tbuckley/cabot-search huggingface dataset:
Genetic and Structural Analysis of SARS-CoV-2 Spike Protein for Universal Epitope Selection
Authors: Christopher Markosian, Daniela I. Staquicini, Prashant Dogra, Esteban Dodero-Rojas, Joseph H. Lubin, Fenny H.F. Tang, Tracey L. Smith, Vinícius G. Contessoto, Steven K. Libutti, Zhihui Wang, Vittorio Cristini, Sagar D. Khare, Paul C. Whitford, Stephen K. Burley, José N. Onuchic, Renata Pasqualini, Wadih Arap
Journal: Molecular Biology and Evolution (2022)

Evaluation of immunogenic epitopes for universal vaccine development in the face of ongoing SARS-CoV-2 evolution remains a challenge. Herein, we investigate the genetic and structural conservation of an immunogenically relevant epitope (C662-C671) of spike (S) protein across SARS-CoV-2 variants to determine its potential utility as a broad-spectrum vaccine candidate against coronavirus diseases. Comparative sequence analysis, structural assessment, and molecular dynamics simulations of C662-C671 epitope were performed. Mathematical tools were employed to determine its mutational cost. We found that the amino acid sequence of C662-C671 epitope is entirely conserved across the observed major variants of SARS-CoV-2 in addition to SARS-CoV. Its conformation and accessibility are predicted to be conserved, even in the highly mutated Omicron variant. Costly mutational rate in the context of energy expenditure in genome replication and translation can explain this strict conservation. These observations may herald an approach to developing vaccine candidates for universal protection against emergent variants of coronavirus.
FLGS-01. Development of novel topical fluorescent probe for intraoperative rapid detection of glioma
Authors: Shota Tanaka, Yosuke Kitagawa, Mako Kamiya, Takenori Shimizu, Yasuteru Urano, Nobuhito Saito
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Fluorescence imaging is an important surgical adjunct in malignant glioma surgery. 5-aminolevulinic acid (5-ALA) has been proven effective for radical tumor resection and extended progression-free survival in a phase III randomized trial and therefore integrated into surgery for malignant glioma. Importantly, however, some limitations still exist in its use, which include false positivity and false negativity as well as inability of re-administration. In this study, we aimed to develop a novel, spray-type fluorescent probe using hydroxymethyl rhodamine green (HMRG) as a fluorescent scaffold. METHODS We have previously established a fluorescent probe library comprised of more than 320 kinds of HMRG probes. They have HMRG as a fluorescent scaffold with various types of dipeptides attached to it. Primary probe screening was performed using the homogenized tumor samples from patients with glioblastoma operated at our institution. Secondary screening followed using the selected probes and fresh tumor samples obtained from patients with glioblastoma operated from 2016 until 2018. Diced electrophoresis gel (DEG) assay, two-dimensional gel electrophoresis followed by a multi-well plate-based fluorometric assay, was performed to identify responsible enzymes for the selected probe. Further experiments with inhibitors, real-time PCR, immunohistochemistry, and western blotting were performed for confirmation. RESULTS Proline-arginine-HMRG (PR-HMRG) was selected as a candidate probe based upon the above two-step screenings. It achieved 79.4% accuracy in receiver operating characteristic curve analysis. Calpain-1 was found to be responsible to cleave PR-HMRG probe by DEG-proteome analysis. Calpain-1 protein was highly expressed in tumor tissues which reacted to PR-HMRG probe. CONCLUSIONS Our innovative screening method was able to find PR-HMRG as a novel fluorescent probe effective for rapid detection of glioblastoma. A preclinical study is planned to assess the efficacy and safety of the selected probe.
Abstract P199: Association Of High Left Ventricular Ejection Fraction With Incident Heart Failure, And Impact Of Adiposity On Ejection Fraction
Authors: Philimon N Gona, Jane J Lee, Gerald Chi, Lebo Gafane-Matemane, Christopher J O'Donnell, Warren J Manning, Michael L Chuang
Journal: Circulation (2022)

