tbuckley/cabot-search huggingface dataset:
Functional genotype classification groups distinguish disease severity in recessive dystrophic epidermolysis bullosa
Authors: Pirunthan Pathmarajah, Edward Eid, Jaron Nazaroff, Jodi So, Vaishali Mittal, Nicki Harris, Shufeng Li, Anne W Lucky, Emily S Gorell, Kathleen G Peoples, Elena Pope, Irene Lara-Corrales, Amy S Paller, Karen Wiss, Marissa J Perman, Lawrence F Eichenfield, Moise L Levy, Kimberly D Morel, Maria T García-Romero, Catherine C McCuaig, Melissa Saber, M Peter Marinkovich, Anthony Oro, Anna L Bruckner, Jean Y Tang
Journal: British Journal of Dermatology (2025)

Abstract Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic disorder due to pathogenic variants in the COL7A1 gene. In this study we determined the association between different categories of COL7A1 variants and clinical disease severity in 236 RDEB patients in North America. Published reports or in-silico predictions were used to assess the impact of pathogenic variants in COL7A1 on type VII collagen (C7) protein function. Three impact categories were postulated: genotypes that would likely cause a low impact on C7 function (splice B/missense, missense/missense), medium impact [premature termination codon (PTC)/splice B, splice A/splice B, PTC/missense, splice A/missense, splice B/splice B] and high impact (PTC/PTC, PTC/splice A, splice A/splice A). Splice A variants are predicted to cause downstream PTCs while splice B variants cause in-frame exon skipping and are therefore less deleterious. Severity of functional impact was significantly associated with history of gastrostomy tube placement, esophageal dilation, hand surgery, anemia, renal disease, chronic wounds, diffuse skin involvement and history of squamous cell carcinoma. Odds of death were 3.25 (1.24-8.50, p=0.02) higher in the high vs medium impact group. High impact group patients had worse clinical outcomes. Functional genotype categories are a feasible approach to risk stratify patients based on predicted C7 function.
Relating ecological diversity to genetic discontinuity across bacterial species
Authors: Hemanoel Passarelli-Araujo, Thiago M. Venancio, William P. Hanage
Journal: Genome biology (2025)

Genetic discontinuity represents abrupt breaks in genomic identity among species. Advances in genome sequencing have enhanced our ability to track and characterize genetic discontinuity in bacterial populations. However, exploring the degree to which bacterial diversity exists as a continuum or sorted into discrete and readily defined species remains a challenge in microbial ecology. Here, we aim to quantify the genetic discontinuity ( $$\delta$$ ) and investigate how this metric is related to ecology. We harness a dataset comprising 210,129 genomes to systematically explore genetic discontinuity patterns across several distantly related species, finding clear breakpoints which vary depending on the taxa in question. By delving into pangenome characteristics, we uncover a significant association between pangenome saturation and genetic discontinuity. Closed pangenomes are associated with more pronounced breaks, exemplified by Mycobacterium tuberculosis. Additionally, through a machine learning approach, we detect key features such as gene conservation patterns and functional annotations that significantly impact genetic discontinuity prediction. Our study clarifies bacterial genetic patterns and their ecological impacts, enhancing the delineation of species boundaries and deepening our understanding of microbial diversity.
Global status and attributable risk factors of breast, cervical, ovarian, and uterine cancers from 1990 to 2021
Authors: Tianye Li, Haoxiang Zhang, Mengyi Lian, Qionghua He, Mingwei Lv, Lingyun Zhai, Jianwei Zhou, Kongming Wu, Ming Yi
Journal: Journal of Hematology & Oncology (2025)

