tbuckley/cabot-search huggingface dataset:
Abstract 12692: Overexpression of Myocardial Inducible Nitric Oxide Synthase Exacerbates Cardiac Dysfunction and Beta-Adrenergic Desensitization in Streptozotocin-Induced Diabetic Mice
Authors: Yixi Liu, Che Cheng, Xiaoqiang Sun, Jing Cao, Peng Zhou, David Herrington, Dalane Kitzman, David Zhao, Heng Jie Cheng
Journal: Circulation (2020)

Background: Recent evidence links impaired nitric oxide (NO) signaling pathway in the pathogenesis of diabetes-induced cardiac dysfunction. However, the different nitric oxide synthases (NOS) isoforms involved in this pathology are controversial. Recent reports have shown that in failing myocardium, increased inducible NOS (iNOS) contributes to the attenuation of β-adrenergic receptor (AR)-mediated inotropic effect. The alteration and functional significance of cardiac iNOS in diabetic cardiomyopathy (DCM) are unclear. We assessed the hypothesis that increased cardiomyocyte iNOS expression and stimulation may inhibit myocyte contraction, relaxation, [Ca 2+ ] i transient ([Ca 2+ ] iT ), and depress its response to β-AR stimulation, thereby directly contributing to the functional impairment in DCM. Methods: Left ventricular (LV) myocyte protein levels of 3 NOS and myocyte functional responses were evaluated in 2 groups of wild-type female mice (11/group): control and DCM-induced by streptozotocin (STZ) (at 10 weeks after receiving 200 mg/kg STZ, ip). In DCM, we further assessed myocyte contractile and ([Ca 2+ ] iT ) responses to β-AR stimulation by isoproterenol (ISO, 10 -8 M) with and without pretreatment of myocytes with a selective iNOS inhibitor, 1400W (10 -5 M). Results: Compared with controls, DCM myocytes had significantly increased iNOS (1.76 vs 1.03) with decreased eNOS (0.29 vs 0.34), but relatively unchanged nNOS (0.17 vs 0.18). These changes were followed by significantly reduced basal cell contraction (dL/dt max , 73.8 vs 140.7 μm/s), relaxation (dR/dt max , 61.5 vs 121.1 μm/s) and [Ca 2+ ] iT (0.17 vs 0.20). ISO-stimulated increases in dL/dt max (32% vs 59%), dR/dt max (30% vs 55%) and [Ca 2+ ] iT (17% vs 31%) were also significantly reduced. Moreover, in DCM myocytes, pretreatment with 1400W markedly improved myocyte basal contraction (128.0 μm/s) and relaxation (111.7 μm/s). The ISO-induced increases in dL/dt max (55%), dR/dt max (52%), and [Ca 2+ ] iT (29%) were also significantly augmented. Conclusions: Our findings indicate that myocardial iNOS is activated in diabetic mice and suggest that increased iNOS expression contributes to depressed myocardial contractility, impaired [Ca 2+ ] i regulation and β-adrenergic hyporesponsiveness.
Abstract 15211: Outcomes of Coronary Venous Dissection During Coronary Sinus Lead Placement for Cardiac Resynchronization Therapy
Authors: Johnny Chahine, Oussama Wazni, Chandra K Ala, Bryan Baranowski, Walid Saliba, Khaldoun Tarakji, John Rickard, Mohamed Kanj, Bruce Wilkoff, Bruce Lindsay, Ayman Hussein
Journal: Circulation (2018)

Introduction: The risk of coronary sinus (CS) dissection when placing a CS lead for cardiac resynchronization therapy (CRT) increases with challenging coronary anatomy and/or forceful manipulation ...
Abstract 15153: Functional Cardiac Adaptation to 60 Days Strict Head-Down-Tilt Bedrest
Authors: Fabian Hoffmann, Jeremy Rabineau, Dennis Mehrkens, Bernd W Johannes, Enrico G Caiania, Pierre-Francois Migeotte, Jens Jordan, Jens Tank
Journal: Circulation (2020)

