue (autopsy versus surgical specimen), low tumor content, subclonal variants below detection thresholds, or limitations of classifier reference sets.

CONCLUSION: LRS allows for comprehensive molecular characterization of pediatric brain tumors from a single library preparation, with methylation-based classification often available within an hour of sequencing initiation. This integrated approach has the potential to accelerate diagnostic workflows, reduce tissue requirements, tailor neurosurgical approaches, and facilitate timely treatment decisions in pediatric neuro-oncology.},
}

@article {pmid42922907,
year = {2026},
author = {Back, AL and Price, CJ and McGregor, BA and Markell, A},
title = {Preparing the body for psilocybin therapy: receptive and generative interoception in cancer patients.},
journal = {Frontiers in psychiatry},
volume = {17},
number = {},
pages = {1890966},
pmid = {42922907},
issn = {1664-0640},
abstract = {Cancer patients arrive for psilocybin therapy with bodies altered by illness and treatment - bodies that they have learned to brace against, dissociate from, or scan for threat. Research on psilocybin-assisted therapy for cancer-related depression and anxiety consistently identifies the quality of the acute subjective experience - reflected in constructs such as acceptance, surrender, boundlessness, and emotional breakthrough - as a key predictor of therapeutic benefit. Yet most preparation protocols focus on cognitive intention-setting and basic mindfulness while neglecting to address the body directly. We propose that anxiety and depression in this setting may involve a somatic substrate that has not been adequately specified. We distinguish two capacities to 'feel into the body' relevant to psychedelic therapy: interoception as perception (the perceptual access to bottom-up bodily signal) and interoceptive engagement (the broader capacity that links bodily perception to posture, breath, structural intent, and affective stance). We describe a six-category phenomenological taxonomy of somatic experiences in psilocybin therapy (exteroceptive, deep somatic, visceral, vestibular, nociceptive, emergent). We also map receptive practices, designed to improve interoception as perception, and generative practices, designed to improve interoceptive engagement. The framework is grounded in current predictive-coding accounts of interoception, but does not depend on any single neuroscientific model. An ongoing Phase 2 trial of group retreat psilocybin therapy for metastatic cancer patients will provide an initial test of our hypothesis that interoceptive training may influence therapeutic outcomes in psilocybin therapy for patients with cancer.},
}

@article {pmid42923939,
year = {2026},
author = {von Eckstaedt, HV and Weng, KY and Jimenez, DF and DeWald, S and Hall, E and Lai, J and Singh, N},
title = {Frailty characterization and patient-reported outcomes in patients with immune checkpoint inhibitor-related inflammatory arthritis and polymyalgia rheumatica.},
journal = {Rheumatology advances in practice},
volume = {10},
number = {4},
pages = {rkag122},
pmid = {42923939},
issn = {2514-1775},
support = {K23 AR079588/AR/NIAMS NIH HHS/United States ; R03 AG082857/AG/NIA NIH HHS/United States ; },
abstract = {OBJECTIVES: Immune checkpoint inhibitors (ICIs) have been associated with immune-related adverse events (irAEs), including inflammatory arthritis and polymyalgia rheumatica. We aimed to (i) characterize frailty status in patients who develop ICI-related inflammatory arthritis (ICI-IA) and immunotherapy-related polymyalgia rheumatica (ICI-PMR) and (ii) describe patient-reported outcomes (PROs) across key domains of the disease experience, stratified by frailty status.

METHODS: Consecutive new referrals to our Rheumatology-irAE clinic between April 2024 and April 2025 for evaluation of ICI-IA or ICI-PMR were recruited to this cross-sectional study. Frailty and PROs were measured using validated surveys. PROMIS-29 domain scores were summarized descriptively for patients classified as robust/pre-frail versus frail. Given the small sample size, no inferential statistical testing was performed and no P-values are reported.

RESULTS: A total of 14 patients (eight males and six females) were included, of whom 10 were characterized as robust or pre-frail and 4 as frail. The mean ages were similar between those robust/prefrail and frail patients. Two patients in each group had ICI-PMR. Two patients in the frail group were diagnosed with ICI-IA, compared with eight patients in the pre-frail group. Frail patients reported higher median scores in the fatigue and pain interference domains (median T-score fatigue 67.9 [IQR 65.5-70.6] versus 53.0 [IQR 48.6-57.1]; median T-score pain interference 66.7 [IQR 66.4-68.9] versus 58.2 [IQR 57.5-62.3]). Median social roles and activities and physical function scores were also lower in the frail group.

CONCLUSION: In this small cross-sectional cohort, (i) frailty was present in approximately one-third of patients with ICI-related rheumatic irAEs and (ii) patients classified as frail reported higher fatigue and pain interference scores on PROMIS-29. These observations are descriptive and hypothesis-generating, and are intended to inform the design of larger prospective studies of frailty assessment and geriatric-informed care in this population.},
}

@article {pmid42924846,
year = {2026},
author = {Glover, LM and Gillman, MG and Green, MD and O'Brien, SN and Casanova, R and Floyd, JS and Kooperberg, C and Odden, MC and Rich, SS and Rotter, JI and Shah, A and Tindle, HA and Wood, AC and Gerszten, R and Reiner, A and Garcia, L and Cai, Y and Akinyemiju, T and O'Brien, EC and Sims, M and Raffield, LM},
title = {Role of Plasma Proteins in the Association Between Socioeconomic Status and Cardiovascular Disease Events: Results From Trans-Omics for Precision Medicine Cohorts.},
journal = {Journal of the American Heart Association},
volume = {15},
number = {21},
pages = {e043751},
doi = {10.1161/JAHA.125.043751},
pmid = {42924846},
issn = {2047-9980},
mesh = {Humans ; Female ; *Blood Proteins/analysis/metabolism ; Middle Aged ; Socioeconomic Disparities in Health ; *Cardiovascular Diseases/blood/epidemiology ; Aged ; Male ; *Social Class ; Risk Factors ; Risk Assessment ; Proteomics/methods ; Stroke/blood/epidemiology ; Low Socioeconomic Status ; Heart Disease Risk Factors ; Biomarkers/blood ; Incidence ; Coronary Disease/blood/epidemiology ; Multiomics ; },
abstract = {BACKGROUND: Socioeconomic status (SES) is strongly associated with cardiovascular disease burden and risk. Plasma proteins may elucidate a biological mechanism through which low SES increases the risk of cardiovascular disease.

METHODS: Participants from the following 3 cohorts were included: the Multi-Ethnic Study of Atherosclerosis (n=2139), Jackson Heart Study (n=967), and Women's Health Initiative (n=1104). SES was approximated using a cumulative score (range 0-3) across education, income, and employment status. A meta-analysis of Cox proportional hazards ratios was used to assess the association between SES and incident events for coronary heart disease (CHD) and stroke. Linear regression was used within each cohort to determine associations between SES and Olink proteins (n=1270 proteins) and the results were meta-analyzed across cohorts. Regression-based mediation analysis was used to determine whether the identified proteins were statistical mediators of the association of SES and incident events.

RESULTS: Higher SES scores were associated with a lower risk of CHD (hazard ratio [HR], 0.74 [95% CI, 0.63-0.87]) and stroke (HR, 0.81 [95% CI, 0.66-1.00]). After correcting for multiple testing (P<3.937×10[-5]), 233 proteins were associated with SES in the meta-analysis. Of these 233 proteins, 21 had a significant indirect effect on SES and CHD. Because the SES-stroke association was not statistically significant, proteins were not tested as mediators.

CONCLUSIONS: Our analysis of multiple cohorts identified evidence of different proteomic pathways associated with SES and cardiovascular disease. This work suggests that exogenous social factors (eg, SES) may influence cardiovascular disease via proteomic profiles.},
}

Humans
Female
*Blood Proteins/analysis/metabolism
Middle Aged
Socioeconomic Disparities in Health
*Cardiovascular Diseases/blood/epidemiology
Aged
Male
*Social Class
Risk Factors
Risk Assessment
Proteomics/methods
Stroke/blood/epidemiology
Low Socioeconomic Status
Heart Disease Risk Factors
Biomarkers/blood
Incidence
Coronary Disease/blood/epidemiology
Multiomics

@article {pmid42925035,
year = {2026},
author = {Bender Ignacio, RA and Jonsson, C and Perazzolo, S and Stephen, Z and Hanscom, B and Burnham, E and Bryson-Cahn, P and Youngblood, C and Duan, L and Angeldekao, A and Wood, G and Padullo, E and Hartman, M and Adams Waldorf, KM and Acosta, EP and Bushman, L and Anderson, PL and Belaunzaran-Zamudio, PF and Crawford, KW and Collier, A and Ho, RJY},
title = {A novel injectable drug-combination nanoparticle containing three antiretrovirals designed for HIV treatment: A first-in-human trial.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag504},
pmid = {42925035},
issn = {1537-6613},
abstract = {BACKGROUND: Long-acting antiretroviral therapy may improve adherence and decrease stigma, yet affordable combination formulations for global usage are lacking. The TLC-ART program engineered an injectable 3-drug combination in a novel nanoparticle (DcNP) product "TLC-ART 101," composed of lopinavir (LPV), ritonavir (RTV), and tenofovir (TVF) and two lipid excipients. We report safety and pharmacokinetics from this first-in-human study.

METHODS: Three dose cohorts of people without HIV received a single subcutaneous dose of 1.5, 3.0 or 4.0 mL in an adaptive trial of up to64 days. LPV, RTV, and TFV were measured over time in plasma, peripheral blood mononuclear cells (PBMC), and lymph nodes (n=2).

RESULTS: All 12 participants completed the study. One participant experienced anaphylaxis, and four had non-serious hypersensitivity events (rash, lip swelling, generalized pruritis). All participants had grade 1-2 injection-site reactions.. At the highest dose, median LPV T1/2 was 17 days, and LPV was detectable through two months in most participants. RTV T1/2 was 12hrs. Plasma TFV T1/2 was 3.5 days; TFV-diphosphate was detected intracellularly through 14 days. Total exposure (AUC) was higher in peripheral blood mononuclear cells versus plasma for all 3 drugs.

CONCLUSIONS: The first human application of this novel HIV DcNP resulted in detection of LPV through two months and TFV up to four days in plasma, and no meaningful prolongation of RTV. Systemic hypersensitivity was common, and although IgE elevation was not observed, additional mechanistic understanding is required prior to further development of this DcNP pipeline.},
}

@article {pmid42925505,
year = {2026},
author = {Gaevert, JA and Mayer-Blackwell, K and Pogorelyy, MV and Schattgen, SA and Kirk, AM and Duan, S and Van de Velde, LA and Souquette, AH and Awad, W and St James, DG and Clark, NA and Duque, DL and Allen, EK and Lythe, G and Molina-Paris, C and Crawford, JC and Fiore-Gartland, A and Bradley, P and Minervina, AA and Thomas, PG},
title = {Infection history and TCR sequence features shape the breadth of TCR cross-reactivity.},
journal = {Cell reports},
volume = {45},
number = {11},
pages = {118182},
doi = {10.1016/j.celrep.2026.118182},
pmid = {42925505},
issn = {2211-1247},
abstract = {The T cell receptor (TCR) repertoire enables recognition of a vast array of pathogens, despite containing far fewer unique TCRs than the diversity of encountered epitopes. This potential contradiction is resolved by TCR cross-reactivity, whereby individual TCRs recognize multiple distinct epitopes. However, the features defining broadly cross-reactive TCRs remain poorly understood. Here we systematically analyze TCRs from mice sequentially infected with influenza viruses containing naturally occurring single amino acid variants of the D[b]NP366 epitope. We identify 967 unique paired TCR sequences across 18 infection histories and test 22 representative TCRs against 172 epitope variants, yielding 3,784 TCR-epitope interaction measurements. These TCRs exhibit a continuum of cross-reactivity, with infection history influencing both TCR sequence similarity and reactivity profiles. We find specific TCR sequence features associated with broader cross-reactivity, highlighting the interplay between epitope exposure, TCR diversity, and function, and providing insights into CD8[+] T cell adaptability, immune memory, and vaccine design.},
}

@article {pmid42918423,
year = {2026},
author = {Slamon, DJ and Hortobagyi, GN and Stroyakovskiy, D and Yardley, DA and Huang, CS and Crown, J and Bardia, A and Chia, S and Im, SA and Martin, M and Loi, S and Xu, B and Hurvitz, SA and Barrios, CH and Fernández, AC and Untch, M and Visco, F and Perez, AL and Miller, M and Majumdar, S and Peyrard, S and Taran, T and Fasching, PA},
title = {Overall survival with adjuvant ribociclib plus nonsteroidal aromatase inhibitor in patients with high-risk HR+/HER2- early breast cancer: Six-year follow-up of the NATALEE trial.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2026.10.1288},
pmid = {42918423},
issn = {1569-8041},
abstract = {BACKGROUND: Ribociclib plus nonsteroidal aromatase inhibitor (NSAI) demonstrated a statistically significant invasive disease-free survival (iDFS) benefit over NSAI alone in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) at the primary efficacy analysis of the phase 3 NATALEE trial. This prespecified 6-year analysis assessed overall survival (OS) and other efficacy outcomes as well as safety.

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

RESULTS: With a median OS follow-up of 66.5 months, ribociclib plus NSAI demonstrated an OS benefit over NSAI alone (6-year ΔOS, 2.1%; HR, 0.809 [95% CI: 0.661-0.989]; nominal 1-sided P = .019), which was generally consistent across key subgroups. An increasing iDFS benefit with ribociclib plus NSAI was also observed (6-year ΔiDFS, 5.3%; HR, 0.741 [95% CI: 0.646-0.849]; nominal 1-sided P < .0001), which was also generally consistent across key subgroups. DDFS (HR, 0.744 [95% CI: 0.646-0.858]) and DRFS (HR, 0.738 [95% CI: 0.634-0.858]) results supported these findings. No new safety signals were observed.

CONCLUSIONS: This prespecified descriptive 6-year OS analysis demonstrated positive OS results with a clinically relevant benefit of ribociclib plus NSAI, consistent with the increasing reduction in recurrence risk. These results reinforce the benefit of ribociclib plus NSAI in the adjuvant setting across the broad NATALEE-eligible population.

CLINICAL TRIAL REGISTRATION: NCT03701334 (ClinicalTrials.gov).},
}

@article {pmid42918577,
year = {2026},
author = {Orvain, C and Othus, M and Halpern, AB and Basom, RS and Davis, C and Sandmaier, BM and Walter, RB},
title = {Risk Factors for Admission to the Intensive Care Unit and Mortality in Allogeneic Hematopoietic Cell Transplant Recipients with Acute Myeloid Leukemia.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2026.10.037},
pmid = {42918577},
issn = {2666-6367},
abstract = {BACKGROUND: Adults with acute myeloid leukemia (AML) are at risk of requiring intensive care unit (ICU)-level care following allogeneic hematopoietic cell transplantation (HCT). Risk factors for admission to the ICU and outcomes are, however, poorly defined.

OBJECTIVE: To assess risk factors associated with ICU admission in such patients, identify variables associated with ICU mortality, and analyze the outcome of ICU survivors in comparison to HCT recipients not admitted to the ICU.

STUDY DESIGN: Here, we retrospectively analyzed a cohort of 1,265 adults with MDS/AML or AML who received an allograft while in first or second remission between 2006 and 2023.

RESULTS: The cumulative incidence of ICU admission was 9.2% on day +100 after HCT. HCT-comorbidity index (hazard ratio [HR]=1.15, P=0.005), treatment-related mortality (TRM) score (HR=1.07, P=0.004), and graft from an HLA-mismatched donor (HR=2.19, P=0.018) were independently associated with ICU admission. Within 100 days of ICU admission, 50 patients (43%) died; poor performance status (odds ratio [OR]=5.45, P=0.005), higher TRM score (OR per one unit increase=1.14, P=0.035), and secondary AML (OR=2.71 P=0.035) were associated with increased day +100 mortality after ICU admission. In a landmark analysis, patients admitted to the ICU during the first 100 days after HCT and alive at day +150 had significantly higher NRM (HR=2.36, P<0.001) after multivariable adjustment.

CONCLUSION: Together, these results highlight that ICU admission is common after allografting in adults with AML and is associated with high mortality. Identification of patients at increased risk may, ultimately, help develop possible preventive strategies and allow testing in particularly vulnerable individuals.},
}

@article {pmid42611962,
year = {2026},
author = {Bootsma, ML and Sharifi, MN and Sperger, JM and Schehr, JL and Stump, WM and Bakhtiar, H and Mannino, M and Carreno, V and Chang, AH and Stahlfeld, C and Abella, E and Dar, M and Durnen, K and Krause, HM and Gallo, D and Taylor, AK and Grivas, P and Barata, PC and Sethakorn, N and Leal, TA and Truica, CI and O'Regan, RM and Wei, XX and Hall, WA and Emamekhoo, H and Kyriakopoulos, CE and Jarrard, DF and Serritella, A and Ma, VT and McKay, RR and Wisinski, KB and Tagawa, S and Dehm, SM and Lang, JM and Zhao, SG},
title = {Longitudinal Phenotyping of Circulating Tumor Cells Using a Scalable Deep Learning Framework.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {32},
number = {21},
pages = {4988-4999},
doi = {10.1158/1078-0432.CCR-26-0754},
pmid = {42611962},
issn = {1557-3265},
support = {R01CA292799//National Institutes of Health (NIH)/ ; 4DP2CA271832//National Institutes of Health (NIH)/ ; 5KL2TR002374//National Institutes of Health (NIH)/ ; P50CA269011//National Institutes of Health (NIH)/ ; R50CA293840//National Institutes of Health (NIH)/ ; 23TACT01//Prostate Cancer Foundation (PCF)/ ; Challenge award//Prostate Cancer Foundation (PCF)/ ; 22YOUN12//Prostate Cancer Foundation (PCF)/ ; W81XWH-22-1-0830//U.S. Department of War (DOW)/ ; HT9425-25-1-0258//U.S. Department of War (DOW)/ ; HT9425-25-1-0259//U.S. Department of War (DOW)/ ; HT9425-23-1-0164//U.S. Department of War (DOW)/ ; 10-23//Mary Kay Ash Foundation (MKF)/ ; P01CA298991//National Institutes of Health (NIH)/ ; R01CA276269//National Institutes of Health (NIH)/ ; },
mesh = {Humans ; *Neoplastic Cells, Circulating/pathology/metabolism ; *Deep Learning ; *Biomarkers, Tumor ; *Neoplasms/pathology/blood/diagnosis/mortality ; Phenotype ; *Single-Cell Analysis/methods ; Microscopy, Fluorescence ; },
abstract = {PURPOSE: Circulating tumor cells (CTC) provide a minimally invasive window into metastatic disease and treatment response, but their clinical utility has been constrained by manual, subjective, low-throughput identification in multichannel fluorescence microscopy data.

EXPERIMENTAL DESIGN: To address this limitation, we developed and clinically validated the System for Enhanced Evaluation of Tumor Cells (SEE-TC), a deep learning approach for scalable, reproducible phenotyping of individual circulating cells. SEE-TC was developed and evaluated on more than 8.5 million cells from 3,386 blood samples spanning six cancer types, enabling generalization across heterogeneous imaging conditions, staining panels, and acquisition platforms.

RESULTS: SEE-TC achieved single-cell segmentation accuracy on par with humans, learned biologically relevant latent cellular representations that correlate with established morphologic and immunofluorescent biomarkers, and reliably distinguished CTCs from background populations without reliance on arbitrary thresholds. When applied longitudinally, SEE-TC provides a quantitative, patient-level readout of CTC burden over time, which was significantly associated with worse overall survival across multiple cancer types.

CONCLUSIONS: To our knowledge, this is the first fully automated artificial intelligence approach to single-cell segmentation and CTC phenotyping. By transforming CTC analysis from a human-dependent task into a scalable and reproducible digital assay, SEE-TC enables high-fidelity longitudinal monitoring of tumor burden and supports broader clinical deployment of CTC-based liquid biopsies in precision oncology. It is currently being deployed to identify CTCs and quantify target expression for both prognostic and predictive biomarker evaluation in multiple prospective clinical trials on a commercial platform.},
}

Humans
*Neoplastic Cells, Circulating/pathology/metabolism
*Deep Learning
*Biomarkers, Tumor
*Neoplasms/pathology/blood/diagnosis/mortality
Phenotype
*Single-Cell Analysis/methods
Microscopy, Fluorescence

@article {pmid42914984,
year = {2026},
author = {Martin, AC and Cattin, AL and Lockwood, PK and Zepeda-Rivera, MA and Becker, C and Barber, T and Lobon, I and Thakkar, K and Bickley, LJ and Tippu, Z and Marandino, L and Miletić, M and Meader, L and Green, M and Bell, D and Hanley, B and Yus, BI and Byrne, F and Spencer, C and Shepherd, STC and Fendler, A and Au, L and Deng, D and Sanromán, ÁF and Rudman, S and Larkin, J and Litchfield, K and Gutierrez, MG and Turajlić, S},
title = {Bacteria inside kidney tumors associate with myeloid inflammation and disease progression: A TRACERx Renal study.},
journal = {Med (New York, N.Y.)},
volume = {},
number = {},
pages = {101335},
doi = {10.1016/j.medj.2026.101335},
pmid = {42914984},
issn = {2666-6340},
abstract = {BACKGROUND: Intratumoral bacteria are increasingly recognized as active contributors to neutrophil-driven inflammation and disease progression in solid tumors. Yet, in clear cell renal cell carcinoma (ccRCC), where myeloid inflammation is a key feature of aggressive disease, live bacterial presence, their intratumoral distribution, and interaction with the tumor microenvironment remain unexplored.

METHODS: We genetically characterized the microbiome of primary ccRCC tumors across two independent cohorts (TRACERx: 616 samples, 143 patients; The Cancer Genome Atlas [TCGA]: 511 samples and patients), confirming live bacterial presence through culture. Multi-regional sampling enabled within-tumor analysis of bacterial distribution. Associations with the tumor microenvironment were explored at scale using bulk RNA sequencing (RNA-seq) across both cohorts and corroborated in depth through spatial transcriptomics and in vitro infection assays.

FINDINGS: Across both cohorts, the commensal Cutibacterium emerged as the dominant genus, accumulating in discrete niches enriched toward the tumor center and associating with more advanced (TRACERx p = 0.024; TCGA p = 0.0011) tumors and shorter progression-free survival (TRACERx p = 0.0022; TCGA p = 4.4 × 10[-4]). Both across and within tumors, Cutibacterium accumulation associated with neutrophil recruitment and myeloid inflammation. In vitro, Cutibacterium induced sustained expression of neutrophil-attracting chemokines in macrophages, recapitulating patient tumor findings.

CONCLUSIONS: These findings establish intratumoral bacteria as novel prognostic components of the ccRCC tumor microenvironment and suggest an active role in shaping local myeloid inflammation, laying the groundwork for investigating their potential as therapeutic targets.

