tbuckley/cabot-search huggingface dataset:
A new metric to understand the association between heart rate variability and menstrual regularity
Authors: Kimia Heydari, Elizabeth J. Enichen, Ben Li, Joseph C. Kvedar
Journal: npj Digital Medicine (2025)

Cardiovascular disease is underdiagnosed and undertreated in women compared to men. Wearable technologies (wearables) help shed light on women's cardiovascular by collecting continuous cardiovascular data and correlating it with hormonal fluctuations across the menstrual cycle. In this context, Jasinski et al. propose that the new metric, cardiovascular amplitude, enables non-invasive monitoring of female physiology and health across the menstrual cycle.
Ventilation practices in acute brain injured patients and association with outcomes: the VENTIBRAIN multicenter observational study
Authors: Chiara Robba, Daniele Giardiello, Chiara Almondo, Karim Asehnoune, Rafael Badenes, Raphael Cinotti, Muhammed Elhadi, Francesca Graziano, Raimund Helbok, Lidan Jiang, Wenjin Chen, John G Laffey, Antonio Messina, Christian Putensen, Marcus J Schultz, Sarah Wahlster, Paola Rebora, Stefania Galimberti, Fabio Silvio Taccone, Giuseppe Citerio
Journal: Intensive Care Medicine (2025)
Urine-free response criteria predict progression-free survival in multiple myeloma: a post hoc analysis of BMT CTN 0702
Authors: Rahul Banerjee, Amber R. Fritz, Othman S. Akhtar, Ciara L. Freeman, Andrew J. Cowan, Nina Shah, Heather J. Landau, Shaji K. Kumar, Dan T. Vogl, Yvonne A. Efebera, Philip L. McCarthy, David H. Vesole, Adam Mendizabal, Amrita Y. Krishnan, George Somlo, Edward A. Stadtmauer, Marcelo C. Pasquini
Journal: Leukemia (2025)
Astrocyte heterogeneity reveals region-specific astrogenesis in the white matter
Authors: Riccardo Bocchi, Manja Thorwirth, Tatiana Simon-Ebert, Christina Koupourtidou, Solène Clavreul, Keegan Kolf, Patrizia Della Vecchia, Sara Bottes, Sebastian Jessberger, Jiafeng Zhou, Gulzar Wani, Gregor-Alexander Pilz, Jovica Ninkovic, Annalisa Buffo, Swetlana Sirko, Magdalena Götz, Judith Fischer-Sternjak
Journal: Nature Neuroscience (2025)

Abstract Astrocyte heterogeneity has been well explored, but our understanding of white matter (WM) astrocytes and their distinctions from gray matter (GM) astrocytes remains limited. Here, we compared astrocytes from cortical GM and WM/corpus callosum (WM/CC) using single-cell RNA sequencing and spatial transcriptomics of the murine forebrain. The comparison revealed similarities but also significant differences between WM and GM astrocytes, including cytoskeletal and metabolic hallmarks specific to WM astrocytes with molecular properties also shared with human WM astrocytes. When we compared murine astrocytes from two different WM regions, the cortex and cerebellum, we found that they exhibited distinct, region-specific molecular properties, with the cerebellum lacking, for example, a specific cluster of WM astrocytes expressing progenitor and proliferation genes. Functional experiments confirmed astrocyte proliferation in the WM/CC, but not in the cerebellar WM, suggesting that the WM/CC may be a source of continued astrogenesis.
