tbuckley/cabot-search huggingface dataset:
Abstract P183: Elevated Phq-9 Scores In Black And Hispanic Young Adults
Authors: Janna D Stephens, Jillian Randolph, Sophia Leissa, Carla Miller, Bernadette Melnyk, Lora E Burke, Brenda Buffington, Alai Tan
Journal: Circulation (2022)

Background: The ASPIRE study is a NIH funded clinical trial seeking to reduce cardiovascular disease risk factors in young adults who identify as Black and Hispanic through the provision of an individualized, text message-based intervention. The intervention has been developed specifically for this demographic group through formative research and seeks to understand the moderating and mediating effects of depressive symptoms, self-efficacy, and discrimination on weight loss maintenance over the 12 months. The goal of this preliminary analysis is to describe baseline depressive symptoms in this population to both conceptualize the mental health needs of students and increase the accessibility of established resources through developing community informed referral guidelines. Methods: Participants are recruited into a behavior change clinical trial and randomly assigned to either an intervention group with a health coach or an attention control group. Participants completed the Patient Health Questionnaire for adults (PHQ-9) as a part of baseline surveys. This questionnaire assesses depressive symptoms through 10 self-administered questions. Scores ranging from 5-9 indicate mild symptoms 10-14 moderate symptoms, 15-19 moderately severe, and 20-27 severe symptoms of depression. Participant data is stored in REDCap and preliminary analysis was pulled and summarized for total scores from the PHQ-9 for all participants who have completed a baseline visit. There is no missing data. Results: Preliminary baseline data from a large Midwestern community college (N=101; 72% female; mean age = 20.8 (SD=2.02)) indicate the significant experience of depressive symptoms amongst participants. More than 58% of our sample screened for at least mild symptoms of depression. More significantly, greater than 21% of the sample indicates at least moderate symptoms of depression. Discussion and Conclusion: There is no comprehensive nationwide data to which we can compare these results, however the American College Health (ACH) National College Health Assessment completed in undergraduate students indicated that 50% of students surveyed had no significant symptoms of depression on the Kessler 6 scale. Therefore, we believe levels of depressive symptoms may be higher in this population of community college students who identify as Black or Hispanic. Due to high levels of depressive symptoms, the research team has since engaged in participatory research methods with the community advisory board and other members of the community to enhance study protocols and identify community-based resources to serve as referrals for participants who score above 5 on the PHQ-9.
Clinical annotations for prostate cancer research: Defining data elements, creating a reproducible analytical pipeline, and assessing data quality.
Authors: Niamh M. Keegan, Samantha E Vasselman, Ethan Barnett, Barbara Nweji, Emily Carbone, Alexander Blum, Michael J. Morris, Dana E. Rathkopf, Susan F. Slovin, Daniel Costin Danila, Karen A. Autio, Howard I. Scher, Philip W. Kantoff, Wassim Abida, Konrad H. Stopsack
Journal: Journal of Clinical Oncology (2022)

