tbuckley/cabot-search huggingface dataset:
Clinical relevance of computationally derived tubular features and their spatial relationships with the interstitial microenvironment in minimal change disease/focal segmental glomerulosclerosis
Authors: Fan Fan, Qian Liu, Jarcy Zee, Takaya Ozeki, Dawit Demeke, Yingbao Yang, Markus Bitzer, Christopher L O'Connor, Alton B Farris, Bangcheng Wang, Manav Shah, Jackson Jacobs, Laura Mariani, Kyle Lafata, Jeremy Rubin, Yijiang Chen, Lawrence Holzman, Jeffrey B Hodgin, Anant Madabhushi, Laura Barisoni, Andrew Janowczyk
Journal: Kidney International (2025)

Visual scoring of tubular damage has limitations in capturing the full spectrum of structural changes and prognostic potential. Here, we investigated if computationally quantified tubular features can enhance prognostication and reveal spatial relationships with interstitial fibrosis. Deep-learning and image-analysis approaches were employed on 254/266 Periodic acid Schiff-stained whole slide image (WSI) kidney biopsies from participants in the NEPTUNE/CureGN prospective observational cohort studies (135/153 with focal segmental glomerulosclerosis (FSGS) and 119/113 with minimal change disease (MCD)) to segment cortex, tubular lumen (TL), epithelium (TE), nuclei (TN), and basement membrane (TBM). One hundred four pathomic features were extracted from these segmented tubular substructures and aggregated at the patient level using summary statistics. In the NEPTUNE dataset, tubular features were quantified at the WSI level and in manually segmented regions of mature interstitial fibrosis and tubular atrophy (IFTA), pre-IFTA, and non-IFTA. Minimum Redundancy Maximum Relevance was then used to select features most associated with disease progression and proteinuria remission. Ridge-penalized Cox models evaluated their predictive discrimination compared to clinical/demographic data and visual-assessment. Models were evaluated in the CureGN dataset. Nine features were predictive of disease progression and/or proteinuria remission. Models with tubular features had high prognostic accuracy in both NEPTUNE and CureGN, and higher prognostic accuracy for both outcomes compared to conventional parameters alone in NEPTUNE. TBM thickness/area and TE flattening and/or reduced cell size progressively increased from non- to pre- and mature IFTA. Previously underrecognized computationally derived and quantifiable tubular characteristics may contribute to improving prognostic accuracy and risk stratification in patients with FSGS/MCD. Future studies are needed to test their generalizability across different diseases and populations before they can be deployed in clinical practice.
Human Airway Epithelial BAFF is Reduced in Early Life but Virally-induced via JAK/STAT
Authors: Elizabeth Chorvinsky, None Surajit Bhattacharya, Kyle Salka, Bethlehem Solomon Bera, Allison Welham, Ethan Mondell, Geovanny F Perez, Dinesh Pillai, Jyoti Jaiswal, None Gustavo Nino, Maria J Gutierrez
Journal: Journal of Allergy and Clinical Immunology (2025)
Dynamic oxygenation subgroup bringing new insights in ARDS: more predictive of outcomes and response to PEEP than static PaO <sub>2</sub> /FiO <sub>2</sub>
Authors: Yu Bai, Shengsong Chen, Haopu Yang, Xu Huang, Jingen Xia, Qingyuan Zhan
Journal: Thorax (2025)

Background Acute respiratory distress syndrome (ARDS) is a rapidly evolving condition. Dynamic assessments using patient trajectories may provide novel insights into disease heterogeneity. The primary objective of this study was to develop and validate dynamic oxygenation subgroups of ARDS based on longitudinal arterial oxygen tension/fractional inspired oxygen (PaO 2 /FiO 2 ) ratios from the day of ARDS diagnosis to day 3. The secondary objective was to determine whether these dynamic physiological subgroups are more effective in predicting patient outcomes and treatment response than the Berlin criteria-defined