tbuckley/cabot-search huggingface dataset:
Abstract P494: Gene-Level Gene-Environment Interaction Testing Reveals Rare Variants With Large Impacts on the Omega-3 Fatty Acid-Inflammation Relationship
Authors: Kenneth E Westerman, Chirag Patel, James Meigs, Alisa Manning
Journal: Circulation (2024)

Dietary omega-3 fatty acid (dN3FA) intake affects plasma N3FA (pN3FA) concentrations, circulating biomarkers of chronic inflammation such as high-sensitivity C-reactive protein (hsCRP), and ultimately cardiometabolic disease risk. Genetic variation may modify the N3FA-inflammation relationship, facilitating applications in precision medicine and possibly explaining variable intervention trial responses. Here, we explored the dual hypothesis that pN3FA mediates the dN3FA-hsCRP relationship and that genetic variants across the frequency spectrum modify this association. Regression models in the UK Biobank (N = 342,120) tested main effects of oily fish intake (a primary dietary source of N3FA; measured by food frequency questionnaire) on hsCRP and its mediation by pN3FA (measured by nuclear magnetic resonance; N = 188,701). Three genome-wide interaction studies tested modification of the dN3FA-hsCRP (“full”), dN3FA-pN3FA (“upstream”), and pN3FA-hsCRP (“downstream”) associations. Regression covariates included demographics, lifestyle indicators, socioeconomic measures, and genetic principal components. Variant-specific GWIS were followed by gene-level enrichment testing using the MAGMA tool. Replication of gene-based signals was conducted in the Women’s Genome Health Study (WGHS; N = 23,294) by testing the interaction of the top variant in each gene with total dN3FA impacting hsCRP. Oily fish intake associated most strongly with hsCRP compared to other questionnaire-based estimates of fish or fish oil intake, with statistical evidence that plasma N3FA mediated approximately 100% of this diet-inflammation relationship. While the “full” genetic interaction analysis did not produce any FDR-significant gene-level interactions, the “upstream” analysis uncovered nine genes, including a cluster containing the biologically-relevant fatty acid desaturases FADS1 and FADS2 , and the “downstream” analysis uncovered four genes. Primary variant interaction effect sizes were small (e.g., -0.02 std. dev. bN3FA / std. dev. fish / allele for the top FADS1 variant rs174560), but in-depth follow-up at these genes revealed allelic spectra including rare variants with substantially larger effects (e.g., -0.11 for a FADS1 missense variant with allele frequency of 0.14%, after conditioning on rs174560). WGHS results supported the overall robustness of the findings (consistent interaction effect signs at 8/10 loci), replicated specific signals (p = 0.04 for FADS1 rs174560), and implicated additional inflammatory biomarkers (e.g., fibrinogen and ICAM-1 for the top GLTSCR1 variant). In conclusion, we report (1) the novel epidemiological finding that pN3FA fully mediates the dN3FA-hsCRP relationship, and (2) specific genes with large-effect rare variants that modify the upstream (absorption) and downstream (inflammatory pathways) components of this relationship.
Abstract P375: Cardiometabolic Risk Factors and Socioeconomic Status Indices in Young Adults in Latin America: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Adriana Buitrago-Lopez, Cristina Pellegrino Baena, Jose Faria Neto
Journal: Circulation (2024)

