@article {pmid41536779,
year = {2026},
author = {Martinelli, G and Solomon, SR and Mukherjee, S and Santoro, A and Strickland, SA and Vives, S and Ravandi, F and Walter, RB and Cook, RJ and Lech-Maranda, E and Calbacho, M and Wierzbowska, A and Marconi, G and Acuña-Cruz, E and Cano-Ferri, I and Bertolini, F and Rzymski, T and Paoli, A and Merlo, GM and Auriol, FK and Zicari, S and Galleu, A and Gupta, I and Montesinos, P},
title = {Dual FLT3/PIM inhibitor dapolsertib in acute myeloid leukemia: results from the phase 1/2 DIAMOND-01 trial.},
journal = {Blood neoplasia},
volume = {3},
number = {1},
pages = {100178},
pmid = {41536779},
issn = {2950-3280},
abstract = {Acute myeloid leukemia (AML) is an aggressive hematopoietic cancer with poor survival outcomes. Despite improvements with recent FMS-like tyrosine kinase 3 (FLT3) inhibitors, resistance is common, and responses are short. Dapolsertib (MEN1703) is a novel, first-in-class dual inhibitor of PIM (proviral integration site for Moloney murine leukemia virus) and FLT3 kinases, with activity in both FLT3-mutated and wild-type cells. A phase 1/2 open-label, multicenter, dose-escalation study (DIAMOND-01) investigated the maximum tolerated dose (MTD) of single-agent dapolsertib and assessed its safety, efficacy, pharmacokinetic (PK) profile, pharmacodynamic biomarkers, and genomics in patients with AML with no standard therapeutic options available. Seventy-three patients received oral doses of dapolsertib ranging from 25 to 150 mg per day (14 consecutive days over 21-day cycles). In the dose-escalation phase, the MTD was 125 mg and was selected for dose expansion. The most common grade ≥3 adverse events in patients receiving 125 mg were pneumonia (38%), thrombocytopenia (30%), and anemia (27%); most of these events were deemed not treatment related. For patients receiving 125 mg dapolsertib (n = 55), the overall response rate was 9%, with a median 2.07-month duration of response, and 4 of 5 responses were observed in patients with isocitrate dehydrogenase 1 (IDH1)/IDH2 mutations. PK analysis indicated rapid absorption of oral dapolsertib, an elimination half-life suitable for once daily dosing and a PK independent of formulation and IDH mutational status. Pharmacodynamic activity was confirmed in 50% of evaluable patients. Overall, dapolsertib demonstrated modest single-agent activity in patients with AML. This trial was registered at www.clinicaltrials.gov as #NCT03008187.},
}

@article {pmid41535609,
year = {2026},
author = {Gottimukkala, KSV and Lane, DD and Cunningham, R and Malik, HS and Jwa, Y and Cassidy, ME and Castelli, JMP and Enstrom, MR and Poljakov, K and Gastelum, G and Ho, SH and Tassa, C and Adair, JE},
title = {CRISPR-AuNP: physicochemical optimization of a gold nanoparticle platform for cost-effective and modular non-viral gene editing in HSPCs.},
journal = {Gene therapy},
volume = {},
number = {},
pages = {},
pmid = {41535609},
issn = {1476-5462},
abstract = {Efficient delivery of CRISPR ribonucleoproteins into primary hematopoietic stem and progenitor cells (HSPCs) is essential for durable gene editing therapies but remains challenging. Here, we advance a modular, benchtop-assembled gold-polymer hybrid nanoparticle (CRISPR-AuNP) platform that enables non-viral delivery of multiple CRISPR systems into HSPCs. Guided by a mechanistic understanding of Cas9's interaction with gold surfaces, we engineered the formulation by conjugating pre-formed RNP-polymer complexes, assembled using thiolated polyethyleneimine-polyethylene glycol, to gold nanoparticles. This system achieved efficient editing in primary CD34+ HSPCs for Cas9, Cas12a, and Cas12a-M29-1 without compromising cell viability. Notably, the nanoformulation can be assembled in under 2 h in a PCR tube for less than $70/million HSPCs treated. This work establishes a scalable, cost-effective, and accessible gene editing system with the potential to democratize CRISPR applications in HSPC research and therapy.},
}

@article {pmid41535474,
year = {2026},
author = {Cheng, H and Su, Y and Pan, X and Xu, Y and Xie, E and Du, J and Chen, DG and Dai, X and Gottardo, R and Greenberg, PD and Li, G},
title = {The ubiquitin ligase KLHL6 drives resistance to CD8[+] T cell dysfunction.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {41535474},
issn = {1476-4687},
abstract = {The multifaceted dysfunction of tumour-infiltrating T cells, including exhaustion and mitochondrial dysfunction, remains a major obstacle in cancer immunotherapy[1-6]. Transcriptomic and epigenomic regulation of T cell dysfunction have been extensively studied[7-9], but the role of proteostasis in regulating these obstacles remains less defined. Here we combined computational analyses of atlases of T cell exhaustion and mitochondrial fitness with performed targeted in vivo CRISPR screens, which identified the E3 ubiquitin ligase KLHL6 as a dual-negative regulator of both T cell exhaustion and mitochondrial dysfunction. Mechanistically, KLHL6 expression promoted TOX poly-ubiquitination and subsequent proteasomal degradation, thereby attenuating the transition of progenitor exhausted T cells towards terminal exhaustion. Simultaneously, KLHL6 maintained mitochondrial fitness by constraining the excessive mitochondrial fission that occurs during chronic T cell receptor stimulation by means of post-translational regulation of the PGAM5-Drp1 axis. However, KLHL6 is naturally downregulated by T cell receptor ligation, mitigating its potentially beneficial ubiquitin ligase activities during exposure to chronic stimulation. Enforcing KLHL6 expression in T cells markedly improved efficacy and long-term persistence against tumours and during viral infections in vivo. These findings uncover KLHL6 as a multifunctional, clinically actionable target for cancer immunotherapy, and highlight the potential of modulating proteostasis and ubiquitin modification to improve immunotherapy.},
}

@article {pmid41535386,
year = {2026},
author = {Li, J and Hu, J and Yun, H and Mei, Z and Wang, X and Luo, K and Guasch-Ferré, M and Han, X and Truong, B and Merino, J and Jia, C and Ruiz-Canela, M and Rebholz, CM and Moon, EH and Alkis, T and Liu, G and Yao, J and Zhang, X and Porneala, BC and Salas-Salvadó, J and Wang, TJ and Dupuis, J and Selvin, E and Guo, X and Bhupathiraju, SN and Brody, JA and Liu, Y and Wood, AC and North, KE and Jung, SY and Liu, CT and Sotoodehnia, N and Liu, S and Tinker, LF and Eliassen, AH and Manson, JE and Florez, JC and Gerszten, RE and Clish, CB and Liang, L and Lemaitre, RN and Tucker, KL and Rich, SS and Rotter, JI and Martínez-González, MA and Rexrode, KM and Meigs, JB and Boerwinkle, E and Kaplan, RC and Hu, FB and Yu, B and Qi, Q},
title = {Circulating metabolites, genetics and lifestyle factors in relation to future risk of type 2 diabetes.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {41535386},
issn = {1546-170X},
support = {R00DK122128//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; U01DK140761//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; R01DK081572//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; R01DK134672//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; R01DK119268; R01DK126698; U01DK140761; R01DK120870//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; 23POST1020455//American Heart Association (American Heart Association, Inc.)/ ; NNF24OC0095435//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; R01HL153178//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; K24HL152440//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL136266//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL060712//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL060712; R01HL170904//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01AG085320//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; },
abstract = {The human metabolome reflects complex metabolic states affected by genetic and environmental factors. However, metabolites associated with type 2 diabetes (T2D) risk and their determinants remain insufficiently characterized. Here we integrated blood metabolomic, genomic and lifestyle data from up to 23,634 initially T2D-free participants from ten cohorts. Of 469 metabolites examined, 235 were associated with incident T2D during up to 26 years of follow-up, including 67 associations not previously reported across bile acid, lipid, carnitine, urea cycle and arginine/proline, glycine and histidine pathways. Further genetic analyses linked these metabolites to signaling pathways and clinical traits central to T2D pathophysiology, including insulin resistance, glucose/insulin response, ectopic fat deposition, energy/lipid regulation and liver function. Lifestyle factors-particularly physical activity, obesity and diet-explained greater variations in T2D-associated versus non-associated metabolites, with specific metabolites revealed as potential mediators. Finally, a 44-metabolite signature improved T2D risk prediction beyond conventional factors. These findings provide a foundation for understanding T2D mechanisms and may inform precision prevention targeting specific metabolic pathways.},
}

@article {pmid41534004,
year = {2026},
author = {Liang, EC and Jeon, Y and Qiao, Y and Wu, X and Huang, JJ and Portuguese, AJ and Basom, R and Torkelson, A and Kirchmeier, D and Braathen, K and Cowan, AJ and Shadman, M and Hirayama, AV and Till, BG and Kimble, EL and Wu, Q and Gauthier, J},
title = {Time-Series Clustering Captures Patterns of Early Immune Effector Cell-Associated Hematotoxicity That Are Predictable Using Tree-Based Models.},
journal = {JCO clinical cancer informatics},
volume = {10},
number = {},
pages = {e2500148},
doi = {10.1200/CCI-25-00148},
pmid = {41534004},
issn = {2473-4276},
mesh = {Humans ; Cluster Analysis ; *Immunotherapy, Adoptive/adverse effects/methods ; Male ; Female ; Middle Aged ; Time Factors ; },
abstract = {PURPOSE: Immune effector cell-associated hematotoxicity (ICAHT) is a major cause of nonrelapse mortality after chimeric antigen receptor (CAR) T-cell therapy. We hypothesized that unsupervised time-series clustering could better identify archetypal patterns of early hematotoxicity compared to the early ICAHT (eICAHT) grading system.

METHODS: We applied unsupervised k-means time-series clustering based on Euclidean distances to longitudinal absolute neutrophil count (ANC) data from days +0 through +30 post-CAR T-cell infusion in 691 patients treated at our center (training set: n = 483, 70%; test set: n = 208, 30%).

RESULTS: Within our training set, we identified an optimal cluster solution based on four ANC recovery clusters, which were labeled as very good, good, poor, and very poor. We trained a random forest (RF) model including the top five most important features (day +3, +4, +5, +26, and +27 ANC values) to predict the cluster assignments. Within our test set, we applied the RF model to predict cluster assignments. Compared with the eICAHT criteria, the RF-predicted clusters were more compact and better separated (Dunn index: 0.078 v 0.034; average silhouette width: 0.12 v 0.010). In addition, the RF model identified patients in the good recovery cluster with intermediate overall survival (hazard ratio [HR], 1.70 [95% CI, 1.05 to 2.74]; P = .029; reference, very good), which was not captured by grade 2 eICAHT (HR, 1.37 [95% CI, 0.80 to 2.35]; P = .25; reference, grade 0-1).

CONCLUSION: Unsupervised time-series clustering identified distinct and clinically relevant patterns of hematotoxicity after CAR T-cell therapy. We trained and tested an RF model that accurately predicted cluster assignments using only five features. Predictions can be generated using our online web application.},
}

Humans
Cluster Analysis
*Immunotherapy, Adoptive/adverse effects/methods
Male
Female
Middle Aged
Time Factors

@article {pmid41533748,
year = {2025},
author = {Boeckh, M and Xie, H and Stevens-Ayers, T and Sircy, L and Zamora, D and Goldman, JD and Woods, CW and Stapleton, RD and Rubenfeld, G and Kalil, A and Jerome, KR and Dasgupta, S and Limaye, AP},
title = {Cytomegalovirus DNAemia in Hospitalized Adults With SARS-CoV-2 Infection Requiring Supplemental Oxygen: Virologic and Clinical Characteristics and Association With Outcomes.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf649},
pmid = {41533748},
issn = {1537-6613},
support = {//Merck Investigator Study/ ; },
abstract = {BACKGROUND: Cytomegalovirus (CMV) reactivation occurs in the context of coronavirus disease 2019 (COVID-19); however, the viral kinetics, risk factors, and clinical outcomes are poorly defined.

METHODS: We examined the association of CMV DNAemia with clinical outcomes among participants of a randomized trial of remdesivir with or without baricitinib (National Institute of Allergy and Infectious Diseases [NIAID], Adaptive COVID-19 Treatment Trial 2 [ACTT-2]). Plasma CMV DNAemia from CMV-seropositive participants with COVID-19 (NIAID ordinal scale [OS] 5, 6, or 7 at entry) were assessed longitudinally by quantitative polymerase chain reaction. Factors associated with CMV DNAemia, and clinical outcomes were analyzed by Cox regression and proportional odds models.

RESULTS: Of 772 trial participants with available samples, 643 (83%) were CMV seropositive. Baseline CMV serostatus was not associated with COVID-19 outcomes. The cumulative incidence of CMV DNAemia among seropositive persons by day 28 was overall 11% (baseline OS 5, 6.3%; OS 6, 16.4%; OS 7, 24.7%), and was associated with older age, baseline OS, male sex, lymphopenia, and systemic corticosteroid use, while remdesivir and baricitinib did not affect risk. CMV DNAemia was associated with a lower probability of improvement by day 29 (adjusted hazard ratio, 0.3 [95% confidence interval, .17-.56]), with a more pronounced delay of recovery with higher CMV viral load. CMV DNAemia was also associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and death.

CONCLUSIONS: In hospitalized adults with COVID-19 requiring oxygen, CMV viremia occurs within well-defined clinical risks and is independently associated with delayed recovery from illness, higher SARS-CoV-2 viral load, and increased mortality.},
}

@article {pmid41532388,
year = {2026},
author = {Cassaday, RD and DeAngelo, DJ},
title = {Patients First: Navigating Asparaginase-Based Treatment in Young Adults With Acute Lymphoblastic Leukemia.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70195},
pmid = {41532388},
issn = {1096-8652},
abstract = {This CME/CE integrates real patient stories, current evidence, evolving guideline recommendations, and expert clinical experience to equip hematology/oncology clinicians with practical strategies for successful asparaginase-based therapy in young adults with acute lymphoblastic leukemia (ALL). The overarching goal is to improve outcomes for young adults with ALL through more consistent application of pediatric-inspired regimens, optimized asparaginase use, and comprehensive, patient-centered care. Leukemia experts synthesize the latest evidence on the efficacy and safety of asparaginase-based ALL treatment for young adults. Using a case-based approach, the curriculum provides structured guidance on mitigation, monitoring, and management of key asparaginase-related toxicities. Practical recommendations include therapeutic drug monitoring of asparaginase activity, detection of clinical and silent hypersensitivity reactions, and timely substitution of Escherichia coli-derived asparaginase with Erwinia-derived asparaginase to preserve therapeutic activity and efficacy after immune-mediated inactivation. Beyond treatment selection and toxicity management, the activity addresses system-level and psychosocial barriers that uniquely affect young adults with ALL, such as distance from specialty centers, employment and family responsibilities, lower rates of clinical trial participation, and survivorship concerns. To view this activity, and obtain CME/CE credit, click here.},
}

@article {pmid41531135,
year = {2026},
author = {Hayek, H and Halasa, NB and Hill, JA},
title = {Establishing Permanence, Not Patchwork: Sustaining Coordinated Research Networks for Immunocompromised Populations.},
journal = {Transplant infectious disease : an official journal of the Transplantation Society},
volume = {},
number = {},
pages = {e70168},
doi = {10.1111/tid.70168},
pmid = {41531135},
issn = {1399-3062},
}

@article {pmid41530145,
year = {2026},
author = {Brzoska, T and Kaminski, TW and Katoch, O and Menchikova, EV and Alagbe, AE and Tashbook, SE and Tofovic, SP and Jonassaint, JC and St Croix, CM and Watkins, SC and Howe, S and Field, JJ and Seyerle, AA and Pradhan-Sundd, T and Laurie, C and Pankratz, ND and Smith, NL and Goode, EL and Pankow, JS and Kooperberg, C and Kato, GJ and Zhang, Y and Novelli, EM and Gladwin, MT and Jackson, EK and Nouraie, SM and Sundd, P},
title = {CD39 polymorphism enables lung thrombosis in sickle cell disease.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-68396-2},
pmid = {41530145},
issn = {2041-1723},
support = {R01HL128297//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL141080//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL166345//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 18TPA34170588//American Heart Association (American Heart Association, Inc.)/ ; 23TPA1074022//American Heart Association (American Heart Association, Inc.)/ ; },
abstract = {Sickle cell disease (SCD) is the most common monogenic-hemolytic disorder affecting people of African ancestry. Adenosine diphosphate (ADP) released following intravascular hemolysis activates platelets by stimulating purinergic receptors to promote thrombosis. Despite brisk intravascular hemolysis, which releases high levels of ADP into plasma, and evidence of platelet and hemostatic activation, it remains elusive why only a subset of SCD patients develop lung thrombosis. Using real-time in vivo lung microscopy, we report a surprising finding that humanized SCD mice are protected from ADP-induced lung thrombosis, which is secondary to the degradation of ADP by CD39 present in circulating extracellular vesicles released by the lung endothelium. ADP-induced platelet aggregation is also impaired in the blood of SCD patients with elevated levels of CD39[+] extracellular vesicles. CD39 polymorphism rs3176891A→G is associated with the incidence of lung thrombosis in SCD patients but not healthy humans of African ancestry. Remarkably, CD39[+] extracellular vesicles are fewer and ADP-induced platelet aggregation is higher in the blood of SCD patients with rs3176891G allele. This study identifies a novel extracellular vesicle-dependent mechanism preventing lung thrombosis in SCD and reveals how CD39 polymorphisms may impair this protection to increase the risk for lung thrombosis in a subset of SCD patients.},
}

@article {pmid41530119,
year = {2026},
author = {Ykema, MR and Davis, MA and Kasal, DN and Jennewein, MF and Lo, E and Singh, J and Beaver, S and Cross, N and Melief, E and Reed, S and Press, C and Brandt, DS and McClary, WD and Mohamath, R and Fusco, P and Bakken, J and Casper, C and Hartwig, AT and Gerhardt, A and Bowen, RA and Voigt, EA},
title = {Intranasal replicon vaccine establishes mucosal immunity and protects against H5N1 and H7N9 influenza.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {434},
pmid = {41530119},
issn = {2041-1723},
mesh = {Animals ; *Influenza Vaccines/immunology/administration & dosage/genetics ; Administration, Intranasal ; *Immunity, Mucosal/immunology ; *Influenza A Virus, H5N1 Subtype/immunology/genetics ; Ferrets ; Mice ; *Orthomyxoviridae Infections/prevention & control/immunology/virology ; *Replicon/immunology ; Female ; *Influenza A Virus, H7N9 Subtype/immunology/genetics ; Humans ; Mice, Inbred BALB C ; Antibodies, Viral/immunology ; *Influenza, Human/prevention & control/immunology/virology ; Injections, Intramuscular ; Hemagglutinin Glycoproteins, Influenza Virus/immunology/genetics ; },
abstract = {Seasonal and pandemic influenza viruses are continuous threats to human health, requiring rapid development of vaccines to multiple evolving viral strains. RNA vaccine technologies have the adaptability and manufacturability to facilitate pandemic preparedness but have limited flexibility in their route of administration, reducing the ability to establish local protective immune responses such as respiratory mucosal immunity. Here, we describe monovalent and bivalent replicon vaccines against A/Vietnam/1203/2004 H5N1 and A/Anhui/PA-1/2013 H7N9. These replicon vaccines express either H5 or H7 hemagglutinin and are formulated with a nanostructured lipid carrier (NLC) that permits both intramuscular (IM) and intranasal (IN) dosing. In mice, IM vaccination established systemic humoral and cellular responses but no detectable mucosal response, while IN administration induced robust systemic and mucosal immunity. The replicon-NLC vaccines protected against morbidity and mortality in ferret challenge models, establishing this intranasally-administered replicon-NLC vaccine platform as a potential pandemic response tool.},
}

Animals
*Influenza Vaccines/immunology/administration & dosage/genetics
Administration, Intranasal
*Immunity, Mucosal/immunology
*Influenza A Virus, H5N1 Subtype/immunology/genetics
Ferrets
Mice
*Orthomyxoviridae Infections/prevention & control/immunology/virology
*Replicon/immunology
Female
*Influenza A Virus, H7N9 Subtype/immunology/genetics
Humans
Mice, Inbred BALB C
Antibodies, Viral/immunology
*Influenza, Human/prevention & control/immunology/virology
Injections, Intramuscular
Hemagglutinin Glycoproteins, Influenza Virus/immunology/genetics

@article {pmid41528117,
year = {2026},
author = {Johnson, M and Cai, Y and Vasconcelos, AG and Orchard, P and Auer, PL and Lettre, G and Wen, J and Franceschini, N and Kooperberg, C and Sun, W and Hsu, L and Raffield, LM and Reiner, AP},
title = {Whole Blood Transcriptomic Analysis of Sickle Cell Trait.},
journal = {European journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ejh.70114},
pmid = {41528117},
issn = {1600-0609},
support = {phs001237/HL/NHLBI NIH HHS/United States ; R01HL152439/HL/NHLBI NIH HHS/United States ; R01HL146500/HL/NHLBI NIH HHS/United States ; U01HG01172/HG/NHGRI NIH HHS/United States ; /NH/NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; //Fred Hutchinson Cancer Center/ ; 3U54HG003067-13S1//Broad Institute of MIT and Harvard, and the Northwest Genomics Center (NWGC)/ ; HHSN268201500014C/HL/NHLBI NIH HHS/United States ; X01HL153408//Broad Institute of MIT and Harvard, and the Northwest Genomics Center (NWGC)/ ; },
abstract = {Sickle cell trait (SCT) is the heterozygous carrier state for the HBB missense variant which causes sickle cell disease (SCD). SCT has been associated with increased risk of venous thromboembolism and chronic kidney disease as well as alterations in clinical laboratory parameters. To investigate differential gene expression in SCT, we used RNA sequencing of whole blood samples collected from 805 African American female participants (143 SCT; 660 controls) from the Women's Health Initiative Long Life Study (mean age = 76). We identified 226 differentially expressed genes (DEGs) in SCT compared to non-carriers (FDR < 0.05). Enriched pathways included those related to erythropoiesis, hemoglobin synthesis, and proteasomal degradation. Many of the SCT-associated DEGs were previously reported as differentially expressed in blood from individuals with SCD. Among the DEGs associated with SCT, we observed enrichment of upregulated ubiquitin-related genes normally downregulated during the later stages of erythroid differentiation, a pattern previously reported in SCD. Several of the SCT-associated DEGs highlight mechanisms that potentially link hemolysis or erythropoiesis to hypoxic kidney tubular injury. Future investigation of these genes using single cell transcriptomic analysis in relevant tissues may be useful in understanding mechanisms for adverse health outcomes in individuals with SCT.},
}

@article {pmid41526345,
year = {2026},
author = {Strickler, JH and Cercek, A and Siena, S and André, T and Ng, K and Van Cutsem, E and Wu, C and Paulson, AS and Hubbard, JM and Coveler, AL and Fountzilas, C and Kardosh, A and Kasi, PM and Lenz, HJ and Ciombor, K and Elez, E and Bajor, DL and Cremolini, C and Sanchez, F and Nayeri, M and Feng, W and Bieda, M and Bekaii-Saab, TS},
title = {Tucatinib plus trastuzumab for chemotherapy-refractory, HER2 + , RAS wild-type metastatic colorectal cancer (MOUNTAINEER): final analysis.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-67824-z},
pmid = {41526345},
issn = {2041-1723},
abstract = {MOUNTAINEER was a multicenter, open-label, phase 2 trial (NCT03043313) that evaluated the efficacy and safety of tucatinib plus trastuzumab, a dual HER2-targeted chemotherapy-free regimen. Patients were included if they had chemotherapy-refractory, HER2+, RAS wild-type unresectable or metastatic colorectal cancer. This final analysis reports updated efficacy and safety after a median follow-up of 32.4 months. Of the 84 patients who received tucatinib plus trastuzumab, the confirmed objective response rate was 39.3%; median duration of response was 15.2 months. Median progression-free survival was 8.1 months and overall survival was 23.9 months. Efficacy was relatively similar across central HER2+ testing methods. No clear association of treatment response with co-occurring biomarker alterations was seen. Few patients discontinued treatment due to adverse events; no treatment-emergent deaths occurred. Tucatinib plus trastuzumab showed clinically meaningful efficacy and favorable safety. Efficacy was observed irrespective of central HER2+ testing methods and in patients with heterogeneous tumor biomarker profiles.},
}

@article {pmid41524276,
year = {2026},
author = {Tan, Y and Kim, BJ and Mujal, AM and Chen, ACY and Weis, AM and Bergaggio, E and Micevic, G and Xie, H and Park, JS and Hor, JL and Papanicolaou, M and Shobaki, N and Domizi, P and Delconte, RB and Vendramin, R and Hegde, S and Han, S and Su, Y and Hacohen, N},
title = {Training Tomorrow's Leaders in Cancer Immunology.},
journal = {Cancer immunology research},
volume = {},
number = {},
pages = {OF1-OF8},
doi = {10.1158/2326-6066.CIR-25-1479},
pmid = {41524276},
issn = {2326-6074},
abstract = {The transition from trainee to independent investigator is one of the most challenging and formative phases of a scientific career. It requires not only scientific expertise but also the skills to lead, mentor, manage, and communicate effectively. The Arthur and Sandra Irving Cancer Immunology Symposium serves as a platform for established investigators to mentor trainees and early-career faculty as they navigate this transition to independence. Through sharing personal experiences and lessons from their own careers, senior leaders provide guidance on the scientific, professional, and personal challenges that shape a successful career in cancer immunology-emphasizing how curiosity, persistence, and a translational mindset can make a lasting real-world impact. This commentary highlights key themes, including leadership, communication, recruitment, and fundraising. Altogether, these insightful thoughts provide a framework for the next generation of cancer immunologists as they establish their independent careers as future leaders in the field.},
}

@article {pmid41524253,
year = {2026},
author = {Stolla, M and Bailey, SL and Chauhan, A and Byrne, DA and Ting, L and Klotz, P and Pulido, JN and Lehr, EJ and Youssef, S and Lawrence, J and Limanek, A and Alcorn, K and Ryan, P and Stout, DM},
title = {A pilot trial of long-distance shipped, extended- and cold-stored platelets in 100% plasma for cardiothoracic surgical bleeding.},
journal = {Transfusion},
volume = {},
number = {},
pages = {},
doi = {10.1111/trf.70076},
pmid = {41524253},
issn = {1537-2995},
support = {W81XWH-12-1-0441//U.S. Department of Defense/ ; },
abstract = {BACKGROUND: In this pilot trial, we tested the feasibility of conducting a randomized controlled trial in cardiac surgery patients using extended-, 100% plasma-, cold-stored, and long-distance-shipped platelets (CSPs).

