tbuckley/cabot-search huggingface dataset:
Prevalence, progress, and subgroup disparities in pharmacological antidepressant treatment of those who screen positive for depressive symptoms: A repetitive cross-sectional study in 19 European countries
Authors: Shanquan Chen, Tamsin J. Ford, Peter B. Jones, Rudolf N. Cardinal
Journal: The Lancet Regional Health - Europe (2022)

The European Mental Health Action Plan (EMHAP) 2013-2020 promoted community-based mental health services. One potential success indicator is the provision of antidepressant medication to those needing it.Public data from two surveys (Health Survey for England, UK; Survey of Health, Ageing and Retirement in Europe) covered 19 European countries across EMHAP phases one (2011-2015) and two (2015-2018). People screening positive for depressive symptoms by self-report were included. The primary outcome was antidepressant use: using country-specific weighted regression models, we estimated temporal trends and subgroup disparities in antidepressant receipt, with secondary analysis by country-level measures including healthcare expenditure.Across 37,250 participants, after controlling for age, sex, wealth, and physical disability, antidepressant use (amongst those screening positive) increased significantly in 14/19 countries, with the smallest increase being in Slovenia (adjusted OR[AOR] for trend=1.68[1.20-2.36]) and the highest increase being in Germany (AOR for trend=10.07[7.54-13.46]) and Austria (AOR for trend=10.07[7.32-13.74]). The overall proportion using antidepressants was positively associated with national health expenditure (coefficient=5.43[1.62-9.25]), but not with gross national income per capita or the number of psychiatrists, general practitioners, or psychiatric hospital beds. In 15/19 countries, antidepressants were used less by ≥65-year-olds than 50-64-year-olds, with the smallest differential reported in Luxembourg (AOR=0.70[0.49, 0.98]) and the highest in Germany (AOR=0.28[0.21, 0.37]); this disparity widened in 12/15 countries. Men used antidepressants less than women in 8/19 countries, across phases. In 13/19 countries, people with physical disability were more likely to receive antidepressants, with the smallest gap in Italy (AOR=1.42[1.12-1.80]) and the largest in Israel (AOR=2.34[1.46-3.74]); this disparity narrowed in 5/13 countries. Disparity by wealth was found in 8/19 countries, but its temporal trend varied.Usage of antidepressants by those with depressive symptoms has increased, with wide variation between countries and subgroups. Disparities across age, sex, and disability should prompt further research.Medical Research Council (grants MC_PC_17213 and MR/W014386/1), UK National Institute for Health Research (NIHR) Applied Research Collaboration (ARC) East of England, NIHR Cambridge Biomedical Research Centre (BRC-1215-20014).
Calorie restriction improves metabolic state independently of gut microbiome composition: a randomized dietary intervention trial
Authors: Solomon A. Sowah, Alessio Milanese, Ruth Schübel, Jakob Wirbel, Ece Kartal, Theron S. Johnson, Frank Hirche, Mirja Grafetstätter, Tobias Nonnenmacher, Romy Kirsten, Marina López-Nogueroles, Agustín Lahoz, Kathrin V. Schwarz, Jürgen G. Okun, Cornelia M. Ulrich, Johanna Nattenmüller, Arnold von Eckardstein, Daniel Müller, Gabriele I. Stangl, Rudolf Kaaks, Tilman Kühn, Georg Zeller
Journal: Genome Medicine (2022)

The gut microbiota has been suggested to play a significant role in the development of overweight and obesity. However, the effects of calorie restriction on gut microbiota of overweight and obese adults, especially over longer durations, are largely unexplored.Here, we longitudinally analyzed the effects of intermittent calorie restriction (ICR) operationalized as the 5:2 diet versus continuous calorie restriction (CCR) on fecal microbiota of 147 overweight or obese adults in a 50-week parallel-arm randomized controlled trial, the HELENA Trial. The primary outcome of the trial was the differential effects of ICR versus CCR on gene expression in subcutaneous adipose tissue. Changes in the gut microbiome, which are the focus of this publication, were defined as exploratory endpoint of the trial. The