Background: Metabolic syndrome components in children and adolescents have gained attention in low- and middle-income countries due to variability in their effects and measures across socioeconomic status (SES) determinants. Socioeconomic disparities have been studied related to health, and this fact still poses a serious challenge that raises concerns, especially in low-and middle-income countries, where the classification of the population relies on different determinants from wealthier countries. We conducted a systematic review and meta-analysis to illustrate the effects of measures of metabolic syndrome components across SES in Latin American (LA) young adults. Methods: We searched PubMed/MEDLINE, Web of Science, Lilacs (Bireme), Embase and Scopus for LA studies published before September 2023. Included studies were those with participants aged 6-19 years in whom metabolic syndrome (MS) components were analyzed across SES in LA. The quality of observational studies was assessed using the adapted New Castle Ottawa quality tool. Blood pressure, abdominal obesity, body mass index, body fat, glucose levels and insulin resistance data were synthesized, and a random effect model was used to measure the collective effect of overweight/obesity and lipid profile on higher SES levels compared with middle and low SES levels. The protocol of this review was registered with the International Prospective Register of Systematic Reviews database (registration number: CRD42020222378) and was developed following PRISMA statements. Results: Sixty-three eligible articles (n=255, 521 participants) from nine LA countries were selected. SES definitions were used in 41 studies from five countries with similar criteria. Obesity and overweight (odds ratio: 1.57, 95% confidence interval: 1.18-1.96) and altered lipid profiles were significantly associated with higher SES compared to lower SES. However, high-density lipoprotein-cholesterol levels were lower in patients with a lower SES. The heterogeneity observed could be explained by age, sex, nutrition patterns, standardized cardiometabolic measures, and temporally collected data due to rapid transitions in LA countries. Conclusions: Cardiometabolic components may be associated with higher SES in LA countries. As national SES definitions have been used around LA countries to classify populations, this definition needs to be standardized around LA countries to guide national programs to intensify cardiovascular health and prevent detrimental effects in young people.
Patient and Graft Outcomes of Kidney Transplant Recipients with Anti-Human Neutrophil Antigen Antibodies
Authors: Christina Irene Mejia, Goni Katz-Greenberg, Beth W. Colombe, Pooja Singh, Anju Yadav
Journal: Journal of the American Society of Nephrology (2020)

Mejia, Christina Irene; Katz-Greenberg, Goni; Colombe, Beth W.; Singh, Pooja; Yadav, Anju Author Information
Long-term efficacy, safety and biocompatibility of a novel sirolimus eluting iron bioresorbable scaffold in a porcine model
Authors: Ya-Nan Gao, Hong-Tao Yang, Zi-Feng Qiu, Feng Qi, Qian-Hong Lu, Jian-Feng Zheng, Zi-Wei Xi, Xin Wang, Li Li, Gui Zhang, De-Yuan Zhang, Yu-Die Lu, Hai-Ping Qi, Hong Qiu, Run-Lin Gao, Yu-Feng Zheng
Journal: Bioactive Materials (2024)

Iron is considered as an attractive alternative material for bioresorbable scaffolds (BRS). The sirolimus eluting iron bioresorbable scaffold (IBS), developed by Biotyx Medical (Shenzhen, China), is the only iron-based BRS with an ultrathin-wall design. The study aims to investigate the long-term efficacy, safety, biocompatibility, and lumen changes during the biodegradation process of the IBS in a porcine model. A total of 90 IBSs and 70 cobalt-chromium everolimus eluting stents (EES) were randomly implanted into nonatherosclerotic coronary artery of healthy mini swine. The multimodality assessments including coronary angiography, optical coherence tomography, micro-computed tomography, magnetic resonance imaging, real-time polymerase chain reaction (PCR), and histopathological evaluations, were performed at different time points. There was no statistical difference in area stenosis between IBS group and EES group at 6 months, 1year, 2 years and 5 years. Although the scaffolded vessels narrowed at 9 months, expansive remodeling with increased mean lumen area was found at 3 and 5 years. The IBS struts remained intact at 6 months, and the corrosion was detectable at 9 months. At 5 years, the iron struts were completely degraded and absorbed in situ, without in-scaffold restenosis or thrombosis, lumen collapse, aneurysm formation, and chronic inflammation. No local or systemic toxicity and abnormal histopathologic manifestation were found in all experiments. Results from real-time PCR indicated that no sign of iron overload was reported in scaffolded segments. Therefore, the IBS shows comparable efficacy, safety, and biocompatibility with EES, and late lumen enlargement is considered as a unique feature in the IBS-implanted vessels.
Safety of Immunosuppression in A Prospective Cohort of Inflammatory Bowel Disease Patients with a HIstoRy of CancEr: SAPPHIRE Registry
Authors: Steven H. Itzkowitz, Yue Jiang, Cristina Villagra, Jean-Frederic Colombel, Keith Sultan, Dana J. Lukin, David M. Faleck, Ellen Scherl, Shannon Chang, LeaAnn Chen, Seymour Katz, Joann Kwah, Arun Swaminath, Francesca Petralia, Virginia Sharpless, David Sachar, Lina Jandorf, Jordan E. Axelrad
Journal: Clinical Gastroenterology and Hepatology (2024)
Racial/ethnic differences in biologic treatment patterns among patients with psoriasis: A prospective analysis of patients in the CorEvitas Psoriasis Registry
Authors: Clinton W. Enos, Julie Z. Yi, Ana Ormaza Vera, Robert R. McLean, Adam P. Sima, Thomas Eckmann, Abby S. Van Voorhees
Journal: Journal of the American Academy of Dermatology (2024)
Development and validation of machine learning algorithms based on electrocardiograms for cardiovascular diagnoses at the population level
Authors: Sunil Vasu Kalmady, Amir Salimi, Weijie Sun, Nariman Sepehrvand, Yousef Nademi, Kevin Bainey, Justin Ezekowitz, Abram Hindle, Finlay McAlister, Russel Greiner, Roopinder Sandhu, Padma Kaul
Journal: npj Digital Medicine (2024)