STUDY DESIGN AND METHODS: We conducted a single center, controlled, double-blind pilot study in adult patients undergoing elective redo or complex cardiothoracic surgery. Patients were allocated in a week-based block randomization scheme to receive either room temperature-stored platelets (RTPs) or CSPs shipped from a Texas-based blood center and stored between 10 and 14 days. The primary outcome was defined as the feasibility of recruitment and accrual. Several other secondary endpoints were assessed. All platelet units were screened for aggregates using RTP release criteria.

RESULTS: In a post-hoc "as treated" analysis, 15 patients received RTPs, and 9 received CSPs (including 3 who received both). We found that most CSPs (58%) were not usable for transfusion due to the presence of aggregates. This resulted in an excess of subjects receiving RTPs; consequently, the final nine transfused participants were allocated to receive CSPs without randomization. We accrued 0.7 evaluable subjects/month of active enrollment, which was below our desired primary outcome feasibility target of ≥1.2. One death within 28 days occurred in the RTP transfusion group, while none occurred in the CSPs group. In vitro testing yielded contradictory results.

CONCLUSION: Due to slow recruitment and the abundance of aggregates in CSPs, this pilot trial does not support the feasibility of the study protocol.},
}

@article {pmid41521409,
year = {2025},
author = {Lindsay, J and Yeoh, D and Teh, BW and Reynolds, GK and Henden, A and McQuilten, Z and Wheeler, M and Hamilton, A and Nelson, A and Nakagaki, M and Sandhu, S and Slavin, MA and , },
title = {Consensus guidelines for antibacterial prophylaxis in patients with neutropenia.},
journal = {Internal medicine journal},
volume = {55 Suppl 7},
number = {},
pages = {115-135},
doi = {10.1111/imj.70250},
pmid = {41521409},
issn = {1445-5994},
mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use ; *Antibiotic Prophylaxis/standards/methods ; Australia/epidemiology ; Neoplasms/drug therapy ; *Neutropenia/drug therapy/chemically induced ; },
abstract = {Since the publication of the Australian consensus guidelines in 2011, the routine use of prophylactic antibiotics in patients with neutropenia has remained controversial, because of concern that the risks of promoting antimicrobial resistance outweighed the level of evidence that their use reduced mortality. Populations at risk have changed over this period and now include a multitude of new cancer therapies, such as targeted cancer therapies and immunotherapies. Emerging understanding about the importance and role of the microbiome in defining treatment response and patterns of antibiotic resistance has also expanded. In addition, the management of neutropenic fever has improved significantly through the development and routine implementation of sepsis pathways. These updated consensus guidelines review recent evidence for the use of antibacterial prophylaxis in adults and children receiving cancer therapies associated with neutropenia. Recommendations presented in these guidelines were based on evaluating current evidence for the benefits and harms of antibacterial prophylaxis while considering the current Australian and New Zealand healthcare setting. In most circumstances, the potential harm of antibiotic resistance, adverse effects of antibiotics and disruption to the microbiome, outweighed the benefit of reducing the incidence of infection, without a benefit in mortality.},
}

Humans
*Anti-Bacterial Agents/therapeutic use
*Antibiotic Prophylaxis/standards/methods
Australia/epidemiology
Neoplasms/drug therapy
*Neutropenia/drug therapy/chemically induced

@article {pmid41521394,
year = {2026},
author = {O'Keefe, GE and Navarro, SL and Zheng, Z and Randolph, TW and Shelton, M and Elizaga, N and Qiu, Q and Nagana, GGA and Raftery, D},
title = {Metabolic profiles in adults with trauma receiving enteral nutrition support: A metabolomic cohort study.},
journal = {JPEN. Journal of parenteral and enteral nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1002/jpen.70051},
pmid = {41521394},
issn = {1941-2444},
support = {R01GM127790/NH/NIH HHS/United States ; T32 GM121290/NH/NIH HHS/United States ; //NIDDK P30 DK035816 (Nutrition and Obesity Research Center)/ ; },
abstract = {BACKGROUND: We aimed to identify metabolic changes after injury and potential mechanisms whereby nutrition support may influence metabolites and pathways. We analyzed 45 metabolites in 67 trauma patients.

METHODS: We performed a metabolomic cohort study in critically ill adults with trauma using nuclear magnetic resonance to quantify 45 metabolites in plasma. We divided the cohort into two groups based on the median amount of protein intake calculated by averaging over the first 7 days of nutrition support. Using linear mixed models, we tested the hypotheses that metabolite concentrations would differ over time and the rate of change is altered by the amount of enteral protein intake.

RESULTS: Five metabolites in each of the low (median = 0.6 [IQR, 0.4-0.8] gm/kg/day) and high (1.5 [1.1-1.7] gm/kg/day) protein intake groups were different by day 3 compared with baseline. Twenty metabolites in the low-protein intake group and 14 metabolites in the high-protein intake group were different by day 7 compared with baseline. There was no evidence that the rate of metabolite change over time differs by protein intake group. Quantitative enrichment analysis indicated that branched chain amino acid (BCAA) catabolism was one of the most altered pathways in both groups.

CONCLUSION: In critically ill trauma patients, metabolites, particularly those linked with BCAA metabolism, are altered over time but not influenced by the amount of enteral protein intake during the first week.},
}

@article {pmid40911901,
year = {2026},
author = {Dela Cruz, FS and Stewart, EA and Surdez, D and Daley, JD and Soragni, A and Tomazou, EM and Alvarez-Perez, J and Feinberg, TY and Amatruda, JF and Ganapathi, SS and Ohm, JE and Heske, CM and Cohen-Gogo, S and Pesic, D and Nash, JO and Shlien, A and Roundhill, EA and Burchill, SA and Crompton, BD and Lawlor, ER and Loeb, DM and Delattre, O and Mora, J and Scotlandi, K and Reed, DR and Grohar, PJ and Grünewald, TGP and Kovar, H and Bailey, KM},
title = {Advancing Preclinical Biology for Ewing Sarcoma: An International Effort.},
journal = {Molecular cancer therapeutics},
volume = {25},
number = {1},
pages = {48-70},
pmid = {40911901},
issn = {1538-8514},
mesh = {*Sarcoma, Ewing/pathology ; Humans ; Animals ; *Bone Neoplasms/pathology ; Mice ; Disease Models, Animal ; Xenograft Model Antitumor Assays ; },
abstract = {Ewing sarcoma is an aggressive bone and soft-tissue cancer affecting adolescents and young adults. In vitro and in vivo models of Ewing sarcoma have been instrumental in advancing our understanding of Ewing sarcoma biology and essential in evaluating potential therapies, particularly for metastatic or relapsed disease for which effective treatment options remain limited. Through an international collaborative effort between the Children's Oncology Group Bone Tumor Committee and the Euro Ewing Consortium, we review the current landscape of preclinical modeling used in Ewing sarcoma research encompassing both in vitro (cell lines and tumor organoids) and in vivo (mouse and nonmammalian xenografts) model systems. We discuss factors that can influence experimental results, provide testing considerations for both in vitro and in vivo studies, and descriptions of existing preclinical data repositories. We highlight current needs in Ewing sarcoma modeling and the importance of enhanced international cooperative research and patient advocacy efforts which will be critical in expanding our resources of biologically relevant Ewing sarcoma models to enable translation of preclinical findings into effective therapeutic strategies for patients with Ewing sarcoma.},
}

*Sarcoma, Ewing/pathology
Humans
Animals
*Bone Neoplasms/pathology
Mice
Disease Models, Animal
Xenograft Model Antitumor Assays

@article {pmid41521011,
year = {2026},
author = {Kanzaria, A and Arora, S and Naik, A and Dhanushkodi, N and Ho, CC and Kaur, N and Zhang, J and Ren, X and Fromm, JR and Shadman, M and Smith, S and Gopal, A and Roncador, G and Holland, E and Naresh, KN},
title = {Biomarkers Informed by Single-Cell and Spatial Transcriptomics - Biomarkers for Grade 3 Follicular Lymphoma.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {},
number = {},
pages = {100958},
doi = {10.1016/j.modpat.2026.100958},
pmid = {41521011},
issn = {1530-0285},
abstract = {Follicular lymphoma (FL) patients have variable outcomes, underscoring the need for biomarkers for improved risk stratification. Current FL grading systems, based on subjective centroblast counts, suffer from poor reproducibility, despite evidence linking grade 3 FL to worse prognosis. We aimed to identify objective biomarkers for centroblasts and centrocytes to improve FL prognostication. We reanalyzed publicly available spatial and single-cell transcriptomic data from normal germinal centers (GCs) and FL samples. Reanalysis revealed distinct gene expression profiles: AICDA (AID) and CXCR4 highly expressed in GC dark zone cells (centroblasts), and CD40 and TFRC (CD71) in light zone cells (centrocytes). Single-cell RNA sequencing of FL samples further showed AID and CXCR4 overexpression in malignant Grade 3A cells and CD40 and CD71 in grade 1-2 cells. We validated these findings using immunohistochemistry (IHC) (single and multiplex) on tonsils and 59 FL specimens (42 Grade 1-2, 17 Grade 3). Grade 3 FL showed significantly higher expression of AID, CD71, and Ki67 compared to grade 1-2; with CXCR4 approaching significance. Receiver operating characteristic (ROC) curve analysis identified optimal cut-offs for AID (1.54%), CXCR4 (21.9%), Ki67 (21.6%), and CD71 (7.57%) to distinguish grade 3 from grade 1-2 FL, with AID showing the best discriminatory ability. Crucially, AID expression evaluation showed reproducibility across two different digital algorithms and two independent visual observers. Furthermore, we observed a trend toward shorter disease-specific survival (DSS) in patients with both FL grade 3 and high AID expression. This prognostic observation held true regardless of whether AID overexpression was assessed via digital evaluation (cut-off: 1.54%) or visual estimation (cut-off: 2%). In conclusion, AID, CXCR4, CD71, and Ki67 are promising biomarkers for objectively identifying FL grade 3, potentially enhancing the reproducibility of grading and serving as independent prognostic tools. Further clinical validation in uniformly treated FL cohorts is warranted.},
}

@article {pmid41520338,
year = {2026},
author = {Janssens, DH and Codomo, CA and Otto, DJ and Silberstein, L and Ahmad, K and Henikoff, S},
title = {Sequential RNA polymerase II activation drives human hematopoiesis.},
journal = {Cell reports},
volume = {45},
number = {1},
pages = {116802},
doi = {10.1016/j.celrep.2025.116802},
pmid = {41520338},
issn = {2211-1247},
abstract = {Promoter-proximal pausing of RNA polymerase II (Pol II) primes genes for rapid activation, yet how Pol II dynamics are temporally organized in adult stem cells to enable fast and flexible responses to environmental cues remain unknown. To address this, we developed sciCUT&Tag2in1 for joint profiling of Pol II and histone modifications in single cells. By profiling over 200,000 CD34[+] hematopoietic stem cells (HSCs) and progenitors, we identify a Pol II regulatory cascade that directs the response to granulocyte colony-stimulating factor (G-CSF)-induced inflammatory stress. HSCs are activated by elevated Pol II occupancy and reduced Polycomb repression of immune response genes. Lineage commitment proceeds through sequential modes of Pol II activation, beginning with rapid pause-and-release genes, followed by slower initiate-and-release of Polycomb-repressed targets. sciCUT&Tag2in1 defines the temporal logic of how adult stem cells use paused Pol II to enable flexible lineage decisions, providing a powerful tool for studying the intersection of development, inflammation, and disease.},
}

@article {pmid41520058,
year = {2026},
author = {Fuller, H and Agasaro, OP and Guevara, JM and Darst, BF},
title = {Pre-diagnostic circulating untargeted metabolomics and risk of overall and clinically significant prostate cancer: a systematic review and meta-analysis.},
journal = {British journal of cancer},
volume = {},
number = {},
pages = {},
pmid = {41520058},
issn = {1532-1827},
support = {P50 CA097186/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; R00 CA246063/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Metabolomic dysregulation contributes to prostate cancer (PCa) pathogenesis, and studies suggest that circulating metabolites have strong potential to act as clinical biomarkers. However, evidence of associations between circulating metabolites with overall and clinically significant PCa risk has not been quantitively aggregated.

METHODS: We performed a systematic review and meta-analysis of untargeted pre-diagnostic circulating metabolomic studies across four clinically distinct outcomes: overall, low- to intermediate-risk, high- to very high-risk, and lethal PCa, each compared to controls.

RESULTS: Twelve studies were identified in the systematic review, and up to 408 metabolites were meta-analysed across the four PCa outcomes. Three, eleven, and nineteen metabolites were significantly associated with risk of overall, high- to very high-risk, and lethal PCa, respectively. Metabolites associated with high- to very high-risk PCa were significantly enriched for lipids. Limited evidence of correlation between metabolite effects across outcomes was identified, highlighting potentially unique metabolite drivers of high-risk and lethal PCa. In follow-up analyses, 13 of the significant metabolites were found to be modifiable by drugs and/or diet.

CONCLUSIONS: These findings suggest a strong potential for metabolites to inform risk of lethal PCa, which could inform risk-stratified screening strategies and facilitate the identification of targets for PCa prevention.},
}

@article {pmid41519271,
year = {2026},
author = {Nicholas, JC and Alkis, T and Bis, JC and Boerwinkle, E and Brody, JA and Clish, CB and de Vries, PS and Gao, Y and Gerzsten, RE and Guo, X and Johnson, AD and Larson, MG and Lemaitre, RN and Psaty, BM and Ramachandran, V and Reiner, AP and Rich, SS and Rodriguez, B and Rong, J and Rotter, JI and Simino, J and Smith, NL and Wilson, J and Yao, J and Morrison, AC and Yu, B and Raffield, LM},
title = {Fibrinogen-Associated Plasma Metabolites and Implications for Coagulation, Inflammation, and Vascular Diseases.},
journal = {Journal of thrombosis and haemostasis : JTH},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtha.2025.12.016},
pmid = {41519271},
issn = {1538-7836},
abstract = {BACKGROUND: Fibrinogen is a critical coagulation factor that plays an essential role in thrombosis and is elevated in individuals with chronic inflammation. Here, we used fibrinogen as a representative quantitative measure of pro-coagulant risk and evaluated metabolites associated with fibrinogen levels through non-targeted plasma metabolomic profiling (Broad and Metabolon platforms).

METHODS: Our analysis included 10,533 individuals across six U.S. based cohorts representing diverse population groups. The cross-sectional relationship between each of 789 tested metabolites and plasma fibrinogen concentration was assessed with adjustment for relevant covariates such as age, sex, body mass index, and circulating lipoprotein levels.

RESULTS: Meta-analysis of per-cohort results revealed 270 metabolites significantly associated with fibrinogen level (FDR adjusted p-value < 0.05). Lipid species such as glycerophospholipids, sphingolipids, and fatty acyls were prevalent among significantly associated metabolites; some of these may capture effects of inflammation, as supported by sensitivity analyses adjusted for C-reactive protein. Significant associations between fibrinogen levels and serotonin, thyroxine, and sex-hormone derivatives may capture endogenous influences on fibrinogen levels. Exogenous compounds and microbial co-metabolites significantly associated with fibrinogen also implicate lifestyle and microbiome risk-factors. Only a portion of fibrinogen-associated metabolites (30%) have been associated with a cardiovascular disease outcome in a prior study, suggesting the associations discovered here may provide insights on vascular biology which case-control studies may not yet be powered to detect.

CONCLUSIONS: These findings contribute to a growing list of metabolite biomarkers that may influence coagulation and inflammation pathways and may thereby contribute to vascular risk.},
}

@article {pmid41519253,
year = {2026},
author = {Thornburgh, S and Farland, LV and Harris, HR and Sonneville, KR and Neblett, MF and Field, AE and Chavarro, JE and Missmer, SA and Gaskins, AJ},
title = {Disordered Eating Behaviors during Adolescence and Risk of Endometriosis: A Prospective Cohort Study.},
journal = {Fertility and sterility},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.fertnstert.2025.12.027},
pmid = {41519253},
issn = {1556-5653},
abstract = {OBJECTIVE: Disordered eating behaviors may impact the gynecologic health of adolescents through effects on menstrual cycle function and body size; however, few studies have evaluated these associations. This study aimed to prospectively investigate the associations between individual disordered eating behaviors during adolescence, and the risk of subsequent endometriosis diagnosis.

DESIGN: Prospective, longitudinal cohort (1996-2021).

SUBJECTS: Female participants (n = 11773) from the Growing Up Today Study.

EXPOSURE: Frequency of binge eating, laxative use, and self-induced vomiting over the past year were self-reported on repeated questionnaires during follow-up.

MAIN OUTCOME MEASURES: Physician-diagnosed endometriosis was reported on repeated questionnaires during follow-up. Multivariable logistic regression models with generalized estimating equations were used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).

RESULTS: Over 25 years of follow-up, we identified 269 incident cases of endometriosis (2.3%), 190 of which were reported as laparoscopically confirmed. A total of 32% of girls reported ever binge eating, 14% reported self-induced vomiting to lose weight, and 9% reported ever using laxatives to lose weight. The odds of laparoscopically-confirmed endometriosis diagnosis was more than three-fold higher (aOR=3.07, 95% CI 1.74, 5.40) for girls who cumulatively reported self-induced vomiting more than monthly during follow-up, compared to girls who never reported self-induced vomiting. A similar effect estimate (aOR=2.41, 95% CI 1.40, 4.12 was noted for girls who reported weekly or more frequent self-induced vomiting at least once during follow-up compared to girls who reported never vomiting. Cumulative exposure to binge eating during follow-up was not associated with diagnosis of laparoscopically-confirmed endometriosis; however, girls who reported a highest ever engagement in binge eating of weekly or more had 52% lower (aOR=0.47, 95% CI 0.25, 0.90) odds of laparoscopically-confirmed endometriosis, compared to girls who reported less than weekly binge eating. Laxative use was not strongly associated with endometriosis diagnosis, although estimates were imprecise.

CONCLUSIONS: We observed that females with a greater frequency of self-induced vomiting were more likely to be diagnosed with endometriosis during follow-up, while girls with a history of frequent binge eating had a lower likelihood of endometriosis diagnosis. We found no association between laxative use and endometriosis.},
}

@article {pmid41518882,
year = {2025},
author = {Summers, C and Mallhi, K and Persinger, H and Fan, X and Gooley, TA and Dahlberg, AE and Burroughs, LM and Thakar, MS and Bhatt, NS and Petrovic, A and Hadland, B and Carpenter, PA and Baker, KS and Bleakley, M},
title = {Outcomes following hematopoietic cell transplantation for children, adolescents and young adults with relapsed acute lymphoblastic leukemia.},
journal = {Cytotherapy},
volume = {28},
number = {3},
pages = {102004},
doi = {10.1016/j.jcyt.2025.102004},
pmid = {41518882},
issn = {1477-2566},
abstract = {BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) is a common consolidation therapy for recurrent acute lymphoblastic leukemia (ALL), reducing relapse risk but causing significant morbidity, mortality, and potential impairment of growth and development in children, adolescents, and young adults (CAYA). Avoiding or delaying HCT could prevent such complications. New targeted therapies, including CD19 chimeric antigen receptor (CAR) T cells, have increased the number of recurrent ALL patients who might achieve long-term remission without HCT. However, outcomes of delaying HCT beyond second complete remission (CR2) in the modern era remain unclear.

OBJECTIVE: To compare outcomes of HCT performed in CR2 versus third or later remission (CR3+) in CAYA with ALL.

METHODS: We retrospectively reviewed CAYA who underwent first HCT for ALL in CR2 (n = 81) or CR3+ (n = 44) at our institution from 2000-2020.

RESULTS: For all patients, estimated 1-year overall survival (OS), relapse, and nonrelapse mortality (NRM) were 76%, 20.8%, and 9.6%; 3-year estimates were 69%, 30%, and 9.6%, respectively. At 3 years, OS was 77% for CR2 versus 53% for CR3+, and NRM was 6% versus 16%. Adjusted hazard ratios (HR) for CR3+ versus CR2 were: overall mortality HR 1.87 (95% CI, 1.06-3.31), relapse HR 1.28 (95% CI, 0.66-2.50), and NRM HR 2.63 (95% CI, 1.08-6.39).

CONCLUSIONS: CAYA with ALL undergoing HCT in CR3+ experienced higher NRM and worse survival compared to those transplanted in CR2. Efforts to reduce NRM in multiply relapsed patients are required.},
}

@article {pmid41515121,
year = {2025},
author = {Park, J and Kadro, ZO and Honvoh, GD and Domeniciello, AF and Ramsden, CE and Faurot, KR and Miller, VE},
title = {Associations Between Dietary Intakes of Omega-3 Fatty Acids, Blood Levels, and Pain Interference in People with Migraine: A Path Analysis of Randomized Trial Data.},
journal = {Nutrients},
volume = {18},
number = {1},
pages = {},
pmid = {41515121},
issn = {2072-6643},
support = {RO1-AT007813/AT/NCCIH NIH HHS/United States ; Intramural Program/AG/NIA NIH HHS/United States ; T32-AT003378/AT/NCCIH NIH HHS/United States ; Gift to the Department of Physical Medicine and Rehabilitation//Dr. John M. Davis/ ; },
mesh = {Humans ; *Migraine Disorders/diet therapy/blood ; Female ; Male ; *Docosahexaenoic Acids/blood/administration & dosage ; *Eicosapentaenoic Acid/blood/administration & dosage ; Adult ; *Fatty Acids, Omega-3/blood/administration & dosage ; Middle Aged ; *Diet ; *Pain ; },
abstract = {Background/Objectives: Increasing evidence supports the hypothesis that dietary intervention can improve pain among individuals with headaches, including migraine, a highly prevalent condition that can be disabling. Non-pharmacologic treatments for migraine are particularly attractive. In this secondary analysis of 182 participants enrolled in a randomized controlled trial of a dietary intervention designed to increase omega-3 (n-3) compared with a control diet, we examined the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both thought to decrease inflammatory processes. Methods: Path models with two time points (baseline and 16 weeks after randomization), were used to test the relationships between exposures of n-3 blood levels and self-reported dietary intake on outcomes of pain interference using the PROMIS pain interference scale and the Headache Impact Test (HIT-6). Model building was based on our published conceptual model. Results: Good fit was demonstrated for both models (EPA model: CFI = 0.984, RMSEA = 0.039, and SRMR = 0.045; DHA model: CFI = 0.981, RMSEA = 0.040, and SRMR = 0.040). Both EPA and DHA in the blood at 16 weeks were associated with lower levels of pain interference, but the effect for EPA was stronger (B = -0.56, p < 0.001 for EPA, and B = -0.43, p = 0.057 for DHA). Conclusions: Our findings are consistent with an indirect pathway linking diet to pain interference through blood levels of EPA and DHA in migraine.},
}

Humans
*Migraine Disorders/diet therapy/blood
Female
Male
*Docosahexaenoic Acids/blood/administration & dosage
*Eicosapentaenoic Acid/blood/administration & dosage
Adult
*Fatty Acids, Omega-3/blood/administration & dosage
Middle Aged
*Diet
*Pain

@article {pmid41514630,
year = {2025},
author = {Alban, J and Bowen, RC and Reichstein, DA and McKean, M and Lutzky, J and Weis, E and Carvajal, RD and Dulka, S and Morse, BG and Butler, MO and Rapisuwon, S and Kim, KB and Chandrasekaran, S and Warner, AB and Zager, JS and Chmielowski, B and Patel, SP and Hernandez-Aya, LF and Correa, ZM and Fecher, LA and Najjar, YG and Montazeri, K and Shoushtari, AN and Javed, A and Gombos, DS and Salama, AKS and Tsai, K and Miller, FH and Khushalani, N and Seedor, RS and Lipson, EJ and Reddy, SA and Buchbinder, E and Bhatia, S and Pavlick, A and Mehmi, I and Aaberg, T and Ikeguchi, AP and Kim, IK and Walter, SD and Singh, AD and Sullivan, RJ and Choi, JS and Williams, BK and Orloff, M and Mruthyunjaya, P and Schollenberger, MD and Gandhi, N and Harbour, JW and Chandra, S},
title = {Metastatic Uveal Melanoma Surveillance: A Delphi Panel Consensus.},
journal = {Cancers},
volume = {18},
number = {1},
pages = {},
pmid = {41514630},
issn = {2072-6694},
abstract = {BACKGROUND/OBJECTIVES: Uveal melanoma is a rare but aggressive intraocular malignancy that metastasizes in up to half of patients, most commonly to the liver, despite effective local treatment. In the absence of robust evidence, there are no standardized guidelines for post-treatment surveillance, resulting in wide variation in imaging modalities, frequency, and duration across physicians and institutions. This study aimed to develop expert consensus recommendations for surveillance strategies in patients with uveal melanoma.

METHODS: A modified Delphi method was conducted across three iterative survey rounds between September 2024 and February 2025 using an online platform. Panelists included medical oncologists, ocular oncologists, radiologists, and surgical oncologists from North America. A multidisciplinary steering committee developed statements addressing risk-based surveillance using both molecular and clinical prognostic factors, including gene expression profiling (GEP) and PRAME status. Consensus was defined a priori as ≥70% of panelists rating a statement 7-9 on a 9-point Likert scale.

RESULTS: Forty-nine experts were invited, and 41 completed at least one survey round. The panel represented 17 U.S. states, Washington, D.C., and two Canadian provinces. Twelve statements reached stable consensus, including recommendations for imaging modality, frequency, and duration in intermediate- and high-risk patients. Although there was agreement that low-risk patients warrant surveillance, no consensus was reached on the optimal approach for this group.

CONCLUSIONS: This is the first study to provide consensus-based guidance incorporating GEP and PRAME status into surveillance recommendations for uveal melanoma, offering a standardized framework to guide clinical practice and future research.},
}

@article {pmid41514580,
year = {2025},
author = {Pettenger-Willey, CM and Laszlo, GS and Gang, M and Cole, FM and Godwin, CD and Erraiss, S and Chanana, P and Kehret, AR and Li, J and Barton, JW and Yochim, MM and Rodríguez-Arbolí, E and Walter, RB},
title = {DNA Damage Sensing and TP53 Function as Modulators of Sensitivity to Calicheamicin-Based Antibody-Drug Conjugates for Acute Leukemia.},
journal = {Cancers},
volume = {18},
number = {1},
pages = {},
pmid = {41514580},
issn = {2072-6694},
support = {N/A//Pfizer/ ; U54-DK106829/DK/NIDDK NIH HHS/United States ; T32-HL007093//National Heart Lung and Blood Institute/ ; },
abstract = {BACKGROUND/OBJECTIVES: Approved for treatment of acute leukemia, gemtuzumab ozogamicin (GO) and inotuzumab ozogamicin (InO) are antibody-drug conjugates (ADCs) that deliver a toxic calicheamicin (CLM) derivative. The resistance mechanisms to GO/InO remain incompletely understood.

