tbuckley/cabot-search huggingface dataset:
First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial
Authors: Lin Shen, Yanqiao Zhang, Ziyu Li, Xiaotian Zhang, Xiangyu Gao, Bo Liu, Yusheng Wang, Yi Ba, Ning Li, Ruixing Zhang, Jingdong Zhang, Ye Chen, Jian Chen, Mingzhu Huang, Yang Fu, Mulin Liu, Zheng Liu, Jun Zhao, Wei Li, Jia Wei, Changzheng Li, Nong Xu, Zengqing Guo, Bangwei Cao, Lian Liu, Peng Nie, Lixin Wan, Lili Sheng, Zhenyang Liu, Yifu He, Kangsheng Gu, Guowu Wu, Weibo Wang, Futong Zhang, Wensheng Qiu, Jun Guo, Jieer Ying, Hongming Pan, Huiting Xu, Yuan Yuan, Yuansong Bai, Zhenghua Wang, Jiye Xu, Xuehong Zhao, Hao Liu, Xizhi Zhang, Wenxiang Dai, Hongyan Xu, Ming Liu, Lin Xie, Yong Tang, Jianying Jin, Xiujuan Qu, Xuefeng Fang, Mingwei Huang, Hao Chen, Zhendong Zheng, Ying Wang, Daqing Wang, Xiaoqin Li, Guohua Yu, Haiyan Liu, Yongjian Zhou, Diansheng Zhong, Shan Zeng, Mafei Kang, Meiqing Wang, Yong Gao, Wenxin Li, Zejun Wang, Minghui Zhang, Jinghua Zhang, Qingshan Li, Shujuan Sun, Aimin Zang, Lizhu Lin, Ming Xie, Zhixiang Zhuang, Tao Zhang, Zhifang Yao, Dongmei Lu, Wei Liu, Mingxiu Hu, Zhongmin Maxwell Wang, Baiyong Li, Michelle Xia, Jiajia Zhang, Xiangji Ying, Drew M. Pardoll, Jiafu Ji
Journal: Nature Medicine (2025)
TRIPLE Score: GPVI and CD36 Expression Predict a Prothrombotic Platelet Function Phenotype
Authors: Alexander P. Bye, Neline Kriek, Carly Kempster, Joanne L. Dunster, Joanne L. Mitchell, Tanya Sage, Suzannah Rawlings, Maria V. Diaz Alonso, Valentina Shpakova, Abigail Whyte, Leanne Dymott, Sharon Mark, Mark Brunton, Joana Batista, Harriet McKinney, Patrick Thomas, Kate Downes, Amanda J. Unsworth, Neil Ruparelia, Charlie Mckenna, Chris I. Jones, Jonathan M. Gibbins
Journal: Circulation Research (2025)
Evaluating CK20 and MCPyV Antibody Clones in Diagnosing Merkel Cell Carcinoma
Authors: Begum Yeni Erdem, Can Baykal, Yasemin Ozluk, Melin A. Ahmed, Erol Kozanoglu, Pinar Saip, Nesimi Buyukbabani, Sule Ozturk Sari
Journal: Endocrine Pathology (2025)