Female-specific cancers, particularly breast, cervical, ovarian, and uterine cancers, account for nearly 40% of all cancers in women. This study aimed to analyze the global epidemiological trends of these cancers from 1990 to 2021, offering insights into their evolving patterns and providing valuable information for health policymakers to allocate healthcare resources more effectively. Data from the Global Burden of Disease Study 2021 (GBD 2021) were used to comprehensively assess the global incidence, mortality, and disability-adjusted life years (DALYs) of female-specific cancers. Age-standardized rates facilitated cross-regional comparisons, accounting for differences in population size and demographics. The socio-demographic index (SDI) was employed to categorize regions and evaluate correlations between cancer burden and economic level. In addition, risk factors attributable to female-specific cancer deaths and DALYs were assessed based on the comparative risk assessment model of the GBD project. From 1990 to 2021, the global burden of female-specific cancers increased at varying rates. In 2021, breast cancer accounted for 2.08 million incident cases, 0.66 million deaths, and 20.25 million DALYs globally. In comparison, cervical, ovarian, and uterine cancers had lower burdens, with 0.67 million, 0.30 million, and 0.47 million incident cases, respectively. Age-standardized rates of breast, ovarian, and uterine cancers showed positive correlations with SDI, while cervical cancer exhibited a negative correlation. Attributable risk factors for breast cancer-associated deaths in 2021 included dietary risks, high body-mass index (BMI), high fasting plasma glucose, alcohol use, tobacco use, and low physical activity. Additional risk factors were unsafe sex and tobacco use for cervical cancer, high BMI and occupational risks for ovarian cancer, and high BMI for uterine cancer. The burden of female-specific cancers has increased in recent decades, with significant demographic and regional discrepancies. These findings highlight the urgent need for targeted public health interventions to mitigate the global impact of these cancers.
IL-2-loaded liposomes modified with sorafenib derivative exert a synergistic anti-melanoma effect via improving tumor immune microenvironment and enhancing antiangiogenic activity
Authors: Xuan Huang, Kudelaidi Kuerban, Jajun Fan, Danjie Pan, Huaning Chen, Jiayang Liu, Songna Wang, Dianwen Ju, Yi Zhun Zhu, Jiyong Liu, Li Ye
Journal: Asian Journal of Pharmaceutical Sciences (2025)
Tumor-Specific Liquid Metal Nitric Oxide Nanogenerator for Enhanced Breast Cancer Therapy
Authors: Chen Su, Jianhan Lin, Cong Li, Xinyu Wang, Donghui Pan, Lizhen Wang, Yuping Xu, Chongyang Chen, Kangfan Ji, Jinqiang Wang, Daozhen Chen, Min Yang, Zhen Gu, Junjie Yan
Journal: Asian Journal of Pharmaceutical Sciences (2025)

Nitric oxide (NO) modulates several cancer-related physiological processes and has advanced the development of green methods for cancer treatment and integrated platforms for combination or synergistic therapies. Although a nanoengineering strategy has been proposed to overcome deficiencies of NO gas or small NO donor molecules, such as short half-life, lipophilicity, non-selectivity, and poor stability, it remains challenging to prepare NO nanomedicines with simple composition, multiple functions and enhanced therapeutic efficacy. Herein, we build a liquid metal nanodroplet (LMND)-based NO nanogenerator (LMND@HSG) that is stabilized by a bioreducible guanylated hyperbranched poly(amido amine) (HSG) ligand. Mechanically, the tumor microenvironment specifically triggers a cascade process of glutathione elimination, reactive oxygen species (ROS) generation, and NO release. According to actual demand, the ROS and NO concentrations could be readily controlled by tuning the LMND and HSG feed amounts. Along with the intrinsic anticancer property of LMND (ROS-mediated apoptosis and anti-angiogenesis), LMND@HSG administration could further enhance tumor growth suppression compared with LMND and HSG alone. From this study, leveraging LMND for NO gas therapy provides more possibilities for the prospect of LMND-based anticancer nanomedicines.
Symptom Evolution in Individuals with Ongoing Symptomatic COVID-19 and Post COVID-19 Syndrome After SARS-CoV-2 Vaccination Versus Influenza Vaccination
Authors: Khaled Rjoob, Michela Antonelli, Benjamin Murray, Erika Molteni, Nathan Cheetham, Liane S Canas, Marc Modat, Joan Capdevila Pujol, Christina Hu, Vicky Bowyer, Jonathan Wolf, Tim D Spector, Sebastien Ourselin, Alexander Hammers, Emma L Duncan, Claire J Steves, Carole H Sudre
Journal: Journal of Infection (2025)
Visualizing Enterohepatic Circulation In Vivo by Sensitive 19F MRI with a Fluorinated Ferrous Chelate-Based Small Molecule Probe
Authors: Lingxuan Li, Ao Li, Junjie Wang, Juan Shao, Huijie Zhou, Zixiong Peng, Hongyu Lin, Jinhao Gao
Journal: Biomaterials (2025)
Proteomics: An In‐Depth Review on Recent Technical Advances and Their Applications in Biomedicine
Authors: Jing Liang, Jundan Tian, Huadong Zhang, Hua Li, Lixia Chen
Journal: Medicinal Research Reviews (2025)