Introduction: High left ventricular ejection fraction (LVEF) has been associated with excess cardiovascular disease (CVD) morbidity and mortality among women with CVD. We sought to determine if high EF is associated with incident heart failure (HF) in a community-dwelling cohort of adults. Secondarily, we examined relationships between various adiposity measures and high EF, as obesity is associated with HF with preserved EF. Methods: 1794 participants aged 65±9y (53% women) of the Framingham Offspring cohort underwent cardiac MRI 2002-2006 to determine LV EF and mass (LVM). Anthropometric measures and clinical covariates were collected at the adjacent Offspring cycle 7 visit. Adiposity measures included body mass index (BMI) and waist circumference (WC). A healthy referent subset (no hypertension, diabetes, smoking, or history of CVD) was used to determine sex-specific upper 90 th percentile cutpoints (P90) for high EF. Cox proportional hazards regression models were used to assess event-free survival for the outcome of HF (adjudicated by 3 physician investigators). Multivariable-adjusted (MV) logistic regression analysis was used to determine clinical factors associated with high EF. Adiposity measures were considered categorically (as BMI≥30kg/m 2 and WC &gt; 102 or 88 cm (men, women)) and as continuous variables. Results: P90 cutpoints for high EF were 72.5% (men) and 75.1% (women). Prevalence of high EF was 16.0% (men) and 14.7% (women). Over median 13.2 years of follow up there were 68 incident HF events. In MV-adjusted Cox models accounting for age, sex, hypertension, smoking, diabetes, and indexed LVM, the HF outcome was associated with greater age (hazard ratio, HR=3.13/10y, 95%CI 2.30 - 4.27), LVMi (HR=1.24/5g per m 2 , CI 1.12 - 1.36) and high EF (HR=2.26, CI 1.35 - 3.77). MV-adjusted logistic regression models showed high EF was associated with each measure of adiposity. High BMI (≥30) had odds ratio (OR) = 1.38 (CI 1.04 - 1.84), high WC (&gt;102 or 88): OR=1.55 (1.12 - 2.09), continuous BMI: OR=1.03 (CI 1.01 - 1.06), continuous WC: OR=1.02 (1.01 - 1.03). In each of these models ORs for age ranged 1.52 to 1.54, hypertension 1.74 to 1.86. Conclusion: High EF was associated with greater hazard of incident heart failure in middle-aged and older adults. High EF was associated with increasing age, hypertension, and greater adiposity (measured by either BMI or WC). This work extends prior findings in women with CVD to a community-dwelling cohort of both sexes. Further work is needed to determine whether general or central measures of obesity are more strongly associated with high EF.
Novel Mechanisms of Exosome-Mediated Phagocytosis of Dead Cells in Injured Heart
Authors: Mallikarjun Patil, Sherin Saheera, Praveen K. Dubey, Asher Kahn-Krell, Prem Kumar Govindappa, Sarojini Singh, Sultan Tousif, Qinkun Zhang, Hind Lal, Jianyi Zhang, Gangjian Qin, Prasanna Krishnamurthy
Journal: Circulation Research (2021)

[Figure: see text].
Abstract 11805: Identifying Novel Genetic Variants Associated With an Increased Risk of Cerebrovascular Disease Using a Large-Scale Bio-Medical Database
Authors: Fahad Alkhalfan, Alex Gyftopoulos, Yi-Ju Chen, Charles H Williams, James A Perry, Charles C Hong
Journal: Circulation (2021)