METHODS: We performed a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 screen for CLM sensitivity genes, and then performed confirmatory cytotoxicity assays.

RESULTS: Several DNA damage pathway regulation genes were identified, most notably TP53. Across 13 acute leukemia cell lines, the six TP53-mutant cell lines (TP53[MUT]) were indeed 10- to 1000-fold less sensitive to CLM than the seven TP53[WT] cell lines. In five TP53[WT/KO] syngeneic cell line pairs we generated, TP53[KO] cells were significantly less sensitive to CLM than their TP53[WT] counterparts. In TP53[WT] but not TP53[MUT] cells, the MDM2 inhibitor and p53 activator, idasanutlin, enhanced CLM cytotoxicity, demonstrating that decoupling of cells from MDM2-p53 regulation sensitizes leukemia cells to CLM. The ATM inhibitors AZD1390 and lartesertib also significantly enhanced CLM efficacy but did so independent of the TP53 status. In contrast, neither an ATR inhibitor, Chk1/Chk2 inhibitor, Chk2 inhibitor, or a PARP inhibitor significantly impacted CLM-induced cytotoxicity across the thirteen cell lines. Together, our studies identify ATM, MDM2, and TP53-which are in the same cellular response to DNA damage pathway-as key modulators of CLM-induced cytotoxicity in acute leukemia cells.

CONCLUSIONS: These results support further evaluation of combination therapies with corresponding small-molecule inhibitors (currently pursued for therapy of other cancers) toward clinical testing as novel strategies to increase the efficacy of CLM-based ADCs such as GO and InO.},
}

@article {pmid41513413,
year = {2026},
author = {Segawa, I and Ortblad, KF and Kadama, H and Natukunda, D and Muwonge, TR and Laker, EAO and Nsubuga, R and Akello, S and Tamale, WJ and Kiragga, A and Mujugira, A},
title = {Optimising community pharmacy PrEP delivery for cisgender female sex workers in Uganda: Protocol for a mixed-methods study.},
journal = {BMJ open},
volume = {16},
number = {1},
pages = {e111220},
doi = {10.1136/bmjopen-2025-111220},
pmid = {41513413},
issn = {2044-6055},
mesh = {Humans ; Uganda/epidemiology ; *Sex Workers/statistics & numerical data ; Female ; *HIV Infections/prevention & control ; *Pre-Exposure Prophylaxis/methods ; *Health Services Accessibility ; *Community Pharmacy Services/organization & administration ; Pharmacies ; Research Design ; },
abstract = {INTRODUCTION: Pre-exposure prophylaxis (PrEP) use among cisgender female sex workers (FSWs), a population at disproportionately high HIV acquisition risk in Uganda, remains suboptimal. Uptake and continued use are constrained by barriers, such as limited clinical hours, long distances to access facility-based PrEP services, and high mobility among FSWs. Community pharmacies may offer a more accessible PrEP delivery model due to extended operating hours and convenient locations. This study aims to evaluate the accessibility and capacity of pharmacies in Kampala, Uganda, to serve as potential sites for PrEP delivery.

METHODS AND ANALYSIS: We will conduct a concurrent mixed-methods study combining geospatial mapping, structured surveys, a discrete choice experiment (DCE), and in-depth interviews (IDIs). First, the study will compare the reach and accessibility of PrEP services through community pharmacies versus public healthcare facilities. To highlight PrEP service reach, we will use geospatial analysis to map pharmacies, PrEP clinics, FSW hotspots (i.e., areas where sex is exchanged), and HIV incidence. We will also calculate a PrEP facility needs ratio (number of PrEP facilities/HIV incidence) for each of Kampala's administrative divisions and estimate travel distance and time to access PrEP services using cost-distance analysis. Perceived accessibility of PrEP services will be assessed through FSW surveys (n=50) and IDIs (n=20-30), guided by Levesque's framework. Then, we will evaluate pharmacy capacity via surveys (n=274) and IDIs (n=20-30), exploring infrastructure, resources, and staff perspectives, informed by the Consolidated Framework for Implementation Research. Additionally, a DCE will be embedded in the pharmacy survey to elicit staff preferences for delivery approaches and analysed using mixed logit models. Finally, we will integrate quantitative and qualitative findings to provide a broad assessment of whether pharmacies are suitable venues for PrEP delivery to FSWs in Kampala. Enrolment will begin by April 2026 for FSWs and July 2026 for pharmacy staff.

ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Infectious Diseases Institute Research Ethics Committee (IDI-REC-2025-175) and the Uganda National Council for Science and Technology (HS6178ES). Written informed consent will be obtained from all participants. We will disseminate study findings through stakeholder meetings, scientific conferences, and peer-reviewed publications.},
}

Humans
Uganda/epidemiology
*Sex Workers/statistics & numerical data
Female
*HIV Infections/prevention & control
*Pre-Exposure Prophylaxis/methods
*Health Services Accessibility
*Community Pharmacy Services/organization & administration
Pharmacies
Research Design

@article {pmid41509490,
year = {2025},
author = {Liu, D and Song, B and Li, Z and Zhang, S and Fabiha, T and Zhao, J and Inoki, A and Piccand, J and Soh, CL and Dixon, G and Zhong, A and Hu, N and Luo, R and Ozlusen, B and Menon, V and Zhou, T and Qiu, X and Gradwohl, G and Yang, D and Dey, K and Sun, W and Li, W and Huangfu, D},
title = {A stem cell knockout village reveals lineage rewiring and a non-canonical islet cell fate in monogenic diabetes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41509490},
issn = {2692-8205},
abstract = {Genetics studies have identified a core set of regulators essential for pancreatic β cell development, many of which are mutated in monogenic diabetes. However, how these mutations alter developmental trajectories to produce pathological cell states remains elusive. Here we introduce a knockout village framework that enables longitudinal scRNA-seq profiling of 79 human pluripotent stem cell mutant lines targeting 30 developmental regulators, including 15 diabetes genes, across five islet differentiation stages. We show that loss of lineage regulators impairs β cell formation in a stage-specific manner and rewires developmental trajectories towards competing lineages. Notably, several monogenic diabetes gene mutations drive a shift from β cells to enterochromaffin (EC)-like cells, a recently recognized non-canonical islet cell fate. These EC-like cells exhibit incomplete activation of hormone regulation programs, along with elevated neuron signatures. Leveraging the diversity of cell fate outcomes across mutants, we predicted and experimentally validated ISL1 as a key downstream effector of PDX1 and PAX6 that safeguards β cell identity against an EC-like fate. Together, our findings reveal cell fate rewiring as a widespread, previously underappreciated pathological mechanism in monogenic diabetes and establish a scalable platform for uncovering developmental vulnerabilities in human genetic disorders.},
}

@article {pmid41509443,
year = {2025},
author = {Yanagi, KS and Chen, BJ and Kunjo, SO and Topalidou, I and Lehrbach, N},
title = {Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41509443},
issn = {2692-8205},
abstract = {The ubiquitin proteasome system (UPS) is the primary mechanism for targeted protein degradation in eukaryotic cells. Dysfunction of this system is a driver of human disease and a hallmark of aging and late-onset neurodegenerative disorders. Understanding the mechanisms that ensure robust protein turnover may provide new avenues for treatment in these contexts. E3 ubiquitin ligases play critical roles in supplying ubiquitinated substrates to the proteasome, with HUWE1 being an enormous, versatile, and highly conserved member of this family. Here, we show that the C. elegans HUWE1 ortholog, EEL-1, contributes to robust protein turnover during challenges to the proteolytic capacity of the proteasome. We demonstrate that the ability of EEL-1/HUWE1 to safeguard protein turnover requires ubiquitin-binding domains within the substrate-binding arena and the HECT-type ubiquitin ligase activity, supporting a model in which EEL-1 ensures degradation by increasing ubiquitination of pre-ubiquitinated substrates. EEL-1 contains extensive lysine-deficient regions, found at conserved locations in its substrate-binding arena. Through unbiased mutagenesis screening and precise engineering of the EEL-1 protein, we uncover that introducing lysine residues into these regions is detrimental to UPS function. Together, our findings indicate a central and evolutionarily ancient role for EEL-1/HUWE1 in maintaining optimal UPS function and support targeting this E3 for therapeutic manipulation.},
}

@article {pmid41512237,
year = {2026},
author = {Castellino, SM and Li, H and Herrera, AF and LeBlanc, M and Parsons, SK and Unger, JM and Punnett, A and Hodgson, D and Keller, FG and Drachtman, RA and Lamble, A and Forlenza, CJ and Doan, A and Rutherford, SC and Evens, AM and Little, RF and Smith, MA and Hoppe, BS and Song, JY and Smith, SM and Friedberg, JW and Kelly, KM},
title = {Three-Year Follow-Up of Nivolumab-AVD Versus Brentuximab Vedotin-AVD in Adolescents With Advanced-Stage Classic Hodgkin Lymphoma on S1826.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2500203},
doi = {10.1200/JCO-25-00203},
pmid = {41512237},
issn = {1527-7755},
abstract = {We present a subset analysis on the adolescent cohort of the S1826 randomized phase three trial, comparing nivolumab, doxorubicin, vinblastine, dacarbazine (N-AVD) to brentuximab vedotin-AVD (BV-AVD) in newly diagnosed advanced-stage (AS, stages III and IV) classic Hodgkin lymphoma (cHL). Among 994 patients enrolled, 24% (n = 240) were age 12-17 years. The 3-year progression-free survival (PFS) was significantly higher in the N-AVD group (93% [95% CI, 87 to 96]) compared with the BV-AVD group (82% [95% CI, 73 to 88]; hazard ratio, 0.37 [95% CI, 0.17 to 0.80]). One N-AVD and two BV-AVD patients received protocol-specified residual site radiotherapy (RT). Rates of febrile neutropenia and sepsis were low in both groups. Severe immune-related adverse events were infrequent, although thyroid dysfunction was seen in 7% with N-AVD. Sensory neuropathy (grade ≥2) was more frequent with BV-AVD (14% v 7%) by clinician report. Although premature discontinuation of therapy was reported in 12 N-AVD patients and four BV-AVD patients, no PFS events were noted in the N-AVD group. Patient-reported outcomes indicated less toxicity with N-AVD. N-AVD demonstrated high 3-year PFS in adolescents with AS cHL, with minimal RT use. S1826 exemplifies the benefits of harmonized clinical trial protocols, resulting in timely access to novel agents for adolescents.},
}

@article {pmid41512041,
year = {2026},
author = {Gao, J and Brusselmans, M and Carvalho, LM and Suchard, MA and Baele, G and Matsen, FA},
title = {Biological causes and impacts of rugged tree landscapes in phylodynamic inference.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {2},
pages = {e2510938123},
doi = {10.1073/pnas.2510938123},
pmid = {41512041},
issn = {1091-6490},
support = {R01 AI162611/AI/NIAID NIH HHS/United States ; R01 AI153044/AI/NIAID NIH HHS/United States ; S10OD028685//Fred Hutchinson Cancer Center (FHCRC)/ ; G0E1420N//Fonds Wetenschappelijk Onderzoek (FWO)/ ; G098321N//Fonds Wetenschappelijk Onderzoek (FWO)/ ; 101094685//EC | ERC | HORIZON EUROPE European Research Council (ERC)/ ; },
mesh = {*Phylogeny ; Bayes Theorem ; Genetic Variation ; Models, Genetic ; },
abstract = {Phylodynamic analysis has been instrumental in elucidating epidemiological and evolutionary dynamics of pathogens. Bayesian phylodynamics integrates out phylogenetic uncertainty, which is typically substantial in phylodynamic datasets due to limited genetic diversity. Phylodynamic inference does not, however, scale with modern datasets, partly due to difficulties in traversing tree space. Here, we characterize tree space and landscape in phylodynamic inference and assess its impacts on analysis difficulty and key biological estimates. By running extensive Bayesian analyses of 15 classic large phylodynamic datasets and carefully analyzing the posterior samples, we find that the posterior tree landscape is diffuse yet rugged, leading to widespread tree sampling problems that usually stem from sequences in a small part of the tree. We develop clade-specific diagnostics to show that a few sequences-including putative recombinants and recurrent mutants-frequently drive the ruggedness and sampling problems, although existing data-quality tests show limited power to detect them. The sampling problems can significantly impact phylodynamic inferences or distort major biological conclusions; the impact is usually stronger on "local" estimates (e.g., introduction history) associated with particular clades than on "global" parameters (e.g., demographic trajectory) governed by general tree shape. We evaluate existing Markov chain Monte Carlo diagnostics and diagnostics developed here, and offer strategies for optimizing phylodynamic analysis settings and mitigating sampling problem impacts. Our findings highlight the need and directions to develop efficient traversal over rugged tree landscapes, ultimately advancing scalable and reliable phylodynamics.},
}

*Phylogeny
Bayes Theorem
Genetic Variation
Models, Genetic

@article {pmid41510809,
year = {2025},
author = {Sutliff, NA and Chao, E and Bennett, SR and Nip, Y and Lakhdari, O and Canton, DA and Zhu, Y and Tapscott, SJ},
title = {Identification of KHDC1L, a DUX4-regulated protein, as a novel plasma biomarker in facioscapulohumeral muscular dystrophy.},
journal = {Human molecular genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/hmg/ddaf183},
pmid = {41510809},
issn = {1460-2083},
abstract = {Facioscapulohumeral muscular dystrophy (FSHD) is caused by aberrant expression of the double homeobox transcription factor DUX4 in skeletal muscle. Because direct measurement of DUX4 in FSHD muscle is technically challenging, DUX4-regulated transcripts in muscle biopsies have been used as surrogates; however, this approach is invasive, limited to a single muscle, and less suitable for repeated monitoring. Thus, we sought to identify DUX4-regulated circulating biomarkers that could integrate DUX4 activity across all affected muscles and enable more frequent measurement. We performed mass spectrometry on conditioned media from DUX4-inducible immortalized human myoblasts (MB135iDUX4) and identified a top candidate-KHDC1L, the protein product of a DUX4-regulated mRNA previously shown to correlate with DUX4 expression in muscle. Western blotting confirmed KHDC1L release into the supernatant of DUX4-expressing cells. Plasma profiling demonstrated elevated KHDC1L levels in individuals with FSHD compared to healthy controls, supporting its role as a circulating readout of DUX4 activity. These findings suggest that plasma KHDC1L is a potential pharmacodynamic marker of DUX4 activity, providing a minimally invasive tool for disease monitoring and a potential response marker to evaluate emerging FSHD therapies.},
}

@article {pmid41052404,
year = {2026},
author = {Valtis, YK and Lin, C and Nemirovsky, D and Devlin, S and Rejeski, K and Curran, KJ and Wang, X and Shah, NN and Jeyakumar, N and Miller, K and Zhang, A and Kota, VK and Al Darobi, AH and Muhsen, I and Sasine, J and Aldoss, I and Advani, AS and Reshef, R and Chen, EC and Kopmar, N and Tsai, SB and Hilal, T and Shah, BD and Faramand, R and Solh, MM and Tan, V and Bezerra, E and Battiwalla, M and Ramakrishnan, A and Mathews, J and Shaughnessy, P and Mountjoy, L and Hoeg, RT and Dykes, KC and Logan, AC and Kumaran, MV and Schwartz, M and Tracy, S and Moore, J and Odstrcil Bobillo, S and Frey, NV and Connor, M and Ladha, A and Dholaria, B and Sutherland, K and Roloff, GW and Muffly, LS and Park, JH},
title = {CAR HEMATOTOX independently predicts outcomes after CD19 CAR-T therapy for acute lymphoblastic leukemia.},
journal = {Blood advances},
volume = {10},
number = {1},
pages = {276-288},
doi = {10.1182/bloodadvances.2025017526},
pmid = {41052404},
issn = {2473-9537},
mesh = {Humans ; Male ; Female ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/mortality/diagnosis ; Middle Aged ; Adult ; *Immunotherapy, Adoptive/methods/adverse effects ; *Antigens, CD19/immunology ; Treatment Outcome ; Prognosis ; *Receptors, Chimeric Antigen/immunology ; Aged ; Young Adult ; Adolescent ; },
abstract = {Chimeric antigen receptor (CAR) T-cell (CAR-T) treatment for B-cell acute lymphoblastic leukemia (ALL) induces high initial response rates, but most patients relapse. Low disease burden (often defined as <5% blasts in the bone marrow) is associated with better outcomes. CAR HEMATOTOX (HT) is a score using prelymphodepletion hematologic and inflammatory parameters to predict outcomes in lymphoma. Here, we assess its prognostic utility in a large multicenter adult B-cell ALL cohort. Patients who received brexucabtagene autoleucel across 33 centers in North America were included as part of the Real-World Outcomes Collaborative of CAR-T in Adult ALL (ROCCA) consortium. An independent cohort of 61 patients with ALL treated with an investigational CD19 CAR-T therapy at 1 center was also described. Among 199 ROCCA consortium patients, 43 (22%) patients with HTlow scores had lower rates of delayed neutrophil recovery than those with HThigh scores (26% vs 52%, P = .002) and fewer severe infections (2.5% vs 18.8%, P = .011). They also had higher response rates, overall survival (OS), and event-free survival (EFS), as well as lower nonrelapse mortality and cumulative incidence of relapse. The survival differences remained significant after multivariable adjustment for disease burden and other covariates. In the investigational cohort of 61 patients, patients with HTlow scores had improved OS and EFS, as well as higher peak CAR-T expansion. In summary, CAR HT score is a prognostic factor independent of disease burden in adult ALL. HTlow score is associated with superior outcomes after CD19 CAR-Ts and higher CAR-T expansion in a single-center cohort. These trials were registered at www.clinicaltrials.gov as #NCT01044069 and #NCT01860937.},
}

Humans
Male
Female
*Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/mortality/diagnosis
Middle Aged
Adult
*Immunotherapy, Adoptive/methods/adverse effects
*Antigens, CD19/immunology
Treatment Outcome
Prognosis
*Receptors, Chimeric Antigen/immunology
Aged
Young Adult
Adolescent

@article {pmid41509676,
year = {2026},
author = {Sloan, A and Mortezavi, M and Gerhart, J and Banerjee, A and Alami, NN and Najera, I and Ahadieh, S and Dalam, AB and Schiffer, JT and Patel, R and Johnston, C},
title = {Orolabial and Genital Herpes Clinical Trials: A Meta-analysis of Endpoints.},
journal = {Open forum infectious diseases},
volume = {13},
number = {1},
pages = {ofaf776},
pmid = {41509676},
issn = {2328-8957},
abstract = {Although several antiviral agents are licensed for the treatment of orolabial and genital herpes simplex virus infections, new therapies are needed. Trial design is challenging for these indications due to the heterogeneity of endpoints in prior trials. We conducted a systematic review and meta-analysis of randomized placebo-controlled trials published between 1995 and 2024 consisting of adults with established herpes simplex virus infection who were immunocompetent and nonpregnant. A total of 22 articles met the inclusion criteria. For episodic treatment, endpoints included time to healing, proportion with an aborted lesion, and time to cessation of symptoms. For daily suppressive therapy, endpoints included time to first recurrence, proportion recurrence-free at 1 year, and total shedding rate. We observed that over the last 30 years, clinical trials have used various endpoints with nonstandardized definitions. A reassessment of appropriate endpoints along with regulatory guidance would assist with consistent study design for evaluation of new agents.},
}

@article {pmid41509072,
year = {2025},
author = {White, AN and Ingersoll, R and Eswaraka, J and Uthamanthil, R and Roble, G and Chitty, AI and Nikolaidis, N and Vinard, A and Kraft, M and Winter, MK},
title = {Voices from the Bench: Focus Group Insights on Shared Research Resource Sustainability Amid Federal Policy Shifts.},
journal = {Journal of biomolecular techniques : JBT},
volume = {36},
number = {4},
pages = {25-34},
pmid = {41509072},
issn = {1943-4731},
mesh = {Humans ; Focus Groups ; United States ; *Biomedical Research/economics ; },
abstract = {Shared Research Resources (SRRs) are essential for sustaining research excellence, particularly in financially constrained environments. This study examines how federal policy uncertainties exacerbate existing challenges in SRR operations and management. Findings from focus groups-including over 220 leaders in academic administration and SRRs-highlight that staffing, funding, and cross-campus collaboration disproportionately impact resource-limited institutions, widening disparities in research capabilities. Evaluating SRRs' role in supporting research during financial instability is critical. Active administrative engagement in supporting SRRs helps institutions to secure funding and align priorities with institutional goals. SRRs improve operational efficiency through shared infrastructure models and standardized procurement policies, reducing duplication and optimizing resource utilization. Workforce adaptability is key to sustainability, with cross-training and strategic recruitment fostering resilience amid financial uncertainty. This study underscores the interconnected nature of funding diversification, leadership alignment, operational efficiency, workforce adaptability, and policy reform in sustaining SRR systems. This study draws on collective insights from SRR staff across all organizational levels, from technical personnel and directors to administrators and institutional leaders, to capture a comprehensive, ground-level perspective on the conditions necessary for long-term viability. Institutions that recognize SRRs as strategic partners in addressing systemic research barriers will be better positioned to foster a more equitable, efficient, and sustainable research ecosystem.},
}

Humans
Focus Groups
United States
*Biomedical Research/economics

@article {pmid41506486,
year = {2026},
author = {Gem, H and Ebadi, M and Sebastian, G and Abasaeed, R and Lloid, M and Dean, DR and Rashidi, A},
title = {Longitudinal multi-compartment oral mucositis assessment in adults undergoing myeloablative allogeneic hematopoietic cell transplantation: a contemporary prospective cohort analysis.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2026.01.004},
pmid = {41506486},
issn = {2666-6367},
abstract = {BACKGROUND: Oral mucositis (OM) is a frequent, debilitating complication of myeloablative allogeneic hematopoietic cell transplantation (HCT). OM grading tools used in HCT practice rely on subjective or summary scoring, potentially missing clinically important detail.

OBJECTIVE: To test the performance of Oral Mucositis Assessment Scale (OMAS), a validated comprehensive OM assessment tool that collects granular objective findings from 7 intraoral sites, in a contemporary cohort.

STUDY DESIGN: We longitudinally evaluated site-specific OM characteristics using OMAS in 47 myeloablative allogeneic HCT recipients.

RESULTS: A total of 249 assessments were completed at baseline (pre-conditioning) and on days +7, +14, +21, +28, and +84 post-transplant. Total and site-specific scores strongly correlated with patient-controlled analgesia use. Day +7 involvement of floor of mouth (P = 0.013), soft palate (P = 0.008), and ventrolateral tongue (P = 0.003) were associated with a greater total mucositis score. OM was overall more severe in men, driven by higher scores on day +7 (P = 0.013) and in the soft palate (P = 0.013). Graft-versus-host disease prophylaxis regimens based on post-transplantation cyclophosphamide or methotrexate led to more severe day +14 OM than those based on mycophenolate mofetil (P = 0.028).

CONCLUSION: In this prospective analysis of myeloablative allogeneic HCTs in a contemporary cohort, OMAS provided clinically relevant, granular, site-specific data not captured by popular summary-based scoring systems. We expect our findings to facilitate the development of effective strategies to prevent and treat OM.},
}

@article {pmid41506266,
year = {2026},
author = {Lu, G and Zhang, S and Feng, M and Kim, E and Cho, D and Kim, JH and Caris, H and Silberstein, L and Choi, GB and Huh, JR},
title = {In vivo detection of immune responses via cytokine activity labeling.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2025.12.011},
pmid = {41506266},
issn = {1097-4172},
abstract = {While much is known about the identity and regulation of cytokine-producing cells, the cell types that respond to cytokines remain largely uncharacterized. To address this knowledge gap, we developed "cytokine cellular locating platforms" (CyCLoPs), a reporter system that translates cytokine receptor engagement into a genetically traceable signal. In vitro, CyCLoPs demonstrated high specificity, robust signal-to-background ratios, and broad applicability for probing diverse cytokine receptor interactions. In vivo, interleukin (IL)-17A-CyCLoPs reporter mice enabled the identification of IL-17A-responsive intestinal epithelial cells predominantly localized in the ileal villi following commensal bacterial colonization. Interferon-gamma (IFN-γ)-CyCLoPs reporter mice allowed for the detection of IFN-γ-exposed CD8[+] T cells within tumors, which expressed CD36, CD38, and leptin receptor and displayed gene signatures associated with reduced effector function. Collectively, CyCLoPs offers a platform for the direct visualization and characterization of cytokine-induced cellular responses and provides a tool for investigating how cytokines orchestrate distinct immunological outcomes in health and disease.},
}

@article {pmid41504443,
year = {2026},
author = {Kara, D and Pancera, M and Hassanzadeh-Ghassabeh, G and Schoonooghe, S and Masic, V and Hartley-Tassell, L and Mishra, BP and Ve, T and Haselhorst, T and von Itzstein, M and Hansman, GS},
title = {Structural insights into a broadly reactive nanobody that binds pathogenic and non-pathogenic lagoviruses.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0199025},
doi = {10.1128/jvi.01990-25},
pmid = {41504443},
issn = {1098-5514},
}

@article {pmid41503158,
year = {2026},
author = {Elz, AE and Gratz, D and Long, A and Sowerby, D and Hadadianpour, A and Newell, EW},
title = {Evaluating the practical aspects and performance of commercial single-cell RNA sequencing technologies.},
journal = {NAR genomics and bioinformatics},
volume = {8},
number = {1},
pages = {lqaf215},
pmid = {41503158},
issn = {2631-9268},
mesh = {*Single-Cell Analysis/methods/economics ; Humans ; *Sequence Analysis, RNA/methods/economics ; Transcriptome ; Gene Expression Profiling/methods ; Leukocytes, Mononuclear/metabolism ; Receptors, Antigen, T-Cell/genetics ; },
abstract = {The rapid development of updated and new commercially available single-cell transcriptomics platforms provides users with a range of experimental options. Cost, sensitivity, throughput, flexibility, and ease of use all influence the selection of an optimal workflow. We performed a comprehensive comparison of single-cell transcriptomic approaches using multiple standardized PBMCs from different donors. We report on standard single-cell metrics, including cell recovery, sequencing efficiency, sensitivity, cell annotation, and differential gene expression for seven recently available kits that interrogate whole transcriptome mRNA, and two that incorporate TCR profiling. We also discuss workflow throughput, sample requirements, timing, cost, and labor as critical factors to consider. Apart from the platform-specific experimental constraints, our findings highlight how differences in cell recovery and sensitivity influence the ability to resolve niche cell subtypes such as CD4 + and CD8 + T-cells. Platforms with higher intra-sample variation had reduced sequencing efficiency, which cumulatively impacts reproducibility and overall experiment cost. By including TCR chain recovery for multiple donors, we provide the first comparison of T-cell specific performance in the only assays available for single cell TCR recovery. This work provides a basis by which users can balance performance and practical considerations when selecting a single-cell RNA sequencing platform.},
}

*Single-Cell Analysis/methods/economics
Humans
*Sequence Analysis, RNA/methods/economics
Transcriptome
Gene Expression Profiling/methods
Leukocytes, Mononuclear/metabolism
Receptors, Antigen, T-Cell/genetics

@article {pmid41503123,
year = {2026},
author = {Özpolat, T and Byrne, DA and Bailey, SL and Chauhan, A and Reisz, JA and Johnson, HJ and Doan, J and Ronquillo, M and Adili, R and Fu, X and D'Alessandro, A and Stolla, M},
title = {Transfusion-induced functional and metabolic shifts in stored platelets: limitations of in vitro assessment.},
journal = {Blood vessels, thrombosis & hemostasis},
volume = {3},
number = {1},
pages = {100120},
pmid = {41503123},
issn = {2950-3272},
abstract = {The impact of the stored platelet extracellular environment on function and the ability of platelets to change their function upon transfer into in vivo environments remain poorly understood. Human platelets were stored ex vivo at 20°C to 24°C (room temperature-stored platelets [RTPs]) or 1°C to 6°C (cold-stored platelets [CSPs]) and tested for function in the concomitant storage plasma or fresh plasma. In mice, we tested platelet function after ex vivo storage in concomitant plasma and after transfusion to mice ex vivo and in vivo. We also investigated stored platelet-rich plasma before and after transfusion to mice for metabolomics by liquid chromatography-tandem mass spectrometry. In in vitro, human RTPs showed a greater ability than CSPs to improve αIIbβ3 integrin activation upon dilution with fresh frozen plasma. Mouse RTPs' in vitro integrin activation improved more than that for CSPs after transfusion. Surprisingly, in mice, CSPs facilitated significantly greater platelet accumulation than RTPs in vivo. In contrast, fibrin generation was significantly more robust in RTPs than in CSPs during the early stages of hemostasis. In mouse RTPs, more metabolites changed significantly upon transfusion than in mouse CSPs. Transfusion decreased carnitine species, fatty acid metabolites, and amino acids only in RTPs, whereas polyamines decreased only in CSPs. The recovery from storage-induced oxidative stress was more complete in RTPs than in CSPs. Our findings highlight the severe limitations of in vitro testing of stored platelets. Platelet-rich plasma undergoes profound changes in metabolomic composition following transfusion. We further demonstrate the ability of platelets to undergo marked changes upon transfusion in RTPs more so than CSPs.},
}

@article {pmid41502557,
year = {2026},
author = {Franzese, C and Tanadini-Lang, S and Verellen, D and Wiersema, L and Hörner-Rieber, J and Romero, AM and Pasquier, D and Bruynzeel, A and Boda-Heggemann, J and Depuydt, T and Sibolt, P and Douir, N and Kuncman, Ł and Beijst, C and Stephens, H and de la Pinta, C and Cuccia, F and Milder, M and Nicosia, L and Onishi, H and Louie, AV and Sahgal, A and Lo, SS and Slotman, BJ and Guckenberger, M and Scorsetti, M},
title = {Clinical practice, barriers to implementation, and priorities for equitable access of Stereotactic Body Radiation Therapy: An analysis of the global status by the ESTRO SBRT Focus Group.},
journal = {Clinical and translational radiation oncology},
volume = {57},
number = {},
pages = {101096},
pmid = {41502557},
issn = {2405-6308},
abstract = {BACKGROUND: Stereotactic Body Radiation Therapy (SBRT) has become an established treatment for several primary and metastatic malignancies; however, considerable heterogeneity remains in its definition, clinical indications, and technical delivery.