Five ways to enhance the diversity and quality of health data
Authors: Paola Quattroni, Ash Routen, Joe Alderman, Claire Argent, Samuel Cushworth, Hajira Dambha-Miller, Rose Drummond, Alastair Denniston, Pushali Ganguli, Nicola Hamilton, Uwaye Ideh, Sara Khalid, Aden Kwok, Elinor Laws, Xiaoxuan Liu, Vahe Nafilyan, Jo Palmer, Marta Pineda-Moncusi, Alexia Sampri, Holly Tibble, Fatemeh Torabi, Jonathan Valabhji, Diana Withrow, Claire Welsh, Angela M. Wood, Ashley Akbari, Kamlesh Khunti
Journal: Nature Medicine (2025)
The Mediterranean diet displays an immunomodulatory effect that correlates with beneficial changes in carotid atherosclerosis
Authors: Ana María Ruiz-León, Miguel Camafort, Aleix Sala-Vila, Rosa Gilabert, Isabel Núñez, Sara Castro-Barquero, Montserrat Fitó, Rosa María Lamuela-Raventós, Xavier Pintó, Ana García-Arellano, Emilio Ros, Ramon Estruch, Rosa Casas
Journal: Cardiovascular Research (2025)
In situ UNIversal Orthogonal Network (UNION) bioink deposition for direct delivery of corneal stromal stem cells to corneal wounds
Authors: Lucia G Brunel, Betty Cai, Sarah M Hull, Uiyoung Han, Thitima Wungcharoen, Gabriella Maria Fernandes-Cunha, Youngyoon Amy Seo, Patrik K Johansson, Sarah C Heilshorn, David Myung
Journal: Bioactive Materials (2025)
Aortic Valve Calcification Is Induced by the Loss of ALDH1A1 and Can Be Prevented by Agonists of Retinoic Acid Receptor Alpha: Preclinical Evidence for Drug Repositioning
Authors: Mickael Rosa, Annabelle Dupont, David M. Smadja, Jérôme Soquet, Johan Abdoul, Thibault Pamart, Flavien Vincent, Christina Le Tanno, Eloise Borowczac, Timothée Bigot, Alexandre Ung, Bertrand Vaast, Mélanie Daniel, Ramadan Jashari, Frédéric Mouquet, Cedric Delhaye, Yoann Sottejeau, Jeanne Rancic, Delphine Corseaux, Francis Juthier, Bart Staels, Sophie Susen, Eric Van Belle
Journal: Circulation (2025)

BACKGROUND: To date, the only effective treatment of severe aortic stenosis is valve replacement. With the introduction of transcatheter aortic valve replacement and extending indications to younger patients, the use of bioprosthetic valves (BPVs) has considerably increased. The main inconvenience of BPVs is their limited durability because of mechanisms similar as the fibro-calcifying processes observed in native aortic stenosis. One of the major gaps of the field is to identify therapeutic targets to prevent or slow the fibro-calcifying process leading to severe and symptomatic aortic stenosis. The aim was to identify new targets for anticalcification drugs to prevent aortic and BPV calcification using an unbiased translational approach. METHODS: Explanted valves were collected from patients and organ donor hearts. A comparative transcriptomic analysis was performed on valvular interstitial cells (VIC) obtained from calcified (bicuspid and tricuspid) versus control valves. The mechanisms and consequences of aldehyde dehydrogenase 1 family member A1 (ALDH1A1) downregulation were analyzed in VIC cultures from control human aortic valves. ALDH1A1 was inhibited or silenced and its impact on osteogenic marker expression and calcification processes assessed in VIC. The effect of all-trans retinoic acid on calcification was tested on human VIC cultures and on 2 animal models: the model of subcutaneous implantation of bovine pericardium in rats and the model of xenograft aortic valve replacement in juvenile sheep. RESULTS: Transcriptome analysis of human VIC identified ALDHA1 as the most downregulated gene in VIC from calcified versus control valves. In human VIC, ALDH1A1 expression is downregulated by TGF-β1 in a SMAD2/3-dependent manner. ALDH1A1 inhibition promotes an osteoblast-like VIC phenotype and increases calcium deposition through inhibition of retinoic acid receptor alpha signaling. Conversely, VIC treatment with retinoids decreases calcium deposition and attenuates VIC osteoblast activity. Last, all-trans retinoic acid inhibits calcification development of aortic BPV in both in vivo models and improves aortic valve echocardiographic parameters in the xenograft sheep model. CONCLUSIONS: These results show that ALDH1A1 is downregulated in calcified valves, hence promoting VIC transition into an osteoblastic phenotype. Retinoic acid receptor alpha agonists, including all-trans retinoic acid through a drug repositioning strategy, represent a promising and innovative pharmacological approach to prevent calcification of native aortic valves and BPV.