Introduction: Cerebrovascular disease occurs because of a complex interplay between vascular, environmental, and genetic factors. It is the second leading cause of disability worldwide. Understanding who may be genetically predisposed to cerebrovascular disease can help guide preventative efforts. We aim to utilize the UK Biobank to identify genetic variants associated with an increased risk of cerebrovascular disease. Methods: The UK Biobank is a prospective cohort containing clinical and genetic data gathered from over 500,000 individuals. We used Plink’s GLM options to analyze associations between genotypes and phenotypic manifestations of the disease. We defined cerebrovascular disease by selecting the ICD-10 codes G45, G46, I63-I67 and I69. We compared cases to age- and gender-matched controls with a case-to-control ratio of 20:1. Related individuals and those with confounding diagnoses such as coronary artery disease and other atherosclerotic conditions were excluded from the controls. Results: There were 9,726 and 6,699 instances of cerebrovascular disease as a primary or secondary diagnosis. We identified 189 variants in 8 different genes with p ≤ 1x 10 -6 . Identified genes have a minor allele frequency ≥ 0.5%. Variants with the highest significance were identified in close proximity to sequences encoding PITX2 (Paired like homeodomain 2; p = 2.4 x 10 -9 , OR = 1.1), LPA (Lipoprotein(a); p = 6.1 x 10 -9 , OR = 7.3), LRRTM4 (leucine rich repeat transmembrane neuronal 4; p = 1.8 x 10 -8 , OR = 1.08), and CDKN2B-AS1 (CDKN2B antisense RNA 1; p = 4.5 x 10 -8 , OR = 0.93). Conclusions: Through genome-wide analysis using ICD-10 codes as a phenotype for cerebrovascular diseases, we identified several novel genetic variants that are significantly associated with the incidence of cerebrovascular disease in the UK Biobank. Some of the associated genes were previously shown to be associated with atrial fibrillation ( PITX2 ), and atherosclerosis ( LPA and CDKN2B-AS1 ), solidifying the contribution of these two clinical risk factors to cerebrovascular accidents. LRRTM4 was previously associated with cognitive impairment, supporting a biologically plausible link to cerebrovascular disease. Future studies are warranted to confirm the findings of this analysis.
Abstract P207: Dietary Diversity And Quality And Cvd Risk Factors In The Reasons For Geographic And Racial Differences In Stroke (REGARDS)
Authors: Ji Yun Tark, Brian Heckler, Hyunkyoung Kim, Nikhil S Padhye, Suzanne E Judd, Monika Safford, Dariush Mozaffarian, Marcia C de Oliveira Otto
Journal: Circulation (2022)

Background: Diet diversity and quality are each recommended to promote a healthy diet and prevent chronic disease. Yet, little is known on how diet diversity relates to diet quality or cardiometabolic health, particularly in underrepresented subgroups disproportionally affected by poor nutrition and CVD. Aims: To determine relationships of 1) dietary diversity with diet quality, and 2) diet diversity and quality with CVD risk factors (blood pressure, plasma LDL-C, HDL-C, triglycerides, total:HDL ratio, CRP, glucose) in a diverse population of U.S. adults. Methods: We evaluated 21,350 Black and White adults aged ≥45 years in REGARDS. A validated dietary questionnaire at baseline was used to estimate two distinct aspects of diet diversity: food count (no. of food items eaten at least once a week) and dissimilarity (Jaccard distance, capturing diversity of attributes of foods eaten). Diet quality was estimated using the AHA-2020 and AHEI-2010 scores. Cross-sectional associations with CVD risk factors were examined using multivariable linear regression. Results: Food count and dissimilarity each inversely correlated with diet quality scores (r ranging from -0.04 to -0.11). In multivariable models, diet diversity had mixed or mostly null associations with CVD risk factors (See Table). For instance, food count inversely associated with HDL-C and LDL-C; while dissimilarity inversely associated with plasma glucose but positively with triglycerides. In contrast, AHA-2020 and AHEI-2010 were consistently favorably associated with nearly all CVD risk factors. Associations of diet diversity were similar in Blacks and Whites, while most associations of diet quality were stronger among Whites ( P -interaction &lt; 0.0015). Conclusion: Diet diversity metrics were not associated with diet healthfulness or most CVD risk factors among U.S. adults. Our findings support a focus on diet quality, with adequate intake of healthful food groups, rather than diversity, to promote cardiometabolic health.
Diffuse Linear Pattern of Pericardial FDG Activity in Pericardial Metastasis From Squamous Cell Lung Carcinoma
Authors: Jun Zhang, Jun Gao, Aisheng Dong, Yang Wang
Journal: Clinical Nuclear Medicine (2021)

