tbuckley/cabot-search huggingface dataset:
Microbial diversity and fitness in the gut–brain axis: influences on developmental risk for Alzheimer’s disease
Authors: Angelo M. Jamerlan, Seong Soo A. An, John P. Hulme
Journal: Gut Microbes (2025)

The gut-brain axis (GBA) denotes the dynamic and bidirectional communication system that connects the gastrointestinal tract and the central nervous system (CNS). This review explored this axis, focusing on the role of microbial diversity and fitness in maintaining gastrointestinal health and preventing neurodegeneration, particularly in Alzheimer's disease (AD). Gut dysbiosis, characterized by the imbalance in populations of beneficial and harmful bacteria, has been associated with increased systemic inflammation, neuroinflammation, and the progression of AD through pathogenic mechanisms involving amyloid deposition, tauopathy, and increased blood-brain barrier (BBB) permeability. Emerging evidence highlighted the therapeutic potential of probiotics, dietary interventions, and intermittent fasting in restoring microbial balance, reducing inflammation, and minimizing neurodegenerative risks. Probiotics and synbiotics are promising in helping improve cognitive function and metabolic health, while dietary patterns like the Mediterranean diet were linked to decreased neuroinflammation and enhanced gut-brain communication. Despite significant advancement, further research is needed to elucidate the specific microbial strains, metabolites, and mechanisms influencing brain health. Future studies employing longitudinal designs and advanced omics technologies are essential to developing targeted microbiome-based therapies for managing AD-related disorders.
Corrigendum to “Overcoming P-glycoprotein-mediated multidrug resistance in cancer cells through micelle-forming PHPMA-b-PPO diblock copolymers for doxorubicin delivery” [Journal of Controlled Release 381 (2025) 113645]
Authors: Martin Kaňa, Alena Braunová, Daniil Starenko, Markéta Frejková, Jan Bouček, Blanka Říhová, Marek Kovář, Tomáš Etrych, Milada Šírová
Journal: Journal of Controlled Release (2025)
Protection against experimental necrotizing enterocolitis by fecal filtrate transfer requires an active donor virome
Authors: Malene Roed Spiegelhauer, Simone Margaard Offersen, Xiaotian Mao, Michela Gambino, Dennis Sandris Nielsen, Duc Ninh Nguyen, Anders Brunse
Journal: Gut Microbes (2025)

Necrotizing enterocolitis (NEC) remains a frequent catastrophic disease in preterm infants, and fecal filtrate transfer (FFT) has emerged as a promising prophylactic therapy. This study explored the role of virome viability for the protective effect of FFT. Using ultraviolet (UV) irradiation, we established a viral inactivation protocol and administered FFT, UV-inactivated FFT (iFFT) or sterile saline orally to preterm piglets at risk for experimental NEC. The gut pathology and barrier properties were assessed, while the microbiome was explored by 16S rRNA amplicon and metavirome sequencing. Like in prior studies, FFT reduced NEC severity and intestinal inflammation, while these effects were absent in the iFFT group. Unexpectedly, piglets receiving FFT exhibited mild side effects in the form of early-onset diarrhea. The FFT also converged the gut colonization by increased viral heterogeneity and a reduced abundance of pathobionts like Clostridium perfringens and Escherichia. In contrast, the gut microbiome of iFFT recipients diverged from both FFT and the controls. These findings highlight the clear distinction between the ability of active and inactivate viromes to modulate gut microbiota and decrease pathology. The efficacy of FFT may be driven by active bacteriophages, and loss of virome activity could have consequences for the treatment efficacy.
Fabp4 is essential for the maintenance of leukemia stem cells while sparing hematopoietic stem cells
Authors: Cheng Xing, Huifang Zhang, Mengqiu Zheng, Qian Lu, Yujia Tao, Shina Xu, Yang Xiao, Long Liang, Haodong Xu, Shuqian Xu, Hongling Peng, Yue Sheng
Journal: Leukemia (2025)
Routes of Marijuana Use — Behavioral Risk Factor Surveillance System, 22 U.S. States and Two Territories, 2022
Authors: Zerleen S. Quader, Douglas R. Roehler, Alana M. Vivolo-Kantor, Jean Y. Ko
Journal: MMWR Morbidity and Mortality Weekly Report (2025)