FUNDING: This work was supported by the Francis Crick Institute (Cancer Research UK, MRC, Wellcome Trust). TRACERx Renal is funded by Cancer Research UK (C50947/A18176).},
}

@article {pmid42917135,
year = {2026},
author = {Irving, R and Dasari, A and Duke, S and Wi, S and Hughes, RM and Spuches, AM and Lim, KH},
title = {Zn2+-Induced Dissociation of Transthyretin Tetramers Generates Toxic, Seeding-Active Misfolded Oligomers.},
journal = {Biochemistry},
volume = {65},
number = {19},
pages = {3017-3025},
doi = {10.1021/acs.biochem.6c00448},
pmid = {42917135},
issn = {1520-4995},
support = {P30CA016086/CA/NCI NIH HHS/United States ; GM163276/GM/NIGMS NIH HHS/United States ; DMR-1644779//Division of Materials Research/ ; NA//State of Florida/ ; },
mesh = {*Prealbumin/chemistry/metabolism/genetics ; *Zinc/chemistry/metabolism ; *Protein Folding ; Humans ; Nuclear Magnetic Resonance, Biomolecular ; Protein Multimerization ; },
abstract = {The aggregation of transthyretin (TTR) is a hallmark of ATTR amyloidosis. Accumulating evidence suggests that metal ions, particularly Zn2+, promote TTR aggregation; however, the molecular mechanism underlying Zn2+-induced misfolding remains poorly understood. Here, we present a comprehensive biophysical characterization of Zn2+-induced misfolding of wild-type transthyretin (TTRwt) under physiologically relevant conditions. Two-dimensional 1H/15N HSQC NMR analyses reveal that Zn2+ binding induces millisecond-time scale conformational exchange that destabilizes the native tetramer. These structural and dynamic perturbations promote the formation of small, toxic oligomeric species capable of self-propagation through the seeding of native TTR. Comparative structural analyses using solid-state NMR also show that Zn2+-induced oligomers adopt broadly native-like secondary structures, but exhibit distinct non-native molecular conformations. The early stages of misfolding were further investigated using 19F NMR of TTRwt containing fluorinated tryptophan residues. Notably, 19F NMR not only reports on Zn2+ binding but also enables direct detection of a transient monomeric intermediate generated upon tetramer dissociation, a key species in the amyloidogenic cascade. Together, these findings define the structural and dynamic basis of Zn2+-mediated TTR misfolding and establish combined solution and solid-state NMR approaches as powerful tools for probing metal-induced misfolding landscapes in TTR and related amyloidogenic proteins.},
}

*Prealbumin/chemistry/metabolism/genetics
*Zinc/chemistry/metabolism
*Protein Folding
Humans
Nuclear Magnetic Resonance, Biomolecular
Protein Multimerization

@article {pmid42918306,
year = {2026},
author = {Fitzpatrick, MJ and Yuan, J and Akuma, DC and Allbee, AW and Bledsoe, JR and Capa, I and Chen, E and Chen, M and Chen, PH and Chen, X and Chen, W and Cheng, J and Delio, M and Gisriel, SD and Haque, M and High, Z and Hu, Z and Jacobsen, J and Kibler, CE and Lee, WY and Li, L and Li, P and Li, S and Martin, A and Matsumoto, NP and Menon, MP and Nardi, V and Pozdnyakova, O and Rets, A and Rozenova, KA and Sadigh, S and Shuai, W and Silva, O and Soma, L and Sparger, CC and Sun, Y and Tian, X and Venkataraman, G and Wang, E and Wang, W and Wu, X and Xie, W and Xie, Y and Young, KH and Yang, G and Yang, R and Yang, Y and Zhang, L and Zhang, S and Zhang, X and Zhang, J and Zhang, QY and Zhou, J and Zhou, X and Zhou, Y and Wang, HY and Hasserjian, RP and Medeiros, LJ and Pan, Z},
title = {Acute Erythroid Leukemia Associated With Myeloid Neoplasms: Clinicopathologic Features and Evidence of Clonal Continuity.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {},
number = {},
pages = {101107},
doi = {10.1016/j.modpat.2026.101107},
pmid = {42918306},
issn = {1530-0285},
abstract = {Acute erythroid leukemia (AEL) is a rare and aggressive variant of leukemia with erythroid differentiation. AEL can arise de novo or transform from underlying myeloid neoplasms (MNs); however, the clinicopathologic and molecular genetic features associated with AEL transformation are poorly defined. Through a multi-institutional collaboration, we characterized 116 cases of AEL transformed from MNs, predominantly myelodysplastic neoplasms (MDS; 59%, n=68) and BCR::ABL1-negative myeloproliferative neoplasms (MPN; 28%, n=33). Median age at AEL diagnosis was 66 years (range, 26-94 years) with a male-to-female ratio of 1.3:1. At initial MN diagnosis, the MDS group had a significantly higher rate of complex karyotypes (76% vs. 8%; P < 0.0001) and TP53 mutations (98% vs. 11%; P < 0.0001), and a shorter median time to transformation (7.6 vs. 82.4 months; P < 0.0001), compared with the MPN group. Conversely, the MPN group preferentially acquired complex karyotypes and co-mutations including TP53 and TET2, during progression. Consequently, at the time of AEL transformation, both groups exhibited similar frequencies of complex karyotypes (94% vs. 92%; P = 0.6574) and TP53 mutations (100% vs. 92%; P = 0.1176) and a dismal median overall survival (1.4 vs. 1.5 months; P = 0.7893). Notably, among 58 cases with longitudinal cytogenetic and molecular data, 100% shared at least one genetic aberration between the MN and AEL stages, suggesting a direct clonal relationship. Taken together, these findings show that AEL can clonally evolve from underlying MNs through distinct initial molecular genetic pathways that ultimately converge into an adverse genetic landscape with poor prognosis.},
}

@article {pmid42914562,
year = {2026},
author = {Tong, APS and Poljakov, K and Lane, DD and Laidlaw, G and Monsky, W and McGregor, H and Yeung, RS and Grassberger, C and Altreuter, D and Hall, ET and Bhatia, S and Zhang, M and Fong, L and Som, A},
title = {Reprogramming the tumor microenvironment from within: intratumoral immunoadjuvants in cancer immunotherapy.},
journal = {Journal for immunotherapy of cancer},
volume = {14},
number = {10},
pages = {},
pmid = {42914562},
issn = {2051-1426},
abstract = {The immunosuppressive tumor microenvironment (TME) limits antigen presentation, immune trafficking, and therapeutic durability. Tumors range from immunoreactive microenvironments with pre-existing immune infiltration to immunosuppressive microenvironments characterized by myeloid-driven immunosuppression, dense stromal barriers, and effector T-cell exclusion. Intratumoral immunoadjuvants facilitate the transition of immunosuppressive TMEs toward immunoreactive states through activation of local innate immune signaling, chemokine-driven effector T-cell recruitment, and myeloid reprogramming, while amplifying pre-existing immunity in immunoreactive tumors. However, clinical translation is challenged by poor local retention and heterogeneous tumor architecture. This review integrates TME biology with advances in biomaterial-formulated delivery. Key immunoadjuvant classes, including STING, TLR, and RIG-I agonists, cytokines, and oncolytic viruses, are discussed with hydrogel depots, polymeric nanoparticles, and collagen-binding platforms that enhance retention and controlled release. Physical modulation through methods such as ultrasound and radiation is examined as a complementary approach to disrupt stromal barriers. A framework is proposed for matching immunoadjuvant class, biomaterial carrier, and dosing schedule to tumor-specific immunologic features that can drive lasting antitumor immunity.},
}

@article {pmid42914583,
year = {2026},
author = {Maskarinec, G and Laxamana, MA and Lim, U and Hullar, MAJ and Lampe, JW and Shepherd, JA and Franke, AA and Wilkens, LR and Le Marchand, L},
title = {The association of the gut microbiome with intermediate markers of breast cancer risk-mammographic density and blood steroid hormones-in the multiethnic cohort study.},
journal = {Cancer treatment and research communications},
volume = {49},
number = {},
pages = {101497},
doi = {10.1016/j.ctarc.2026.101497},
pmid = {42914583},
issn = {2468-2942},
abstract = {INTRODUCTION: The gut microbiota may influence breast cancer risk through different biologic pathways. This analysis examined the association of the gut microbial composition with percent mammographic density (PMD), a strong predictor of breast cancer risk.

METHODS: Postmenopausal women in the Adiposity Phenotype Study, a cross-sectional subset of the Multiethnic Cohort, from five racial/ethnic groups, provided a stool sample. Extracted bacterial DNA was sequenced for the V1-V3 region of the 16S rRNA gene. Bioinformatic analysis determined alpha-diversity and the abundance of 10 phyla and 152 genera. PMD was assessed in routine mammograms taken before stool collection with a quantitative computer-assisted method. Blood levels of estrogen metabolites were assessed using standard assays. General linear models regressed PMD on gut microbial diversity, phyla, and genera while adjusting for relevant covariates.

RESULTS: Of 649 women (69.1 ± 2.7 years), 311 had low (<15%) and 338 had high (>=15%) PMD. Whereas alpha diversity or phyla were not associated with PMD, 10 genera were nominally related to PMD (p < 0.05) but not after adjusting for multiple comparisons: 7 positively (Bifidobacterium, Blautia, Dialister, Eubacterium_fissicatena_group, Lachnospira, Lachnospiraceae_UCG-008, Lachnospiraceae_uncultured) and 3 inversely (Alistipes, Senegalimassilia, Eubacterium_oxidoreducens_group), potentially implicating estrogen metabolism and short-chain fatty acid production. All blood steroid metabolites were significantly related to PMD, but only SHBG was associated with 2 genera after Bonferroni adjustment.

CONCLUSIONS: The nominal associations detected in this analysis suggest that certain gut microbiota may be associated with PMD, a marker of risk but not a measure of breast cancer incidence, due to their ability to affect circulating hormones or SCFA production.},
}

@article {pmid42856183,
year = {2026},
author = {Xu, G and Yee, JX and IIcisin, SM and Kaul, SN and Mayer-Blackwell, K and Moelhman, E and Glass, DR and Minervina, AA and Karuna, ST and Sobieszczyk, ME and Hart, MR and Thomas, PG and Skene, PJ and De Rosa, SC and McElrath, MJ and Fiore-Gartland, A and Newell, EW},
title = {HIV-1 prime-boost vaccination shapes distinct clonal trajectories and memory precursor states of Env- and Gag-specific T cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42856183},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; K99 AI185149/AI/NIAID NIH HHS/United States ; UM1 AI068618/AI/NIAID NIH HHS/United States ; R01 CA264646/CA/NCI NIH HHS/United States ; U19 AI128914/AI/NIAID NIH HHS/United States ; R01 AI136514/AI/NIAID NIH HHS/United States ; },
abstract = {Despite decades of HIV-1 vaccine development, the clonal and cellular determinants of durable vaccine-induced T cell memory remain incompletely understood. Here, we combined antigen-specific T cell receptor (TCR) identification, longitudinal TCR sequencing, and single-cell multi-omics to characterize Env- and Gag-specific memory precursor T cells elicited by the HIV Vaccine Trials Network (HVTN) 505 DNA prime-recombinant adenovirus serotype 5 (rAd5) boost (DNA/rAd5) vaccine regimen. We developed a generalizable high-throughput approach to identify HIV-1 Env- and Gag-specific TCRs and found distinct patterns of clonal expansion, persistence, and contribution to memory between Env- and Gag-specific CD8[+] T cell responses. The DNA prime and rAd5 boost differentially shaped these repertoires, with rAd5-induced clones contributing proportionally more to the Gag-specific than to the Env-specific memory precursor compartment. Single-cell immune profiling further revealed distinct memory precursor states, with Env-specific responses enriched for GZMB [+] PRF1 [+] cytotoxic effector-memory (EM) CD8[+] T cells and Gag-specific responses containing a larger cycling/proliferative population. Together, these findings demonstrate that heterologous DNA/rAd5 vaccination generates antigen-specific CD8[+] T cell memory with distinct clonal trajectories and cellular programs, providing new insights into how vaccine platform and antigen-specificity shape the durability and functional properties of HIV-1 specific cellular immunity.},
}

@article {pmid42910448,
year = {2026},
author = {Subramanian, AK and Avery, RK and Syed, A and Matsuo, T and Boeckh, M and Razonable, RR and Fishman, JA},
title = {Building a One-Year Transplant Infectious Diseases Fellowship: A North American Perspective From Established Programs.},
journal = {Transplant infectious disease : an official journal of the Transplantation Society},
volume = {},
number = {},
pages = {},
doi = {10.1111/tid.70349},
pmid = {42910448},
issn = {1399-3062},
}

@article {pmid42913880,
year = {2026},
author = {Palazzo, L and Hansell, L and Wernli, KJ and Brown, M and Snidarich, M and Louie, T and Long, S and Walsh, C and Coronado, GD and DeCell Arnp, K and Lodhi, S and Leone, RJ and Wysham, N and Triplette, M},
title = {Determinants of lung cancer screening follow-up care in community care settings: A qualitative multi-case study in the ACCELL trial.},
journal = {Chest},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chest.2026.10.019},
pmid = {42913880},
issn = {1931-3543},
abstract = {BACKGROUND: Adherence to lung cancer screening (LCS) follow-up is essential to achieve mortality benefits from screening. However, population-based studies demonstrate follow-up is <50% in clinical settings. Determinants (barriers and facilitators) of LCS follow-up in community settings are under-studied.

RESEARCH QUESTION: What are determinants of LCS follow-up in community settings?

STUDY DESIGN AND METHODS: This qualitative multi-case study informed a pre-post intervention trial, testing pragmatic interventions to address LCS follow-up in community settings. We conducted rapid ethnographic assessments (REA) through virtual and in person site visits of LCS delivery in three community-based healthcare systems in Washington state. Additionally at the two future intervention sites, we conducted provider and patient interviews. Interview transcripts were analyzed using Rapid Group Analysis Process. All data were triangulated according to Consolidated Framework for Implementation Research and National Institute on Minority Health and Health Disparities Research Framework domains.

RESULTS: Twenty-eight organizational leaders, providers, and staff participated in REA. Thirty-one patients and 15 providers from the future intervention sites participated in interviews. Determinants of LCS follow-up in the intervention domain included role of primary care, LCS complexity and care process standardization. In the inner setting domain (organization and clinic), screening prioritization, EHR use, radiology support, and context of wellness visits affected LCS. The main theme in the outer setting domain was the influence of social determinants of health on LCS. In the individuals domain, shared beliefs in LCS and LCS education and information sharing were key. In the process implementation domain, clinical champions and use of data and metrics were crucial.

INTERPRETATION: Integrated findings suggest determinants related to LCS complexity, care fragmentation, socioeconomic status and language, and limitations of PCPs could be overcome through more centralized approaches. However, increased use of EHR tools, increased education and standardizing LCS performance metrics may enable follow-up in decentralized settings.

CLINICAL TRIALS REGISTRATION: NCT06324110.},
}

@article {pmid42856124,
year = {2026},
author = {Azizoglu, A and Bijman, EY and Brent, R},
title = {Evolverator: An engineered yeast system to drive rapid continuous in vivo evolution of proteins.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42856124},
issn = {2692-8205},
support = {R21 CA223901/CA/NCI NIH HHS/United States ; },
abstract = {Continuous in vivo evolution of non-essential proteins requires an engineered link between target protein and host cell fitness, which is difficult to establish and vulnerable to escape mutations. We systematically designed and tested Saccharomyces cerevisiae gene circuits guided by quantitative mathematical models that predicted circuit, organism, and population behavior. We identified four generalizable design principles for escape-resistant continuous evolution and built the Evolverator, a yeast platform that couples protein binding to proliferation rate while suppressing escape mutations. We used the Evolverator to improve human estrogen receptor ligand affinity and generate stronger yeast repressors from the bacterial LacI protein. The resulting variants revealed previously undescribed hER substitutions within and outside the binding pocket, as well as LacI mutations that enhance repression in yeast despite reduced activity in Escherichia coli. Our work establishes a generalizable, model-guided framework for building yeast strains to allow continuous evolution of diverse protein functions in vivo.},
}

@article {pmid42905934,
year = {2026},
author = {Talavera, IC and Thomas, KK and Graham, JB and Swarts, JL and Vick, SC and MacLean, F and Potchen, NB and Warrier, L and Tsegaye, AT and Hughes, SM and Hladik, F and Chohan, BH and Ngure, K and Mugo, N and Lingappa, JR and Lund, JM and , },
title = {Genital Tract and Circulating CD8+ T Cell Phenotypes Vary Across the Menstrual Cycle.},
journal = {American journal of reproductive immunology (New York, N.Y. : 1989)},
volume = {96},
number = {4},
pages = {},
pmid = {42905934},
issn = {1600-0897},
support = {T32 AI007509/AI/NIAID NIH HHS/United States ; AI129715/NH/NIH HHS/United States ; T32AI083203/NH/NIH HHS/United States ; R01 AI131914/NH/NIH HHS/United States ; R01 AI141435/NH/NIH HHS/United States ; R01 AI141435/AI/NIAID NIH HHS/United States ; T32AI007140/NH/NIH HHS/United States ; T32AI007509/NH/NIH HHS/United States ; T32 AI007140/AI/NIAID NIH HHS/United States ; R01 HD114505/HD/NICHD NIH HHS/United States ; R01 HD114505/NH/NIH HHS/United States ; R01 AI131914/AI/NIAID NIH HHS/United States ; T32 AI083203/AI/NIAID NIH HHS/United States ; R01 AI129715/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; Female ; *CD8-Positive T-Lymphocytes/immunology ; Adult ; *Vagina/immunology ; *Luteal Phase/immunology ; *Menstrual Cycle/immunology ; Cytokines/metabolism ; *Cervix Uteri/immunology ; Follicular Phase/immunology ; Phenotype ; *Memory T Cells/immunology ; Young Adult ; Immunologic Memory ; },
abstract = {PROBLEM: The menstrual cycle consists of two main phases: the follicular phase, characterized by rising estradiol and low progesterone, and the luteal phase, marked by elevated progesterone following ovulation. Changes in sex hormones have profound physiological effects, yet their impact on immunity remains poorly understood. The prevailing theory suggests that reduced immunity during the luteal phase facilitates embryo implantation but also increases susceptibility to infections. Thus, defining the impact of the menstrual cycle on genital and systemic immunity is critical to understanding how immunity at different sites may be affected.

METHOD OF STUDY: We examined phenotypic differences in T cells from ectocervical and vaginal tissue biopsies and blood samples collected from 58 women in the follicular phase and 20 women in the luteal phase using flow cytometry and measured seventy-one cytokines and chemokines from serum and cervicovaginal secretions.

RESULTS: The proportions of CD8+ memory T cell subsets varied with menstrual phase, with a higher frequency of central memory cells during the luteal phase and more TEMRA cells during the follicular phase. Cervical CD8+ T cells exhibited higher frequencies of CD38 and CD39 during the luteal phase. We found higher CCL15 and IL-2 concentrations in cervicovaginal fluid, and higher CXCL12 in serum, during the follicular phase. During the luteal phase, CXCL13 was higher in cervicovaginal secretions.

CONCLUSIONS: Our findings provide insight into how menstrual phase modulates genital CD8+ T cell phenotypes and memory subsets throughout the cycle and may influence immunity in distinct tissue compartments with consequences for local infection vulnerability.},
}

Humans
Female
*CD8-Positive T-Lymphocytes/immunology
Adult
*Vagina/immunology
*Luteal Phase/immunology
*Menstrual Cycle/immunology
Cytokines/metabolism
*Cervix Uteri/immunology
Follicular Phase/immunology
Phenotype
*Memory T Cells/immunology
Young Adult
Immunologic Memory

@article {pmid42907159,
year = {2026},
author = {Colgan, JN and Gooley, TA and Pedersen, JB and Hadland, B and Summers, C and Carpenter, PA and Delaney, CC and Milano, F and Dahlberg, A},
title = {Prospective phase 2 trial of high- and intermediate-intensity myeloablative conditioning for cord blood transplantation.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2026021974},
pmid = {42907159},
issn = {2473-9537},
abstract = {Umbilical cord blood transplantation (UCBT) is an important alternative donor strategy for patients with high-risk hematologic malignancies. While myeloablative conditioning (MAC) is associated with superior disease control following UCBT compared to reduced-intensity conditioning (RIC), its benefits can be offset by non-relapse mortality (NRM). Intermediate-intensity MAC may preserve the anti-leukemic effects of historically high-intensity MAC while reducing NRM. We conducted a prospective phase 2 trial evaluating outcomes of patients undergoing UCBT following either high-intensity or intermediate-intensity MAC. A total of 132 patients were enrolled between 2006 and 2022, with acute leukemia being the predominant indication. The primary endpoint was overall survival (OS), with secondary endpoints including relapse-free survival (RFS), relapse and NRM. For the overall study population at 1 year, OS was 78% (95% CI, 70-85%) and RFS was 72% (95% CI, 64-79%). Outcomes were comparable between conditioning regimens, with encouragingly low NRM observed in patients receiving intermediate-intensity conditioning, including in the pediatric cohort. Among patients with acute leukemia, measurable residual disease (MRD) positivity at transplant was not associated with an increase in relapse, supporting enhanced GVL following UCBT. These findings were particularly notable in patients with AML. These data demonstrate that UCBT following intermediate intensity MAC is a viable strategy that may reduce toxicity while preserving disease control in selected patients. Collectively, these findings support the unique anti-leukemic properties of UCBT and reinforce its role as a highly effective donor platform for high-risk leukemia in children and adults. This trial was registered at ClinicalTrials.gov as NCT00719888.},
}

@article {pmid42907166,
year = {2026},
author = {Choe, M and Bhatt, NS and Keenan, C and Rivers, J and Leger, KJ and Tarlock, K and Wilkes, JJ and Summers, C and Bleakley, M and Dahlberg, A and Thakar, MS},
title = {Maintenance ALK inhibitor after hematopoietic cell transplantation in patients with anaplastic large cell lymphoma.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2026022085},
pmid = {42907166},
issn = {2473-9537},
}

@article {pmid42907170,
year = {2026},
author = {Aljawai, YM and Ueda Oshima, M and Astha, V and Litvinovich, I and He, M and Layton, SA and Bupp, C and Ahn, KW and Bolaños-Meade, J and Gooptu, M and Lazaryan, A and Al Malki, MM and Stefanski, HE and Shaw, BE and Spellman, SR and Auletta, JJ and Devine, SM and Juckett, MB and Elmariah, H},
title = {Hematopoietic Cell Transplantation Outcomes in the Era of Post-Transplant Cyclophosphamide: Comprehensive Donor Analysis.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2026021883},
pmid = {42907170},
issn = {2473-9537},
abstract = {Donor types influence outcomes after allogeneic hematopoietic cell transplantation (HCT), but their relative impact in the post-transplant cyclophosphamide (PTCy) era is uncertain. We performed a multicenter retrospective cohort study using Center for International Blood and Marrow Transplant Research data for adults with acute leukemia or myelodysplastic syndromes undergoing first HCT from matched sibling donors (MSD), 8/8 matched unrelated donors (MUD), 7/8 mismatched unrelated donors (MMUD), or haploidentical donors between 2017 and 2023 with PTCy-based graft-versus-host disease (GVHD) prophylaxis. The primary cohort included 12,617 patients: 1,263 MSD, 4,117 MUD, 1,426 MMUD, and 5,811 haploidentical recipients. In multivariable models adjusted for donor age and clinical covariates, overall survival (OS) was lower with MUD (hazard ratio [HR], 1.16; 95% CI, 1.00-1.34, p=0.004), MMUD (HR, 1.32; 95% CI, 1.12-1.55, p<0.001), and haploidentical donors (HR, 1.43; 95% CI, 1.24-1.64, p<0.001) compared with MSD. GVHD-free, relapse-free survival (GRFS) was similar for MUD and MSD (reference) but lower with MMUD and haploidentical donors. Compared to MSD, all other donor groups had lower relapse risk but higher non-relapse mortality and acute GVHD, with similar chronic GVHD. In sensitivity analyses excluding donor-age adjustment, compared to MSD, OS was similar for MUD and MMUD, and GRFS was improved with MUD and similar for MMUD and haploidentical donors. These findings suggest that PTCy narrows outcome differences across donor types, shifting donor selection from rigid hierarchies and supporting timely HCT using the best available donor.},
}