ABSTRACT Proteins hold pivotal importance since many diseases manifest changes in protein activity. Proteomics techniques provide a comprehensive exploration of protein structure, abundance, and function in biological samples, enabling the holistic characterization of overall changes in organisms. Nowadays, the breadth of emerging methodologies in proteomics is unprecedentedly vast, with constant optimization of technologies in sample processing, data collection, data analysis, and its scope of application is steadily transitioning from the bench to the clinic. Here, we offer an insightful review of the technical developments in proteomics and its applications in biomedicine over the past 5 years. We focus on its profound contributions in profiling disease spectra, discovering new biomarkers, identifying promising drug targets, deciphering alterations in protein conformation, and unearthing protein–protein interactions. Moreover, we summarize the cutting‐edge technologies and potential breakthroughs in the proteomics pipeline and provide the principal challenges in proteomics. Based on these, we aspire to broaden the applicability of proteomics and inspire researchers to enhance our understanding of complex biological systems by utilizing such techniques.
Why the belief in meritocracy is so pervasive
Authors: Ian R. Hadden, Céline Darnon, Lewis Doyle, Matthew J. Easterbrook, Sébastien Goudeau, Andrei Cimpian
Journal: Trends in Cognitive Sciences (2025)

People worldwide tend to believe that their societies are more meritocratic than they actually are. We propose the belief in meritocracy is widespread because it is rooted in simple, seemingly obvious causal–explanatory intuitions. Our proposal suggests solutions for debunking the myth of meritocracy and increasing support for equity-oriented policies.
Glycolysis Dictates Response to Fasting-Mimicking Diet in Breast Cancer
Journal: Cancer Discovery (2025)

Major Finding: Fasting-mimicking diet plus chemotherapy exhibits high response rates in triple-negative breast cancer.Concept: Tumors of complete responders exhibit an early downregulation of glucose metabolism genes and pathways. Impact: Early downregulation of glycolysis may be a predictive biomarker of response to fasting-mimicking diets.
Locally producing antibacterial peptide to deplete intratumoral pathogen for preventing metastatic breast cancer
Authors: Shizhen Geng, Tingting Xiang, Yaru Shi, Mengnian Cao, Danyu Wang, Jing Wang, Xinling Li, Haiwei Song, Zhenzhong Zhang, Jinjin Shi, Junjie Liu, Airong Li, Ke Sun
Journal: Acta Pharmaceutica Sinica B (2025)