Abstract Artificial intelligence-enabled electrocardiogram (ECG) algorithms are gaining prominence for the early detection of cardiovascular (CV) conditions, including those not traditionally associated with conventional ECG measures or expert interpretation. This study develops and validates such models for simultaneous prediction of 15 different common CV diagnoses at the population level. We conducted a retrospective study that included 1,605,268 ECGs of 244,077 adult patients presenting to 84 emergency departments or hospitals, who underwent at least one 12-lead ECG from February 2007 to April 2020 in Alberta, Canada, and considered 15 CV diagnoses, as identified by International Classification of Diseases, 10th revision (ICD-10) codes: atrial fibrillation (AF), supraventricular tachycardia (SVT), ventricular tachycardia (VT), cardiac arrest (CA), atrioventricular block (AVB), unstable angina (UA), ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), pulmonary embolism (PE), hypertrophic cardiomyopathy (HCM), aortic stenosis (AS), mitral valve prolapse (MVP), mitral valve stenosis (MS), pulmonary hypertension (PHTN), and heart failure (HF). We employed ResNet-based deep learning (DL) using ECG tracings and extreme gradient boosting (XGB) using ECG measurements. When evaluated on the first ECGs per episode of 97,631 holdout patients, the DL models had an area under the receiver operating characteristic curve (AUROC) of &lt;80% for 3 CV conditions (PTE, SVT, UA), 80–90% for 8 CV conditions (CA, NSTEMI, VT, MVP, PHTN, AS, AF, HF) and an AUROC &gt; 90% for 4 diagnoses (AVB, HCM, MS, STEMI). DL models outperformed XGB models with about 5% higher AUROC on average. Overall, ECG-based prediction models demonstrated good-to-excellent prediction performance in diagnosing common CV conditions.
A Modular Communicative Leadless Pacing–Defibrillator System
Authors: Reinoud E Knops, Michael S Lloyd, Paul R Roberts, David J Wright, Lucas V A Boersma, Rahul Doshi, Paul A Friedman, Petr Neuzil, Carina Blomström-Lundqvist, Maria Grazia Bongiorni, Martin C Burke, Daniel Gras, Steven P Kutalek, Anish K Amin, Eugene Y Fu, Laurence M Epstein, Jose Maria Tolosana, Thomas D Callahan, Johan D Aasbo, Ralph Augostini, Harish Manyam, Devi G Nair, Blandine Mondésert, Wilber W Su, Chris Pepper, Marc A Miller, Jon Grammes, Karim Saleh, Christelle Marquie, Faisal M Merchant, Yong-Mei Cha, Colin Cunnington, David S Frankel, Julie West, Elizabeth Matznick, Bryan Swackhamer, Amy J Brisben, Jonathan Weinstock, Kenneth M Stein, Vivek Y Reddy, Lluis Mont
Journal: New England Journal of Medicine (2024)

The subcutaneous implantable cardioverter-defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing-defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown.
Predicting recurrent chat contact in a psychological intervention for the youth using natural language processing
Authors: Silvan Hornstein, Jonas Scharfenberger, Ulrike Lueken, Richard Wundrack, Kevin Hilbert
Journal: npj Digital Medicine (2024)

Abstract Chat-based counseling hotlines emerged as a promising low-threshold intervention for youth mental health. However, despite the resulting availability of large text corpora, little work has investigated Natural Language Processing (NLP) applications within this setting. Therefore, this preregistered approach (OSF: XA4PN) utilizes a sample of approximately 19,000 children and young adults that received a chat consultation from a 24/7 crisis service in Germany. Around 800,000 messages were used to predict whether chatters would contact the service again, as this would allow the provision of or redirection to additional treatment. We trained an XGBoost Classifier on the words of the anonymized conversations, using repeated cross-validation and bayesian optimization for hyperparameter search. The best model was able to achieve an AUROC score of 0.68 ( p &lt; 0.01) on the previously unseen 3942 newest consultations. A shapely-based explainability approach revealed that words indicating younger age or female gender and terms related to self-harm and suicidal thoughts were associated with a higher chance of recontacting. We conclude that NLP-based predictions of recurrent contact are a promising path toward personalized care at chat hotlines.
Antagonizing GIPR adds fire to the GLP-1R flame
Authors: Aaron Novikoff, Timo D. Müller
Journal: Trends in Endocrinology and Metabolism (2024)

