tbuckley/cabot-search huggingface dataset:
Real-world feasibility, accuracy and acceptability of automated retinal photography and AI-based cardiovascular disease risk assessment in Australian primary care settings: a pragmatic trial
Authors: Wenyi Hu, Zhihong Lin, Malcolm Clark, Jacqueline Henwood, Xianwen Shang, Ruiye Chen, Katerina Kiburg, Lei Zhang, Zongyuan Ge, Peter van Wijngaarden, Zhuoting Zhu, Mingguang He
Journal: npj Digital Medicine (2025)

We aim to assess the real-world accuracy (primary outcome), feasibility and acceptability (secondary outcomes) of an automated retinal photography and artificial intelligence (AI)-based cardiovascular disease (CVD) risk assessment system (rpCVD) in Australian primary care settings. Participants aged 45–70 years who had recently undergone all or part of a CVD risk assessment were recruited from two general practice clinics in Victoria, Australia. After consenting, participants underwent retinal imaging using an automated fundus camera, and an rpCVD risk score was generated by a deep learning algorithm. This score was compared against the World Health Organisation (WHO) CVD risk score, which incorporates age, sex, and other clinical risk factors. The predictive accuracy of the rpCVD and WHO CVD risk scores for 10-year incident CVD events was evaluated using data from the UK Biobank, with the accuracy of each system assessed through the area under the receiver operating characteristic curve (AUC). Participant satisfaction was assessed through a survey, and the imaging success rate was determined by the percentage of individuals with images of sufficient quality to produce an rpCVD risk score. Of the 361 participants, 339 received an rpCVD risk score, resulting in a 93.9% imaging success rate. The rpCVD risk scores showed a moderate correlation with the WHO CVD risk scores (Pearson correlation coefficient [PCC] = 0.526, 95% CI: 0.444–0.599). Despite this, the rpCVD system, which relies solely on retinal images, demonstrated a similar level of accuracy in predicting 10-year incident CVD (AUC = 0.672, 95% CI: 0.658-0.686) compared to the WHO CVD risk score (AUC = 0.693, 95% CI: 0.680-0.707). High satisfaction rates were reported, with 92.5% of participants and 87.5% of general practitioners (GPs) expressing satisfaction with the system. The automated rpCVD system, using only retinal photographs, demonstrated predictive accuracy comparable to the WHO CVD risk score, which incorporates multiple clinical factors including age, the most heavily weighted factor for CVD prediction. This underscores the potential of the rpCVD approach as a faster, easier, and non-invasive alternative for CVD risk assessment in primary care settings, avoiding the need for more complex clinical procedures.
Prevalence and pathogenic activity of anti-Desmocollin-3 antibodies in patients with pemphigus vulgaris and pemphigus foliaceus
Authors: Maud Maho-Vaillant, Alexandre Lemieux, Christophe Arnoult, Léopoldine Lebourgeois, Vivien Hébert, Thara Jaworski, Billal Tedbirt, Fabienne Jouen, Olivier Boyer, Sébastien Calbo, Pascal Joly, Marie-Laure Golinski
Journal: British Journal of Dermatology (2025)

Desmocollin-3 (DSC3) is a calcium-dependent desmosomal cadherin that plays an essential role in cell-cell adhesion. IgG antibodies (Abs) directed against the extracellular (EC) domain of DSC3 have occasionally been detected in rare types of pemphigus. Investigations into the prevalence of anti-EC-DSC3 IgG Abs and those targeting the intracellular (IC) domain of DSC3 in pemphigus vulgaris and pemphigus foliaceus sera, and their potential pathogenic activity, have yielded conflicting results. To assess the prevalence and pathogenicity of Abs directed against the EC and IC domains of DSC3 in patients with