Background: Reduced physical activity increases the risk for heart failure. Myocardial strain measurements capture subtle abnormalities in myocardial function. We tested the hypothesis that bedrest deconditioning produces cardiac dysfunction in healthy persons. Methods: In the AGBRESA study, which assessed artificial gravity through centrifugation as potential countermeasure for space travel, 24 healthy persons (8 women) were submitted to 60 days strict -6°-head-down-tilt bedrest. 8 subjects each were included in a control group or groups subjected to continuous artificial gravity training on a short-arm centrifuge [30 minutes/day] or intermittent centrifugation [6x5 min/day]. We assessed cardiac morphology, function, strain and hemodynamics by cardiac-MRI (baseline, end of bedrest, recovery) and echocardiography (baseline, end of bedrest). Before and after bedrest, we assessed orthostatic heart rate responses as measure of cardiovascular deconditioning. Results: We conducted a pooled analysis because cardiovascular responses to bedrest did not differ between groups. Supine heart rate (baseline: 64±9.6bpm; bedrest: 72.3±10.5bpm; recovery: 69.6±10.5bpm, p &lt;0.0001) and diastolic blood-pressure (69.6±7.3mmHg; bedrest: 78.5±6.9mmHg; recovery: 70.3±6.3mmHg, p &lt;0.0001) increased with bedrest. With head-up tilt, heart rate increased 22.8±10.5bpm before and 45.9±213bpm at the end of bedrest ( p &lt;0.0001) consistent with cardiovascular deconditioning. Cardiac-output decreased from 6.6±0.9l/min to 6±1l/min at end of bedrest (recovery: 6.8±1.2l/min, p =0.0096). Left ventricular ejection fraction and mass-index did not change. Echocardiographic global longitudinal strain (baseline: -19.90±2.1%; bedrest: -18.1±2.1%, p &lt;0.0001) decreased, whereas global circumferential strain in MRI tended to increase (baseline: -18.6±1.7%; bedrest: -19.1±1.6%, p =0.0843). After four days of recovery MRI measurements had returned to baseline. Conclusion: In healthy persons, cardiovascular deconditioning through 60 days head-down-tilt bedrest does not lead to cardiac atrophy or sustained reductions in cardiac performance. The transient nature of cardiac strain changes suggests functional rather than structural changes in the heart.
Muscle Degeneration: Preparation of Stretchable Nanofibrous Sheets with Sacrificial Coaxial Electrospinning for Treatment of Traumatic Muscle Injury (Adv. Healthcare Mater. 8/2021)
Authors: Oanh‐Vu Pham‐Nguyen, Young Ju Son, Tae‐wan Kwon, Junhyung Kim, Yun Chan Jung, Jong Bae Park, Byung‐Jae Kang, Hyuk Sang Yoo
Journal: Advanced Healthcare Materials (2021)

In article number 2002228 by Byung-Jae Kang, Hyuk Sang Yoo, and co-workers, a new method of fabricating nano-scaled gelatin nanofibers is introduced for treatment of volumetric loss of muscle. Myoblasts experiencing stepwise stretching of the gelatin nanofibers exhibit enhanced transition to myotubes. Muscle transplanted with stem cells/gelatin nanofibers exhibit higher recovery efficacy of muscle functions.
Single‐cell RNA sequencing profiling in a patient with discordant primary cutaneous B‐cell and T‐cell lymphoma reveals micromilieu‐driven immune skewing
Authors: C. Jonak, N. Alkon, K. Rindler, T.B. Rojahn, L.E. Shaw, S. Porkert, W. Weninger, F. Trautinger, G. Stingl, P. Tschandl, L. Cerroni, M. Farlik, P.M. Brunner
Journal: British Journal of Dermatology (2021)