Whole-genome sequencing analysis identifies rare, large-effect noncoding variants and regulatory regions associated with circulating protein levels
Authors: Gareth Hawkes, Kartik Chundru, Leigh Jackson, Kashyap A. Patel, Anna Murray, Andrew R. Wood, Caroline F. Wright, Michael N. Weedon, Timothy M. Frayling, Robin N. Beaumont
Journal: Nature Genetics (2025)

Abstract The contribution of rare noncoding genetic variation to common phenotypes is largely unknown, as a result of a historical lack of population-scale whole-genome sequencing data and the difficulty of categorizing noncoding variants into functionally similar groups. To begin addressing these challenges, we performed a cis association analysis using whole-genome sequencing data, consisting of 1.1 billion variants, 123 million noncoding aggregate-based tests and 2,907 circulating protein levels in ~50,000 UK Biobank participants. We identified 604 independent rare noncoding single-variant associations with circulating protein levels. Unlike protein-coding variation, rare noncoding genetic variation was almost as likely to increase or decrease protein levels. Rare noncoding aggregate testing identified 357 conditionally independent associated regions. Of these, 74 (21%) were not detectable by single-variant testing alone. Our findings have important implications for the identification, and role, of rare noncoding genetic variation associated with common human phenotypes, including the importance of testing aggregates of noncoding variants.
Cross-ancestry genome-wide association study and systems-level integrative analyses implicate new risk genes and therapeutic targets for depression
Authors: Yifan Li, Xinglun Dang, Rui Chen, Zhaowei Teng, Junyang Wang, Shiwu Li, Yingying Yue, Brittany L. Mitchell, Yong Zeng, Yong-Gang Yao, Ming Li, Zhongchun Liu, Yonggui Yuan, Tao Li, Zhijun Zhang, Xiong-Jian Luo
Journal: Nature Human Behaviour (2025)
Distinct effects of early-stage and late-stage socioeconomic factors on brain and behavioral traits
Authors: Qiang Xu, Su Lui, Yuan Ji, Jingliang Cheng, Long Jiang Zhang, Bing Zhang, Wenzhen Zhu, Zuojun Geng, Guangbin Cui, Quan Zhang, Weihua Liao, Yongqiang Yu, Hui Zhang, Bo Gao, Xiaojun Xu, Tong Han, Zhenwei Yao, Wen Qin, Feng Liu, Meng Liang, Jilian Fu, Jiayuan Xu, Peng Zhang, Wei Li, Dapeng Shi, Caihong Wang, Jia-Hong Gao, Zhihan Yan, Feng Chen, Jiance Li, Jing Zhang, Dawei Wang, Wen Shen, Yanwei Miao, Junfang Xian, Meiyun Wang, Zhaoxiang Ye, Xiaochu Zhang, Xi-Nian Zuo, Kai Xu, Shijun Qiu, Chunshui Yu, Chunshui Yu, Quan Zhang, Junping Wang, Xue Zhang, Xinjun Suo, Congcong Yuan, Hui Xue, Tianying Gao, Junpeng Liu, Yanjun Li, Xi Guo, Lixue Xu, Jiajia Zhu, Huaigui Liu, Fangshi Zhao, Jie Sun, Yongjie Xu, Huanhuan Cai, Jie Tang, Yaodan Zhang, Yongqin Xiong, Xianting Sun, Nannan Pan, Jiayang Yang, Nana Liu, Ya Wen, Dan Zhu, Bingjie Wu, Wenshuang Zhu, Qingqing Diao, Yujuan Cao, Bingbing Yang, Lining Guo, Yingying Xie, Jiahui Lin, Zhimin Li, Yan Zhang, Kaizhong Xue, Zirui Wang, Junlin Shen, Meng Liang, Xuejun Zhang, Hao Ding, Qian Su, Mulin Jun Li, Shijie Zhang, Lun Ma, Yan Bai, Min Guan, Wei Wei, Peifang Miao, Fuhong Duan, Yafei Guo, Weijian Wang, Lijuan Zheng, Li Lin, Yunfei Wang, Han Zhang, Xinyuan Zhang, Zhao Qing, Sichu Wu, Junxia Wang, Yi Sun, Yang He, Xi-Nian Zuo, Zhe Zhang, Yin-Shan Wang, Quan Zhou, Tian Tian, Yi Liang, Yujie Liu, Hui Zeng, Jingxian Chen, Haitao Ge, Peng Xu, Cailuan Lu, Chen Wu, Xiaoying Yang, Yuzhao Wang, Yankai Wu, Xuran Feng, Ling Li, Duo Gao, Rujing Zha, Ying Li, Lizhuang Yang, Ying Chen, Ling Zuo, Jianqiao Ge, Guoyuan Yang, Wen Wang, Linfeng Yan, Yang Yang, Jin Zhang, Qian Wang, Xiaoxia Qu, Ying Wang, Fei Yuan, Li Hu, Jizhen Li, Weiwei Wang, Yujing Zhou, Miaomiao Long, Lihua Liu, Xiaohu Li, Xiaoshu Li, Yunjun Yang, Nengzhi Xia, Weihua Liao, Shuai Yang, Youming Zhang, Jing Zhang, Guangyao Liu, Laiyang Ma, Xiaochun Wang, Ying Lei, Bo Gao, Gang Zhang, Kang Yuan, Jingjing Xu, Xiaojun Guan, Yuankai Lin, Hui Juan Chen, Yuchuan Fu, Yi Lu, Jun Guo, Hao Lu, Yue Wu
Journal: Nature Neuroscience (2025)
Left Ventricular Entry to Reduce Brain Lesions During Catheter Ablation: A Randomized Trial