pemphigus. Anti-DSC3 IgG and IgA directed against the EC and IC domains of DSC3 were assayed in 146 patients with pemphigus using a newly developed addressable laser bead immunoassay. The pathogenicity of these autoAbs was first tested in vitro using a keratinocyte dissociation assay with patients' sera or from C57BL/6 mice immunized with recombinant IC-DSC3. In vivo pathogenicity was tested by passive transfer of an anti-IC-DSC3 monoclonal Ab (mAb) derived from a hybridoma (A9) into neonatal mice. Anti-EC-DSC3 or anti-IC-DSC3 IgG and/or IgA Abs were detected in 21.2% of sera from patients with pemphigus vs. 4.0% (P < 0.001) and 5.0% (P < 0.001) of sera from healthy donors, respectively. Most anti-DSC3 Abs corresponded to IgA. Anti-IC-DSC3 Abs were detected in 44% of patients with pemphigus whose serum anti-desmoglein (DSG) 1-3 Ab profile was inconsistent with their clinical and histological features, according to compensation theory. Anti-IC-DSC3 IgG and IgA Abs induced a dissociation of the keratinocyte monolayer in vitro, which was abolished by preadsorption of these IgG or IgA fractions with recombinant IC-DSC3. In addition, IgG from mice immunized with recombinant IC-DSC3 induced acantholysis in vitro. Finally, in neonatal mice, the passive transfer of an anti-IC-DSC3 mAb in combination with anti-DSG1-3 Abs exacerbated blister formation. Our findings suggest that anti-IC-DSC3 Abs are pathogenic and explain the discordance seen in some patients with regard to their clinical phenotype and their anti-DSG1-3 Ab profile.
Coronary CT Anatomy-Based Prediction of Invasively Assessed Hemodynamic Significance in Middle-Aged Patients With Right Coronary Artery Anomaly: The NARCO Study
Authors: Anselm W. Stark, René L. Matthey-de-l’Endroit, Adriana Ferroni, Ryota Kakizaki, Marius R. Bigler, Flavio G. Biccirè, Yasushi Ueki, Andreas Haeberlin, Matthias Siepe, Isaac Shiri, Stephan Windecker, Lorenz Räber, Christoph Gräni
Journal: Circulation (2025)
Upregulation of <i>Lactobacillus spp</i> . in gut microbiota as a novel mechanism for environmental eustress-induced anti-pancreatic cancer effects
Authors: Yiyi Liang, Min Du, Xin Li, Jian Gao, Qian Li, Huimin Li, Jin Li, Xiang Gao, Hui Cong, Yimeng Huang, Xinran Li, Liwei Wang, Jiujie Cui, Yu Gan, Hong Tu
Journal: Gut Microbes (2025)

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited effective treatment options. Emerging evidence links enriched environment (EE)-induced eustress to PDAC inhibition. However, the underlying mechanisms remain unclear. In this study, we explored the role of gut microbiota in PDAC-suppressive effects of EE. We demonstrated that depletion of gut microbiota with antibiotics abolished EE-induced tumor suppression, while fecal microbiota transplantation (FMT) from EE mice significantly inhibited tumor growth in both subcutaneous and orthotopic PDAC models housed in standard environment. 16S rRNA sequencing revealed that EE enhanced gut microbiota diversity and selectively enriched probiotic Lactobacillus, particularly L. reuteri. Treatment with L. reuteri significantly suppressed PDAC tumor growth and increased natural killer (NK) cell infiltration into the tumor microenvironment. Depletion of NK cells alleviated the anti-tumor effects of L. reuteri, underscoring the essential role of NK cell-mediated immunity in anti-tumor response. Clinical analysis of PDAC patients showed that higher fecal Lactobacillus abundance correlated with improved progression-free and overall survival, further supporting the therapeutic potential of L. reuteri in PDAC. Overall, this study identifies gut microbiota as a systemic regulator of PDAC under psychological stress. Supplementation of psychobiotic Lactobacillus may offer a novel therapeutic strategy for PDAC.