Primary cutaneous lymphomas comprise a heterogeneous group of B-cell and T-cell malignancies which often show an indolent course, but can progress to aggressive disease in a subset of patients. Diagnosis is often delayed owing to clinical and histopathological similarities with benign inflammatory conditions. Especially during early disease, cancer cells are present at relatively low percentages compared with the inflammatory infiltrate, an interplay that is currently only insufficiently understood.To improve diagnostics and perform molecular characterization of a complex type of primary cutaneous lymphoma.Single-cell RNA sequencing (scRNA-seq) was performed and combined with T-cell and B-cell receptor sequencing.We were able to diagnose a patient with concurrent mycosis fungoides (MF) and primary cutaneous follicle centre lymphoma (PCFCL), appearing in mutually exclusive skin lesions. Profiling of tumour cells and the tissue microenvironment revealed a type-2 immune skewing in MF, most likely guided by the expanded clone that also harboured upregulation of numerous pro-oncogenic genes. By contrast, PCFCL lesions exhibited a more type-1 immune phenotype, consistent with its indolent behaviour.These data not only illustrate the diagnostic potential of scRNA-seq, but also allow the characterization of specific clonal populations that shape the unique tissue microenvironment in clinically distinct types of lymphoma skin lesions.
Abstract 16606: Home Blood Pressure Monitoring Postpartum Detects Masked Hypertension in Women With a History of Preeclampsia
Authors: Virginia R Nuckols, Amy K Stroud, Debra Brandt, Mark K Santillan, Donna A Santillan, Janet M Catov, Carl A Hubel, Gary L Pierce
Journal: Circulation (2020)

Introduction: One-third of women with a history of preeclampsia (hxPE), a hypertensive pregnancy disorder, develop chronic hypertension (HTN) within five years postpartum. Twenty-four hour ambulatory blood pressure monitoring (ABPM) shows that 12% of women with hxPE have ‘masked’ HTN. Masked HTN is undetected in routine clinical assessment but is associated with elevated cardiovascular disease risk. ABPM (gold-standard) or home blood pressure monitoring (HBPM) is needed to identify masked HTN. HBPM is a well-tolerated, inexpensive alternative to ABPM. However, the ability of HBPM to detect masked postpartum HTN using new AHA/ACC HTN guidelines is unknown. The purpose of this study was to compare ABPM and HBPM in the identification of masked and sustained HTN among young women with hxPE and healthy pregnancy (HP) controls 1-3 years postpartum. Methods: Women with hxPE (N=22; age 33 ± 5 yrs) and HP controls (N=26; age 34 ± 4 yrs) were assessed 18 ± 6 months postpartum. Seated office blood pressure (BP) was collected with an automated brachial cuff and averaged over three trials. ABPM (Mobil-o-graph) was conducted with a portable, automated brachial cuff and averaged over 38 ± 2 awake and asleep BP recordings. Participants completed HBPM (Microlife) morning and evening for seven consecutive days. BP thresholds for HTN were determined according to 2017 AHA/ACC clinical guidelines. Results: HTN was more prevalent among women with hxPE compared with HP assessed by office BP (59 vs. 15 %, P=0.002) and ABPM (68 vs. 31 %, P=0.01) but not HBPM (41 vs 19 %, P=0.10). The prevalence of masked HTN did not differ between women with hxPE and HP (14 vs. 19%, P=0.71) assessed by ABPM. In the entire cohort, HBPM detected 50% of masked HTN cases identified by ABPM. HBPM agreed with ABPM on HTN status (κ = 0.49, P=0.002). HBPM and ABPM detected uncontrolled HTN in three of four women with hxPE prescribed anti-hypertensive medication. Conclusion: HxPE is associated with a higher prevalence of HTN 1-3 yrs postpartum compared with controls, but the prevalence of masked HTN did not differ. ABPM and HBPM showed concordant classification of HTN using current BP guidelines. These findings indicate that HBPM may be a valuable pre-screening tool for early identification and management of HTN postpartum.
Pharmacological activation of STING blocks SARS-CoV-2 infection
Authors: Minghua Li, Max Ferretti, Baoling Ying, Hélène Descamps, Emily Lee, Mark Dittmar, Jae Seung Lee, Kanupriya Whig, Brinda Kamalia, Lenka Dohnalová, Giulia Uhr, Hoda Zarkoob, Yu-Chi Chen, Holly Ramage, Marc Ferrer, Kristen Lynch, David C. Schultz, Christoph A. Thaiss, Michael S. Diamond, Sara Cherry
Journal: Science Immunology (2021)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic, resulting millions of infections and deaths with few effective interventions available. Here, we demonstrate that SARS-CoV-2 evades interferon (IFN) activation in respiratory epithelial cells, resulting in a delayed response in bystander cells. Since pretreatment with IFNs can block viral infection, we reasoned that pharmacological activation of innate immune pathways could control SARS-CoV-2 infection. To identify potent antiviral innate immune agonists, we screened a panel of 75 microbial ligands that activate diverse signaling pathways and identified cyclic dinucleotides (CDNs), canonical STING agonists, as antiviral. Since CDNs have poor bioavailability, we tested the small molecule STING agonist diABZI, and found that it potently inhibits SARS-CoV-2 infection of diverse strains including variants of concern (B.1.351) by transiently stimulating IFN signaling. Importantly, diABZI restricts viral replication in primary human bronchial epithelial cells and in mice in vivo. Our study provides evidence that activation of STING may represent a promising therapeutic strategy to control SARS-CoV-2.
Assessment of Feasibility of Face Covering in School-Aged Children With Autism Spectrum Disorders and Attention-Deficit/Hyperactivity Disorder
Authors: Benjamin Aaronson, Sara Nelson Glick, Christa Jefferis Kirk, William A. McCloud, Tyler R. Sasser, Danielle M. Zerr, Janet A. Englund
Journal: JAMA Network Open (2021)