@article {pmid42907492,
year = {2026},
author = {Wu, CI and Banda, K and Arora, R and Soong, TR and Radke, M and Dillon, M and Nik-Zainal, S and Swisher, EM and Sailem, HZ},
title = {HRDPath: an explainable multi-model deep learning architecture for predicting homologous recombination deficiency from histopathology images.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42907492},
issn = {2041-1723},
support = {/WT_/Wellcome Trust/United Kingdom ; 225974/Z/22/Z//Wellcome Trust (Wellcome)/ ; },
mesh = {Female ; Humans ; *Deep Learning ; *Ovarian Neoplasms/genetics/pathology ; *Homologous Recombination/genetics ; Biomarkers, Tumor/genetics ; *Cystadenocarcinoma, Serous/genetics/pathology ; },
abstract = {Homologous recombination deficiency (HRD) is a critical biomarker for guiding treatment decisions in high-grade serous tubo-ovarian carcinoma (HGSOC), a cancer with few reliable biomarkers. However, existing genomics-based tests for HRD are variable, expensive, and time-consuming. We develop HRDPath, a patient-level deep learning architecture that predicts HRD status from whole slide images, requiring no additional molecular testing. HRDPath is validated across three cohorts of female patients and achieves an AUC of 0.846, significantly outperforming previously reported results in HGSOC. By incorporating multiple slides per patient and targeted optimization strategies, we strengthen the model clinical utility, with both specificity and sensitivity reaching 0.90. Our interpretability pipeline enhances model trustworthiness and reveals important clinical and biological insights into HRD-positive cancers, highlighting the associated morphological and pathological changes at the cellular and tissue levels. HRDPath provides a foundation for an accessible and scalable digital biomarker to improve treatment stratification in ovarian cancer globally.},
}

Female
Humans
*Deep Learning
*Ovarian Neoplasms/genetics/pathology
*Homologous Recombination/genetics
Biomarkers, Tumor/genetics
*Cystadenocarcinoma, Serous/genetics/pathology

@article {pmid42908394,
year = {2026},
author = {Sharma, S and Martinez Di Pietro, B and Nandula, A and Goplani, T and Chen, H and Armenian, S and Bhat, A and Blythe, N and Border, W and Leger, KJ and Leisenring, WM and Meacham, LR and Narasimhan, S and Nathan, PC and Sachdeva, R and Sadak, K and Stratton, K and Chow, EJ and Edwards, LA and Boyle, PM},
title = {Early Prediction of Cardiomyopathy in Pediatric Cancer Survivors Using Echocardiographic Video-Based Deep Learning.},
journal = {Echocardiography (Mount Kisco, N.Y.)},
volume = {43},
number = {10},
pages = {},
pmid = {42908394},
issn = {1540-8175},
support = {K23HL183696/NH/NIH HHS/United States ; //Seattle Foundation Medical Funds Program/ ; R01 CA211996/CA/NCI NIH HHS/United States ; U10CA180886/NH/NIH HHS/United States ; //Rally Foundation/ ; R21CA277746/NH/NIH HHS/United States ; UG1 CA189955/CA/NCI NIH HHS/United States ; //Unravel Pediatric Cancer Foundation/ ; U10 CA180886/CA/NCI NIH HHS/United States ; //Seattle Children's Research Institute/ ; //Catherine Holmes Wilkins Charitable Foundation/ ; UG1CA189955/NH/NIH HHS/United States ; K23 HL183696/HL/NHLBI NIH HHS/United States ; R01CA211996/NH/NIH HHS/United States ; R21 CA277746/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Deep Learning ; Child ; *Cardiomyopathies/diagnostic imaging/diagnosis ; Female ; *Echocardiography/methods ; Male ; *Cancer Survivors ; Adolescent ; Child, Preschool ; Prognosis ; Young Adult ; *Video Recording/methods ; Predictive Value of Tests ; Infant ; *Neoplasms/complications ; },
abstract = {PURPOSE: Cardiomyopathy (CM) is a leading cause of late mortality in childhood cancer survivors, but it is often identified only after irreversible cardiac remodeling has already occurred. In this proof-of-concept study, we assessed whether deep learning applied to routine echocardiographic videos can identify features predictive of future CM.

METHODS: We analyzed parasternal short-axis clips from cancer survivors ≤21 years old at cancer diagnosis. 3D deep convolutional neural networks were trained to classify CM-positive versus CM-negative studies from echocardiograms conducted up to five years prior to CM diagnosis. The performance was assessed on internal hold-out validation (Center 1) and external validation cohorts (Centers 2, 3). The model's prognostic value was evaluated by stratifying patients into high- and low-risk groups for developing CM, and probability of future CM was assessed using cumulative incidence and proportional hazards regression analysis.

RESULTS: The model achieved an area under the receiver operating characteristic curve (AUROC) of 0.87±0.05 and an area under the precision-recall curve (AUPRC) of 0.74±0.07 on the internal hold-out set. External validation showed near-chance single-study discrimination (AUROC 0.55±0.02 and 0.60±0.03; AUPRC 0.22±0.02 and 0.21±0.03 for Centers 2 and 3, respectively). Nevertheless, analysis of the external cohort showed significantly higher probability of CM in high- versus low-risk groups (hazard ratio 2.78, 95% CI = 1.52-5.10, p = 0.00056).

CONCLUSION: Deep learning models have the potential to identify subtle echocardiographic markers years before CM diagnosis in pediatric cancer survivors and could serve as a preliminary step toward risk-guided CM surveillance. Further refinement and validation are needed to determine the utility of deep learning for early identification of pathologic cardiac remodeling in this population.},
}

Humans
*Deep Learning
Child
*Cardiomyopathies/diagnostic imaging/diagnosis
Female
*Echocardiography/methods
Male
*Cancer Survivors
Adolescent
Child, Preschool
Prognosis
Young Adult
*Video Recording/methods
Predictive Value of Tests
Infant
*Neoplasms/complications

@article {pmid42895480,
year = {2026},
author = {Malcomson, FC and O'Connell, CP and Farhat, Z and Buchanan, DD and Frone, MN and Hatton, JN and Katki, HA and Kim, J and Le Marchand, L and Phipps, AI and Potter, JD and Sinha, R and Stewart, DR and Vogtmann, E and Jenkins, MA and Loftfield, E},
title = {Gut microbiome-related plasma metabolites and risk of colorectal cancer.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-26-0718},
pmid = {42895480},
issn = {1538-7755},
abstract = {BACKGROUND: Perturbations in gut microbiome composition and altered levels of related metabolites may be related to colorectal cancer (CRC). This study assessed whether pre-diagnostic, circulating, microbiome-related metabolite concentrations were associated with CRC risk.

METHODS: We undertook a nested case-control study of 739 participants in the Colon Cancer Family Registry Cohort (312 cases, 427 controls). Median follow-up time from blood draw to diagnosis was 7 years. Pre-diagnostic plasma concentrations of 70 metabolites were quantified by targeted liquid chromatography-tandem mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for metabolite concentrations and CRC risk using multivariable conditional logistic regression models. Stratified analyses were conducted by sex, Lynch syndrome diagnosis, and age at tumor onset.

RESULTS: The primary bile acids, cholate and chenodeoxycholate, were positively associated with CRC incidence, overall and among females. The odds of CRC were higher in individuals in the highest compared with the lowest quartiles of cholate (ORQ4vQ1=1.61, 95% CI=1.05-2.49) and chenodeoxycholate (ORQ4vQ1=1.60, 95% CI=1.03-2.50). Two short-chain fatty acids (caproate, valerate) and three metabolites involved in phenylalanine and tyrosine metabolism (cinnamoylglycine, phenylpropionate, 4-ethylphenylsulfate) were suggested to be associated, positively and negatively, respectively, with incident CRC but these associations did not withstand correction for multiple comparisons. In stratified analyses, some differences were observed according to sex, Lynch syndrome diagnosis, and age at tumor onset.

CONCLUSIONS: Circulating microbiome-related metabolites, including bile acids and short-chain fatty acids, may be associated with CRC risk.

IMPACT: These findings provide insight into potential pathways linking the gut microbiome to colorectal carcinogenesis.},
}

@article {pmid42895728,
year = {2026},
author = {Chrisman, SPD and Bollinger, BJ and Flaat, A and Sahlberg, J and Zhou, C and Mendoza, JA and Brooks, MA and Palermo, TM and Hansen, CR and Rivara, FP},
title = {Mobile Subthreshold Exercise Program (MSTEP) for Youth With Prolonged Concussion Recovery: A Randomized Clinical Trial.},
journal = {JAMA pediatrics},
volume = {},
number = {},
pages = {},
pmid = {42895728},
issn = {2168-6211},
abstract = {IMPORTANCE: Research suggests that aerobic exercise improves recovery for youth with concussion; however, prior studies primarily focused on acute concussion and required multiple in-person visits.

OBJECTIVE: To determine whether a virtually delivered aerobic exercise program improves recovery following concussion compared to a stretching control and examine potential moderators.

A randomized clinical trial was conducted from 2021 to 2025 comparing the Mobile Subthreshold Exercise Program (MSTEP) to a stretching control for 11- to 18-year-olds with concussion up to 1 year from injury. Participants were recruited from a variety of outpatient locations in 4 US states (Washington, Utah, Wisconsin, and Oregon). Recruitment and data collection occurred from March 2021 until October 2025, and data analysis occurred from November 2025 to April 2026.

INTERVENTIONS: Youth randomized to MSTEP were provided activity trackers and an aerobic exercise program initiated at 60% of heart rate maximum. Exercise was advanced in intensity and duration over 6 weeks through weekly videoconferencing calls. Youth in the control group were given stretching exercises and similar weekly calls.

MAIN OUTCOMES AND MEASURES: Primary outcomes included (1) concussive symptoms and (2) health-related quality of life (HRQoL). Secondary outcomes included sleep, depression, and anxiety. Moderation by sex, age, and time since injury was examined. Patients were followed up for 6 months.

RESULTS: The sample included 210 participants, among whom 122 (58.1%) were female, mean (SD) age was 15.1 (2.2) years, and mean (SD) time since injury was 73.3 (63.3) days. Covariate-adjusted regression analysis showed significant improvement in concussive symptoms and HRQoL at all time points, with greater improvement in MSTEP compared to control at the 3-month time point for both concussive symptoms (β, -3.15; 95% CI, -6.05 to -0.25; adjusted P = .04) and HRQoL (β, 4.15; 95% CI, 0.64-7.66; adjusted P = .04). No significant differences by group were seen at 6 months. Nonlinear mixed-effects modeling with exponential decay showed significantly faster symptom recovery in MSTEP compared to control (difference in rates, -0.68; 95% CI, -2.22 to -0.04; P = .002). Secondary outcomes (sleep, depression, and anxiety) improved in all participants but were not different by group. Benefit of the intervention was only significant for individuals less than 3 months from injury (concussive symptoms: β, -4.44; 95% CI, -7.99 to -0.90; unadjusted P = .01; HRQoL: β, 6.64; 95% CI, 2.55-10.72; unadjusted P = .002). No evidence was found for moderation by other factors.

CONCLUSIONS AND RELEVANCE: Per the results of this randomized clinical trial, an aerobic exercise program improves speed of recovery following concussion for youth compared to stretching and can be delivered remotely. However, this type of program appears to be most beneficial for individuals with acute or subacute injury (<3 months since injury).

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04688255.},
}

@article {pmid42897296,
year = {2026},
author = {Melão, BVLA and Jardim, DL and Li, R and Collins, K and Agarwal, N and Grivas, P and Briganti, A and Necchi, A and Cheng, L and Spiess, PE},
title = {Rare prostate cancer histologies: detection, characteristics and treatment.},
journal = {Nature reviews. Urology},
volume = {},
number = {},
pages = {},
pmid = {42897296},
issn = {1759-4820},
abstract = {Relatively rare histologies of prostate cancer collectively account for <5% of all prostate cancers and comprise mucinous adenocarcinoma, intraductal carcinoma, ductal adenocarcinoma, neuroendocrine prostate cancer (including treatment-emergent small-cell neuroendocrine carcinoma), sarcomatoid carcinoma and basal cell carcinoma. These histologies have distinct morphological, molecular and clinical features from each other and the most common histological type, acinar adenocarcinoma. The perceived rarity of these histologies often reflects sampling limitations rather than biological prevalence, as many treatment-emergent phenotypes are seldom encountered in routine practice owing to the infrequent use of metastatic biopsies. These histologies demonstrate aggressive behaviour, atypical metastatic patterns and reduced responsiveness to conventional therapies. Despite their clinical importance, these entities remain under-represented in standard guidelines and clinical trials. Histological types and subtypes, such as ductal, mucinous, intraductal, neuroendocrine and sarcomatoid carcinomas, pose diagnostic and therapeutic challenges, and conventional screening with PSA exhibits limitations, so they are often diagnosed at advanced stages. Multiparametric MRI, immunohistochemistry and genomic profiling are crucial tools for accurate recognition and risk stratification. Histological type-specific genomic alterations, including DNA repair deficiencies, RB1 and TP53 loss, and mismatch repair mutations, provide potential therapeutic opportunities, but treatment recommendations are still largely extrapolated from acinar adenocarcinoma. Limited retrospective data suggest worse outcomes for patients with a rare histology than those with typical acinar adenocarcinoma, highlighting the urgent need for prospective registries and dedicated clinical trials. Rare histologies of prostate cancer are an under-recognized source of morbidity and mortality. Improved diagnostic precision, incorporation of molecular profiling and collaborative data collection efforts are essential to develop evidence-based strategies.},
}

@article {pmid42897340,
year = {2026},
author = {Di, M and Huntington, SF and Voutsinas, JM and Wu, VQ and Ujjani, CS and Ramsey, SD and Huang, JJ and Gopal, AK and Shadman, M},
title = {Survival Outcomes in Chronic Lymphocytic Leukemia During the Novel Agent Era: A Population-Based Analysis.},
journal = {Cancer medicine},
volume = {15},
number = {10},
pages = {e72408},
pmid = {42897340},
issn = {2045-7634},
mesh = {Humans ; *Leukemia, Lymphocytic, Chronic, B-Cell/mortality/drug therapy/epidemiology ; SEER Program ; Female ; Aged ; Male ; Middle Aged ; United States/epidemiology ; Aged, 80 and over ; Treatment Outcome ; Piperidines ; *Antineoplastic Agents/therapeutic use ; },
abstract = {Chemoimmunotherapy (CIT) had long been used to treat chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) until 2014 when the first novel agent, ibrutinib, was approved in the United States. Numerous novel therapies have since become available. Nevertheless, as novel therapies have largely replaced CIT in CLL/SLL, its impact on survival has yet to be examined on the population level. In this study, we used the SEER (Surveillance, Epidemiology, and End Results) database to compare survival in patients with CLL/SLL before and after the approval of the first novel therapy. We included 9913 patients who started treatment within 2 years of CLL/SLL diagnosis. In the multivariable analyses, the overall survival improved significantly (hazard ratio [HR]: 0.86, 95% confidence interval: 0.81, 0.92), and death from CLL/SLL and other cancer (subdistribution-HR: 0.69 and 0.77) also decreased significantly. Nevertheless, CLL/SLL remains the main cause of death during the novel agent era.},
}

Humans
*Leukemia, Lymphocytic, Chronic, B-Cell/mortality/drug therapy/epidemiology
SEER Program
Female
Aged
Male
Middle Aged
United States/epidemiology
Aged, 80 and over
Treatment Outcome
Piperidines
*Antineoplastic Agents/therapeutic use

@article {pmid42904423,
year = {2026},
author = {Madden, DA and Dusic, E and Rios, IE and Zayhowski, K and Tantay, LJ and Sinnott-Armstrong, N and Aguayo-Romero, R and Rabinowitz, S and Ramos, MA and Baker, K and Reisner, SL and Horowitz, CR},
title = {From Collection to Collaboration: Building Ethical Frameworks for Genetic Research.},
journal = {Behavioral medicine (Washington, D.C.)},
volume = {52},
number = {3-4},
pages = {286-297},
pmid = {42904423},
issn = {1940-4026},
support = {R01 HG013145/HG/NHGRI NIH HHS/United States ; },
mesh = {Humans ; Female ; Male ; Adult ; *Community-Based Participatory Research/ethics ; *Genetic Research/ethics ; Middle Aged ; *Transgender Persons/psychology ; Gender-Nonconforming Persons ; Aged ; Young Adult ; Cooperative Behavior ; Genomics/ethics ; Gender Identity ; Data Collection/methods/ethics ; },
abstract = {Transgender, nonbinary, and gender diverse (TNGD) communities are not routinely included as partners in the research that will impact them. The expansion of genomic and gender identity data collection has allowed researchers to explore transgender identity genomics research (TIGR), or associations between genomics and gender identity. We used a community-based participatory research (CBPR) approach to explore TNGD perspectives on TIGR in order to advance ethical practices, minimize harms, and maximize potential benefits. An Executive Stakeholder Board of TNGD community members, advocates, clinicians, and ethics, legal, genomics, and health equity scholars co-developed recruitment strategies, data collection tools, analytic strategies, and a dissemination plan which informed qualitative interviews with 31 U.S.-based TNGD adults. The mean age was 34 years (range = 19-73). Twelve participants were nonbinary, 12 were trans women, and 7 were trans men. The majority (61%) were people of color. Using reflexive thematic analysis, we conceptualized four themes related to ethical TIGR research practices: 1) Are we represented? 2) Are we protected? 3) Are we benefiting? 4) Are we understood? Findings underscore the importance of conducting any TIGR or genomics research with and not on TNGD communities. Ethical research benefits from sustained partnership, transparency, and reflexivity, particularly amidst ideologically motivated threats to inclusive science. Centering TNGD voices in, and recommendations for, genomics strengthens both scientific rigor and community trust. The incongruity of attempting to interrupt a CBPR study focused on ethical research practices in TIGR underscores the contradiction between stated federal commitments to research integrity and the actions taken. (4,064 words).},
}

Humans
Female
Male
Adult
*Community-Based Participatory Research/ethics
*Genetic Research/ethics
Middle Aged
*Transgender Persons/psychology
Gender-Nonconforming Persons
Aged
Young Adult
Cooperative Behavior
Genomics/ethics
Gender Identity
Data Collection/methods/ethics

@article {pmid42905834,
year = {2026},
author = {Gao, Q and Wei, K and Pan, D and Xu, C and Xi, Y and Zhang, Y and Augert, A and MacPherson, D and Jia, D},
title = {CREBBP loss drives immune evasion by epigenetically silencing STING and MHC-I in small cell lung cancer.},
journal = {Science advances},
volume = {12},
number = {43},
pages = {eaef1693},
pmid = {42905834},
issn = {2375-2548},
mesh = {Animals ; *CREB-Binding Protein/genetics/deficiency/metabolism ; Mice ; *Lung Neoplasms/genetics/immunology/pathology/metabolism/drug therapy ; *Epigenesis, Genetic ; *Small Cell Lung Carcinoma/genetics/immunology/pathology/metabolism/drug therapy ; STING Protein ; *Membrane Proteins/genetics ; Humans ; Histone Deacetylase Inhibitors/pharmacology ; Gene Expression Regulation, Neoplastic ; Histones/metabolism ; Acetylation ; Cell Line, Tumor ; Gene Silencing ; *Tumor Escape/genetics ; Tumor Microenvironment/immunology/genetics ; Immunoediting, Cancer ; },
abstract = {Most small cell lung cancers (SCLCs) exhibit low immunogenicity and intrinsic resistance to immunotherapy, yet the underlying mechanisms remain poorly understood. Here, we identify CREBBP loss, a frequent genetic alteration in SCLC, as a key suppressor of tumor cell-intrinsic immune responses that drives an immune-cold tumor microenvironment in Rb1/Trp53-driven autochthonous mouse models. Consistently, Crebbp deletion promotes immune escape in syngeneic SCLC models. Mechanistically, Crebbp loss suppresses Sting and major histocompatibility complex class-I expression by reducing histone H3 acetylation. Notably, HDAC inhibition restores histone acetylation, reactivates these silenced genes, and induces tumor cell-intrinsic immune responses. Moreover, pharmacological HDAC inhibition synergizes with immune checkpoint blockade to suppress tumor growth in both Crebbp-mutant and Crebbp-wild-type SCLCs, with a more prominent effect in Crebbp-mutant tumors. Collectively, these findings establish CREBBP loss as a key mechanism of immune evasion and immunotherapy resistance in SCLC, highlighting HDAC inhibition as a promising strategy to enhance immunotherapy efficacy.},
}

Animals
*CREB-Binding Protein/genetics/deficiency/metabolism
Mice
*Lung Neoplasms/genetics/immunology/pathology/metabolism/drug therapy
*Epigenesis, Genetic
*Small Cell Lung Carcinoma/genetics/immunology/pathology/metabolism/drug therapy
STING Protein
*Membrane Proteins/genetics
Humans
Histone Deacetylase Inhibitors/pharmacology
Gene Expression Regulation, Neoplastic
Histones/metabolism
Acetylation
Cell Line, Tumor
Gene Silencing
*Tumor Escape/genetics
Tumor Microenvironment/immunology/genetics
Immunoediting, Cancer

@article {pmid42905855,
year = {2026},
author = {DeWolf, S and Siegel, SJ and Schmalz, J and Saber, W and Albanese, A and Dong, J and Martens, MJ and Logan, B and Iovino, L and Ingersoll-Ohmdahl, K and Winn, N and Chen, E and Kaminski, J and Neuberg, D and Hebert, K and Keskula, P and Zavistaski, J and Steinberg, L and Schichter, I and Katsamakis, Z and Cagnin, L and Hernandez, V and Warren, M and Applegate, K and Bar, M and Chhabra, S and Choi, SW and Clark, W and Das, S and Jenq, R and Jones, RJ and Levine, JE and Murthy, H and Rashidi, A and Riches, M and Sandhu, K and Sung, AD and Larkin, K and Al Malki, MM and Gooptu, M and Elmariah, H and Alousi, A and Runaas, L and Shaffer, B and Rezvani, A and El Jurdi, N and Loren, AW and Scheffey, D and Sanders, C and Hamadani, M and Dudakov, JA and Bien, S and Robins, H and Horowitz, M and Bolaños-Meade, J and Holtan, S and Bhatt, AS and Perales, MA and Kean, LS},
title = {Graft-versus-host disease prophylaxis shapes T cell biology and immune reconstitution after hematopoietic cell transplant.},
journal = {Science translational medicine},
volume = {18},
number = {872},
pages = {eaef7406},
doi = {10.1126/scitranslmed.aef7406},
pmid = {42905855},
issn = {1946-6242},
mesh = {Humans ; *Graft vs Host Disease/prevention & control/immunology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *T-Lymphocytes/immunology ; *Immune Reconstitution/immunology ; Receptors, Antigen, T-Cell/metabolism ; Cyclophosphamide/therapeutic use ; Female ; Methotrexate/therapeutic use ; Tacrolimus/therapeutic use ; },
abstract = {Successful hematopoietic cell transplant requires immunosuppression to prevent graft-versus-host disease (GVHD), a lethal, T cell-mediated complication. The phase 3 BMT CTN 1703 trial demonstrated superior GVHD-free/relapse-free survival for posttransplant cyclophosphamide (PT-Cy)-based GVHD prophylaxis versus tacrolimus/methotrexate (Tac/MTX), but the T cell biology underpinning these outcomes remains unknown. To determine this, 324 patients were coenrolled onto BMT CTN 1801 to investigate the distinct T cell immune reconstitution pathways of these regimens, including extensive evaluation of T cell receptor (TCR) repertoire, via sequencing of 2359 longitudinal samples and 180,432,350 T cells. Multimodal T cell analysis revealed that PT-Cy was associated with pan-T cell deletion followed by delayed T cell expansion from a smaller founder population compared with Tac/MTX. This created a T cell diversity bottleneck, leading to reduced TCR repertoire diversity for 2 years posttransplant. Reduced TCR diversity, more common in patients receiving PT-Cy, was linked to protection against chronic GVHD when patients were analyzed without regard to study arm. Leveraging donor- and host-specific TCR clonal analysis, we determined that PT-Cy-mediated T cell depletion also depleted pathogen-specific TCRs, rendering PT-Cy patients more likely to lack detectable graft-derived pathogen-specific TCRs early after transplant, which was associated with an increased risk of severe infection. This study reveals how distinct immunosuppression strategies uniquely remodel T cell immunity and shape divergent transplant outcomes.},
}

