tbuckley/cabot-search huggingface dataset:
Extracellular vesicle as therapeutic agents in anti-aging: Mechanistic insights and future potential
Authors: Hyejoo Yoon, Junyeong Jo, Hyesun Hyun, Gyuwon Lee, Seoyoung Ma, Jungho Sohn, Dong Kyung Sung, Chae Young Han, Minkyung Kim, Duhyeong Hwang, Hyunji Lee, Yuseon Shin, Kyung Taek Oh, Chaemin Lim
Journal: Journal of Controlled Release (2025)
Long-acting glucose-responsive insulin with swift onset-of-action
Authors: Wei Liu, Juan Zhang, Yanfang Wang, Yaqin He, Yuanwu Wang, Xiangqian Wei, Yuejun Yao, Jianchang Xu, Wentao Zhang, Tao Sheng, Haibin Dai, Jinqiang Wang, Zhen Gu
Journal: Journal of Controlled Release (2025)
SegQC: a segmentation network-based framework for multi-metric segmentation quality control and segmentation error detection in volumetric medical images
Authors: Bella Specktor-Fadida, Liat Ben-Sira, Dafna Ben-Bashat, Leo Joskowicz
Journal: Medical Image Analysis (2025)

Quality control (QC) of structures segmentation in volumetric medical images is important for identifying segmentation errors in clinical practice and for facilitating model development by enhancing network performance in semi-supervised and active learning scenarios. This paper introduces SegQC, a novel framework for segmentation quality estimation and segmentation error detection. SegQC computes an estimate measure of the quality of a segmentation in volumetric scans and in their individual slices and identifies possible segmentation error regions within a slice. The key components of SegQC include: 1) SegQCNet, a deep network that inputs a scan and its segmentation mask and outputs segmentation error probabilities for each voxel in the scan; 2) three new segmentation quality metrics computed from the segmentation error probabilities; 3) a new method for detecting possible segmentation errors in scan slices computed from the segmentation error probabilities. We introduce a novel evaluation scheme to measure segmentation error discrepancies based on an expert radiologist's corrections of automatically produced segmentations that yields smaller observer variability and is closer to actual segmentation errors. We demonstrate SegQC on three fetal structures in 198 fetal MRI scans - fetal brain, fetal body and the placenta. To assess the benefits of SegQC, we compare it to the unsupervised Test Time Augmentation (TTA)-based QC and to supervised autoencoder (AE)-based QC. Our studies indicate that SegQC outperforms TTA-based quality estimation for whole scans and individual slices in terms of Pearson correlation and MAE for fetal body and fetal brain structures segmentation as well as for volumetric overlap metrics estimation of the placenta structure. Compared to both unsupervised TTA and supervised AE methods, SegQC achieves lower MAE for both 3D and 2D Dice estimates and higher Pearson correlation for volumetric Dice. Our segmentation error detection method achieved recall and precision rates of 0.77 and 0.48 for fetal body, and 0.74 and 0.55 for fetal brain segmentation error detection, respectively. Ranking derived from metrics estimation surpasses rankings based on entropy and sum for TTA and SegQCNet estimations, respectively. SegQC provides high-quality metrics estimation for both 2D and 3D medical images as well as error localization within slices, offering important improvements to segmentation QC.