METHODS: In May 2025, the SBRT Focus Group of the European Society for Radiotherapy and Oncology (ESTRO), in collaboration with International Stereotactic Radiosurgery Society (ISRS), the Radiosurgery Society (RSS), and the Japanese Society for Radiation Oncology (JASTRO), conducted a global survey. A 44-item questionnaire explored SBRT indications, technical aspects, dose/fractionation, and barriers to implementation. Descriptive statistics summarized the responses.

RESULTS: Overall, 289 professionals from 59 countries participated. Routine use of SBRT was reported by 96.6 % of respondents, with lung, bone, liver and prostate as the most frequent indications. Pancreatic tumor (48.4 %), renal cell carcinoma (46.4 %), and ventricular tachycardia (12.4 %) represented emerging indications. C-arm linacs (89.2 %) and in-room Cone beam CT (CBCT) (92.0 %) were the dominant technologies. Motion management relied mainly on 4D-CT internal target volume (ITV) (88.9 %) and deep inspiration breath-hold (DIBH) (57.8 %). Fractionation was consistent for lung and prostate but heterogeneous for liver, and pancreas. Only 3.5 % reported routine use of online adaptive SBRT, while 61.5 % reported artificial intelligence (AI) use, mainly for organs-at-risk delineation. Key barriers included limited clinical trial funding (35.2 %), high equipment costs (34.2 %), insufficient reimbursement (27.7 %), and workforce shortages (33.9 %).

CONCLUSIONS: This ESTRO international survey provides the first global overview of SBRT practices. It demonstrates broad adoption but also substantial variability, highlighting the need for consensus guidelines, greater trial access, and expanded education to harmonize SBRT delivery and ensure equitable care worldwide.},
}

@article {pmid41499715,
year = {2026},
author = {Wan, YH and Pernikoff, S and Aldridge, NT and Lang, K and Dudley, HM and Scharffenberger, SC and Kher, G and Phipps, W and Pancera, M and Boonyaratanakornkit, J and McGuire, AT},
title = {Monoclonal neutralizing antibodies elicited by infection with Kaposi sarcoma-associated herpesvirus reveal critical sites of vulnerability on gH/gL.},
journal = {PLoS pathogens},
volume = {22},
number = {1},
pages = {e1013772},
doi = {10.1371/journal.ppat.1013772},
pmid = {41499715},
issn = {1553-7374},
abstract = {Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic virus that causes Kaposi sarcoma, primary effusion lymphoma and multicentric Castleman disease. A vaccine that prevents KSHV infection or serves in the treatment of KSHV-related diseases represents a critical unmet need, however, the types of immune responses a vaccine should elicit have not been well defined. The gH/gL glycoprotein complex is an important target of KSHV-neutralizing antibodies, but the epitope specificities targeted by these antibodies remain unknown. Here, we isolated 12 gH/gL-specific monoclonal antibodies (mAbs) from KSHV-infected donors and performed structure/function analyses. These mAbs bind recombinant gH/gL with nanomolar affinities and epitope binning analyses revealed that the mAbs bind to 5 epitope clusters on gH/gL. Seven mAbs were able to neutralize KSHV infection of epithelial cell lines. Two potent neutralizing mAbs mapped to the EphA2 binding site as determined by inhibition of the receptor-ligand interaction and negative stain electron microscopy (nsEM) of the mAb/gH/gL complex. The epitopes of other neutralizing mAbs targeting novel sites of vulnerability were determined by a combination of cryogenic electron microscopy and nsEM. Together, these mAbs help to define the relevant epitope targets for KSHV vaccine design, have utility in understanding the role of antibodies in preventing KSHV infection, enable the development of immunotherapy approaches, and provide valuable tools to understand the molecular details of the KSHV entry process.},
}

@article {pmid41498421,
year = {2025},
author = {Ulschmid, C and Li, X and Wang, T and Logan, BR and Pidala, JA and MacMillan, ML and Kitko, CL and Lee, SJ and Spellman, SR and Saber, W},
title = {Validated Clinical Risk Score for Acute Graft-Versus-Host Disease in Adult Allogeneic Hematopoietic Cell Transplantation.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025016938},
pmid = {41498421},
issn = {2473-9537},
abstract = {Acute graft-versus-host disease (aGVHD) contributes to significant morbidity following allogeneic hematopoietic cell transplantation (alloHCT). We aimed to develop and validate a clinical score to identify patients with significantly different risk for developing aGVHD. Analysis included adults who underwent alloHCT during 2008-2019. Eligibility criteria were widely inclusive of transplant indications, donor types, graft types, conditioning regimens, and GVHD prophylaxis regimens. The final cohort of 21,796 patients was randomly split into training and validation cohorts, with 15,258 (70%) and 6,538 (30%) patients, respectively. The primary outcome was grades II-IV aGVHD, and the secondary outcome grades III-IV aGVHD, by day 100 post-transplant. Risk scores were developed using the training cohort, tested using the validation cohort, and stratified into 4 percentile groups. Odds of aGVHD II-IV by day 100 post-transplant were 1.50 (95% CI, 1.29-1.75; P < .0001) for the 25-50 percentile group, 2.0 (95% CI, 1.78-2.40; P < .0001) for the 50-75 percentile group, and 3.1 (95% CI, 2.72-3.65; P < .0001) for the > 75 percentile group compared to the ≤ 25 percentile group in the validation cohort. Odds of aGVHD III-IV by day 100 post-transplant were 1.4 (95% CI; 1.11-1.74, P = .0043) in the 25 to 50 percentile group, 2.0 (95% CI, 1.61-2.49, P < .0001) in the 50 to 75 percentile group, and 3.2 (95% CI, 2.64-3.98, P < .0001) in the > 75 percentile group compared to the ≤ 25 percentile group in the validation cohort. Here we have developed the first validated, widely inclusive clinical risk score for the development of aGVHD following alloHCT.},
}

@article {pmid41497599,
year = {2025},
author = {Trofimov, A and Montague, Z and Russell, ML and Ignacio, RB and Stevens-Ayers, T and Zamora, D and Mielcarek, M and Boeckh, MJ and Matsen, F and Nourmohammad, A},
title = {Genetic and environmental imprints on T cell receptor repertoires as predictors of graft-versus-host disease.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41497599},
issn = {2692-8205},
abstract = {Hematopoietic cell transplantation (HCT) as potentially curative treatment for patients with hematologic malignancies relies on T cells to mediate the potentially curative graft-versus-tumor (GVT) effect, which may be associated with graft-versus-host disease (GVHD), a potentially life-threatening complication. T cells recognize peptides presented by Human Leukocyte Antigen (HLA) molecules. It is commonly believed that matching HLA alleles between donors and recipients ensures similarity in their T cell receptor (TCR) repertoires, thereby reducing the risk of GVHD and graft rejection. However, TCR repertoires are shaped by multiple factors beyond HLA genetics, including sex, age, and immune history. The extent to which genetic variation and past infections influence TCR repertoire composition and GVHD risk remains unclear. Here, we show that while HLA haplotypes contribute to broad TCR repertoire differences, recent viral infections significantly impact TCR composition and influence GVHD risk. Analyzing 401 patients who were uniformly transplanted from healthy HLA-identical sibling HCT donors, we introduced HLA-TCR coherence, a metric that quantifies the extent to which an individual's TCR repertoire reflects their HLA haplotype. We find that higher TCR-HLA coherence is associated with greater HLA heterozygosity and an increased incidence of severe acute GVHD (grade 3-4) in transplant recipients. Furthermore, in silico identification of virus-associated TCRs (vaTCRs) using TCR sequencing and viral serology reveal specific vaTCRs predictive of either increased or decreased GVHD risk. These findings suggest that beyond HLA allele matching, donor-specific immune history and repertoire characteristics are critical determinants of GVHD risk. Thus, a more systematic integration of donor immune history may offer a complementary avenue for refining donor selection and potentially improving transplant outcomes.},
}

@article {pmid41497576,
year = {2025},
author = {Jones, JD and Valenzuela, Y and Pacheco, M and Nelson, L},
title = {Research Participation Among American Indian and Alaskan Native Individuals Living With Parkinson's Disease.},
journal = {Parkinson's disease},
volume = {2025},
number = {},
pages = {3207928},
pmid = {41497576},
issn = {2090-8083},
abstract = {BACKGROUND: There is a notable gap in racial and ethnic representation in Parkinson's disease (PD) research, particularly among American Indian and Alaska Native (AIAN) populations, despite a higher prevalence of PD in these groups. This study investigated research participation among AIAN individuals in terms of perceived access to research opportunities, willingness to participate, and potential concerns about participation.

METHODS: Data were obtained from the online Fox Insight (FI) study. A total sample of 4412 individuals who self-reported their race as White (n = 4363) or AIAN (n = 49) were selected. The Attitudes and Beliefs Regarding Research and Genetic Testing for PD survey was administered to assess participants' attitudes and knowledge about the research process, opportunities, and preferences.

RESULTS: A significantly smaller proportion of AIAN individuals (34.7%) reported concurrent or past participation in PD research compared with White non-AIAN participants (52.9%). Despite this lower participation rate and limited knowledge of research opportunities, a large majority of AIAN individuals (89.8%) expressed a willingness to participate in research. Additionally, both AIAN and White non-AIAN participants reported similar rates of concerns about research participation. Among AIAN individuals, the most common barriers were distance from research site, transportation, and time commitments.

CONCLUSION: These findings highlight that low research participation among AIAN individuals may be more associated with low engagement from the research community rather than unwillingness or relatively greater research concerns. Building stronger partnerships with tribal communities and involving community leaders to build trust may improve research representation among AIAN populations.},
}

@article {pmid41495267,
year = {2026},
author = {Werwath, KE and Lawn, RB and Salem, MT and Li, T and Mitchell, BL and Shen, H and Gordon, SD and Kung, B and Stafford, C and Vemuri, M and Ratanatharathorn, A and Meijsen, J and Shadyab, AH and Kooperberg, C and Koenen, KC and Crandall, CJ and Martin, NG and Duncan, LE},
title = {Trans-ancestry GWAS of hot flashes reveals potent treatment target and overlap with psychiatric disorders.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-025-01305-8},
pmid = {41495267},
issn = {2730-664X},
support = {MH125358//U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/ ; },
abstract = {BACKGROUND: Most women experience hot flashes (hot flushes) during the menopause transition. Menopausal hot flashes typically persist for years, and for a sizeable minority of women, are substantially impairing. Genetic investigations can improve understanding of hot flash etiology.

METHODS: We conducted a trans-ancestry genome-wide association study (GWAS) of hot flashes (N = 149,560) among post-menopausal women age 35-88. The outcome variable was self-reported hot flashes in four samples (total n = 42,489) and menopausal hormone therapy as a proxy in one sample (n = 107,071). We estimated the heritability of hot flashes and genetic correlations with psychiatric phenotypes using linkage disequilibrium score regression.

RESULTS: In our trans-ancestry meta-analysis, the top locus lies on chromosome 4 in the neurokinin 3 receptor gene (TACR3, p = 7.2×10[-41]). We also identify another locus on chromosome 4 with top SNP rs13107507 (p = 3.5×10[-8]). Gene results implicate TACR3, GRID1, NUDT4, and PHF21B. SNP heritability is estimated to be 8% (h[2]liab = .08, h[2]SNP = .04, se = .02). Genetic correlations are statistically significant between hot flashes and PTSD (rg = 0.25, p = 0.01), schizophrenia (rg = 0.17, p = 0.02), depression (rg = 0.21, p = 0.01), and ADHD (rg = .22, p = 0.03).

CONCLUSIONS: These genomic findings are consistent with independent, robust basic science research which led to a recently developed treatment for hot flashes, namely, a neurokinin 3 receptor antagonist. This non-hormonal class of hot flash drugs blocks the receptor coded for by the top locus reported here (TACR3, the neurokinin 3 receptor gene). Hot flash GWAS results provide an example of how GWAS findings can point to potent treatment targets for complex brain phenotypes.},
}

@article {pmid41495079,
year = {2026},
author = {Yao, TH and Treekitkarnmongkol, W and Putluri, N and Sankaran, D and Nguyen, T and Balasenthil, S and Hurd, MW and Chen, M and Brand, RE and Lampe, PD and Kamal, AHM and Putluri, V and Hu, TY and Maitra, A and Koay, EJ and Killary, AM and Sen, S and Kundu, S},
title = {Machine learning-based multimodal biomarkers enable accurate diagnosis and early detection of pancreatic ductal adenocarcinoma.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {658},
pmid = {41495079},
issn = {2045-2322},
abstract = {While there has been some progress on discovering clinically validated biomarkers for early detection in pancreatic ductal adenocarcinoma (PDAC), several challenges remain. Most approaches rely on single-modality biomarkers with limited sensitivity and/or specificity. Using data from a multicenter study with an age-matched cohort (n = 203 with healthy controls n = 46, pancreatitis controls n = 36, and diagnosed cases n = 121), we developed a machine learning approach integrating 2,096 microRNAs, 125 metabolites, and CA19-9. Our method performs unsupervised selection of an optimal subset of biomarkers with maximal discriminatory power for diagnosis and early detection. In training data, the selected biomarker panel achieved [Formula: see text] area under the curve (AUC) and [Formula: see text] sensitivity when controlling specificity at [Formula: see text]. The classification results under the selected multimodal panel generalize well for validation samples. The panel outperforms recently proposed microRNA-based approaches and identifies key biomarkers (such as aminobutyric acid and homovanillic acid) with high classification importance. Decision tree–based cut-offs are derived to enhance clinical interpretability, revealing the association between the low aminobutyric acid level and non-cancer status. These results highlight the superior discriminative ability and interpretability of the proposed multimodal biomarker panel, offering a promising tool for PDAC diagnosis and early detection.},
}

@article {pmid41494888,
year = {2025},
author = {Kwendakwema, CN and Lan, KF and Kim, HN and Gopal, AK and Menon, MP},
title = {HIV, HBV, and HCV Testing in Newly Diagnosed Diffuse Large B-Cell Lymphoma: Experience From a Comprehensive Cancer Center.},
journal = {Clinical lymphoma, myeloma & leukemia},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.clml.2025.12.010},
pmid = {41494888},
issn = {2152-2669},
abstract = {PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype non-Hodgkin lymphoma. HIV, hepatitis B (HBV), and hepatitis C (HCV) infections are DLBCL risk factors. DLBCL remains a leading cause of cancer-related morbidity and mortality in those with HIV. DLBCL treatments can also increase the HBV reactivation risk and acute liver injury in HCV. We assessed HBV, HCV, and HIV screening rates in DLBCL patients receiving systemic therapy in a comprehensive cancer system.

MATERIALS AND METHODS: We analyzed newly diagnosed DLBCL patients receiving anti-CD20 therapies between January 2018 and December 2023. Patients were considered screened if they had viral testing or a prior diagnosis within 12 months before to 3 months after starting treatment. We used chi-squared and Fisher's exact tests to examine associations between patients who were and were not screened HBV, HCV, and HIV. We used univariate and multivariate logistic regression to identify the factors associated with screening.

RESULTS: A total of 535 patients with DLBCL were treated (median age 64, 42% female, 82% white). Among these patients, 410 (77%) had HBV testing or a known infection, 275 (51.4%) had HIV testing or a known infection, and 307 (53%) had HCV testing or a known infection. Younger people were more likely to be tested for HIV and HCV. There was no association between age and HBV testing.

CONCLUSION: Pre-treatment HIV, HBV, and HCV screening rates in newly diagnosed DLBCL patients remains suboptimal. Interventions to increase viral testing in this population could help reduce treatment-related morbidity and mortality.},
}

@article {pmid41494138,
year = {2026},
author = {Hicks, LK and Messersmith, HJ and Al Hadidi, S and Banerjee, R and Derman, BA and Kumar, S and Wildes, TM and Bal, S and Bhella, S and Chmielewski, C and Costello, C and Dabney, R and Hartley-Brown, M and Langerak, A and Lipe, B and Martin, T and McCurdy, A and Mian, H and Riva, E and Seth, R and Subramanian, L and Mikhael, J},
title = {Treatment of Multiple Myeloma: ASCO-Ontario Health (Cancer Care Ontario) Living Guideline.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502587},
doi = {10.1200/JCO-25-02587},
pmid = {41494138},
issn = {1527-7755},
abstract = {PURPOSE: To provide updated guidance regarding the therapy for multiple myeloma.

METHODS: ASCO and Ontario Health (Cancer Care Ontario) convened a joint Expert Panel and conducted an updated systematic review of the literature.

RESULTS: The updated review identified a total of 161 relevant randomized trials.

UPDATED RECOMMENDATIONS: Daratumumab therapy may be offered to patients with high-risk smoldering myeloma. Quadruplet therapy with daratumumab or isatuximab, combined with bortezomib, lenalidomide, and dexamethasone, should be offered as initial therapy for transplant eligible patients. They should also be offered at least lenalidomide maintenance, with or without daratumumab, carfilzomib, and/or dexamethasone. Quadruplet therapy with daratumumab or isatuximab, combined with bortezomib, lenalidomide, and dexamethasone, should be offered as therapy for suitable transplant-ineligible patients. Patients with relapsed or refractory multiple myeloma should be offered triplet therapy or T-cell redirecting therapies according to a set of recommended principles.Additional information is available at www.asco.org/hematologic-malignancies-guidelines.},
}

@article {pmid41493894,
year = {2026},
author = {Ramírez, P and Lankowski, AJ and Gallardo-Cartagena, JA and Gonzales, P and Valencia, J and Lama, JR and León, M and Salvatierra, J and Sanchez, H and Cabello, R and Konda, KA and Sanchez, JL and , },
title = {Implementation of Daily Oral PrEP at HIV/AIDS Service Organizations in Lima, Peru: Early Findings From the PrEP PERU Demonstration Study.},
journal = {Journal of the International Association of Providers of AIDS Care},
volume = {25},
number = {},
pages = {23259582251411793},
pmid = {41493894},
issn = {2325-9582},
mesh = {Humans ; Peru/epidemiology ; *Pre-Exposure Prophylaxis/methods ; Male ; Adult ; *HIV Infections/prevention & control/epidemiology ; Prospective Studies ; Homosexuality, Male/statistics & numerical data ; Administration, Oral ; *Anti-HIV Agents/administration & dosage/therapeutic use ; *Tenofovir/administration & dosage/therapeutic use ; Medication Adherence ; COVID-19/epidemiology ; },
abstract = {BackgroundDespite global declines in HIV incidence, new infections continue to rise in Latin America. Oral tenofovir-based HIV pre-exposure prophylaxis (PrEP) is effective and can reduce incidence where implemented. PrEP PERU is a prospective cohort study evaluating daily oral PrEP delivery at HIV/AIDS service organizations (ASOs) in Peru.MethodsWe assessed 12-month PrEP retention and adherence among men who have sex with men (MSM) enrolled at 4 ASOs in Lima before the COVID-19 pandemic. The analysis included participants with ≥12 months of follow-up before the March 2020 lockdown. Follow-up visits occurred at weeks 4, 12, and quarterly thereafter. We used robust Poisson regression to evaluate associations between baseline characteristics and 2 outcomes: retention (attending ≥3 follow-up visits within 12 months) and optimal adherence (proportion of days covered ≥80%).ResultsAmong 264 MSM who initiated PrEP, median age was 31 years (IQR: 27-37). Retention at 12 months was 71%, and 55% achieved optimal adherence. Retention was associated with age ≥30 and bisexual identity in adjusted models. Optimal adherence was associated with being employed at baseline.ConclusionsPrEP delivery through ASOs in Lima is feasible and supports sustained engagement among MSM. Targeted strategies are needed to improve outcomes among younger individuals.},
}

Humans
Peru/epidemiology
*Pre-Exposure Prophylaxis/methods
Male
Adult
*HIV Infections/prevention & control/epidemiology
Prospective Studies
Homosexuality, Male/statistics & numerical data
Administration, Oral
*Anti-HIV Agents/administration & dosage/therapeutic use
*Tenofovir/administration & dosage/therapeutic use
Medication Adherence
COVID-19/epidemiology

@article {pmid41493843,
year = {2026},
author = {He, AR and Bouattour, M and Gupta, VG and Evesque, L and Zhen, DB and Park, JO and Sookprasert, A and Salvatierra, A and Vaccaro, G and Oh, SC and Ostoich, SA and Satoh, T and Kuzko, A and Żotkiewicz, M and Rokutanda, N and Oh, DY},
title = {Predictors of overall survival in advanced biliary tract cancer in the phase 3 TOPAZ-1 study.},
journal = {Hepatology communications},
volume = {10},
number = {1},
pages = {},
pmid = {41493843},
issn = {2471-254X},
}

@article {pmid41491041,
year = {2026},
author = {Ahmad, K and Wooten, M and Takushi, BN and Vidaurre, V and Chen, X and Henikoff, S},
title = {Cell-cycle-dependent repression of histone gene transcription by histone H4.},
journal = {Nature structural & molecular biology},
volume = {},
number = {},
pages = {},
pmid = {41491041},
issn = {1545-9985},
abstract = {In all eukaryotes, DNA replication is coupled to histone synthesis to coordinate chromatin packaging of the genome. Canonical histone genes coalesce in the nucleus into the histone locus body (HLB), where gene transcription and 3' mRNA processing occurs. Both histone gene transcription and mRNA stability are reduced when DNA replication is inhibited, implying that the HLB senses the rate of DNA synthesis. In Drosophila melanogaster, the S-phase-induced histone genes are tandemly repeated in an ~100 copy array, whereas, in humans, these histone genes are scattered. In both organisms, these genes coalesce into HLBs. Here, we use a transgenic histone gene reporter and RNA interference in Drosophila to identify canonical H4 histone as a unique repressor of histone synthesis during the G2 phase in germline cells. Using cytology and CUT&Tag chromatin profiling, we find that histone H4 uniquely occupies histone gene promoters in both Drosophila and human cells. Our results suggest that repression of histone genes by soluble histone H4 is a conserved mechanism that coordinates DNA replication with histone synthesis in proliferating cells.},
}

@article {pmid41489165,
year = {2026},
author = {Yang, Z and Rizopoulos, D and Newcomb, LF and Erler, NS},
title = {Time-Dependent Predictive Accuracy Metrics in the Context of Interval Censoring and Competing Risks.},
journal = {Biometrical journal. Biometrische Zeitschrift},
volume = {68},
number = {1},
pages = {e70108},
pmid = {41489165},
issn = {1521-4036},
support = {CA253910/NH/NIH HHS/United States ; },
mesh = {Humans ; *Biometry/methods ; Time Factors ; Male ; Prostatic Neoplasms ; Models, Statistical ; ROC Curve ; },
abstract = {Evaluating the performance of a prediction model is a common task in medical statistics. Standard accuracy metrics require the observation of the true outcomes. This is typically not possible in the setting with time-to-event outcomes due to censoring. Interval censoring, the presence of time-varying covariates, and competing risks present additional challenges in obtaining those accuracy metrics. In this study, we propose two methods to deal with interval censoring in a time-varying competing risk setting: a model-based approach and the inverse probability of censoring weighting (IPCW) approach, focusing on three key time-dependent metrics: area under the receiver-operating characteristic curve, Brier score, and expected predictive cross-entropy. The evaluation is conducted over a medically relevant time interval of interest, [ t , Δ t) $[t, \Delta t)$ . The model-based approach includes all subjects in the risk set, using their predicted risks to contribute to the accuracy metrics. In contrast, the IPCW approach only considers the subset of subjects who are known to be event-free or experience the event within the interval of interest. We performed a simulation study to compare the performance of the two approaches with regard to the three metrics. Furthermore, we demonstrated the three metrics using the two approaches on an example prostate cancer surveillance cohort. Risk predictions were generated from a joint model handling the interval-censored cancer progression and the competing event, early treatment, and repeatedly measured biomarkers.},
}

