tbuckley/cabot-search huggingface dataset:
Indoor Air Pollution and Airway Health
Authors: Jared Radbel, Meghan E Rebuli, Howard Kipen, Emily Brigham
Journal: Journal of Allergy and Clinical Immunology (2024)

Because of the disproportionate amount of time that people spend indoors and the complexities of air pollutant exposures found there, indoor air pollution is a growing concern for airway health. Both infiltration of outdoor air pollution into the indoor space and indoor sources (such as smoke from tobacco products, cooking or heating practices and combustion of associated fuels, and household materials) contribute to unique exposure mixtures. Although there is substantial literature on the chemistry of indoor air pollution, research focused on health effects is only beginning to emerge and remains an important area of need to protect public health. We provide a review of emerging literature spanning the past 3 years and relating indoor air exposures to airway health, with a specific focus on the impact of either individual pollutant exposures or common combustion sources on the lower airways. Factors defining susceptibility and/or vulnerability are reviewed with consideration for priority populations and modifiable risk factors that may be targeted to advance health equity.
Incidence of liver complications with hemochromatosis associated HFE p.C282Y homozygosity: The role of central adiposity
Authors: Mitchell R. Lucas, Luke C. Pilling, Janice L. Atkins, David Melzer
Journal: Hepatology (2024)

The HFE p.C282Y+/+ (homozygous) genotype and central adiposity both increase liver disease and diabetes risks, but combined effects are unclear. We estimated waist-to-hip ratio (WHR) associations with incident clinical outcomes in routine care in p.C282Y+/+ participants in the UK Biobank community cohort.
Integrative single-cell and spatial transcriptomic analyses identify a pathogenic cholangiocyte niche and TNFRSF12A as therapeutic target for biliary atresia
Authors: Man-Huan Xiao, Dong Ma, Sihan Wu, Zaoli Huang, Peishi Liang, Huadong Chen, Zhihai Zhong, Wei Li, Fen Wang, Yanlai Tang, Juncheng Liu, Hong Jiang, Xuyang Feng, Zhenhua Luo
Journal: Hepatology (2024)

Biliary atresia (BA) is a devastating fibroinflammatory biliary disease that is the leading indication for pediatric liver transplants worldwide. Although cholangiocytes are the primary target cells, the pathogenic mechanisms involving cholangiocytes remain elusive. Here, we aimed to characterize the pathogenic role of cholangiocytes in BA.
Changes in bodyweight after initiating antiretroviral therapy close to HIV-1 seroconversion: an international cohort collaboration
Authors: Nikos Pantazis, Caroline A Sabin, Sophie Grabar, Marc Van der Valk, Inma Jarrin, Ard van Sighem, Laurence Meyer, Christina Carlander, John Gill, Alain Volny Anne, Bruno Spire, Shema Tariq, Fiona Burns, Dominique Costagliola, Elisa Ruiz-Burga, Giota Touloumi, Kholoud Porter
Journal: The Lancet HIV (2024)
Rethinking the roles of oncogenes: How does oncoprotein loss worsen liver carcinogenesis?
Authors: Angélique Gougelet
Journal: Hepatology (2024)

1Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, F-75006, Paris, France 2Team « Oncogenic functions of beta-catenin signaling in the liver », Équipe labellisée Ligue Nationale contre le Cancer, F-75013, Paris, France Correspondence Angélique Gougelet, Centre de Recherche des Cordeliers, 15, rue de l'école de médecine, 75006 Paris, France. Email: [email protected]
Health equity through CMS collaboration with startups and digital health innovations
Authors: Serena C. Y. Wang, Grace Nickel, Jethro C. C. Kwong, Joseph C. Kvedar
Journal: npj Digital Medicine (2024)

