tbuckley/cabot-search huggingface dataset:
A physiologically-based digital twin for alcohol consumption—predicting real-life drinking responses and long-term plasma PEth
Authors: Henrik Podéus, Christian Simonsson, Patrik Nasr, Mattias Ekstedt, Stergios Kechagias, Peter Lundberg, William Lövfors, Gunnar Cedersund
Journal: npj Digital Medicine (2024)

Abstract Alcohol consumption is associated with a wide variety of preventable health complications and is a major risk factor for all-cause mortality in the age group 15-47 years. To reduce dangerous drinking behavior, eHealth applications have shown promise. A particularly interesting potential lies in the combination of eHealth apps with mathematical models. However, existing mathematical models do not consider real-life situations, such as combined intake of meals and beverages, and do not connect drinking to clinical markers, such as phosphatidylethanol (PEth). Herein, we present such a model which can simulate real-life situations and connect drinking to long-term markers. The new model can accurately describe both estimation data according to a χ 2 -test (187.0 &lt; T χ2 = 226.4) and independent validation data (70.8 &lt; T χ2 = 93.5). The model can also be personalized using anthropometric data from a specific individual and can thus be used as a physiologically-based digital twin. This twin is also able to connect short-term consumption of alcohol to the long-term dynamics of PEth levels in the blood, a clinical biomarker of alcohol consumption. Here we illustrate how connecting short-term consumption to long-term markers allows for a new way to determine patient alcohol consumption from measured PEth levels. An additional use case of the twin could include the combined evaluation of patient-reported AUDIT forms and measured PEth levels. Finally, we integrated the new model into an eHealth application, which could help guide individual users or clinicians to help reduce dangerous drinking.
A Hydrogel Dressing Comprised of Silk Fibroin, Ag Nanoparticles, and Reduced Graphene Oxide for NIR Photothermal‐Enhanced Antibacterial Efficiency and Skin Regeneration
Authors: Shaorong Yan, Shuo Xu, Yu Wang, Jun You, Chuanlong Guo, Xiaochen Wu
Journal: Advanced Healthcare Materials (2024)

Bacterial infection, inflammation, and excessive oxidative stress are the primary factors that contribute to delayed healing of skin wounds. In this study, a multifunctional wound dressing (SF/Ag@rGO hydrogel) is developed to promote the healing of infected skin wounds by combining the inherent antibacterial activity of Ag nanoparticles (NPs) with near-infrared (NIR)-assisted antibacterial therapy. Initially, L-ascorbic acid is used as a reducing agent and PVP-K17 as a stabilizer and dispersant, this facilitates the synthesis of reduced graphene oxide loaded with Ag NPs (Ag@rGO). Ag@rGO is then blended with a silk fibroin (SF) solution to form an instantly gelling SF/Ag@rGO hydrogel that exhibits rapid self-healing, injectability, shape adaptability, NIR responsiveness, antioxidant, high tissue adhesion, and robust mechanical properties. In vitro and in vivo experiments show that the SF/Ag@rGO hydrogel demonstrates strong antioxidant and photothermal antibacterial capabilities, promoting wound healing through angiogenesis, stimulating collagen generation, alleviating inflammation, antioxidant, and promoting cell proliferation, indicating that the SF/Ag@rGO hydrogel dressing is an ideal candidate for clinical treatment of full-thickness bacterial-stained wounds.
Evolution of invasive pneumococcal disease by serotype 3 in adults: a Spanish three-decade retrospective study
Authors: Sara Calvo-Silveria, Aida González-Díaz, Inmaculada Grau, José María Marimón, Emilia Cercenado, M Dolores Quesada, Antonio Casabella, Nieves Larrosa, José Yuste, Dàmaris Berbel, Marta Alonso, Fe Tubau, Sophie Belman, Irene Cadenas-Jiménez, Antonio J. Martín-Galiano, M Ángeles Domínguez, Sara Martí, Josefina Liñares, Román Pallarés, Jordi Càmara, Carmen Ardanuy
Journal: The Lancet Regional Health - Europe (2024)
FFA-GPT: an automated pipeline for fundus fluorescein angiography interpretation and question-answer
Authors: Xiaolan Chen, Weiyi Zhang, Pusheng Xu, Ziwei Zhao, Yingfeng Zheng, Danli Shi, Mingguang He
Journal: npj Digital Medicine (2024)