Humans
*Biometry/methods
Time Factors
Male
Prostatic Neoplasms
Models, Statistical
ROC Curve

@article {pmid41488889,
year = {2026},
author = {Jain, J and Pugh, K and Handa, S and Dvorak-Kornaus, KM and Zhao, Q and Walter, RB and Cook, R and Saultz, J and Swords, R and Li, J and Laszlo, GS and Grieselhuber, NR and Mims, AS and Larkin, KTM and Sahasrabudhe, K and Blachly, JS and Behbehani, GK and Eisfeld, AK and Long, M and Srisuwananukorn, A and Koenig, KL and Borate, U},
title = {Safety of gemtuzumab ozogamicin with cytarabine, daunorubicin, and midostaurin induction in FLT3-mutated AML.},
journal = {Blood neoplasia},
volume = {3},
number = {1},
pages = {100171},
pmid = {41488889},
issn = {2950-3280},
abstract = {This phase 1 study investigated the addition of gemtuzumab ozogamicin (GO) to intensive chemotherapy with cytarabine, daunorubicin, and midostaurin in 21 patients with newly diagnosed (ND) FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML). Four dose levels of GO were evaluated. The use of GO was tolerable, with all dose-limiting toxicities similar to those seen in standard-of-care treatment. After induction, the median time to platelet recovery was 26 days, and the median time to absolute neutrophil count (ANC) recovery was 27 days. The maximum tolerated dose was cytarabine 100 mg/m[2] on days 1 to 7, midostaurin 50 mg twice daily on days 8 to 21, daunorubicin 60 mg/m[2] on days 1 to 3, and GO 3 mg/m[2] on days 1 and 4. For the 18 patients who were evaluable for response after induction therapy, 16 patients (76%) achieved a composite complete response (complete remission [CR] + CR with incomplete hematologic recovery), and 2 (10%) had stable disease. Of the 14 patients who proceeded to consolidation, 5 discontinued the study for transplant, 1 for disease progression, and 1 for physician discretion. Seven patients completed consolidation therapy, all of whom achieved a CR. In total, 13 of the 21 patients (62%) received a hematopoietic stem cell transplant. Our results show that GO can safely be combined with intensive chemotherapy with midostaurin in ND, FLT3-mutated AML. This trial was registered at www.clinicaltrials.gov as #NCT03900949.},
}

@article {pmid41488033,
year = {2026},
author = {Courville, EL and Seifert, R and Sadigh, S and Chen, X and Calli, JL and Hasserjian, R and Siddon, AJ},
title = {Joining the National Resident Matching Program Fellowship Match: the hematopathology experience.},
journal = {Academic pathology},
volume = {13},
number = {1},
pages = {100230},
pmid = {41488033},
issn = {2374-2895},
abstract = {Hematopathology fellowships are a critical subspecialty within the field of pathology, and with a progressively earlier and earlier fellowship interview timeline, hematopathology decided to join the Pathology Fellowship Match in 2025. The pros and cons of participating in the National Resident Matching Program Match were evaluated, and ultimately it was decided to be undertaken. The National Resident Matching Program requires that 75% of programs and fellowship positions should be entered in order to sponsor the Match. The Society for Hematopathology Education Committee lead the process to recruit hematopathology fellowships into the Match, initiating a survey to assess initial interest, creating a listserv for program director questions, and maintaining a website with programs that ultimately decided to participate. The initial survey results showed that 79% of hematopathology program directors responded "yes" or "maybe" to whether they would participate in a formal Match. The Society for Hematopathology Education Committee then proceeded with a memorandum of understanding to show commitment to the Match. Multiple efforts to disseminate information followed, including informational webinars, social media outreach, and emails to program directors. Ultimately 83% of hematopathology fellowships participated in the 2025 Match, with 85% of positions filling, and 94.7% of hematopathology applicants matching. A follow-up program director survey showed that 98% of respondents planned to participate in the 2026 Match. This feedback solidifies that the Pathology Fellowship Match has shown mutual benefit for programs and applicants.},
}

@article {pmid41487700,
year = {2026},
author = {Ruiz, E and Gay, HA and Ixquiac, M and Velarde, A and Sun, B and García-Ramirez, J and Laugeman, E and Li, B and Michalski, J and de Falla, V and Hugo, G and Van Rheenen, J},
title = {Lessons Learned From an Epic Transformation of a Radiation Oncology Department in Guatemala: Keys to Success.},
journal = {Advances in radiation oncology},
volume = {11},
number = {1},
pages = {101928},
pmid = {41487700},
issn = {2452-1094},
abstract = {PURPOSE: We describe the radical modernization of a radiation oncology department in a developing country, Guatemala, from 2015 to the beginning of 2024. The Instituto de Cancerología y Hospital Dr. Bernardo del Valle S (INCAN) is the only public radiotherapy clinic serving patient referrals from the Ministry of Public Health and Social Assistance program.

METHODS AND MATERIALS: We describe the state of the radiation oncology department in 2015 versus 2024 while chronicling its gradual transformation. This multifaceted collaboration involved academic centers, government agencies, International Atomic Energy Agency (IAEA), industry, and nonprofits and continues to this day. We analyze the infrastructure, staff, radiotherapy equipment, physics equipment, patient careCo-60 decommissioning, and educational initiatives.

RESULTS: We graphically illustrate the impact of these changes in treatment delivery time, consults, follow-up visits, CT simulations, new patients treated in each linear accelerator, new patients treated with 2D, 3D, IMRT/VMAT, and superficial techniques, new patients treated with 2D LDR, 2D HDR, or 3D techniques, causes of linear accelerator downtime, and weekly patients on treatment. We provide a figure of the various sequential and parallel steps to modernize a radiation oncology department. We describe the complexities of radioisotope repatriation and safe disposal. We provide a comprehensive table of wisdom pearls regarding project governance, team, education, finances, culture, and language. We also discuss the impact of artificial intelligence in contouring.

CONCLUSION: The transformation of the INCAN radiation oncology department in Guatemala is a testimony to many's hard work, vision, and perseverance for the betterment of Guatemalan patients while facing incredible financial hardship. We hope that what we have learned in the past nine years will help others achieve even greater success in a shorter time.},
}

@article {pmid41479450,
year = {2025},
author = {Collienne, L and Matsen, FA},
title = {Tree rearrangement graphs admit paths of decreasing Robinson-Foulds distance.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {41479450},
issn = {2331-8422},
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, 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 exhibit trees for which no strictly decreasing NNI path exists.},
}

@article {pmid41486674,
year = {2026},
author = {Kanetsky, PA and Almstrup, K and Cherlin, S and Cortessis, VK and Ferlin, A and Gietema, JA and González-Neira, A and Grotmol, T and Hamilton, RJ and Haugen, TB and Kiemeney, LA and Kim, J and Krausz, C and Lessel, D and Lothe, RA and Nead, KT and Nsengimana, J and Poynter, JN and Rajpert-DeMeyts, E and Richiardi, L and Schwartz, SM and Skotheim, RI and Stewart, DR and Turnbull, C and Wiklund, F and Zheng, T and Nathanson, KL and McGlynn, KA and , },
title = {The Testicular Cancer Consortium (TECAC): Filling Knowledge Gaps in the Genetic Etiology of Testicular Germ Cell Tumors.},
journal = {Andrology},
volume = {},
number = {},
pages = {e70168},
pmid = {41486674},
issn = {2047-2927},
support = {PC-35142/GF/NIH HHS/United States ; CAN2012/823//Swedish Cancer Society/ ; PK01-2007-0375//Norwegian Cancer Society/ ; PR-2006-0387//Norwegian Cancer Society/ ; III-FIS PI17/01822//Spanish Ministry of Health Instituto Carlos/ ; 101136622//European Union/ ; CN-67009/GF/NIH HHS/United States ; D15D18000410001//Italian Ministry for Education, University and Research/ ; CAN2019/0343//Swedish Cancer Society/ ; R01CA114478/GF/NIH HHS/United States ; 71081//Norwegian Cancer Society/ ; R01CA104786/GF/NIH HHS/United States ; 2010/808//Swedish Cancer Society/ ; S-12/07//Nordic Cancer Union/ ; C588/A19167//Cancer Research UK Programme/ ; HHSN26120130003C/GF/NIH HHS/United States ; U01 CA164947/CA/NCI NIH HHS/United States ; 2019/011633//Swedish Research Council/ ; 270870//Norwegian Cancer Society/ ; //Movember Foundation/ ; R01CA085914/GF/NIH HHS/United States ; U01CA164947/GF/NIH HHS/United States ; ZO1-CP-10144//National Cancer Institute, Intramural Research Program/ ; 2011/484//Swedish Cancer Society/ ; P30CA016520/GF/NIH HHS/United States ; 2008/708//Swedish Cancer Society/ ; 418975//Norwegian Cancer Society/ ; Dell'ElceFamilyFund//Princess Margaret Cancer Foundation/ ; 70113348//Deutsche Krebshilfe/ ; 223319//Norwegian Cancer Society/ ; },
abstract = {BACKGROUND: The Testicular Cancer Consortium (TECAC) was established in 2012 and is comprised of researchers from over 25 centers in Europe and North America. TECAC's overarching goal is to investigate the genetic susceptibility of testicular germ cell tumors (TGCT) to better understand their biology, impact prevention strategies, and inform treatment decisions.

OBJECTIVES: To provide an overview of TECAC genetic and phenotypic holdings.

MATERIALS AND METHODS: TECAC has composed by-laws describing the consortium structure and governance, codified the processes for manuscript development and data transfer, and developed guidance for the transfer of biological samples and access to data.

RESULTS: TECAC has assembled a vast amount of genetic information on males with TGCT-including SNP-array data on over 13,500 cases, whole-exome sequencing data on over 4500 cases, and low-pass whole-genome sequence data on over 2700 cases. Genetic information on males without TGCT (controls) is derived from studies designed to assess risk factors for TGCT and from publicly available resources. When available, corresponding phenotypic information is collected and harmonized. Fifteen publications have resulted from genetic and phenotypic information curated by TECAC.

DISCUSSION: The sharing of genetic and phenotypic data by TECAC centers to inform large studies of TGCT susceptibility has led to novel insights into the genetic architecture of this cancer, including the roles of genes involved in male germ cell development, sex determination, chromosomal segregation, and RNA transcription. These findings would not have been achievable by individual centers or smaller collaborative efforts.

CONCLUSION: We invite investigators from any discipline who have access to collections of germline DNA, somatic cell DNA, or genomic information on males with TGCT to consider joining TECAC to further strengthen our efforts to reduce the global burden of TGCT.},
}

@article {pmid41484087,
year = {2026},
author = {Kinsella, S and Evandy, CA and Cooper, K and Kirsche, E and Warren, M and deRoos, P and Cardinale, A and Iovino, L and Granadier, D and Smith, CW and Hopwo, K and Sullivan, LB and Velardi, E and Dudakov, JA},
title = {Damage-induced pyroptosis drives endogenous thymic regeneration by activating the purinergic receptor P2Y2.},
journal = {Cell death & disease},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41419-025-08345-x},
pmid = {41484087},
issn = {2041-4889},
support = {ASH Scholar//American Society of Hematology (ASH)/ ; R01-HL145276//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01-HL165673//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U01-AI70035//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {T cell recovery is critical following damage, such as hematopoietic cell transplantation (HCT), with increased reconstitution associated with improved clinical outcomes. Endogenous thymic regeneration, a crucial process for restoring immune competence following cytoreductive therapies such as HCT conditioning, is often delayed, limiting T cell reconstitution. Fully understanding the molecular mechanisms driving regeneration is therefore crucial for uncovering therapeutic targets that can be exploited to enhance thymic function. Here, we identified that CD4+ CD8+ thymocytes rapidly and acutely undergo lytic cell death, specifically pyroptosis, following acute damage caused by ionizing radiation, and release damage-associated molecular patterns (DAMPS) into the thymic microenvironment, including ATP. Extracellular ATP stimulates the P2Y2 purinergic receptor on thymic epithelial cells (TECs)-a stromal cell crucial for supporting T cell development-resulting in the upregulation FOXN1, the master TEC transcription factor. Targeting the P2Y2 receptor with a P2Y2 agonist, UTPγS, promotes rapid regeneration of the TEC compartment in vivo following acute damage. These findings reveal a novel damage-sensing mechanism employed by the thymus where thymocytes adopt an alternative cell death mechanism which promotes thymic repair via P2Y2 signaling in TECs. This work identifies P2Y2 as a promising therapeutic target for enhancing thymus regeneration and improving immune recovery after HCT.},
}

@article {pmid41484084,
year = {2026},
author = {Zhang, S and Tang, TH and Kinsella, S and Mazziotta, F and Schweizer, MT and McAfee, MS and Munkhbat, A and Su, Y and Voillet, V and Martin, LE and Smith, CW and Asano, Y and Hailemariam, M and Bakhtiari, J and Lee, B and Yeung, C and Chen, H and Rizzi, AM and Chen, DG and Furiya, K and Horst, N and Zhang, T and Le, P and McKenna, K and Oda, SK and Rongvaux, A and Greenberg, PD and Schmitt, TM and Chapuis, AG},
title = {A CD8αβ co-receptor modified to contain an intracellular CD28 signaling tail enhances TCR-engineered T cell function independent of solid-tumor-associated co-stimulatory ligands.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-67446-5},
pmid = {41484084},
issn = {2041-1723},
support = {P01CA225517//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P01CA18029-41//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {Adoptive transfer of T cells engineered with tumor-specific T cell receptors (TCRs) has shown limited efficacy in solid tumors, hindered by insufficient persistence, tumor trafficking, and dependence on tumor-associated co-stimulatory ligands. In a phase I trial (NCT04639245) for patients with metastatic MAGE-A1-expressing tumors and adequate organ function; one participant received treatment, which was well-tolerated. In this case and NSG murine models, infusion of CD4/CD8 T cells co-expressing a class-I MAGE-A1-specific TCR and CD8αβ, failed to control tumor progression. To enhance function downstream of TCR signaling, here we investigate the adaptability of TCR components to synthetic modification. Leveraging the obligate co-expression of CD8αβ required for class-I TCR function in CD4 T cells, we identify CD8β as a tractable site for engineering without loss of function. In vitro screening demonstrates incorporation of the CD28 intracellular tail, yielding a CD8/CD28 chimeric co-receptor, most effectively enhances cytokine production, T cell persistence, and tumor control in immunodeficient murine models while preserving stem-like transcriptional features compared to native CD8β. Further rational modification of the CD28 binding motifs improves tumor control in vivo with increased intratumoral accumulation and reduced exhaustion. This benefit also extends to PRAME and WT1-specific TCRs in vitro supporting generalizability.},
}

@article {pmid41482160,
year = {2025},
author = {Masurekar, AN and Burkett, KM and Rahgozar, A and Walter, RB and Othus, M and Abrol, K and Mortezaagha, P and Thyagu, S and Nampoothiri, RV and Kennah, M and Kekre, N and Giguere, P and Abduallah, Y and Atkins, H and Cieniak, C and Berardi, P and Ramsay, T and Mallick, R and Carrier, M and Bredeson, C and Allan, D},
title = {Defining the Limits of Pre-Transplant Risk Prediction in AML: Evidence from Machine Learning and Regression Models.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.12.996},
pmid = {41482160},
issn = {2666-6367},
abstract = {BACKGROUND: Allogeneic hematopoietic cell transplantation (allo-HCT) for acute myeloid leukemia (AML) is associated with considerable morbidity and mortality. Machine learning (ML) techniques are increasingly applied to predict outcomes in medicine.

OBJECTIVES: To evaluate the role of ML in predicting overall survival (OS) after allo-HCT for AML and compare ML with traditional Cox regression.

STUDY DESIGN: Using an internal cohort of 2,253 patients and 14 pre-allo-HCT variables, we developed three models: Cox regression with time-varying coefficients (Cox-TVC), Elastic-net Cox Regression (Cox-EN), and Random Survival Forest (RSF). Performance was evaluated using multiple metrics including C-index, net reclassification improvement (NRI) and decision curve analysis (DCA). Patients were stratified into tertiles of model predicted 24-month mortality. External validation was performed in 252 single-center patients with uniform measurable residual disease (MRD) assessment.

RESULTS: Model-derived risk scores strongly correlated (r=0.886-0.963). Across models, age ≥ 60 years, MRD positivity, and adapted European LeukemiaNet (aELN) adverse risk were the strongest predictors. Effects of age attenuated over time (HR for age ≥60: 2.59 [95% CI: 1.54-4.35] at 1 year, 1.92 [95% CI: 1.04-3.56] at 5 years). Compared with Hematopoietic Cell Transplant Comorbidity-Index (HCT-CI) and aELN, models improved risk stratification (NRI: 31-44%, p <0.001). Discrimination remained modest but was higher in external cohort compared with internal cohort (0.69-0.71 versus 0.60-0.61), likely reflecting uniform MRD assessment. At a 25% risk threshold for clinical decision-making, models identified approximately 1 additional high-risk patient per 100 versus HCT-CI, or aELN. At 2-years, 25-27% of patients categorized as low-risk had died, while 44.6-47.2% categorized as high-risk were alive.

CONCLUSIONS: ML approaches improved risk stratification over HCT-CI and aELN but performed comparably with Cox model. Individual outcome prediction using static pre-transplant models remained modest. Progress will require MRD standardization, richer data. and dynamic peri- and post-transplant modeling.},
}

@article {pmid41482012,
year = {2025},
author = {Dussault, N and Ma, J and Ivey, N and Bernal, T and Clifton, D and Jones, CA and Santivasi, WL},
title = {Caring through Complexity: Developing a Palliative Care Opioid and Stimulant Use Disorder Workflow.},
journal = {Journal of pain and symptom management},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jpainsymman.2025.12.017},
pmid = {41482012},
issn = {1873-6513},
abstract = {CONTEXT: Caring for individuals with serious illness and opioid or stimulant use disorder (OUD/STuD) is complex. Palliative care (PC) providers often lack addiction medicine training and report discomfort managing this population.

OBJECTIVES: This quality improvement project aimed to assess PC team comfort, provide targeted education, and create an institutional PC workflow around caring for individuals with OUD/STuD.

METHODS: This project was conducted within an academic health system's PC program. A pre-intervention survey assessed baseline comfort caring for individuals with OUD/StUD. The intervention included the development and dissemination of 1) an evidence-based, locally adapted workflow guiding opioid prescribing and clinic management protocols stratified by substance use risk and 2) educational sessions on buprenorphine for pain, substance use risk assessment, and safe opioid management. During implementation, the workflow was iteratively updated based on challenges identified in patient cases (i.e., diagnostic uncertainty, unexpected urine toxicology screens). A post-intervention survey assessed changes in provider comfort after implementation.

RESULTS: Of the 27 individuals who completed the pre-survey (response rate 73%), 66% felt uncomfortable overall caring for individuals with OUD/StUD; among prescribers, only 19% felt comfortable managing opioids for this population. The workflow was applied to ten patients (ages 38-76; all with cancer). In the post survey (n=23, response rate 62%), fewer respondents (35%) felt uncomfortable overall caring for individuals with OUD/StUD and a majority of prescribers (52%) felt comfortable managing opioids for this population.

CONCLUSION: Developing evidence-based, locally adapted workflows and educational sessions can improve PC provider comfort around caring for patients with OUD/StUD.},
}

@article {pmid41478442,
year = {2025},
author = {Kotini-Shah, P and Duran-Luciano, P and Kansal, M and Nasrollahi, F and Lee, UJ and Yuan, Y and Rangel, MO and Kaplan, R and Ponce, SG and Shah, SJ and Cai, J and Bilsker, MS and Pu, M and Hurwitz, BE and Rodriguez, CJ},
title = {Global Longitudinal Strain Reference Values in the Hispanic/Latino Population: Echocardiographic Study of Latinos (ECHO-SOL).},
journal = {The American journal of cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amjcard.2025.12.014},
pmid = {41478442},
issn = {1879-1913},
abstract = {Global Longitudinal Strain (GLS) is a sensitive measure for detecting early cardiac dysfunction, but prone to variability by age, race/ethnicity, and sex. To date, GLS has not been described in Hispanics/Latinos, nor has GLS been associated with heart failure risk factors. Data from the Echocardiographic-Study of Latinos, a population-based study of Hispanics/Latinos in the United States, was used. A reference healthy sample was used to define the 95[th]-percentile lower limit of normal GLS value of -14.2% which was applied to the target population to describe the distribution of GLS across age, gender and Hispanic/Latino background groups. The proportion of normal/abnormal GLS and left ventricular ejection fraction (LVEF) are described; as well as the proportion of abnormal GLS across prevalent heart failure risk factors (hypertension, obesity, and diabetes). Survey statistics and weighted frequencies were used in all analyses. The study sample consisted of 1,818 adult participants (mean age 56.4 years; 42.6% female). The overall ECHO-SOL target population had a mean GLS of -17.6% with 12.1% having prevalent abnormal GLS. GLS was significantly worse in men than women and abnormal GLS was more prevalent among individuals of Cuban background than any other Hispanic/Latino background group. More than half (56.4%) of individuals with abnormal GLS had values within the normal LVEF range and there was worsening GLS values with increasing heart failure risk factor burden (p<0.01). In conclusion, our study establishes the first Hispanic/Latino-specific GLS reference values, emphasizing the importance of representative populations in the derivation of myocardial deformation thresholds. Abnormal GLS was prevalent among Hispanics/Latinos and increasing heart failure risk factor burden correlated with worsening GLS, reinforcing the role of risk factors in early cardiovascular risk assessment.},
}

@article {pmid41478324,
year = {2025},
author = {Ahmed, S and Kumar, A and Carpenter, P and Herrera, A and Kelly, K and Pinnix, C and Rutherford, S and Grover, N and Evens, A and Lynch, R and Kenkre, V and Merryman, R and Sauter, C and Nishihori, T and Moskowitz, A and Awan, F and Svoboda, J and Winter, J and Allen, P and Ermoian, R and Ansell, S and Aljuhaishi, T and Nieto, Y and Hamadani, M and Perales, MA},
title = {ASTCT Clinical Practice Recommendations for Transplantation in Classical Hodgkin Lymphoma.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.12.944},
pmid = {41478324},
issn = {2666-6367},
abstract = {Autologous hematopoietic cell transplantation (auto-HCT) remains the standard therapeutic approach for patients with chemotherapy-sensitive relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). Over the past decade, the therapeutic landscape for cHL has evolved substantially with the introduction of novel agents, including antibody-drug conjugates and immune checkpoint inhibitors, which have demonstrated significant efficacy in the relapsed setting and are now incorporated into frontline treatment regimens. These advances have not only expanded the armamentarium available for disease management but have also led to improved long-term outcomes, raising important considerations regarding the optimal sequencing of therapies and the evolving role of transplantation in the modern treatment paradigm. Hematopoietic cell transplantation (HCT) remains a cornerstone in the management of cHL; however, consensus is lacking regarding the optimal timing of auto-HCT, the sequencing and integration of novel therapeutic agents, the potential role of maintenance therapy following auto-HCT, and the appropriate indications and timing for allogeneic (allo) HCT. Therefore, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines undertook a project to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 20 consensus statements with key recommendations as follows: (1) use of auto-HCT consolidation after salvage therapy in the first relapse setting, for patients with chemotherapy-sensitive R/R cHL in complete response; (2) preferred use of pre-HCT salvage therapy regimens with novel agents; (3) consultation for allo-HCT in eligible patients who have disease relapse after auto-HCT; (4) guidance regarding optimal stem cell donor source; (5) selection of conditioning regimen for both auto-HCT and allo-HCT; and (6) preferred graft versus host disease prophylaxis in the modern era. These clinical practice recommendations serve as a tool to guide clinical management of R/R cHL.},
}

@article {pmid41477868,
year = {2026},
author = {Lee, J and Jung, H and Kim, EG and Ahn, J and Haffner, MC and Nelson, PS and Kim, KP and Lee, JK and Yi, EC and Kim, KM},
title = {Phenotypic discovery and therapeutic evaluation of an ITGA3B1-targeting antibody-drug conjugate for bladder cancer.},
journal = {Science advances},
volume = {12},
number = {1},
pages = {eady0041},
pmid = {41477868},
issn = {2375-2548},
mesh = {*Urinary Bladder Neoplasms/drug therapy/metabolism/pathology ; Humans ; *Immunoconjugates/pharmacology/therapeutic use/chemistry ; Animals ; Cell Line, Tumor ; Mice ; Xenograft Model Antitumor Assays ; *Integrin alpha3beta1/antagonists & inhibitors/metabolism/immunology ; Oligopeptides/pharmacology/chemistry ; Proteomics ; Drug Discovery ; Phenotype ; Integrin alpha3 ; },
abstract = {Antibody-drug conjugates (ADCs) require antibodies with both high specificity and efficient internalization, features often overlooked by conventional discovery pipelines that rely on preselected antigens and recombinant proteins. Here, we describe an integrated phenotypic platform that combines target-unbiased live-cell biopanning with in situ chemical cross-linking and mass spectrometry to concurrently identify internalizing antibodies and their membrane-bound cognate antigens in a native cellular context. Using this approach, we identified 2E7, an antibody with rapid internalization and specificity for the integrin α3β1 (ITGA3B1) heterodimer. Integrated transcriptomic and proteomic analyses revealed pronounced overexpression of ITGA3B1 across multiple solid tumors, with particularly elevated levels in aggressive bladder cancer subtypes. A 2E7-MMAE (monomethyl auristatin E) ADC exhibited potent, dose-dependent antitumor activity in bladder cancer xenograft models, leading to tumor regression and prolonging survival. This study establishes a generalizable framework for function-first ADC discovery and nominates ITGA3B1 as a promising therapeutic target in bladder cancer.},
}

*Urinary Bladder Neoplasms/drug therapy/metabolism/pathology
Humans
*Immunoconjugates/pharmacology/therapeutic use/chemistry
Animals
Cell Line, Tumor
Mice
Xenograft Model Antitumor Assays
*Integrin alpha3beta1/antagonists & inhibitors/metabolism/immunology
Oligopeptides/pharmacology/chemistry
Proteomics
Drug Discovery
Phenotype
Integrin alpha3