static oxygenation subgroups. Methods We used group-based trajectory modelling to construct longitudinal oxygenation subgroups over the first 3 days following ARDS diagnosis, based on five ARDS databases. Additionally, we compared these longitudinal subgroups with static Berlin criteria-defined mild, moderate and severe subgroups in terms of clinical characteristics, outcomes and positive end-expiratory pressure (PEEP) responses. Results A total of 814 and 2505 patients with ARDS were included in the training cohort (Chinese ARDS Database) and validation cohorts (FACTT, SAILS, ALVEOLI and MIMIC-IV), respectively. We derived three longitudinal oxygenation subgroups: group 1 (n=406, 49.88%), group 2 (n=302, 37.10%) and group 3 (n=106, 13.02%). The PaO 2 /FiO 2 of the three subgroups exhibited the following trends over time: persistently low, gradually increasing and rapidly improving. The mortality differences across the three longitudinal subgroups (62.59% vs 35.79% vs 17.39%) were significantly greater than those in Berlin criteria-defined subgroups (57.53% vs 41.34% vs 32.18%; χ²=55.65 vs 13.45, p=0.001 for heterogeneity comparison). Additionally, treatment heterogeneity (high vs low PEEP) was more pronounced in longitudinal subgroups (interaction p=0.001) compared with Berlin subgroups (interaction p=0.72). The longitudinal subgroup exhibited variations in patient demographics, PaO 2 /FiO 2 development trajectory and PEEP treatment response, compared with the subgroup defined by the Berlin criteria. Conclusions We identified three longitudinal oxygenation subgroups of ARDS that were more predictive of prognosis and response to PEEP than the subgroups defined by static PaO 2 /FiO 2 ratios in the ARDS Berlin criteria.
Systematic review and meta-analysis of the efficacy of biologic and targeted synthetic therapies in sarcoidosis
Authors: Katie Bechman, Kathryn Biddle, Aitana Miracle, Kelly He, Mark Gibson, Mark D Russell, Sarah Walsh, Peter Brex, Amit S Patel, Katherine J Myall, Sam Norton, Surinder S Birring, James Galloway
Journal: Thorax (2025)

Objectives Infliximab, an anti-TNF agent, is used to treat sarcoidosis that does not respond to corticosteroids or second-line agents. The efficacy of other anti-TNF agents, non-TNF biologics and targeted synthetic therapies remains unclear. This study aims to evaluate the role of these therapies in the management of multisystem sarcoidosis. Methods We conducted a systematic literature search to identify trials of biological and targeted synthetic therapies in sarcoidosis. Meta-analyses examined %-predicted forced vital capacity (FVC), as mean change from baseline. Heterogeneity was measured using the I 2 statistic. Vote counting based on the direction of effect, as recommended by the Cochrane network, was used to synthesise study estimates. Results The search identified 6777 records. Sixteen studies met the inclusion criteria. These included 8 randomised control trials (RCTs) and 8 single-arm trials. Fourteen studies evaluated biologic therapies: infliximab (n=5), adalimumab (n=2), etanercept (n=2), golimumab (n=1), rituximab (n=1), anakinra (n=1), sarilumab (n=1), ustekinumab (n=1) and efzofitimod (n=1). Two trials assessed the targeted synthetic therapy tofacitinib. Risk of bias was high in five of eight RCTs. Meta-analysis of %-predicted FVC showed modest improvement with treatment (mean change: 4.79% (95% CI 1.22 to 8.35), driven by anti-TNF trials 5.70% (95% CI 1.61 to 9.78). Heterogeneity was substantial (I²=76.3%). In data synthesis using vote counting, infliximab, adalimumab, efzofitimod and tofacitinib demonstrated a positive direction of effect across all estimates, though improvements in several outcomes did not reach thresholds for minimal clinically important differences. Conclusions Meta-analysis supports infliximab use in pulmonary sarcoidosis, although improvements in lung function are modest. There is limited but promising evidence for the use of adalimumab and tofacitinib in cutaneous disease and efzofitimob in pulmonary disease. Study interpretation is limited by small sample sizes and heterogeneity in study design and population. PROSPERO registration number CRD42024599560