Authors: Gregory M. Marcus, Roderick Tung, Edward P. Gerstenfeld, Trisha F. Hue, Feng Lin, Jing Cheng, J. Peter Weiss, Wendy S. Tzou, Henry Hsia, Ashkan Ehdaie, Daniel H. Cooper, T. Jared Bunch, Jeffrey Arkles, Babak Nazer, Adam Lee, Alexios Hadjis, Duy T. Nguyen, Mihail G. Chelu, Joshua Moss, Jonathan C. Hsu, Miguel Valderrábano, Prashant D. Bhave, Andrew D. Beaser, Arvindh Kanagasundram, Oussama Wazni, Jason Bradfield, Grace Wall, Kathleen Chang, Michelle Yang, Gabrielle Montenegro, Sabrina Jarrott, Joel H. Kramer, Anthony S. Kim, Yvonne M. Morris, William P. Dillon
Journal: Circulation (2025)

BACKGROUND: Catheter ablation of ventricular arrhythmias, one of the most rapidly growing procedures in cardiac electrophysiology, is associated with magnetic resonance imaging–detected brain lesions in more than half of cases. Although a retrograde aortic approach is conventional, modern tools enable entry through a transseptal approach that may avoid embolization of debris from the arterial system. We sought to test the hypothesis that a transseptal puncture would mitigate brain injury compared with a retrograde aortic approach. METHODS: The TRAVERSE trial (Transseptal Versus Retrograde Aortic Ventricular Entry to Reduce Systemic Emboli) was a multicenter randomized controlled comparative effectiveness trial. Patients with left ventricular arrhythmias undergoing catheter ablation procedures were randomly assigned to a transseptal puncture approach compared (1:1) with a retrograde aortic approach. The primary outcome was the presence of an acute brain lesion detected by magnetic resonance imaging. Secondary outcomes included clinically manifest complications, procedural efficacy, and 6-month neurocognitive assessments. RESULTS: Among the 62 patients randomly assigned to a retrograde aortic approach with postoperative brain magnetic resonance imaging, 28 (45%) exhibited an acute brain lesion compared with 19 of the 69 (28%) of those randomized to a transseptal puncture ( P =0.036). No differences in clinically manifest complications or procedural efficacy were observed. More patients in the retrograde aortic arm were categorized as having a high likelihood of cognitive impairment at 6 months (33% compared with 19% of those in the transseptal arm), but substantial loss to follow-up was present. CONCLUSIONS: Among patients undergoing left ventricular catheter ablation procedures, a transseptal approach reduced the risk of acute brain lesions by nearly half compared with a retrograde aortic approach without sacrificing safety or efficacy. Given a likely embolic pathogenesis, the brain magnetic resonance imaging findings may reflect a propensity to other organ damage; these findings may extend to other procedures requiring left ventricular entry. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03946072
PTEN mutations impair CSF dynamics and cortical networks by dysregulating periventricular neural progenitors
Authors: Tyrone DeSpenza, Emre Kiziltug, Garrett Allington, Daniel G. Barson, Stephen McGee, David O’Connor, Stephanie M. Robert, Kedous Y. Mekbib, Pranav Nanda, Ana B. W. Greenberg, Amrita Singh, Phan Q. Duy, Francesca Mandino, Shujuan Zhao, Anna Lynn, Benjamin C. Reeves, Arnaud Marlier, Stephanie A. Getz, Carol Nelson-Williams, Hermela Shimelis, Lauren K. Walsh, Junhui Zhang, Wei Wang, Mackenzi L. Prina, Annaliese OuYang, Asan F. Abdulkareem, Hannah Smith, John Shohfi, Neel H. Mehta, Evan Dennis, Laetitia R. Reduron, Jennifer Hong, William Butler, Bob S. Carter, Engin Deniz, Evelyn M. R. Lake, R. Todd Constable, Mustafa Sahin, Siddharth Srivastava, Kellen Winden, Ellen J. Hoffman, Marina Carlson, Murat Gunel, Richard P. Lifton, Seth L. Alper, Sheng Chih Jin, Michael C. Crair, Andres Moreno-De-Luca, Bryan W. Luikart, Kristopher T. Kahle
Journal: Nature Neuroscience (2025)
Secure and federated genome-wide association studies for biobank-scale datasets
Authors: Hyunghoon Cho, David Froelicher, Jeffrey Chen, Manaswitha Edupalli, Apostolos Pyrgelis, Juan R. Troncoso-Pastoriza, Jean-Pierre Hubaux, Bonnie Berger
Journal: Nature Genetics (2025)