trial comprised a 12-week intervention period, a 12-week maintenance period, and a final follow-up period of 26 weeks.Both diets resulted in ~5% weight loss. However, except for Lactobacillales being enriched after ICR, post-intervention microbiome composition did not significantly differ between groups. Overall weight loss was associated with significant metabolic improvements, but not with changes in the gut microbiome. Nonetheless, the abundance of the Dorea genus at baseline was moderately predictive of subsequent weight loss (AUROC of 0.74 for distinguishing the highest versus lowest weight loss quartiles). Despite the lack of consistent intervention effects on microbiome composition, significant study group-independent co-variation between gut bacterial families and metabolic biomarkers, anthropometric measures, and dietary composition was detectable. Our analysis in particular revealed associations between insulin sensitivity (HOMA-IR) and Akkermansiaceae, Christensenellaceae, and Tanerellaceae. It also suggests the possibility of a beneficial modulation of the latter two intestinal taxa by a diet high in vegetables and fiber, and low in processed meat.Overall, our results suggest that the gut microbiome remains stable and highly individual-specific under dietary calorie restriction.The trial, including the present microbiome component, was prospectively registered at ClinicalTrials.gov NCT02449148 on May 20, 2015.
Deep Ensemble Machine Learning Framework for the Estimation of PM2.5 Concentrations
Authors: Wenhua Yu, Shanshan Li, Tingting Ye, Rongbin Xu, Jiangning Song, Yuming Guo
Journal: Environmental Health Perspectives (2022)

Background: Accurate estimation of historical PM2.5 (particle matter with an aerodynamic diameter of less than 2.5μm) is critical and essential for environmental health risk assessment. Objectives: The aim of this study was to develop a multiple-level stacked ensemble machine learning framework for improving the estimation of the daily ground-level PM2.5 concentrations. Methods: An innovative deep ensemble machine learning framework (DEML) was developed to estimate the daily PM2.5 concentrations. The framework has a three-stage structure: At the first stage, four base models [gradient boosting machine (GBM), support vector machine (SVM), random forest (RF), and eXtreme gradient boosting (XGBoost)] were used to generate a new data set of PM2.5 concentrations for training the next-stage learners. At the second stage, three meta-models [RF, XGBoost, and Generalized Linear Model (GLM)] were used to estimate PM2.5 concentrations using a combination of the original data set and the predictions from the first-stage models. At the third stage, a nonnegative least squares (NNLS) algorithm was employed to obtain the optimal weights for PM2.5 estimation. We took the data from 133 monitoring stations in Italy as an example to implement the DEML to predict daily PM2.5 at each 1km×1km grid cell from 2015 to 2019 across Italy. We evaluated the model performance by performing 10-fold cross-validation (CV) and compared it with five benchmark algorithms [GBM, SVM, RF, XGBoost, and Super Learner (SL)]. Results: The results revealed that the PM2.5 prediction performance of DEML [coefficients of determination (R2)=0.87 and root mean square error (RMSE)=5.38μg/m3] was superior to any benchmark models (with R2 of 0.51, 0.76, 0.83, 0.70, and 0.83 for GBM, SVM, RF, XGBoost, and SL approach, respectively). DEML displayed reliable performance in capturing the spatiotemporal variations of PM2.5 in Italy. Discussion: The proposed DEML framework achieved an outstanding performance in PM2.5 estimation, which could be used as a tool for more accurate environmental exposure assessment. https://doi.org/10.1289/EHP9752
Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer
Authors: Gabriel N. Hortobagyi, Salomon M. Stemmer, Howard A. Burris, Yoon-Sim Yap, Gabe S. Sonke, Lowell Hart, Mario Campone, Katarina Petrakova, Eric P. Winer, Wolfgang Janni, Pierfranco Conte, David A. Cameron, Fabrice André, Carlos L. Arteaga, Juan P. Zarate, Arunava Chakravartty, Tetiana Taran, Fabienne Le Gac, Paolo Serra, Joyce O’Shaughnessy
Journal: New England Journal of Medicine (2022)