There is a need for digital health innovation focused on bettering the health of marginalized populations. These communities, often insured by Medicaid and Medicare, face complex healthcare barriers that technology can address—emphasizing the role of the Center for Medicaid and Medicare Services (CMS) in fostering innovation. Dasari et al. identify four areas of CMS collaboration with startups: enhancing consumer awareness, leveraging telehealth, streamlining cross-state licensing and billing, and adopting technology-enabled tools.
eRNA-IDO: A One-stop Platform for Identification, Interactome Discovery, and Functional Annotation of Enhancer RNAs
Authors: Yuwei Zhang, Lihai Gong, Ruofan Ding, Wenyan Chen, Hao Rong, Yanguo Li, Fawziya Shameem, Korakkandan Arshad Ali, Lei Li, Qi Liao
Journal: Genomics Proteomics & Bioinformatics (2024)

Abstract Growing evidence supports the transcription of enhancer RNAs (eRNAs) and their important roles in gene regulation. However, their interactions with other biomolecules and their corresponding functionality remain poorly understood. In an attempt to facilitate mechanistic research, this study presents eRNA-IDO, the first integrative computational platform for the identification, interactome discovery, and functional annotation of human eRNAs. eRNA-IDO comprises two modules: eRNA-ID and eRNA-Anno. Functionally, eRNA-ID can identify eRNAs from de novo assembled transcriptomes. eRNA-ID includes eight kinds of enhancer makers, enabling users to customize enhancer regions flexibly and conveniently. In addition, eRNA-Anno provides cell-/tissue-specific functional annotation for both new and known eRNAs by analyzing the eRNA interactome from prebuilt or user-defined networks between eRNAs and protein-coding genes. The prebuilt networks include the Genotype-Tissue Expression (GTEx)-based co-expression networks in normal tissues, The Cancer Genome Atlas (TCGA)-based co-expression networks in cancer tissues, and omics-based eRNA-centric regulatory networks. eRNA-IDO can facilitate research on the biogenesis and functions of eRNAs. The eRNA-IDO server is freely available at http://bioinfo.szbl.ac.cn/eRNA_IDO/.
Flow inefficiencies in non-obstructive HCM revealed by kinetic energy and hemodynamic forces on 4D-flow CMR
Authors: K Pola, Z Ashkir, S Myerson, H Arheden, H Watkins, S Neubauer, P M Arvidsson, B Raman
Journal:  (2024)

Abstract Aims Patients with non-obstructive hypertrophic cardiomyopathy (HCM) exhibit myocardial changes which may cause flow inefficiencies not detectable on echocardiogram. We investigated whether left ventricular (LV) kinetic energy (KE) and hemodynamic forces (HDF) on 4D-flow cardiovascular magnetic resonance (CMR) can provide more sensitive measures of flow in non-obstructive HCM. Methods and results Ninety participants (70 with non-obstructive HCM and 20 healthy controls) underwent 4D-flow CMR. Patients were categorized as phenotype positive (P+) based on maximum wall thickness (MWT) ≥ 15 mm or ≥13 mm for familial HCM, or pre-hypertrophic sarcomeric variant carriers (P−). LV KE and HDF were computed from 4D-flow CMR. Stroke work was computed using a previously validated non-invasive method. P+ and P− patients and controls had comparable diastolic velocities and LV outflow gradients on echocardiography, LV ejection fraction, and stroke volume on CMR. P+ patients had greater stroke work than P− patients, higher systolic KE compared with controls (5.8 vs. 4.1 mJ, P = 0.0009), and higher late diastolic KE relative to P− patients and controls (2.6 vs. 1.4 vs. 1.9 mJ, P &amp;lt; 0.0001, respectively). MWT was associated with systolic KE (r = 0.5, P &amp;lt; 0.0001) and diastolic KE (r = 0.4, P = 0.005), which also correlated with stroke work. Systolic HDF ratio was increased in P+ patients compared with controls (1.0 vs. 0.8, P = 0.03) and correlated with MWT (r = 0.3, P = 0.004). Diastolic HDF was similar between groups. Sarcomeric variant status was not associated with KE or HDF. Conclusion Despite normal flow velocities on echocardiography, patients with non-obstructive HCM exhibited greater stroke work, systolic KE and HDF ratio, and late diastolic KE relative to controls. 4D-flow CMR provides more sensitive measures of haemodynamic inefficiencies in HCM, holding promise for clinical trials of novel therapies and clinical surveillance of non-obstructive HCM.
Age-associated temporal decline in butyrate-producing bacteria plays a key pathogenic role in the onset and progression of neuropathology and memory deficits in 3×Tg-AD mice
Authors: Paula M. Chilton, Smita S. Ghare, Benjamin T. Charpentier, Scott A. Myers, Aakarsha V. Rao, Joseph F. Petrosino, Kristi L. Hoffman, John C. Greenwell, Neetu Tyagi, Jyotirmaya Behera, Yali Wang, Lucy J. Sloan, JingWen Zhang, Christopher B. Shields, Gregory E. Cooper, Leila Gobejishvili, Scott R. Whittemore, Craig J. McClain, Shirish S. Barve
Journal: Gut Microbes (2024)