Pericardial metastasis usually shows focal pericardial FDG activity. Diffuse linear pattern of pericardial FDG activity is uncommon. We present a case of pericardial metastasis from squamous cell lung carcinoma showing diffuse linear pericardial FDG activity mimicking tuberculous pericarditis.
Vesicoureteral Reflux in Nonfunctioning Renal Allograft Incidentally Detected in a Posttransplant 99mTc-DTPA Scan
Authors: Mohsen Qutbi
Journal: Clinical Nuclear Medicine (2021)

In the present note, a case with rising serum creatinine shortly posttransplantation was referred for 99mTc-DTPA scan. The previous nonfunctioning renal allograft in the left hemipelvis showed no finding during dynamic phase of scan and filling phase of bladder but revealed a high-grade vesicoureteral reflux (VUR) in postvoid image, which can be responsible, partly, for the patient's present and prior symptoms.
Author's correction for Euro Surveill. 2022;27(16)
Journal: Eurosurveillance (2022)

© This work is licensed under a Creative Commons Attribution 4.0 International License. Closure This is a corrected article applying to the following content: Vaccine-induced and naturally-acquired protection against Omicron and Delta symptomatic infection and severe COVID-19 outcomes, France, December 2021 to January 2022
Abstract 10887: The Under-Representation of Blacks, Females and Elderly in Randomized Controlled Trials of Heart Failure with Preserved Ejection Fraction: Meta-Analyses of Randomized Controlled Trials and Observational Studies
Authors: Ibrahim Khayyat, Hani Khayyat, Thao HUYNH
Journal: Circulation (2021)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is particularly prevalent in Blacks, women and elderly. Paradoxically, these patients are generally under-represented in randomized controlled trials (RCTs). We aim to compare the representation of Blacks, females and elderly in RCTs and observational studies of HFpEF therapies. Our secondary objective was to evaluate the secular trends of enrollment of these populations in the RCTs of HFpEF. Methods: We conducted a comprehensive database search of PubMed and EMBASE to identify HFpEF RCTs and HFpEF observational studies. Two independent readers extracted data on the proportions of Blacks, females and the mean age of patients enrolled in these studies. We compared the weighted means of age, proportions of blacks and proportions of females in the RCTs to those of observational studies. We divided the RCTs in three groups (enrollment prior to 2010, 2010-2015 and 2015 to 2020). Finally, we ascertained the secular trend of enrollment of Blacks, females and mean age of patients in the RCTs. Results: Our search yielded 17 RCTs and 9 observational studies. The trials included a total of 19,432 patients. There were marked under-enrollment of Blacks and females in the RCTs compared to the observational studies (Table 1). Furthermore, the weighted mean age of patients with HFpEF was also lower than that in the observational studies. From 1997-2020, the enrollment of females and elderly have increased, however, the enrollment of Blacks remained low in the RCTs of HFpEF. Conclusions: Blacks, women and elderly remain underrepresented in RCTs of HFpEF. Future RCTs of HFpEF should aim to enroll more Blacks, females and elderly so that the benefits of novel therapies can be validated in these special populations with high prevalence of HFpEF.
68Ga-DOTATATE PET/CT in Primary Pulmonary Lymphoepithelioma-Like Carcinoma
Authors: Qihang Shang, Yizhen Pang, Tinghua Meng, Bing Hao, Haojun Chen
Journal: Clinical Nuclear Medicine (2021)

Primary pulmonary lymphoepithelioma-like carcinomas (LELCs) are extremely rare tumors with better prognosis than other types of lung malignancies. In this case, we present 18F-FDG and 68Ga-DOTATATE PET/CT findings in a 52-year-old woman with pathologically confirmed pulmonary LELC. The pulmonary LELC presented mild 18F-FDG but avid 68Ga-DOTATATE uptake, indicating that the somatostatin receptor 2 may be highly expressed in LELCs. Therefore, 68Ga-DOTATATE PET/CT is a useful tool for tumor detection and initial staging in patients with LELCs.
Abstract P053: A Confirmatory Factor Analysis Of The Whole Food Plant-based Diet Attitudes And Beliefs Survey
Authors: Christine Jovanovic, Angela Pfammatter, Elyse Daly, Bonnie Spring
Journal: Circulation (2022)