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.
Albendazole–ivermectin co-formulation for the treatment of Trichuris trichiura and other soil-transmitted helminths: a randomised phase 2/3 trial
Authors: Alejandro Krolewiecki, Stella Kepha, Pedro E Fleitas, Lisette van Lieshout, Woyneshet Gelaye, Augusto Messa, Javier Gandasegui, Jaime Algorta, Valdemiro Novela, Áuria de Jesus, Martin Rono, Dawit Degarege, Dereje Bedane, Jusper Mwahanje, Inácio Mandomando, Charles Mwandawiro, Wendemagegn Enbiale, José Muñoz, Alejandro Krolewiecki, Stella Kepha, Pedro E Fleitas, Lisette van Lieshout, Woyneshet Gelaye, Augusto Messa Jr, Javier Gandasegui, Jaime Algorta, Valdemiro Novela, Auria De Jesus, Martin Rono, Dawit Degearege, Dereje Bedane, Jusper Mwahanje, Inacio Mandomando, Charles Mwandawiro, Wendemagegn Enbiale, Jose Muñoz
Journal: The Lancet Infectious Diseases (2025)
Baseline characteristics of patients in the Chinese Bronchiectasis Registry (BE-China): a multicentre prospective cohort study
Authors: Jin-Fu Xu, Hui-Zhen Zheng, Hai-Wen Lu, Ling-Wei Wang, Bin Wu, Xiao-Dong Lv, Hong Luo, Jian Feng, Yuan-Yuan Li, Lin Liu, Jin-Guang Jia, Wei-Qiang Mo, Hong-Yan Gu, Jing-Bo Jiang, Dao-Xin Wang, Bin Wang, Li Li, Zhi Yuan, Wen Li, Min Xie, Zhi-Jun Jie, Xiao-Yun Fan, Dan Li, Xinlun Tian, Min Zhang, Wei-Jie Guan, Hong Fan, Yuan-Lin Song, Jian He, De-Jie Chu, Chun-Ling Du, Jian-Quan Zhang, Chao Cao, Jie-Ming Qu, James D Chalmers
Journal: The Lancet Respiratory Medicine (2025)
Total criminalisation of abortion is a threat to sexual and reproductive health in Brazil
Authors: Michelle Fernandez, Luísa M M Fernandes, Melania M R de Amorim
Journal: BMJ (2025)

The proposed constitutional amendment would be a massive setback for reproductive rights and health in Brazil, write <b>Michelle Fernandez</b>, <b>Luísa Fernandes</b>, and <b>Melania de Amorim</b>
R21 in Matrix-M adjuvant in UK malaria-naive adult men and non-pregnant women aged 18–45 years: an open-label, partially blinded, phase 1–2a controlled human malaria infection study
Authors: Navin Venkatraman, Daniel Silman, Duncan Bellamy, Lisa Stockdale, Georgina Bowyer, Nick J Edwards, Oliver Griffiths, Fernando Ramos Lopez, Jonathan Powlson, Catherine Mair, Pedro M Folegatti, Mehreen S Datoo, Richard Morter, Angela M Minassian, Ian Poulton, Katharine A Collins, Florian Brod, Philip Angell-Manning, Eleanor Berrie, Nathan Brendish, Greg Glenn, Louis Fries, Jake Baum, Andrew M Blagborough, Rachel Roberts, Alison M Lawrie, Brian Angus, David J M Lewis, Saul N Faust, Katie J Ewer, Adrian V S Hill
Journal: The Lancet Microbe (2025)
The Impact of Health Insurance on Mortality
Authors: Helen Levy, Thomas C. Buchmueller
Journal: Annual Review of Public Health (2025)

A 2008 review in the Annual Review of Public Health considered the question of whether health insurance improves health. The answer was a cautious yes because few studies provided convincing causal evidence. We revisit this question by focusing on a single outcome: mortality. Because of multiple high-quality studies published since 2008, which exploit new sources of quasi-experimental variation as well as new empirical approaches to evaluating older data, our answer is more definitive. Studies using different data sources and research designs provide credible evidence that health insurance coverage reduces mortality. The effects, which tend to be strongest for adults in middle age or older and for children, are generally evident shortly after coverage gains and grow over time. The evidence now unequivocally supports the conclusion that health insurance improves health.
Epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial
Authors: Joshua D. Brody, Judit Meszaros Jørgensen, David Belada, Régis Costello, Marek Trněný, Umberto Vitolo, David John Lewis, Yasmin H. Karimi, Anna Sureda, Marc Andre, Björn E. Wahlin, Pieternella J. Lugtenburg, Tony Jiang, Kubra Karagoz, Andrew J Steele, Aqeel Abbas, Liwei Wang, Malene Risum, Raul Cordoba
Journal: Blood (2025)