In a previous analysis of this phase 3 trial, first-line ribociclib plus letrozole resulted in significantly longer progression-free survival than letrozole alone among postmenopausal patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether overall survival would also be longer with ribociclib was not known.Here we report the results of the protocol-specified final analysis of overall survival, a key secondary end point. Patients were randomly assigned in a 1:1 ratio to receive either ribociclib or placebo in combination with letrozole. Overall survival was assessed with the use of a stratified log-rank test and summarized with the use of Kaplan-Meier methods after 400 deaths had occurred. A hierarchical testing strategy was used for the analysis of progression-free survival and overall survival to ensure the validity of the findings.After a median follow-up of 6.6 years, 181 deaths had occurred among 334 patients (54.2%) in the ribociclib group and 219 among 334 (65.6%) in the placebo group. Ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole. Median overall survival was 63.9 months (95% confidence interval [CI], 52.4 to 71.0) with ribociclib plus letrozole and 51.4 months (95% CI, 47.2 to 59.7) with placebo plus letrozole (hazard ratio for death, 0.76; 95% CI, 0.63 to 0.93; two-sided P = 0.008). No new safety signals were observed.First-line therapy with ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole in patients with HR-positive, HER2-negative advanced breast cancer. Median overall survival was more than 12 months longer with ribociclib than with placebo. (Funded by Novartis; MONALEESA-2 ClinicalTrials.gov number, NCT01958021.).
Abstract P4-10-13: Area deprivation index and rurality in relation to financial toxicity among breast cancer surgical patients - Investigating geospatial differences in risk profiles
Authors: Joseph P Corkum, Victor Zhu, Victor Agbafe, Carrie Chu, Jessica Suarez Colen, Rachel Greenup, Anaeze C. Offodile
Journal: Cancer Research (2022)

Abstract Background: Financial toxicity (FT) depicts the burden of cancer treatment-costs and is associated with lower quality-of-life and survival in breast cancer survivors. We examined the relationship between geospatial location, represented by rurality and Area Deprivation Index (ADI), and risk of FT.Study Design: A single-institution, cross-sectional study was performed on adult female surgical breast cancer patients. Chart reviews were used to obtain patient information while FT was identified using a validated instrument. Patients’ home addresses were used to determine rurality using the Rural Urban Continuum Codes and linked to national ADI score. Tertile ADI groups enabled statistical analysis and multivariate logistic regression models were developed to determine the independent effects of geospatial location and FT.Results: A total of 568 surgical breast cancer patients were included. Univariate analyses showed significant differences across ADI tertiles with respect to race/ethnicity, marital status, insurance type, education, and rurality. Following multivariate analysis, advanced cancer stage (OR 2.26, CI: 1.15-4.44), and escalating ADI (OR 1.012, CI:1.005-1.020) were associated with worsening FT. Increasing age (OR 0.976, CI: 0.96- 0.992), marital status (OR 0.458, CI: 0.299-0.699), receipt of bilateral mastectomy (OR 0.558, CI: 0.323-0.964) were protective of FT. Increasing ADI was also significantly associated with use of coping strategiesConclusion: FT was significantly associated with areas of higher socioeconomic deprivation as measured by the ADI. However, rurality was not found to be a significant predictor of FT. ADI may be used to facilitate pre-operative screening of at-risk populations and the deployment of community-based interventions to alleviate FT. Multivariate logistic regression analysis results. Citation Format: Joseph P Corkum, Victor Zhu, Victor Agbafe, Carrie Chu, Jessica Suarez Colen, Rachel Greenup, Anaeze C. Offodile. Area deprivation index and rurality in relation to financial toxicity among breast cancer surgical patients - Investigating geospatial differences in risk profiles [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-13.