Alterations in the gut-microbiome-brain axis are increasingly being recognized to be involved in Alzheimer's disease (AD) pathogenesis. However, the functional consequences of enteric dysbiosis linking gut microbiota and brain pathology in AD progression remain largely undetermined. The present work investigated the causal role of age-associated temporal decline in butyrate-producing bacteria and butyrate in the etiopathogenesis of AD. Longitudinal metagenomics, neuropathological, and memory analyses were performed in the 3×Tg-AD mouse model. Metataxonomic analyses showed a significant temporal decline in the alpha diversity marked by a decrease in butyrate-producing bacterial communities and a concurrent reduction in cecal butyrate production. Inferred metagenomics analysis identified the bacterial acetyl-CoA pathway as the main butyrate synthesis pathway impacted. Concomitantly, there was an age-associated decline in the transcriptionally permissive acetylation of histone 3 at lysines 9 and 14 (H3K9/K14-Ac) in hippocampal neurons. Importantly, these microbiome-gut-brain changes preceded AD-related neuropathology, including oxidative stress, tau hyperphosphorylation, memory deficits, and neuromuscular dysfunction, which manifest by 17–18 months. Initiation of oral administration of tributyrin, a butyrate prodrug, at 6 months of age mitigated the age-related decline in butyrate-producing bacteria, protected the H3K9/K14-Ac status, and attenuated the development of neuropathological and cognitive changes associated with AD pathogenesis. These data causally implicate age-associated decline in butyrate-producing bacteria as a key pathogenic feature of the microbiome-gut-brain axis affecting the onset and progression of AD. Importantly, the regulation of butyrate-producing bacteria and consequent butyrate synthesis could be a significant therapeutic strategy in the prevention and treatment of AD.
Microbiota–gut–brain axis: interplay between microbiota, barrier function and lymphatic system
Authors: Miaomiao Zhuang, Xun Zhang, Jun Cai
Journal: Gut Microbes (2024)

The human gastrointestinal tract, boasting the most diverse microbial community, harbors approximately 100 trillion microorganisms comprising viruses, bacteria, fungi, and archaea. The profound genetic and metabolic capabilities of the gut microbiome underlie its involvement in nearly every facet of human biology, from health maintenance and development to aging and disease. Recent recognition of microbiota – gut – brain axis, referring to the bidirectional communication network between gut microbes and their host, has led to a surge in interdisciplinary research. This review begins with an overview of the current understandings regarding the influence of gut microbes on intestinal and blood-brain barrier integrity. Subsequently, we discuss the mechanisms of the microbiota – gut – brain axis, examining the role of gut microbiota-related neural transmission, metabolites, gut hormones and immunity. We propose the concept of microbiota-mediated multi-barrier modulation in the potential treatment in gastrointestinal and neurological disorders. Furthermore, the role of lymphatic network in the development and maintenance of barrier function is discussed, providing insights into lesser-known conduits of communication between the microbial ecosystem within the gut and the brain. In the final section, we conclude by describing the ongoing frontiers in understanding of the microbiota – gut – brain axis's impact on human health and disease.
The ESMO Tumour-Agnostic Classifier and Screener (ETAC-S): a tool for assessing tumour-agnostic potential of molecularly guided therapies and for steering drug development
Authors: C.B. Westphalen, D. Martins-Branco, J.R. Beal, C. Cardone, N. Coleman, A.M. Schram, S. Halabi, S. Michiels, C. Yap, F. André, F. Bibeau, G. Curigliano, E. Garralda, S. Kummar, R. Kurzrock, S. Limaye, S. Loges, A. Marabelle, C. Marchió, J. Mateo, J. Rodon, T. Spanic, G. Pentheroudakis, V. Subbiah
Journal: Annals of Oncology (2024)