Sharing data across institutions for genome-wide association studies (GWAS) would enhance the discovery of genetic variation linked to health and disease1,2. However, existing data-sharing regulations limit the scope of such collaborations3. Although cryptographic tools for secure computation promise to enable collaborative analysis with formal privacy guarantees, existing approaches either are computationally impractical or do not implement current state-of-the-art methods4–6. We introduce secure federated genome-wide association studies (SF-GWAS), a combination of secure computation frameworks and distributed algorithms that empowers efficient and accurate GWAS on private data held by multiple entities while ensuring data confidentiality. SF-GWAS supports widely used GWAS pipelines based on principal-component analysis or linear mixed models. We demonstrate the accuracy and practical runtimes of SF-GWAS on five datasets, including a UK Biobank cohort of 410,000 individuals, showcasing an order-of-magnitude improvement in runtime compared to previous methods. Our work enables secure collaborative genomic studies at unprecedented scale. SF-GWAS is a workflow for secure, federated genome-wide association studies, implementing accurate, privacy-preserving principal-component analysis, linear/logistic regression and linear mixed model methods for biobank-scale multisite analyses.
Reactivation of Oxidized Soluble Guanylate Cyclase as a Novel Treatment Strategy to Slow Progression of Calcific Aortic Valve Stenosis: Preclinical and Randomized Clinical Trials to Assess Safety and Efficacy
Authors: Bin Zhang, Maurice Enriquez-Sarano, Hartzell V. Schaff, Hector I. Michelena, Carolyn M. Roos, Michael A. Hagler, Heyu Zhang, Grace Casaclang-Verzosa, Runqing Huang, Anna Bartoo, Sushant Ranadive, Michael J. Joyner, Sorin Pislaru, Vuyisile Nkomo, Walter K. Kremers, Philip Araoz, Gurpreet Singh, Michael A. Walters, Jon Hawkinson, Kevin Y. Cunningham, Jaeyun Sung, Brandon Dunagan, Ze Yi, Jordan D. Miller
Journal: Circulation (2025)

BACKGROUND: Pharmacological treatments for fibrocalcific aortic valve stenosis (FCAVS) have been elusive for &gt;50 years. Here, we tested the hypothesis that reactivation of oxidized sGC (soluble guanylate cyclase), the primary receptor for nitric oxide, with ataciguat is a safe and efficacious strategy to slow progression of FCAVS. METHODS: We used quantitative real-time reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry to characterize sGC signaling and the biological effects of ataciguat on signaling cascades related to nitric oxide, calcification, and fibrosis in excised human aortic valve tissue, aortic valve interstitial cells, and mouse aortic valves. We then conducted randomized, placebo-controlled phase I (14-day safety/tolerance) and phase II (6-month efficacy) trials in patients with moderate aortic valve stenosis. RESULTS: In excised human tissue, we found robust losses in sGC signaling despite upregulation of sGC subunits. In vitro, ataciguat increased sGC signaling and reduced BMP2 (bone morphogenetic protein 2) signaling in aortic valve interstitial cells. In mice with established FCAVS, treatment with ataciguat attenuated BMP signaling and slowed progression of valve calcification and dysfunction. In a phase I, randomized, placebo-controlled trial, treatment with ataciguat for 2 weeks was safe and well tolerated in patients with moderate FCAVS ( https://www.clinicaltrials.gov ; Unique identifier: NCT02049203). In a separate phase II, randomized, placebo-controlled trial, treatment with ataciguat for 6 months slowed the progression of aortic valve calcification and tended to slow the progression of valvular and ventricular dysfunction in patients with moderate FCAVS ( https://www.clinicaltrials.gov ; Unique identifier: NCT02481258). CONCLUSIONS: Collectively, this study highlights the therapeutic potential of the targeted restoration of the diseased/inactive form of sGC for treatment of FCAVS. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02049203. URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02481258.