@article {pmid41476111,
year = {2025},
author = {Van Buren, E and Zhang, Y and Li, X and Selvaraj, MS and Li, Z and Zhou, H and Palmer, ND and Arnett, DK and Blangero, J and Boerwinkle, E and Cade, BE and Carlson, JC and Carson, AP and Chen, YI and Curran, J and Duggirala, R and Fornage, M and Franceschini, N and Graff, M and Gu, C and Guo, X and He, J and Heard-Cosa, N and Hou, L and Hung, YJ and Kalyani, RR and Kardia, SLR and Kenny, E and Kooperberg, C and Kral, BG and Lange, L and Levy, D and Li, C and Liu, S and Lloyd-Jones, D and Loos, RJF and Manichaikul, AW and Martin, LW and Mathias, R and Minster, RL and Mitchell, BD and Mychaleckyj, JC and Naseri, T and North, K and O'Connell, J and Perry, JA and Peyser, PA and Psaty, BM and Raffield, LM and Vasan, RS and Redline, S and Reiner, AP and Rich, SS and Smith, JA and Spitzer, B and Tang, H and Taylor, KD and Tracy, R and Viali, S and Yanek, L and Zhao, W and , and Rotter, JI and Peloso, GM and Natarajan, P and Lin, X},
title = {cellSTAAR: incorporating single-cell-sequencing-based functional data to boost power in rare variant association testing of noncoding regions.},
journal = {Nature methods},
volume = {},
number = {},
pages = {},
pmid = {41476111},
issn = {1548-7105},
support = {R35-CA197449//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; U19-CA203654//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; U01-HG012064//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; U01-HG009088//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; R01HL173044//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92021F00229//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92021F00229//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01- HL072524//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL104135-04S1//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01-HL054472//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01-HL054473//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01-HL054495//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01-HL054509//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL055673-18S1//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HHSN268201700001I/HL/NHLBI NIH HHS/United States ; HHSN268201700002I/HL/NHLBI NIH HHS/United States ; HHSN268201700005I/HL/NHLBI NIH HHS/United States ; HHSN268201700004I/HL/NHLBI NIH HHS/United States ; R01-HL153805//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R03- HL154284//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00001/HL/NHLBI NIH HHS/United States ; HHSN268201500003I/HL/NHLBI NIH HHS/United States ; N01-HC-95159//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00005/HL/NHLBI NIH HHS/United States ; N01-HC-95160//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00002/HL/NHLBI NIH HHS/United States ; N01-HC-95161//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00003/HL/NHLBI NIH HHS/United States ; N01-HC-95162//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00006/HL/NHLBI NIH HHS/United States ; N01-HC-95163//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00004/HL/NHLBI NIH HHS/United States ; N01-HC-95164//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00007/HL/NHLBI NIH HHS/United States ; N01-HC-95165//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95166//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95167//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95168//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95169//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071051//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071205//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01- HL071250//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071251//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071258//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071259//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HHSN268201600018C/HL/NHLBI NIH HHS/United States ; HHSN268201600001C/HL/NHLBI NIH HHS/United States ; HHSN268201600002C/HL/NHLBI NIH HHS/United States ; HHSN268201600003C/HL/NHLBI NIH HHS/United States ; HHSN268201600004C/HL/NHLBI NIH HHS/United States ; HL105756//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 1R35-HL135818//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01- HL113338//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HL046389//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00001/HL/NHLBI NIH HHS/United States ; HHSN268201500003I/HL/NHLBI NIH HHS/United States ; N01-HC-95159//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00003/HL/NHLBI NIH HHS/United States ; N01-HC-95162//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00006/HL/NHLBI NIH HHS/United States ; N01-HC-95163//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00004/HL/NHLBI NIH HHS/United States ; N01-HC-95164//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 75N92020D00007/HL/NHLBI NIH HHS/United States ; N01-HC-95165//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95166//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95167//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95168//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; N01-HC-95169//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071051//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071205//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01- HL071250//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071251//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071258//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL071259//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL142711//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL127564//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL142711//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01-HL127564//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; UL1-TR-000040//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1-TR-001079//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1-TR-001420//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1-TR001881//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1-TR-000040//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1-TR-001079//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1-TR-001420//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UL1-TR001881//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; DK063491//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; R01-DK117445//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; DK063491//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; UL1-RR033176//U.S. Department of Health & Human Services | NIH | National Center for Research Resources (NCRR)/ ; UL1-RR033176//U.S. Department of Health & Human Services | NIH | National Center for Research Resources (NCRR)/ ; R01-MD012765//U.S. Department of Health & Human Services | NIH | National Institute on Minority Health and Health Disparities (NIMHD)/ ; },
abstract = {Understanding how rare genetic variants influence complex traits remains a major challenge, particularly when these variants lie in noncoding regions of the genome. The effects of variants within candidate cis-regulatory elements (cCREs) often depend on the cell type, making interpretation difficult. Here we introduce cellSTAAR, which integrates whole-genome sequencing data with single-cell assay for transposase-accessible chromatin using sequencing data to capture variability in chromatin accessibility across cell types via the construction of cell-type-specific functional annotations and regulatory elements. To reflect the uncertainty in cCRE-gene linking, cellSTAAR uses a comprehensive strategy to link cCREs to their target genes. We applied cellSTAAR to data from the Trans-Omics for Precision Medicine consortium (n ≈ 60,000) and replicated our findings using the UK Biobank (n ≈ 190,000). Across four lipid traits, cellSTAAR improved the detection of biologically meaningful associations and enhanced biological interpretability. These results demonstrate the potential of cell-type-aware approaches to boost discovery in rare variant whole-genome sequencing association studies.},
}

@article {pmid41474700,
year = {2025},
author = {Kwendakwema, CN and Eastment, MC and Wanje, G and Richardson, BA and Mwaringa, E and Sherr, K and Mandaliya, KN and Barnabas, RV and Jaoko, W and McClelland, RS},
title = {Cross-sectional study evaluating organizational climate, change commitment, and change efficacy for predicting family planning clinics' success in increasing HIV counseling and testing in Mombasa, Kenya.},
journal = {PLOS global public health},
volume = {5},
number = {12},
pages = {e0005542},
pmid = {41474700},
issn = {2767-3375},
abstract = {Increasing HIV testing and counselling (HTC) is a first step to reducing HIV transmission. Implementing HTC in family planning (FP) clinics has been proposed to increase HIV testing coverage in at-risk populations. The Systems Analysis and Improvement Approach (SAIA) was used to improve HTC rates in FP clinics in Mombasa, Kenya. This hypothesis-generating exploratory analysis evaluated the associations between organizational climate characteristics, organizational readiness for implementing change, and successful implementation of HTC. Surveys were conducted with clinic managers and staff from FP clinics implementing SAIA to increase HTC. Likert-style questions were used to characterize organizational climate metrics and organizational readiness for implementing change (ORIC). Linear regression was performed to examine the association between organizational climate metrics, ORIC domains, and two FP client outcomes: 1) percentage of clients receiving pre-HIV test counseling, and 2) percentage of clients tested for HIV. Eleven clinic staff and 10 clinic managers completed the surveys. For clinic staff, higher innovation and flexibility scores were associated with higher change commitment (β = 0.20, CI 0.09-0.31, p = 0.001) and change efficacy (β = 0.17, CI 0.07-0.26, p = 0.002). Higher clinic manager scores for innovation and flexibility were associated with a higher change commitment (β = 0.44, CI 0.04-0.84, p = 0.03). Additionally, clinic managers' scores for management support (β = 0.25, CI 0.06-0.45, p = 0.01), commitment to facility (β = 0.78, CI 0.60-0.96, p = 0.001), and relative priority (β = 0.24, CI 0.08-0.39, p = 0.004) were positively associated with higher change commitment and change efficacy. In contrast, clinic managers' scores for tradition were negatively associated with change commitment (β = -0.38, CI -0.75-0.01, p = 0.05). Clinic staff perceptions of management support were positively associated with the proportion of clients counseled for HIV testing (β = 1.20, CI 0.08-2.32, p = 0.04). Support from leadership and innovation/flexibility are important predictors of change commitment and change efficacy. Strong management support may increase the likelihood of successful implementation of SAIA to improve HTC.},
}

@article {pmid41473276,
year = {2025},
author = {Nutt, WS and Kluesner, MG and Bingham, E and Gad, E and Miller, D and Zepeda, V and Snyder, AJ and Marsh, SA and Liudahl, SM and Hoffman, M and LeBlanc, L and Volfbeyn, ME and Garrison, SM and Sarvothama, M and Barry, KC and Headley, MB and Marcondes, M and Srivastava, S},
title = {NKTR-255, a polymer-conjugated IL-15, synergizes with CAR-T cell therapy to activate endogenous anti-tumor immunity and improve tumor control.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41473276},
issn = {2692-8205},
abstract = {CAR-T cells have yet to show widespread efficacy in solid tumors due in part to their poor persistence and loss of function in the tumor microenvironment. Further, heterogenous expression of most CAR target antigens in solid tumors can lead to escape of antigen-null tumors that resist CAR-T killing. Strategies to cooperatively boost both CAR-T and endogenous anti-tumor immunity could curb tumor escape and may be critical for achieving durable efficacy in cancer patients. NKTR-255 is a polymer-conjugated IL-15 with extended half-life that can boost endogenous T and NK cells, as well as CD19 CAR-T activity in B cell malignancies. However, whether NKTR-255 is sufficient to overcome CAR-T dysfunction in the suppressive solid tumor microenvironment, and how NKTR-255 and CAR-Ts together re-shape endogenous anti-tumor immunity, is not known. Using an autochthonous mouse model of ROR1[+] lung adenocarcinoma, we show that NKTR-255 significantly boosted accumulation, reduced exhaustion, and improved function of tumor-infiltrating CAR-T cells. Compared with NKTR-255 or CAR-T treatment alone, combination of NKTR-255 and CAR-T therapy synergistically increased tumor-infiltrating CD11b[+] cytotoxic NK cells, activated dendritic cells, and endogenous tumor-specific T cells that preserved a PD-1[+]Tcf1[+] stem-like phenotype. Consequently, NKTR-255 and CAR-T combination therapy induced complete elimination of ROR1[+] tumor and significantly improved survival, with enhanced tumor control dependent on activity of both CAR-Ts and endogenous T cells. Altogether, our data suggest that combining NKTR-255 with CAR-T therapy is a promising strategy to enhance both CAR-T and endogenous anti-tumor immunity to promote coordinated control of aggressive tumors.},
}

@article {pmid41472424,
year = {2025},
author = {Wallace, PK and Jellison, ER and Thornton, S and Kluepfel, K and Back, J and Beadnell, TC and Bebes, A and Behrends, J and Belkina, AC and Black, M and Bogdanoski, G and Bollati-Fogolín, M and Bonte, S and Van der Borght, K and Brinkman, RR and Brundage, K and Bushnell, T and Chiu, DT and Chow, N and Ciccolella, CO and Cochran, M and Czechowska, K and Dagla, K and Daniel, B and de la Cruz, G and Van Duyse, J and Font, LF and Fornas, Ò and Garcia-Garcia, S and Gardner, R and Van Gassen, S and Gimenes, D and Grenfell, R and Grider-Hayes, MJ and Grose, R and Hall, C and Hally, KE and Hameetman, M and Hogg, K and Houston, J and Irish, JM and Isterdael, GV and Jaimes, M and Janetzki, S and Kim, C and Koladiya, A and Lamote, J and Lannigan, J and Leconte, J and Litwin, V and Longhini, A and Loof, N and Lozano-Andrés, E and Lundsten, K and Mage, P and Mair, F and Martins, CG and McCausland, M and McGuire, HM and Meskas, J and Murphy, W and Nolan, J and Oliveira, B and Ordoñez-Rueda, D and Orlowski-Oliver, E and Petersen, CC and Poulton, NJ and Putri, G and Quadrini, KJ and Ramasz, B and Ruhrmund, D and Singh, VV and Small, SJ and Smith, NJ and Spidlen, J and Stegen, C and Tak, T and Thompson, S and Thomson, M and Vocelle, D and Walker, RV and Walsh, RE and Wang, L and Wang, YF and Weglarz, M and Winker, M and Wood, JCS and Woolard, S and Yeh, NY and Yuecel, R and Rajwa, B},
title = {Cyt-Geist: Current and Future Challenges in Cytometry: Reports of the CYTO 2025 Conference Workshops.},
journal = {Cytometry. Part A : the journal of the International Society for Analytical Cytology},
volume = {},
number = {},
pages = {},
doi = {10.1002/cytoa.70002},
pmid = {41472424},
issn = {1552-4930},
}

@article {pmid41470899,
year = {2025},
author = {Kadro, ZO and Rillamas-Sun, E and Langley, BO and Meisner, A and Contento, I and Koch, PA and Ogden Gaffney, A and Hershman, DL and Greenlee, H},
title = {Associations Between the Food Environment and Food Insecurity on Fruit, Vegetable, and Nutrient Intake, and Body Mass Index, Among Urban-Dwelling Latina Breast Cancer Survivors Participating in the &iexcl;Mi Vida Saludable! Trial.},
journal = {Nutrients},
volume = {17},
number = {24},
pages = {},
pmid = {41470899},
issn = {2072-6643},
support = {R01 CA186080/CA/NCI NIH HHS/United States ; R01 CA186080-02S1/CA/NCI NIH HHS/United States ; UL1 TR001873/TR/NCATS NIH HHS/United States ; },
mesh = {Adult ; Aged ; Female ; Humans ; Middle Aged ; *Body Mass Index ; *Breast Neoplasms ; *Cancer Survivors/statistics & numerical data ; *Diet ; *Food Insecurity ; Food Supply ; Fruit ; *Hispanic or Latino/statistics & numerical data ; Urban Population ; Vegetables ; },
abstract = {Background: Socioeconomic disparities may drive cancer inequities in Hispanic/Latino populations. We examined associations of perceived access to healthy foods (AHF) and food insecurity (FI) with diet and body mass index (BMI) changes in Latina breast cancer (BC) survivors. Methods: Latina BC survivors in a 12-month intervention trial aiming to increase fruit/vegetable intake and physical activity were analyzed. AHF was from a modified, validated neighborhood environment scale and dichotomized (low-medium vs. high). FI was defined as eating less and/or going hungry due to a lack of money. AHF and FI surveys were self-reported. Outcomes included dietary intake, diet quality, and BMI. Fruit/vegetable intake was log-transformed. Relationships between AHF and FI and changes in diet and BMI were evaluated using generalized estimating equations. Results: Of women with AHF data (n = 86), 58% reported low-medium access and 42% reported high access. Fruit/vegetable (FV) intake declined overall from baseline to 12 months, with greater reductions among low-medium AHF women (-32%, 95% CI: -51%, -7%) compared with high AHF women (-17%, 95% CI: -40%, +13%). Statistically significant 12-month decreases in total calories, carbohydrates, sugars, and fat occurred in low-medium AHF women but not high AHF women, and changes in total energy density, carbohydrates, sugars, and BMI at 12 months were statistically significantly different between women with low-medium AHF and women with high AHF, p ≤ 0.05. Among 157 women, 23% reported FI. Reductions in fruit/vegetable intake were larger in women with FI (-39%, 95% CI: -57%, -14%) than in women without FI (-10% reductions, 95% CI: -25%, +8%) and between-group differences were significant at both 6 and 12 months, p ≤ 0.05. Most diet measures decreased for both FI and non-FI women, with greater decreases among those with FI. Conclusions: Latina BC survivors with FI or perceived limited AHF experienced greater declines in indicators of healthy diets including FV intake. Future interventions should integrate strategies to measure AHF and FI to address disparate access to healthy food options.},
}

Adult
Aged
Female
Humans
Middle Aged
*Body Mass Index
*Breast Neoplasms
*Cancer Survivors/statistics & numerical data
*Diet
*Food Insecurity
Food Supply
Fruit
*Hispanic or Latino/statistics & numerical data
Urban Population
Vegetables

@article {pmid41469386,
year = {2025},
author = {Li, B and Lin, R and Ni, T and Yan, G and Burns, M and Li, JJ and Yao, Z},
title = {CellScope: high-performance cell atlas workflow with tree-structured representation.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-67890-3},
pmid = {41469386},
issn = {2041-1723},
support = {A-8001562-00-00//Ministry of Education - Singapore (MOE)/ ; A-0008520-00-00//Ministry of Education - Singapore (MOE)/ ; A-8002931-00-00//Ministry of Education - Singapore (MOE)/ ; },
abstract = {Single-cell sequencing enables comprehensive profiling of individual cells, revealing cellular heterogeneity and function with unprecedented resolution. However, current analysis frameworks lack the ability to simultaneously explore and visualize cellular hierarchies at multiple biological levels. To address these limitations, we present CellScope, a promising framework for constructing high-resolution cell atlases at multiple clustering levels. CellScope employs a two-stage manifold fitting process for gene selection and noise reduction, followed by agglomerative clustering, and integrates UMAP visualization with hierarchical clustering to intuitively represent cellular relationships simultaneously at multiple levels-such as cell lineage, cell type, and cell subtype levels. Compared to established pipelines such as Seurat and Scanpy, CellScope comprehensively improves clustering performance, visualization clarity, computational efficiency, and algorithm interpretability, while reducing dependence on hyperparameters across a multitude of single-cell datasets. Most importantly, it can reveal biological insights that other contemporary methods are unable to detect, thereby deepening our understanding of cellular heterogeneity and function, and potentially informing disease research.},
}

@article {pmid41468926,
year = {2025},
author = {Rangarajan, HG and Chellapandian, D and Atshan, R and Ahn, KW and Kumar, S and Knight, TE and Leung, W and Ganguly, S and Williams, KM and Shah, NN and Bhatt, NS and Lust, H and Prestidge, T and Brown, VI and Hayashi, RJ and Choe, M and Saad, A and Bidgoli, A and Thakar, MS and Wirk, B and MacMillan, ML and Lalefar, NR and Hematti, P and Schultz, KR and Phillips, CL and Mehta, PA and Qayed, M and Sharma, A and Broglie, L and Satwani, P},
title = {Impact of Extramedullary Disease at Diagnosis on Outcomes Post Allogeneic Hematopoietic Cell Transplant in Children and Young Adults with Acute Myeloid Leukemia: A CIBMTR Report.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.12.990},
pmid = {41468926},
issn = {2666-6367},
abstract = {BACKGROUND: Conflicting reports exist regarding the impact of extramedullary disease (EMD) at diagnosis upon outcomes after allogeneic hematopoietic cell transplantation (HCT) in children and young adults with acute myeloid leukemia (AML).

OBJECTIVES AND STUDY DESIGN: We retrospectively analyzed the effect of EMD at diagnosis on post-HCT outcomes in a large cohort of children and young adults (21 and younger) who had AML and received their first myeloablative allogeneic HCT for AML during 2008-2019 (N = 938; 52% males). Data were obtained from the Center for International Blood and Marrow Transplant Research database. Patients were grouped based on EMD at diagnosis as bone marrow (BM) involvement only (Group I; n = 630); BM + central nervous system (CNS) involvement (Group II; n = 212), and BM + other EMD ± CNS (Group III n = 96). All patients were in a morphologic complete remission (CR) with no evidence of EMD pre-HCT. Outcomes compared included 3-year progression-free survival (PFS), overall survival (OS), non-relapse mortality (NRM), and relapse incidence(RI).

RESULTS: Group III patients were younger at HCT (Group III median age 3, vs age 11 in Group I, and age 10 in Group II) and more often had high Pediatric Disease Risk Index scores (52% in Group III vs 22% in Group I and 25% in Group II). At a median follow-up of 70 months (range 3-155 months), the 1-year and 3-year PFS, NRM, RI, and OS were similar among all 3 groups on univariate analysis. On multivariable analysis, the presence of EMD was associated with decreased RI: Group II, with a hazard ratio (HR) of 0.70 (95% CI, 0.52-0.94; P = .020) and Group III with an HR of 0.70 (95% CI, 0.46-1.05; P = .086) compared to Group I. There was no difference in PFS (P = .21), NRM (P = .27), and OS (P = .82) among the groups.

CONCLUSION: In our study, in patients with AML who proceeded to HCT in CR, the presence of EMD at diagnosis was not associated with adverse outcomes or increased relapse risk.},
}

@article {pmid41143601,
year = {2026},
author = {Cliff, ERS and Pelaez, GD and Wan, F and Iyengar, V and Zhou, J and Chung, K and Abdel-Razeq, N and Allen, J and Major, A and Sharp, J and Epperla, N and Gould, P and Cherng, HJ and Houshyar, S and Wallace, DS and Lynch, RC and Kallam, A and Mei, MG and Merryman, RW and Fleyshman, M and Rhodes, JM and Kidwell, A and Fenske, TS and Malakhov, N and Mulvey, E and Watkins, MP and Alhaj Moustafa, M and Hilal, T and Nowakowski, GS and Wang, Y and Torka, P and Russler-Germain, DA},
title = {Cell-of-Origin Subtype Predicts Response to Polatuzumab Vedotin in Large B-cell Lymphoma.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {32},
number = {1},
pages = {159-168},
pmid = {41143601},
issn = {1557-3265},
support = {K12 CA167540/CA/NCI NIH HHS/United States ; T32 CA247815/CA/NCI NIH HHS/United States ; K12CA167540//National Cancer Institute (NCI)/ ; T32CA247815//National Cancer Institute (NCI)/ ; //Lymphoma Research Foundation (LRF)/ ; },
mesh = {Humans ; *Lymphoma, Large B-Cell, Diffuse/drug therapy/pathology/mortality ; Male ; Female ; Middle Aged ; Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; Adult ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage ; *Immunoconjugates/administration & dosage/therapeutic use ; Aged, 80 and over ; Prognosis ; Treatment Outcome ; Antibodies, Monoclonal ; },
abstract = {PURPOSE: Polatuzumab vedotin (polatuzumab) was approved for up-front treatment of diffuse large B-cell lymphoma in combination with chemoimmunotherapy (Pola-R-CHP) based on the POLARIX trial. However, when stratified by cell of origin (COO), polatuzumab seems to have greater efficacy in activated B-cell than germinal center B-cell (GCB) subtype disease. Most studies of polatuzumab used RNA expression to assess COO, whereas in routine clinical practice, the immunohistochemistry-based Hans algorithm is used.

EXPERIMENTAL DESIGN: To assess the impact of COO by immunohistochemistry on polatuzumab efficacy, we conducted a multicenter real-world study of adults with large B-cell lymphoma (LBCL) receiving polatuzumab from 2015 to 2024, split by receipt of polatuzumab in first-line versus relapsed/refractory settings. The primary endpoint was overall response rate (ORR) to polatuzumab-based treatment in GCB versus non-GCB relapsed/refractory LBCL.

RESULTS: Of 740 patients, 305 received polatuzumab in the first-line setting and 435 in the relapsed/refractory setting. In the relapsed/refractory cohort, the ORR in non-GCB versus GCB LBCL was 59.7% versus 36.3% [OR, 2.6; 95% confidence interval (CI), 1.77-3.84; P < 0.0001], with a complete response rate of 35.7% versus 17.7% (OR, 2.6; 95% CI, 1.66-4.02; P < 0.0001). Progression-free survival was longer for patients with non-GCB versus GCB COO (HR, 0.64; 95% CI, 0.5-0.83; P = 0.0006). In the first-line cohort, ORR, complete response rate, and progression-free survival were similar in non-GCB versus GCB LBCL, as hypothesized based on outcomes in the Pola-R-CHP arm of POLARIX, suggesting that the addition of polatuzumab overcomes the adverse risk of non-GCB COO in patients receiving R-CHOP.

CONCLUSIONS: Based on these data, COO classification by the Hans algorithm is a strong predictor of polatuzumab efficacy in LBCL, informing real-world treatment decisions.},
}

Humans
*Lymphoma, Large B-Cell, Diffuse/drug therapy/pathology/mortality
Male
Female
Middle Aged
Aged
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects
Adult
*Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage
*Immunoconjugates/administration & dosage/therapeutic use
Aged, 80 and over
Prognosis
Treatment Outcome
Antibodies, Monoclonal

@article {pmid41467901,
year = {2026},
author = {Hanson, F and Hickner, B and Fisher, C and Hein, H and Kukreja, K and Goss, J and Galvan, TN and Leung, DH and Banc-Husu, AM and Masand, P and Patel, K and Lopez-Terrada, D and Heczey, A and Vasudevan, S and Voeller, J},
title = {Case of Advanced Hepatocellular Carcinoma Treated With Transarterial Radioembolization and Subsequent Liver Transplantation in a 22-Month-old.},
journal = {Journal of pediatric hematology/oncology},
volume = {48},
number = {1},
pages = {e35-e40},
doi = {10.1097/MPH.0000000000003152},
pmid = {41467901},
issn = {1536-3678},
mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/pathology ; *Liver Neoplasms/therapy/pathology ; *Liver Transplantation ; *Embolization, Therapeutic/methods ; Infant ; Male ; Yttrium Radioisotopes/therapeutic use ; },
abstract = {Hepatocellular carcinoma (HCC) is a rare malignancy in children, typically requiring chemotherapy, surgical resection, and/or transplant for treatment. Whether HCC arises as a novel tumor (de novo) or in the setting of chronic liver disease determines treatment strategy. We describe a case of a pediatric patient with unresectable HCC due to macrovascular invasion and tumor thrombus of the portal vein who received transarterial radioembolization (TARE) and underwent successful orthotopic liver transplantation outside of Milan criteria.},
}

Humans
*Carcinoma, Hepatocellular/therapy/pathology
*Liver Neoplasms/therapy/pathology
*Liver Transplantation
*Embolization, Therapeutic/methods
Infant
Male
Yttrium Radioisotopes/therapeutic use

@article {pmid41467111,
year = {2026},
author = {Mukhtar, RA and Flanagan, MR},
title = {Locoregional Considerations for Invasive Lobular Carcinoma.},
journal = {Current breast cancer reports},
volume = {18},
number = {1},
pages = {2},
pmid = {41467111},
issn = {1943-4588},
abstract = {PURPOSE OF REVIEW: This article summarizes recent literature on locoregional management of patients with invasive lobular carcinoma (ILC), including approaches to breast surgery, axillary management, and neoadjuvant therapy.

RECENT FINDINGS: Breast conservation therapy is safe in ILC, but has comparatively high rates of positive margins, which can be reduced by routine use of shave margins and oncoplastic surgery. Studies demonstrating the safety of de-escalation of axillary surgery have not included enough patients with ILC to draw strong conclusions; current guidelines do not support omission of sentinel node surgery in most patients with ILC. Neoadjuvant chemotherapy may improve breast conservation and increase nodal pathologic complete response in molecularly selected patients using genomic assays.