Humans
*Graft vs Host Disease/prevention & control/immunology
*Hematopoietic Stem Cell Transplantation/adverse effects
*T-Lymphocytes/immunology
*Immune Reconstitution/immunology
Receptors, Antigen, T-Cell/metabolism
Cyclophosphamide/therapeutic use
Female
Methotrexate/therapeutic use
Tacrolimus/therapeutic use

@article {pmid42856123,
year = {2026},
author = {Ma, J and Kundu, P and Randolph, T and Navarro, S and Hullar, M},
title = {Mediation Analysis with Compositional Exposures.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42856123},
issn = {2692-8205},
abstract = {Understanding the causal pathways linking the gut microbiome to downstream biomarkers and clinical outcomes is central to microbiome research. When the microbiome acts as the exposure, the high dimensionality and compositional structure of the data introduce unique methodological challenges for mediation analysis. To address these challenges, we propose a latent variable mediation framework that captures variation in microbial composition through a microbial balance, defined as the log-ratio between two unknown subsets of taxa. This balance serves as a latent scalar exposure and simplifies the estimation of the overall indirect effect at the community level, while simultaneously identifying specific taxa that contribute to the overall direct and indirect effects. We describe the model's estimation and inference, and illustrate the method using data from the Multiethnic Cohort-Adiposity Phenotype Study, where we examine the mediation pathway from the gut microbiome through lipopolysaccharide-binding protein, a marker of metabolic endotoxemia, to percent liver fat.},
}

@article {pmid42856160,
year = {2026},
author = {O'Brien, S and Fujimoto, MH and Lowe, AR and Berger, AH},
title = {Transcriptional adaptation influences buffering among essential paralog gene families.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42856160},
issn = {2692-8205},
abstract = {Buffering among paralogous genes is a well-described phenomenon in which genetic redundancy provides genetic robustness. Shared function among paralogs allows for a compensation effect when one or more paralog family genes are inactivated. Considering the role of transcriptional adaptation in influencing gene expression among highly homologous genes, we sought to identify whether transcriptional adaptation has a role in paralog buffering. We performed Perturb-seq of 110 paralog gene knockouts and assessed compensatory gene expression effects among paralogs as well as at the whole transcriptome level. This analysis identified six paralog pairs that undergo a transcriptional adaptation following CRISPR-mediated loss of one paralog in the pair. Further, we found that the upregulation of TIA1 following paralog TIAL1 loss requires nonsense-mediated decay, and active nuclear import via the importin IPO8. These data provide a comprehensive evaluation of transcriptional adaptation and show that transcriptional adaptation is recurrent but not pervasive among paralogous human genes.},
}

@article {pmid42892238,
year = {2026},
author = {Yuan, R and Yaniv, B and Grivas, P and Patnaik, MM and Patel, SA and Mittal, K},
title = {Severe Cytopenias Following Radioligand Therapy: A Real-World Analysis.},
journal = {Clinical genitourinary cancer},
volume = {24},
number = {8},
pages = {102684},
doi = {10.1016/j.clgc.2026.102684},
pmid = {42892238},
issn = {1938-0682},
abstract = {INTRODUCTION: Two radiopharmaceuticals are approved for metastatic castration-resistant prostate cancer (mCRPC): Radium-223 and [177]Lu-PSMA-617. While short-term hematologic toxicity is well-studied, the long-term risk of severe cytopenias and therapy-related myeloid neoplasm (t-MN) remains unclear. We compared the risk of severe cytopenias between these 2 agents.

PATIENTS: Adults with prostate cancer with ≥ 1 administration of [177]Lu-PSMA-617 or Radium-223. Exclusion criteria included pre-existing grade ≥ 3 cytopenias in the 30 days prior to first infusion and receipt of alternate radiopharmaceutical.

METHODS: Propensity score matching (PSM) was based on age, race, and prior cancer-directed therapies. Primary endpoints were risk of grade ≥ 3 anemia, thrombocytopenia, and neutropenia, assessed at early (0-12 weeks), intermediate (12-36 weeks), and late (> 36 weeks) timepoints from first infusion.

RESULTS: After PSM, 1015 patients remained in each group with well-balanced baseline characteristics. Radium-223 was associated with higher risk of grade ≥ 3 anemia across all 3 time windows compared with [177]Lu-PSMA-617: early (12.3% vs. 7.4%, RR 1.67, P < .001), intermediate (25.5% vs. 13.5%, RR 1.89, P < .001), and late (27% vs. 13.9%, RR 1.94, P < .001). Radium-223 was associated with higher risk of grade ≥ 3 thrombocytopenia in the intermediate (10.7% vs. 6.7%, RR 1.60, P = .001) and late time windows (11.1% vs. 7.1%, RR 1.57, P = .001) as well as higher risk of grade ≥ 3 neutropenia in the intermediate (3.9% vs. 1.9%, RR 2.10, P = .006) and late time windows (4.5% vs. 2.6%, RR 1.77, P = .01).

CONCLUSION: This large, real-world study demonstrated that Radium-223 is associated with significantly higher risk of severe cytopenias compared with [177]Lu-PSMA-617. Findings may inform appropriate patient selection, and sequencing of radiopharmaceutical therapy. Future studies aimed at evaluating the bone marrow environment may further elucidate the potential for clonal hematopoiesis and therapy-related myeloid neoplasms.},
}

@article {pmid42892305,
year = {2026},
author = {Linden, HM and O'Brien, SR and van de Ven, SM and La Porte, P and Conti, PS and Peddi, PF and Mortimer, JE and Brenin, C and Takalkar, AM and McGuinness, JE and Cheng, E and Rao, A and Peterson, LM and Specht, JM and Wong, TZ and Buck, DA and Brufsky, AM and Ulaner, GA},
title = {Clinical Utility of [[18]F]Fluoroestradiol PET/CT to Guide Second Line Treatment Decision in ER-Positive HER2-Negative Metastatic Breast Cancer After Progression on First Line Endocrine Therapy.},
journal = {Clinical breast cancer},
volume = {26},
number = {11},
pages = {32-39},
doi = {10.1016/j.clbc.2026.09.008},
pmid = {42892305},
issn = {1938-0666},
abstract = {PURPOSE: Many patients with ER-positive HER2-negative metastatic breast cancer (MBC) derive limited benefit from second line endocrine therapy. This study evaluated the impact of [[18]F]fluoroestradiol (FES) PET/CT on second line therapeutic decision-making.

METHODS: Patients with progression of ER-positive HER2-negative MBC on first line endocrine therapy were prospectively enrolled in 17 U.S. centers to undergo [[18]F]FES PET/CT after standard-of-care (SoC) imaging. [[18]F]FES uptake in MBC lesions was evaluated. Treating oncologists completed questionnaires before and after [[18]F]FES PET/CT, detailing therapeutic decisions plus their confidence in the decisions. The primary endpoint was the proportion of patients whose therapeutic management changed after [[18]F]FES PET/CT.

RESULTS: Between January 2023 and May 2024, 45 patients underwent [[18]F]FES PET/CT. Imaging results led to management changes in 17 patients (37.8%; 95% CI, 23.8%-53.5%). Twenty-five patients avoided further diagnostic testing, while 7 patients received additional tests. Oncologist's confidence in second line treatment decision increased on average from 6.6 before [[18]F]FES PET/CT to 8.6 afterward on a ten-point scale (P < .0001). In 25 patients (55.6%), lesions visible on SoC imaging were reported as "absent" (FES-negative) on [[18]F]FES PET/CT, suggesting potential loss or downregulation of ER that functionally binds estrogen.

CONCLUSION: [[18]F]FES PET/CT altered therapeutic management in 37.8% of patients with MBC progressing on first line endocrine therapy and significantly increased oncologist's confidence in treatment selection. This imaging modality could help prevent unnecessary prolongation of ineffective endocrine therapy and delays in initiation of more effective options. Future studies should investigate potential outcome benefits after [[18]F]FES PET/CT-informed management changes.},
}

@article {pmid42894054,
year = {2026},
author = {Brennan, M and Javid, SH and Flanagan, MR and Schmicker, R and Gwin, WR and Fleuret, S and Palmquist, E},
title = {Surgical management in HER2 + de novo metastatic breast cancer: disease progression and survival.},
journal = {Breast cancer research and treatment},
volume = {220},
number = {1},
pages = {},
pmid = {42894054},
issn = {1573-7217},
mesh = {Humans ; *Breast Neoplasms/surgery/pathology/mortality/metabolism ; Female ; *Erb-b2 Receptor Tyrosine Kinases/metabolism ; Retrospective Studies ; Middle Aged ; Disease Progression ; *Mastectomy ; Adult ; Sentinel Lymph Node Biopsy ; Lymph Node Excision ; Aged ; Kaplan-Meier Estimate ; },
abstract = {PURPOSE: Advancements in human epidermal growth factor (HER)-targeted therapy have significantly improved survival in patients with de novo metastatic HER-2 positive (HER2+) breast cancer (dnMBC). The role of breast surgery is debated. We examined which HER2 + dnMBC patients undergo surgery and compared outcomes to systemic therapy alone.

METHODS: We performed a single institution retrospective review of patients with HER2 + dnMBC diagnosed 2011-2023. Data included demographics, clinicopathologic details, treatment information, local and distant disease progression, and survival outcomes. Analyses included logistic regression, Kaplan Meier, and Cox proportional hazards models.

RESULTS: The study included 103 patients. Of these, 42.7% underwent breast surgery (70.5% mastectomy, 29.5% lumpectomy). Of these, 72.7% underwent axillary surgery (38.6% axillary lymph node dissection, 27.3% sentinel lymph node biopsy, 6.8% targeted axillary dissection). The median age at diagnosis was 48 years (surgery) and 56 years (no surgery) (p = 0.10). The surgery group had lower number of metastatic sites (1.3 vs. 1.9, p = 0.003) and exhibited higher rates of local disease progression pre-operatively (39% vs. 23.5%, p = 0.05). Post-operatively, there was no significant difference in local disease progression (17.1% vs. 23.5%, p = 0.42). After adjusting for age, sites of metastases, and number of metastatic sites, those who underwent surgery had improved overall survival (HR 0.33 (0.14-0.77), p = 0.02).

CONCLUSION: Patients with HER2 + dnMBC with lower metastatic disease burden and local disease progression were more likely to undergo breast surgery. There was no significant difference in local disease control post-operatively. The significant association between surgery and improved survival must be interpreted with caution due selection bias in this retrospective study.},
}

Humans
*Breast Neoplasms/surgery/pathology/mortality/metabolism
Female
*Erb-b2 Receptor Tyrosine Kinases/metabolism
Retrospective Studies
Middle Aged
Disease Progression
*Mastectomy
Adult
Sentinel Lymph Node Biopsy
Lymph Node Excision
Aged
Kaplan-Meier Estimate

@article {pmid42894845,
year = {2026},
author = {Balwan, R and Hew, YY and Gurumurthy, G and Ang, XW and Ling, RR and Xu, C and Chee, YJ and Dalan, R and Ho, P and Lim, HY and Lam, BD and Thachil, J and Favaloro, EJ and Fan, BE},
title = {Microplastics, nanoplastics, and thrombogenesis.},
journal = {Research and practice in thrombosis and haemostasis},
volume = {10},
number = {7},
pages = {106931},
pmid = {42894845},
issn = {2475-0379},
mesh = {Humans ; *Microplastics/adverse effects ; *Thrombosis/blood/chemically induced/etiology ; *Blood Coagulation/drug effects ; Animals ; Platelet Activation ; },
abstract = {Micro- and nanoplastics (MNPs) are produced through mechanical, chemical, and ultraviolet-mediated degradation of plastics and may enter the human bloodstream via ingestion, inhalation, dermal exposure, and iatrogenic sources. Their detection in human blood, atheromas, and thrombi has raised concerns that they may contribute to thrombogenesis. We conducted a structured narrative review of English-language studies indexed in PubMed, Embase, and Scopus over the preceding 15 years, up to March 31, 2026. The search identified 981 database records and 39 additional manually identified articles; after removing duplicates and screening, 72 articles were included. Evidence was synthesized according to Virchow's triad, focusing on endothelial injury, altered blood flow, hypercoagulability, cellular uptake, polymer type, surface charge, weathering, and protein corona formation. MNPs may contribute to all 3 components of Virchow's triad. Proposed mechanisms include oxidative endothelial injury, glycocalyx disruption, monocyte adhesion, foam-cell formation, plaque instability, immune cell-mediated microvascular obstruction, platelet activation, NETosis, von Willebrand factor interactions, factor XII activation, thrombin generation, and fibrin-rich clot stabilization. These effects appear to vary with particle size, polymer composition, surface charge, and environmental weathering. However, mechanistic evidence largely comes from polystyrene nanoparticle models, whereas human thrombus and atheroma studies more commonly detect polyethylene and polyvinyl chloride. MNPs are biologically plausible contributors to thrombogenesis, but their clinical relevance remains uncertain. Prospective human studies, standardized contamination-controlled detection methods, and dose-response experiments using clinically relevant particles and concentrations are required.},
}

Humans
*Microplastics/adverse effects
*Thrombosis/blood/chemically induced/etiology
*Blood Coagulation/drug effects
Animals
Platelet Activation

@article {pmid42895475,
year = {2026},
author = {Xiao, F and Qin, F and Luo, X and Slewitzke, SE and Fernandes, GF and Johansson, M and Xiao, X and Zaridze, D and Bojesen, SE and Shete, S and Albanes, D and Aldrich, MC and Tardon, A and Fernandez-Tardon, G and Le Marchand, L and Rennert, G and Bickeböller, H and Wichmann, HE and Risch, A and Muley, T and Rosenberger, A and Field, JK and Davies, MPA and Woll, PJ and Kiemeney, LA and Haugen, A and Zienolddiny, S and Lam, S and Johansson, M and Grankvist, K and Schabath, MB and Andrew, AS and Lazarus, P and Arnold, SM and Zhu, D and Brenner, H and Neuhouser, ML and Hung, RJ and Christiani, DC and McKay, JD and Cai, G and Xia, J and Amos, CI},
title = {Large-scale association study identifies lung cancer susceptibility copy number variants and their potential functional role in genetic instability.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-26-0120},
pmid = {42895475},
issn = {1538-7755},
support = {P30 CA076292/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Genome-wide association studies (GWAS) have identified numerous lung cancer susceptibility loci based on single nucleotide polymorphisms (SNPs), yet a substantial proportion of heritability remains unexplained. We therefore evaluated germline copy number variants (CNVs) as an underexplored source of genetic susceptibility and potential contributors to genomic instability in lung cancer.

METHODS: We conducted a genome-wide analysis of germline CNVs using 19,342 cases and 15,917 controls from the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium, with replication in two independent cohorts. High-confidence CNVs were identified by integrating two CNV callers including PennCNV and modSaRa2. Association analyses were performed using both gene-based and CNV region-based approaches. Polygenic risk scores (PRS) were constructed from top loci, and functional validation was conducted using siRNA-mediated knockdown in lung fibroblast cells.

RESULTS: We identified CNVs in four genomic regions (1p36.22, 2q31.2, 6p21.32, and 19q13.32) significantly or suggestively associated with lung cancer risk. Two loci (1p36.22 and 2q31.2) were consistently supported across both analytical strategies. A CNV-based PRS constructed from four key genes (CLCN6, NFE2L2, OPA3, and PSMB8) was significantly associated with lung cancer risk and replicated across independent datasets. Functional assays demonstrated that knockdown of NFE2L2 and OPA3 increased endogenous DNA damage, supporting a role in genomic stability.

CONCLUSIONS: Germline CNVs contribute to lung cancer susceptibility and may influence carcinogenesis through mechanisms related to genomic instability.

IMPACT: These findings expand our knowledge of the genetic architecture of lung cancer and suggest that the cumulative burden of germline CNVs may contribute to lung cancer susceptibility.},
}

@article {pmid42885562,
year = {2026},
author = {Osarogiagbon, RU and Unger, JM and Doolittle, GC and Ochoa, AC},
title = {Exemplar 1: Clinical Trials Innovations for Rural Areas.},
journal = {Journal of the National Cancer Institute. Monographs},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncimonographs/lgag019},
pmid = {42885562},
issn = {1745-6614},
abstract = {People who reside in rural areas have higher incidence of cancer, limited access to timely high-quality cancer care, and worse survival. Limited clinical trials access for rural residents with cancer exemplifies the challenge of rural cancer care. As clinical trials become more deeply integrated into high quality routine cancer care delivery, finding innovative ways to expand access to rural residents has become a high priority. The fundamental solution is to bring clinical trials to where rural residents routinely receive their care, ideally as close to home as safely possible. We provide examples of innovative solutions to achieve this fundamental goal, including: The NCI Community Oncology Research Program (NCORP) which has sought to integrate National Clinical Trials Network infrastructure into community and rural healthcare delivery infrastructure; support policy changes promoting decentralized clinical trials processes; telehealth strategies to decentralize key clinical trials processes and create virtual clinical trials infrastructure with a centralized research workforce; and to promote pragmatic approaches to engage administrators and clinicians in community and rural healthcare systems who traditionally have not adopted the clinical trials mission.},
}

@article {pmid42886732,
year = {2026},
author = {Koutsakos, M and Crawford, JC and Grzelak, L and Rizzetto, S and Nguyen, AT and Chaurasia, P and Petersen, J and Rowntree, LC and Allen, EK and Tong, SYC and Cheng, AC and Kotsimbos, TC and Luciani, F and Rossjohn, J and Gras, S and Thomas, PG and Nguyen, THO and Kedzierska, K},
title = {TCRαβ repertoire plasticity defines universal CD8+ T cell responses directed at influenza-specific HLA-A*02:01-PB1413-421 epitope.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
volume = {215},
number = {10},
pages = {},
doi = {10.1093/jimmun/vkag270},
pmid = {42886732},
issn = {1550-6606},
support = {L1-2041012//Australian National Health and Medical Research Council (NHMRC)/ ; EL1-2026357//Australian National Health and Medical Research Council (NHMRC)/ ; L2-#2033783//Australian National Health and Medical Research Council (NHMRC)/ ; L2-#2034677//Australian National Health and Medical Research Council (NHMRC)/ ; 1071916//NHMRC/ ; 1122524//NHMRC/ ; 1102792//NHMRC Senior Research Level B Fellow/ ; 1159272//NHMRC Senior Research Level/ ; 1128416//NHMRC CDF2 Fellow/ ; //Melbourne International Research Scholarship and Melbourne International Fee Remission Scholarship/ ; 2008981//NHMRC Investigator Award/ ; //St. Jude Center of Excellence for Influenza Research and Surveillance/ ; HHSN27220140006C//National Institute of Allergy and Infectious Diseases/ ; R01 AI 107625//National Institute of Allergy and Infectious Diseases/ ; R01AI136514//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; *CD8-Positive T-Lymphocytes/immunology ; *Receptors, Antigen, T-Cell, alpha-beta/genetics/immunology/metabolism ; *Influenza, Human/immunology ; *Epitopes, T-Lymphocyte/immunology ; *HLA-A2 Antigen/immunology ; *Influenza A virus/immunology ; Cross Reactions ; },
abstract = {HLA-A*02:01-restricted PB1413+CD8+ T cells provide the broadest reported cross-reactive immunity against influenza A, B, and C viruses. Here, we investigated T cell receptor (TCR) clonotypic signatures within these universal A2/PB1413+CD8+ T cell pools, compared with immunodominant influenza A-specific M158+CD8+ T cells and codominant influenza B-specific A2/HA543+CD8+ memory T cells. Using single-cell reverse transcriptase polymerase chain reaction and RNA sequencing methodologies, we defined TCRαβ repertoire composition and diversity. Our study shows that CD8+ T cells responding to these 3 epitopes differ in magnitude and TCRαβ repertoires in terms of gene usage and sharing, underpinned by specific TCR and structural features for each pMHC-I specificity. Our data demonstrated that the A2/PB1413+CD8+ TCRαβ repertoire encompassed diverse gene segment usage within both TCRα and TCRβ chains. These were, however, greatly variable across HLA-A2*02:01-expressing individuals and lacked any shared features within TRAV, TRBV, TRBJ, and TRAJ gene segments. This A2/PB1413+CD8+ TCRαβ diversity stemmed from the low probability of recombination attributed to a large number of N-insertions in the TCRβ chain. PB1413+CD8+ T cells also displayed remarkable plasticity in recognition of the A2/PB1413 epitope depicted by versatile CD8+ T cell recognition patterns of the universal A2/PB1413 epitope across HLA-A*02:01-expressing individuals. Conversely, TCRαβ repertoires within A2/BHA543+CD8+ and M158+CD8+ T cells displayed common TRAV, TRBV, TRBJ, and TRAJ gene segments, shared across HLA-A*02:01-expressing individuals and recognizing key residues within A2/BHA543 and A2/M158 epitopes. Overall, our data showed a great level of TCRαβ gene usage diversity within universal A2/PB1413+CD8+ T cells, indicating that the TCRαβ clonal plasticity defines universal immunity toward human influenza viruses.},
}

Humans
*CD8-Positive T-Lymphocytes/immunology
*Receptors, Antigen, T-Cell, alpha-beta/genetics/immunology/metabolism
*Influenza, Human/immunology
*Epitopes, T-Lymphocyte/immunology
*HLA-A2 Antigen/immunology
*Influenza A virus/immunology
Cross Reactions

@article {pmid42888021,
year = {2026},
author = {Peng, Y and Wang, M and Abe, SK and Cai, H and Chan, AT and Datta, M and Eliassen, AH and Giovannucci, EL and Hou, T and Huang, BZ and Huang, WY and Inoue, M and Kanehara, R and Koh, WP and Larsson, SC and Liao, LM and Loftfield, E and Marchand, LL and Mavani, P and McCullough, ML and Miller, AB and Moore, SC and Mucci, LA and Prizment, A and Robien, K and Rohan, TE and Sadeghi, H and Sawada, N and Shams-White, MM and Shu, XO and Schulze, MB and Sieri, S and Sinha, R and Skeie, G and Song, M and Stampfer, MJ and Sun, Y and Um, CY and van den Brandt, PA and Wang, F and Wang, R and White, E and Willett, WC and Wolk, A and Yuan, JM and Zheng, W and Haydon, A and MacInnis, RJ and Camargo, MC and Ferrari, P and Giles, GG and Milne, RL and Smith-Warner, SA and Jayasekara, H},
title = {Processed meat, unprocessed red meat, poultry, seafood, and egg intake and stomach cancer risk: a pooled analysis of 20 cohorts.},
journal = {International journal of epidemiology},
volume = {55},
number = {6},
pages = {},
doi = {10.1093/ije/dyag224},
pmid = {42888021},
issn = {1464-3685},
support = {GNT1163120//Australian National Health and Medical Research Council/ ; },
mesh = {Humans ; *Stomach Neoplasms/epidemiology/etiology ; Female ; *Seafood/adverse effects ; *Eggs/adverse effects ; Animals ; Male ; Poultry ; Middle Aged ; *Red Meat/adverse effects ; *Diet/adverse effects ; Risk Factors ; Adult ; Proportional Hazards Models ; *Adenocarcinoma/epidemiology/etiology ; Aged ; Cohort Studies ; Australia/epidemiology ; },
abstract = {BACKGROUND: Processed meat is classified as a carcinogen and unprocessed red meat a probable carcinogen, but their associations with stomach cancer are not established. We evaluated intakes of these food groups and poultry, seafood, and eggs in relation to stomach cancer risk.