Background: Despite emerging evidence that a whole food plant-based diet (WFPBD) can reduce risk for CVD morbidity and mortality, adoption rates in the US remain low (~4%). Little is known about why this disconnect exists, and understanding this is critical to designing and implementing interventions intended to increase WFPBD consumption in the US. However, no validated survey instruments intended for use in US adults has been tested. Objective: The purpose of this study is to validate the WFPBD survey instrument using confirmatory factor analysis (CFA). Methods: Survey development was based on previous research in Australia and Europe, and items include “pros” and “cons” of consuming a WFPBD using constructs from the Social Cognitive Theory and the Transtheoretical Model. Sixty-four statements (33 “con” and 31 “pro”) were presented with five-item Likert scale answer options (strongly disagree to strongly agree). The WFPBD survey was administered to 412 English speaking adults in the US via MTurk. Summary statistics and CFA were used to describe outcomes and reduce the number of survey items while optimizing explained variance. Examination of item variance and covariance was used to iteratively fit a second order twelve factor model, a first order eight factor model, and a first order six factor model. Results: The mean age of participants was 34.9 years, and the sample was 12% (48) African American, 6% (25) Asian, 6% (25) Hispanic, 1% (5) Other, and 75% (309) White. The majority (85.7% (349)) had at least a Bachelor’s degree, and 33% (136) made &gt;$65K. After adjustment for low factor loadings and high cross loadings, the first order six factor model remained significant ( X 2 = 491.87, p &lt; 0.001). This model resulted in the best fit, as indicated by low RMSEA = 0.051 and SRMR = 0.048. The six factors were split between “cons” (social support, instrumental support, self-efficacy, health), and “pros” (instrumental support, health). The largest factor loadings for the latent variable WFPBD “cons” were “I wouldn't get enough energy or strength.” (0.85) and “I am not confident that I know how to prepare plant-based meals.” (0.81), while for the latent variable WFPBD “pros”, the highest factor loadings were for “Have a better quality of life.“ (0.77) and “Be fit.” (0.77). Attitudes towards animals and environmental concerns were not highly implicated and were excluded from the final model. Conclusion: The 25-item WFPBD survey produced internally consistent measures of the latent variables WFPBD “pros” and WFPBD “cons” in this sample of US adults. The reduced survey can be used to assess attitudes and beliefs towards a WFPBD and results can guide behavioral interventions development to promote adoption of a WFPBD. Results suggest the importance of reducing negative perceptions of a WFPBD related to energy and strength, increasing self-efficacy for preparing plant-based meals, and emphasizing health benefits.
Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial
Authors: Vincent C Marconi, Athimalaipet V Ramanan, Stephanie de Bono, Cynthia E Kartman, Venkatesh Krishnan, Ran Liao, Maria Lucia B Piruzeli, Jason D Goldman, Jorge Alatorre-Alexander, Rita de Cassia Pellegrini, Vicente Estrada, Mousumi Som, Anabela Cardoso, Sujatro Chakladar, Brenda Crowe, Paulo Reis, Xin Zhang, David H Adams, E Wesley Ely, Mi-Young Ahn, Miriam Akasbi, Jorge Alatorre-Alexander, Javier David Altclas, Federico Ariel, Horacio Alberto Ariza, Chandrasekhar Atkar, Anselmo Bertetti, Meenakshi Bhattacharya, Maria Luisa Briones, Akshay Budhraja, Aaliya Burza, Adrian Camacho Ortiz, Roberto Caricchio, Marcelo Casas, Valeria Cevoli Recio, Won Suk Choi, Emilia Cohen, Angel Comulada-Rivera, Paul Cook, Dora Patricia Cornejo Juarez, Carnevali Daniel, Luiz Fernando Degrecci Relvas, Jose Guillermo Dominguez Cherit, Todd Ellerin, Dmitry Enikeev, Suzana Erico Tanni Minamoto, Vicente Estrada, Elie Fiss, Motohiko Furuichi, Kleber Giovanni Luz, Jason D. Goldman, Omar Gonzalez, Ivan Gordeev, Thomas Gruenewald, Victor Augusto Hamamoto Sato, Eun Young Heo, Jung Yeon Heo, Maria Hermida, Yuji Hirai, David Hutchinson, Claudio Iastrebner, Octavian Ioachimescu, Manish Jain, Maria Patelli Juliani Souza Lima, Akram Khan, Andreas E. Kremer, Thomas Lawrie, Mark MacElwee, Farah Madhani-Lovely, Vinay Malhotra, Michel Fernando Martínez Resendez, James McKinnell, Patrick Milligan, Cesar Minelli, Miguel Angel Moran Rodriguez, Maria Leonor Parody, Priscila Paulin, Rita de Cassia Pellegrini, Priscilla Pemu, Ana Carolina Procopio Carvalho, Massimo Puoti, Joshua Purow, Mayur Ramesh, Alvaro Rea Neto, Alvaro Rea Neto, Philip Robinson, Cristhieni Rodrigues, Gustavo Rojas Velasco, Jose Francisco Kerr Saraiva, Morton Scheinberg, Stefan Schreiber, Dario Scublinsky, Anete Sevciovic Grumach, Imad Shawa, Jesus Simon Campos, Nidhi Sofat, Mousumi Som, Christoph D. Spinner, Eduardo Sprinz, Roger Stienecker, Jose Suarez, Natsuo Tachikawa, Hasan Tahir, Brian Tiffany, Alexander Vishnevsky, Adilson Westheimer Cavalcante, Kapil Zirpe
Journal: The Lancet Respiratory Medicine (2021)
3MO First-line camrelizumab plus carboplatin and paclitaxel for advanced squamous non-small cell lung cancer: Updated overall survival results from the phase III CameL-sq trial
Authors: C. Zhou, Y. Cheng, J. Chen, X. Xu, G. Chen, Y. Pan, Y. Fang, Q. Wang, Y. Huang, W. Yao, R. Wang, X. Li, W. Zhang, Y. Zhang, J. Shi, P. Cao, D. Wang, D. Lv, H. Luo, Z. Yang
Journal: Annals of Oncology (2022)
Establishing an ad hoc COVID-19 mortality surveillance during the first epidemic wave in Belgium, 1 March to 21 June 2020
Authors: Françoise Renard, Aline Scohy, Johan Van der Heyden, Ilse Peeters, Sara Dequeker, Eline Vandael, Nina Van Goethem, Dominique Dubourg, Louise De Viron, Anne Kongs, Naïma Hammami, Brecht Devleesschauwer, André Sasse, Javiera Rebolledo Gonzalez, Natalia Bustos Sierra
Journal: Eurosurveillance (2021)