Skill dependencies uncover nested human capital
Authors: Moh Hosseinioun, Frank Neffke, Letian Zhang, Hyejin Youn
Journal: Nature Human Behaviour (2025)

Abstract Modern economies require increasingly diverse and specialized skills, many of which depend on the acquisition of other skills first. Here we analyse US survey data to reveal a nested structure within skill portfolios, where the direction of dependency is inferred from asymmetrical conditional probabilities—occupations require one skill conditional on another. This directional nature suggests that advanced, specific skills and knowledge are often built upon broader, fundamental ones. We examine 70 million job transitions to show that human capital development and career progression follow this structured pathway in which skills more aligned with the nested structure command higher wage premiums, require longer education and are less likely to be automated. These disparities are evident across genders and racial/ethnic groups, explaining long-term wage penalties. Finally, we find that this nested structure has become even more pronounced over the past two decades, indicating increased barriers to upward job mobility.
How institutions can better support international early-career researchers
Authors: Marek Lubośny, Pavanee Annasawmy, Itziar Burgués Martínez, Timotej Turk Dermastia, Lucía Espasandín, Joana Filipa Fernandes, Marcos Fontela, Cristina Galobart, Odei Garcia-Garin, Inês Gregório, Natalia Llopis Monferrer, María López-Acosta, Mikołaj Mazurkiewicz, Nerea Piñeiro-Juncal, Amanda Schadeberg, Costanza Scopetani, Anna Sowa, Giuseppe Suaria, Anastasia Tsiola
Journal: Nature Human Behaviour (2025)
Clinical and cost-effectiveness of a home-based health promotion intervention for older people with mild frailty in England: a multicentre, parallel-group, randomised controlled trial
Authors: Kate Walters, Rachael Frost, Christina Avgerinou, Sarah Kalwarowsky, Claire Goodman, Andrew Clegg, Louise Marston, Shengning Pan, Jane Hopkins, Claire Jowett, Rekha Elaswarapu, Benjamin Gardner, Farah Mahmood, Matthew Prescott, Gillian Thornton, Dawn A Skelton, Rebecca L Gould, Claudia Cooper, Vari M Drennan, Kalpa Kharicha, Pip Logan, Rachael Hunter
Journal: The Lancet Healthy Longevity (2025)
Impact of morbilliform drug eruptions on health-related quality of life: a qualitative analysis
Authors: Allison Yan, Matthew Gallardo, Cole Veliky, Jacob McFeeters, Kelsey Nusbaum, Kirsten Johnson, Kristopher Fisher, Abraham Korman, Benjamin Kaffenberger
Journal: British Journal of Dermatology (2025)

Quality of life has not been well-explored in patients hospitalized with morbilliform drug eruptions. We found that morbilliform drug eruptions impacted patients across six major domains: impact on other medical conditions, self-image, medical distrust, impact on diet, mental health, and physical symptoms. Dermatologists and other healthcare providers should remain cognizant of the impacted domains in the counseling and management of this patient population.