Advances in precision oncology led to approval of tumour-agnostic molecularly guided treatment options (MGTOs). The minimum requirements for claiming tumour-agnostic potential remain elusive.
Gut microbiota mediates anxiety-like behaviors induced by chronic infection of <i>Toxoplasma gondii</i> in mice
Authors: Xiaotong Luo, Xiaoying Yang, Shimin Tan, Yongsheng Zhang, Yunqiu Liu, Xiaokang Tian, Yingting Huang, Yuying Zhou, Cheng He, Kun Yin, Daxiang Xu, Xiangyang Li, Fenfen Sun, Renxian Tang, Jianping Cao, Kuiyang Zheng, Yinghua Yu, Wei Pan
Journal: Gut Microbes (2024)

Background Chronic infection with the neurotropic parasite Toxoplasma gondii (T. gondii) can cause anxiety and gut microbiota dysbiosis in hosts. However, the potential role of gut microbiota in anxiety induced by the parasite remains unclear.
Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity
Authors: Kelly M. Jardon, Gijs H. Goossens, Jasper Most, Gianluca Galazzo, Koen Venema, John Penders, Ellen E. Blaak
Journal: Gut Microbes (2024)

Polyphenols exert beneficial effects on host metabolism, which may be mediated by the gut microbiota. We investigated sex-specific differences in microbiota composition and interactions with cardiometabolic parameters after polyphenol supplementation in individuals with overweight/obesity. In a double-blind, randomized, placebo-controlled trial, 19 women and 18 men with normal glucose tolerance and body mass index >25 kg/m2 received epigallocatechin-3-gallate and resveratrol (EGCG+RES, 282 + 80 mg/d) or placebo supplements for 12 weeks. Fecal microbiota composition (16S rRNA gene amplicon sequencing, V3-V4 region), in vivo whole-body fat oxidation (indirect calorimetry), and mitochondrial respiration in permeabilized skeletal muscle fibers (SkM-Ox; ex vivo respirometry) were determined pre- and post-intervention. Overall, EGCG+RES supplementation did not affect gut microbiota composition. Akkermansia, Ruminococcaceae UCG-002, Subdoligranulum, and Lachnospiraceae UCG-004 were more abundant, while Veillonella, Tyzzerella 4, Clostridium innocuum group, Ruminococcus gnavus group, Escherichia-Shigella, and an uncultured Ruminococcaceae family genus were less abundant in women compared to men. In women, only baseline Eubacterium ventriosum group abundance correlated with EGCG+RES-induced changes in SkM-Ox. In men, low Dorea, Barnsiella, Anaerotruncus, Ruminococcus, Subdoligranulum, Coprococcus, Eubacterium ventriosum group, Ruminococcaceae UCG-003, and a Ruminococcaceae family genus abundance, and high Blautia abundance at baseline were associated with improvements in SkM-Ox. Changes in whole-body fat oxidation were not associated with gut microbiota features. We conclude that baseline microbiota composition predicts changes in SkM-Ox as a result of EGCG+RES supplementation in men but not in women. Men may be more prone to diet-induced, gut microbiota-related improvements in cardiometabolic health. These sex-differences should be further investigated in future precision-based intervention studies.
Antibiotic-eluting scaffolds with responsive dual-release kinetics facilitate bone healing and eliminate S. aureus infection
Authors: Eamon J Sheehy, Christian von Diemling, Emily Ryan, Amro Widaa, Peter O' Donnell, Alan Ryan, Gang Chen, Robert T Brady, Adolfo López-Noriega, Stephan Zeiter, T Fintan Moriarty, Fergal J O' Brien
Journal: Biomaterials (2024)