Proportion of patients in phase 2 oncology trials receiving treatments that are ultimately approved
Authors: Charlotte Ouimet, Bianca Fodor, Joseph C Del Paggio, Jonathan Kimmelman
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background Many patients enroll in phase 1 dose expansion cohorts or phase 2 clinical trials (together referred to below as “phase 2”) seeking access to novel treatments. Little is known about the extent to which they benefit by enrolling. Herein, we use a novel metric of benefit—therapeutic proportion—to assess the probability that patients in phase 2 trials receive treatment that eventually advances to FDA (Food and Drug Administration) approval for their condition. Methods We randomly sampled 400 trials identified in a search of Clinicaltrials.gov for cancer phase 2 trials initiated between November 1, 2012 and November 1, 2015. We determined whether the drug/dose/indication tested in each trial advanced to FDA approval within 7.5 years. We determined whether the drug/dose/indication presented substantial clinical benefit using the ESMO-MCBS (European Society for Medical Oncology - Magnitude of Clinical Benefit Scale), or whether it received off-label recommendation in NCCN (National Comprehensive Cancer Network) guidelines. Results Collectively, trials in our sample enrolled 25 002 patient-participants in 608 specific treatment cohorts. A total of 4045 patients received a treatment that advanced to FDA approval (16.2%; 95% CI = 10.3 to 22.7). The therapeutic proportion increased to 19.4% (95% CI = 14.1 to 25.8) when considering NCCN off-label recommendations and decreased to 9.3% (95% CI = 4.7 to 14.6) for FDA-approved regimens considered being of substantial clinical benefit by ESMO-MCBS. Bootstrap test of mean difference showed no statistical difference in proportions based on drug class, trial phase, or sponsorship. Conclusion One in 6 patients in phase 2 clinical trials receives treatments that are eventually approved. This represents a higher therapeutic value than phase 1 trials.
Charting a novel path towards Ebola virus disease preparedness: Considerations for preventive vaccination
Authors: Donovan Guttieres, Charlot Diepvens, Rebecca F. Grais, Jackline Kiarie, Nico Vandaele, Catherine Decouttere
Journal: PLoS Medicine (2025)

In June 2024, Gavi, the Vaccine Alliance, launched a preventive vaccination program against Ebola virus disease (EVD). This marks a historic shift in the management of EVD, allowing at-risk countries across sub-Saharan Africa to request support in implementing preventive vaccination campaigns. This perspective piece shares considerations that can inform how countries approach preventive EVD vaccination and potential unintended consequences. It also provides insights into strategies for vaccines against other epidemic-prone pathogens.
SMARCA4 Inhibits Breast Cancer Progression and Metastasis through RHOA Suppression
Authors: Zheng Sun, Zhuo Li, Yong Wei, Lillian Xu, Xiang Hang, Yibin Kang
Journal: Cancer Research (2025)

Abstract Triple-negative breast cancer (TNBC) presents the most challenging subtype of the disease due to its aggressive nature and lack of targeted therapy options. To identify regulators of TNBC, we conducted a genome-wide CRISPR-knockout screen in both 3D tumor spheroid and 2D cell culture models. The 3D spheroid model displayed unique potential in identifying putative tumor suppressors due to its closer mimicry of in vivo tumor growth conditions. Notably, the chromatin-remodeling SWI/SNF complex emerged as a potent suppressor of tumor spheroid growth. Specifically, loss of the SWI/SNF ATPase subunit SMARCA4 promoted tumor spheroid growth with reduced compactness and enhanced primary tumor growth and metastasis across multiple TNBC models. SMARCA4 was required for the transcription of Rho GTPase activating factor ARHGAP29 by enhancing DNA accessibility through direct binding to its promoter. SMARCA4 loss resulted in reduced ARHGAP29 levels and hyperactive RHOA signaling, subsequently disrupting cell adhesion, facilitating the formation of a loose spheroid structure in vitro, and enhancing breast cancer growth and metastasis in vivo. These results establish SMARCA4 and SWI/SNF as tumor suppressors of TNBC through suppression of RHOA activity.