64 Background: Routine clinical data from the electronic medical record are indispensable for retrospective and prospective observational studies and clinical trials. Their reproducibility is often not assessed. We sought to develop a prostate cancer-specific database with a defined source hierarchy for clinical annotations and to evaluate data reproducibility. Methods: At a comprehensive cancer center, we designed and implemented a clinical database for men with prostate cancer and clinical-grade paired tumor–normal sequencing for whom we performed team-based retrospective clinical data annotation from the electronic medical record, using a prostate cancer-specific data dictionary. We developed an open-source R package for data processing. We then evaluated completeness of data elements, reproducibility of team-based annotation using blinded repeat annotation by a medical oncologist as the reference, and the impact of measurement error on bias in survival analyses. Results: Data elements on demographics, diagnosis and staging, disease state at the time of procuring a genomically characterized sample, and clinical outcomes were piloted and then abstracted for 2,261 patients and their 2,631 genomically profiled samples. Completeness of data elements was generally high, between 55% to 99% for elements of clinical TNM staging, self-reported race, biopsy Gleason score, and presence of variant histologies, both for the team-based annotation and the repeat annotation. Comparing team-based annotation to the repeat annotation (100 patients/samples), reproducibility of annotations was high to very high. For 7 binary data elements, both sensitivity and specificity of the team-based annotation reached or exceeded 90%. The T stage, metastasis date, and presence and date of castration resistance had lower reproducibility. Impact of measurement error on estimates for strong prognostic factors was modest. Conclusions: With a prostate cancer-specific data dictionary and quality control measures, manual team-based annotations can be scalable and reproducible. The data dictionary and the R package for reproducible data processing tools provided (https://stopsack.github.io/prostateredcap) are freely available to help increase data quality in clinical prostate cancer research.
Studying severe long COVID to understand post-infectious disorders beyond COVID-19
Authors: Petter Brodin, Giorgio Casari, Liam Townsend, Cliona O’Farrelly, Ivan Tancevski, Judith Löffler-Ragg, Trine H. Mogensen, Jean Laurent Casanova, Laurent Abel, Alessandro Aiuti, Saleh Al-Muhsen, Fahd Al-Mulla, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Hagit Baris Feldman, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Alexandre Bolze, Anastasiia Bondarenko, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Carlos D. Bustamante, Manish J. Butte, Giorgio Casari, John Christodoulou, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Clifton L. Dalgard, Murkesh Desai, Beth A. Drolet, Jamila El Baghdadi, Sara Espinosa-Padilla, Jacques Fellay, Carlos Flores, José Luis Franco, Antoine Froidure, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Sarah E. Henrickson, Elena W. Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Erich D. Jarvis, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Tomohiro Morio, Lisa F. P. Ng, Antonio Novelli, Giuseppe Novelli, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Jean W. Pape, Rebeca Perez de Diego, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Laurent Renia, Igor Resnick, Carlos Rodríguez-Gallego, Vanessa Sancho-Shimizu, Anna Sediva, Mikko R. J. Seppänen, Mohammed Shahrooei, Anna Shcherbina, Ondrej Slaby, Andrew L. Snow, Pere Soler-Palacín, András N. Spaan, Stuart G. Tangye, Ahmad Abou Tayoun, Stuart E. Turvey, K. M. Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Pawel Zawadzki, Jean-Laurent Casanova
Journal: Nature Medicine (2022)
The Study to Investigate COVID-19 Infection in People Living in Ireland (SCOPI): A seroprevalence study, June to July 2020
Authors: Laura Heavey, Patricia Garvey, Aoife M Colgan, Lelia Thornton, Jeff Connell, Thomas Roux, Meadhbh Hunt, Fiona O'Callaghan, Fiona Culkin, Mary Keogan, Nuala O'Connor, Margaret B O'Sullivan, Siobhán O’Sullivan, Michele Tait, Cillian F De Gascun, Derval Igoe
Journal: Eurosurveillance (2021)

BackgroundRobust data on SARS-CoV-2 population seroprevalence supplement surveillance data in providing evidence for public health action.AimTo conduct a SARS-CoV-2 population-based seroprevalence survey in Ireland.MethodsUsing a cross-sectional study design, we selected population samples from individuals aged 12-69 years in counties Dublin and Sligo using the Health Service Executive Primary Care Reimbursement Service database as a sampling frame. Samples were selected with probability proportional to the general population age-sex distribution, and by simple random sampling within age-sex strata. Antibodies to SARS-CoV-2 were detected using the Abbott Architect SARS-CoV-2 IgG Assay and confirmed using the Wantai Assay. We estimated the population SARS-CoV-2 seroprevalence weighted for age, sex and geographic area.ResultsParticipation rates were 30% (913/3,043) and 44% (820/1,863) in Dublin and Sligo. Thirty-three specimens had detectable SARS-CoV-2 antibodies (1.9%). We estimated weighted seroprevalences of 3.12% (95% confidence interval (CI): 2.05-4.53) and 0.58% (95% CI: 0.18-1.38) for Dublin and Sligo, and 1.69% (95% CI: 1.13-2.41) nationally. This equates to an estimated 59,482 (95% CI: 39,772-85,176) people aged 12-69 years nationally having had infection with SARS-CoV-2, 3.0 (95% CI: 2.0-4.3) times higher than confirmed notifications. Ten participants reported a previous laboratory-confirmed SARS-CoV-2 -infection; eight of these were antibody-positive. Twenty-five antibody-positive participants had not reported previous laboratory-confirmed infection.ConclusionThe majority of people in Ireland are unlikely to have been infected with SARS-CoV-2 by June-July 2020. Non-pharmaceutical public health measures remained key pending widespread availability of vaccination, and effective treatments.
Identification of key genes and carcinogenic pathways in hepatitis B virus-associated hepatocellular carcinoma through bioinformatics analysis
Authors: Sang Hoon Kim, Shin Hwang, Gi-Won Song, Dong-Hwan Jung, Deok-Bog Moon, Jae Do Yang, Hee Chul Yu, Sung-Gyu Lee
Journal: International Journal of Surgery (2022)
Meeting the high expectations for liquid biopsy assays for pediatric brain tumors: Progress and challenges
Authors: Jaclyn A Biegel
Journal: Neuro-Oncology (2022)

