tbuckley/cabot-search huggingface dataset:
Risk-Based Chemical Ranking and Generating a Prioritized Human Exposome Database
Authors: Fanrong Zhao, Li Li, Yue Chen, Yichao Huang, Tharushi Prabha Keerthisinghe, Agnes Chow, Ting Dong, Shenglan Jia, Shipei Xing, Benedikt Warth, Tao Huan, Mingliang Fang
Journal: Environmental Health Perspectives (2021)

BACKGROUND: Due to the ubiquitous use of chemicals in modern society, humans are increasingly exposed to thousands of chemicals that contribute to a major portion of the human exposome.Should a comprehensive and risk-based human exposome database be created, it would be conducive to the rapid progress of human exposomics research.In addition, once a xenobiotic is biotransformed with distinct half-lives upon exposure, monitoring the parent compounds alone may not reflect the actual human exposure.To address these questions, a comprehensive and risk-prioritized human exposome database is needed.OBJECTIVES: Our objective was to set up a comprehensive risk-prioritized human exposome database including physicochemical properties as well as risk prediction and develop a graphical user interface (GUI) that has the ability to conduct searches for content associated with chemicals in our database.METHODS: We built a comprehensive risk-prioritized human exposome database by text mining and database fusion.Subsequently, chemicals were prioritized by integrating exposure level obtained from the Systematic Empirical Evaluation of Models with toxicity data predicted by the Toxicity Estimation Software Tool and the Toxicological Priority Index calculated from the ToxCast database.The biotransformation half-lives (HL B s) of all the chemicals were assessed using the Iterative Fragment Selection approach and biotransformation products were predicted using the previously developed BioTransformer machine-learning method.RESULTS: We compiled a human exposome database of >20,000 chemicals, prioritized 13,441 chemicals based on probabilistic hazard quotient and 7,770 chemicals based on risk index, and provided a predicted biotransformation metabolite database of >95,000 metabolites.In addition, a userinteractive Java software (Oracle)-based search GUI was generated to enable open access to this new resource.DISCUSSION: Our database can be used to guide chemical management and enhance scientific understanding to rapidly and effectively prioritize chemicals for comprehensive biomonitoring in epidemiological investigations.
NEAR-DEATH AND BACK IN 10 DAYS: AN UNEXPECTED CASE OF SARS-COV-2 FULMINANT MYOCARDITIS
Authors: Yetunde A. Fatade, Franck Azobou Tonleu, Avery Calhoun, Mariana Garcia, Tuoyo Mene-Afejuku, An Young, Marc Thames, Minh Ly T Nguyen, Modele Ogunniyi
Journal: Journal of the American College of Cardiology (2021)
SINGLE ANTIPLATELET VERSUS DUAL ANTIPLATELET THERAPY IN PATIENTS AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Mitra Patel, Neha Patel, Ahmed Elzanaty, Cameron Burmeister, Jeremy Tomcho, Sapan Bhuta, Sakhi Patel, Aneesha Patel, Shivani Singh
Journal: Journal of the American College of Cardiology (2021)
nPhase: an accurate and contiguous phasing method for polyploids
Authors: Omar Abou Saada, Andreas Tsouris, Chris Eberlein, Anne Friedrich, Joseph Schacherer
Journal: Genome biology (2021)

Abstract While genome sequencing and assembly are now routine, we do not have a full, precise picture of polyploid genomes. No existing polyploid phasing method provides accurate and contiguous haplotype predictions. We developed nPhase, a ploidy agnostic tool that leverages long reads and accurate short reads to solve alignment-based phasing for samples of unspecified ploidy ( https://github.com/OmarOakheart/nPhase ). nPhase is validated by tests on simulated and real polyploids. nPhase obtains on average over 95% accuracy and a contiguous 1.25 haplotigs per haplotype to cover more than 90% of each chromosome (heterozygosity rate ≥ 0.5%). nPhase allows population genomics and hybrid studies of polyploids.
Anatomical Similarities Between Mitral and Tricuspid Valves in Sheep, Ovis aries, Hearts
Authors: Sohum Kapadia
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