A roadmap toward genome-wide CRISPR screening throughout the organism
Authors: Tess K Fallon, Kristin A Knouse
Journal: Cell Genomics (2025)

Genome-wide CRISPR screening in the organism has tremendous potential to answer long-standing questions of mammalian physiology and disease. However, bringing this powerful technology in vivo presents unique challenges, including delivering a genome-wide sgRNA library to the appropriate cell type, achieving sufficient coverage of the library, and selecting for the phenotype of interest. In this review, we highlight recent advances in sgRNA delivery, library design, and phenotypic readout that can help overcome these technical challenges and thereby bring high-throughput genetic dissection to an increasing number of tissues and questions. We are excited about the potential for ongoing innovation in these areas to ultimately enable genome-wide CRISPR screening in any cell type of interest in the organism, allowing for unprecedented investigation into diverse questions of mammalian physiology and disease.
Circulating Tumor Microenvironment in Metastasis
Authors: Rui Tang, Shujuan Luo, Hui Liu, Yan Sun, Manran Liu, Lu Li, Haoyu Ren, Martin K. Angele, Nikolaus Börner, Keda Yu, Zufeng Guo, Guobing Yin, Haojun Luo
Journal: Cancer Research (2025)

Abstract Activation of invasion and metastasis is a central hallmark of cancer, contributing to the primary cause of death for cancer patients. In the multistep metastatic process, cancer cells must infiltrate the circulation, survive, arrest at capillary beds, extravasate, and form metastatic clones in distant organs. However, only a small proportion of circulating tumor cells (CTCs) successfully form metastases, with transit of CTCs in the circulation being the rate-limiting step. The fate of CTCs is influenced by the circulating tumor microenvironment (cTME), which encompasses factors affecting their biological behaviors in the circulation. This liquid and flowing microenvironment differs significantly from the primary tumor microenvironment or the pre-metastatic niche. This review summarizes the latest advancements in identifying the biophysical cues, key components, and biological roles of the cTME, highlighting the network among biophysical attributes, blood cells, and non-blood factors in cancer metastasis. In addition to the potential of the cTME as a therapeutic target for inhibiting metastasis, the cTME could also represent as a biomarker for predicting patient outcomes and developing strategies for treating cancer.
The landcape of Helicobacter pylori-mediated DNA breaks links bacterial genotoxicity to its oncogenic potential
Authors: Hadas Sibony-Benyamini, Rose Jbara, Tania Shubash Napso, Layan Abu-Rahmoun, Daniel Vizenblit, Michal Easton-Mor, Shira Perez, Alexander Brandis, Tamar Leshem, Avi Peretz, Yaakov Maman
Journal: Genome Medicine (2025)

Helicobacter pylori (H. pylori) infection is a significant risk factor for gastric cancer (GC) development. A growing body of evidence suggests a causal link between infection with H. pylori and increased DNA breakage in the host cells. While several mechanisms have been proposed for this damage, their relative impact on the overall bacterial genotoxicity is unknown. Moreover, the link between the formation of DNA damage following infection and the emergence of cancerous structural variants (SV) in the genome of infected cells remained unexplored. We constructed a high-resolution map of genomic H. pylori-induced recurrent break sites using the END-seq method on AGS human gastric cells before and after infection. We next applied END-seq to cycling and arrested cells to identify the role of DNA replication on break formation. Recurrent H. pylori-mediated break sites were further characterized by analyzing published RNA-seq, DRIP-seq, and GRO-seq data at these sites. γH2AX staining and comet assay were used for DNA breakage quantification. Liquid chromatography-mass spectrometry (LC–MS) assay was used to quantify cellular concentrations of dNTPs. Our data indicated that sites of recurrent H. pylori-mediated DNA breaks are ubiquitous across cell types, localized at replication-related fragile sites, and their breakage is dependent on replication. Consistent with that, we found that H. pylori inflicts nucleotide depletion, and that rescuing the cellular nucleotide pool largely reduced H. pylori-induced DNA breaks. Intriguingly, we found that this genotoxic mechanism operates independently of H. pylori cag pathogenicity island (CagPAI) that encodes for the bacterial type 4 secretion system (T4SS), and its virulence factor, CagA, which was previously implicated in increasing DNA damage by downregulating the DNA damage response. Finally, we show that sites of recurrent H. pylori-mediated breaks coincide with chromosomal deletions observed in patients with intestinal-type GC and that this link potentially elucidates the persistent transcriptional alterations observed in cancer driver genes. Our findings indicate that dNTP depletion by H. pylori is a key component of its genotoxicity and suggest a link between H. pylori genotoxicity and its oncogenic potential.