Access to and use of cannabis in the United States has increased as new product types emerge in the marketplace, and as additional states legalize its use for medical and nonmedical purposes. To tailor education messages for preventing adverse health effects of cannabis use, understanding the routes of use of these products in the general population is important. The 2022 Behavioral Risk Factor Surveillance System included a newly revised optional marijuana module comprising questions on marijuana routes of use among adults aged ≥18 years who used marijuana during the past 30 days (current use). Twenty-two states and two territories administered the optional marijuana module in 2022. Weighted prevalences (with 95% CIs) of current and daily or near-daily marijuana use, as well as prevalence of each route of use, were reported overall and by demographic characteristics and, among women aged ≤49 years, by pregnancy status. Among the 15.3% of respondents who reported current marijuana use, smoking was the most frequent route (79.4%), followed by eating (41.6%), vaping (30.3%), and dabbing (inhaling heated concentrated cannabis) (14.6%). Vaping and dabbing were most prevalent among persons aged 18-24 years. Intervention measures intended for persons who smoke cannabis are important; however, understanding health outcomes associated with other routes of use might have substantial public benefit.
Controlled Substance Prescribing Patterns Among Fatal Overdose Decedents with an Opioid, Stimulant, or Both Contributing to Death — Pennsylvania, 2017–2022
Authors: Stephanie Hayden, Stanley M. Murzynski, Ashley Bolton, Carrie Thomas Goetz
Journal: MMWR Morbidity and Mortality Weekly Report (2025)

Psychostimulant (stimulant)-related overdose death rates have increased sharply in the United States since 2010, and in 2022, 32% of all U.S. overdose deaths involved stimulants. Data on deaths during 2017-2022 from CDC's State Unintentional Drug Overdose Reporting System were linked to 2014-2022 Pennsylvania Prescription Drug Monitoring Program data; the Pennsylvania Department of Health's Office of Drug Surveillance and Misuse Prevention analyzed controlled substance dispensation patterns during the 3 years preceding death among overdose decedents for whom opioids, stimulants, or both contributed to death; statistical analyses were performed on prescription drug dispensation patterns. Comparing overdose deaths in 2022 with those in 2017, deaths involving opioids without stimulants decreased from 2,974 to 1,995, deaths involving stimulants without opioids increased from 300 to 549, and deaths involving both opioids and stimulants increased from 1,703 to 2,346. Irrespective of whether an opioid, stimulant, or both contributed to death, decedents filled more opioid (67.7%, 74.1%, and 63.9%, respectively) than stimulant (10.6%, 11.6%, and 13.4%, respectively) prescriptions preceding death. A higher proportion of stimulant overdose decedents without an opioid contributing to death (74.1%) filled opioid prescriptions compared with decedents whose deaths involved opioids without stimulants or both opioids and stimulants (67.7% and 63.9%, respectively). Opioid prescribing, rather than stimulant prescribing, might be an important potential risk factor for stimulant-related overdose death.
Elexacaftor/tezacaftor/ivacaftor in children aged ≥6 years with cystic fibrosis heterozygous for<i>F508del</i>and a minimal function mutation: Results from a 96-week open-label extension study
Authors: Marcus A Mall, Claire E Wainwright, Julian Legg, Mark Chilvers, Sylvia Gartner, Anna-Maria Dittrich, Florian Stehling, Sarah Conner, Sebastian Grant, Nina Suresh, Tanya G Weinstock, Jane C Davies
Journal: European Respiratory Journal (2025)