Abstract Fundus fluorescein angiography (FFA) is a crucial diagnostic tool for chorioretinal diseases, but its interpretation requires significant expertise and time. Prior studies have used Artificial Intelligence (AI)-based systems to assist FFA interpretation, but these systems lack user interaction and comprehensive evaluation by ophthalmologists. Here, we used large language models (LLMs) to develop an automated interpretation pipeline for both report generation and medical question-answering (QA) for FFA images. The pipeline comprises two parts: an image-text alignment module (Bootstrapping Language-Image Pre-training) for report generation and an LLM (Llama 2) for interactive QA. The model was developed using 654,343 FFA images with 9392 reports. It was evaluated both automatically, using language-based and classification-based metrics, and manually by three experienced ophthalmologists. The automatic evaluation of the generated reports demonstrated that the system can generate coherent and comprehensible free-text reports, achieving a BERTScore of 0.70 and F1 scores ranging from 0.64 to 0.82 for detecting top-5 retinal conditions. The manual evaluation revealed acceptable accuracy (68.3%, Kappa 0.746) and completeness (62.3%, Kappa 0.739) of the generated reports. The generated free-form answers were evaluated manually, with the majority meeting the ophthalmologists’ criteria (error-free: 70.7%, complete: 84.0%, harmless: 93.7%, satisfied: 65.3%, Kappa: 0.762–0.834). This study introduces an innovative framework that combines multi-modal transformers and LLMs, enhancing ophthalmic image interpretation, and facilitating interactive communications during medical consultation.
A T <sub>H</sub> 17-intrinsic IL-1β–STAT5 axis drives steroid resistance in autoimmune neuroinflammation
Authors: William A. Miller-Little, Xing Chen, Vanessa Salazar, Caini Liu, Katarzyna Bulek, Julie Y. Zhou, Xiao Li, Olaf Stüve, Thaddeus Stappenbeck, George Dubyak, Junjie Zhao, Xiaoxia Li
Journal: Science Immunology (2024)

Steroid resistance poses a major challenge for the management of autoimmune neuroinflammation. T helper 17 (T H 17) cells are widely implicated in the pathology of steroid resistance; however, the underlying mechanisms are unknown. In this study, we identified that interleukin-1 receptor (IL-1R) blockade rendered experimental autoimmune encephalomyelitis (EAE) mice sensitive to dexamethasone (Dex) treatment. Interleukin-1β (IL-1β) induced a signal transducer and activator of transcription 5 (STAT5)–mediated steroid-resistant transcriptional program in T H 17 cells, which promoted inflammatory cytokine production and suppressed Dex-induced anti-inflammatory genes. T H 17-specific deletion of STAT5 ablated the IL-1β–induced steroid-resistant transcriptional program and rendered EAE mice sensitive to Dex treatment. IL-1β synergized with Dex to promote the STAT5-dependent expression of CD69 and the development of central nervous system (CNS)–resident CD69 + T H 17 cells. Combined IL-1R blockade and Dex treatment ablated CNS-resident T H 17 cells, reduced EAE severity, and prevented relapse. CD69 + tissue-resident T H 17 cells were also detected in brain lesions of patients with multiple sclerosis. These findings (i) demonstrate that IL-1β–STAT5 signaling in T H 17 cells mediates steroid resistance and (ii) identify a therapeutic strategy for reversing steroid resistance in T H 17-mediated CNS autoimmunity.
The immunoglobulin superfamily ligand B7H6 subjects T cell responses to NK cell surveillance
Authors: Michael Kilian, Mirco J. Friedrich, Kevin Hai-Ning Lu, David Vonhören, Selina Jansky, Julius Michel, Anna Keib, Saskia Stange, Nicolaj Hackert, Niklas Kehl, Markus Hahn, Antje Habel, Stefanie Jung, Kristine Jähne, Felix Sahm, Johannes Betge, Adelheid Cerwenka, Frank Westermann, Peter Dreger, Marc S. Raab, Nadja M. Meindl-Beinker, Matthias Ebert, Lukas Bunse, Carsten Müller-Tidow, Michael Schmitt, Michael Platten
Journal: Science Immunology (2024)