Anlotinib plus penpulimab versus sorafenib in the first-line treatment of unresectable hepatocellular carcinoma (APOLLO): a randomised, controlled, phase 3 trial
Authors: Jian Zhou, Li Bai, Jia Luo, Yuxian Bai, Yaozhen Pan, Xinrong Yang, Yufeng Gao, Rongshu Shi, Wenhua Zhang, Jinfang Zheng, Xiangdong Hua, Aibing Xu, Sheng Hu, Feng Zhang, Xiaojun Yang, Mingxu Da, Rui Wang, Jie Ma, Weidong Jia, Dongmei Quan, Chuang Peng, Wei Yang, Guowen Yin, Yue Qi, Guifang Zhang, Xilin Du, Xiaorong Mao, Zhiqiang Meng, Shunchang Jiao, Jia Fan
Journal: The Lancet Oncology (2025)
Targeting the HER2-ELF3-KRAS axis: a novel therapeutic strategy for KRASG13D colorectal cancer
Authors: Soo-Yeon Hwang, Yoojeong Seo, Seojeong Park, Seul-Ah Kim, Inhye Moon, Yi Liu, Seojeong Kim, Eun Seon Pak, Sehyun Jung, Hyeyoon Kim, Kyung-Hwa Jeon, Seung Hee Seo, Inyoung Sung, Heetak Lee, So-Yeon Park, Younghwa Na, Tae Il Kim, Youngjoo Kwon
Journal: Molecular Cancer (2025)

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, with KRAS mutations playing a significant role in its tumorigenesis. Among the KRAS variants, the G13D mutation is associated with poor prognosis and distinctive biological behaviors. This study focuses on the role of HER2, a critical prognostic and predictive biomarker, in modulating the unique characteristics of KRASG13D-mutated CRCs. We identified a novel transcriptional regulatory network involving HER2, ELF3, and KRAS, with ELF3 acting as a key transcription factor (TF) that regulates KRAS expression under conditions of HER2 overexpression. Our findings reveal that this HER2-ELF3-KRAS axis is exclusively activated in KRASG13D, driving aggressive oncogenic features and conferring resistance to cetuximab (CTX) therapy. Through comprehensive analysis of gene expression profiles, we demonstrated that HER2 is a crucial therapeutic target specifically for KRASG13D CRCs. To explore this further, we introduced YK1, a small molecule inhibitor designed to disrupt the ELF3-MED23 interaction, leading to the transcriptional downregulation of HER2 and KRAS. This intervention significantly attenuated the HER2-ELF3-KRAS axis, sensitizing KRASG13D CRCs to CTX and reducing their tumorigenic potential by inhibiting the epithelial-to-mesenchymal transition process. Our study underscores the importance of HER2 as a key determinant in the unique biological characteristics of KRASG13D CRCs and highlights the therapeutic potential of targeting the HER2-ELF3-KRAS axis. By presenting YK1 as a novel pharmacological approach, we provide a promising strategy for developing tailored interventions for KRASG13D CRCs, contributing to the ongoing efforts in precision medicine for CRCs.
Simultaneous initiation of dolutegravir-based antiretroviral therapy and once-weekly rifapentine and isoniazid for tuberculosis prevention in antiretroviral-naive people with HIV: an open-label, non-randomised, phase 1/2 trial
Authors: Ethel D Weld, Trevor Beattie, Jayajothi Moodley, Manasa Mapendere, Isadora Salles, Belén P Solans, Bareng A S Nonyane, Lubbe Wiesner, Tanya Nielson, Vinodh A Edward, Violet Chihota, Radojka M Savic, Kelly E Dooley, Richard E Chaisson, Gavin J Churchyard
Journal: The Lancet HIV (2025)
FaceAge, a deep learning system to estimate biological age from face photographs to improve prognostication: a model development and validation study
Authors: Dennis Bontempi, Osbert Zalay, Danielle S Bitterman, Nicolai Birkbak, Derek Shyr, Fridolin Haugg, Jack M Qian, Hannah Roberts, Subha Perni, Vasco Prudente, Suraj Pai, Andre Dekker, Benjamin Haibe-Kains, Christian Guthier, Tracy Balboni, Laura Warren, Monica Krishan, Benjamin H Kann, Charles Swanton, Dirk De Ruysscher, Raymond H Mak, Hugo J W L Aerts
Journal: The Lancet Digital Health (2025)
Concept CARs are picking up speed
Authors: Jorge Mansilla-Soto, Michael C Milone
Journal: Molecular Therapy (2025)

The field of adoptive T cell immunotherapy has been dominated by a CAR design that combines antigen recognition through antibody-derived domains and signaling into a single polypeptide. This conventional design redirects the immense cytotoxic potential of T cells towards tumors, and it is the core of several commercially marketed CAR T cell products. Recent research in the field has been focused on developing more effective CAR designs especially for solid tumors. Although most approaches have layered on top of the conventional CAR design, recent studies have taken a step back and redesigned the basic CAR to retain more of the natural structure of immunoreceptors such as the TCR or killer immunoglobulin-like receptors. These redesigned CARs promote enhanced function in preclinical models compared with conventional CAR designs, including in the more challenging solid tumor setting, and several have entered the clinic with emerging data on their activity. These observations highlight the importance of considering CAR design and looking beyond conventional CARs when developing new T cell immunotherapy approaches.