Aims Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was efficacious and safe in children aged 6–11 years with cystic fibrosis (CF) heterozygous for F508del and a minimal function CFTR variant ( F /MF genotypes) in a 24-week, placebo-controlled trial. We conducted a 96-week open-label extension study for children who completed the 24-week parent study. Methods In this phase 3b extension study, dosing was based on weight and age with children weighing &lt;30 kg and aged &lt;12 years receiving ELX 100 mg once daily (qd), TEZ 50 mg qd, and IVA 75 mg every 12 h (q12) and children ≥30 kg or ≥12 years receiving ELX 200 mg qd, TEZ 100 mg qd, and IVA 150 mg q12. Primary endpoint was safety and tolerability. Secondary and other efficacy endpoints included absolute changes from parent study baseline in sweat chloride concentration, LCI 2.5 , ppFEV 1 , and CFQ-R respiratory domain score. Results A total of 120 children were enrolled and dosed. One hundred and eighteen children (98.3%) had adverse events (AEs), which for most were mild (43.3%) or moderate (48.3%) in severity. The most common AEs (≥20% of children) were COVID-19 (58.3%), cough (51.7%), nasopharyngitis (45.0%), pyrexia (40.0%), headache (37.5%), upper respiratory tract infection (30.8%), oropharyngeal pain (26.7%), rhinitis (24.2%), abdominal pain (22.5%), and vomiting (20.0%). Children who transitioned from the placebo and ELX/TEZ/IVA groups of the parent study had improvements from parent study baseline at Week 96 in mean sweat chloride concentration (−57.3 [95% CI: −61.6, −52.9] and −57.5 [95% CI: −62.0, −53.0] mmol·L −1 ), LCI 2..5 (−1.74 [95% CI: −2.09, −1.38] and −2.35 [95% CI: −2.72, −1.97] units), ppFEV 1 (6.1 [95% CI: 2.6, 9.7] and 6.9 [95% CI: 3.2, 10.5] percentage points), and CFQ-R respiratory domain score (6.6 [95% CI: 2.5, 10.8] and 2.6 [95% CI: −1.6, 6.8] points). Conclusions ELX/TEZ/IVA treatment was generally safe and well-tolerated, with a safety profile consistent with parent study and older age groups. After starting ELX/TEZ/IVA, children had robust improvements in sweat chloride concentration and lung function that were maintained through 96 weeks. These results demonstrate the safety and durable efficacy of ELX/TEZ/IVA in this pediatric population. (Clinical Trials.gov, NCT04545515 ; EudraCT, 2020-001404-42)
Is regulatory science ready for artificial intelligence?
Authors: Thomas Hartung, Maurice Whelan, Weida Tong, Robert M Califf
Journal: npj Digital Medicine (2025)

Abstract Trust is key in AI for regulatory science, but its definition is debated. If AI models use different features yet perform similarly, which should be trusted? If scientific theories must be testable, how critical is explainability? At the Global Summit on Regulatory Science (GSRS24), regulators agreed that successful AI adoption requires ongoing dialogue, adaptability, and AI-trained personnel to harness its potential for regulatory responsibilities in the evolving 21st-century landscape.
S-palmitoylation of c-MET by CK2α-mediated zDHHC15 phosphorylation drives glioblastoma stem cell tumorigenicity
Authors: Yang Wang, Zhengxin Chen, Rui Li, Dong Wei, Shuai Wang, Hui Luo, Yiming Tu, Cen Liu, Haibiao Xu, Jiachen Xu, Mingtian Ding, Minghui Meng, Tao Fu, Yangyin Ding, Jun Yin, Wei Wu, Jing Ji, Huibo Wang
Journal: Neuro-Oncology (2025)