Correction: Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells
Authors: Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Jianyu Weng, Peilong Lai, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Qiubin Liang, Yangqiu Li, Xuchao Zhang, Yilong Wu, Pentao Liu, Yao Yao, Duanqing Pei, Xin Du, Peng Li
Journal: Journal of Hematology & Oncology (2025)
Longitudinal Profiling of Circulating Tumor DNA Reveals the Evolutionary Dynamics of Metastatic Prostate Cancer During Serial Therapy
Authors: Yuehui Zhao, Naveen Ramesh, Ping Xu, Emi Sei, Min Hu, Shanshan Bai, Patricia Troncoso, Ana M. Aparicio, Christopher J. Logothetis, Paul G. Corn, Nicholas E. Navin, Amado J. Zurita
Journal: Cancer Research (2025)

Abstract Treatment decisions in metastatic castration-resistant prostate cancer (mCRPC) are mostly guided by clinical variables, but efforts to molecularly monitor the disease remain hampered by challenges in acquiring tumor tissue repeatedly. Here, we simultaneously profiled the genome copy number and exome in longitudinal plasma circulating tumor DNA (ctDNA) acquired before, during, and upon progression to serial treatments with androgen signaling inhibitors (ASI) and taxane chemotherapy from 60 mCRPC patients (2-10 samples per patient). The genomic data was used to delineate the clonal substructure and evolutionary dynamics of each patient, and an evolutionary dynamic index (EDI) was developed to measure the longitudinal changes of the tumor subclones. Treatment with ASI resulted in greater subclonal selection and population structure changes than taxane treatment. The subclones that emerged in association with serial therapy resistance harbored recurrent aberrations in previously identified and new candidate genes, with particular enrichment in genes related to PI3K-AKT signaling. These findings indicate that the integration of detailed clinical and genomics data can provide a framework for future unbiased genomic applications for ctDNA in the clinic to enable precision medicine.