Osteomyelitis (OM) is a progressive, inflammatory infection of bone caused predominately by Staphylococcus aureus. Herein, we engineered an antibiotic-eluting collagen-hydroxyapatite scaffold capable of eliminating infection and facilitating bone healing. An iterative freeze-drying and chemical crosslinking approach was leveraged to modify antibiotic release kinetics, resulting in a layered dual-release system whereby an initial rapid release of antibiotic to clear infection was followed by a sustained controlled release to prevent reoccurrence of infection. We observed that the presence of microbial collagenase accelerated antibiotic release from the crosslinked layer of the scaffold, indicating that the material is responsive to microbial activity. As exemplar drugs, vancomycin and gentamicin-eluting scaffolds were demonstrated to be bactericidal, and supported osteogenesis in vitro. In a pilot murine model of OM, vancomycin-eluting scaffolds were observed to reduce S. aureus infection within the tibia. Finally, in a rabbit model of chronic OM, gentamicin-eluting scaffolds both facilitated radial bone defect healing and eliminated S. aureus infection. These results show that antibiotic-eluting collagen-hydroxyapatite scaffolds are a one-stage therapy for OM, which when implanted into infected bone defects simultaneously eradicate infection and facilitate bone tissue healing.
GSFM: A genome-scale functional module transformation to represent drug efficacy for in silico drug discovery
Authors: Saisai Tian, Xuyang Liao, Wen Cao, Xinyi Wu, Zexi Chen, Jinyuan Lu, Qun Wang, Jinbo Zhang, Luonan Chen, Weidong Zhang
Journal: Acta Pharmaceutica Sinica B (2024)

Pharmacotranscriptomic profiles, which capture drug-induced changes in gene expression, offer vast potential for computational drug discovery and are widely used in modern medicine. However, current computational approaches neglected the associations within gene‒gene functional networks and unrevealed the systematic relationship between drug efficacy and the reversal effect. Here, we developed a new genome-scale functional module (GSFM) transformation framework to quantitatively evaluate drug efficacy for in silico drug discovery. GSFM employs four biologically interpretable quantifiers: GSFM_Up, GSFM_Down, GSFM_ssGSEA, and GSFM_TF to comprehensively evaluate the multi-dimension activities of each functional module (FM) at gene-level, pathway-level, and transcriptional regulatory network-level. Through a data transformation strategy, GSFM effectively converts noisy and potentially unreliable gene expression data into a more dependable FM active matrix, significantly outperforming other methods in terms of both robustness and accuracy. Besides, we found a positive correlation between RSGSFM and drug efficacy, suggesting that RSGSFM could serve as representative measure of drug efficacy. Furthermore, we identified WYE-354, perhexiline, and NTNCB as candidate therapeutic agents for the treatment of breast-invasive carcinoma, lung adenocarcinoma, and castration-resistant prostate cancer, respectively. The results from in vitro and in vivo experiments have validated that all identified compounds exhibit potent anti-tumor effects, providing proof-of-concept for our computational approach.
The AI Revolution in Glaucoma: Bridging Challenges with Opportunities
Authors: Fei Li, Deming Wang, Zefeng Yang, Yinhang Zhang, Jiaxuan Jiang, Xiaoyi Liu, Kangjie Kong, Fengqi Zhou, Clement C Tham, Felipe Medeiros, Ying Han, Andrzej Grzybowski, Linda M Zangwill, Dennis S C Lam, Xiulan Zhang
Journal: Progress in Retinal and Eye Research (2024)
Targeting Claudin-18.2 for cancer therapy: updates from 2024 ASCO annual meeting
Authors: Katherine I. Zhou, John H. Strickler, Hui Chen
Journal: Journal of Hematology & Oncology (2024)