Abstract Background The c-MET signaling pathway is crucial for the self-renewal and tumorigenic capacity of cancer stem cells, including glioblastoma stem cells (GSCs). Despite its recognized importance, the precise mechanisms of c-MET activation in these cells remain elusive. This study aimed to elucidate the key regulatory elements and mechanisms governing c-MET function in GSCs. Methods The mediation of S-palmitoylation and dimerization of c-MET by zDHHC15 was validated using metabolic labeling, acyl-PEG exchange (APE), BS3 crosslinking, and co-immunoprecipitation. The role of the CK2α-zDHHC15-c-MET axis in tumorigenesis, along with the anti-tumor efficacy of TVB-3166, was confirmed through cell proliferation, limiting dilution, and intracranial tumor growth assays. Results We revealed that zDHHC15, a member of the DHHC family of palmitoyl acyltransferases, mediates the palmitoylation of c-MET at Cys801, which is critical for c-MET O-glycosylation, dimerization, and activation. We further identified a novel regulatory loop in which CK2α phosphorylates zDHHC15 at Tyr92, increasing its stability and c-MET binding, thereby enhancing c-MET palmitoylation. zDHHC15 was found to be specifically enriched in GSCs, and its targeted knockdown markedly impaired their self-renewal and tumorigenic capabilities both in vitro and in vivo. Therapeutically, we introduced TVB-3166, an inhibitor of c-MET S-palmitoylation, which demonstrated robust inhibitory effects on GSC growth in orthotopic xenograft models. Conclusions This study establishes the CK2α-zDHHC15-c-MET axis as a pivotal regulatory hub in GSC maintenance and identifies c-MET S-palmitoylation as a novel and promising therapeutic target for the treatment of glioblastoma.
Prognostic value of cardiopulmonary exercise testing in pulmonary arterial hypertension
Authors: Andrea Baccelli, Rocco F Rinaldo, Gulammehdi Haji, Rachel J Davies, Francesco Lo Giudice, Wendy Gin-Sing, Beatrice Vigo, Stefano Centanni, J Simon R Gibbs, Luke S Howard
Journal: European Respiratory Journal (2025)

Background Current guidelines recommend a four-strata model based on World Health Organization functional class (WHO-FC), 6-min walk distance (6MWD), and serum levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) for risk stratification in patients with pulmonary arterial hypertension (PAH) during follow-up. We explored the relevance of using cardiopulmonary exercise testing (CPET) as the exercise parameter in place of 6MWD at first reassessment after treatment initiation in PAH. Methods Incident treatment-naïve patients with idiopathic, heritable, drug/toxins-induced, and connective tissue disease-associated PAH between 2010 and 2022 were analysed. Correlations between CPET and haemodynamic and right ventricular (RV) function parameters were explored and those which were significant were carried forward to assess association with survival. Independent predictors were used to derive a four-strata CPET score. Results 262 patients were included. CPET parameters showed better correlations with haemodynamics and RV function than 6MWD. The CPET score included peak oxygen uptake (peak VO 2 ), the slope relating ventilation to carbon dioxide production (VE/VCO 2 slope), and peak oxygen pulse. The four-strata model based on WHO-FC, BNP, and CPET score predicted survival at the time of the first re-evaluation, with better accuracy than the model including 6MWD (c-index 0.81 versus 0.71). The CPET score on its own also performed well (c-index 0.82) with a greater spread between categories. Treatment-associated changes in peak VO 2 and oxygen pulse predicted survival, while changes in 6MWD did not. Conclusions A simplified four-strata CPET score either alone or included with BNP and WHO-FC accurately predicts survival at follow-up in PAH.
Relationship between theratyping in nasal epithelial cells and clinical outcomes in people with cystic fibrosis
Authors: Felix Ratjen, Sanja Stanojevic, Tarini Gunawardena, Paul D W Eckford, Julie Avolio, Michelle Shaw, Claire Bartlett, Hong Ouyang, Theo J Moraes, Tanja Gonska, Christine Bear
Journal: European Respiratory Journal (2025)