3D-printed microfibers encapsulating stem cells in scaffold with tri-culture and two-stage metformin release for bone/vasculature/nerve regeneration in rats
Authors: Minjia Zhu, Xinyi Li, Le Xiao, Kan Yu, Jingyi Li, Zixiang Dai, Qinrou Zhang, Jialiang Dai, Zihan Jia, Yuxing Bai, Ke Zhang
Journal: Bioactive Materials (2025)
Urine Tumor DNA to Stratify the Risk of Recurrence in Patients Treated with Atezolizumab for Bacillus Calmette-Guérin–unresponsive Non–muscle-invasive Bladder Cancer
Authors: Marie-Pier St-Laurent, Parminder Singh, David J McConkey, M Scott Lucia, Vadim S Koshkin, Kelly L Stratton, Trinity J Bivalacqua, Wassim Kassouf, Sima P Porten, Rick Bangs, Melissa Plets, Ian M Thompson, Joshua J Meeks, Vincent M Caruso, Ceressa T Ward, Brian C Mazzarella, Kevin G Phillips, Vincent T Bicocca, Trevor G Levin, Seth P Lerner, Peter C Black
Journal: European Urology (2025)

As new treatments for bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) emerge, better methods are needed to guide therapeutic decisions. This study analyzed urine tumor DNA (utDNA) from patients treated with atezolizumab in the SWOG S1605 trial to determine whether utDNA profiling can stratify the risk of treatment failure. Urine samples were analyzed using the UroAmp assay at baseline and 3 mo from 89 and 77 patients, respectively. Only 13% of UroAmp-positive patients at baseline achieved a complete response at 6 mo compared with 71% of UroAmp-negative patients (p < 0.001). The 18-mo event-free survival (EFS) was significantly lower for UroAmp-positive patients at baseline (23%) than for UroAmp-negative patients (51%; hazard ratio [HR] 2.8, p < 0.001). Among patients with no clinical evidence of disease at 3 mo (n = 51), the 18-mo EFS was 38% for UroAmp-positive and 86% for UroAmp-negative (HR 3.5, p = 0.01) patients. These findings suggest that utDNA profiling at baseline and after 3 mo of treatment can help identify patients with BCG-unresponsive NMIBC who are less likely to benefit from systemic immunotherapy.
Cytoplasmic and nuclear NFATc3 cooperatively contributes to vascular smooth muscle cell dysfunction and drives aortic aneurysm and dissection
Authors: Xiu Liu, Li Zhao, Deshen Liu, Lingna Zhao, Yonghua Tuo, Qinbao Peng, Fangze Huang, Zhengkun Song, Chuanjie Niu, Xiaoxia He, Yu Xu, Jun Wan, Peng Zhu, Zhengyang Jian, Jiawei Guo, Yingying Liu, Jun Lu, Sijia Liang, Shaoyi Zheng
Journal: Acta Pharmaceutica Sinica B (2025)
Linagliptin synergizes with cPLA2 inhibition to enhance temozolomide efficacy by interrupting DPP4-mediated EGFR stabilization in glioma
Authors: Dongyuan Su, Biao Hong, Shixue Yang, Jixing Zhao, Xiaoteng Cui, Qi Zhan, Kaikai Yi, Yanping Huang, Jiasheng Ju, Eryan Yang, Qixue Wang, Junhu Zhou, Yunfei Wang, Xing Liu, Chunsheng Kang
Journal: Acta Pharmaceutica Sinica B (2025)
Single-cell RNA sequencing reveals Shen-Bai-Jie-Du decoction retards colorectal tumorigenesis by regulating the TMEM131–TNF signaling pathway-mediated differentiation of immunosuppressive dendritic cells
Authors: Yuquan Tao, Yinuo Ma, Limei Gu, Ye Zhang, Qinchang Zhang, Lisha Zhou, Jie Pan, Meng Shen, Xuefei Zhuang, Linmei Pan, Weixing Shen, Chengtao Yu, Dan Dong, Dong Zhang, Tingsheng Ling, Yang Sun, Haibo Cheng
Journal: Acta Pharmaceutica Sinica B (2025)
An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes
Authors: Elisabetta Furlanis, Min Dai, Brenda Leyva Garcia, Thien Tran, Josselyn Vergara, Ana Pereira, Bram L Gorissen, Sara Wills, Anna Vlachos, Ariel Hairston, Deepanjali Dwivedi, Sarah Du, Justin McMahon, Shuhan Huang, Annunziato Morabito, Arenski Vazquez, Soyoun Kim, Anthony T Lee, Edward F Chang, Taha Razzaq, Ahmed Qazi, Geoffrey Vargish, Xiaoqing Yuan, Adam Caccavano, Steven Hunt, Ramesh Chittajallu, Nadiya McLean, Lauren Hewitt, Emily Paranzino, Haley Rice, Alex C Cummins, Anya Plotnikova, Arya Mohanty, Anne Claire Tangen, Jung Hoon Shin, Reza Azadi, Mark A G Eldridge, Veronica A Alvarez, Bruno B Averbeck, Mansour Alyahyay, Tania Reyes Vallejo, Mohammed Soheib, Lucas G Vattino, Cathryn P MacGregor, Carolina Piletti Chatain, Emmie Banks, Viktor Janos Olah, Shovan Naskar, Sophie Hill, Sophie Liebergall, Rohan Badiani, Lili Hyde, Ella Hanley, Qing Xu, Kathryn C Allaway, Ethan M Goldberg, Matthew J M Rowan, Tomasz J Nowakowski, Soohyun Lee, Emilia Favuzzi, Pascal S Kaeser, Lucas Sjulson, Renata Batista-Brito, Anne E Takesian, Leena A Ibrahim, Asim Iqbal, Kenneth A Pelkey, Chris J McBain, Jordane Dimidschstein, Gord Fishell, Yating Wang
Journal: Neuron (2025)
Machine learning identification of enhancers in the rhesus macaque genome
Authors: Jing He, BaDoi N Phan, Willa G Kerkhoff, Aydin Alikaya, Tao Hong, Olivia R Brull, J Megan Fredericks, Morgan Sedorovitz, Chaitanya Srinivasan, Michael J Leone, Olivia M Wirfel, Ashley Brown, Samuel Dauby, Rachel K Tittle, Meng K Lin, Bryan M Hooks, Andreea C Bostan, Omar A Gharbawie, Leah C Byrne, Andreas R Pfenning, William R Stauffer
Journal: Neuron (2025)
Specific targeting of brain endothelial cells using enhancer AAV vectors
Authors: Eric Velazquez-Rivera, Oyshi Dey, Nayoon S Kim, Wenhao Cao, Qiao Ye, Pan Gao, Andy Thai, Jason K Nguyen, Hai Zhang, Jonathan T Ting, M Gopi, Bing Ren, Todd C Holmes, Xiangmin Xu
Journal: Neuron (2025)
Dissecting key contributions of Th2 and Th17 cytokines to atopic dermatitis pathophysiology
Authors: Luca D Meesters, Janou A Y Roubroeks, Aranka Gerritsen, Niels Velthuijs, Jaimy A Klijnhout, Camille Laberthonnière, Ivonne M van Vlijmen-Willems, Matthias Hübenthal, Diana Rodijk-Olthuis, Rens H W Peters, Gijs Rikken, Silke Szymczak, Nanna Fyhrquist, Harri Alenius, Stephan Weidinger, Jos P H Smits, Musa Mhlanga, Huiqing Zhou, Hanna Niehues, Ellen H van den Bogaard
Journal: Journal of Allergy and Clinical Immunology (2025)

In atopic dermatitis (AD), epidermal disease hallmarks are driven by a complex cutaneous inflammatory milieu that varies between patients. How these variable inflammatory signals affect cellular and molecular epidermal AD phenotypes is difficult to study in vivo. We aimed to unravel which AD-associated cytokines drive specific epidermal disease hallmarks. We utilized primary and immortalized keratinocyte-derived human epidermal equivalents stimulated with T helper (Th)2, -17 and -22 cytokines. Morphological, functional and transcriptomic analyses revealed that Th2 cytokines interleukin (IL)-4 and IL-13 were main inducers of a pro-inflammatory and hyperproliferative epidermis. The presence of IL-17A or IL-22 in the Th2 milieu, and especially Th2 + IL-22, most closely resembled AD hallmarks including spongiosis, more severe keratinocyte differentiation defects and epidermal barrier dysfunction. Single-cell spatial transcriptomics showed expansion of keratinocytes expressing high levels of proliferation genes, and downregulation of differentiation genes in the upper epidermal layers. The transcriptomic comparison to in vivo AD lesional skin indicated that the Th2 + IL-22 AD model demonstrated greatest resemblance and identified AD disease marker genes altered by Th2 + IL-22 such as downregulated ACER1 and AKR1C3. Gene expression levels were restored by combinatory exposure to aryl hydrocarbon receptor (AHR) ligand tapinarof and Janus Kinase (JAK) inhibitor tofacitinib. This combined therapeutic approach also completely restored epidermal barrier function and improved morphological disease hallmarks. Our results reveal the important role of IL-22 in the Th2 driven acute AD pathophysiology and highlight the potential of combinatory medicine in targeted treatment of AD.