Central nervous system (CNS) tumors are the most frequent solid tumors in children. Despite remarkable advancements which have led to improved long-term survival, especially for children with embryonal tumors, such as medulloblastoma and atypical teratoid/rhabdoid tumor, the morbidities associated with radiation and chemotherapy are significant. Refinements in diagnosing, staging, and treating children with brain tumors are largely being driven by the elucidation of a rapidly expanding catalog of tumor-associated genomic alterations, as detailed in the most recent edition of the WHO Classification of Central Nervous System Tumors.1 Microarrays and next-generation sequencing (NGS)-based methods for detecting copy number variants, sequence alterations, structural variants, or methylation signatures in DNA and RNA have been optimized for low-input amounts of nucleic acids, even from formalin-fixed and paraffin-embedded tumor specimens.2 These assays can be performed within several days, well within the time frame needed to develop a personalized treatment or management plan. Despite these impressive advancements, however, the utility of these assays still depends on obtaining tumor tissue for histologic, immunophenotypic, and genomic characterization. Patients who are not clinically stable or have tumors in challenging anatomic locations not amenable to surgical intervention are subject to delays in diagnosis, or receive a diagnosis determined by neurologic examination and imaging.
Achievement of guideline recommended diabetes treatment targets and health habits in people with self-reported diabetes in India (ICMR-INDIAB-13): a national cross-sectional study
Authors: Ranjit Mohan Anjana, Ranjit Unnikrishnan, Mohan Deepa, Ulagamathesan Venkatesan, Rajendra Pradeepa, Shashank Joshi, Banshi Saboo, Ashok Kumar Das, Sarita Bajaj, Anil Bhansali, Sri Venkata Madhu, Vinay Kumar Dhandhania, Puthiyaveettil Kottayam Jabbar, Sunil M Jain, Arvind Gupta, Subhankar Chowdhury, Mohammed K Ali, Elangovan Nirmal, Radhakrishnan Subashini, Tanvir Kaur, Rupinder Singh Dhaliwal, Nikhil Tandon, Viswanathan Mohan, Ranjit Mohan Anjana, Ranjit Unnikrishnan, Mohan Deepa, Ulagamathesan Venkatesan, Rajendra Pradeepa, Shashank R Joshi, Banshi Saboo, Ashok Kumar Das, Sarita Bajaj, Anil Bhansali, Sri Venkata Madhu, Vinay Kumar Dhandhania, Puthiyaveettil Kottayam Jabbar, Sunil M Jain, Arvind Gupta, Subhankar Chowdhury, Mohammed K Ali, Elangovan Nirmal, Radhakrishnan Subashini, Tanvir Kaur, Rupinder Singh Dhaliwal, Nikhil Tandon, Viswanathan Mohan
Journal: The Lancet Diabetes & Endocrinology (2022)
Responding to health emergencies in the Eastern Mediterranean region in times of conflict
Authors: Richard Brennan, Rana Hajjeh, Ahmed Al-Mandhari
Journal: The Lancet (2020)

WHO's Eastern Mediterranean region (EMR) is facing emergencies on a scale that is perhaps unprecedented in its history. There is armed conflict in 12 of the region's 22 countries.1,2 The region's 680 million people3 represent 9% of the global population, yet the EMR is home to 43% of those who need humanitarian assistance4 and is the source of 64% of the world's refugees.5
150P Monitoring of PD-L1 expression on circulating immune cells of patients with small cell lung cancer (SCLC) receiving first-line treatment: Prognostic implications
Authors: M.A. Papadaki, M-N. Nikolarakou, E. Vorrias, E-E. Kapetanaki, D. Kalapanida, D. Mavroudis, S. Agelaki
Journal: Annals of Oncology (2022)
Therapeutic Targets for Heart Failure Identified Using Proteomics and Mendelian Randomization
Authors: Albert Henry, María Gordillo-Marañón, Chris Finan, Amand F. Schmidt, João Pedro Ferreira, Ravi Karra, Johan Sundström, Lars Lind, Johan Ärnlöv, Faiez Zannad, Anders Mälarstig, Aroon D. Hingorani, R. Thomas Lumbers
Journal: Circulation (2022)