rMATS-cloud: Large-scale Alternative Splicing Analysis in the Cloud
Authors: Jenea I Adams, Eric Kutschera, Qiang Hu, Chun-Jie Liu, Qian Liu, Kathryn Kadash-Edmondson, Song Liu, Yi Xing
Journal: Genomics Proteomics & Bioinformatics (2025)

Abstract Although gene expression analysis pipelines are often a standard part of bioinformatics analysis, with many publicly available cloud workflows, cloud-based alternative splicing analysis tools remain limited. Our lab released rMATS in 2014 and has continuously maintained it, providing a fast and versatile solution for quantifying alternative splicing from RNA sequencing (RNA-seq) data. Here, we present rMATS-cloud, a portable version of the rMATS workflow that can be run in virtually any cloud environment suited for biomedical research. We compared the time and cost of running rMATS-cloud with two RNA-seq datasets on three different platforms (Cavatica, Terra, and Seqera). Our findings demonstrate that rMATS-cloud handles RNA-seq datasets with thousands of samples, and therefore is ideally suited for the storage capacities of many cloud data repositories. rMATS-cloud is available at https://dockstore.org/workflows/github.com/Xinglab/rmats-turbo/rmats-turbo-cwl, https://dockstore.org/workflows/github.com/Xinglab/rmats-turbo/rmats-turbo-wdl, and https://dockstore.org/workflows/github.com/Xinglab/rmats-turbo/rmats-turbo-nextflow.
Non-infectivity of Hepatitis B Virus Under Nucleoside Analog Therapy Revealed Through Auxiliary Partial Orthotopic Liver Transplantation (APOLT)
Authors: Xiaojie Chen, Guiwen Guan, Lin Wei, Jidong Jia, Xiangmei Chen, Fengmin Lu, Zhijun Zhu
Journal: Clinical and Molecular Hepatology (2025)
Molecular Stratification of Hepatocellular Carcinoma by Metabolic-Signaling Pathways Guides Precision Immunotherapy and TACE Therapy
Authors: Binghua Li, Yanchao Xu, Yican Zhu, Yukun Zhang, Zijie Wu, Tianci Luo, Laizhu Zhang, Weiwei Hu, Decai Yu
Journal: Clinical and Molecular Hepatology (2025)
Decoding the Resistin-CAP1 Pathway in Intermediate Monocytes Mediating Liver Allograft Rejection
Authors: Peijun Yang, Xudan Wang, Weikang Wu, Juzheng Yuan, Xinrui Wang, Rui Ding, Weiwei Cao, Cong Li, Yinjie Wang, Zihan Xi, Kefeng Dou, Xiao Li, Kaishan Tao
Journal: Journal of Hepatology (2025)

Lymphocytes are widely recognized as the primary mediators of cellular rejection post-liver transplantation. However, conventional immunosuppressive regimens that target lymphocytes, such as calcineurin phosphatase inhibitors, corticosteroids, or lymphocyte-depleting antibodies, can only partially mitigate rejection while inducing severe adverse effects. This necessitates the search for novel immunotherapeutic targets. We harnessed the power of single-cell RNA sequencing and spatial transcriptome in 24 rat transplanted liver and peripheral blood single nucleated cells (PBMCs) samples to derive gene expression signatures recapitulating 13 cell phenotypes. We used flow cytometry, multifactor assays and multiple recombinant assays to validate in vitro and in vivo the role of the target protein Resistin on human T-cell function, as well as the Resistin-CAP1 interaction. Gold nanoparticles were used to package Retn siRNA sequences to validate the role of Retn knockdown on acute rejection after liver transplantation. By distinguishing between donor and recipient cells, we delineate the dynamic landscape of immune cells during allograft rejection and their spatial distributions across donors and recipients. Our findings underscore the pivotal role of recipient derived intermediate monocytes in cellular rejection. Using CellChat ligand-receptor analysis, we identify the Resistin-CAP1 pathway as a key mechanism by which intermediate monocytes participate in T cell-mediated rejection reactions. We confirm that Resistin knockdown significantly alleviates acute rejection after rat liver transplantation, markedly extending the survival of recipients using innovative nanogold technology. These findings offer insights into the dynamic changes in the alloimmune microenvironment, pinpointing intermediate monocytes as potential diagnostic and immunotherapeutic targets during allograft rejection. This study holds significant importance in advancing non-invasive diagnostic technologies and immunotherapeutic strategies for allogeneic rejection. This study pioneers the application of spatial transcriptomics in liver transplantation, providing a comprehensive analysis of immune cell spatial distribution, complemented by Souporcell-based chimerism assessment. We demonstrate that intermediate monocytes play a pivotal role in T cell-mediated acute rejection via the Resistin-CAP1 signaling axis. Targeting this pathway using nanogold-siRNA technology effectively mitigates rejection and enhances graft survival. These findings contribute novel insights into the mechanisms of transplant rejection and present promising avenues for the development of targeted therapeutic and diagnostic strategies in liver transplantation.