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have poor outcomes. Gemcitabine + oxaliplatin (GemOx) with rituximab, a standard salvage therapy, yields complete response (CR) rates of approximately 30% and median overall survival (OS) of 10-13 months. Patients with refractory disease fare worse, with a CR rate of 7% for subsequent therapies and median OS of 6 months. Epcoritamab, a CD3xCD20 bispecific antibody approved for the treatment of R/R DLBCL after ≥2 therapy lines, has shown promising safety and efficacy in various combinations. We report results from the phase 1b/2 EPCORE® NHL-2 trial evaluating epcoritamab + GemOx in patients with R/R DLBCL who were ineligible for or had failed autologous stem cell transplant (ASCT). Patients received 48-mg subcutaneous epcoritamab after 2 step-up doses until progression or unacceptable toxicity; GemOx was given Q2W for 8 doses. The primary endpoint was overall response rate (ORR). As of December 15, 2023, 103 patients were enrolled (median follow‑up, 13.2 months). Patients had a median age of 72 years and challenging-to-treat disease: ≥2 prior therapy lines, 62%; prior CAR T, 28%; primary refractory disease, 52%; refractory to last therapy, 70%. ORR/CR rates were 85%/61%. Median duration of CR and OS were 23.6 and 21.6 months. Common treatment‑emergent adverse events were cytopenias and cytokine release syndrome (CRS). CRS events had predictable timing, were primarily low grade (52% overall, 1% grade 3), and resolved without leading to discontinuation. Epcoritamab + GemOx yielded deep, durable responses and favorable long-term outcomes in ASCT‑ineligible R/R DLBCL. NCT04663347
High-throughput drug screening identifies SMAC mimetics as enhancers of NK cell cytotoxicity in chronic myeloid leukemia
Authors: Petra Johanna Nygren, Jonas Otto Vilhelm Bouhlal, Emmi Jokinen, Sofia Forstén, Essi Laajala, Diogo Artur Alves Dias, Shady Adnan Awad, Aleksandr Ianevski, Jay Klievink, Hanna Lähteenmäki, Heikki Kuusanmäki, Mikko Myllymäki, Tiina Kasanen, Khalid Saeed, Dean A Lee, iCAN Flagship, Henrik Hjorth-Hansen, Tero Aittokallio, Olli Dufva, Satu Mustjoki
Journal: Blood (2025)