Unimolecular co-agonists at the GLP-1/GIP receptors have recently achieved remarkable anti-obesogenic feats; yet, in a recent Phase 1 clinical trial, Véniant and colleagues report astounding body-weight loss, and an appreciable safety profile, in participants with obesity using the GLP-1R agonist/GIPR antagonist AMG 133.
Parvalbumin interneuron cell-to-network plasticity: mechanisms and therapeutic avenues
Authors: Michael D. Hadler, Henrik Alle, Jörg R.P. Geiger
Journal: Trends in Pharmacological Sciences (2024)

Alzheimer's disease (AD) and schizophrenia (SCZ) represent two major neuropathological conditions with a high disease burden. Despite their distinct etiologies, patients suffering from AD or SCZ share a common burden of disrupted memory functions unattended by current therapies. Recent preclinical analyses highlight cell-type-specific contributions of parvalbumin interneurons (PVIs), particularly the plasticity of their cellular excitability, towards intact neuronal network function (cell-to-network plasticity) and memory performance. Here we argue that deficits of PVI cell-to-network plasticity may underlie memory deficits in AD and SCZ, and we explore two therapeutic avenues: the targeting of PVI-specific neuromodulation, including by neuropeptides, and the recruitment of network synchrony in the gamma frequency range (40 Hz) by external stimulation. We finally propose that these approaches be merged under consideration of recent insights into human brain physiology.
Gel microspheres enhance the stemness of ADSCs by regulating cell-ECM interaction
Authors: Qiulin He, Youguo Liao, Haonan Zhang, Wei Sun, Wenyan Zhou, Junxin Lin, Tao Zhang, Shaofang Xie, Hongwei Wu, Jie Han, Yuxiang Zhang, Wei Wei, Chenglin Li, Yi Hong, Weiliang Shen, Hongwei Ouyang
Journal: Biomaterials (2024)
Behavioral science should start by assuming people are reasonable
Authors: Jens Koed Madsen, Lee de-Wit, Peter Ayton, Cameron Brick, Laura de-Moliere, Carla J. Groom
Journal: Trends in Cognitive Sciences (2024)

Should policymaking assume humans are irrational? Using empirical, theoretical, and philosophical arguments, we suggest a more useful frame is that human behavior is reasonable. Through identifying goals and systemic factors shaping behavior, we suggest that assuming people are reasonable enables behavioral science to be more effective in shaping public policy.
A validated web-application (GFDC) for automatic classification of glaucomatous visual field defects using Hodapp-Parrish-Anderson criteria
Authors: Arun James Thirunavukarasu, Nikhil Jain, Rohan Sanghera, Federico Lattuada, Shathar Mahmood, Anna Economou, Helmut C Y Yu, Rupert Bourne
Journal: npj Digital Medicine (2024)

Abstract Subjectivity and ambiguity of visual field classification limits the accuracy and reliability of glaucoma diagnosis, prognostication, and management decisions. Standardised rules for classifying glaucomatous visual field defects exist, but these are labour-intensive and therefore impractical for day-to-day clinical work. Here a web-application, Glaucoma Field Defect Classifier (GFDC), for automatic application of Hodapp-Parrish-Anderson, is presented and validated in a cross-sectional study. GFDC exhibits perfect accuracy in classifying mild, moderate, and severe glaucomatous field defects. GFDC may thereby improve the accuracy and fairness of clinical decision-making in glaucoma. The application and its source code are freely hosted online for clinicians and researchers to use with glaucoma patients.
Regulatory mechanisms of PD-1/PD-L1 in cancers
Authors: Xin Lin, Kuan Kang, Pan Chen, Zhaoyang Zeng, Guiyuan Li, Wei Xiong, Mei Yi, Bo Xiang
Journal: Molecular Cancer (2024)