Characterization of screening strategies for Lynch syndrome in Latin America
Authors: Anthony Vladimir Campos-Segura, Karin Alvarez, Alexis German Murillo Carrasco, Benedito Mauro Rossi, Mabel Bohorquez, Florencia Spirandelli, Claudio Benavides, Aina Balto, Adriana Della Valle, Luisina Inés Bruno, Francisco Lopez-Kostner, Marcia Cruz-Correa, Julio Sanchez Del Monte, Jorge Rugeles, Jesica Magalí Ramirez, Ivana Nascimento, Nora Manoukian Forones, Alicia Maria Cock-Rada, Carlos Reyes-Silva, Silvia Avila, Leandro Apolinario, Norma Teresa Rossi, Claudia Martin, Yasser Sulcahuaman, Carlos Alberto Vaccaro, Maria Del Carmen Castro-Mujica, Carlos Mario Muñeton Peña, Roseane V Bicalho F Assis, Elizabeth Silveira-Lucas, Chahuan Badir, Daniel Velez-Bohorquez, Gaston Boggio, Enrique Spirandelli, Florencia Neffa, Patricia Esperon, Florencia Carusso, Carolina Vergara, Mora Amat, María Teresa Pombo, Laura Noro, Marjorie De la Fuente, Tamara Canales, Alessandra Cassana, Gonzalo Carrasco-Avino, Julyann Pérez-Mayoral, Maria Gonzalez Pons, Angélica Hernández Guerrero, Silvia Vidal Millán, Sandra Beatriz Furfuro, Taisa Manuela Bonfim Machado Lopes, Thais Ferreira Bomfim Palma, Juliana Cortes Freitas, Maria Betânia Pereira Toralles, Thamara Claudia Ferreira Melo, Celia Aparecida Marques Pimenta, Luis José Palacios Fuenmayor, Gabriela Galvez-Salazar, Gabriela Jaramillo-Koupermann, Mariella Torres, Walter Hernán Pavicic, Ignacio Alberto Herrando, Juan Pablo Santino, Fabiana Alejandra Ferro, Carlos Afanador Ayala, Luri Drumond Louro, Silvio Conedera, Vessela Kristensen, Giovana Tardin Torrezan, Constantino Dominguez-Barrera, María de la Luz Ayala Madrigal, Melva Gutierrez, Patrik Wernhoff, Eivind Hovig, John-Paul Plazzer, Pål Møller, Yesilda Balavarca, Mev Dominguez-Valentin
Journal: Clinical Gastroenterology and Hepatology (2025)
ESR1 Y537S and D538G mutations drive resistance to CDK4/6 inhibitors in estrogen receptor-positive breast cancer
Authors: Chang-Ching A. Lin, María Rosario Chica-Parrado, Nisha Unni, Ellen Jaeger, Yisheng V. Fang, Lei Guo, Fabiana Napolitano, Pamela Luna, Michelle Harris, Calvin Chao, Lin Xu, Carlos L. Arteaga, Ariella B. Hanker
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Breast cancers with ESR1 mutations are resistant to antiestrogen therapy. In this study, we aimed to investigate the association of ESR1 mutations with resistance to CDK4/6 inhibitors (CDK4/6i) using real-world data analysis and experimental validation. Patients and Methods: A total of 3,958 patients with estrogen receptor-positive (ER+) metastatic breast cancer with DNA sequencing data were analyzed. Breast tumor DNA and circulating tumor (ct) DNA were sequenced using the Tempus xT tumor assay and Tempus xF liquid biopsy, respectively. Patients were stratified into either treated with CDK4/6i (tumor tissue: 1,070; ctDNA: 1,885) or CDK4/6i naïve (tumor tissue: 750; ctDNA: 253). Engineered MCF7 cells carrying ESR1 Y537S or D538G knock-in mutations were used to study antitumor efficacy of the CDK4/6i palbociclib in vitro and in vivo. Results: In both xF and xT assays, ESR1 mutations were the only somatic alterations significantly more frequent in patients who received CDK4/6i compared to those who did not. Knock-in of ESR1 Y537S or ESR1 D538G in MCF7 cells resulted in upregulation of cell cycle-related gene signatures upon treatment with CDK4/6i ± antiestrogen compared to cells with non-mutant ESR1. MCF7 xenografts harboring ESR1 Y537S and D538G mutations established in nude mice were resistant to palbociclib. Conclusions: We report herein real-world and preclinical evidence that ESR1 mutations, particularly Y537S and D538G, can drive resistance to CDK4/6 inhibitors.
Clustering Mycobacterium tuberculosis-specific CD154+CD4+ T cells for distinguishing tuberculosis disease from infection based on single-cell RNA-seq analysis
Authors: Xiaochen Wang, Kaishan Jiang, Wenjin Xing, Qiudan Xin, Qiongjie Hu, Shiji Wu, Ziyong Sun, Hongyan Hou, Yi Ren, Feng Wang
Journal: Journal of Infection (2025)