This cohort study reports the outcomes of using positive behavior supports to promote masking in school-aged children with autism spectrum disorders (ASD) and/or attention-deficit/hyperactivity disorder (ADHD) attending a summer day treatment program.
A Prospective, Non-Randomized, Multicenter, Phase II Study to Assess Safety and Efficacy of the Infusion of Peripheral Blood Stem Cells Obtained from HLA-Haploidentical Familial Donors (mHaploSCI) after Standard Chemotherapy in Elderly Patients with Acute Myeloid Leukemia at Intermediate or Adverse Risk
Authors: Mirko Farina, Massimo Bernardi, Valentina Mancini, Arnalda Lanfranchi, Alessandra Beghin, Enrico Morello, Marta Petullà, Erika Borlenghi, Chiara Cattaneo, Roberto Cairoli, Giuseppe Rossi
Journal: Blood (2017)
TMEM41B acts as an ER scramblase required for lipoprotein biogenesis and lipid homeostasis
Authors: Dong Huang, Bolin Xu, Lu Liu, Lingzhi Wu, Yuangang Zhu, Alireza Ghanbarpour, Yawei Wang, Feng-Jung Chen, Jia Lyu, Yating Hu, Yunlu Kang, Wenjing Zhou, Xiao Wang, Wanqiu Ding, Xin Li, Zhaodi Jiang, Jizheng Chen, Xu Zhang, Hongwen Zhou, John Zhong Li, Chunguang Guo, Wen Zheng, Xiuqin Zhang, Peng Li, Thomas Melia, Karin Reinisch, Xiao-Wei Chen
Journal: Cell Metabolism (2021)
Abstract 16058: Abnormal P Wave Morphology is Associated With Decreased Left Atrial Appendage Ejection Velocity
Authors: Nathaniel D Mcconkey, Peter Malamas, Jovan Plamenac, Robert Park, Frank Weigel, Mario Gonzalez, Gerald Naccarelli, Ankit Maheshwari
Journal: Circulation (2020)

Introduction: P-wave abnormalities measured during periods of sinus rhythm have been associated stroke in people with atrial fibrillation (AF). The majority of AF-related strokes occur from left atrial appendage (LAA) thromboembolism. Electrical and mechanical dysfunction of the left atrium (LA) and left atrial appendage (LAA) can lower the threshold for thromboembolism and stroke. Hypothesis: We aimed to determine whether P-wave abnormalities are associated with decreased LAA ejection velocity (LAAV) on transesophageal echocardiography (TEE). Methods: We conducted a retrospective cross-sectional study. We reviewed patients at a tertiary care medical center who had underwent TEE in sinus rhythm and had an interpretable sinus rhythm ECG within 12 months of TEE. Participants were excluded for history of complex congenital heart disease, age&lt;18, cardiac transplantation, and atrial pacing. Logistic regression analysis was used to estimate the odds ratios of LAAV&lt;40 cm/s for P-wave abnormalities—advanced interatrial block (aIAB), abnormal P-wave terminal force in V1 (aPTFV1), prolonged P-wave duration (PPWD), and abnormal P-wave axis (aPWA). Results: In our final cohort of 169 patients, the odds ratios of aIAB and aPTFV1 for LAAV&lt;40 cm/s after adjustment for CHA 2 DS 2 VASc variables, heart rate during TEE, history of atrial arrhythmias, and left atrial volume index were 2.81 (1.07-7.53) and 2.48 (1.13-5.60), respectively. Conclusions: P-wave abnormalities are independently associated with low LAAV, which may explain their association with AF-related stroke. Further research is needed to determine if incorporation of P-wave analysis will aid AF-related stroke prediction algorithms.
Abstract P053: Increment And Stabilization Of Diabetes Prevalence In The Province Of Quebec, Canada: A Combination Of Lower Mortality And Incidence In Older Adults Only
Authors: Sarah O'Connor, Claudia Blais, Jacinthe Leclerc, Denis Hamel, Marjolaine Dubé, Paul Poirier
Journal: Circulation (2021)