Abstract Merkel cell carcinoma (MCC) is diagnosed through histopathological and immunohistochemical examination of biopsies from skin or other organs. Its distinguishing features include perinuclear dot-like staining with Cytokeratin 20 (CK20) and detection of Merkel cell polyomavirus (MCPyV) using various methods. However, CK20 and MCPyV negative MCC cases have been reported at varying rates. In this single center cross-sectional study, we aimed to determine which clones are more effective in diagnosing MCC by comparing the performance of CK20 antibody clones Ks20.8 and SP33, as well as MCPyV antibody clones Ab3 and CM2B4. Fifty-four patients diagnosed with MCC were included. Among these, 42 cases were primary cutaneous, and 12 cases were nodal MCC. Fifty-two (96.3%) cases were positive with both CK20 clones, while two cases were negative. Clone SP33 stained areas of necrosis, whereas Ks20.8 showed no aberrant staining. MCPyV was detected in 44 cases (81.5%) using clone Ab3 and 39 cases (72.2%) using clone CM2B4. Staining with MCPyV clone Ab3 was diffuse and strong in most cases, while approximately 30% of CM2B4-positive cases exhibited low percentages and/or weak staining, complicating the evaluation. The two CK20-negative cases were also negative with both MCPyV clones. Our data demonstrated that CK20 clone Ks20.8 may be preferred for MCC diagnosis due to its consistent performance and lack of aberrant staining. Similarly, MCPyV clone Ab3 appears superior to CM2B4 for identifying MCPyV-positive cases.
Inference of the demographic histories and selective effects of human gut commensal microbiota over the course of human history
Authors: Jonathan C Mah, Kirk E Lohmueller, Nandita Garud
Journal: Molecular Biology and Evolution (2025)

Abstract Despite the importance of gut commensal microbiota to human health, there is little knowledge about their evolutionary histories, including their demographic histories and distributions of fitness effects (DFE) of mutations. Here, we infer the demographic histories and DFEs for amino-acid changing mutations of 39 of the most prevalent and abundant commensal gut microbial species found in Westernized individuals over timescales exceeding human generations. Some species display contractions in population size and others expansions, with several of these events coinciding with several key historical moments in human history. DFEs across species vary from highly to mildly deleterious, with differences between accessory and core gene DFEs largely driven by genetic drift. Within genera, DFEs tend to be more congruent, reflective of underlying phylogenetic relationships. Together, these findings suggest that gut microbes have distinct demographic and selective histories.
In situ blockade of TNF-TNFR2 axis via oncolytic adenovirus improves antitumor efficacy in solid tumors
Authors: Xiaozhen Kang, Yifeng Han, Mengdi Wu, Yuxin Li, Peng Qian, Chuning Xu, Zhengyun Zou, Jie Dong, Jiwu Wei
Journal: Molecular Therapy (2025)
Heterogeneity of the Treatment Effect with PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer: A Living Interactive Systematic Review and Meta-analysis
Authors: Syed Arsalan Ahmed Naqvi, Irbaz Bin Riaz, Arifa Bibi, Muhammad Ali Khan, Manal Imran, Kaneez Zahra Rubab Khakwani, Ammad Raina, Muhammad Umair Anjum, Ewan K Cobran, Jeremy L Warner, Syed A Hussain, Parminder Singh, Daniel S Childs, Sylvan C Baca, Jacob J Orme, Joaquin Mateo, Neeraj Agarwal, Silke Gillessen, Mohammad Hassan Murad, Oliver Sartor, Alan H Bryce
Journal: European Urology (2025)
Evolution of long scalp hair in humans
Authors: Lo-Yu Chang, Maksim V Plikus, Nina G Jablonski, Sung-Jan Lin
Journal: British Journal of Dermatology (2025)

Abstract The ability to grow long scalp hair is a distinct human characteristic. It probably originally evolved to aid in cooling the sun-exposed head, although the genetic determinants of long hair are largely unknown. Despite ancestral variations in hair growth, long scalp hair is common to all extant human populations, which suggests its emergence before or concurrently with the emergence of anatomically modern humans (AMHs), approximately 300 000 years ago. Long scalp hair in AMHs was also a trait that was selected because it conveyed essential signals related to an individual’s age, sexual maturity, health and social status. Biologically, hair length is primarily determined by the amount of time that a hair follicle spends in the active growth phase (anagen). While anagen duration is typically tightly regulated in most mammals, the inherent ability of a hair follicle to continuously recruit new dividing progenitors to its base, where hair fibre is generated, theoretically removes limits on maximal anagen duration. We propose a model wherein hair cycle progression into and out of anagen is regulated by evolutionary malleable molecular checkpoints. Several animal species and domesticated animal breeds display long body hair, which suggests that extremely long scalp hair in humans emerged via attenuation of an existing out-of-anagen checkpoint mechanism rather than via a newly evolved molecular programme. Studying congenital and somatic mosaicism conditions featuring altered hair length could potentially unveil the currently unknown molecular basis underlying this human trait.
The Future of Microbiome Therapeutics
Authors: Milena Pitashny, Inbar Kesten, Dima Shlon, Dana Ben Hur, Haggai Bar-Yoseph
Journal: Drugs (2025)