Facial clues to conversational intentions
Authors: Judith Holler
Journal: Trends in Cognitive Sciences (2025)

It has long been known that we use words to perform speech acts foundational to everyday conversation, such as requesting, informing, proposing, or complaining. However, the natural environment of human language is face-to-face interaction where we use words and an abundance of visual signals to communicate. The multimodal nature of human language is increasingly recognised in the language and cognitive sciences. In line with this turn of the tide, findings demonstrate that facial signals significantly contribute to communicating intentions and that they may facilitate pragmatically appropriate responding in the fast-paced environment of conversation. In light of this, the notion of speech acts no longer seems appropriate, highlighting the need for a modality-neutral conception, such as social action.
The immune response to the dermatomyositis-specific autoantigen nuclear matrix protein 2 can result in experimental autoimmune myositis
Authors: Yikang Wang, Qingyue Yuan, Yawen Zhao, Qiang Gang, Yuanyuan Ma, Hongjun Hao, Feng Gao, Jianwen Deng, Wei Zhang, Zhaoxia Wang, Yun Yuan, Yiming Zheng
Journal: Annals of the Rheumatic Diseases (2025)
Systematic review and independent validation of genetic factors of radiographic outcome in rheumatoid arthritis identifies a genome-wide association with CARD9
Authors: Seema Devi Sharma, Ryan Malcolm Hum, Nisha Nair, Lysette Marshall, Alice Storrie, John Bowes, Alexander MacGregor, Max Yates, Andrew P Morris, Suzanne Verstappen, Anne Barton, Hanna van Steenbergen, Rachel Knevel, Annette van der Helm-van Mil, Sebastien Viatte
Journal: Annals of the Rheumatic Diseases (2025)

This study aimed to investigate non-HLA genetic mechanisms underlying radiographic severity in rheumatoid arthritis (RA). A systematic review of publications reporting non-HLA genetic associations with radiographic severity in RA across ancestries was undertaken. Experimental validation was performed in the Norfolk Arthritis Register, comprising 1407 patients with available genetic and treatment data followed prospectively for up to 10 years, with 2198 longitudinal radiographs. Genome-wide genotyping was performed with Illumina Human Core Exome Array. Radiographic outcomes (presence of erosions; Larsen score) were modelled longitudinally. Fine mapping and functional annotations to refine associations to potential causative loci were undertaken using FUMA, PolyPhen2, and RegulomeDB. The systematic review identified 102 publications reporting 139 independent associations with radiographic outcome. Association with 15 independent polymorphisms were replicated in the Norfolk Arthritis Register data set, implicating adaptive immune processes (Th1, Th2, and Th17 pathways), cytokine regulation, and osteoclast differentiation. Notably, we refined the association of rs59902911 at the CARD9 locus to an intronic polymorphism within an active enhancer (rs78892335), achieving genome-wide significance and with an effect size exceeding the minimal clinically important difference for each copy of the minor allele (4.78 Larsen units/copy; 95% CI, 3.15-6.41; p = 9.01 × 10-9). This polymorphism is associated with the expression of CARD9 in immune cells, including B cells. We provide a comprehensive list of validated genetic associations with RA outcome and demonstrate that non-HLA polymorphisms can associate with radiographic severity independently of disease susceptibility. This highlights the importance of dedicated genetic outcome studies for patient stratification in precision medicine for RA.