Understanding the mechanisms that regulate T cell immunity is critical for the development of effective therapies for diseases associated with T cell dysfunction, including autoimmune diseases, chronic infections, and cancer. Co-inhibitory “checkpoint molecules,” such as programmed cell death protein-1, balance excessive or prolonged immune activation by T cell–intrinsic signaling. Here, by screening for mediators of natural killer (NK) cell recognition on T cells, we identified the immunoglobulin superfamily ligand B7H6 to be highly expressed by activated T cells, including patient-infused CD19-targeting chimeric antigen receptor (CAR) T cells. Unlike other checkpoint molecules, B7H6 mediated NKp30-dependent recognition and subsequent cytolysis of activated T cells by NK cells. B7H6 + T cells were prevalent in the tissue and blood of several diseases, and their abundance in tumor tissue positively correlated with clinical response in a cohort of patients with immune checkpoint inhibitor–treated esophageal cancer. In humanized mouse models, NK cell surveillance via B7H6 limited the persistence and antitumor activity of CAR T cells, and its genetic deletion enhanced T cell proliferation and persistence. Together, we provide evidence of B7H6 protein expression by activated T cells and suggest the B7H6-NKp30 axis as a therapeutically actionable NK cell–dependent immune checkpoint that regulates human T cell function.
Oxidative phosphorylation regulates B cell effector cytokines and promotes inflammation in multiple sclerosis
Authors: Rui Li, Yanting Lei, Ayman Rezk, None Diego A. Espinoza, Jing Wang, Huiru Feng, Bo Zhang, Isabella P. Barcelos, Hang Zhang, Jing Yu, Xinrui Huo, Fangyi Zhu, Changxin Yang, Hao Tang, Amy C. Goldstein, Brenda L. Banwell, Hakon Hakonarson, Hongwei Xu, Michael Mingueneau, Bo Sun, Hulun Li, Amit Bar-Or
Journal: Science Immunology (2024)

Dysregulated B cell cytokine production contributes to pathogenesis of immune-mediated diseases including multiple sclerosis (MS); however, the underlying mechanisms are poorly understood. In this study we investigated how cytokine secretion by pro-inflammatory (GM-CSF–expressing) and anti-inflammatory (IL-10–expressing) B cells is regulated. Pro-inflammatory human B cells required increased oxidative phosphorylation (OXPHOS) compared with anti-inflammatory B cells. OXPHOS reciprocally modulated pro- and anti-inflammatory B cell cytokines through regulation of adenosine triphosphate (ATP) signaling. Partial inhibition of OXPHOS or ATP-signaling including with BTK inhibition resulted in an anti-inflammatory B cell cytokine shift, reversed the B cell cytokine imbalance in patients with MS, and ameliorated neuroinflammation in a myelin oligodendrocyte glycoprotein (MOG)–induced experimental autoimmune encephalitis mouse model. Our study identifies how pro- and anti-inflammatory cytokines are metabolically regulated in B cells and identifies ATP and its metabolites as a “fourth signal” that shapes B cell responses and is a potential target for restoring the B cell cytokine balance in autoimmune diseases.
Development of an Automated Morphometric Approach to Assess Vascular Outcomes following Exposure to Environmental Chemicals in Zebrafish
Authors: Xiali Zhong, Junzhou Chen, Zhuyi Zhang, Qicheng Zhu, Di Ji, Weijian Ke, Congying Niu, Can Wang, Nan Zhao, Wenquan Chen, Kunkun Jia, Qian Liu, Maoyong Song, Chunqiao Liu, Yanhong Wei
Journal: Environmental Health Perspectives (2024)

Disruptions in vascular formation attributable to chemical insults is a pivotal risk factor or potential etiology of developmental defects and various disease settings. Among the thousands of chemicals threatening human health, the highly concerning groups prevalent in the environment and detected in biological monitoring in the general population ought to be prioritized because of their high exposure risks. However, the impacts of a large number of environmental chemicals on vasculature are far from understood. The angioarchitecture complexity and technical limitations make it challenging to analyze the entire vasculature efficiently and identify subtle changes through a high-throughput in vivo assay.
RNA modifications in pulmonary diseases
Authors: Weiwei Qian, Lvying Yang, Tianlong Li, Wanlin Li, Jian Zhou, Shenglong Xie
Journal: MedComm (2024)

Abstract Threatening public health, pulmonary disease (PD) encompasses diverse lung injuries like chronic obstructive PD, pulmonary fibrosis, asthma, pulmonary infections due to pathogen invasion, and fatal lung cancer. The crucial involvement of RNA epigenetic modifications in PD pathogenesis is underscored by robust evidence. These modifications not only shape cell fates but also finely modulate the expression of genes linked to disease progression, suggesting their utility as biomarkers and targets for therapeutic strategies. The critical RNA modifications implicated in PDs are summarized in this review, including N 6 ‐methylation of adenosine, N 1 ‐methylation of adenosine, 5‐methylcytosine, pseudouridine (5‐ribosyl uracil), 7‐methylguanosine, and adenosine to inosine editing, along with relevant regulatory mechanisms. By shedding light on the pathology of PDs, these summaries could spur the identification of new biomarkers and therapeutic strategies, ultimately paving the way for early PD diagnosis and treatment innovation.
Epigenome-wide association study of lung cancer among never smokers in two prospective cohorts in Shanghai, China
Authors: Mohammad L Rahman, Charles E Breeze, Xiao-Ou Shu, Jason Y Y Wong, Batel Blechter, Andres Cardenas, Xuting Wang, Bu-Tian Ji, Wei Hu, Qiuyin Cai, H Dean Hosgood, Gong Yang, Jianxin Shi, Jirong Long, Yu-Tang Gao, Douglas A Bell, Wei Zheng, Nathaniel Rothman, Qing Lan
Journal: Thorax (2024)