METHODS: Individual-level data for 1 100 370 females and 891 919 males from 20 cohorts were analysed. Diet was assessed at baseline by using food-frequency questionnaires or diet histories generally covering the past year and harmonized across studies. We used Cox regression to estimate multivariable-adjusted study- and sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with each food group and combined study-specific estimates by using random-effects meta-analysis. We repeated analyses using an aggregated dataset combining all studies.

RESULTS: During follow-up (mean = 8-23 years across studies), 8561 invasive gastric adenocarcinomas were diagnosed. Processed meat intake showed weak evidence of an overall association with stomach cancer risk (HR, 1.15 for ≥45 vs <3 g/day; 95% CI, 1.00-1.32 and HR, 1.03 per 25-g/day increment; 95% CI, 0.99-1.07). This association was limited to current smokers (Pinteraction = .01) and differed by geographic region, with evidence for an association in Australian and European studies and no association observed in Asian studies (Pinteraction = .02). Positive associations with stomach cancer were observed for egg intake; no association was found for unprocessed red meat, poultry, or seafood.

CONCLUSION: Higher processed meat intake was associated with a modestly increased risk of stomach cancer among current smokers, although residual confounding by smoking dose remains possible. Findings for eggs warrant further investigation.},
}

Humans
*Stomach Neoplasms/epidemiology/etiology
Female
*Seafood/adverse effects
*Eggs/adverse effects
Animals
Male
Poultry
Middle Aged
*Red Meat/adverse effects
*Diet/adverse effects
Risk Factors
Adult
Proportional Hazards Models
*Adenocarcinoma/epidemiology/etiology
Aged
Cohort Studies
Australia/epidemiology

@article {pmid42888037,
year = {2026},
author = {Roychoudhury, P and Bennett, JC and Elias-Warren, A and Wetzler, E and Starita, LM and Stone, J and Capodanno, B and Prentice, R and Han, PD and Grindstaff, SB and Reinhart, D and Logue, JK and Wolf, CR and Boeckh, M and Lockwood, CM and Perofsky, AC and Viboud, C and Shendure, J and Bedford, T and Carone, M and Englund, JA and Chu, HY},
title = {RSV Molecular Epidemiology Pre- and Post-COVID-19 Pandemic Periods in Seattle, Washington, USA.},
journal = {Influenza and other respiratory viruses},
volume = {20},
number = {10},
pages = {e70332},
pmid = {42888037},
issn = {1750-2659},
support = {//Gates Ventures/ ; },
mesh = {Humans ; Washington/epidemiology ; *Respiratory Syncytial Virus Infections/epidemiology/virology ; *Respiratory Syncytial Virus, Human/genetics/isolation & purification/classification ; Molecular Epidemiology ; Child ; *COVID-19/epidemiology ; Adult ; Child, Preschool ; Female ; Male ; Infant ; Adolescent ; Young Adult ; Pandemics ; Middle Aged ; Whole Genome Sequencing ; },
abstract = {BACKGROUND: Globally, RSV declined to historically low levels following stay-at-home orders in 2020 and re-emerged as restrictions lifted, with large inter-seasonal outbreaks and other shifts in epidemiology. The effect of the pandemic restrictions on genomic diversity has not been well studied.

METHODS: Individuals with respiratory symptoms were enrolled into community-based surveillance studies and provided nasal swabs over three respiratory virus seasons from 2019 to 2022 in the Seattle metropolitan area in Washington State, USA. Samples were tested for RSV by RT-qPCR, with whole genome sequencing performed for a subset.

RESULTS: Among children and adults, respectively, 1.8% (232/13,014) and 0.2% (86/46,042) of samples tested positive for RSV-A and 1.1% (139/13016) and 0.3% (119/46043) for RSV-B. Positive cases were observed in childcare (n = 39), clinic (n = 270), university (n = 20), workplace (n = 32) or nursing facility (n = 1) sites and through at-home self-administered testing (n = 253). Median age for all participants was 33 years (IQR: 23, 48) and 3 years (IQR: 3, 33) for those who tested positive. Cough (≥ 85%) and rhinorrhea (≥ 85%) were the most common symptoms for RSV cases. During 2019-2020, six RSV-A and three RSV-B lineages circulated (majority lineages A.D.1 and B.D.4.1.1). Almost no RSV was detected during 2020-2021. During 2021-2022, RSV-B lineage B.D.E.1 was dominant.

CONCLUSIONS: In a community surveillance study spanning several years, RSV was commonly detected in young children across several sites. Circulation of RSV was disrupted by pandemic mitigation measures, with shifts in genomic diversity detected after lifting of pandemic restrictions.},
}

Humans
Washington/epidemiology
*Respiratory Syncytial Virus Infections/epidemiology/virology
*Respiratory Syncytial Virus, Human/genetics/isolation & purification/classification
Molecular Epidemiology
Child
*COVID-19/epidemiology
Adult
Child, Preschool
Female
Male
Infant
Adolescent
Young Adult
Pandemics
Middle Aged
Whole Genome Sequencing

@article {pmid42890763,
year = {2026},
author = {Yan, G and Li, JJ and Biggin, MD},
title = {Q-SID: Detecting collusion groups from exam question scores with error quantification.},
journal = {Patterns (New York, N.Y.)},
volume = {7},
number = {10},
pages = {101642},
pmid = {42890763},
issn = {2666-3899},
support = {R35 GM140888/GM/NIGMS NIH HHS/United States ; },
abstract = {Collusion in online exams undermines the integrity of exam results. Existing detection methods identify suspicious student pairs and are often limited to multiple-choice formats. We introduce Question-Score Identity Detection (Q-SID), a statistical algorithm that efficiently detects likely collusion groups and quantifies uncertainty using only graded numeric question scores. This enables Q-SID to support a broad range of multiple-choice and non-multiple-choice exams. Q-SID reports two false-positive rates (FPRs) for each collusion group: (1) an empirical FPR, whose null data are from strictly proctored exam datasets, and (2) a synthetic FPR, whose null data are simulated from a copula-based model. Across 34 unproctored exam datasets, including two benchmark datasets with verified positives and negatives from textual analysis, Q-SID performs robustly across exam formats, class sizes, numbers of questions, and levels of complexity. It is more accurate and substantially faster than widely used pairwise statistics and group-level baselines, including answer similarity at group level (ASIg) and clique detection.},
}

@article {pmid42891560,
year = {2026},
author = {Sesay, FA and Balkus, JE and Jaoko, W and Mureithi, M and Mandaliya, K and Mwinyikai, K and Sabo, MC and Shafi, J and Lund, JM and Bukusi, EA and Stewart, J and Soge, OO and McClelland, RS},
title = {Association Between Vaginal Gram Stain Categories and Cervicitis in Kenyan Women Who Engage in Sex Work.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag519},
pmid = {42891560},
issn = {1537-6613},
abstract = {BACKGROUND: Cervicitis is often caused by Chlamydia trachomatis and Neisseria gonorrhoeae, but remains unexplained in approximately half of cases. Studies examining associations between the vaginal microbiota and cervicitis have produced conflicting results.

METHODS: This study analyzed data from a cohort of women who engage in sex work in Mombasa, Kenya (2004-2023). Vaginal microbiota was categorized by Nugent criteria as normal (0-3), intermediate (4-6), or bacterial vaginosis (BV, 7-10). Lactobacillus status by culture was classified as none detected, non-H2O2-producing, or H2O2-producing. Cervicitis was defined as >30 polymorphonuclear cells per high-power field. Modified Poisson regression with generalized estimating equations was used to examine associations between Nugent category, Lactobacillus status, and cervicitis.

RESULTS: Among 1,615 participants (25,322 visits), cervicitis prevalence was 5.8% with normal microbiota, 9.1% with intermediate microbiota (RR 1.39 [95% CI 1.24-1.56]), and 6.8% with BV (RR 1.14 [95% CI 1.02-1.26]). Cervicitis prevalence also varied by Lactobacillus status: 5.1% with none detected, 8.5% with non-H2O2-producing (RR 1.33 [95% CI 1.18-1.50]), and 11.9% with H2O2-producing Lactobacillus (RR 1.70 [95% CI 1.52-1.90]). Findings remained consistent in multivariable analyses.

CONCLUSION: Intermediate microbiota was associated with the greatest cervicitis risk among Gram stain categories, exceeding both normal microbiota and BV. Unexpectedly, cervicitis risk increased progressively from no Lactobacillus to non-H2O2-producing to H2O2-producing Lactobacillus. These findings suggest that intermediate microbiota may represent a state in which proinflammatory pathways from BV and Lactobacillus-dominated microbiota intersect, potentially driving enhanced neutrophil recruitment. Future studies should test this hypothesis.},
}

@article {pmid42856267,
year = {2026},
author = {Gogarten, SM and Martschenko, DO and Patel, R and Sinnott-Armstrong, N},
title = {Large language model-based bibliometric evaluation of population descriptors in human genetics.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42856267},
issn = {2692-8205},
abstract = {As the use of population descriptors such as race, ethnicity, and ancestry have become increasingly common in modern genetics research, there have been growing calls to critically examine their use. Most notably, in 2023, the National Academies of Science, Engineering, and Medicine (NASEM) published a report titled Using Population Descriptors in Genetics and Genomics Research: A New Framework for an Evolving Field, which included eight specific and actionable recommendations for researchers to implement the ethical and accurate use of population descriptors in genetic research. Here, we use the 2023 NASEM report as a benchmark to analyze the use of population descriptors in genome-wide association studies (GWAS). We develop a general toolkit for large language model-based bibliometrics, operationalize the reporťs recommendations into an evaluation framework, and apply this framework to evaluate all 4,007 papers from the GWAS Catalog published between 2007 and 2025 with full text available on PubMedCentral. We find significant improvements in adherence to NASEM report recommendations over time. However, most improvements predate the publication of the NASEM report itself, suggesting the report functioned primarily as a synthesis of existing best practices rather than a catalyst for change. We conclude by highlighting opportunities for growth in the field of human genetics.},
}

@article {pmid42882897,
year = {2026},
author = {Wang, Z and Afshar, N and Hodge, AM and Jayasekara, H and Koutros, S and van den Brandt, PA and Wolk, A and Wang, M and Hou, T and Adami, HO and Åkesson, A and Arcan, C and Bertrand, KA and Bittoni, M and Bogumil, D and Cai, H and Cross, AJ and Eliassen, AH and Freudenheim, JL and Gierach, GL and Giovannucci, EL and Huang, WY and Jakszyn, P and Kanehara, R and Kirsh, VA and Koh, WP and Kroenke, CH and Lacey, JV and Liao, LM and Loftfield, E and Ma, C and Marchand, LL and Martinez, ME and Miller, AB and Moore, SC and Mucci, LA and Munro, HM and Neuhouser, ML and Petrick, JL and Poynter, JN and Preston, MA and Prizment, A and Rees, S and Robien, K and Rohan, TE and Sandin, S and Sawada, N and Schernhammer, ES and Shams-White, MM and Shrubsole, MJ and Shu, XO and Sinha, R and Sieri, S and Song, M and Stampfer, MJ and Stolzenberg-Solomon, RZ and Triplette, M and Um, CY and Visvanathan, K and VoPham, T and Wang, F and Wang, R and Wang, SS and Wang, Y and Weiderpass, E and Wilkens, L and Willett, WC and Yuan, JM and Zheng, W and Rothman, N and Lynch, BM and Silverman, DT and Smith-Warner, SA and Milne, RL},
title = {Consumption of Processed Meat and Unprocessed Red Meat and Risk of Bladder Cancer: A Pooled Analysis of 30 Cohort Studies.},
journal = {Cancers},
volume = {18},
number = {19},
pages = {},
pmid = {42882897},
issn = {2072-6694},
support = {75N92021D00002/HL/NHLBI NIH HHS/United States ; U01 CA164974/CA/NCI NIH HHS/United States ; UM1 CA173640/CA/NCI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; R01 CA039742/CA/NCI NIH HHS/United States ; P30 CA033572/CA/NCI NIH HHS/United States ; U01 CA202979/CA/NCI NIH HHS/United States ; UM1 CA182910/CA/NCI NIH HHS/United States ; U01 CA199277/CA/NCI NIH HHS/United States ; UM1 CA164917/CA/NCI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; U01 CA063673/CA/NCI NIH HHS/United States ; U01 CA167462/CA/NCI NIH HHS/United States ; P01 CA087969/CA/NCI NIH HHS/United States ; IIG_FULL_2020_036//World Cancer Research Fund Netherlands/ ; U01 CA176726/CA/NCI NIH HHS/United States ; R01 CA144034/CA/NCI NIH HHS/United States ; U01 CA167552/CA/NCI NIH HHS/United States ; U01 CA086308/CA/NCI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; P30 CA023100/CA/NCI NIH HHS/United States ; R01 CA077398/CA/NCI NIH HHS/United States ; UM1 CA167462/CA/NCI NIH HHS/United States ; U01 CA164973/CA/NCI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; U01 AG018033/AG/NIA NIH HHS/United States ; UM1 CA182876/CA/NCI NIH HHS/United States ; },
abstract = {Background: Processed meat and unprocessed red meat are considered carcinogenic and 'probably carcinogenic' to humans, respectively, but findings for bladder cancer remain inconsistent. Objectives: We assessed associations between processed meat and unprocessed red meat intake and bladder cancer risk using data from the Pooling Project of Prospective Studies of Diet and Cancer. Methods: Associations with bladder cancer risk were assessed using individual-level data from 30 cohort studies from North America, Europe, Australia and Asia. Diet was assessed at enrolment using validated food frequency questionnaires or diet histories. Following a pre-specified analysis plan, study- and sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression, adjusted for smoking status and duration and other potential confounders, and pooled using inverse-variance-weighted random-effects meta-analysis. Results: During median follow-up across cohorts of 8-29 years, among 2,575,971 participants, 20,780 were diagnosed with bladder cancer. Processed meat intake was associated with increased bladder cancer risk (HR comparing ≥40 with <5 g/day = 1.08; 95% CI: 1.02-1.15; HR per 20 g/day = 1.02; 95% CI: 1.00-1.03). Weaker evidence of association with increased risk was also observed for unprocessed red meat (HR comparing ≥100 with <20 g/day = 1.06; 95% CI: 1.00-1.13; HR per 50 g/day = 1.01; 95% CI: 0.99-1.03). There was no evidence of heterogeneity by study, sex, or region. Conclusions: Higher intakes of processed meat and unprocessed red meat were associated with a small increase in risk of bladder cancer. These findings are consistent with existing public health recommendations to limit consumption of red and processed meat.},
}

@article {pmid42882001,
year = {2026},
author = {Xu, X and Burwick, NR and Baxter, SK and Boothby, AB and Fan, VS and Salk, JJ},
title = {Sustained Platelet Improvement Temporally Associated with Dupilumab in Chronic Immune Thrombocytopenia: A Case Study.},
journal = {Journal of clinical medicine},
volume = {15},
number = {19},
pages = {},
pmid = {42882001},
issn = {2077-0383},
abstract = {Introduction: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by reduced platelet counts. Dupilumab, an IL-4 receptor antagonist, is effective in allergic and auto-inflammatory diseases; however, use in ITP remains unexplored. Case Presentation: A 78-year-old male with chronic ITP, maintained on a thrombopoietin receptor agonist (TPO-RA) with an average platelet count of around 78,000/μL, demonstrated a sustained rise in platelet counts (>100,000/μL) shortly following initiation of dupilumab for an unrelated chronic obstructive pulmonary disease. This improvement enabled a stepwise reduction in TPO-RA to <20% of his base dosage while maintaining adequate platelet levels for three years since. Despite detailed patient interviews and chart review, we were unable to identify any clinical factors besides commencement of dupilumab as a potential explanation. If indeed causative, we speculate that a TPO-RA-sparing effect of dupilumab might occur via disruption of IL-4 signaling, leading to inhibited Th9 cell activation and subsequent IL-21 production to restore Treg/Th17 balance, thus contributing to decreased platelet destruction. Discussion: This case supports a potential role for dupilumab in the treatment of chronic ITP. To our knowledge, it is the first report suggesting a therapeutic benefit of IL-4 blockade in this disease. Identification of predictive immunologic biomarkers, such as cytokine profiles or T-cell subset signatures, might help identify patients most likely to benefit from IL-4 pathway modulation. Further controlled studies are warranted to clarify the immunologic mechanisms underlying this response and to assess the therapeutic potential of targeting the IL-4 axis in ITP.},
}

@article {pmid42845279,
year = {2026},
author = {Varnum-Finney, B and Heck, AM and Srivatsan, SR and Dozono, S and Wellington, R and Chankhunthod, AB and Nourigat-McKay, C and Dignum, T and Trapnell, C and Hadland, B},
title = {Multiplexed single cell transcriptomics optimizes mesodermal patterning and hemogenic endothelial output from murine embryonic stem cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42845279},
issn = {2692-8205},
abstract = {BACKGROUND: Early patterning of mesodermal precursor populations is a key step of hematopoietic development in the embryo. To better understand this process, we employed sci-Plex, a high-throughput method of measuring multiplexed perturbations at the single-cell level, to evaluate the transcriptional response of mouse embryonic stem cells subjected to a gradient of two key morphogens in early mesoderm/hematopoietic development, Activin and BMP4.

RESULTS: sci-Plex revealed varying combinations of Activin and BMP4 temporally influenced mesoderm patterning in vitro and subsequent production of cell types reflecting their in vivo counterparts. We leveraged sci-Plex data to further optimize the generation of intraembryonic-like hemogenic endothelial cells that serve as the precursors of definitive hematopoietic lineages, including hematopoietic stem cells.

CONCLUSIONS: This study highlights the utility of sci-Plex to dissect how dose and temporal integration of interacting signal pathways determines cell fates and serves as a resource to analyze cell fate choices in early mesoderm patterning at single cell resolution.},
}

@article {pmid42845533,
year = {2026},
author = {Bussey-Sutton, CR and Gray, CN and Wu, BJ and Peterson, JJ and Burgos, SD and Mills, CA and Herring, LE and Browne, EP and Turner, AW and Margolis, DM and Emerman, M and Strahl, BD},
title = {RelB proximity proteomics and CRISPR screening define chromatin regulators of noncanonical NF-κB control of HIV latency and reactivation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42845533},
issn = {2692-8205},
abstract = {Activation of the non-canonical NF-κB pathway via RelB/p52 signaling by SMAC mimetics such as AZD5582 is a promising strategy to induce HIV expression from latency, but the chromatin mechanisms linking RelB/p52 to proviral regulation remain poorly defined. Here, we combine RelB BioID proteomics, targeted HIV-CRISPR screening, and pharmacologic validation to identify ncNF-κB-associated regulators of HIV expression. RelB BioID revealed an extensive interaction network of chromatin and transcriptional regulators in basal and AZD5582-activated states. Basally associated RelB proteins included NSD2, SWI/SNF components, UHRF1, and DNMT1, while AZD5582-enriched proteins included p300, USP7, LSD1/KDM1A, NuRD components, SIN3A, and HBO1/KAT7. Functional screening using a custom guide RNA library targeting all BioID-identified factors identified regulators that promote HIV reactivation, including HBO1/KAT7, NSD2, and SIN3A, and regulators that restrict HIV expression, including p300, CHD4, and USP7. Because KAT7/HBO1 and p300 encode acetyltransferases with opposing screen phenotypes, we tested whether their catalytic activities contribute to HIV transcriptional regulation and found that, consistent with the CRISPR screen, KAT7/HBO1 inhibition reduced AZD5582-induced reactivation, whereas p300 inhibition enhanced it. Together, these data define a resource linking the RelB-associated chromatin landscape to HIV latency and reactivation.},
}

@article {pmid42880233,
year = {2026},
author = {Sohn, MH and Dubocanin, D and Vollger, MR and Kwon, Y and Minkina, A and Munson, KM and Hart, SFM and Ranchalis, JE and Parmalee, NL and Sedeño-Cortés, AE and Ou, J and Neph, SJ and Au, NYT 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 Mitchell, MW and Pham, MM and Scheinfeldt, LB and Smith, G and Ryke, E and Smith, JD and Sutherlin, L and Swanson, EG and Weiss, JM and , and Carvalho, CMB and Coorens, THH 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 a cancer.},
journal = {Cell},
volume = {189},
number = {21},
pages = {6630-6647.e8},
doi = {10.1016/j.cell.2026.09.033},
pmid = {42880233},
issn = {1097-4172},
support = {DP5 OD029630/OD/NIH HHS/United States ; T32 GM007454/GM/NIGMS NIH HHS/United States ; U01 HG013744/HG/NHGRI NIH HHS/United States ; UM1 DA058220/DA/NIDA NIH HHS/United States ; },
mesh = {Humans ; *Telomere/genetics/metabolism ; *Mutation ; *Melanoma/genetics/pathology ; Epigenesis, Genetic ; Centromere/metabolism ; Telomerase/metabolism ; },
abstract = {Cancer genomes harbor extensive somatic genetic and epigenetic variation, yet large portions of the genome remain inaccessible to conventional reference-based analyses. Here, we demonstrate that pairing a near-telomere-to-telomere (near-T2T) diploid assembly of a donor with deep short- and long-read sequencing of their melanoma reveals that 16% of somatic variants localize to sequences absent from GRCh38, with satellite repeats acting as hotspots for UV-associated mutagenesis. Centromere kinetochore binding domains emerge as focal sites of chromosome arm aneuploidy breakpoints and somatic genetic variation, features we further demonstrate are also present in non-cancerous tissues. By contrast, extensive epigenetic remodeling of kinetochore binding domains appears specific to oncogenesis. Single-molecule telomere analyses reconstruct the cycle of telomere erosion and telomerase-mediated extension during tumor evolution, while haplotype-resolved chromatin maps reveal widespread somatic epimutations impacting regulatory elements. Together, these findings define previously inaccessible dimensions of somatic variation and establish a framework for telomere-to-telomere studies of human mosaicism.},
}

Humans
*Telomere/genetics/metabolism
*Mutation
*Melanoma/genetics/pathology
Epigenesis, Genetic
Centromere/metabolism
Telomerase/metabolism

@article {pmid42880546,
year = {2026},
author = {Iovino, L and Ma, N and Davis, C and Glockling, L and Basom, R and Milano, F and Gauthier, J and Ali, N and Gooley, T and Mielcarek, MB and Sandmaier, BM and Wu, QV and Sorror, ML},
title = {Comprehensive, simplified, and objective comorbidity assessment before allogeneic hematopoietic cell transplantation: a comparative cohort study.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2026.10.022},
pmid = {42880546},
issn = {2666-6367},
abstract = {BACKGROUND: Pretransplant comorbidity assessment informs risk stratification before allogeneic hematopoietic cell transplantation (allo-HCT), but the optimal balance among comprehensiveness, simplicity, and objectivity of the information captured under the available comorbidity indices (CI) remains uncertain.