SUMMARY: The locoregional management of patients with ILC requires special considerations based on its unique features. ILC specific studies are needed to address knowledge gaps for patients diagnosed with this common tumor type.},
}

@article {pmid41466427,
year = {2025},
author = {Kareithi, T and Roche, SD and Meisner, A and Omollo, V and Ong'wen, PA and Harkey, K and Kiptinness, C and Otieno, P and Juma, L and Malen, RC and Anyona, MO and Curran, K and Banerjee, P and Gichuru, E and Asewe, M and Yu, K and Pintye, J and Mugambi, ML and Shah, PD and Sharma, M and Were, D and Ngure, K and Bukusi, EA and Ortblad, KF and , },
title = {Testing different models of pharmacy-based HIV pre- and post-exposure prophylaxis initiation and management in Kenya: protocol for a cluster-randomized controlled trial.},
journal = {Trials},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13063-025-09384-7},
pmid = {41466427},
issn = {1745-6215},
support = {INV-033052/GATES/Gates Foundation/United States ; R00 MH121166/MH/NIMH NIH HHS/United States ; },
abstract = {BACKGROUND: In Kenya, as in many African countries, private pharmacies are ubiquitous, frequently accessed, and underutilized for the delivery of HIV prevention services. Whether enabling private pharmacies to initiate and manage clients on HIV pre- and post-exposure prophylaxis (PrEP and PEP) leads to greater uptake and continuation than the current standard-pharmacy referral to clinic-based PrEP/PEP-is unknown. To address this gap and inform how private pharmacies might partner with the public sector, we are testing several models of pharmacy-delivered PrEP/PEP in comparison to the current standard.

METHODS: The Pharm PrEP cRCT is a 60-pharmacy, four-arm cluster-randomized controlled trial ongoing in Central and Western Kenya (first enrollment: 26 June 2023). Eligible pharmacies were licensed by the government, had a private room, and were willing to complete research activities (including a 3-day provider training). Study pharmacies were randomized 1:1:1:1 to (1) client-sustained delivery, in which clients pay pharmacies 250 KES (~$2 USD) per PrEP/PEP visit; (2) implementor-sustained delivery, in which clients pay nothing and implementors pay pharmacies 250 KES per PrEP/PEP visit; (3) implementor-sustained + counselor-supported delivery, in which clients pay nothing, delivery is supported by an HIV testing services (HTS) counselor, and implementors pay pharmacies 100 KES (~$1 USD) per PrEP/PEP visit; or 4) referral (control), in which clients pay nothing and implementors pay pharmacies 100 KES per referral to clinic-based PrEP/PEP. Pharmacies delivering PrEP/PEP receive supporting commodities free from government stock. Primary outcomes are PrEP initiation and continuation (any refilling) reported by clients 60 days post-enrollment; secondary outcomes include PEP initiation, PEP-to-PrEP transition, repeat PEP use, PrEP/PEP initiation, and PrEP/PEP continuation at 60 and 270 days post-enrollment. Primary analyses will compare each intervention arm to the control; secondary analyses will compare intervention arms to one another. We will additionally assess implementation outcomes (e.g., acceptability, feasibility, cost) from client and provider perspectives.

DISCUSSION: This trial will generate evidence on the potential benefits of leveraging private pharmacies for delivery of PrEP and PEP and the relative effectiveness of pharmacy delivery when subsidized by clients, implementors, and/or supported by HTS counselors. The findings may inform enabling policy and approaches for scale-up.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05842122. Registered on April 5, 2023.},
}

@article {pmid41461908,
year = {2025},
author = {, and Alberts, T and Albritton, CF and Alcazar, R and Aljabri, Z and Alvarez, M and Aradhey, A and Ayalew, M and Azizian, N and Balayah, Y and Ball, DD and Barragan, E and Beshoar, C and Best, L and Biggane, E and Biggane, J and Blick, J and Blosser, M and Brown, AK and Campbell, MC and Canizares, Z and Chanhuhwa, FN and Chen, Y and Chin, DR and Chowdhury, K and Collins, T and Compton, B and Da Silva, J and Davis, NR and DeCaro, N and Delgadillo, F and Deng, Y and Duncan, J and Egwu, AC and Ekalle, GD and Elnawam, N and Enke, R and Ewhe, N and Ferrel, MA and Fierst, J and Freymiller, G and Fuller, K and Fulton-Wright, L and Gaysinskaya, V and Gill, T and Gillespie, E and Gonzalez Moreno, P and Goodwin, S and Graham, N and Graham, ME and Graves, JL and Grob, E and Gutierrez, R and Hager, A and Hakim, ST and Harris, A and Hoffman, AM and Hoffmann, T and Horton, AM and Hughes, A and Humphries, EM and Ikechi-Konkwo, JS and Ishtiaq, A and Jackson, R and James, JR and James, K and Jamison, SA and Jimenez, A and Johnson, R and Kauffman, A and Kaur, H and Kc, K and Keeton, A and Kelly, OE and Kerr, J and Kucher, N and Kuehu, DL and Larson, WA and Lee, J and Lee, A and Leek, JT and Lemaic, D and Liburd, LE and Lopez, AF and Mahmanzar, M and Mamae, K and Manjikian, R and Marone, M and Marquez, K and Martinson, A and Mavruk Eskipehlivan, S and Medrano, A and Melendrez-Vallard, M and Meller, R and Méndez, LB and Mendez Gonzalez, MP and Mesquita, N and Miller, CM and Mohd-Ibrahim, I and Mortensen, P and Mosher, S and Muja, A and Nasrin, N and Nasu, M and Nguyen, MH and Nguyen, BT and Nishiguchi, M and O'Connor, LM and Okie, D and Olowookorun, T and Ostrovsky, A and Ozuna, K and Pandey, A and Patel, SB and Paul, G and Pawar, S and Pearson, A and Petrik, D and Platero, J and Pontino, C and Pratap, AP and Pratap, S and Qin, Y and Rai, SK and Ray, N and Repesh, E and Rhinehardt, K and Roche, B and Rodriguez, A and Roy, S and Roy, S and Sawa, A and Schatz, MC and Sen, SK and Serikawa, R and Smith, T and Smith, L and Sniezek, J and Stewart, RD and Suarez-Martinez, EB and Taganna, J and Tan, FJ and Tsotakos, N and Udolisa, N and Ulbricht, K and Veo, T and Vessio, J and Walker, L and Wang, O and Wang, Q and Wappel, R and Wesby, K and Whitford, M and Wild, N and Xie, X and Yang, H and York, S and Zirkle, L},
title = {Unearthing soil biodiversity through collaborative genomic research and education.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {41461908},
issn = {1546-1718},
support = {75N92023P00302//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 75N92022P00232//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U24HG013013//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 2000157//National Science Foundation (NSF)/ ; 1839895//National Science Foundation (NSF)/ ; 2011934//National Science Foundation (NSF)/ ; 2221924//National Science Foundation (NSF)/ ; 5T34GM151403//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
}

@article {pmid41461276,
year = {2025},
author = {Fan, YY and Salinas, ML and Mullens, DA and Davidson, LA and Goldsby, JS and Ivanov, IV and Jayaraman, A and Cai, JJ and Levy, L and Hullar, MA and Navarro, SL and Lampe, JW and Chapkin, RS},
title = {Pesco-vegetarian food components promote colonocyte ferroptosis in preclinical mouse models and a randomized crossover trial in healthy human adults.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {101287},
doi = {10.1016/j.tjnut.2025.101287},
pmid = {41461276},
issn = {1541-6100},
abstract = {BACKGROUND: Diet plays a critical role in colorectal cancer (CRC) prevention. Pesco-vegetarians, who consume both high fiber and fish containing n-3 polyunsaturated fatty acid (PUFA), have the lowest CRC risk. Ferroptosis is a form of regulated cell death characterized by the accumulation of lipid hydroperoxides that has emerged as a target for anti-cancer therapies.

OBJECTIVES: To assess the broad utility of diet modulation as a promising avenue to modulate ferroptosis in the colon.

METHODS: (i) Immortalized young adult mouse colonic epithelial cells (YAMC) were treated with control linoleic acid (LA) or docosahexaenoic acid (DHA) ± butyrate, followed by cell viability and lipid peroxidation measurements. (ii) Mice were fed diets containing fish oil and highly fermentable pectin (FP) vs. control corn oil and poorly fermentable cellulose (CC). Colons were isolated and used for bulk and single cell RNA-Seq analysis. (iii) A crossover pilot study was conducted by supplementing 30 healthy adults with soluble corn fiber (33 g/d) + fish oil (7.7 g/d n-3 PUFA) (SCF+FO) or maltodextrin + corn oil (MD+CO) for 30 d followed by a 60 d wash period and then 30 d of MD+CO or SCF+FO. Exfoliated colonocyte mRNA was isolated from stool and RNA-seq was performed for transcriptomic analysis.

RESULTS: In vitro treatment of DHA and butyrate reduced YAMC cell viability (P < 0.05), increased lipid peroxidation, a key biomarker of ferroptosis, compared to the counterpart group. In vivo FP-fed mice promoted lipid peroxidation in colonocytes relative to the control CC-fed mice (P < 0.05), and the induction of ferroptosis transcriptional networks exclusively in colonic epithelial cells. Furthermore, human subjects supplemented with SCF+FO exhibited an upregulation in intestinal ferroptosis related gene expression, as compared to similar doses of MD+CO.

CONCLUSIONS: Our findings demonstrate that dietary fish oil and fermentable fiber combination induces ferroptosis exclusively in colonocytes.

REGISTRATION: The human pilot study was registered at clinicaltrials.gov (NCT04211766).},
}

@article {pmid41446208,
year = {2025},
author = {Gómez-Garzón, C and Chen, Q and O'Brien, VP and Salama, NR},
title = {Metaplasia Enables Stomach Colonization by Fusobacterium animalis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41446208},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R00 CA263036/CA/NCI NIH HHS/United States ; R01 AI054423/AI/NIAID NIH HHS/United States ; R21 CA270512/CA/NCI NIH HHS/United States ; },
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 gastric 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. Overall, our data support a model in which H. pylori-induced metaplasia makes the stomach susceptible to secondary infection by another cancer-associated microbe, F. animalis.},
}

@article {pmid41446058,
year = {2025},
author = {Schaefer-Babajew, D and Binet, L and Santos, GSS and Ruprecht, C and Deimel, LP and ElTanbouly, MA and Gharrassi, D and Uhe, C and Yao, KH and Hernandez, B and Agrawal, P and Gazumyan, A and Stamatatos, L and Hartweger, H and Nussenzweig, MC},
title = {Antibody Mediated Diversification of Primary and Secondary Immune Responses.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41446058},
issn = {2692-8205},
support = {P01 AI100148/AI/NIAID NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; UM1 AI144462/AI/NIAID NIH HHS/United States ; UM1 AI191237/AI/NIAID NIH HHS/United States ; },
abstract = {Humoral immune responses are characterized by increasing antibody affinity and diversity over time. Increased affinity is mediated by a combination of immunoglobulin gene somatic mutation and iterative cycles of selection in germinal centers. Less is understood about how diversity increases in parallel with affinity. Here we examine the role of antibody feedback in diversifying immune responses in mice that produce B cells that are incapable of secreting antibodies. To this end, we produced two strains of mice, one that expresses only membrane and secreted forms of IgM, and a second that produces only the membrane bound form of IgM. Analysis of primary and secondary immune responses show that antibody feedback significantly diversifies both primary and secondary immune responses even when antibodies are present at levels that are 10-30 fold lower than physiologic. The data have significant implication for sequential vaccination approaches aimed at shepherding immunity to produce broadly neutralizing antibodies to highly diversified pathogens such as HIV-1 and Influenza.},
}

@article {pmid41332789,
year = {2025},
author = {Ruediger, CT and Styler, BS and Sawyer, EM and Spiri, S and King, G and Walsh, ME and Brar, GA and Jorgens, DM and Ünal, E},
title = {Tom70-mediated mitochondria-nuclear envelope contacts regulate nuclear pore complex inheritance during gametogenesis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41332789},
issn = {2692-8205},
support = {T32 GM132022/GM/NIGMS NIH HHS/United States ; R01 AG071869/AG/NIA NIH HHS/United States ; R35 GM134886/GM/NIGMS NIH HHS/United States ; T32 GM007127/GM/NIGMS NIH HHS/United States ; T32 GM007232/GM/NIGMS NIH HHS/United States ; R01 AG071801/AG/NIA NIH HHS/United States ; },
abstract = {Gametogenesis rejuvenates the cellular lineage and excludes senescence-associated factors from gametes. In Saccharomyces cerevisiae, this involves sequestration of nuclear constituents into the Gametogenesis-Uninherited Nuclear Compartment (GUNC), which is excluded from gametes. Here we identify the conserved mitochondrial import receptor Tom70 as a key regulator of GUNC-mediated exclusion. Loss of TOM70 disrupts the sequestration of nuclear pore complexes, but not senescence-associated aggregates and nucleolar components, into the GUNC. Tom70's role appears independent of its canonical function in mitochondrial import and instead reflects a meiosis-specific requirement for mitochondria-nuclear envelope tethering. During meiosis II, Tom70 concentrates around the GUNC, where it recruits the nuclear envelope tethering protein Cnm1. Loss of CNM1 partially phenocopies tom70∆, consistent with parallel tethering interactions. These findings uncover a previously unrecognized organelle contact-dependent pathway that remodels the nuclear envelope to support selective nuclear inheritance. More broadly, they highlight how organelle contacts integrate with nuclear quality control to safeguard gamete integrity.},
}

@article {pmid41461080,
year = {2025},
author = {Lucia, MS and Callis, S and Tangen, C and Almutairi, F and Chatzitolios, A and Kravtsov, O and Lenon, S and Manuchua, V and Simko, JP and Szecsei, CM and Yeh, YA and Zhang, L and Iczkowski, KA},
title = {Whole-Slide Telepathology Grading of Prostate Cancer in Biopsies Using ISUP Criteria: Inter- and Intra-Observer Concordance and Implications for Active Surveillance.},
journal = {The Journal of urology},
volume = {},
number = {},
pages = {101097JU0000000000004919},
doi = {10.1097/JU.0000000000004919},
pmid = {41461080},
issn = {1527-3792},
abstract = {INTRODUCTION: Subjectivity of prostate cancer (PCa) grading impacts biomarker investigations, assessments of imaging, and treatment decisions, especially for active surveillance. We conducted the first telepathology concordance study of PCa needle biopsy grading using contemporary International Society of Urologic Pathology guidelines.

METHODS: Whole slide images (n=120) of PCa biopsy cases across grade groups (GG), were examined by 11 urologic pathologists. Forty cases were blindly regraded, over-sampling cases with lower agreement on first review. Pathologists provided GG, percentage and type of pattern Gleason 4, and tumor length. Consensus for a case was defined as GG agreement by ≥7 pathologists. GG agreement among and within pathologists was measured using model-based weighted Kappa statistics (κw).

RESULTS: Consensus was achieved on 86/120 (72%) cases. Of 34 cases not achieving consensus, most were GG2 vs GG1 (41%) or GG2 vs GG3 (38%). The inter-rater κw was 0.34 (95% CI 0.28, 0.39) indicating fair agreement. Forty regraded cases had an intra-rater κw of 0.49 (95% CI 0.46, 0.53; moderate agreement). Sixty-four percent of the repeated grades agreed. Of the repeated ratings that did not agree, 39% involved GG1 vs GG2. Of the GG1 vs GG2 paired repeated ratings, 77% reported 1-10% pattern 4, and indicated common observation was "poorly-formed glands."

DISCUSSION: Inter- and intra-rater variability in GG is significant, particularly discerning GG1 from GG2 with ≤10% grade 4. These observations have profound implications for treatment decisions (surveillance vs definitive therapy) and studies of new biomarkers and imaging of prostate cancer.},
}

@article {pmid41460964,
year = {2025},
author = {Abramson, JS and Straus, DJ and Bartlett, NL and Burke, JM and Lynch, RC and Domingo-Domenech, E and Hess, BT and Schuster, SR and Linhares, Y and Gandhi, MD and Shah, HR and Jurczak, W and Re, A and Hahn, U and Prince, HM and Guo, W and Davis, G and Ho, L and Fanale, M and Yasenchak, CA and Lee, HJJ},
title = {Brentuximab Vedotin and Nivolumab in Combination With Chemotherapy for Nonbulky, Early-Stage Classical Hodgkin Lymphoma.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025030190},
pmid = {41460964},
issn = {1528-0020},
abstract = {Most patients with early-stage classical Hodgkin lymphoma (cHL) are treated with doxorubicin, bleomycin, vinblastine, and dacarbazine with or without radiation therapy, although studies are now evaluating the incorporation of novel agents paired with abbreviated chemotherapy. We present the efficacy and safety of brentuximab vedotin (BV) and nivolumab in combination with doxorubicin and dacarbazine (AN+AD) in patients with early-stage cHL. In this phase 2 study, patients with non-bulky (<10 cm) Ann Arbor stage I or II cHL received 4 cycles of AN+AD. The primary endpoint was complete response (CR) rate at end of treatment (EOT) by investigator. At the time of this analysis, 154 patients received ≥1 dose of AN+AD. The objective response rate at EOT was 96% (95% CI, 91.7-98.6), and the CR rate was 92% (95% CI, 86.0-95.4). In the favorable (n=56) and unfavorable (n=97) subgroups, CR rates were 95% (95% CI, 85.1-98.9) and 91% (95% CI, 83.1-95.7), respectively. The proportion of patients with duration of CR of at least 2 years was 96% (95% CI, 90.9-98.4). At a median follow-up of 27.9 months, the estimated 2-year PFS rate was 97% (95% CI, 92.0-98.8). Any-grade and grade ≥3 treatment-emergent adverse events occurred in 99% and 44% of patients, respectively; no events of febrile neutropenia were reported. Any-grade treatment-emergent immune-mediated adverse events occurred in 22% of patients. One disease-related death was reported after the safety reporting period. Results from this study support the use of BV and nivolumab in combination with limited chemotherapy in patients with non-bulky, early-stage cHL. ClinicalTrials.gov: NCT03646123.},
}

@article {pmid41460962,
year = {2025},
author = {Nguyen, C and Funes, J and Ghale, R and Duong, N and Victor, K and Gipson, B and Zhang, ZJ and Dai, A and Li, R and Armijo, GK and Huang, AS and Martinez, M and Chen, Y and Ghazarian, DM and Docampo, MD and Pathak, KV and Pirrotte, P and Markey, KA and Peled, JU and Paredes, J and Burgos da Silva, M and van den Brink, MRM},
title = {Enterococcus induces MHC-II expression by the intestinal epithelium during murine graft-versus-host disease.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024028248},
pmid = {41460962},
issn = {1528-0020},
abstract = {Intestinal Enterococcus domination has been associated with an increased risk of mortality by acute graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (allo-HCT), a curative-intent treatment for patients with hematologic malignancies. In this study, we investigate the interactions between Enterococcus and the intestinal epithelium as a mechanism to aggravate GVHD. We observed that endogenous intestinal Enterococcus outgrowth was associated with increased GVHD mortality and major histocompatibility complex class II (MHC-II) expression by intestinal epithelial cells (IECs) in the colon in an MHC-disparate mouse model of GVHD. Monocolonization of non-transplanted gnotobiotic mice with E. faecalis was sufficient to induce colonic MHC-II expression. Conversely, select species within the genus Enterococcus, as well as a consortium of four anaerobic commensal bacteria including Blautia producta, did not affect colonic MHC-II expression in gnotobiotic mice. In addition, E. faecalis colonization also induced inflammatory responses in CD4+ T cells and NK cells from the colonic lamina propria, the two main sources of interferon-gamma production that drives MHC-II expression in non-professional antigen-presenting cells. We further explored the potential therapeutic benefit of establishing colonization resistance against E. faecalis through administration of a lantibiotic-producing B. producta strain after allo-HCT. Colonization of transplanted mice with a consortium of commensal bacteria containing the lantibiotic-producing B. producta strain prevented intestinal Enterococcus domination post-transplant and improved GVHD survival. Our results demonstrate a potential mechanism by which Enterococcus aggravates GVHD through increased MHC-II expression in the intestinal epithelium. Targeting the Enterococcus-epithelium-MHC-II axis thus presents a therapeutic opportunity to prevent lethal GVHD.},
}

@article {pmid41279209,
year = {2025},
author = {Awany, D and Ariefdien, DT and Mendelsohn, SC and Rozot, V and Mulenga, H and Nyangu, S and Tameris, M and Moloantoa, T and Katona, A and Maruri, F and Noor, F and Panchia, R and Hlongwane, K and Stanley, K and van der Heijden, YF and Hadley, K and Gartland, AF and Innes, C and Brumskine, W and Dheda, K and Jaumdally, S and Perumal, T and Martinson, N and Leslie, A and Fourie, B and Hiemstra, A and Malherbe, ST and Walzl, G and Naidoo, K and Churchyard, G and Chegou, NN and Sterling, TR and Hatherill, M and Scriba, TJ},
title = {Inflammatory Biomarkers of Asymptomatic and Symptomatic Tuberculosis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279209},
issn = {2692-8205},
abstract = {A large proportion of individuals with tuberculosis (TB) are asymptomatic. The biological and inflammatory underpinnings of asymptomatic TB are unknown and may differ from symptomatic TB. We characterised blood transcriptomic and proteomic profiles in South African community screening vs. health facility-based triage cohorts. Asymptomatic TB shared core transcriptomic and proteomic features with symptomatic TB, including upregulation of innate, interferon and inflammatory pathways and downregulation of T and B cell pathways. Integration of transcriptomic and proteomic data from asymptomatic TB individuals identified two distinct sub-clusters characterized by higher or lower bacterial burden, blood IFN-γ responses, BMI, and chest radiographic abnormalities, suggesting different disease severity. We identified a new blood transcriptomic signature of asymptomatic TB. However, diagnostic performance of transcriptomic and proteomic markers was weaker for asymptomatic TB than symptomatic TB, suggesting that policy development for community-based, asymptomatic TB screening should not adopt biomarkers developed for symptomatic TB triage without further optimization.},
}

@article {pmid41460828,
year = {2025},
author = {Osuga, H and Chan, MC and Brower, K and Ray, LJ and Chowning, JT},
title = {Ten simple rules for running a virtual program to introduce computational biology at the high school level.},
journal = {PLoS computational biology},
volume = {21},
number = {12},
pages = {e1013830},
pmid = {41460828},
issn = {1553-7358},
}

@article {pmid41460282,
year = {2025},
author = {Woolf-King, SE and Dalton, MR and Firkey, M and Sheinfil, A and Bucci, V and Estrada, B and Ramos, J and Hahn, JA and Bricker, J and Gump, B and Bendinskas, KG and Maisto, SA},
title = {A Randomized Feasibility/Acceptability Trial of Acceptance and Commitment Therapy for People with HIV Who Drink at Unhealthy Levels.},
journal = {AIDS and behavior},
volume = {},
number = {},
pages = {},
pmid = {41460282},
issn = {1573-3254},
support = {R34AA026246/AA/NIAAA NIH HHS/United States ; R34AA026246-03S1/AA/NIAAA NIH HHS/United States ; },
abstract = {Unhealthy alcohol use is prevalent among people with HIV (PWH) and associated with significant health-related consequences. We describe here a randomized feasibility/acceptability trial of a brief, telephone-delivered transdiagnostic acceptance and commitment therapy (ACT) intervention for PWH who drink at unhealthy levels. This pilot trail was designed to match the procedures of a planned definitive RCT that will compare the ACT intervention to a brief alcohol intervention (BI). We randomly assigned PWH and unhealthy alcohol use 1:1 to either the ACT or the BI intervention and collected self-report and biomarker data post-treatment and again at 3-, 6-, and 12-months. The primary objectives of this pilot trial were to assess feasibility of recruitment, retention, and intervention delivery, and acceptability of intervention content. We also collected preliminary primary (alcohol use) and secondary (symptoms of anxiety, depression, and experiential avoidance) outcome data to examine general patterns of results at a purely descriptive level. In total, 192 participants were screened, 117 of whom were eligible, and 49 of whom were randomized to either the ACT (n = 24) or BI (n = 25) condition. Results provided evidence of feasibility and acceptability indicating that a definitive trial should proceed. Preliminary outcome data also suggested that ACT is a promising treatment for unhealthy alcohol use and co-morbid symptoms of depression, anxiety, and experiential avoidance. A definitive trial is currently underway and will determine the comparative efficacy of ACT versus BI for unhealthy alcohol use for PWH.},
}

@article {pmid41459934,
year = {2025},
author = {Reed, JC and Downs, C and McAllister, K and Mauer, C and McClurkan, CL and Wilson, D and Holzhauer, K and Dickerson, JA and Cannon, CA and Babu, TM and Golden, MR and Koelle, DM and Greninger, AL},
title = {Differentiating mpox infection and vaccination using a validated multiplex orthopoxvirus IgG serology assay.},
journal = {Journal of clinical microbiology},
volume = {},
number = {},
pages = {e0154825},
doi = {10.1128/jcm.01548-25},
pmid = {41459934},
issn = {1098-660X},
abstract = {UNLABELLED: The resurgence of monkeypox virus (MPXV) has increased demand for validated serological assays to assess exposure and immunity. Cross-reactivity among orthopoxviruses, stemming from high sequence conservation, complicates distinguishing antibody responses from natural MPXV infection versus vaccination or other orthopoxvirus exposures. We validated the Meso Scale Discovery (MSD) V-PLEX Orthopoxvirus Panel 1 (IgG) Kit, which quantifies antibody levels to five MPXV antigens and their vaccinia virus (VACV) orthologs, following Good Clinical Laboratory Practice guidelines. We assessed assay performance using serum from 26 individuals with prior mpox, 52 JYNNEOS vaccine recipients, and 179 unexposed controls. The assay reliably detected antibody responses in all exposed cohorts with peak levels observed 2 months post-vaccination. Antibody levels to specific antigens also correlated with Modified Vaccinia Ankara neutralization titer, particularly for MPXV B6R/VACV B5R, MPXV E8L/VACV D8L, and MPXV M1R/VACV L1. Receiver operating characteristic analysis showed that some individual antigens achieved high sensitivity and specificity for exposure detection (area under the curve [AUC] > 0.96 for VACV D8L, MPXV B6R, VACV B5R); however, individual antigens performed poorly in distinguishing infection from vaccination. In contrast, antibody level ratios between some MPXV and VACV orthologs effectively differentiated MPXV infection from vaccinia vaccination with high sensitivity and specificity (e.g., MPXV A35R/VACV A33R ortholog ratio, AUC = 0.97, sensitivity = 0.97, specificity = 0.96). Our findings validate the MSD assay for clinical research and serosurveillance to assess MPXV immunity and support the utility of ortholog pair ratio analysis as a strategy to discriminate vaccinated and infected individuals.