The aetiology of lung cancer among individuals who never smoked remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Epigenetic alterations, particularly DNA methylation (DNAm) changes, have emerged as potential drivers. Yet, few prospective epigenome-wide association studies (EWAS), primarily focusing on peripheral blood DNAm with limited representation of never smokers, have been conducted.
Novel autoantibodies help diagnose anti-SSA antibody negative Sjögren disease and predict abnormal labial salivary gland pathology
Authors: Maxwell Parker, Zihao Zheng, Michael R Lasarev, Michele C Larsen, Addie Vande Loo, Roxana A Alexandridis, Michael A Newton, Miriam A Shelef, Sara S McCoy
Journal: Annals of the Rheumatic Diseases (2024)

Sjögren disease (SjD) diagnosis often requires either positive anti-SSA antibodies or a labial salivary gland biopsy with a positive focus score (FS). One-third of patients with SjD lack anti-SSA antibodies (SSA-), requiring a positive FS for diagnosis. Our objective was to identify novel autoantibodies to diagnose 'seronegative' SjD.
Targeted isolation of antiviral cinnamoylphloroglucinol-terpene adducts from Cleistocalyx operculatus by building blocks-based molecular networking approach
Authors: Jianguo Song, Ruili Huang, Jialiao Cai, Zhenlong Wu, Lijun Hu, Wanyang Sun, Xiaojun Huang, Rongrong He, Wei Tang, Wencai Ye, Ying Wang
Journal: Acta Pharmaceutica Sinica B (2024)

The building blocks-based molecular network (BBMN) strategy was applied to the phytochemical investigation of
Dapagliflozin and quality of life measured using the <scp>EuroQol</scp> 5‐dimension questionnaire in patients with heart failure with reduced and mildly reduced/preserved ejection fraction
Authors: Mingming Yang, Toru Kondo, Atefeh Talebi, Pardeep S. Jhund, Kieran F. Docherty, Brian L. Claggett, Muthiah Vaduganathan, Erasmus Bachus, Adrian F. Hernandez, Carolyn S.P. Lam, Silvio E. Inzucchi, Felipe A. Martinez, Rudolf A. de Boer, Mikhail N. Kosiborod, Akshay S. Desai, Lars Køber, Piotr Ponikowski, Marc S. Sabatine, Scott D. Solomon, John J.V. McMurray
Journal: European Journal of Heart Failure (2024)

ABSTRACT Aims Although much is known about the usefulness of heart failure (HF)‐specific instruments for assessing patient well‐being, less is known about the value of generic instruments for the measurement of health‐related quality of life (HRQL) in HF. The aim of this study was to assess the relationship between the EuroQol 5‐dimension 5‐level (EQ‐5D‐5L) visual analogue scale (VAS) and index scores, clinical characteristics, and outcomes in patients with HF and the effect of dapagliflozin on these scores. Methods and results We performed a patient‐level pooled analysis of the DAPA‐HF and DELIVER trials, which investigated the effectiveness and safety of dapagliflozin in patients with HF and reduced ejection fraction (HFrEF) and mildly reduced/preserved ejection fraction (HFmrEF/HFpEF), respectively. Patients reporting higher (better) EQ‐5D‐5L VAS and index scores had a lower prevalence of comorbidities, including atrial fibrillation and hypertension, than patients with a worse score. They were also more likely to have better investigator‐reported (New York Heart Association class) and patient‐self‐reported (Kansas City Cardiomyopathy Questionnaire) health status and lower median N‐terminal pro‐B‐type natriuretic peptide levels. Compared to patients with the lowest scores (Q1), those with higher EQ‐5D‐5L VAS scores had better outcomes: the hazard ratio for the composite of cardiovascular death or worsening HF was 0.81 (95% confidence interval 0.72–0.91) in Q2, 0.74 (0.65–0.84) in Q3, and 0.62 (0.54–0.72) in Q4. The risk of each component of the composite outcome, and all‐cause death, was also lower in patients with better scores. Similar findings were observed for the index score. Treatment with dapagliflozin improved both EQ‐5D‐5L VAS and index scores across the range of ejection fraction. Conclusions Both higher (better) EQ‐5D‐5L VAS and index scores were associated with better outcomes. Dapagliflozin treatment improved EQ‐5D‐5L VAS and index scores, irrespective of ejection fraction.
Frailty in patients on dialysis
Authors: Gordon Chun-Kau Chan, Kamyar Kalantar-Zadeh, Jack Kit-Chung Ng, Na Tian, Aine Burns, Kai-Ming Chow, Cheuk-Chun Szeto, Philip Kam-Tao Li
Journal: Kidney International (2024)