Background In people with cystic fibrosis (pwCF), human nasal epithelial cultures (HNECs) can be used to assess response to CFTR modulators. However, thresholds of in vitro responses that predict clinical benefit remain poorly understood. In this study we describe the concordance between in vitro response in HNECs and clinical outcomes in pwCF harbouring the F508del variant, treated with either Lumacaftor/Ivacaftor, Tezacaftor/Ivacaftor or Elexacaftor/Tezacaftor/Ivacaftor. Methods Response of HNECs to CFTR modulators was assessed by CFTR-mediated chloride current stimulated by forskolin or inhibited by CFTRInh-172 in both pwCF and healthy controls. Clinical response was defined as the change in Forced Expiratory Volume in 1 s (FEV 1 ), Lung Clearance Index (LCI), sweat chloride or the cystic fibrosis questionnaire respiratory domain (CFQr) between baseline and within 3 months after the start of modulator treatment. Results In 58 unique in vitro :clinical pairs, in vitro measures of functional rescue correlated with changes in FEV 1 , LCI and sweat chloride, but not CFQr. The concordance between in vitro response and clinical outcomes was highest when a composite outcome was used. For example, an in vitro response of 10% of healthy controls had positive and negative predictive values of 90.5 and 100%, respectively, for a clinical response in either FEV 1 , LCI or sweat chloride. Conclusions We identified thresholds of nasal epithelial cell theratype response in pwCF to predict clinical benefit from CFTR modulator therapy. The utility of this therapy testing platform to predict a clinical response improves when multiple clinical outcome measures are combined.
Safety and efficacy of combined portal and hepatic vein embolisation in patients with colorectal liver metastases (DRAGON1): a multicentre, single-arm clinical trial
Authors: Remon Korenblik, Sinéad James, Jens Smits, Rafael Díaz-Nieto, Rob Davis, Benjamin K Y Chan, Joris I Erdmann, IJsbrand A J Zijlstra, Pieter J W Arntz, Otto Kollmar, Martin H Hoffmann, David G Vass, Richard Lindsay, Matteo Serenari, Alberto Cappelli, Paul D Gobardhan, Farshad Imani, Yiliam Fundora Suarez, Fernando Gómez Muños, Dirk J Grünhagen, Adriaan Moelker, Kay J Pieterman, Jörg Kleeff, Walter A Wohlgemuth, Eric Herrero, Arantxa Gelabert, Stefan Breitenstein, Nico Seeger, Olivier Detry, Laurent Gerard, Per A Sandström, Bergthor Björnsson, Luca A Aldrighetti, Francesco De Cobelli, Wouter K G Leclercq, Laurens J van Baardewijk, Daniel Croagh, Diederick W De Boo, T Peter Kingham, Fourat Ridouani, Peter Metrakos, David Valenti, Jennifer Kalil, Åsmund A Fretland, Ulrik Carling, Guillaume Martel, Stephen Ryan, Venkatesha Udupa, Andrew Macdonald, Jordan C Tasse, Gregor A Stavrou, Elmar Spuentrup, Francisco G Borobia, Eva Criado, Ernesto Sparrelid, Martin Delle, Jordi Navinés-López, Jaume Sampere Moragues, Esteban Cugat Andorrà, Andreas Schnitzbauer, Thomas J Vogl, Jan Heil, John N Primrose, Sachin Modi, Suomi M G Fouraschen, Reinoud P H Bokkers, Marieke T de Boer, Inne H M Borel Rinkes, Maarten L J Smits, Thomas Gruenberger, Ivan Baclija, Kevin G Billingsley, David C Madoff, Alejandro Serrablo, Luis Sarriá, Xiaoying Wang, Qu Xudong, Bjorn Winkens, Steven W L Olde Damink, Marc H A Bemelmans, Maxime J L Dewulf, Christoph A Binkert, Erik Schadde, Christiaan van der Leij, Ronald M van Dam
Journal: The Lancet Regional Health - Europe (2025)
Advanced Materials for Biological Field‐Effect Transistors (Bio‐FETs) in Precision Healthcare and Biosensing
Authors: Minal Pandey, Manish Bhaiyya, Prakash Rewatkar, Jitendra B. Zalke, Nitin P. Narkhede, Hossam Haick
Journal: Advanced Healthcare Materials (2025)