The human microbiome exerts profound influence over various biological processes within the body. Unlike many host determinants, it represents a readily accessible target for manipulation to promote health benefits. However, existing commercial microbiome-directed products often exhibit low efficacy. Advancements in technology are paving the way for the development of novel microbiome therapeutics, across a wide range of indications. In this narrative review, we provide an overview of state-of-the-art technologies in late-stage development, examining their advantages and limitations. By covering a spectrum, from fecal-derived products to live biotherapeutics, phage therapy, and synthetic biology, we illuminate the path toward the future of microbiome therapeutics.
Dapagliflozin plus calorie restriction for remission of type 2 diabetes: multicentre, double blind, randomised, placebo controlled trial
Authors: Yuejun Liu, Ying Chen, Jianhua Ma, Jiayang Lin, Changqin Liu, Xuejun Li, Yong Xu, Hongyu Kuang, Lixin Shi, Yaoming Xue, Bo Feng, Dalong Zhu, Guang Wang, Jinkui Yang, Xinhua Xiao, Xuefeng Yu, Jiaqiang Zhou, Yuqian Bao, Qing Su, Minzhi Lyu, Xiaomu Li, Huijie Zhang, Xiaoying Li
Journal: BMJ (2025)

Abstract Objective To assess the effect of dapagliflozin plus calorie restriction on remission of type 2 diabetes. Design Multicentre, double blind, randomised, placebo controlled trial. Setting 16 centres in mainland China from 12 June 2020 to 31 January 2023. Participants 328 patients with type 2 diabetes aged 20-70 years, with body mass index &gt;25 and diabetes duration of &lt;6 years. Interventions Calorie restriction with dapagliflozin 10 mg/day or placebo. Main outcome measures Primary outcome: incidence of diabetes remission (defined as glycated haemoglobin &lt;6.5% and fasting plasma glucose &lt;126 mg/dL in the absence of all antidiabetic drugs for at least 2 months); secondary outcomes: changes in body weight, waist circumference, body fat, blood pressure, glucose homoeostasis parameters, and serum lipids over 12 months. Results Remission of diabetes was achieved in 44% (73/165) of patients in the dapagliflozin group and 28% (46/163) of patients in the placebo group (risk ratio 1.56, 95% confidence interval (CI) 1.17 to 2.09; P=0.002) over 12 months, meeting the predefined primary endpoint. Changes in body weight (difference −1.3 (95% CI −1.9 to −0.7) kg) and homoeostasis model assessment of insulin resistance (difference −0.8, −1.1 to −0.4) were significantly greater in the dapagliflozin group than in the placebo group. Likewise, body fat, systolic blood pressure, and metabolic risk factors were significantly more improved in the dapagliflozin group than in the placebo group. In addition, no significant differences were seen between the two groups in the occurrence of adverse events. Conclusion The regimen of dapagliflozin plus regular calorie restriction achieved a much higher rate of remission of diabetes compared with calorie restriction alone in overweight or obese patients with type 2 diabetes. Trial registration ClinicalTrials.gov NCT04004793 .
Worsening of Heart Failure in Outpatients With Transthyretin Amyloidosis and Cardiomyopathy in the APOLLO-B Trial
Authors: Marianna Fontana, Mathew S Maurer, Julian D Gillmore, Shaun Bender, Patrick Y Jay, Scott D Solomon
Journal: Journal of the American College of Cardiology (2025)