Background COVID-19-related mortality in Belgium has drawn attention for two reasons: its high level, and a good completeness in reporting of deaths. An ad hoc surveillance was established to register COVID-19 death numbers in hospitals, long-term care facilities (LTCF) and the community. Belgium adopted broad inclusion criteria for the COVID-19 death notifications, also including possible cases, resulting in a robust correlation between COVID-19 and all-cause mortality. Aim To document and assess the COVID-19 mortality surveillance in Belgium. Methods We described the content and data flows of the registration and we assessed the situation as of 21 June 2020, 103 days after the first death attributable to COVID-19 in Belgium. We calculated the participation rate, the notification delay, the percentage of error detected, and the results of additional investigations. Results The participation rate was 100% for hospitals and 83% for nursing homes. Of all deaths, 85% were recorded within 2 calendar days: 11% within the same day, 41% after 1 day and 33% after 2 days, with a quicker notification in hospitals than in LTCF. Corrections of detected errors reduced the death toll by 5%. Conclusion Belgium implemented a rather complete surveillance of COVID-19 mortality, on account of a rapid investment of the hospitals and LTCF. LTCF could build on past experience of previous surveys and surveillance activities. The adoption of an extended definition of ‘COVID-19-related deaths’ in a context of limited testing capacity has provided timely information about the severity of the epidemic.