Protein tyrosine phosphatase receptor δ serves as the orexigenic asprosin receptor
Authors: Ila Mishra, Wei Rose Xie, Juan C Bournat, Yang He, Chunmei Wang, Elizabeth Sabath Silva, Hailan Liu, Zhiqiang Ku, Yinghua Chen, Bernadette O Erokwu, Peilin Jia, Zhongming Zhao, Zhiqiang An, Chris A Flask, Yanlin He, Yong Xu, Atul R Chopra
Journal: Cell Metabolism (2022)
LIKE DEFUSING A BOMB! IMPLICATIONS OF MISDIAGNOSING THE PRIMARY CULPRIT OF A PATIENT WITH DE NOVO HEART FAILURE WITH REDUCED EJECTION FRACTION AND MULTIPLE ETIOLOGIES
Authors: Alfredo Lamela, Hector E. Sepulveda Alemany, Erica G. Otero-Cardenas, Marcel A. Mesa Pabon
Journal: Journal of the American College of Cardiology (2022)
Genetic and Clinical Features of Blau Syndrome among Chinese Patients with Uveitis
Authors: Zhenyu Zhong, Jiadong Ding, Guannan Su, Weiting Liao, Yu Gao, Yunyun Zhu, Yang Deng, Fuzhen Li, Liping Du, Yuan Gao, Peizeng Yang
Journal: Ophthalmology (2022)
Deep learning-enabled assessment of cardiac allograft rejection from endomyocardial biopsies
Authors: Jana Lipkova, Tiffany Y. Chen, Ming Y. Lu, Richard J. Chen, Maha Shady, Mane Williams, Jingwen Wang, Zahra Noor, Richard N. Mitchell, Mehmet Turan, Gulfize Coskun, Funda Yilmaz, Derya Demir, Deniz Nart, Kayhan Basak, Nesrin Turhan, Selvinaz Ozkara, Yara Banz, Katja E. Odening, Faisal Mahmood
Journal: Nature Medicine (2022)
Nintedanib plus chemotherapy for nonsmall cell lung cancer with idiopathic pulmonary fibrosis: a randomised phase 3 trial
Authors: Kohei Otsubo, Junji Kishimoto, Masahiko Ando, Hirotsugu Kenmotsu, Yuji Minegishi, Hidehito Horinouchi, Terufumi Kato, Eiki Ichihara, Masashi Kondo, Shinji Atagi, Motohiro Tamiya, Satoshi Ikeda, Toshiyuki Harada, Shinnosuke Takemoto, Hidetoshi Hayashi, Keita Nakatomi, Yuichiro Kimura, Yasuhiro Kondoh, Masahiko Kusumoto, Kazuya Ichikado, Nobuyuki Yamamoto, Kazuhiko Nakagawa, Yoichi Nakanishi, Isamu Okamoto
Journal: European Respiratory Journal (2022)

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease implicated as an independent risk factor for lung cancer. However, optimal treatment for advanced lung cancer with IPF remains to be established. We performed a randomised phase 3 trial (J-SONIC) to assess the efficacy and safety of nintedanib plus chemotherapy (experimental arm) compared with chemotherapy alone (standard-of-care arm) for advanced nonsmall cell lung cancer (NSCLC) with IPF.Chemotherapy-naïve advanced NSCLC patients with IPF were allocated to receive carboplatin (area under the curve of 6 on day 1) plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) (100 mg·m-2 on days 1, 8 and 15) every 3 weeks with or without nintedanib (150 mg twice daily, daily). The primary end-point was exacerbation-free survival (EFS).Between May 2017 and February 2020, 243 patients were enrolled. Median EFS was 14.6 months in the nintedanib plus chemotherapy group and 11.8 months in the chemotherapy group (hazard ratio (HR) 0.89, 90% CI 0.67-1.17; p=0.24), whereas median progression-free survival was 6.2 and 5.5 months, respectively (HR 0.68, 95% CI 0.50-0.92). Overall survival was improved by nintedanib in patients with nonsquamous histology (HR 0.61, 95% CI 0.40-0.93) and in those at GAP (gender-age-physiology) stage I (HR 0.61, 95% CI 0.38-0.98). Seven (2.9%) out of 240 patients experienced acute exacerbation during study treatment.The primary end-point of the study was not met. However, carboplatin plus nab-paclitaxel was found to be effective and tolerable in advanced NSCLC patients with IPF. Moreover, nintedanib in combination with such chemotherapy improved overall survival in patients with nonsquamous histology.