With the recent rapid growth in transcatheter mitral and tricuspid valve interventions, it has become increasingly important to understand detailed anatomy of the valves. In this study, we investigated the similarities, differences, and associations between the dimensions of the atrioventricular valves in a sheep model, as sheep heart valves have a similar morphology to human valves. A systematic dissection of twenty-five sheep hearts was performed, with annular circumference measurement, and sub-valvular anatomy documentation. There was a significant association (r=0.865; p=0.007) between the circumference of the mitral and tricuspid annuli. Authors also identified significantly more chordae tendinea in the subvalvular mitral apparatus compared to the tricuspid valve (15.8±1.2 vs. 13.9±1.5; p&lt;0.001). In conclusion, there is a significant association between the size of mitral and tricuspid valve annuli, and the morphology of leaflets and subvalvular apparatus is different between the two valves. These findings could have important implications in transcatheter device design, sizing, and optimal intervention timing.
Association of Cancer Screening Deficit in the United States With the COVID-19 Pandemic
Authors: Ronald C. Chen, Kevin Haynes, Simo Du, John Barron, Aaron J. Katz
Journal: JAMA Oncology (2021)

The COVID-19 pandemic led to sharp declines in cancer screening. However, the total deficit in screening in the US associated with the pandemic and the differential impact on individuals in different geographic regions and by socioeconomic status (SES) index have yet to be fully characterized.To quantify the screening rates for breast, colorectal, and prostate cancers associated with the COVID-19 pandemic in different geographic regions and for individuals in different SES index quartiles and estimate the overall cancer screening deficit in 2020 across the US population.This retrospective cohort study uses the HealthCore Integrated Research Database, which comprises single-payer administrative claims data and enrollment information covering approximately 60 million people in Medicare Advantage and commercial health plans from across geographically diverse regions of the US. Participants were individuals in the database in January through July of 2018, 2019, and 2020 without diagnosis of the cancer of interest prior to the analytic index month.Analytic index month and year.Receipt of breast, colorectal, or prostate cancer screening.Screening for all 3 cancers declined sharply in March through May of 2020 compared with 2019, with the sharpest decline in April (breast, -90.8%; colorectal, -79.3%; prostate, -63.4%) and near complete recovery of monthly screening rates by July for breast and prostate cancers. The absolute deficit across the US population in screening associated with the COVID-19 pandemic was estimated to be 3.9 million (breast), 3.8 million (colorectal), and 1.6 million (prostate). Geographic differences were observed: the Northeast experienced the sharpest declines in screening, while the West had a slower recovery compared with the Midwest and South. For example, percentage change in breast cancer screening rate (2020 vs 2019) for the month of April ranged from -87.3% (95% CI, -87.9% to -86.7%) in the West to -94.5% (95% CI, -94.9% to -94.1%) in the Northeast (decline). For the month of July, it ranged from -0.3% (95% CI, -2.1% to 1.5%) in the Midwest to -10.6% (-12.6% to -8.4%) in the West (recovery). By SES, the largest screening decline was observed in individuals in the highest SES index quartile, leading to a narrowing in the disparity in cancer screening by SES in 2020. For example, prostate cancer screening rates per 100 000 enrollees for individuals in the lowest and highest SES index quartiles, respectively, were 3525 (95% CI, 3444 to 3607) and 4329 (95% CI, 4271 to 4386) in April 2019 compared with 1535 (95% CI, 1480 to 1589) and 1338 (95% CI, 1306 to 1370) in April 2020. Multivariable analysis showed that telehealth use was associated with higher cancer screening.Public health efforts are needed to address the large cancer screening deficit associated with the COVID-19 pandemic, including increased use of screening modalities that do not require a procedure.
Abstract 14549: ApoB Antisense Treatment Increases the Clearance of Apolipoprotein (a) From Mature Lp(a) Particles
Authors: Gissette Reyes-Soffer, Marianna Pavlyha, Colleen Ngai, Tiffany Thomas, Stephen Holleran, Rajasekhar Ramakrishnan, Wahida Karmally, Renu Nandakumar, Henry Ginsberg
Journal: Circulation (2017)

Background: Mipomersen is an antisense oligonucleotide drug that targets apoB and is approved for the treatment of homozygous familial hypercholesterolemia. In healthy volunteers, we found that the...
Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation
Authors: Amanda Olson, Ruitao Lin, David Marin, Hind Rafei, Mustafa H. Bdiwi, Peter F. Thall, Rafet Basar, Ala Abudayyeh, Pinaki Banerjee, Fleur M. Aung, Indresh Kaur, Glorette Abueg, Sheetal Rao, Roy Chemaly, Victor Mulanovich, Gheath Al-Atrash, Amin M. Alousi, Borje S. Andersson, Paolo Anderlini, Qaiser Bashir, Karla M. Castro, May Daher, Isabel M. Galvan, Chitra Hosing, Jin S. Im, Roy B. Jones, Partow Kebriaei, Issa Khouri, Rohtesh Mehta, Jeffrey Molldrem, Yago Nieto, Betul Oran, Uday Popat, Muzaffar Qazilbash, Gabriela Rondon, Neeraj Saini, Bryan Spencer, Samer Srour, Dominique Washington, Melissa Barnett, Richard E. Champlin, Elizabeth J. Shpall, Katayoun Rezvani
Journal: Journal of Clinical Oncology (2021)

BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option.We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed.Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement.Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT.
The Excitement of Change. A Book of Personal Growth.
Journal: Annals of Internal Medicine (1976)

Benjamin V. White and Helen White, authors of The Excitement of Change—A Book of Personal Growth attempt to share with readers a large number of true-life experiences which people have gone through on their onward march to a new and fuller life. This new life is attained only through a real change, which is an inward experience. This experience usually begins in a period of crisis.
Frequency and phenotypic expression in childhood and early adulthood of loss of function mutations in the Melanocortin 4 Receptor in a UK birth cohort
Authors: K H Wade, B Y H Lam, A Melvin, W Pan, L J Corbin, D A Hughes, K Rainbow, J H Chen, K Duckett, X Liu, J Mokrosińsk, Alexander Mörseburg, S Neaves, A Williamson, C Zhang, I S Farooqi, G S H Yeo, N J Timpson, S O'Rahilly
Journal: Nature Medicine (2021)
SUDDEN ONSET PLATYPNEA-ORTHODEOXIA SYNDROME IN A 30-YEAR-OLD: THE CASE OF AN UNMASKED PERSISTENT LEFT SUPERIOR VENA CAVA
Authors: Naga Vaishnavi Gadela, Seth Fakess, Shailendra Upadhyay, Mohiudden Cheema, Naveen Sablani
Journal: Journal of the American College of Cardiology (2021)
Metabotropic Glutamate Receptor 5 in Natural Killer Cells Attenuates Liver Fibrosis by Exerting Cytotoxicity to Activated Stellate Cells
Authors: Won‐Mook Choi, Tom Ryu, Jun‐Hee Lee, Young‐Ri Shim, Myung‐Ho Kim, Hee‐Hoon Kim, Ye Eun Kim, Keungmo Yang, Kyurae Kim, Sung Eun Choi, Won Kim, Seok‐Hwan Kim, Hyuk Soo Eun, Won‐Il Jeong
Journal: Hepatology (2021)

Background and Aims The important roles of glutamate and metabotropic glutamate receptor 5 (mGluR5) in HSCs have recently been reported in various liver diseases; however, the mechanism linking the glutamine/glutamate metabolism and mGluR5 in liver fibrosis remains unclear. Here, we report that mGluR5 activation in natural killer (NK) cells attenuates liver fibrosis through increased cytotoxicity and interferon‐γ (IFN‐γ) production in both mice and humans. Approach and Results Following 2‐week injection of carbon tetrachloride (CCl 4 ) or 5‐week methionine‐deficient and choline‐deficient diet, liver fibrosis was more aggravated in mGluR5 knockout mice with significantly decreased frequency of NK cells compared with wild‐type mice. Consistently, NK cell–specific mGluR5 knockout mice had aggravated CCl 4 ‐induced liver fibrosis with decreased production of IFN‐γ. Conversely, in vitro activation of mGluR5 in NK cells significantly increased the expression of anti‐fibrosis‐related genes including Ifng , Prf1 (perforin), and Klrk1 (killer cell lectin like receptor K1) and the production of IFN‐γ through the mitogen‐activated extracellular signal‐regulated kinase/extracellular signal‐related kinase pathway, contributing to the increased cytotoxicity against activated HSCs. However, we found that the uptake of glutamate was increased in activated HSCs, resulting in shortage of extracellular glutamate and reduced stimulation of mGluR5 in NK cells. Consequently, this could enable HSCs to evade NK cell cytotoxicity in advanced liver fibrosis. In vivo , pharmacologic activation of mGluR5 accelerated CCl 4 ‐induced liver fibrosis regression by restoring NK cell cytotoxicity. In humans, mGluR5 activation enhanced the cytotoxicity of NK cells isolated from healthy donors, but not from patients with cirrhosis with significantly reduced mGluR5 expression in NK cells. Conclusions mGluR5 plays important roles in attenuating liver fibrosis by augmenting NK cell cytotoxicity, which could be used as a potential therapeutic target for liver fibrosis.
A quantitative analysis of research publications focused on skin of color: Representation in academic dermatology journals
Authors: Michelle Militello, Mindy D. Szeto, Colby L. Presley, Kayd J. Pulsipher, Chandler W. Rundle, Kristen H. Ward, Ezra Hoover, Robert P. Dellavalle
Journal: Journal of the American Academy of Dermatology (2021)
INCIDENCE OF NONVALVULAR ATRIAL FIBRILLATION IN AGED TYPE 2 DIABETES MELLITUS PATIENTS: FROM JPAD COHORT STUDY
Authors: Chisa Matsumoto, Hisao Ogawa, Yoshihiko Saito, Sadanori Okada, Hirofumi Soejima, Mio Sakuma, Izuru Masuda, Masafumi Nakayama, Naofumi Doi, Hideaki Jinnouchi, Masako Waki, Takeshi Morimoto
Journal: Journal of the American College of Cardiology (2021)
INCREASE OF ALL CAUSE OUT-OF-HOSPITAL CARDIAC ARRESTS DURING COVID-19 PANDEMIC LOCKDOWN: DATA FROM A LOW COVID-19 MORBIDITY COUNTRY
Authors: Mindaugas Lizaitis, Greta Rodevic, Aurelija Martinonyte, Laurynas Dieckus, Ignas Badaras, Kamile Cerlinskaite, Vilhelmas Bajoras, Povilas Budrys, Aleksandr Volodko, Egle Urbonaite, Pranas Serpytis, Jelena Celutkiene, Giedrius Davidavicius
Journal: Journal of the American College of Cardiology (2021)
Robot-induced hallucinations in Parkinson’s disease depend on altered sensorimotor processing in fronto-temporal network
Authors: Fosco Bernasconi, Eva Blondiaux, Jevita Potheegadoo, Giedre Stripeikyte, Javier Pagonabarraga, Helena Bejr-Kasem, Michela Bassolino, Michel Akselrod, Saul Martinez-Horta, Frederic Sampedro, Masayuki Hara, Judit Horvath, Matteo Franza, Stéphanie Konik, Matthieu Bereau, Joseph-André Ghika, Pierre R. Burkhard, Dimitri Van De Ville, Nathan Faivre, Giulio Rognini, Paul Krack, Jaime Kulisevsky, Olaf Blanke
Journal: Science Translational Medicine (2021)