Background: Heart failure (HF) is a highly prevalent disorder for which disease mechanisms are incompletely understood. The discovery of disease-associated proteins with causal genetic evidence provides an opportunity to identify new therapeutic targets. Methods: We investigated the observational and causal associations of 90 cardiovascular proteins, which were measured using affinity-based proteomic assays. First, we estimated the associations of 90 cardiovascular proteins with incident heart failure by means of a fixed-effect meta-analysis of 4 population-based studies, composed of a total of 3019 participants with 732 HF events. The causal effects of HF-associated proteins were then investigated by Mendelian randomization, using cis -protein quantitative loci genetic instruments identified from genomewide association studies in more than 30 000 individuals. To improve the precision of causal estimates, we implemented an Mendelian randomization model that accounted for linkage disequilibrium between instruments and tested the robustness of causal estimates through a multiverse sensitivity analysis that included up to 120 combinations of instrument selection parameters and Mendelian randomization models per protein. The druggability of candidate proteins was surveyed, and mechanism of action and potential on-target side effects were explored with cross-trait Mendelian randomization analysis. Results: Forty-four of ninety proteins were positively associated with risk of incident HF ( P &lt;6.0×10 –4 ). Among these, 8 proteins had evidence of a causal association with HF that was robust to multiverse sensitivity analysis: higher CSF-1 (macrophage colony-stimulating factor 1), Gal-3 (galectin-3) and KIM-1 (kidney injury molecule 1) were positively associated with risk of HF, whereas higher ADM (adrenomedullin), CHI3L1 (chitinase-3-like protein 1), CTSL1 (cathepsin L1), FGF-23 (fibroblast growth factor 23), and MMP-12 (matrix metalloproteinase-12) were protective. Therapeutics targeting ADM and Gal-3 are currently under evaluation in clinical trials, and all the remaining proteins were considered druggable, except KIM-1. Conclusions: We identified 44 circulating proteins that were associated with incident HF, of which 8 showed evidence of a causal relationship and 7 were druggable, including adrenomedullin, which represents a particularly promising drug target. Our approach demonstrates a tractable roadmap for the triangulation of population genomic and proteomic data for the prioritization of therapeutic targets for complex human diseases.
Fighting in a wasteland: deleterious metabolites and antitumor immunity
Authors: McLane J. Watson, Greg M. Delgoffe
Journal: Journal of Clinical Investigation (2022)

As cancers progress, they produce a local environment that acts to redirect, paralyze, exhaust, or otherwise evade immune detection and destruction. The tumor microenvironment (TME) has long been characterized as a metabolic desert, depleted of essential nutrients such as glucose, oxygen, and amino acids, that starves infiltrating immune cells and renders them dysfunctional. While not incorrect, this perspective is only half the picture. The TME is not a metabolic vacuum, only consuming essential nutrients and never producing by-products. Rather, the by-products of depleted nutrients, "toxic" metabolites in the TME such as lactic acid, kynurenine, ROS, and adenosine, play an important role in shaping immune cell function and cannot be overlooked in cancer immunotherapy. Moreover, while the metabolic landscape is distinct, it is not unique, as these toxic metabolites are encountered in non-tumor tissues, where they evolutionarily shape immune cells and their response. In this Review, we discuss how depletion of essential nutrients and production of toxic metabolites shape the immune response within the TME and how toxic metabolites can be targeted to improve current cancer immunotherapies.
Long Noncoding RNA <i>MIAT</i> Controls Advanced Atherosclerotic Lesion Formation and Plaque Destabilization
Authors: Francesca Fasolo, Hong Jin, Greg Winski, Ekaterina Chernogubova, Jessica Pauli, Hanna Winter, Daniel Y. Li, Nadiya Glukha, Sabine Bauer, Susanne Metschl, Zhiyuan Wu, Marlys L. Koschinsky, Muredach Reilly, Jaroslav Pelisek, Wolfgang Kempf, Hans-Henning Eckstein, Oliver Soehnlein, Ljubica Matic, Ulf Hedin, Alexandra Bäcklund, Claes Bergmark, Valentina Paloschi, Lars Maegdefessel
Journal: Circulation (2021)