OBJECTIVE(S): Here, we are comparing the performance of different CIs of assessing pre-HCT comorbidities and predicting outcomes.

STUDY DESIGN: We calculated the HCT-CI, the augmented HCT-CI (augHCT-CI), and the recently proposed simplified comorbidity index (SCI) based on a set of fewer comorbidities. We generated a fourth, objective HCT-CI (objHCT-CI), constructed from the measurable components of the augHCT-CI. We analyzed data from 3,473 consecutive single-center allo-HCT recipients transplanted from 2008-2022. We estimated the Harrell's C-index of the four CIs, their time-dependent ROC (Receiver Operating Characteristic) curve, and their ability of stratifying cumulative incidence of non-relapse mortality (NRM) and overall survival (OS).

RESULTS: All four indices significantly stratified NRM and OS (P<0.001). C-indices for NRM were 0.600 for HCT-CI, 0.632 for augHCT-CI, 0.628 for SCI, and 0.610 for objHCT-CI; corresponding C-indices for OS were 0.584, 0.612, 0.587, and 0.591. On the question on comprehensiveness versus simplicity, among 951 patients classified as SCI score 0, the augHCT-CI identified additional risk heterogeneity: 1-year NRM was 5.4%, 8.1%, and 10.9% for augHCT-CI scores 0, 1-2, and ≥3, respectively (Gray P=0.025), and OS differed significantly across these groups (P<0.0001).

CONCLUSION(S): Performance of all indices was comparable. SCI offers simplicity, but may lose prognostic granularity among patients classified as lowest risk. Future tools should improve reproducibility and automation without sacrificing clinically meaningful comorbidity information.},
}

@article {pmid42523218,
year = {2026},
author = {Bauer, MS and Kumar, S and Donald-Paladino, M and Li, D and Klupt, KA and Glögl, M and Escamilla, AMF and Schlichthaerle, T and Muratspahić, E and Wang, X and Schmiderer, L and Kenny, S and Coventry, B and Faezov, B and Chen, W and Shida, AF and Lee, GR and Hsia, Y and Kibler, RD and Elowitz, MB and Lietha, D and Nabet, B and Baker, D},
title = {De novo design of selective kinase modulators.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42523218},
issn = {2692-8205},
abstract = {Protein kinases are critical regulators of cellular signaling, but precise modulation of their activity remains challenging due to their high structural conservation. Here, we present de novo designed genetically encoded miniproteins capable of activating or inhibiting focal adhesion kinase (FAK) by directly targeting the kinase domain itself. Among 96 binders designed to stabilize distinct conformational states of FAK, 33 modulated kinase activity. Biochemical characterization of the four most potent modulators revealed that two designs inhibit FAK with low-nanomolar IC50 values while the remaining two potentiated FAK activity by more than two-fold. When expressed in cells, the modulators preserved the same inhibitory and activating effects observed in vitro, establishing that designed conformational binders can directly tune FAK signaling in living cells. Taking advantage of the high similarity between kinases, we redesigned the FAK inhibitors to inhibit Src kinase. Our approach establishes a versatile platform for selective and genetically encoded kinase control as a way to rewire cell signaling and as a starting point for the discovery of novel modulatory sites of kinases.},
}

@article {pmid42873797,
year = {2026},
author = {Saini, J and Wong, T and Schwarz, M and McClure, R and Shepherd, A and Zeng, J and Rengan, R},
title = {An operational key performance indicator framework and reference data from a multi-room pencil beam scanning proton therapy center.},
journal = {PloS one},
volume = {21},
number = {10},
pages = {e0360926},
pmid = {42873797},
issn = {1932-6203},
mesh = {Longitudinal Studies ; *Proton Therapy/standards ; Facility Design and Construction ; Health Facility Size ; Quality Improvement ; Workflow ; Humans ; Retrospective Studies ; *Quality Indicators, Health Care/standards/statistics & numerical data ; Radiotherapy Planning, Computer-Assisted ; Efficiency, Organizational/standards/statistics & numerical data ; Reference Values ; *Health Facilities ; *Health Facility Administration/standards/statistics & numerical data ; },
abstract = {PURPOSE: Multi-room proton therapy centers face unique operational challenges related to shared beam delivery systems, extended treatment hours, and high clinical complexity. This study presents a structured framework of key performance indicators (KPIs) and reports longitudinal single-institution operational reference data from a multi-room proton therapy center to support operational assessment and continuous quality improvement.

METHODS AND MATERIALS: Operational KPIs were retrospectively evaluated for calendar year 2024 at a three-room proton therapy center utilizing pencil beam scanning. KPIs were categorized into three areas: beam performance, treatment planning and pre-treatment workflow, and treatment room operations. Beam performance metrics included site- and room-specific uptime and beam pauses. Treatment planning metrics quantified CT simulation-to-patient scheduling timelines with attribution to physician, dosimetry, and physics components. Treatment room operations metrics included appointment variance, slot utilization, and waiting-for-beam (WFB) time. Data were collected automatically using a commercial analytics platform integrating radio-frequency identification tracking and oncology information system. Metrics were analyzed longitudinally and stratified by treatment room, disease site, and workflow component.

RESULTS: For calendar year 2024, aggregate site uptime was 95.3%, weighted according to clinical operating time across the three treatment rooms; individual room uptimes ranged from 91.8% to 97.2%. Beam pauses were frequent but brief, resulting in 2,238 minutes of cumulative lost treatment time across 2024, equivalent to approximately 0.5% of total clinical operating time. Annual mean treatment planning time was 8.5 business days, with physician-related activities contributing the greatest variability across disease sites. Monthly average appointment variance ranged from 5 to 11 minutes, with most treatments initiated within 10 minutes of scheduled time. Across 2024, slot utilization was stable, with 73% of fractions completed within scheduled slots. Mean overrun and underrun durations were modest, although P90 overrun durations exceeded 10 minutes throughout the year. Mean WFB times were low and consistent, ranging from 1.5 to 2.3 minutes.

CONCLUSIONS: This study presents a practical KPI framework and a single-institution operational reference data for multi-room proton therapy center. These metrics may support longitudinal monitoring, identification of workflow inefficiencies, data-driven decision-making, and future multi-institutional benchmarking efforts.},
}

Longitudinal Studies
*Proton Therapy/standards
Facility Design and Construction
Health Facility Size
Quality Improvement
Workflow
Humans
Retrospective Studies
*Quality Indicators, Health Care/standards/statistics & numerical data
Radiotherapy Planning, Computer-Assisted
Efficiency, Organizational/standards/statistics & numerical data
Reference Values
*Health Facilities
*Health Facility Administration/standards/statistics & numerical data

@article {pmid42875015,
year = {2026},
author = {Amaravadi, H and Prusynski, RA and Fishman, P and Phipps, AI and Leland, NE and Mroz, TM},
title = {Incentives for Access: Changes in Admissions and Care Delivery for Metastatic Cancer Patients in Medicare Skilled Nursing Facilities, After the Patient-Driven Payment Model.},
journal = {Journal of applied gerontology : the official journal of the Southern Gerontological Society},
volume = {},
number = {},
pages = {7334648261494384},
doi = {10.1177/07334648261494384},
pmid = {42875015},
issn = {1552-4523},
abstract = {BackgroundCancer patients experience suboptimal care in skilled nursing facilities (SNFs). Medicare's Patient-Driven Payment Model (PDPM) incentivized SNFs to admit complex patients, potentially promoting admissions without appropriate changes in care delivery.ObjectiveTo evaluate changes in SNF admissions, rehabilitation therapy volume, and chemotherapy/radiation around admission or discharge, following PDPM and COVID-19.MethodsAdjusted interrupted time series examining 1,125,782 hospital stays from metastatic cancer patients, using 100% Traditional Medicare claims (2018-2021).ResultsPDPM was associated with increased SNF admissions (0.47 pp/month; 95% CI: [0.17, 0.76]) and an immediate reduction in therapy volume (-24.95 minutes per day, 95% CI: [-26.40, -23.48]). Chemotherapy use remained low, but increased by 21% at PDPM implementation, without subsequent slope change (RR: 1.21; 95% CI: [1.01, 1.46]); radiation was unchanged. COVID-19 reversed admission gains. SNF admissions for metastatic cancer patients increased without sustained changes in cancer-relevant care delivery, warranting investigation of health outcomes and outcome-driven policy.},
}

@article {pmid42878338,
year = {2026},
author = {Houghton, AM},
title = {Analytical and technical advances collide to produce novel insights into the tumor immune microenvironment.},
journal = {American journal of respiratory and critical care medicine},
volume = {},
number = {},
pages = {},
doi = {10.1093/ajrccm/aamag447},
pmid = {42878338},
issn = {1535-4970},
}

@article {pmid42878707,
year = {2027},
author = {Lakkaraja, M and Schmitt, EG and Sood, AK and Chen, K and Modi, AJ and Verbsky, JW and Torgerson, T and Wahbeh, G and Petrovic, A and Baker, KS and Cooper, MA and Burroughs, LM},
title = {Hematopoietic cell transplantation using treosulfan-based conditioning for IL-10 receptor deficiency.},
journal = {Journal of human immunity},
volume = {3},
number = {1},
pages = {},
pmid = {42878707},
issn = {3065-8993},
support = {1K08AI182483/NH/NIH HHS/United States ; P30CA015704/NH/NIH HHS/United States ; //Children's Discovery Institute of Washington University's Center for Pediatric Immunology/ ; //St. Louis Children's Hospital/ ; //American Society of Hematology/ ; //Cancer and Blood Disorders Center/ ; /CA/NCI NIH HHS/United States ; },
abstract = {IL-10 receptor deficiency is a life-threatening inborn error of immunity associated with early-onset inflammatory bowel disease. Hematopoietic cell transplantation (HCT) using treosulfan-based conditioning resulted in excellent survival with full donor engraftment. Importantly, anakinra effectively served as a bridge to HCT.},
}

@article {pmid42879280,
year = {2026},
author = {Greene, JE and Ahmad, K and Henikoff, S},
title = {Histone H3K27 methylation states are sequentially catalyzed in cycling cells.},
journal = {Cell reports},
volume = {45},
number = {10},
pages = {118149},
doi = {10.1016/j.celrep.2026.118149},
pmid = {42879280},
issn = {2211-1247},
abstract = {Polycomb domains form at silenced genes and are marked by histone H3 lysine 27 tri-methylation, but it is unclear how this methylation is maintained following DNA replication in proliferating cells. Here, we use CUT&Tag chromatin profiling to track the dynamics of H3K27 methylation in human cells. We find that tri-methylation in Polycomb domains is maintained by stepwise methylation after DNA replication. Outside of Polycomb domains, thousands of transcriptionally inactive genes gain histone H3K27 di-methylation hours after DNA replication. Acute treatment with small-molecule inhibitors of the Polycomb repressive complex 2 (PRC2) histone methyltransferase slows H3K27 methylation during S-phase of the cell cycle and increases acetylation of the residue. This effect is most pronounced at Polycomb domains replicating in early S-phase, thereby suggesting that early replication and slow histone methylation confer plasticity to developmentally silenced genes. Together, our results explain how H3K27 modification patterns are faithfully duplicated in rapidly proliferating cells.},
}

@article {pmid42879732,
year = {2026},
author = {Vo, PT and Walter, RB and Gooley, TA and Hamlin, DK and Haaf, R and Wong, R and Matesan, M and Santos, EB and Dorman, E and Lewis, DH and Behnia, S and Emery, RC and Li, Y and Orozco, JJ and Vesselle, H and Wilbur, DS and Storb, R and Sandmaier, BM},
title = {First-In-Human Study of [211]At-CD45 Radioimmunotherapy With Nonmyeloablative Conditioning Hematopoietic Cell Transplantation for Adults With Hematologic Malignancies.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2600877},
doi = {10.1200/JCO-26-00877},
pmid = {42879732},
issn = {1527-7755},
abstract = {PURPOSE: Relapse is the dominant cause of failure after allogeneic hematopoietic cell transplantation (HCT) for aggressive hematologic malignancies. CD45-directed radioimmunotherapy (RIT) has been investigated to intensify conditioning and augment antitumor efficacy. After gaining clinical experience with β-emitting radionuclides, attention is now shifting toward α-emitters, such as astatine-211 ([211]At), for their more potent and precise radiation delivery with minimized toxicity to surrounding tissues.

PATIENTS AND METHODS: To our knowledge, in this first-in-human, two-stage dose-finding study, we administered a single infusion of [211]At-labeled anti-CD45 monoclonal antibody before nonmyeloablative conditioning with fludarabine/2-3 Gy total body irradiation and allografting from HLA-matched or single-allele-mismatched donors in 45 adults (38-74 years of age) at a high relapse risk from myeloid malignancies or acute leukemia.

RESULTS: Seventeen patients were treated in stage I with 85-591 μCi/kg of [211]At. The patient receiving 591 μCi/kg developed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), thereby establishing 500 μCi/kg as the protocol-defined maximum tolerated dose and prompting initiation of stage II at that dose in 28 patients. Infusion reactions were mild. [211]At-CD45 RIT did not delay hematopoietic recovery, impair donor chimerism, or increase graft-versus-host disease (GVHD) rates. In stage II, six patients (all receiving sirolimus as part of GVHD prophylaxis for unrelated donor HCT) experienced VOD/SOS. Among the 13 patients with circulating blasts at baseline, blasts cleared in 12 before initiation of fludarabine/total body irradiation, demonstrating immediate cytotoxic activity. Estimated 1-year relapse-free and overall survival were 42% (95% CI, 28%-56%) and 49% (34%-62%), respectively.

CONCLUSION: [211]At-CD45 RIT can be incorporated into nonmyeloablative conditioning, with liver toxicity defining activity limits. Evidence of antitumor efficacy supports phase II evaluation.},
}

@article {pmid42856697,
year = {2026},
author = {Yaseen, F and Hippe, DS and Cui, S and Fu, J and Wang, S and Deng, L and Ye, T and Kinahan, PE and Zeng, J and Gennari, JH and Bowen, SR},
title = {Uncertainty-Aware Multiscale Treatment Response Forecasting in Advanced Non-Small Cell Lung Cancer Using Residual-Variance Conformal Prediction.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {42856697},
support = {R01 CA204301/CA/NCI NIH HHS/United States ; R01 CA258997/CA/NCI NIH HHS/United States ; },
abstract = {Voxel-level prediction of treatment response from longitudinal Fluorodexoyglucose (FDG) positron emission tomography / computed tomography (PET/CT) can enable spatially adaptive dose planning in advanced non-small cell lung cancer (NSCLC), but point predictions alone lack the uncertainty quantification needed for safe clinical decision-making. Standard conformal prediction (CP) provides distribution-free coverage but yields spatially uniform intervals and assumes exchangeability-an assumption violated by intra-tumoral spatial correlation. We propose a multiscale CP framework built on a re-optimized VoxelForecast generalized least squares model that explicitly captures voxel-level covariance. Variogram sensitivity analysis identified the Stable model as significantly superior to previouly used Matérn family. The framework combines hierarchical nested leave-one-patient-out calibration, which restores exchangeability for valid voxel-level coverage, with residual-variance CP (VarCP), which learns a heteroscedastic, location-dependent scale to produce adaptive intervals while preserving finite-sample marginal coverage guarantees. On two prospective NSCLC trial cohorts-FLARE-RT (N=25 locally advanced, chemoradiotherapy; 11,100 voxels) and BRIGHT (N=19 metastatic, chemoimmunotherapy; 26,980 voxels)-multiscale feature integration reduced voxel-level prediction error by 35% and 31%, respectively. VarCP maintained nominal coverage while producing 7-18% (FLARE-RT) and 4-8% (BRIGHT) narrower voxel-level intervals than a hierarchically calibrated standard CP baseline (paired Wilcoxon signed-rank, significant at most miscoverage levels), with comparable lesion-level gains (7-18% and 6-10%) via median-based aggregation of voxel residuals. VarCP delivers tighter yet mathematically guaranteed spatial uncertainty maps, supporting both voxel-level dose-adjustment and whole-lesion treatment planning in advanced NSCLC.},
}

@article {pmid42859918,
year = {2026},
author = {Domingues, A and Spector, LG and Tettamanti, G and Feychting, M and Nikkilä, A and Auvinen, A and Alimam, W and Abuhamed, J and Scheuer, ME and Lupo, PJ and Heck, JE and Hansen, J and Mueller, BA and Nelson, H and MacLehose, R and Marcotte, E},
title = {Maternal smoking and risk of childhood cancer: a report from the Childhood Cancer and Leukemia International Consortium.},
journal = {International journal of epidemiology},
volume = {55},
number = {5},
pages = {},
pmid = {42859918},
issn = {1464-3685},
support = {R01 CA286051/CA/NCI NIH HHS/United States ; 5R01CA286051/CA/NCI NIH HHS/United States ; T32 CA099936/CA/NCI NIH HHS/United States ; T32 ES010957/ES/NIEHS NIH HHS/United States ; //T32 ES010957/ ; },
mesh = {Humans ; Female ; Pregnancy ; *Prenatal Exposure Delayed Effects/epidemiology ; *Smoking/epidemiology/adverse effects ; Case-Control Studies ; Child ; *Neoplasms/epidemiology ; Risk Factors ; Male ; Child, Preschool ; Logistic Models ; Infant ; United States/epidemiology ; Odds Ratio ; Sweden/epidemiology ; Adult ; Adolescent ; Infant, Newborn ; *Maternal Exposure ; Finland/epidemiology ; },
abstract = {BACKGROUND: Although tobacco is an established carcinogen and components of tobacco smoke may cross the placental membrane, past studies of maternal prenatal smoking and childhood cancer have resulted in mixed or null results. However, many studies have relied on case-control methods and may be susceptible to various biases. We aimed to elucidate the nature of the relationship between maternal prenatal smoking and childhood cancer through a multinational analysis of prospectively recorded record-linkage studies with probabilistic bias methods.

METHODS: Data for this analysis came from existing population-based case-control record-linkage studies in the Childhood Cancer and Leukemia International Consortium, with studies from the USA, Sweden, Finland, and Denmark, including more than 20 000 cases and 300 000 controls. We assessed the association between maternal prenatal smoking and childhood cancer using logistic regression. Additionally, we conducted probabilistic bias analysis to investigate the effect of exposure misclassification using sensitivities and specificities from biomarker-based validation studies.

RESULTS: Both before and after bias adjustment, maternal smoking was not found to be associated with most cancers investigated. Maternal prenatal smoking was inversely associated with paediatric melanoma [bias-adjusted odds ratio (OR) 0.68, 95% simulation interval (SI): 0.47-0.98] and skin carcinomas and other/unspecified carcinomas (bias-adjusted OR: 0.72, 95% SI: 0.52-0.96), and positively associated and unspecified malignant tumours (bias-adjusted OR: 1.50, 95% SI: 1.21-1.84).

CONCLUSIONS: This analysis supports previous findings that there is little evidence of an effect of maternal prenatal smoking on childhood cancer risk, with few potential exceptions. However, due to numerous other detrimental effects, public health efforts should continue to further reduce its prevalence.},
}

Humans
Female
Pregnancy
*Prenatal Exposure Delayed Effects/epidemiology
*Smoking/epidemiology/adverse effects
Case-Control Studies
Child
*Neoplasms/epidemiology
Risk Factors
Male
Child, Preschool
Logistic Models
Infant
United States/epidemiology
Odds Ratio
Sweden/epidemiology
Adult
Adolescent
Infant, Newborn
*Maternal Exposure
Finland/epidemiology

@article {pmid42860034,
year = {2026},
author = {Lo, E and Clein, A and Tam, M and Trimble, S and Hardin, M and Ramirez, A and Kaldjian, E and Yu, EY and Cheng, HH and Yezefski, TA and Hsieh, AC and Grivas, P and Montgomery, B and Nelson, PS and Schweizer, MT and Sabath, DE and Blinka, S},
title = {Circulating Tumor Cell Synaptophysin and Androgen Receptor Expression Reflect Prostate Cancer Phenotypes in Metastatic Disease.},
journal = {The Prostate},
volume = {},
number = {},
pages = {},
doi = {10.1002/pros.70267},
pmid = {42860034},
issn = {1097-0045},
support = {R37 CA230617/CA/NCI NIH HHS/United States ; R01 GM135362/GM/NIGMS NIH HHS/United States ; R01 CA276308/CA/NCI NIH HHS/United States ; P50CA097186/CA/NCI NIH HHS/United States ; R37CA268450/CA/NCI NIH HHS/United States ; P30CA015704/CA/NCI NIH HHS/United States ; T32CA009515/CA/NCI NIH HHS/United States ; P01CA163227/CA/NCI NIH HHS/United States ; P01CA298991/CA/NCI NIH HHS/United States ; R01CA266452/CA/NCI NIH HHS/United States ; //Prostate Cancer Foundation/ ; DBG-25-1373505-01-RMC//American Cancer Society/ ; //Seattle Translational Tumor Research/ ; //Nancy & Dick Bernheimer/ ; //Matthews Family/ ; //Thomas & Patricia Wright Memorial Funds/ ; //Larry & Virginia Gordon Endowed Chair in Prostate and Bladder Cancer Research/ ; PC230420//CDMRP/ ; W81XWH-17-2-0043//DOD/ ; },
abstract = {BACKGROUND: Chronic exposure to androgen receptor (AR)-targeted therapies can drive lineage plasticity, leading to treatment resistance and neuroendocrine prostate cancer (NEPC), characterized by loss of AR expression and acquisition of neuroendocrine (NE) markers including synaptophysin (SYP). We evaluated concordance between circulating tumor cell (CTC) AR and SYP expression patterns and evidence of NE differentiation defined by clinical, pathologic, and genomic features.

METHODS: CTCs from patients with metastatic castration-resistant prostate cancer (mCRPC) were analyzed using the RareCyte platform with quantitative immunofluorescence imaging for SYP and AR. In patients with ≥ 5 CTCs, associations of CTC phenotype with PSA at collection and overall survival (OS) were assessed using the Wilcoxon rank-sum test, Fisher's exact test, and Kaplan-Meier analysis. Patients were retrospectively classified as AR-positive adenocarcinoma or NE-differentiated based on clinical, pathologic, and genomic data.

RESULTS: The AR/SYP CTC assay was analytically validated using cell-line spike-in models, achieving > 90% accuracy for both biomarkers. Of 52 patients with mCRPC, 27 had ≥ 5 evaluable CTCs and were included in the primary CTC phenotype analyses. The NE-differentiated cohort had a higher fraction of SYP-positive CTCs (median 28.6% vs 0.0%, p = 0.0084), whereas the AR-positive adenocarcinoma cohort had a higher fraction of AR-positive CTCs (median 96.7% vs 0.0%, p = 0.0004). Classification based on high AR or SYP expression (≥ 80% of CTCs positive) significantly distinguished cohorts and was associated with tissue histology (p = 0.0048). PSA at CTC collection was lower in the NE-differentiated cohort (median 3.83 vs 486.89 ng/mL; 95% CI: -1016 to -190.9). OS did not significantly differ between groups.