Frailty is a condition that is frequently observed among patients undergoing dialysis. Frailty is characterized by a decline in both physiological state and cognitive state, leading to a combination of symptoms, such as weight loss, exhaustion, low physical activity level, weakness, and slow walking speed. Frail patients not only experience a poor quality of life, but also are at higher risk of hospitalization, infection, cardiovascular events, dialysis-associated complications, and death. Frailty occurs as a result of a combination and interaction of various medical issues in patients who are on dialysis. Unfortunately, frailty has no cure. To address frailty, a multifaceted approach is necessary, involving coordinated efforts from nephrologists, geriatricians, nurses, allied health practitioners, and family members. Strategies such as optimizing nutrition and chronic kidney disease-related complications, reducing polypharmacy by deprescription, personalizing dialysis prescription, and considering home-based or assisted dialysis may help slow the decline of physical function over time in subjects with frailty. This review discusses the underlying causes of frailty in patients on dialysis and examines the methods and difficulties involved in managing frailty among this group.
Identifying long-term survivors and those at higher or lower risk of relapse among patients with cytogenetically normal acute myeloid leukemia using a high-dimensional mixture cure model
Authors: Kellie J. Archer, Han Fu, Krzysztof Mrózek, Deedra Nicolet, Alice S. Mims, Geoffrey L. Uy, Wendy Stock, John C. Byrd, Wolfgang Hiddemann, Jan Braess, Karsten Spiekermann, Klaus H. Metzeler, Tobias Herold, Ann-Kathrin Eisfeld
Journal: Journal of Hematology & Oncology (2024)

Abstract Patients with cytogenetically normal acute myeloid leukemia (CN-AML) may harbor prognostically relevant gene mutations and thus be categorized into one of the three 2022 European LeukemiaNet (ELN) genetic-risk groups. Nevertheless, there remains heterogeneity with respect to relapse-free survival (RFS) within these genetic-risk groups. Our training set included 306 adults on Alliance for Clinical Trials in Oncology studies with de novo CN-AML aged &lt; 60 years who achieved a complete remission and for whom centrally reviewed cytogenetics, RNA-sequencing, and gene mutation data from diagnostic samples were available (Alliance trial A152010). To overcome deficiencies of the Cox proportional hazards model when long-term survivors are present, we developed a penalized semi-parametric mixture cure model (MCM) to predict RFS where RNA-sequencing data comprised the predictor space. To validate model performance, we employed an independent test set from the German Acute Myeloid Leukemia Cooperative Group (AMLCG) consisting of 40 de novo CN-AML patients aged &lt; 60 years who achieved a complete remission and had RNA-sequencing of their pre-treatment sample. For the training set, there was a significant non-zero cure fraction ( p = 0.019) with 28.5% of patients estimated to be cured. Our MCM included 112 genes associated with cure, or long-term RFS, and 87 genes associated with latency, or shorter-term time-to-relapse. The area under the curve and C-statistic were respectively, 0.947 and 0.783 for our training set and 0.837 and 0.718 for our test set. We identified a novel, prognostically relevant molecular signature in CN-AML, which allows identification of patient subgroups independent of 2022 ELN genetic-risk groups. Trial registration Data from companion studies CALGB 8461, 9665 and 20202 (trials registered at www.clinicaltrials.gov as, respectively, NCT00048958, NCT00899223, and NCT00900224) were obtained from Alliance for Clinical Trials in Oncology under data sharing study A152010. Data from the AMLCG 2008 trial was registered at www.clinicaltrials.gov as NCT01382147.
Young Patients Without Genetic Risk Have Low Chance of Second Breast Cancer
Authors: Emily Harris
Journal: JAMA (2024)

Kristen D. Brantley, PhD, MPH; Shoshana M. Rosenberg, ScD, MPH; Laura C. Collins, MD; Kathryn J. Ruddy, MD, MPH; Rulla M. Tamimi, ScD; Lidia Schapira, MD; Virginia F. Borges, MD, MMSc; Ellen Warner, MD, MSc; Steven E. Come, MD; Yue Zheng, MS; Gregory J. Kirkner, MPH; Craig Snow, MHA; Eric P. Winer, MD; Ann H. Partridge, MD, MPH