Both G protein–coupled and immunoreceptor tyrosine-based activation motif receptors mediate venous thrombosis in mice
Authors: Jean Marie N. Mwiza, Robert H. Lee, David S. Paul, Lori A. Holle, Brian C. Cooley, Bernhard Nieswandt, Wyatt J. Schug, Tomohiro Kawano, Nigel Mackman, Alisa S. Wolberg, Wolfgang Bergmeier
Journal: Blood (2022)
Aldafermin in patients with non-alcoholic steatohepatitis (ALPINE 2/3): a randomised, double-blind, placebo-controlled, phase 2b trial
Authors: Stephen A Harrison, Manal F Abdelmalek, Guy Neff, Nadege Gunn, Cynthia D Guy, Naim Alkhouri, Mustafa R Bashir, Bradley Freilich, Anita Kohli, Arun Khazanchi, Muhammad Y Sheikh, Mark Leibowitz, Mary E Rinella, Mohammad S Siddiqui, Mark Kipnes, Sam E Moussa, Ziad H Younes, Meena Bansal, Seth J Baum, Brian Borg, Peter J Ruane, Paul J Thuluvath, Mildred Gottwald, Mujib Khan, Charles Chen, Liza Melchor-Khan, William Chang, Alex M DePaoli, Lei Ling, Hsiao D Lieu
Journal: The Lancet. Gastroenterology & hepatology (2022)
FLAIL TRICUSPID VALVE DUE TO PAPILLARY MUSCLE RUPTURE IN INFANT WITH CONGENITAL COMPLETE HEART BLOCK - A RARE COMPLICATION OF NEONATAL LUPUS.
Authors: Jeffrey Nafash, David B. Meyer, Chalese Richardson, Preeta Dhanantwari, Eliza Uster, Elizabeth Mitchell
Journal: Journal of the American College of Cardiology (2022)
Evaluating the Effects of BPA and TBBPA Exposure on Pregnancy Loss and Maternal–Fetal Immune Cells in Mice
Authors: Jasmine M. Reed, Philip Spinelli, Sierra Falcone, Miao He, Calla M. Goeke, Martha Susiarjo
Journal: Environmental Health Perspectives (2022)

Bisphenol A (BPA) exposure has been linked to miscarriages and pregnancy complications in humans. In contrast, the potential reproductive toxicity of BPA analogs, including tetrabromobisphenol A (TBBPA), is understudied. Furthermore, although environmental exposure has been linked to altered immune mediators, the effects of BPA and TBBPA on maternal-fetal immune tolerance during pregnancy have not been studied. The present study investigated whether exposure resulted in higher rates of pregnancy loss in mice, lower number of regulatory T cells (Tregs), and lower indoleamine 2,3 deoxygenase 1 (Ido1) expression, which provided evidence for mechanisms related to immune tolerance in pregnancy.The purpose of this investigation was to characterize the effects of BPA and TBBPA exposure on pregnancy loss in mice and to study the percentage and number of Tregs and Ido1 expression and DNA methylation.Analysis of fetal resorption and quantification of maternal and fetal immune cells by flow cytometry were performed in allogeneic and syngeneic pregnancies. Ido1 mRNA and protein expression, and DNA methylation in placentas from control and BPA- and TBBPA-exposed mice were analyzed using real-time quantitative polymerase chain reaction, immunofluorescence, and bisulfite sequencing analyses.BPA and TBBPA exposure resulted in higher rates of hemorrhaging in early allogeneic, but not syngeneic, conceptuses. In allogeneic pregnancies, BPA and TBBPA exposure was associated with higher fetal resorption rates and lower maternal Treg number. Importantly, these differences were associated with lower IDO1 protein expression in trophoblast giant cells and higher mean percentage Ido1 DNA methylation in embryonic day 9.5 placentas from BPA- and TBBPA-exposed mice.BPA- and TBBPA-induced pregnancy loss in mice was associated with perturbed IDO1-dependent maternal immune tolerance. https://doi.org/10.1289/EHP10640.