CONCLUSION: SYP and AR CTC expression showed strong concordance with tissue histology and clinical features of NE differentiation and AR-positive adenocarcinoma. These findings support the feasibility of CTC immunophenotyping to characterize lineage-associated phenotypes including SYP-expressing NE differentiation in mCRPC. Prospective validation in larger cohorts with matched tissue biopsies is needed to define the clinical utility of this approach.},
}

@article {pmid42860046,
year = {2026},
author = {Mongiovi, JM and Prince, N and Pacheco, JA and Lin, N and Townsend, MK and Trabert, B and Wentzensen, N and Lasky-Su, JA and Eliassen, AH and Clish, CB and Tworoger, SS and Zeleznik, OA and Sasamoto, N},
title = {Plasma metabolomic profiles associated with breastfeeding history and subsequent ovarian cancer risk.},
journal = {JNCI cancer spectrum},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncics/pkag108},
pmid = {42860046},
issn = {2515-5091},
abstract = {BACKGROUND: Breastfeeding reduces ovarian cancer risk, but the underlying biological mechanisms remain unclear.

METHODS: We examined the association between a previously reported metabolite-based breastfeeding score with incident epithelial ovarian cancer risk in case-control studies nested within the Nurses' Health Studies (NHS/NHSII, n = 436) and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 300) using conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for each study and conducted a meta-analysis. We investigated 606 individual breastfeeding-metabolite associations among 9,904 mid-life parous women in NHS/NHSII and 663 one-year postpartum women in the Vitamin D Antenatal Asthma Reduction Trial (VDAART). Metabolites associated with breastfeeding at p ≤ 0.05 after multiple testing correction for number of effective tests (NEF) were then assessed for their associations with ovarian cancer. Metabolite set enrichment analysis using Normalized Enrichment Score (NES) identified metabolite classes associated with breastfeeding using false discovery rate (FDR) were used for multiple testing correction.

RESULTS: The highest quartile of metabolite-based breastfeeding score was inversely associated with ovarian cancer risk (meta-analyzed odds ratio [OR]=0.62, 95%CI=0.39-0.99). Of the 14 individual metabolites associated with breastfeeding in NHS/NHSII and also measured in VDAART, similar direction of associations was observed for 11 metabolites. Phosphatidylcholines (PCs; NES=1.94; FDR=0.004) and phosphatidylethanolamines (PEs; NES=1.82; FDR=0.01) were positively enriched with increased breastfeeding duration. Ten metabolites including PCs and PEs were positively associated with breastfeeding and inversely associated with ovarian cancer.

CONCLUSION(S): Our results suggest alterations of systemic metabolism, particularly among PC and PE pathways, provide insight into biological pathways underlying the inverse breastfeeding-ovarian cancer association.},
}

@article {pmid42862393,
year = {2026},
author = {Zhu, A and Schenk, JM and Gulati, R and Beatty, SJ and VanDoren, M and Lin, DW and Porter, MP and Morrissey, C and Dash, A and Gore, JL and Etzioni, R and Plymate, SR and Neuhouser, ML and Wright, JL},
title = {Impact of a dietary and exercise intervention on health-related quality of life of prostate cancer patients on active surveillance with overweight/obesity: a secondary analysis of a randomized controlled trial.},
journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer},
volume = {34},
number = {11},
pages = {},
pmid = {42862393},
issn = {1433-7339},
mesh = {Humans ; Male ; *Prostatic Neoplasms/therapy/psychology/complications ; *Quality of Life ; Middle Aged ; Aged ; *Overweight/therapy/complications ; *Obesity/therapy/complications ; Surveys and Questionnaires ; *Exercise ; Weight Loss ; *Watchful Waiting ; *Exercise Therapy/methods ; },
abstract = {PURPOSE: Quality of life (QOL) is important for men on active surveillance (AS) for prostate cancer (PCa). To improve QOL, interventions such as those focused on diet and exercise have been proposed. However, their effectiveness remains unclear, especially in individuals with overweight/obesity.

METHODS: We previously conducted and published a randomized controlled trial of a lifestyle intervention for PCa patients on AS with overweight/obesity. Men were randomized to as follows: (1) 6-month diet and exercise intervention with a 7% weight loss goal vs (2) provided US Dietary and Physical Activity Guidelines. Herein, we report the secondary QOL findings from the trial. QOL was assessed at baseline and conclusion of the intervention via four validated questionnaires. Linear regression and two-sided t-tests evaluated mean differences. Subset analyses of the questionnaires were performed using cut-points correlating with clinical assessments.

RESULTS: Between 2016 and 2020, 100 men completed the trial. The intervention group had a mean weight loss of 7.1% vs 1.8% in controls. Despite this, no significant difference was observed between groups in general QOL (EQ-5D-5L), urinary QOL (IPSS), PCa-related QOL (EPIC-26), or PCa specific anxiety (MAX-PC). However, exploratory subgroup analyses demonstrated that participants with poor "bowel function," low "sexual bother," and good "sexual function" had clinically significant improvements of 12 (95% CI 0.1-24.0), 22 (95% CI 4.2-39.0), and 19 points (95% CI 4.4-34.0) on the EPIC-26.

CONCLUSION: In this secondary analysis of a previously published randomized trial, a 6-month diet and exercise intervention did not improve overall QOL among men with overweight/obesity on AS for PCa. While diet and exercise interventions may not universally improve QOL in this population, they remain important for broader health benefits and may offer targeted value for certain patients.},
}

Humans
Male
*Prostatic Neoplasms/therapy/psychology/complications
*Quality of Life
Middle Aged
Aged
*Overweight/therapy/complications
*Obesity/therapy/complications
Surveys and Questionnaires
*Exercise
Weight Loss
*Watchful Waiting
*Exercise Therapy/methods

@article {pmid42862790,
year = {2026},
author = {Younes, S and Chinyengetere, F and Russell, V and Thakkar, D and Mason, EF and Juskevicius, R and Kovach, AE and Li, S and Yin, CC and O'Malley, DP and Koff, JL and Jaye, DL and Love, C and Shingleton, JR and Owusu, D and Batra, A and Biral, LPA and Thacker, E and Parker, C and Happ, L and Chapman Fredricks, J and Lossos, IS and Ondrejka, SL and Hsi, E and Tse, E and Au-Yeung, RKH and Bhagat, G and Leeman-Neill, RJ and Chadburn, A and Czader, M and Fedoriw, Y and Naresh, KN and Dave, SS and Natkunam, Y},
title = {Elucidating the Gene Expression Signature of Rosai-Dorfman Disease: A Study from the Atlas of Blood Cancer Genomes Initiative.},
journal = {Cancer research communications},
volume = {},
number = {},
pages = {},
doi = {10.1158/2767-9764.CRC-25-0834},
pmid = {42862790},
issn = {2767-9764},
abstract = {Rosai-Dorfman disease (RDD) is a rare histiocytic disorder characterized by accumulation of large histiocytes in nodal and/or extranodal sites. The underlying biology of RDD and factors that distinguish it from the other histiocyte disorders are poorly understood. To better understand the disease biology, we employed whole transcriptome RNA sequencing to study the gene expression profiles of RDD as part of the Atlas of Blood Cancer Genomes (ABCG) initiative. Gene expression profiles of RDD (N=23) were then compared to two other histiocytoses (Langerhans cell histiocytosis (LCH, N=15) and Erdheim-Chester disease (ECD, N=4), which are most often considered in the clinicopathologic differential diagnosis of RDD. We found that gene expression levels by RNA sequencing correlated well with known immunohistochemistry results for diagnostic markers for all three diseases, highlighting the ability to use RNA-based approaches for diagnosis of these tumors. RDD samples showed enrichment of gene sets related to B cells and the IL27 pathway. In contrast, LCH showed enrichment of gene sets related to resting dendritic cells and the HNF3A pathway. We found significant differences in the composition of the microenvironment with an enrichment of memory B cells, plasma cells and CD8 T cells in the RDD microenvironment and enrichment of dendritic cells in the LCH microenvironment. In summary, our study demonstrates unique gene expression signatures in RDD that show overlap as well as distinctive patterns from LCH or ECD. These novel gene expression signatures encompass pathways that could potentially contribute to the pathogenesis and targeted treatment of this rare histiocytic entity.},
}

@article {pmid42868246,
year = {2026},
author = {Kalyan, A and Bradford, MC and Dubnicka, A and Terrones, I and Yao, K and Runco, DV and Pihoker, C and Baker, KS and Ronsley, R},
title = {Body Composition Assessment and Correlation to Metabolic Profile in Survivors of Childhood Brain Tumors.},
journal = {Journal of pediatric hematology/oncology},
volume = {},
number = {},
pages = {},
doi = {10.1097/MPH.0000000000003300},
pmid = {42868246},
issn = {1536-3678},
abstract = {INTRODUCTION: Survivors of childhood brain tumors (CBT) are at increased risk for metabolic syndrome, contributing to long-term cardiometabolic morbidity. BMI may underestimate risk by failing to capture altered body composition in this population. More precise tools such as air displacement plethysmography (ADP) may improve early risk detection. This study aimed to identify ADP-derived markers of adiposity and characterize early metabolic abnormalities at the end of cancer therapy.

METHODS: This was a prospective, single-visit study enrolling pediatric survivors of high-grade CBT aged 2 to 21 years, off therapy for <5 years. Data included anthropometric measurements, metabolic markers (glucose, insulin, lipids, adiponectin, leptin, IL-6), and body composition (fat mass, fat-free mass, percent fat, measured by ADP). Descriptive statistics were used to summarize demographics and clinical characteristics, and categorical variables were presented as counts and percentages. Pearson correlation coefficients were calculated for log adiponectin versus percent body fat and BMI z-score.

RESULTS: Thirty survivors of CBT (n=30; age: 6 to 23 y) were evaluated a median of 0.3 years after treatment. Over half were normal weight (53%), and 47% were overweight or obese; 20% had hypertension and 23% had elevated waist circumference. Body composition (n=29) showed high adiposity, with a mean fat mass of 33% and 59% having elevated fat percentage. Metabolic assessment demonstrated early cardiometabolic dysfunction: insulin resistance and significant insulin resistance by HOMA-IR were seen in 50% and 33%, respectively, and lipid abnormalities and the metabolic syndrome were seen in 27% and 15%, respectively. Higher adiposity was associated with worse metabolic health, with greater fat mass percentage in insulin-resistant patients (P<0.01) and higher BMI z-score (P=0.02). Adiponectin was inversely correlated with fat mass% (r=-0.72), but not with BMI z-score.

CONCLUSION: Childhood brain tumor survivors demonstrated a high prevalence of metabolic abnormalities and excess adiposity shortly after therapy completion. BMI underestimated abnormal adiposity compared with ADP-derived body composition assessment, supporting the need for comprehensive metabolic screening and early intervention during survivorship.},
}

@article {pmid42868995,
year = {2026},
author = {Newell, EW},
title = {The narrow path to CD8[+] T cell recognition of mutant p53.},
journal = {Immunity},
volume = {59},
number = {10},
pages = {2617-2619},
doi = {10.1016/j.immuni.2026.09.020},
pmid = {42868995},
issn = {1097-4180},
mesh = {Humans ; *Tumor Suppressor Protein p53/genetics/immunology ; *CD8-Positive T-Lymphocytes/immunology ; Mutation ; Animals ; *Neoplasms/immunology/genetics/therapy ; Antigen Presentation/immunology ; Antigens, Neoplasm/immunology ; Immunotherapy ; },
abstract = {Shared cancer driver mutations offer attractive targets for cancer immunotherapy, but their expression does not necessarily put them within the reach of a T cell response. In this issue of Immunity, Haratani et al. identify distinct barriers to the processing, presentation, and recognition of neoantigens generated from mutant p53 that help explain this gap.},
}

Humans
*Tumor Suppressor Protein p53/genetics/immunology
*CD8-Positive T-Lymphocytes/immunology
Mutation
Animals
*Neoplasms/immunology/genetics/therapy
Antigen Presentation/immunology
Antigens, Neoplasm/immunology
Immunotherapy

@article {pmid42870635,
year = {2026},
author = {Nixon, AB and Enserro, DM and Bender, DP and Liu, Y and Starr, MD and Brady, JC and Gonzalez Bosquet, J and Rimel, BJ and Holman, LL and Rivard, C and Veljovich, DS and Fehniger, J and Moroney, JW and Backes, FJ and Cadungog, M and Powell, MA and Castellano, T and Secord, AA and MacKay, HJ},
title = {Blood-based biomarkers in patients with recurrent, persistent, or metastatic endometrial cancer treated with olaparib and cediranib: Results from NRG-GY012.},
journal = {Cancer},
volume = {132},
number = {20},
pages = {e70649},
doi = {10.1002/cncr.70649},
pmid = {42870635},
issn = {1097-0142},
support = {1U10 CA180822//BIQSFP Funding and National Cancer Institute/ ; U10CA180868//BIQSFP Funding and National Cancer Institute/ ; },
mesh = {Humans ; Female ; Phthalazines/administration & dosage ; *Endometrial Neoplasms/drug therapy/blood/pathology/mortality ; *Biomarkers, Tumor/blood ; Indoles ; Piperazines/administration & dosage ; Quinazolines/administration & dosage ; *Neoplasm Recurrence, Local/drug therapy/blood/pathology ; Prognosis ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Interleukin-6/blood ; Middle Aged ; Aged ; Progression-Free Survival ; },
abstract = {BACKGROUND: The NRG-GY012 phase 2 trial evaluated olaparib, cediranib, and the combination in 120 patients with recurrent, persistent, or metastatic endometrial cancer (EC). Predictive and prognostic associations between blood-based biomarkers and clinical outcomes were assessed.

METHODS: Plasma samples collected at baseline, cycle 4 day 1, and disease progression were analyzed for circulating protein biomarkers (Angiome). The primary analysis evaluated the predictive impact of IL-6 on progression-free survival (PFS) and overall survival (OS). The predictive and prognostic impact of all other markers on PFS and OS were also evaluated.

RESULTS: Ninety-six baseline plasma samples were included in this analysis. Results from GOG-218 identified IL-6 was predictive of clinical benefit using a threshold of 2.9 pg/mL. Although the 2.9 pg/mL cut point did not validate in GY012, IL-6 associated with OS using the median level of 4.2 pg/mL as the cut point. Although patients with >4.2 pg/mL IL-6 had worse prognosis, higher IL-6 levels were associated with longer OS benefit in the cediranib arms (pintx = .085). In secondary analyses, osteopontin (OPN) and placental growth factor (PlGF) potentially predicted benefit. Patients with higher OPN levels had shorter OS in the olaparib arm, whereas patients with lower OPN had longer OS in the cediranib arms (pintx = .035). Patients with higher PlGF benefited more from cediranib (PFS, pintx = .030; OS, pintx = .024). Multiple prognostic markers were also identified.

CONCLUSIONS: IL-6 may be predictive of outcome; OPN and PlGF represent novel potential predictive biomarkers, in EC patients receiving anti-angiogenic therapy. Further evaluation is warranted.},
}

Humans
Female
Phthalazines/administration & dosage
*Endometrial Neoplasms/drug therapy/blood/pathology/mortality
*Biomarkers, Tumor/blood
Indoles
Piperazines/administration & dosage
Quinazolines/administration & dosage
*Neoplasm Recurrence, Local/drug therapy/blood/pathology
Prognosis
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use
*Interleukin-6/blood
Middle Aged
Aged
Progression-Free Survival

@article {pmid42871344,
year = {2026},
author = {Bulstra, CA and Dai, X and Ngure, K and Rosenberg, MS and Wamuti, BM and Hontelez, JAC and Salomon, JA and Ortblad, KF and Bärnighausen, T},
title = {The impact of male circumcision on risk of HIV infection in sub-Saharan Africa: a household fixed-effects analysis of 279,351 men from 29 countries.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1810573},
pmid = {42871344},
issn = {2296-2565},
support = {K99 MH121166/MH/NIMH NIH HHS/United States ; R00 MH121166/MH/NIMH NIH HHS/United States ; },
mesh = {Humans ; *Circumcision, Male/statistics & numerical data ; Male ; *HIV Infections/epidemiology/prevention & control ; Africa South of the Sahara/epidemiology ; Cross-Sectional Studies ; Adult ; Adolescent ; Young Adult ; Middle Aged ; Health Surveys ; Family Characteristics ; Risk Factors ; },
abstract = {INTRODUCTION: While voluntary medical male circumcision (VMMC) reduces the individual-level risk of HIV acquisition by approximately 60% in randomised-controlled trials, little is known about the 'real-world' long-term effect of medical and traditional male circumcision on the cumulative risk of HIV infection. We estimate the association between these for the first time using a quasi-experimental study design-a household fixed-effects analysis-for sub-Saharan Africa, the global region with the largest HIV burden.

METHODS: We pooled individual-level cross-sectional data from the nationally-representative Demographic and Health Surveys and AIDS Indicator Surveys across all sub-Saharan African countries in which the surveys included data on both male circumcision and HIV status. We estimated the association between male circumcision and HIV status using modified Poisson regression models with household fixed-effects-which control for unobserved and observed confounding shared by men living in the same household-and included additional individual-level controls for demographic characteristics, socio-economic factors, and sexual behaviour.

RESULTS: We included individual data from 279,351 male participants in 48 nationally-representative surveys conducted in 29 countries between 2003 and 2018. The mean survey-level prevalence of male circumcision was 65.9% (median 84.5%, IQR 28.8-68.1%) and HIV was 5.6% (median 2.5%, IQR 1.2-10.2%). We estimated that male circumcision was associated with a significant nearly one-fifth reduction in the cumulative risk of HIV infection (adjusted risk ratio 0.81, 95% CI 0.73-0.89).

CONCLUSION: Male circumcision was associated with a significant reduction in the risk of HIV infection in sub-Saharan Africa over the past two decades. Increased political and financial commitment to VMMC could likely lead to further reductions in HIV prevalence, especially when rolled out as a HIV prevention option in combination with other interventions.},
}

Humans
*Circumcision, Male/statistics & numerical data
Male
*HIV Infections/epidemiology/prevention & control
Africa South of the Sahara/epidemiology
Cross-Sectional Studies
Adult
Adolescent
Young Adult
Middle Aged
Health Surveys
Family Characteristics
Risk Factors

@article {pmid42872245,
year = {2026},
author = {Gupta, H and Allison, MA and Mossavar-Rahmani, Y and Perreira, KM and Gallo, LC and Oelsner, EC and Evenson, KR and Daviglus, M and Garcia-Bedoya, O and Sotres-Alvarez, D and Isasi, CR and Kaplan, R and Matsushita, K and Schrack, JA and Martinez-Amezcua, P},
title = {Association of psychological and financial distress with physical activity among Hispanic/Latino populations during the COVID-19 lockdowns in the United States.},
journal = {Journal of health equity},
volume = {3},
number = {1},
pages = {2712532},
pmid = {42872245},
issn = {2994-4694},
support = {R01 HL146132/HL/NHLBI NIH HHS/United States ; N01 HC065233/HL/NHLBI NIH HHS/United States ; N01 HC065236/HL/NHLBI NIH HHS/United States ; N01 HC065235/HL/NHLBI NIH HHS/United States ; N01 HC065234/HL/NHLBI NIH HHS/United States ; N01 HC065237/HL/NHLBI NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; },
abstract = {We examined the links between COVID-19-related concerns, psychological distress, material hardship, and physical activity (PA) among Hispanic/Latino adults in the U.S. during the pandemic. We conducted a cross-sectional analysis of data from 243 participants in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), collected between January and July 2021. Participants underwent phone interviews assessing COVID-19 concerns, psychological distress via the PHQ-4, and material hardship. PA was measured with wrist-worn accelerometers over seven days, tracking total activity counts/day, active minutes/day, and activity fragmentation (active-to-sedentary transition probability, ASTP). We used regression models adjusted for demographic, behavioral, and health covariates. Participants (mean age = 62; 67% female) showed high psychological distress (63%) and material hardship (33%), with 39% reporting COVID-19 concerns. Concerns were linked to lower total activity counts (β = -231, 95% CI: [-459, -3]) and active minutes/day (β = -42.1, 95% CI: [-76.7, -7.4]) in adjusted models. While ASTP was higher among individuals with COVID-19 concerns, this association diminished after full adjustment. No significant links were found between material hardship or distress and PA. COVID-19-related concerns were associated with reduced and fragmented physical activity, suggesting that addressing psychosocial stressors may help improve health behaviors in this population during public health emergencies.},
}

@article {pmid42873652,
year = {2026},
author = {Pulvino, AT and Sardaro, MLS and Quinn, WG and Christopher, ER and Koenig, S and Lucore, JM and Vidal-Cruchez, O and Mallott, EK and Kuthyar, S and Lee, W and Chitta, S and Gray, S and Williams, LE and Curley, JP and Liechty, ER and Ben-Sahra, I and Amato, KR},
title = {Bile, sulphur and carbohydrate metabolic variation co-occur with host adiposity in mice colonized with primate microbiota.},
journal = {Microbial genomics},
volume = {12},
number = {10},
pages = {},
doi = {10.1099/mgen.0.001848},
pmid = {42873652},
issn = {2057-5858},
mesh = {Animals ; Mice ; Humans ; *Adiposity ; *Bile/metabolism ; Macaca mulatta ; *Sulfur/metabolism ; *Carbohydrate Metabolism ; Multiomics ; Feces/microbiology ; *Gastrointestinal Microbiome ; Cecum/microbiology ; Liver/metabolism ; Metagenomics ; Primates/microbiology ; Microbiota ; },
abstract = {Although mechanistic links between the microbiome and chronic disease are increasingly well defined, how microbiomes facilitate normal variation in host metabolism remains less clear. Building on our recent demonstration that pooled faecal inocula from different primate species can cause relative differences in mouse host adiposity, we define potential mechanisms by which this could occur. Using existing samples from germ-free mice inoculated with faecal samples from humans (Homo sapiens), rhesus macaques (Macaca mulatta) and squirrel monkeys (Saimiri boliviensis), we integrate shotgun metagenomics of caecal contents, liquid chromatography-MS-MS metabolomics of serum and caecal contents and hepatic RNA-sequencing. Our multi-omic analysis reveals that the relative increase in adiposity previously observed in macaque-donor mice is associated with differences in hepatic cysteine catabolism and bile metabolism pathway features. These data suggest that bile and sulphur co-metabolic variation may mediate increased bile pool hydrophobicity. We also observed variation in caecal microbiome composition as well as host hepatic retinol signalling and lipid metabolism between treatments. When considered together with the observation that macaque-donor mice consumed less food than the other treatment groups, our results support the hypothesis that increased bile pool hydrophobicity results in increased dietary energy extraction. Our findings provide a foundation for future mechanistic testing of new hypotheses for understanding how the intestinal microbiomes of different primate species regulate lipid homeostasis in a mouse host.},
}

Animals
Mice
Humans
*Adiposity
*Bile/metabolism
Macaca mulatta
*Sulfur/metabolism
*Carbohydrate Metabolism
Multiomics
Feces/microbiology
*Gastrointestinal Microbiome
Cecum/microbiology
Liver/metabolism
Metagenomics
Primates/microbiology
Microbiota