Highly conserved brain vascular receptor ALPL mediates transport of engineered AAV vectors across the blood-brain barrier
Authors: Tyler C Moyer, Brett A Hoffman, Weitong Chen, Ishan Shah, Xiao-Qin Ren, Tatiana Knox, Jiachen Liu, Wei Wang, Jiangyu Li, Hamza Khalid, Anupriya S Kulkarni, Munachiso Egbuchulam, Joseph Clement, Alexis Bloedel, Matthew Child, Rupinderjit Kaur, Emily Rouse, Kristin Graham, Damien Maura, Zachary Thorpe, Ambreen Sayed-Zahid, Charlotte Hiu-Yan Chung, Alexander Kutchin, Amy Johnson, Johnny Yao, Jeffrey Thompson, Nilesh Pande, Mathieu E Nonnenmacher
Journal: Molecular Therapy (2025)

Delivery of systemically administered therapeutics to the central nervous system (CNS) is restricted by the blood-brain barrier (BBB). Bioengineered Adeno-Associated Virus (AAV) capsids have been shown to penetrate the BBB with great efficacy in mouse and non-human primate models, but their translational potential is often limited by species selectivity and undefined mechanisms of action. Here, we apply our RNA-guided TRACER AAV capsid evolution platform to generate VCAP-102, an AAV9 variant with markedly increased brain tropism following intravenous delivery in both rodents and primates. Relative to AAV9, VCAP-102 demonstrates 20- to 400-fold increased gene transfer across multiple brain regions. We identify alkaline phosphatase (ALPL) as the primary receptor used by VCAP-102 to cross the BBB and demonstrate that direct binding of VCAP-102 to human ALPL can initiate receptor-mediated transcytosis in a cell barrier model. Our work identifies VCAP-102 as a cross-species CNS gene delivery vector with a strong potential for clinical translation and establishes ALPL as a brain delivery shuttle capable of efficient BBB transport to maximize CNS delivery of biotherapeutics.
Treatment sequences in BRAF-V600-mutated non-small cell lung cancer: First-line targeted therapy versus first-line (chemo-) immunotherapy
Authors: Marcel Wiesweg, Ali Alaffas, Anna Rasokat, Felix Carl Saalfeld, Maximilian Rost, Christin Assmann, Franziska Herster, Moritz Hilbrandt, Frank Griesinger, Anna Kron, Julia Roeper, Franziska Glanemann, Cornelia Kropf-Sanchen, Martin Reck, Jonas Kulhavy, Albrecht Stenzinger, Jürgen Wolf, Martin Sebastian, Martin Schuler, Martin Wermke, Nikolaj Frost, Hans-Georg Kopp, Petros Christopoulos, Matthias Scheffler
Journal: Journal of Thoracic Oncology (2025)

Targeted treatment of patients with metastatic BRAF-V600-mutated non-small-cell lung cancer (NSCLC) using BRAF/MEK-inhibitors is effective but limited by acquired resistance. Patients with BRAF-mutant NSCLC may derive long-lasting benefit from immune checkpoint inhibition with PD-1/-L1 antibodies (IO). While IO is the preferred first-line therapy in BRAF-mutated melanoma, the optimal treatment sequence in BRAF-mutated NSCLC is not defined. Retrospective study of the clinical outcome of patients with metastatic BRAF-V600-mutated NSCLC diagnosed in the German national Network Genomic Medicine Lung Cancer (nNGM). We identified 205 patients with BRAF-V600-mutated NSCLC. 175 patients received first-line therapy with dabrafenib/trametinib (DAB/TRM, 65.1%), IO alone (19.4%), or chemo-IO (15.4%). Overall survival (OS) and time-to-treatment failure of first-line therapy (TTF) was identical for patients receiving first-line DAB/TRM (median OS 28.0 months) or chemo/IO (27.8 months, HR 1.1, p=0.68). Female patients had superior OS (HR 0.65, p=0.049, confirmed in multivariate model), which was mainly driven by superior OS of female versus male patients receiving first-line DAB/TRM (OS HR 0.53, p=0.015). There was no gender difference in survival of patients receiving IO-based first-line treatment (OS HR 1.02). Surprisingly, high PD-L1 status (TPS ≥50%) associated with shortened time-to-treatment failure in first-line (HR 1.83, p=0.002, confirmed in multivariate models adjusting for gender; OS with non-significant trend, HR 1.4), regardless of whether the first-line regimen was IO-based or targeted therapy. Targeted or IO-based first-line treatment of BRAF-V600-mutated NSCLC have similar survival outcomes. Gender and PD-L1 status may support decision making at the individual patient level.