The sexual dimorphism of kidney growth in mice and humans
Authors: Denise Laouari, Paul Vergnaud, Takuo Hirose, Mohamad Zaidan, Marion Rabant, Clément Nguyen, Martine Burtin, Christophe Legendre, Patrice Codogno, Gerard Friedlander, Dany Anglicheau, Fabiola Terzi
Journal: Kidney International (2022)
Intratumoral heterogeneity of MYC drives medulloblastoma metastasis and angiogenesis
Authors: Nan Qin, Eunice Paisana, Maike Langini, Daniel Picard, Bastian Malzkorn, Carlos Custódia, Rita Cascão, Frauke-Dorothee Meyer, Lena Blümel, Sarah Göbbels, Kübra Taban, Jasmin Bartl, Nicole Bechmann, Catleen Conrad, Jan Gravemeyer, Jürgen C Becker, Anja Stefanski, Stéphanie Puget, João T Barata, Kai Stühler, Ute Fischer, Jörg Felsberg, Olivier Ayrault, Guido Reifenberger, Arndt Borkhardt, Graeme Eisenhofer, Claudia C Faria, Marc Remke
Journal: Neuro-Oncology (2022)

Abstract Background Intratumoral heterogeneity is crucially involved in metastasis, resistance to therapy, and cancer relapse. Amplifications of the proto-oncogene MYC display notable heterogeneity at the single-cell level and are associated with a particularly dismal prognosis in high-risk medulloblastomas (MBs). The aim of this study was to establish the relevance of interclonal cross-talk between MYC-driven and non-MYC-driven MB cells. Methods We used fluorescence in situ hybridization, single-cell transcriptomics, and immunohistochemistry, in vitro isogenic cell models, non-targeted proteomics, mass spectrometry-based metabolite quantification, HUVECs tube formation assay, and orthotopic in vivo experiments to investigate interclonal cross-talk in MB. Results We found that the release of lactate dehydrogenase A (LDHA) from MYC-driven cells facilitates metastatic seeding and outgrowth, while secretion of dickkopf WNT signaling pathway inhibitor 3 from non-MYC-driven cells promotes tumor angiogenesis. This tumor-supporting interaction between both subclones was abrogated by targeting the secretome through pharmacological and genetic inhibition of LDHA, which significantly suppressed tumor cell migration. Conclusion Our study reveals the functional relevance of clonal diversity and highlights the therapeutic potential of targeting the secretome to interrupt interclonal communication and progression in high-risk MB.
Insights and Opportunities in STEMI Care in China
Authors: Hani Jneid
Journal: JAMA Cardiology (2022)

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OUTCOMES IN ESRD AND CKD PATIENTS UNDERGOING NON-DURABLE PERCUTANEOUS LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION: INSIGHTS FROM UNITED STATES RENAL DATA SYSTEM
Authors: Tarun Dalia, Wan-Chi Chan, Harsh Mehta, Sagar Ranka, Amandeep Goyal, Prakash Acharya, Andrew Sauer, Andrija Vidic, Zubair Shah
Journal: Journal of the American College of Cardiology (2022)