Evaluating methods for the prediction of cell-type-specific enhancers in the mammalian cortex
Authors: Nelson J Johansen, Niklas Kempynck, Nathan R Zemke, Saroja Somasundaram, Seppe De Winter, Marcus Hooper, Deepanjali Dwivedi, Ruchi Lohia, Fabien Wehbe, Bocheng Li, Darina Abaffyová, Ethan J Armand, Julie De Man, Eren Can Ekşi, Nikolai Hecker, Gert Hulselmans, Vasilis Konstantakos, David Mauduit, John K Mich, Gabriele Partel, Tanya L Daigle, Boaz P Levi, Kai Zhang, Yoshiaki Tanaka, Jesse Gillis, Jonathan T Ting, Yoav Ben-Simon, Jeremy Miller, Joseph R Ecker, Bing Ren, Stein Aerts, Ed S Lein, Bosiljka Tasic, Trygve E Bakken
Journal: Cell Genomics (2025)

Identifying cell-type-specific enhancers is critical for developing genetic tools to study the mammalian brain. We organized the "Brain Initiative Cell Census Network (BICCN) Challenge: Predicting Functional Cell Type-Specific Enhancers from Cross-Species Multi-Omics" to evaluate machine learning and feature-based methods for nominating enhancer sequences targeting mouse cortical cell types. Methods were assessed using in vivo data from hundreds of adeno-associated virus (AAV)-packaged, retro-orbitally delivered enhancers. Open chromatin was the strongest predictor of functional enhancers, while sequence models improved prediction of non-functional enhancers and identified cell-type-specific transcription factor codes to inform in silico enhancer design. This challenge establishes a benchmark for enhancer prioritization and highlights computational and molecular features critical for identifying functional cortical enhancers, advancing efforts to map and manipulate gene regulation in the mammalian cortex.
When data disappear: public health pays as US policy strays
Authors: Thomas McAndrew, Andrew A Lover, Garrik Hoyt, Maimuna S Majumder
Journal: The Lancet Digital Health (2025)

Presidential actions on Jan 20, 2025, by President Donald Trump, including executive orders, have delayed access to or led to the removal of crucial public health data sources in the USA. The continuous collection and maintenance of health data support public health, safety, and security associated with diseases such as seasonal influenza. To show how public health data surveillance enhances public health practice, we analysed data from seven US Government-maintained sources associated with seasonal influenza. We fit two models that forecast the number of national incident influenza hospitalisations in the USA: (1) a data-rich model incorporating data from all seven Government data sources; and (2) a data-poor model built using a single Government hospitalisation data source, representing the minimal required information to produce a forecast of influenza hospitalisations. The data-rich model generated reliable forecasts useful for public health decision making, whereas the predictions using the data-poor model were highly uncertain, rendering them impractical. Thus, health data can serve as a transparent and standardised foundation to improve domestic and global health. Therefore, a plan should be developed to safeguard public health data as a public good.