Presence hallucination in Parkinson’s disease (PD) is shown to arise from errors in sensorimotor integration and frontotemporal disconnection.
Structural Variants Selected during Yak Domestication Inferred from Long-Read Whole-Genome Sequencing
Authors: Shangzhe Zhang, Wenyu Liu, Xinfeng Liu, Xin Du, Ke Zhang, Yang Zhang, Yongwu Song, Yunnan Zi, Qiang Qiu, Johannes A Lenstra, Jianquan Liu
Journal: Molecular Biology and Evolution (2021)

Abstract Structural variants (SVs) represent an important genetic resource for both natural and artificial selection. Here we present a chromosome-scale reference genome for domestic yak (Bos grunniens) that has longer contigs and scaffolds (N50 44.72 and 114.39 Mb, respectively) than reported for any other ruminant genome. We further obtained long-read resequencing data for 6 wild and 23 domestic yaks and constructed a genetic SV map of 372,220 SVs that covers the geographic range of the yaks. The majority of the SVs contains repetitive sequences and several are in or near genes. By comparing SVs in domestic and wild yaks, we identified genes that are predominantly related to the nervous system, behavior, immunity, and reproduction and may have been targeted by artificial selection during yak domestication. These findings provide new insights in the domestication of animals living at high altitude and highlight the importance of SVs in animal domestication.
COATED-PLATELETS ENHANCE TIA/STROKE RISK PREDICTION IN ASYMPTOMATIC CAROTID STENOSIS PATIENTS FOLLOWED WITH CAROTID DOPPLER SURVEILLANCE
Authors: Mohamad Khattab, Arleen Ramirez-Jimenez, Andrea Vincent, George Dale, Calin Prodan, Angelia Kirkpatrick
Journal: Journal of the American College of Cardiology (2021)
Long-term safety of lumacaftor–ivacaftor in children aged 2–5 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a multicentre, phase 3, open-label, extension study
Authors: Jordana E Hoppe, Mark Chilvers, Felix Ratjen, John J McNamara, Caroline A Owen, Simon Tian, Rachel Zahigian, Alexandra G Cornell, Susanna A McColley
Journal: The Lancet Respiratory Medicine (2021)
LEFT VENTRICULAR MASS ON POSITRON EMISSION TOMOGRAPHY VALIDATION AGAINST CARDIOVASCULAR MAGNETIC RESONANCE
Authors: Ahmed Ibrahim Ahmed, Maan Malahfji, Yushui Han, Aaron K. Jung, Talal Alnabelsi, Faisal Nabi, Dipan Shah, Ahmed Aljizeeri, John Mahmarian, Mouaz Al-Mallah
Journal: Journal of the American College of Cardiology (2021)
CARDIOVASCULAR RISK AND ROUTE OF ESTROGEN ADMINISTRATION IN TRANSGENDER WOMEN: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Keila Turino Miranda, Cindy Kalenga, Nathalie Saad, Sandra Dumanski, Danica Chang, Diane Lorenzetti, Caitlin McClurg, Darlene Sola, Sofia Ahmed
Journal: Journal of the American College of Cardiology (2021)
Antisense oligonucleotide-based treatment of retinitis pigmentosa caused by USH2A exon 13 mutations
Authors: Kalyan Dulla, Ralph Slijkerman, Hester C. van Diepen, Silvia Albert, Margo Dona, Wouter Beumer, Janne J. Turunen, Hee Lam Chan, Iris A. Schulkens, Lars Vorthoren, Cathaline den Besten, Levi Buil, Iris Schmidt, Jiayi Miao, Hanka Venselaar, Jingjing Zang, Stephan C.F. Neuhauss, Theo Peters, Sanne Broekman, Ronald Pennings, Hannie Kremer, Gerard Platenburg, Peter Adamson, Erik de Vrieze, Erwin van Wijk
Journal: Molecular Therapy (2021)