Establishing Core Competencies for Antimicrobial Stewardship Teams: A Consensus Development Using the Modified Delphi Technique; an ESGAP position paper
Authors: Joana Alves, Jeroen Schouten, Karin Thursky, Ran Nir Paz, Jordi Rello, David Chien Lye, Tomislav Kostyanev, Jacob Strahilevitz, Katja de With, Aleksandra Barac, Ezgi Gülten, Diane Ashiru-Oredope, Giorgia Caruana, Nathan Peiffer-Smadja, Rita Murri, Lucy Catteau, Bojana Beović
Journal: Clinical Microbiology and Infection (2025)
Superior Antiviral Efficacy of Combined 3CL Protease and RdRp Inhibition Compared to 3CL Protease Inhibitor Monotherapy in Hospitalized COVID-19 Patients
Authors: Yuan Gao, Jiaying Zhang, Muxin Liu, Qiushi Bu, Li Chen, Wenlong Yang, Jun Li, Wujun Xiong, Xuan Liang, Kaiyu Zhang, Yixi Dong, Longzhen Zhou, Jinbo Zhuang, Zhijie Gong, Yunyi Gao, Liang Fu, Hongzhou Lu, Xinyu Zhang, Zhongjie Hu
Journal: Journal of Infection (2025)
Mn-coordination Driven Glutamine and Cancer Stemness Dual-tailored Nano-herb for High-efficiency Activation of Dendritic Cells
Authors: Fanchen Yan, Hailong Tian, Shanshan Liu, Jing Zhang, Chen Yang, Lihua Chen, Yaying Zhang, Yuanshen Cao, Yunfeng Song, Canhua Huang, Haiyuan Zhang
Journal: Biomaterials (2025)
Dose-Escalated Stereotactic Versus Conventional Radiotherapy for Painful Bone Metastases (ROBOMET): A Multicenter, Patient-Blinded Randomized Clinical Trial
Authors: Carole Mercier, Charlotte Billiet, Piet Ost, Katrien Vandecasteele, Geert De Kerf, Michaël Claessens, Steven Van Laere, Peter Vermeulen, Luc Dirix, Yolande Lievens, Dirk Verellen, Piet Dirix
Journal: Journal of Clinical Oncology (2025)

PURPOSE To test whether dose-escalated single fraction (SF) stereotactic body radiotherapy (SBRT) of 20 Gy to painful bone metastases is superior to conventional SF three-dimensional (3D) conformal radiotherapy (RT) to a standard dose of 8 Gy in achieving complete pain response (CR). METHODS A single-blind, randomized, controlled, phase III trial (ROBOMET) included 126 patients with up to three painful bone metastases, randomly assigned between April 2019 and October 2022 at multiple centers in Belgium. Inclusion criteria were uncomplicated painful bone metastases (worst pain score ≥2 on a 0-10 pain scale) arising from a solid tumor. Treatment consisted of either a single SBRT fraction of 20 Gy or a single conventional RT fraction of 8 Gy. The primary end point was the proportion of patients with a CR 1 month after RT scored according to the International Consensus on Palliative Radiotherapy Endpoints analyzed as per an intention-to-treat principle. RESULTS After 1 month, 16 of 63 (25% [95% CI, 15 to 38]) patients treated with conventional RT achieved CR versus 23 of 63 (37% [95% CI, 25 to 50]) treated with SBRT ( P = .25). After 3 months, 15 of 63 (24% [95% CI, 14 to 36]) patients achieved CR after conventional RT versus 21 of 63 (33% [95% CI, 22 to 46]) after SBRT ( P = .32). Among patients evaluable after 3 months and treated per protocol, the SBRT group had more complete responders (21/39, 54% [95% CI, 37 to 70]) than the conventional RT group (15/48, 31% [95% CI, 19 to 46]; P = .048). CONCLUSION SBRT failed to demonstrate improved CR rates after 1 month.