Abstract Biological Field Effect Transistors (Bio‐FETs) are redefining the standard of biosensing by enabling label‐free, real‐time, and extremely sensitive detection of biomolecules. At the center of this innovation is the fundamental empowering role of advanced materials, such as graphene, molybdenum disulfide, carbon nanotubes, and silicon. These materials, when harnessed with the downstream biomolecular probes like aptamers, antibodies, and enzymes, allow Bio‐FETs to offer unrivaled sensitivity and precision. This review is an exposition of how advancements in materials science have permitted Bio‐FETs to detect biomarkers in extremely low concentrations, from femtomolar to attomolar levels, ensuring device stability and reliability. Specifically, the review examines how the incorporation of cutting‐edge materials architectures, like flexible / stretchable and multiplexed designs, is expanding the frontiers of biosensing and contributing to the development of more adaptable and user‐friendly Bio‐FET platforms. A key focus is placed on the synergy of Bio‐FETs with artificial intelligence (AI), the Internet of Things (IoT), and sustainable materials approaches as fast‐tracking toward transition from research into practical healthcare applications. The review also explores current challenges such as material reproducibility, operational durability, and cost‐effectiveness. It outlines targeted strategies to address these hurdles and facilitate scalable manufacturing. By emphasizing the transformative role played by advanced materials and their cementing position in Bio‐FETs, this review positions Bio‐FETs as a cornerstone technology for the future healthcare solution for precision applications. These advancements would lead to an era where material innovation would herald massive strides in biomedical diagnostics and subsume.
Association Between Occupational Exposure and Sinus Surgery Outcomes in Chronic Rhinosinusitis: A Prospective Study
Authors: G. Vansteelant, D. A. E. Dietz de Loos, S. Ronsmans, M. Samaha, D. Langer, S. Keirsbilck, P. Rombaux, C. Huart, M. Jorissen, W. Fokkens, B. Nemery, P. W. Hellings, V. Hox
Journal: Allergy (2025)
Sedentary Behavior and Light-Intensity Physical Activity During Pregnancy and Cardiovascular Health: A Science Advisory From the American Heart Association
Authors: Kara M. Whitaker, Bethany Barone Gibbs, Marie-France Hivert, Nour Makarem, Elizabeth Moxley, Jason Vaught, Kelly R. Evenson
Journal: Circulation (2025)

The Physical Activity Guidelines for Americans supports sitting less and moving more. Growing evidence suggests that a waking behavior profile with less sedentary behavior and more light-intensity physical activity is associated with more favorable cardiovascular health. Remarkably, little is known about how these behaviors relate to cardiovascular health during pregnancy. The purpose of this American Heart Association science advisory is to describe the existing evidence on device-measured sedentary behavior and light-intensity physical activity in relation to cardiovascular health during pregnancy and to make specific calls to action for future research to improve health outcomes and to promote health equity. Outcomes included adverse pregnancy outcomes associated with increased risk of cardiovascular disease and the American Heart Association’s Life’s Essential 8 health factor components (blood pressure, lipids, glucose, and gestational weight gain). Findings from observational studies are mixed, with preliminary evidence demonstrating an association between high sedentary behavior and increased risk of hypertensive disorders of pregnancy, shorter gestational age at delivery, low or high birth weight, and elevated maternal blood pressure, lipids, glucose, and gestational weight gain. Findings for light-intensity physical activity are limited by fewer studies and are less compelling. Experimental evidence evaluating the impact of decreasing sedentary behavior or increasing light-intensity physical activity on pregnancy cardiovascular health is weak. Future observational studies with rigorous longitudinal designs and larger, diverse samples are needed to characterize associations and to inform the design of adequately powered randomized controlled trials testing the impact of decreasing sedentary behavior and increasing light-intensity physical activity on cardiovascular health during pregnancy.
Efficacy and safety of SYSA1902 versus reference ustekinumab in moderate-to-severe plaque psoriasis: A multicenter, randomized, phase III study
Authors: Lixin Xia, Guoying Miao, Xiumin Yang, Yumei Li, Yunsheng Liang, Yanling Li, Linfeng Li, Liping Ma, Furen Zhang, Rixin Chen, Xinsuo Duan, Lihua Wang, Yanyan Feng, Ziyan Li, Fengyan Lu, Jinyan Wang, Shuping Guo, Jiawen Zhao, Liming Wu, Yong Cui, Shanshan Li, Chao Ji, Xiaodong Li, Tiechi Lei, Juanli Fan, Xinghua Gao
Journal: Journal of the American Academy of Dermatology (2025)