Abstract Immune evasion contributes to cancer growth and progression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) and programmed cell death ligands (PD-Ls) are considered to be the major immune checkpoint molecules. The interaction of PD-1 and PD-L1 negatively regulates adaptive immune response mainly by inhibiting the activity of effector T cells while enhancing the function of immunosuppressive regulatory T cells (Tregs), largely contributing to the maintenance of immune homeostasis that prevents dysregulated immunity and harmful immune responses. However, cancer cells exploit the PD-1/PD-L1 axis to cause immune escape in cancer development and progression. Blockade of PD-1/PD-L1 by neutralizing antibodies restores T cells activity and enhances anti-tumor immunity, achieving remarkable success in cancer therapy. Therefore, the regulatory mechanisms of PD-1/PD-L1 in cancers have attracted an increasing attention. This article aims to provide a comprehensive review of the roles of the PD-1/PD-L1 signaling in human autoimmune diseases and cancers. We summarize all aspects of regulatory mechanisms underlying the expression and activity of PD-1 and PD-L1 in cancers, including genetic, epigenetic, post-transcriptional and post-translational regulatory mechanisms. In addition, we further summarize the progress in clinical research on the antitumor effects of targeting PD-1/PD-L1 antibodies alone and in combination with other therapeutic approaches, providing new strategies for finding new tumor markers and developing combined therapeutic approaches.
Signal switching may enhance processing power of the brain
Authors: Jennifer M. Groh, Meredith N. Schmehl, Valeria C. Caruso, Surya T. Tokdar
Journal: Trends in Cognitive Sciences (2024)

Our ability to perceive multiple objects is mysterious. Sensory neurons are broadly tuned, producing potential overlap in the populations of neurons activated by each object in a scene. This overlap raises questions about how distinct information is retained about each item. We present a novel signal switching theory of neural representation, which posits that neural signals may interleave representations of individual items across time. Evidence for this theory comes from new statistical tools that overcome the limitations inherent to standard time-and-trial-pooled assessments of neural signals. Our theory has implications for diverse domains of neuroscience, including attention, figure binding/scene segregation, oscillations, and divisive normalization. The general concept of switching between functions could also lend explanatory power to theories of grounded cognition.
Trends in the global, regional, and national burden of testicular cancer from 1990 to 2019: an observational study with 30-year global data
Authors: Xianghong Zhou, Zilong Zhang, Cheng Ruan, Yuwei Wu, Bin Zeng, Xinyang Su, Qiming Yuan, Yifan Li, Qiang Wei, Shi Qiu
Journal: International Journal of Surgery (2024)

Testicular cancer (TC) is currently the most common malignancy in young and middle-aged men. A comprehensive assessment of TC burden is in lack.
The Molecular Microscope Diagnostics System (MMDx) May Have the Potential to Differentiate Molecular T Cell-Mediated Rejection (TCMR) Among Kidney Transplant Recipients with Chronic-Active TCMR
Authors: Thomas Schachtner, Lukas Weidmann, Dusan Harmacek, Kai C. López, Raphael Korach, Nicola Bortel, Thomas F. Mueller
Journal: Journal of the American Society of Nephrology (2023)

Schachtner, Thomas; Weidmann, Lukas; Harmacek, Dusan; López, Kai C.; Korach, Raphael; Bortel, Nicola; Mueller, Thomas F. Author Information
The effect of acupuncture on gastrointestinal recovery after abdominal surgery: a narrative review from clinical trials
Authors: Qi Kong, Li-Ming Chen, Chu-Yu Liu, Wei Li, Pei-Hao Yin
Journal: International Journal of Surgery (2024)

Abdominal surgery is a critical surgery, with more and more attention being paid to postoperative life quality and associated complications in recent years. Among these complications, postoperative gastrointestinal dysfunction is the most common complication of abdominal surgery. Acupuncture therapy is a treatment approach based on the Traditional Chinese Medicine theory, and its feasibility in aiding gastrointestinal recovery after abdominal surgery is supported by both Traditional Chinese Medicine theory and animal experiments. A lot of clinical research has been conducted to evaluate its efficacy, albeit with limitations, and at preliminary stages. Moreover, intervention timing, acupoint selection, and patient benefits should also be considered in clinical practices. This article summarizes the progress of clinical research on acupuncture therapy in gastrointestinal recovery after abdominal surgery and discusses related issues and operations, with the aim to provide new insights and prospects for the incorporation of acupuncture into the Enhanced Recovery After Surgery protocol.