IMPORTANCE: Mpox continues to spread around the world, with recent data showing increasing incidence in the United States. While there are multiple Food and Drug Administration (FDA)-authorized real-time PCR tests for diagnostic use, there are no FDA-authorized serological tests and few laboratory-developed serological tests offered. We evaluated the Meso Scale Discovery V-PLEX Orthopoxvirus Panel 1 (IgG) Kit according to Good Clinical Laboratory Practice guidelines and found that the assay reliably detected antibody responses in monkeypox virus (MPXV)- and vaccinia virus (VACV)-exposed cohorts and could distinguish them from unexposed cohorts. Intriguingly, we found that antibody level ratios between certain MPXV and VACV orthologs could distinguish prior mpox infection from vaccinia vaccination. Overall, these data highlight the use of multi-antigen panels in challenging scenarios for serological testing, such as the cross-reactivity presented by orthopoxviruses.},
}

@article {pmid41446269,
year = {2025},
author = {Lin, C and Gheorghe, V and Chou, J and Alibai, S and Kim, S and Nazanin, EA and Xu, Y and Ma, X and Wilson, LL and Moser, RD and Kemp, CJ and Chen, J and Kopetz, S and Hart, T},
title = {Functional modules predict cancer-relevant genetic interactions in mammalian cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41446269},
issn = {2692-8205},
abstract = {Genetic interactions can reveal gene function and identify cancer-relevant synthetic lethals, but systematic mapping in human cells is constrained by inefficient reagents, vast combinatorial search space, and diversity of cell types. Here, we leverage principles from yeast genetic networks to identify human gene modules enriched for genetic interactions. Using our Cas12a-based In4mer combinatorial knockout platform, we screen all pairwise interactions within receptor tyrosine kinase and DNA damage response modules across eight diverse cancer cell lines. We identify hundreds of unreported synthetic lethals, including a dense network within the protein glycosylation machinery, and confirm that interactions in 2D cell culture are maintained in more physiologically relevant models. Our targeted modules show up to 16-fold enrichment of interaction density, providing a scalable strategy for systematic interaction mapping.},
}

@article {pmid41446115,
year = {2025},
author = {Soares, RF and Chang, CH and Koerich, LB and Malik, HS and Kuhn, GCS},
title = {Retention of a single Cenp-C gene in different syntenic locations in the montium group of Drosophila species.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41446115},
issn = {2692-8205},
abstract = {Chromosome segregation in eukaryotes requires the orchestrated interaction of chromosomes with microtubules, mediated by the kinetochore multiprotein complex that assembles on specific chromosomal regions known as centromeres. In most eukaryotes, two centromeric proteins, CenH3 and Cenp-C, are essential for centromere function. In Drosophila, the localization of CenH3 (referred to as Cid in Drosophila) depends on its chaperone CAL1 and Cenp-C. Previous studies have shown that both Cid and Cenp-C underwent a coincident gene duplication and likely functional specialization in the Drosophila subgenus. Independently, Cid duplications led to Cid1, Cid3, and Cid4 paralogs in the montium group (Sophophora subgenus), but it is unknown whether this group also underwent parallel duplications of Cenp-C. Here, we investigate this possibility by analyzing sequenced genomes of 23 montium group species. We identified Cenp-C genes in five distinct syntenic loci; we named these genes Cenp-C1b, Cenp-C1c, Cenp-C1d, Cenp-C1e and Cenp-C3. Despite their distinct synteny, most montium group species only encode a single Cenp-C; their phylogeny mirrors the species phylogeny, and they appear to have retained Cenp-C protein motifs indicative of function. A closer examination revealed that these Cenp-C genes resulted from gene translocations or alternate retention (duplication followed by loss of the ancestral copy); only one species, D. vulcana, retains two intact Cenp-C paralogs. Therefore, unlike the Drosophila genus, the co-retention of three Cid paralogs in the montium group has not resulted in a coincident Cenp-C paralog co-retention. Our work highlights differences in functional retention and likely specialization of the two most conserved centromeric proteins in eukaryotes.},
}

@article {pmid41459525,
year = {2025},
author = {Chapuis, AG and Orozco, JJ and Milano, F},
title = {Intrathecal rituximab for the treatment of Epstein-Barr virus-associated encephalitis.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1736017},
pmid = {41459525},
issn = {1664-3224},
mesh = {Humans ; *Rituximab/administration & dosage/therapeutic use ; *Epstein-Barr Virus Infections/drug therapy/virology/diagnosis/immunology ; Injections, Spinal ; *Herpesvirus 4, Human ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Encephalitis, Viral/drug therapy/diagnosis/virology/etiology ; Male ; Adult ; Treatment Outcome ; Female ; *Immunologic Factors/administration & dosage ; Middle Aged ; },
abstract = {Epstein-Barr virus (EBV)-associated encephalitis is seen in patients who have undergone allogeneic hematopoietic stem cell transplant and can be associated with significant morbidity and mortality. The mainstay of treatment has been antiviral therapy with nucleoside analogues and reduction of immunosuppression. Here, we describe an adult patient diagnosed with refractory EBV-associated encephalitis within 30 days post-allogeneic transplant successfully treated with intrathecal rituximab, which, to our knowledge, is the first case treated in this manner.},
}

Humans
*Rituximab/administration & dosage/therapeutic use
*Epstein-Barr Virus Infections/drug therapy/virology/diagnosis/immunology
Injections, Spinal
*Herpesvirus 4, Human
*Hematopoietic Stem Cell Transplantation/adverse effects
*Encephalitis, Viral/drug therapy/diagnosis/virology/etiology
Male
Adult
Treatment Outcome
Female
*Immunologic Factors/administration & dosage
Middle Aged

@article {pmid41452615,
year = {2025},
author = {Unger, JM and Fisch, MJ and Jones, SMW and Henry, NL and Hershman, DL},
title = {Baseline Fatigue and Severe Toxic Effects in Patients With Cancer Receiving Systemic Therapy.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
pmid = {41452615},
issn = {2374-2445},
abstract = {IMPORTANCE: Fatigue is a common symptom reported by patients with cancer, yet its role as a predictor of treatment-related toxic effects has not been well characterized. Understanding whether fatigue measured at treatment initiation may be associated with subsequent toxic effects could help guide individualized treatment planning and symptom monitoring.

OBJECTIVE: To evaluate the association between baseline patient-reported fatigue and the risk of adverse events (AEs) in cancer treatment trials.

This cohort study and pooled analysis assessed baseline fatigue data from 17 SWOG phase 2 and 3 trials conducted from 1990 to 2022. Patients were enrolled across multiple cancer types and treatment settings. Data analysis was performed from March 1, 2023, to October 17, 2025.

EXPOSURES: Baseline fatigue, classified on a 5-point Likert scale, analyzed as binary thresholds (eg,
MAIN OUTCOMES AND MEASURES: Adverse events were classified using the Common Terminology Criteria for Adverse Events (CTCAE), with multiple versions mapped to version 4. Symptomatic AEs followed the Patient-Reported Outcomes-CTCAE framework; laboratory-based or measurable toxic effects were considered objective (hematologic vs nonhematologic). Primary outcomes were grade 3 or higher (severe), grade 4 or higher (life-threatening), and grade 5 (fatal) AEs. Odds ratios (ORs) were estimated using generalized estimating equations. To account for confounding, the analysis was clustered by trial and adjusted for age, sex, race, and obesity.

RESULTS: Among 7086 patients (mean [SD] age, 62.1 [15.2] years; 2107 females [29.7%] and 4979 males [70.3%]) with prostate, lung, colorectal, lymphoma, breast, melanoma, ovarian, or pancreatic cancer, 103 738 AEs were reported. At baseline, 2771 participants (39.1%) reported some or more fatigue. Proportions with maximum AEs rated grade 3 or higher, grade 4 or higher, and grade 5 were 3128 participants (44.1%), 1001 (14.1%), and 62 (0.9%), respectively. Compared with those reporting no or minimal fatigue, patients with some fatigue or more had higher risks of severe or worse toxic effects (odds ratio [OR], 2.09; 95% CI, 1.58-2.78; P < .001), life-threatening or fatal toxic effects (OR, 1.96; 95% CI, 1.36-2.82; P < .001), and fatal toxic effects (OR, 2.35; 95% CI, 1.07-5.19; P = .03). A dose-response pattern was evident: patients reporting quite a lot or very much fatigue had an approximately 5-fold higher risk of fatal toxic effects (OR, 4.99; 95% CI, 1.84-13.51; P = .002). Findings were consistent across symptomatic, hematologic, and nonhematologic AE categories.

CONCLUSIONS AND RELEVANCE: This cohort study found that baseline patient-reported fatigue was associated with an increased risk of cancer treatment-related toxic effects. Fatigue assessments at treatment initiation may serve as an early clinical marker of risk for toxic effects and may help inform personalized treatment strategies and symptom monitoring.},
}

@article {pmid41451118,
year = {2025},
author = {McNeil, AJ and Parks, K and Pogharian, M and Cowen, EW and Lehman, J and Lee, SJ and Zhao, A and Pavletic, SZ and Saknite, I and Coco, J and Fabbri, D and Tkaczyk, ER and Dawant, BM},
title = {Improving U-Net Segmentation of Cutaneous Chronic Graft-Versus-Host Disease in Clinical Photographs with Semi-Supervised Training.},
journal = {Proceedings of SPIE--the International Society for Optical Engineering},
volume = {13407},
number = {},
pages = {},
pmid = {41451118},
issn = {0277-786X},
support = {IK2 CX001785/CX/CSRD VA/United States ; R01 HL169944/HL/NHLBI NIH HHS/United States ; TL1 TR002244/TR/NCATS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; },
abstract = {Measuring skin involvement in chronic graft-versus-host disease (cGVHD) currently requires expert manual assessment, which is costly, time-consuming, and shows high interrater disagreement (>20% surface area). In our previous work, automated image analysis showed promise for measuring affected skin area under controlled photography conditions. Our aim is to improve the performance of these methods in standard clinical photographs without the need for costly expert annotations using a semi-supervised approach. A baseline U-Net model was trained in a fully supervised manner using 360 3D photographs from 36 cGVHD patients, with expert-marked ground truth contours of affected skin. The model was then iteratively retrained by incorporating an additional 5648 unlabeled photographs from 83 new patients using a semi-supervised method. Testing on clinical photographs of 20 held-out patients, the median surface area error improved from 19.2% (interquartile range 6.3 - 33.8) at baseline to 10.2% (4.5 - 22.6) after retraining. Semi-supervised training therefore provides an effective method for translating a pre-trained U-Net segmentation model to standard clinical photographs, without the need for additional expert annotations. Such models could help standardize cGVHD assessment and tracking, alleviating the need for costly expert evaluations and providing a reliable tool that would significantly enhance the current standard of manual assessment.},
}

@article {pmid41448908,
year = {2025},
author = {Mukui, I and Peacock, S and Donnell, D and Gati-Mirembe, B and Krows, M and Bukusi, EA and Imaan, L and Kotze, P and Gill, KM and Macdonald, P and Louw, C and Jaggernath, M and Marais, A and Peters, RPH and Delany-Moretlwe, S and Ward, A and du Preez, P and Kasaro, M and Gandhi, M and Heffron, R and Celum, C and , },
title = {High prevalence and incidence of curable sexually transmitted infections among young women using oral HIV pre-exposure prophylaxis in sub-Saharan Africa: results from the INSIGHT Cohort study.},
journal = {Sexually transmitted infections},
volume = {},
number = {},
pages = {},
doi = {10.1136/sextrans-2025-056625},
pmid = {41448908},
issn = {1472-3263},
abstract = {BACKGROUND: HIV pre-exposure prophylaxis (PrEP) programmes in Africa reach young women at risk of sexually transmitted infections (STIs). We evaluated curable STI prevalence, incidence and risk factors among women initiating PrEP.

METHODS: From August to December 2022, sexually active women aged 16-30 years from 15 South African sites, and one site each in Eswatini, Kenya, Malawi, Uganda and Zambia were enrolled into the INSIGHT cohort and offered oral emtricitabine/tenofovir PrEP with follow-up at 1, 3 and 6 months. At each visit, STI symptoms were assessed and treatment provided based on syndromic management or diagnostic testing. Diagnostic tests included nucleic acid amplification for Chlamydia trachomatis and Neisseria gonorrhoeae, the rapid OSOM for Trichomonas vaginalis at enrolment and month 6, and serological testing for syphilis at enrolment using rapid plasma reagin with confirmatory Treponema pallidum particle agglutination. Prevalence and incidence of each STI were calculated, and predictors assessed using multivariable regression.

RESULTS: Of 3087 participants offered daily oral PrEP with a median age of 23 (IQR 21-27), 3011 had STI results and 30.9% had one or more STIs, with 15.7% reporting symptoms. The prevalence of C. trachomatis, N. gonorrhoeae, T. vaginalis and syphilis was 20.8%, 6.8%, 6.0% and 4.4%, respectively. The incidence of one or more STIs (C. trachomatis, N. gonorrhoeae or T. vaginalis) was 49.3/100 person-years (95% CI 45.3 to 53.4) with 12.7% reporting symptoms. The incidence of C. trachomatis was 30.6/100 person-years (95% CI 27.5 to 33.7), N. gonorrhoeae 10.8/100 person-years (95% CI 9.0 to 12.6) and T. vaginalis 11.5/100 person-years (95% CI 9.7 to 13.4). An incident STI diagnosis was associated with low alcohol use (adjusted incidence rate ratio (aIRR) 1.3; 95% CI 1.0 to 1.6) and moderate alcohol use (aIRR 1.4; 95% CI 1.1 to 1.8), and having an STI diagnosed at enrolment (aIRR 1.8; 95% CI 1.5 to 2.1).

CONCLUSION: The high prevalence and incidence of STIs among African women initiating PrEP, most of whom did not report symptoms, highlights the need for aetiologic testing to detect STIs, guide treatment and reduce reproductive health sequelae and risk of transmission.

TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT05746065.},
}

@article {pmid41427323,
year = {2025},
author = {Raman, P and Khan, H and Young, JM and Tsukiyama, T and Malik, HS},
title = {Dynamic evolution of EZHIP, an inhibitor of the Polycomb Repressive Complex 2 in mammals.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41427323},
issn = {2692-8205},
abstract = {The Polycomb Repressive Complex 2 (PRC2) is an ancient, conserved chromatin-interacting complex that controls gene expression, facilitating differentiation and cellular identity during development. Its regulation is critical in most eukaryotes. EZHIP was recently characterized as a PRC2 inhibitor and 'oncohistone mimic' in mammals. Although Ezhip expression is typically restricted to the germline, its aberrant expression in pediatric brain tumors inhibits PRC2-mediated H3K27 methylation and drives disease progression. To gain a deeper understanding of its normal functions, we systematically examined Ezhip evolution across 70 mammals using comparative genomics, synteny analysis, and motif discovery. Bolstering previous work, we find that Ezhip originated and has been strictly retained on the X chromosome in placental mammals. In addition to the highly conserved H3K27M-like histone mimic motif, our motif analysis reveals seven previously unidentified EZHIP motifs, including a putative nuclear localization signal, and tandem repeats that are largely well-conserved in placental mammals, except in some lineages. We hypothesize that these motifs are also critical to EZHIP's functions, including in PRC2 interaction and inhibition. We show that Ezhip has evolved under strong diversifying selection in primates and underwent dynamic expansions and losses across species. Some paralogs, such as Ezhip2 in primates, also evolved under positive selection. Based on its evolutionary attributes and germ-cell expression, we propose that Ezhip arose and evolved rapidly due to inter-parental conflict over fetal development in utero in placental mammals. Our work provides a foundation for further investigations into EZHIP's essential, potentially multifaceted roles in mammalian reproduction and disease.},
}

@article {pmid41427272,
year = {2025},
author = {Vaz, J and Zhu, S and Useche, M and Shih, L and Marchiano, E and Beronja, S and Clurman, BE and Rodriguez, C and Barber, B and Chan, M and Gujral, TS},
title = {Subtype-Specific Dependencies and Drug Vulnerabilities Enable Precision Therapeutics in Head and Neck Cancer.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41427272},
issn = {2692-8205},
abstract = {Molecular heterogeneity in head and neck squamous cell carcinoma (HNSCC) is well recognized, yet existing subtype frameworks remain largely descriptive and have not translated into therapeutic decision-making. Here, we establish a mechanistic platform that converts transcriptomic diversity into drug-actionable tumor states. Integrating multi-cohort RNA-seq from 727 tumors across five independent datasets, genome-scale CRISPR dependency maps, and pharmacologic screening, we define distinct tumor survival circuits across HPV-negative HNSCC and nominate subtype-matched therapeutic strategies. These circuits encompass a proliferative axis (MYC, MET/FAK, inflammatory and translational programs), an epithelial-differentiated/adhesion program, an EMT-like state with stromal activation, and mitochondrial/oxidative metabolic states, each mapping to selective liabilities (e.g., mitotic/autophagy control, ERBB/PI3K and cadherin signaling, OXPHOS/mitochondrial translation, and G2/M-integrin-Notch pathways, respectively). We then develop a transcriptomic predictor of EGFR-inhibitor response using machine learning and validate it in prospectively collected, fresh patient-derived 3D microtumors. The resulting 13-gene signature identifies erlotinib-responsive tumors (R = 0.93) and maps biologically to an epithelial-differentiated state, outperforming EGFR expression alone. Our study establishes a subtype-to-dependency-to-therapy framework, enabling precision stratification and providing a clinically feasible path for prospective biomarker deployment.},
}

@article {pmid41448830,
year = {2025},
author = {Yamada, MM and Chandrasekhar, S and Gooley, TA and Chen, RE and Doolittle-Amieva, C and Ansstas, G and Bhatia, S and Hall, ET and Nghiem, PT and Park, SY and Chen, DY},
title = {Real-world outcomes of talimogene laherparepvec as salvage therapy for advanced melanoma.},
journal = {Journal for immunotherapy of cancer},
volume = {13},
number = {12},
pages = {},
pmid = {41448830},
issn = {2051-1426},
support = {P01 CA225517/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Melanoma/drug therapy/mortality/therapy/pathology ; Male ; Female ; Middle Aged ; Aged ; *Salvage Therapy/methods ; Adult ; *Oncolytic Virotherapy/methods ; Aged, 80 and over ; *Biological Products/therapeutic use/pharmacology ; Treatment Outcome ; Herpesvirus 1, Human ; *Skin Neoplasms/mortality ; Retrospective Studies ; },
abstract = {BACKGROUND: Talimogene laherparepvec (T-VEC) is an oncolytic herpes simplex virus therapy approved for treatment of unresectable and metastatic melanoma. However, real-world use often occurs in heavily pretreated patients, where evidence of effectiveness remains limited. This study evaluates treatment responses and clinical factors influencing T-VEC outcomes in patients with diverse treatment histories.

METHODS: We analyzed patients with metastatic melanoma treated with T-VEC between 2015 and 2024. Objective responses (OR), complete response (CR) and partial response were assessed using univariate and multivariate Cox regression models. Durability of responses, progression-free survival (PFS), and overall survival (OS) were evaluated using Kaplan-Meier estimates.

RESULTS: Among 121 patients, 105 (87%) patients received ≥1 prior lines of systemic therapy; 48 (40%) had a current or prior history of distant metastatic disease, and 42 (35%) had both injectable and non-injectable disease at the T-VEC initiation. Median PFS was 12.2 months (95% CI 6.2 to 20.9), and median OS was 35.5 months (95% CI 25.8 to 63.9). Of 113 evaluable patients, 76 (67%, 95% CI 58% to 76%) achieved an OR, including 39 (35%, 95% CI 26% to 44%) CR. The probability OR by 6 months was 56% (95% CI 46% to 65%). Of the 39 patients achieving CR, 37 (95%) remained alive and progression-free at last follow-up (median 19.1 months). In multivariate analysis, the adjusted HR (aHR) for OR in patients with non-injectable distant metastases at T-VEC initiation relative to those without was 0.43 (95% CI 0.23 to 0.78; p=0.006). The aHR for OR among those immunosuppressed compared with those not immunosuppressed was 0.18 (95% CI 0.04 to 0.69; p=0.013), indicating a reduced likelihood of response for patients who were immunosuppressed. Unadjusted HRs for achieving an OR after 1, 2, and ≥3 prior therapies (vs none) were 1.20 (95% CI 0.57 to 2.52; p=0.627), 1.21 (95% CI 0.52 to 2.80; p=0.653), and 0.77 (95% CI 0.35 to 1.68; p=0.507), respectively.

CONCLUSIONS: This study demonstrates T-VEC's potential efficacy in achieving meaningful disease control and response durability in patients with unresectable and/or metastatic melanoma, including those with diverse prior-treatment histories and comorbidities.},
}

Humans
*Melanoma/drug therapy/mortality/therapy/pathology
Male
Female
Middle Aged
Aged
*Salvage Therapy/methods
Adult
*Oncolytic Virotherapy/methods
Aged, 80 and over
*Biological Products/therapeutic use/pharmacology
Treatment Outcome
Herpesvirus 1, Human
*Skin Neoplasms/mortality
Retrospective Studies

@article {pmid41448829,
year = {2025},
author = {Balduzzi, A and Valsecchi, MG and Tran, TH and Zuna, J and Leoni, V and Cario, G and Fazio, G and Gandemer, V and Tasian, SK and van der Sluis, IM and Peccatori, N and Parasole, R and Monterisi, S and Loh, ML and Devidas, M and Hunger, SP and Kairalla, JA and De Lorenzo, P and Silverman, LB and Biondi, A},
title = {Philadelphia chromosome-positive acute lymphoblastic leukaemia in children and adolescents: A changing treatment landscape and a methodological challenge.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.70288},
pmid = {41448829},
issn = {1365-2141},
support = {//Ministero della Salute/ ; NW25-03-00276//Agentura Pro Zdravotnický Výzkum České Republiky/ ; U10CA180886/CA/NCI NIH HHS/United States ; U10CA180899/CA/NCI NIH HHS/United States ; 1U01CA232486/CA/NCI NIH HHS/United States ; 1U01CA243072/CA/NCI NIH HHS/United States ; 70112958//Deutsche Krebshilfe/ ; },
}

@article {pmid41447755,
year = {2025},
author = {Nair, MS and Scarborough, J and Reddy, CA and Bommireddy, AR and Brooks, E and Almassi, N and Weight, CJ and Campbell, S and Ornstein, MC and Nizam, A and Gilligan, T and Wee, C and Gupta, S and Scott, JG and Mastroianni, A and Tendulkar, R and Mian, OY},
title = {Trimodality Therapy for Bladder Cancer: A Single Institution Retrospective Analysis of Factors Associated With Outcomes for High-Risk Patients Undergoing Organ-Sparing Therapy.},
journal = {Clinical genitourinary cancer},
volume = {24},
number = {1},
pages = {102477},
doi = {10.1016/j.clgc.2025.102477},
pmid = {41447755},
issn = {1938-0682},
abstract = {PURPOSE: We sought to define patient and disease characteristics associated with outcomes after trimodality therapy (TMT) for high-risk nonmuscle invasive and muscle invasive bladder cancer (MIBC). A retrospective analysis of a large single institution cohort treated with bladder preservation therapy was performed to identify factors associated with survival.

METHODS AND MATERIALS: Patients with high-risk non-MIBC or MIBC who underwent definitive bladder sparing treatment between 2006 and 2022 were included. Variables for analysis included age, sex, Charlson Comorbidity Index (CCI), surgical candidacy, neoadjuvant/induction chemotherapy (NAC), tumor size, presence of hydronephrosis, carcinoma in-situ, and histologic subtype. Kaplan-Meier analysis was done to calculate rates of overall survival (OS) and disease-free survival (DFS), while cumulative incidence analysis was done to calculate rates of cancer specific mortality (CSM) and local recurrence. Cox proportional hazards regression was done to identify factors associated with OS and DFS. Competing risk regression was done to identify factors associated with CSM and local recurrence.

RESULTS: 226 patients were included in the cohort with a median follow up of 18.9 months (range 0.9-172.3). The median age was 79 years (range 49-98) and 79.2% were male. On univariate Cox proportional hazards regression, younger age, NAC, and cystectomy candidacy were associated with improved OS (P < .0001, HR = 1.05, 95% CI, 1.03-1.08; P = .04, HR = 0.62, 95% CI, 0.39-0.99; P < .0001, HR = 0.42, 95% CI, 0.27-0.65; respectively). On multivariable analysis, only younger age and cystectomy eligibility were associated with improved OS (P = .002, HR = 1.04, 95% CI, 1.02-1.07; P = .006, HR = 0.52, 95% CI, 0.33-0.83; respectively).

CONCLUSION: This study finds cystectomy eligibility to be associated with improved survival and underscores the importance of multi-disciplinary assessment in determining candidacy for organ preserving therapy in MIBC patients.},
}

@article {pmid41446897,
year = {2025},
author = {Zhai, G and Bar, M and Cowan, AJ and Rubinstein, S and Shi, Q and Zhang, N and Xie, E and Ma, W},
title = {AI for evidence-based treatment recommendation in oncology: a blinded evaluation of large language models and agentic workflows.},
journal = {Frontiers in artificial intelligence},
volume = {8},
number = {},
pages = {1683322},
pmid = {41446897},
issn = {2624-8212},
abstract = {BACKGROUND: Evidence-based medicine is crucial for clinical decision-making, yet studies suggest that a significant proportion of treatment decisions do not fully incorporate the latest evidence. Large Language Models (LLMs) show promise in bridging this gap, but their reliability for medical recommendations remains uncertain.

METHODS: We conducted an evaluation study comparing five LLMs' recommendations across 50 clinical scenarios related to multiple myeloma diagnosis, staging, treatment, and management, using a unified evidence cutoff of June 2024. The evaluation included three general-purpose LLMs (OpenAI o1-preview, Claude 3.5 Sonnet, Gemini 1.5 Pro), one retrieval-augmented generation (RAG) system (Myelo), and one agentic workflow-based system (HopeAI). General-purpose LLMs generated responses based solely on their internal knowledge, while the RAG system enhanced these capabilities by incorporating external knowledge retrieval. The agentic workflow system extended the RAG approach by implementing multi-step reasoning and coordinating with multiple tools and external systems for complex task execution. Three independent hematologist-oncologists evaluated the LLM-generated responses using standardized scoring criteria developed specifically for this study. Performance assessment encompassed five dimensions: accuracy, relevance, comprehensiveness, hallucination rate, and clinical use readiness.

RESULTS: HopeAI demonstrated superior performance across accuracy (82.0%), relevance (85.3%), and comprehensiveness (74.0%), compared to OpenAI o1-preview (64.7, 57.3, 36.0%), Claude 3.5 Sonnet (50.0, 51.3, 29.3%), Gemini 1.5 Pro (48.0, 46.0, 30.0%), and Myelo (58.7, 56, 32.7%). Hallucination rates were consistently low across all systems: HopeAI (5.3%), OpenAI o1-preview (3.3%), Claude 3.5 Sonnet (10.0%), Gemini 1.5 Pro (8.0%), and Myelo (5.3%). Clinical use readiness scores were relatively low for all systems: HopeAI (25.3%), OpenAI o1-preview (6.0%), Claude 3.5 Sonnet (2.7%), Gemini 1.5 Pro (4.0%), and Myelo (4.0%).

CONCLUSION: This study demonstrates that while current LLMs show promise in medical decision support, their recommendations require careful clinical supervision to ensure patient safety and optimal care. Further research is needed to improve their clinical use readiness before integration into oncology workflows. These findings provide valuable insights into the capabilities and limitations of LLMs in oncology, guiding future research and development efforts toward integrating AI into clinical workflows.},
}