Outpatient worsening heart failure (HF), defined by initiation or intensification of diuretics, is adversely prognostic for patients with either reduced or preserved ejection fraction. This study sought to investigate the prognostic value of outpatient worsening HF in transthyretin amyloidosis with cardiomyopathy and the effect of patisiran treatment. Post hoc analyses of the APOLLO-B trial (NCT03997383) evaluated the associations between outpatient worsening HF (defined by oral diuretic initiation or intensification), measures of disease progression, and a composite endpoint of all-cause mortality and cardiovascular (CV) events. We further examined the effect of patisiran on outpatient worsening HF over 24 months (ie, during the double-blind and open-label extension periods). In APOLLO-B, 144 (40.1%) patients had no event, 157 (43.7%) had outpatient worsening HF, 13 (3.6%) required an urgent HF visit, 118 (32.9%) had a CV hospitalization, and 47 (13.1%) died. Outpatient worsening HF was associated with an increased risk of all-cause mortality and CV events (HR: 2.21; 95% CI: 1.58-3.08), as well as a greater deterioration in 6-minute walk test distance, Kansas City Cardiomyopathy Questionnaire-Overall Summary score, and NYHA functional class and a greater increase in N-terminal prohormone of B-type natriuretic peptide. Addition of outpatient diuretic initiation or intensification to the composite endpoint of all-cause mortality and CV events increased the overall number of patients having an event from 141 to 215 (a 52% increase). Patisiran reduced the risk of outpatient worsening HF (HR: 0.70; 95% CI: 0.51-0.96) over 24 months. During APOLLO-B, outpatient worsening HF in patients with transthyretin amyloidosis with cardiomyopathy was frequent, prognostic, and reduced by patisiran.
GRINA alleviates hepatic ischemia‒reperfusion injury-induced apoptosis and ER-phagy by enhancing HRD1-mediated ATF6 ubiquitination
Authors: Hongjun Yu, Chaoqun Wang, Baolin Qian, Bing Yin, Shanjia Ke, Miaoyu Bai, Shounan Lu, Yanan Xu, Zhigang Feng, Zihao Li, Xinglong Li, Yongliang Hua, Zhongyu Li, Dong Chen, Yongzhi Zhou, Zhanzhi Meng, Yao Fu, Yong Ma
Journal: Journal of Hepatology (2025)
Radiation Segmentectomy for Early Hepatocellular Carcinoma is Curative
Authors: Riad Salem, Siddharth A Padia, Beau B Toskich, Jon D Callahan, Kirk D Fowers, Brian S Geller, Guy E Johnson, Laura Kulik, Tushar C Patel, Robert J Lewandowski, Edward Kim
Journal: Journal of Hepatology (2025)

In this Expert Opinion, we provide the rationale for concluding that radiation segmentectomy (using RADSEG method), a technique of administrating ablative, complete necrosis-inducing trans-arterial Yttrium-90 (Y90) radiotherapy in limited-disease burden hepatocellular carcinoma (HCC), is curative. Currently, curative options for early stage and other carefully selected HCC patients include transplantation, resection, and ablation. Because of issues with organ availability, co-morbidities preventing resection, and tumor size and location limiting ablation, other treatments are necessary for this selected patient population. RADSEG method has evolved into an intra-arterial approach in this setting, with long-term outcomes comparable to ablation, resection, and transplantation. It is proposed that yttrium-90 radioembolization, applying RADSEG technique, be formally recognized as curative for early HCC.
The evolution of pediatric transgender healthcare in Flanders: Trends in referrals, intakes and gender-affirming interventions over the last 15 years
Authors: Silvia Ciancia, Laura Bruneel, Judith Van Schuylenbergh, Daniel Klink, Karlien Dhondt, Robin Heyse, Joz Motmans, Martine Cools
Journal: International Journal of Transgender Health (2025)