Correction to “Effectiveness of an unguided modular online intervention for highly anxious parents in preventing anxiety in their children: a parallel group randomised controlled trial” [The Lancet Regional Health—Europe, Volume 45, October 2024, 101038]
Authors: Abby Dunn, James Alvarez, Amy Arbon, Stephen Bremner, Chloe Elsby-Pearson, Richard Emsley, Christopher Jones, Peter Lawrence, Kathryn J. Lester, Natalie Morson, Julia Simner, Abigail Thomson, Sam Cartwright-Hatton
Journal: The Lancet Regional Health - Europe (2025)
Glypican-3 as a Radiotheranostic Target for Neuroendocrine Prostate Cancer
Authors: Woonghee Lee, Joon-Yong Chung, Kwamena E Baidoo, Divya Nambiar, Falguni Basuli, Ilsa Coleman, Martin Bakht, Chennan Li, Jinho Shin, Se Un Jeong, Yong Mee Cho, Himisha Beltran, Peter S Nelson, Adam G Sowalsky, Peter L Choyke, Freddy E Escorcia
Journal: European Urology (2025)
The influence of early life exposures on the infant gut virome
Authors: Yichang Zhang, Josué L. Castro-Mejía, Ling Deng, Shiraz A. Shah, Jonathan Thorsen, Cristina Leal Rodríguez, Leon E. Jessen, Moïra B. Dion, Bo Chawes, Klaus Bønnelykke, Søren J. Sørensen, Hans Bisgaard, Sylvain Moineau, Marie-Agnès Petit, Jakob Stokholm, Dennis S. Nielsen
Journal: Gut Microbes (2025)

The factors influencing the establishment of the gut bacterial community in early life are fairly well studied. However, the factors shaping the infant gut virome remain elusive. Interestingly, early life gut virome imbalances have recently been linked with increased risk of developing diseases like type 1 diabetes and asthma. We utilized the deeply phenotyped COPSAC2010 cohort to investigate how environmental factors influence the gut virome at one year age. We demonstrate that the presence of older siblings as well as residential location (urban or rural) had the strongest impact on gut virome composition at 1 year of age. A total of 16,118 species-level clustered viral representative contigs (here termed viral Operational Taxonomic Units - vOTUs) were identified and of these 2105 vOTUs varied in abundance with environmental exposures. Of these vOTUs 94.1% were phages mainly predicted to infect Bacteroidaceae, Prevotellaceae, and Ruminococcaceae. Strong co-abundance of phages and their bacterial hosts was confirmed underlining the predicted phage-host connections. Furthermore, we found some gut viruses affected by environmental factors encode enzymes involved in the utilization and degradation of major dietary components, potentially affecting infant health by influencing the bacterial host metabolic capacity. These findings provide a valuable insights for understanding the early life factors that predispose to autoimmune and metabolic disorders.
Correction: Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1
Authors: Warren Fiskus, Christopher P Mill, Christine Birdwell, John A Davis, Kaberi Das, Steffen Boettcher, Tapan M Kadia, Courtney D DiNardo, Koichi Takahashi, Sanam Loghavi, Michael J Soth, Tim Heffernan, Gerard M McGeehan, Xinjia Ruan, Xiaoping Su, Christopher R Vakoc, Naval Daver, Kapil N Bhalla
Journal: Blood Cancer Journal (2025)
Therapeutic Potential of Vascular Adhesion Protein‐1 (VAP‐1)/Semicarbazide‐Sensitive Amine Oxidase (SSAO) Inhibitors: Current Medicinal Chemistry and Emerging Opportunities
Authors: Pinaki Bhattacharjee, Malliga R. Iyer
Journal: Medicinal Research Reviews (2025)

ABSTRACT Semicarbazide‐sensitive amine oxidase (SSAO) is a vascular enzyme and expressed in high concentrations in vascular smooth muscle cells (VSMCs), localized in the caveolae of the plasma membrane, and the endothelial cells. SSAO is classified as a copper amine oxidase and encoded by the amine oxidase copper‐containing 3 gene. SSAO exists both as a soluble protein and as a tissue‐bound transmembrane protein. The latter is often called vascular adhesion protein 1. Vascular adhesion protein‐1 or VAP‐1, encoded by the AOC3 gene, is a pro‐inflammatory and multifunctional molecule belonging to the SSAO family. It assists the transformation of primary amines to aldehydes resulting in the production of hydrogen peroxide and ammonia. Work from the last two decades, has shown that VAP‐1/SSAO plays a role in several physiological and pathological processes, making it a potentially valuable target for therapeutic development. In this review, we provide a detailed overview of the inhibitors of VAP‐1/SSAO that are being developed specifically for the treatment of inflammatory diseases. Here in we have highlighted important aspects of the compounds investigated in therapeutic applications. Furthermore, we have outlined potential avenues for innovation with the aim of maximizing the therapeutic efficacy of VAP‐1/SSAO inhibitors in clinical settings.