Introduction: In the last decade, an increase in the prevalence and a reduction in the incidence of diabetes have been observed in many countries including Canada. Yet, some Canadian provinces depicted an elevation in incidence rates among younger age groups. Our objective was to document these trends in the province of Quebec from fiscal years 2001 to 2017. Hypothesis: Prevalence is increasing because of raising incidence in individuals aged &lt;50 years. Methods: Prevalence, incidence and all-cause mortality among cases of diabetes ≥20 years were assessed using the Quebec Integrated Chronic Disease Surveillance System (n=6,551,045 in 2017). Estimations were age-standardized or stratified by 10-year age groups. Results: In 2017, the crude prevalence and incidence of diabetes were 9.9% [99% confidence interval: 9.9-10.0] (n=651,370) and 6.0 per 1,000 inhabitants [5.9-6.0] (n=35,355), respectively. Between 2001 and 2017, the age-standardized prevalence increased by 43% (6.3% [6.3-6.3] to 9.0% [9.0-9.1]), while age-standardized incidence decreased by 29% (8.3 per 1,000 [8.2-8.4] to 5.9 per 1,000 [5.9-6.0]). In every age group, the prevalence increased steadily with progressive stabilization from 2011 and onward, except for the 60-69 years old group who depicted a reduction from 2012 to 2017. Incidence remained stable among &lt;50 years old, while it decreased for ≥50 years (-26%, -33%, -36% for 50-59, 60-69 and ≥70 years old, respectively) (Figure 1). Age-standardized mortality among adults with diabetes decreased by 24% (20.7 per 1,000 [20.1-21.3] to 15.8 per 1,000 [15.4-16.3]). Mortality rates decreased by 27% among the 40-49 years old, with greater reductions in older age groups (-28%, -35%, -34% in the 50-59, 60-69 and ≥70 years, respectively). Conclusions: The rise and stabilization of diabetes prevalence could be due to a reduction in incidence in patients aged ≥50 years and mortality among all age groups. Prevention of diabetes should be a priority among individuals aged &lt;50 years as diabetes incidence is not decreasing.
Post-acute effects of SARS-CoV-2 infection in individuals not requiring hospital admission: a Danish population-based cohort study
Authors: Lars Christian Lund, Jesper Hallas, Henrik Nielsen, Anders Koch, Stine Hasling Mogensen, Nikolai Constantin Brun, Christian Fynbo Christiansen, Reimar Wernich Thomsen, Anton Pottegård
Journal: The Lancet Infectious Diseases (2021)
PEPPRO: quality control and processing of nascent RNA profiling data
Authors: Jason P. Smith, Arun B. Dutta, Kizhakke Mattada Sathyan, Michael J. Guertin, Nathan C. Sheffield
Journal: Genome biology (2021)

Abstract Nascent RNA profiling is growing in popularity; however, there is no standard analysis pipeline to uniformly process the data and assess quality. Here, we introduce PEPPRO, a comprehensive, scalable workflow for GRO-seq, PRO-seq, and ChRO-seq data. PEPPRO produces uniformly processed output files for downstream analysis and assesses adapter abundance, RNA integrity, library complexity, nascent RNA purity, and run-on efficiency. PEPPRO is restartable and fault-tolerant, records copious logs, and provides a web-based project report. PEPPRO can be run locally or using a cluster, providing a portable first step for genomic nascent RNA analysis.
Abstract 16912: Cardiac Microstructural Associations With Pulse Pressure Differ by Sex
Authors: Gerran Salto, Alan C Kwan, Ewa Osypiuk, Plamen Stantchev, Elizabeth H Kim, Pranoti Hiremath, Susan Cheng
Journal: Circulation (2020)