Mutations in USH2A are among the most common causes of syndromic and non-syndromic retinitis pigmentosa (RP). The two most recurrent mutations in USH2A, c.2299delG and c.2276G > T, both reside in exon 13. Skipping exon 13 from the USH2A transcript presents a potential treatment modality in which the resulting transcript is predicted to encode a slightly shortened usherin protein. Morpholino-induced skipping of ush2a exon 13 in zebrafish ush2armc1 mutants resulted in the production of usherinΔexon 13 protein and a completely restored retinal function. Antisense oligonucleotides were investigated for their potential to selectively induce human USH2A exon 13 skipping. Lead candidate QR-421a induced a concentration-dependent exon 13 skipping in induced pluripotent stem cell (iPSC)-derived photoreceptor precursors from an Usher syndrome patient homozygous for the c.2299delG mutation. Mouse surrogate mQR-421a reached the retinal outer nuclear layer after a single intravitreal injection and induced a detectable level of exon skipping until at least 6 months post-injection. In conclusion, QR-421a-induced exon skipping proves to be a highly promising treatment option for RP caused by mutations in USH2A exon 13.
Synthetic infrared nano-photosensitizers with hierarchical zoom-in target-delivery functionalities for precision photodynamic therapy
Authors: Jing Xia, Ming Qian, Qichao Yao, Zhipeng Meng, Hongyan Cui, Liuwei Zhang, Yachen Li, Suli Wu, Jingyun Wang, Qixian Chen, Xiaojun Peng
Journal: Journal of Controlled Release (2021)
COLLAGEN TURNOVER BIOMARKERS IN ATRIAL FIBRILLATION AND THEIR USE IN CLINICAL MANAGEMENT AND THE STUDY OF INFLAMMATORY PATHOGENESIS
Authors: Keaton Wieschhaus, Dimpi Patel, Emily Bontekoe, Jake Goldstein, Debra Hoppensteadt, Lowell Steen, Jawed Fareed, Mushabbar Syed
Journal: Journal of the American College of Cardiology (2021)
SGLT2 inhibitors reduce all-cause mortality
Authors: Orly F. Kohn
Journal: Annals of Internal Medicine (2021)

Source Citation Silverii GA, Monami M, Mannucci E. Sodium–glucose co-transporter-2 inhibitors and all-cause mortality: a meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2021;23:1052-6. 33283969
SARS-CoV-2 interacts with platelets and megakaryocytes via ACE2-independent mechanism
Authors: Shu Shen, Jingyuan Zhang, Yaohui Fang, Sihong Lu, Jun Wu, Xin Zheng, Fei Deng
Journal: Journal of Hematology & Oncology (2021)

Abstract Evidence suggests that platelets may directly interact with SARS-CoV-2, raising the concern whether ACE2 receptor plays a role in this interaction. The current study showed that SARS-CoV-2 interacts with both platelets and megakaryocytes despite the limited efficiency. Abundance of the conventional receptor ACE2 and alternative receptors or co-factors for SARS-CoV-2 entry was characterized in platelets from COVID-19 patients and healthy persons as well as human megakaryocytes based on laboratory tests or previously reported RNA-seq data. The results suggest that SARS-CoV-2 interacts with platelets and megakaryocytes via ACE2-independent mechanism and may regulate alternative receptor expression associated with COVID-19 coagulation dysfunction.