Long noncoding RNAs (lncRNAs) are important regulators of biological processes involved in vascular tissue homeostasis and disease development. The present study assessed the functional contribution of the lncRNA myocardial infarction-associated transcript (MIAT) to atherosclerosis and carotid artery disease. We profiled differences in RNA transcript expression in patients with advanced carotid artery atherosclerotic lesions from the Biobank of Karolinska Endarterectomies. The lncRNA MIAT was identified as the most upregulated noncoding RNA transcript in carotid plaques compared with nonatherosclerotic control arteries, which was confirmed by quantitative real-time polymerase chain reaction and in situ hybridization. Experimental knockdown of MIAT, using site-specific antisense oligonucleotides (LNA-GapmeRs) not only markedly decreased proliferation and migration rates of cultured human carotid artery smooth muscle cells (SMCs) but also increased their apoptosis. MIAT mechanistically regulated SMC proliferation through the EGR1 (Early Growth Response 1)-ELK1 (ETS Transcription Factor ELK1)-ERK (Extracellular Signal-Regulated Kinase) pathway. MIAT is further involved in SMC phenotypic transition to proinflammatory macrophage-like cells through binding to the promoter region of KLF4 and enhancing its transcription. Studies using Miat-/- and Miat-/-ApoE-/- mice, and Yucatan LDLR-/- mini-pigs, as well, confirmed the regulatory role of this lncRNA in SMC de- and transdifferentiation and advanced atherosclerotic lesion formation. The lncRNA MIAT is a novel regulator of cellular processes in advanced atherosclerosis that controls proliferation, apoptosis, and phenotypic transition of SMCs, and the proinflammatory properties of macrophages, as well.
Radiation-Induced Meningioma in a Case of Medulloblastoma Treated 11 Years Ago—Detected on 68Ga-DOTANOC PET/CT
Authors: Indraja D. Dev, Ameya D. Puranik, Venkatesh Rangarajan, Tejpal Gupta, Nilendu C. Purandare, Archi Agrawal, Sneha Shah
Journal: Clinical Nuclear Medicine (2021)

Abstract Medulloblastomas, especially the sonic hedgehog subgroup, are treated aggressively with surgery and chemoradiotherapy, as they are associated with high local site recurrence rate and poor overall survival. Radiation-induced meningioma is the most common delayed complication of craniospinal irradiation. This needs to be differentiated from meningeal or ependymal metastases as the later need aggressive management. We report one such rare case, in a patient who completed treatment for medulloblastoma 11 years ago, was in remission, and now presented with dural-based lesions.
Abstract 058: Subclinical Myocardial Injury, Coagulopathy, And Inflammation In Covid-19: A Meta-analysis
Authors: Oluwabunmi Ogungbe, Baridosia Kumbe, Oluwadamilola Fadodun, Latha T, Diane Meyer, Adetoun Asala, Patricia Davidson, Cheryl Dennison Himmelfarb, Wendy Post, Yvonne Commodore-mensah
Journal: Circulation (2022)

Introduction: Infection with the SARS-CoV-2 virus can lead to myocardial injury, with cardiac biomarker elevations. Objective: To quantify the association between biomarkers of myocardial injury, coagulation, and severe COVID-19 and death in hospitalized patients. Methods: Studies were identified from PubMed, Embase, CINAHL, Cochrane, Web of Science, and Scopus, published between December 2019 to August 2021. Effect estimates for association between markers of myocardial injury (Troponin), myocardial stretch (N-terminal-pro hormone BNP, NT-proBNP), and coagulopathy (D-Dimer) and death or severe/critical COVID-19 were pooled using random-effects models. Odds Ratios (OR), Hazard Ratios (HR), and 95% Confidence Intervals (CI) were pooled separately and reported by outcomes of critical/severe COVID-19 and death. A meta-analysis of proportions summarized pooled prevalence of co-morbidities. Results: We included 62 articles, with 41,013 patients. Pooled proportion of patients with hypertension history was 39% (95% CI: 34-44%); diabetes, 21% (95% CI: 18%-24%); coronary artery disease, 13% (95% CI: 10-16%); chronic obstructive pulmonary disease, 7% (95% CI: 5-8%), and cancer, 5% (95% CI: 4-7%). Elevated troponin was associated with higher pooled odds of critical/severe COVID-19 and death [Odds Ratio (OR: 1.77, 95% CI: 1.42-2.18)] ( Figure ); also, separately for death (OR: 1.72, 95% CI: 1.32-2.25), and critical/severe COVID-19 (OR: 1.93, 95% CI: 1.45-2.40). Elevated NT-proBNP were associated with higher odds for severe COVID-19/death (OR: 3.00, 95% CI: 1.58-5.70). Elevated D-dimer levels was significantly associated with critical/severe COVID-19 and death (OR: 1.38, 95% CI: 1.07-1.79). Conclusions: This meta-analysis synthesizes evidence showing that myocardial injury, and coagulopathy are complications of COVID-19. Patients who have recovered from COVID-19 may benefit from minimally invasive assessment for markers of myocardial injury, stretch and coagulopathy for early risk stratification.