@article {pmid41808993,
year = {2026},
author = {Chen, X and Argos, M and Yu, B and Boerwinkle, E and Qi, Q and Kaplan, R and Franceschini, N and Sofer, T},
title = {Explaining the unexplained admixture mapping signals via rare variants: the HCHS/SOL.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41808993},
issn = {2692-8205},
support = {R01 HG013163/HG/NHGRI NIH HHS/United States ; R01 HL141824/HL/NHLBI NIH HHS/United States ; R56 HG013163/HG/NHGRI NIH HHS/United States ; },
abstract = {In admixed populations, formed by a mixing of two or more previously isolated populations, genomic segments can be traced to their ancestral populations ("ancestries"). Admixture mapping (AM) associates local ancestry with outcomes in admixed populations, detecting signals when causal variants differ in frequency or effect across ancestral populations. Prior work showed that adjusting for nearby GWAS-identified common variants does not fully explain some AM signals. Here, we assessed two approaches to explain the previously unexplained AM signal: (1) including sets of rare variants; (2) increasing the genomic region considered when searching for common variants. We studied these hypotheses comprehensively using a whole-genome sequencing dataset coupled with metabolomics from the Hispanic Community Health Study/Study of Latinos. We detected multiple sets of rare variants with replicated association with metabolite levels. Yet these rare variants appear to explain only a small fraction of the AM signal, while inclusion of common variants from a larger genomic region appears to explain the majority of the AM signals.},
}

@article {pmid42845382,
year = {2026},
author = {Schuerger, C and Biswas, S and Ng, KP and Cardone, L and Gu, X and Ganguly, S and Tohme, R and Durmaz, A and Stich, M and Lindner, DJ and Jha, B and Mian, OY and Saunthararajah, Y},
title = {Urothelial-lineage master transcription factor hub proteomics shows mechanisms impeding urothelial cancer cell differentiation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42845382},
issn = {2692-8205},
support = {R21 CA263430/CA/NCI NIH HHS/United States ; P30 CA043703/CA/NCI NIH HHS/United States ; S10 OD018205/OD/NIH HHS/United States ; U54 CA274513/CA/NCI NIH HHS/United States ; R01 CA204373/CA/NCI NIH HHS/United States ; P01 HL146372/HL/NHLBI NIH HHS/United States ; R01 CA190578/CA/NCI NIH HHS/United States ; },
abstract = {Urothelial cancer (UC) cells of the luminal subtype exhibit partial, incomplete differentiation towards umbrella cells that line bladder lumen, seen by morphology and gene expression. Differentiation is stalled even though the cells express master transcription factors (MTFs) that drive luminal urothelial differentiation, e.g., FOXA1 and CEBPB, at levels seen in normal differentiated urothelium. We therefore analyzed the FOXA1/CEBPB MTF hub by mass spectrometry. SWI/SNF coactivator complex (CoA) components, e.g., SMARCA4, ARID1A, that read the epigenetic activation mark histone 3 lysine 27 acetylation (H3K27ac) and use ATP-hydrolysis to 'open' chromatin, were the most abundant proteins pulled-down with FOXA1/CEBPB. However, genes for these and other CoA, e.g., CREBBP, EP300 that write H3K27ac, were mutated/deleted in >95% of UCs in clinical series. Also contained in the hub were corepressors (CoR) that erase H3K27ac and 'close' chromatin, e.g., HDAC1, CHD4 - genes for these CoR were recurrently gained in UCs. Chromatin analyses showed H3K27ac-centered remodeling was needed to activate umbrella but not constitutively accessible cell growth/division/housekeeping genes. Restoring ARID1A into ARID1A-mutated UC cells using lentiviral transduction, or inhibiting CoR with siRNA or small molecules, activated umbrella genes and terminated replications. In summary, UC-genesis selects for loss- and gain-of-function of CoA and CoR respectively in the urothelial-lineage MTF hub; small molecule CoR-inhibitors are candidate remedies to renew maturation towards terminal differentiated-fates.},
}

@article {pmid42853487,
year = {2026},
author = {Collienne, L and Matsen Iv, FA},
title = {Tree Rearrangement Graphs Admit Paths of Decreasing Robinson-Foulds Distance.},
journal = {Bulletin of mathematical biology},
volume = {88},
number = {11},
pages = {},
pmid = {42853487},
issn = {1522-9602},
support = {R01 AI162611/AI/NIAID NIH HHS/United States ; R01-AI162611/NH/NIH HHS/United States ; DMS-1929284//National Science Foundation/ ; },
mesh = {*Phylogeny ; Mathematical Concepts ; *Models, Genetic ; Computer Simulation ; Computational Biology ; Algorithms ; },
abstract = {Tree rearrangements such as Nearest Neighbor Interchange (NNI) and Subtree Prune and Regraft (SPR) are commonly used to explore phylogenetic treespace. Computing distances based on them, however, is often intractable, so the efficiently computable Robinson-Foulds (RF) distance is used in practice. We investigate how the RF distance behaves along paths in the NNI and SPR graphs, where trees are nodes and edges represent single rearrangements. We show that any two trees are connected by a path along which the RF distance to the target decreases monotonically in the NNI graph and strictly in the SPR graph; we also show that a strictly decreasing NNI path does not always exist.},
}

*Phylogeny
Mathematical Concepts
*Models, Genetic
Computer Simulation
Computational Biology
Algorithms

@article {pmid42854111,
year = {2026},
author = {Hurvitz, SA and Layman, RM and Curigliano, G and Pistilli, B},
title = {Reply to: When PIK3CA Wild-Type Becomes a Biomarker Blind Spot.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2601653},
doi = {10.1200/JCO-26-01653},
pmid = {42854111},
issn = {1527-7755},
}

@article {pmid42854752,
year = {2026},
author = {McDougall, RP and Mattes, MD and Tseng, YD and Martin, EJ and Simone, CB and Robbins, JR},
title = {Assessing palliative care education and attitudes among radiation oncology residents.},
journal = {Annals of palliative medicine},
volume = {15},
number = {5},
pages = {71},
doi = {10.21037/apm-2026-0037},
pmid = {42854752},
issn = {2224-5839},
mesh = {Humans ; *Radiation Oncology/education ; *Palliative Care ; *Internship and Residency ; Male ; Cross-Sectional Studies ; Female ; *Attitude of Health Personnel ; United States ; Surveys and Questionnaires ; Adult ; Curriculum ; },
abstract = {BACKGROUND: Palliative care (PC) plays a vital role in radiation oncology (RO), but the breadth, quality, and effectiveness of formal PC education and radiation-specific palliative care (RSPC) during residency vary widely. A better understanding of how RO residents view their current training and where they see room for improvement can help guide future educational efforts. The study aims to evaluate RO residents' experiences with and attitudes toward PC and RSPC education, identify perceived gaps in training, gather suggestions for important topics, and determine preferred ways to optimally incorporate PC teaching into the existing resident schedule framework.

METHODS: From January through May 2025, a national cross-sectional survey was sent to 552 PGY-3 to PGY-5 U.S. RO residents using a REDCap-based online platform. The anonymous survey collected demographic information and inquired about the adequacy of current PC education, areas of additional instruction, and preferred learning formats and scheduling. Quantitative data were summarized descriptively, and mapped to the corresponding structured categories where relevant.

RESULTS: A total of 110 responses were received (response rate 19.9%). Most respondents identified as White (60.9%) and male (65.4%) from programs with 5-9 (40.7%) or 10-14 (35.2%) residents. While 89.0% reported access to a dedicated PC specialist, only 27.5% reported access to an RSPC specialist. Nearly all respondents supported the need for formal training in RSPC (96.0%) and general PC (84.2%). Although 45.5% reported faculty-led instruction in PC or RSPC, 15.8% indicated receiving no formal training in either area. Topics of greatest interest included symptom management, hospice care, ethical issues for PC, spinal stereotactic body radiation therapy (SBRT), and on-call management for RSPC. Residents preferred case-based, quarterly modules lasting 30-60 minutes as the most feasible educational format.

CONCLUSIONS: RO residents widely recognize the importance of structured PC and RSPC training but report significant variability in current educational offerings. Programs may enhance preparedness and patient care by integrating concise, case-based, and specialty-relevant PC content into existing curricula. These findings highlight the need for standardized national efforts to strengthen PC education within RO training.},
}

Humans
*Radiation Oncology/education
*Palliative Care
*Internship and Residency
Male
Cross-Sectional Studies
Female
*Attitude of Health Personnel
United States
Surveys and Questionnaires
Adult
Curriculum

@article {pmid42855271,
year = {2026},
author = {Sanchez-Vizcaino, C and Hippe, DS and Safwat, AA and Kharaji, M and Wang, M and Cheng, D and Canton, G and Pimentel, KD and Klein-Murrey, L and Hatsukami, TS and Yuan, C and Akoum, NW and Balu, N and Tirschwell, DL and Mossa-Basha, M},
title = {The Added Value of Vessel Wall MRI Over CTA for Differentiating Large-Artery Atherosclerotic and Cardioembolic Stroke in the Anterior and Posterior Circulations.},
journal = {AJNR. American journal of neuroradiology},
volume = {},
number = {},
pages = {},
doi = {10.3174/ajnr.A9664},
pmid = {42855271},
issn = {1936-959X},
abstract = {BACKGROUND AND PURPOSE: Differentiation between stroke etiologies is essential for secondary prevention; however, etiologic classification remains challenging in many ischemic strokes. We evaluated whether magnetic resonance vessel wall imaging (VWI) plaque markers improve computed tomography angiography (CTA)-based differentiation between cardioembolic (CE) and large-artery atherosclerotic (LAA) stroke in the anterior and posterior circulations, as a step toward improving etiologic classification beyond current criteria.

METHODS: We retrospectively included patients with unilateral anterior or posterior circulation ischemic stroke between June 2022 and April 2024 across an academic health system, classified as LAA or CE according to modified TOAST criteria. Imaging markers included CTA-derived noncalcified plaque extent (>30% stenosis), VWI-derived intracranial plaque enhancement (IPE) extent, and intraplaque hemorrhage (IPH) presence, restricted to arterial segments upstream from the infarct. Given potential territory-specific plaque differences, analyses were stratified by circulation. Multivariable logistic regression models assessed associations of CTA and VWI markers with stroke etiology. Associations with LAA were summarized using adjusted odds ratios (aOR; plaque extent variables per 1-SD increase). Overall performance for discriminating between LAA and CE etiologies was assessed using the area under the receiver operating characteristic curve (AUC).

RESULTS: Among 193 patients (median age, 70 years; 60% male), 137 had anterior circulation strokes (65 LAA, 72 CE) and 56 had posterior circulation strokes (38 LAA, 18 CE). In anterior circulation strokes, VWI markers improved discrimination over CTA alone (AUC, 0.57 for CTA alone vs 0.76 for CTA+VWI; p<0.001); CTA-derived noncalcified plaque extent (aOR, 1.7; p=0.02), IPH (aOR, 7.0; p<0.001), and IPE extent (aOR, 1.9; p=0.005) were independently associated with LAA. In posterior circulation strokes, IPE extent improved discrimination over CTA alone (AUC, 0.77 for CTA alone vs 0.84 for CTA+VWI; p=0.02); IPE extent (aOR, 2.2; p=0.02) and CTA-derived noncalcified plaque extent (aOR, 5.9; p=0.002) were independently associated with LAA. IPH was not significantly associated with posterior circulation stroke etiology (p=0.26).

CONCLUSIONS: VWI adds complementary value for differentiating LAA and CE stroke etiologies in both vascular territories, supporting a pragmatic CTA-VWI approach for etiologic characterization beyond stenosis assessment alone.},
}

@article {pmid42856579,
year = {2026},
author = {Govande, AA and Ramsey, B and Unlu, I and Amundsen, SK and Nagy, TA and Hassan, A and Smiley, M and Trautman, C and Whiteley, AT and Smith, GR and Kim, S and Lim, HC},
title = {RecBCD Prevents Bacterial Autoimmunity by Clearing Self-DNA Ends Produced During Replication Termination.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42856579},
issn = {2692-8205},
support = {R35 GM118120/GM/NIGMS NIH HHS/United States ; R35 GM143203/GM/NIGMS NIH HHS/United States ; },
abstract = {Viral-induced DNA damage triggers both eukaryotic and prokaryotic innate immunity. Here, we report that self-DNA ends generated routinely during normal termination of bacterial replication suffice to trigger the P2-encoded OLD antiphage system. Normally, these physiological triggers are cleared by the dual helicase-nuclease activities of the conserved RecBCD enzyme, which acts as an immune safeguard analogous to mammalian TREX1 exonuclease and plant DBR1 debranching enzyme. However, when this clearance fails, the transient self-DNA ends persist and are recognized by ATP-bound OLD dimers via a positively charged channel across their ATPase subunits. ATP hydrolysis then activates OLD to cleave tRNAs, causing cytotoxicity. Single-cell microscopy reveals that dozens of OLD molecules associate with kilobases of adjacent DNA, amplifying the sparse physiological DNA end signal. Our findings reveal how an endogenous byproduct poses a constant autoimmune threat in bacteria, highlighting a universal molecular conflict across kingdoms and the convergent solutions evolved to resolve it.},
}

@article {pmid42856585,
year = {2026},
author = {Merino-Galan, L and Arora, S and Glatzer, G and Jensen, M and Rajendran, A and Holland, EC and Pattwell, SS},
title = {Transcriptomic analysis reveals differential regulation of synaptic components in pediatric and adult brain tumors.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42856585},
issn = {2692-8205},
support = {K22 CA258953/CA/NCI NIH HHS/United States ; R35 CA253119/CA/NCI NIH HHS/United States ; },
abstract = {Neuronal-cancer cell interactions are a key component of brain tumor pathophysiology, yet many fundamental questions remain unanswered - with even more remaining unasked. Here, we present a comprehensive brain tumor reference map generated from bulk RNA-seq data of ~4,300 adult and pediatric brain tumors-including various glioma subtypes, medulloblastomas, ependymomas, and meningiomas-alongside ~1,400 healthy brain samples. By analyzing synaptic processes and synaptic gene expression across tumor types, we reveal the complexity of neuron-tumor crosstalk and its potential impact on patient survival. Our findings identify key synaptic signaling pathways and dysregulated patterns in brain tumors, including HNRNPH2 upregulation, a key factor in RNA processing and metabolism, in gliomas and medulloblastomas. Additionally, we highlight the role of cholinergic signaling, particularly CHRNA9, as a driver of glioma progression, which is also upregulated in WNT and Group 4 medulloblastomas, ependymomas, and meningiomas. Furthermore, P2 purinergic signaling emerges as a key player in glioma progression. These insights lay the groundwork for future studies exploring whether targeting these pathways could reprogram the tumor microenvironment toward an anti-tumor state, ultimately leading to novel therapeutic strategies and improved patient outcomes.},
}

@article {pmid42858234,
year = {2026},
author = {Becker, H and Walter, B and Haeusser, LA and Trampert, J and Zago, M and Surender, S and Maise, L and Volos, P and Erdmann, S and Kuhlburger, L and Falkner, A and Tsiami, F and Dörner, L and Maric, M and Skotnicki, A and Jägle, H and Echeverria, D and Jackson, S and Tripathi, A and Segarra-Visent, X and Bhandari, A and Beck, S and Tatagiba, M and Nahnsen, S and Claassen, M and Haraszti, R and Szulzewsky, F and Holland, EC and Merk, DJ and Tabatabai, G},
title = {Fanconi anemia pathway disruption drives lomustine sensitivity in glioma.},
journal = {Neuro-oncology},
volume = {},
number = {},
pages = {},
doi = {10.1093/neuonc/noag254},
pmid = {42858234},
issn = {1523-5866},
abstract = {BACKGROUND: Therapeutic options for progressive glioblastoma remain limited, with chlorethyl-cyclohexyl-nitrosourea (CCNU, lomustine) among the approved treatments. Beyond MGMT gene promoter methylation, molecular determinants of CCNU sensitivity or resistance are ill- defined.

METHODS: We employed genome-wide functional knockout screening using the CRISPR-Cas9 technology to identify and subsequently validate modulators of response to CCNU in experimental glioma. We established an immunocompetent glioma mouse model to enable functional interrogation of Fanconi anemia pathway (FA) genes in tumor growth and synthetic lethal interactions in vivo using the RCAS/tv-a somatic gene delivery system.

RESULTS: Multiple FA pathway members recurrently emerged as potent synthetic lethal interactors of CCNU treatment. In vivo knockdown of Fancm accelerated tumor onset and significantly increased CCNU sensitivity. Consistently, FA pathway inhibition enhanced CCNU efficacy across in vitro, ex vivo and in vivo models.

CONCLUSION: Together, these findings identify FA pathway components as key synthetic lethal interactors of CCNU response and reveal a therapeutically actionable vulnerability in glioblastoma.},
}

@article {pmid42858314,
year = {2026},
author = {Applin, SN and Andrasik, MP and Hawes, SE and Dickson, K and Blakey, W},
title = {Meeting patients where they are: The Tacoma MAX clinic's collaborative low-barrier approach to HIV care.},
journal = {AIDS care},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/09540121.2026.2744848},
pmid = {42858314},
issn = {1360-0451},
abstract = {In Tacoma, Washington, people with HIV (PWH) face significant barriers to care. This study compares viral suppression and patient-centered outcome effectiveness of co-located Ryan White (RW) and MAX (low-barrier, walk-in, engaging previously disengaged PWH with unsuppressed viral loads (VL) clinics.Mixed-methods, prospective cohort study of MAX/RW participants surveyed/interviewed at baseline, 6 and 12 months, assessing VL suppression (86 qualitative interviews coded thematically across six health/medical care domains). Eligibility criteria: VL >200 copies/mL (last 12 months), out of care ≥12 months, or facing engagement barriers. EMR VL data were collected between January 2020 and February 2025.Participants enrolled: 30 MAX and 70 RW. Viral suppression by timeline: -6 months (69.6% MAX, 78.4% RW; p = 0.4). -2.5 years (60.0% MAX, 92.1% RW; p = 0.003). MAX had higher baseline rates of housing instability (p = 0.11) and mental illness (p = 0.02) but cited immediate access, non-judgmental care, and wraparound services as being "lifesaving", with fewer unmet mental health needs and greater care access and education.Low-barrier models play a vital role in re-engaging PWH facing barriers. While RW achieved higher long-term viral suppression, MAX achieved improved trust, health literacy, and retention-foundations for long-term health. Integrated, patient-centered approaches can complement traditional care and address service gaps.},
}

@article {pmid42848909,
year = {2026},
author = {Yu, Q and Kim, H and Seidel, S and Acosta-Clark, JF and Martin, BK and O'Connor, K and Daza, RM and Gasperini, M and Nathans, JF and Lam, M and Gamo, E and Vijay Kumar, S and Kuo, L and Lalanne, JB and Simeonov, KP and Pepper, M and Trapnell, C and Gray, JM and Choi, J and Qiu, C and Shendure, J},
title = {A DNA Typewriter records the cell lineage history of a mouse, from zygote to late organogenesis.},
journal = {Science (New York, N.Y.)},
volume = {},
number = {},
pages = {eael0508},
doi = {10.1126/science.ael0508},
pmid = {42848909},
issn = {1095-9203},
abstract = {Mammalian biology unfolds over time, within tissues and organs opaque to our eyes and instruments. We applied DNA Typewriter, a sequential molecular recorder, to record the cell lineage of a mouse over nearly two weeks of development. From one embryo, we reconstruct a time-calibrated, parsimony-supported, zygote-rooted phylogeny of 1.28 million transcriptionally profiled cells. A burst of editing unequivocally marks the daughters of the first cleavage, which serve as inline replicates. We quantify clonal dominance arising during gastrulation. Tree siblings share cell type far above chance; heterotypic siblings mark terminal differentiations. Temporal sweeps of clade co-occurrence recover a dated hierarchy of cell-type couplings; imputed labels for internal nodes recapitulate known state paths. A lineage-anchored ontogeny of mammalian development, long out of reach, is coming into view.},
}

@article {pmid42852882,
year = {2026},
author = {Gómez-Garzón, C and O'Brien, VP and Chen, Q and Garman, KS and Salama, NR},
title = {Metaplasia creates a permissive niche for select Fusobacterium species in the stomach.},
journal = {mBio},
volume = {},
number = {},
pages = {e0174726},
doi = {10.1128/mbio.01747-26},
pmid = {42852882},
issn = {2150-7511},
abstract = {Infection with Helicobacter pylori is the major risk factor for gastric cancer worldwide; yet the exact mechanisms behind this link remain unclear. H. pylori-associated tissue changes often disrupt the gastric microbiome, enabling secondary gastric colonization by oral bacteria. Among these secondary colonizers, Fusobacterium species have documented associations with several gastrointestinal cancers. We found that both F. animalis and F. nucleatum invade cultured human gastric adenocarcinoma cells, but F. animalis exhibited higher adherence and invasion, and hypoxic conditions promoted higher bacterial survival. Both adherence and invasion were inhibited by exogenous GalNAc, a glycan commonly observed in membrane glycoproteins of adenocarcinoma cells and a target of the fusobacterial adhesin Fap2. Using a mouse model of stomach metaplasia, we found that F. animalis colonized gastric tissue only after metaplasia onset, growing in multispecies biofilms in the mucus layer, while F. nucleatum colonized neither healthy nor metaplastic gastric tissue. Metaplasia led to upregulation of Gal-GalNAc in the stomach, and reduced gastric acidity allowed higher F. animalis loads in this model. By contrast, inflammation and the presence of H. pylori did not significantly influence stomach colonization by F. animalis. Further assessment of additional Fusobacterium species and strains revealed that whereas all tested species can invade gastric cancer cells in vitro, only F. animalis and F. polymorphum robustly colonize the metaplastic gastric tissue of the mouse model similar to F. animalis. Overall, our data support a model in which H. pylori-induced metaplasia makes the stomach susceptible to secondary infection by other cancer-associated microbes, including some Fusobacterium species.IMPORTANCEHelicobacter pylori infection is the primary risk factor for gastric cancer worldwide, yet the underlying cancer-promoting mechanisms are not fully defined. Our study shows that metaplasia, a precancerous condition typically triggered by H. pylori and characterized by specific changes in gene expression and tissue remodeling, can enable secondary infection by other cancer-associated bacteria. Specifically, we found that certain species of the genus Fusobacterium, linked to several gastrointestinal cancers, colonize the stomach only after the onset of metaplasia. Metaplasia-associated changes in the stomach include altered surface sugars and reduced acidity, which together may create a more permissive environment for bacterial growth. Our findings support a model in which disruptions of gastric tissue architecture induced by chronic H. pylori infection facilitate colonization by other cancer-related bacteria, contributing to the growing body of evidence highlighting the role of bacteria in cancer development.},
}

@article {pmid42844522,
year = {2026},
author = {Bhatia, S and D'Angelo, S and Nghiem, P},
title = {Perspectives on 10 years of Immune Checkpoint Inhibitors in Merkel Cell Carcinoma: A Podcast.},
journal = {Targeted oncology},
volume = {},
number = {},
pages = {},
pmid = {42844522},
issn = {1776-260X},
abstract = {Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with a poor prognosis, particularly in patients with advanced disease. The introduction of immune checkpoint inhibitors (ICIs) approximately 10 years ago has dramatically improved outcomes for patients with advanced MCC. Current US Food and Drug Administration-approved ICIs in this setting include the PD-L1 inhibitor avelumab and PD-1 inhibitors pembrolizumab and retifanlimab. In this podcast, we summarize key studies of ICIs in advanced MCC, including clinical trials and real-world studies, and discuss clinical evidence related to practical considerations, such as elective discontinuation of ICI treatment, and treatment of patients with immunocompromised or immunosuppressed status. We also discuss initial findings from studies of ICI-based combinations in patients with advanced MCC and ICI treatment in earlier stages of MCC, and highlight the emerging role of circulating tumor DNA for predicting disease recurrence. Overall, these developments demonstrate the positive impact of ICIs in the treatment of MCC and illustrate ongoing efforts to further improve patient outcomes.},
}