Natural killer (NK) cells have proven to be safe and effective immunotherapies, associated with favorable treatment responses in chronic myeloid leukemia (CML). Augmenting NK cell function with oncological drugs could improve NK cell-based immunotherapies. Here, we used a high-throughput drug screen consisting of over 500 small-molecule compounds to systematically evaluate the effects of oncological drugs on primary NK cells against CML cells. We identified SMAC mimetics as potent enhancers of NK cell cytotoxicity in both cell lines and primary patient samples. In contrast, several drug classes, including glucocorticoids and tyrosine kinase inhibitors such as dasatinib, inhibited NK cell cytotoxicity. Single-cell RNA sequencing revealed drug-induced transcriptomic changes in both NK and target CML cells. SMAC mimetics upregulated NF-κB target genes in NK cells, potentially contributing to their enhanced cytotoxicity. Inhibitory drugs dexamethasone, dasatinib, and sotrastaurin prevented NK cell transition to an activated state and suppressed the expression of IFN-γ by NK cells, thus preventing IFN-γ mediated target cell transcriptomic response. In conclusion, we discovered that SMAC mimetics sensitize cancer cells to NK cell mediated killing, with potential clinical applications especially in patients with advanced phase CML.
Targeting DOT1L and EZH2 synergizes in breaking the germinal center identity of Diffuse Large B-cell Lymphoma
Authors: Camiel Göbel, Rachele Niccolai, Marnix Hugo Philip de Groot, Jayashree Jayachandran, Joleen Traets, Daan Juri Kloosterman, Sebastian Gregoricchio, Ben Morris, Maaike Kreft, Ji-Ying Song, Leyla Azarang, Eirini Kasa, Nienke Oskam, Daniel de Groot, Liesbeth Hoekman, Onno Bleijerveld, Marie José Kersten, Muhammad Assad Aslam, Fred van Leeuwen, Heinz Jacobs
Journal: Blood (2025)
Age and biologic survival in patients with moderate-to-severe psoriasis: A cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR)
Authors: Oras A Alabas, Kayleigh J Mason, Zenas Z N Yiu, Catherine H Smith, Richard B Warren, Christopher E M Grifﬁths, Jonathan Barker, Simon Morrison, Anthony Bewley, Ian Evans, Christopher Griffiths, Shehnaz Ahmed, Brian Kirby, Elise Kleyn, Philip Laws, Philip Hampton, Oras Alabas, Kathleen McElhone, Zenas Yiu, Teena Mackenzie, Tess McPherson, Ruth Murphy, Anthony Ormerod, Shernaz Walton, Nick Reynolds, Catherine Smith, Alexa Shipman, Christina Ye, Olivia Hughes, Richard Warren, Richard Weller, Girish Gupta, Vera Zietemann
Journal: British Journal of Dermatology (2025)

Abstract Background The current management of psoriasis does not differentiate between young and old patients in selecting the safest and/or most effective biologic. Objectives To explore the effect of age at treatment initiation in response to biologics in patients with moderate-to-severe psoriasis in the UK and Eire. Methods Data from patients registering to the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007-2024 on first course of Tumour Necrosis Factor (TNF), interleukin (IL) 12/13, IL-17 and IL-23 inhibitors (i) with at least 6 months’ follow-up were included. Patients aged ≥16 years at registration were grouped into 16-24, 25-34, 35-44, 45-54, 55-64, 65-74, and ≥75 year cohorts with 45-54 years as the Reference Cohort. Biologic survival was defined as the time between treatment initiation to its discontinuation associated with ineffectiveness or occurrence of adverse events (AEs). Adjusted hazard ratio (aHR) with 95% confidence interval (CI) was estimated using a flexible parametric model to compare discontinuing therapy between age groups. Each model included exposure (biologic class), effect modifier (age groups), interaction terms, baseline demographic, clinical, and disease severity covariates. Results There were 14,294 patients included; 847 (6%) 16-24; 2,502 (18%) 25-34; 3,575 (25%) 35-44; 3,863 (27%) 45-54; 2,338 (16%) 55-64; 954 (7%) 65-74; and 215 (2%) ≥75 years. The interaction effects model showed individuals aged 16-24 years were more likely to discontinue TNFi due to ineffectiveness compared with the Reference Cohort (45-54 years) [aHR (95% CI) 1.30 (1.10, 1.55)]. For survival associated with AEs, individuals aged 55-64 years were at higher risk of discontinuing TNFi and IL12/23i [1.33 (1.13, 1.56) and 1.34 (1.03, 1.75), respectively], those aged 65-74 years were more likely to discontinue TNFi, IL-12/23i and IL-17i [1.89 (1.54, 2.31), 2.00 (1.47, 2.73) and 1.69 (1.08, 2.64), respectively] whereas individuals aged ≥75 years were at higher risk of discontinuing the four biologic classes. Conclusions Psoriasis patients aged 16-24 years are more likely to stop TNFi due to ineffectiveness whereas those aged ≥55 years are more likely to stop biologics due to AEs. These large real-world findings provide important information for clinicians treating people with moderate-to-severe psoriasis across all age groups.