Purpose The expanding number of minors questioning their gender identity and seeking care has led to the constitution of pediatric gender clinics in several countries. The activity of the multidisciplinary Pediatric Gender Team at Ghent University Hospital, Belgium started in 2007. We report on the evolution of referrals, psychological intakes, and trends in the start of gender-affirming medical and surgical interventions from 2007 to 2023.
Disease-modifying pharmacological treatments of type 1 diabetes (T1D): Molecular mechanisms, target checkpoints and possible combinatorial treatments.
Authors: Liudmila Kosheleva, Daniil Koshelev, Francisco Alejandro Lagunas-Rangel, Shmuel Levit, Alexander Rabinovitch, Helgi B Schiöth
Journal: Pharmacological Reviews (2025)

After a century of extensive scientific investigations, there is still no curative or disease-modifying treatment available that can provide long-lasting remission for patients diagnosed with type 1 diabetes (T1D). Although T1D has historically been regarded as a classic autoimmune disorder targeting and destroying pancreatic islet β-cells, significant research has recently demonstrated that β-cells themselves also play a substantial role in the disease's progression, which could explain some of the unfavorable clinical outcomes. We offer a thorough review of scientific and clinical insights pertaining to molecular mechanisms behind pathogenesis and the different therapeutic interventions in T1D covering over 20 possible pharmaceutical intervention treatments. The interventions are categorized as immune therapies, treatments targeting islet endocrine dysfunctions, medications with dual modes of action in immune and islet endocrine cells, and combination treatments with a broader spectrum of activity. We suggest that these collective findings can provide a valuable platform to discover new combinatorial synergies in search of the curative disease-modifying intervention for T1D. SIGNIFICANCE STATEMENT: This research delves into the underlying causes of T1D and identifies critical mechanisms governing β-cell function in both healthy and diseased states. Thus, we identify specific pathways that could be manipulated by existing or new pharmacological interventions. These interventions fall into several categories: (1) immunomodifying therapies individually targeting immune cell processes, (2) interventions targeting β-cells, (3) compounds that act simultaneously on both immune cell and β-cell pathways, and (4) combinations of compounds simultaneously targeting immune and β-cell pathways.
Semaphorin 3s signaling in the central nervous system: Mechanisms and therapeutic implication for brain diseases
Authors: Ya-Ping Lu, Yi-Ling Luo, Zhou-Yue Wu, Chao Han, Yin-Zhi Jin, Jun-Ming Han, Shu-Yang Chen, Fei Teng, Feng Han, Xiu-Xiu Liu, Ying-Mei Lu
Journal: Pharmacology & Therapeutics (2025)
Preserving information while respecting privacy through an information theoretic framework for synthetic health data generation
Authors: Nadir Sella, Florent Guinot, Nikita Lagrange, Laurent-Philippe Albou, Jonathan Desponds, Hervé Isambert
Journal: npj Digital Medicine (2025)