Multiple classes of therapies targeting claudin-18 isoform 2 (CLDN18.2) are under development for the treatment of advanced gastroesophageal adenocarcinoma and other solid tumors. At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, the final results of the phase 3 SPOTLIGHT trial were presented, demonstrating a significant survival benefit from the addition of the CLDN18.2-specific antibody zolbetuximab to chemotherapy in the first-line treatment of advanced gastroesophageal adenocarcinomas with ≥ 75% CLDN18.2 expression. Early-phase trial results presented at ASCO 2024 showed promising efficacy and safety of the afucosylated CLDN18.2-specific antibody FG-M108 in combination with chemotherapy in the first-line treatment of CLDN18.2-positive advanced gastroesophageal and pancreatic cancers. In addition, several early-phase trials presented at ASCO 2024 investigate other CLDN18.2-targeting approaches in CLDN18.2-positive refractory advanced solid tumors, including the CLDN18.2-targeting antibody–drug conjugates LM-302 and IBI343, the bispecific anti-CLDN18.2/CD3 antibody IBI38, and the chimeric antigen receptor T cell therapy satricabtagene autoleucel. These novel approaches could potentially expand the benefit of CLDN18.2-targeting therapies to a broader range of tumor types and to tumors expressing lower levels of CLDN18.2.
Effectiveness of chest pain center accreditation on the hospital outcome of acute aortic dissection: a nationwide study in China
Authors: Li-Wei Liu, Yi-Kai Cui, Lin Zhang, Dai-Le Jia, Jing Wang, Jia-Wei Gu, Jin-Yan Zhang, Zhen Dong, Xue-Juan Jin, Xiao-Yi Zou, Guo-Li Sun, Yu-Xiang Dai, Ai-Jun Sun, Jun-Bo Ge
Journal: Military Medical Research (2024)

Abstract Background The National Chest Pain Center Program (NCPCP) is a nationwide, quality enhancement program aimed at raising the standard of care for patients experiencing acute chest pain in China. The benefits of chest pain center (CPC) accreditation on acute coronary syndrome have been demonstrated. However, there is no evidence to indicate whether CPC accreditation improves outcomes for patients with acute aortic dissection (AAD). Methods We conducted a retrospective observational study of patients with AAD from 1671 hospitals in China, using data from the NCPCP spanning the period from January 1, 2016 to December 31, 2022. The patients were divided into 2 groups: pre-accreditation and post-accreditation admissions. The outcomes examined included in-hospital mortality, misdiagnosis, and Stanford type A AAD surger y . Multivariate logistic regression was employed to explore the relationship between CPC accreditation and in-hospital outcomes. Furthermore, we stratified the hospitals based on their geographical location (Eastern/Central/Western regions) or administrative status (provincial/non-provincial capital areas) to assess the impact of CPC accreditation on AAD patients across various regions. Results The analysis encompassed a total of 40,848 patients diagnosed with AAD. The post-accreditation group exhibited significantly lower rates of in-hospital mortality and misdiagnosis (12.1% vs. 16.3%, P &lt; 0.001 and 2.9% vs. 5.4%, P &lt; 0.001, respectively) as well as a notably higher rate of Stanford type A AAD surgery (61.1% vs. 42.1%, P &lt; 0.001) compared with the pre-accreditation group. After adjusting for potential covariates, CPC accreditation was associated with substantially reduced risks of in-hospital mortality (adjusted OR 0.644, 95% CI 0.599–0.693) and misdiagnosis (adjusted OR 0.554, 95% CI 0.493–0.624), along with an increase in the proportion of patients undergoing Stanford type A AAD surgery (adjusted OR 1.973, 95% CI 1.797–2.165). Following CPC accreditation, there were significant reductions in in-hospital mortality across various regions, particularly in Western regions (from 21.5 to 14.1%). Moreover, CPC accreditation demonstrated a more pronounced impact on in-hospital mortality in non-provincial cities compared to provincial cities (adjusted OR 0.607 vs. 0.713). Conclusion CPC accreditation is correlated with improved management and in-hospital outcomes for patients with AAD.