Background: Alterations in the orientation and integrity of myocardial fibers can be assessed using ultrasonic image analysis. The ability to detect such microstructural abnormalities may shed light on sex differences in the progression from common risk factors, such as blood pressure elevation, to overt cardiac disease. Methods: In a community-based cohort of N=2510 adults (age 66±9 years, 56% women) without overt cardiovascular disease, we evaluated whether a novel echocardiography-based assessment of left ventricular myocardial microstructure, the signal intensity coefficient (SIC), could detect tissue-level alterations that are associated with blood pressure parameters including pulse pressure, an indirect measure of large artery stiffness and established correlate of adverse cardiac outcomes. Results: We observed that for every 10 mmHg increase in pulse pressure, women had a significantly greater degree of cardiac microstructural alteration (coeff 0.07; s.e. 0.02, P&lt;0.001), whereas this age-adjusted association was not seen in men (coeff -0.01; s.e. 0.02, P=0.65) ( Figure ). Although we observed similar results for systolic, diastolic, and mean arterial pressure, the sex interaction terms were non-significant (P&gt;0.05) for these other parameters. Conclusion: A novel index of myocardial tissue alteration is associated with incremental elevations in pulse pressure in women but not in men. Further research is needed to examine the extent to which cardiac microstructural abnormalities may mediate the risks for cardiac disease in women, particularly those conditions involving large artery stiffening such as heart failure with preserved ejection fraction.
Abstract GMM-045: PAX8 PLAYS AN ESSENTIAL ROLE IN HIGH GRADE SEROUS OVARIAN CANCER VIA ACTIVATION OF MUTANT P53 AND MISLOCALIZED P21
Authors: Dima Ghannam, Eyal Jacob, Reli Kakun, Tanya Wasserman, Lina Korsensky, Ofir Sternfeld, Julia Kagan, Debora Rosa Bublik, Sarit Aviel-Ronen, Keren Levanon, Edmond Sabo, Sarit Larisch, Moshe Oren, Dov Hershkovitz, Ruth Perets
Journal: Clinical Cancer Research (2019)

Abstract High grade serous carcinoma (HGSC) is the most common subtype of ovarian cancer, and a very deadly disease, mostly due to lack of early detection methods. Wide spread disease at diagnosis has delayed the understanding that it often originates from the fallopian tube. This novel understanding has led to increased interest in fallopian tube developmental lineage markers, such as PAX8. In the adult fallopian tube, PAX8 is expressed in the fallopian tube secretory epithelial cell (FTSEC) and its expression is maintained through the process of FTSEC transformation Serous Tubal Intraepithelial Carcinoma (STIC) and to HGSC. We show that PAX8 has an essential pro-proliferative and anti-apoptotic role in HGSC. This role is mediated through direct transcriptional activation of mutated TP53, which often carries missense mutations that potentially lead to gain of function (GOF) oncogenic activities. Surprisingly, mutant p53 binds the p21 promoter and transcriptionally activates the expression of p21, which localizes to the cytoplasm of cells where it plays a non-canonical, pro-proliferative role. While in normal fallopian tube p21 is nuclear as expected, and STIC shows a mix of nuclear and cytoplasmic staining, an analysis of p21 staining in EOC shows that cytoplasmic p21 expression correlates with bad prognostic factors. Together, our findings illustrate that in HGSC TP53 mutations and abnormal p21 localization subvert a normal developmental pathway into a driver of tumor progression. Citation Format: Dima Ghannam, Eyal Jacob, Reli Kakun, Tanya Wasserman, Lina Korsensky, Ofir Sternfeld, Julia Kagan, Debora Rosa Bublik, Sarit Aviel-Ronen, Keren Levanon, Edmond Sabo, Sarit Larisch, Moshe Oren, Dov Hershkovitz, Ruth Perets. PAX8 PLAYS AN ESSENTIAL ROLE IN HIGH GRADE SEROUS OVARIAN CANCER VIA ACTIVATION OF MUTANT P53 AND MISLOCALIZED P21 [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr GMM-045.