Generating synthetic data from medical records is a complex task intensified by patient privacy concerns. In recent years, multiple approaches have been reported for the generation of synthetic data, however, limited attention was given to jointly evaluate the quality and the privacy of the generated data. The quality and privacy of synthetic data stem from multivariate associations across variables, which cannot be assessed by comparing univariate distributions with the original data. Here, we introduce a novel algorithm (MIIC-SDG) for generating synthetic data from electronic records based on a multivariate information framework and Bayesian network theory. We also propose a new metric to quantitatively assess the trade-off between the Quality and Privacy Scores (QPS) of synthetic data generation methods. The performance of MIIC-SDG is demonstrated on different clinical datasets and favorably compares with state-of-the-art synthetic data generation methods, based on the QPS trade-off between several quality and privacy metrics.
Interferon-α biological activity is associated with disease activity and risk of flare in cutaneous lupus erythematosus: a monocentric study of 184 patients
Authors: Quitterie Murat de Montai, Clémence Masseran, Laura Perray, Alexis Mathian, Karim Dorgham, Guy Gorochov, Alexandre Teboul, Camille Francès, Laurent Arnaud, Annick Barbaud, Zahir Amoura, Caroline Charre, François Chasset
Journal: Journal of the American Academy of Dermatology (2025)
An Approach for Psoriasis of Microneedle Patch Simultaneously Targeting Multiple Inflammatory Cytokines and Relapse Related T Cells
Authors: Li Huang, Ying Luo, Le Kuai, Xiaoyou Zhang, Ying Zhang, Zichen Yang, Xiaoya Fei, Jiuyuan Sun, Yue Luo, Yuge Zhao, Tingting Xue, Weimin Yin, Jiao Chang, Jiankun Song, Yongyong Li, Bin Li, Yan Li
Journal: Biomaterials (2025)
Modulation of PRL-1 within placental MSCs instigates the transition between EMT and MET subsequent to hepatic fibrosis
Authors: Jae Yeon Kim, Hyeri Park, Soo Young Park, Se Ho Kim, Ja Yun Lim, Ki Seog Lee, Si Hyun Bae, Gi Jin Kim
Journal: Clinical and Molecular Hepatology (2025)

Background/Aims: Epithelial-to-mesenchymal transition (EMT) plays a crucial role in hepatic fibrogenesis and liver repair in chronic liver disease.Our research highlights the antifibrotic potential of placenta-derived mesenchymal stem cells (PD-MSCs) and the role of phosphatase of regenerating liver-1 (PRL-1) in promoting liver regeneration. Methods:We evaluated the efficacy of PD-MSCs overexpressing PRL-1 (PD-MSCs PRL-1 ) in a bile duct ligation (BDL)-induced rat injury model, focusing on their ability to regulate EMT.Results: PD-MSCs PRL-1 significantly reduced mesenchymal markers by downregulating TGFB1/SMAD2, outperforming naïve PD-MSCs.The transplantation of PD-MSCs PRL-1 enhanced BMP7/SMAD1/5 expression, promoting epithelial marker expression and stimulating BMP7 within hepatocytes, modulating downstream SMAD signaling.Importantly, further validation confirmed that PRL-1 directly interacts with BMP7 in hepatocytes.Conclusions: PRL-1 expression in PD-MSCs PRL-1 restores TGFB1/BMP7 balance, promoting hepatic regeneration through mesenchymal-to-epithelial transition (MET).These findings highlight the therapeutic potential of engineered MSCs for liver disease and suggest innovative strategies for future stem cell therapies.
Unveiling the Intratumor Microbiome in Liver Cancer: Current Insights and Prospective Applications
Authors: Xindi Ke, Shangze Jiang, Qiaoxin Wei, Minghao Sun, Hang Sun, Mingchang Pang, Mei Liu, Lejia Sun, Huayu Yang, Yilei Mao
Journal: Clinical and Molecular Hepatology (2025)

The role of the gut microbiome in the development and progression of liver cancer has long been recognized.However, the presence of microbes in tumors that were previously considered sterile has only recently been discovered.The intratumor microbiome in liver cancer likely originates from various sources, including the gut, hematogenous spread from other mucosal locations, adjacent non-cancerous tissues, and co-metastasis with the tumor cells.As a newly discovered component of the tumor microenvironment, it regulates host immune responses, promotes chronic inflammation, modulates metabolic pathways, and exerts other influences in liver cancer.These unique features offer potential new biomarkers for liver cancer prognosis and treatment response.Exploring the complex interactions between intratumor microbiome and the host to modulate or target the intratumor microbiome may provide new avenues for liver cancer treatment.This article provides a comprehensive review of our current understanding regarding the potential origins of the intratumor microbiome in liver cancer, its unique characteristics, and the underlying mechanisms by which it affects liver cancer.Furthermore, we discuss the promising clinical implications and potential challenges that remain before this knowledge can be fully integrated into clinical practice.