tbuckley/cabot-search huggingface dataset:
Intravenous immunoglobulin therapy in adult patients with idiopathic chronic cardiomyopathy and cardiac parvovirus <scp>B19</scp> persistence: a prospective, double‐blind, randomized, placebo‐controlled clinical trial
Authors: Mark R. Hazebroek, Michiel T.H.M. Henkens, Anne G. Raafs, Job A.J. Verdonschot, Jort J. Merken, Robert M. Dennert, Casper Eurlings, Myrurgia A. Abdul Hamid, Petra F.G. Wolffs, Bjorn Winkens, Hans‐Peter Brunner‐La Rocca, Christian Knackstedt, Pieter van Paassen, Vanessa P.M. van Empel, Stephane R.B. Heymans
Journal: European Journal of Heart Failure (2020)

Previous uncontrolled studies suggested a possible benefit of intravenous immunoglobulin (IVIg) in parvovirus B19 (B19V)-related dilated cardiomyopathy (DCM). This randomized, double-blind, placebo-controlled, single-centre trial investigated the benefits of IVIg beyond conventional therapy in idiopathic chronic DCM patients with B19V persistence.Fifty patients (39 men; mean age 54 ± 11 years) with idiopathic chronic (>6 months) DCM on optimal medical therapy, left ventricular ejection fraction (LVEF) <45%, and endomyocardial biopsy (EMB) B19V load of >200 copies/µg DNA were blindly randomized to either IVIg (n = 26, 2 g/kg over 4 days) or placebo (n = 24). The primary outcome was change in LVEF at 6 months after randomization. Secondary outcomes were change in functional capacity assessed by 6-min walk test (6MWT), quality of life [Minnesota Living with Heart Failure Questionnaire (MLHFQ)], left ventricular end-diastolic volume (LVEDV), and EMB B19V load at 6 months after randomization. LVEF significantly improved in both IVIg and placebo groups (absolute mean increase 5 ± 9%, P = 0.011 and 6 ± 10%, P = 0.008, respectively), without a significant difference between groups (P = 0.609). Additionally, change in 6MWT [median (interquartile range) IVIg 36 (13;82) vs. placebo 32 (5;80) m; P = 0.573], MLHFQ [IVIg 0 (-7;5) vs. placebo -2 (-6;6), P = 0.904] and LVEDV (IVIg -16 ± 49 mL/m2 vs. placebo -29 ± 40 mL/m2 ; P = 0.334) did not significantly differ between groups. Moreover, despite increased circulating B19V antibodies upon IVIg administration, reduction in cardiac B19V did not significantly differ between groups.Intravenous immunoglobulin therapy does not significantly improve cardiac systolic function or functional capacity beyond standard medical therapy in patients with idiopathic chronic DCM and cardiac B19V persistence.ClinicalTrials.gov ID NCT00892112.
Antihypertensive effects of exercise involve reshaping of gut microbiota and improvement of gut-brain axis in spontaneously hypertensive rat
Authors: Wen-Jie Xia, Meng-Lu Xu, Xiao-Jing Yu, Meng-Meng Du, Xu-Hui Li, Tao Yang, Lu Li, Ying Li, Kai B. Kang, Qing Su, Jia-Xi Xu, Xiao-Lian Shi, Xiao-Min Wang, Hong-Bao Li, Yu-Ming Kang
Journal: Gut Microbes (2020)

Exercise (Ex) has long been recognized to produce beneficial effects on hypertension (HTN). This coupled with evidence of gut dysbiosis and an impaired gut-brain axis led us to hypothesize that reshaping of gut microbiota and improvement in impaired gut-brain axis would, in part, be associated with beneficial influence of exercise. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise for 12 weeks, whereas, detrained groups underwent 8 weeks of moderate-intensity exercise followed by 4 weeks of detraining. Fecal microbiota, gut pathology, intestinal inflammation, and permeability, brain microglia and neuroinflammation were analyzed. We observed that exercise training resulted in a persistent decrease in systolic blood pressure in the SHR. This was associated with increase in microbial α diversity, altered β diversity, and enrichment of beneficial bacterial genera. Furthermore, decrease in the number of activated microglia, neuroinflammation in the hypothalamic paraventricular nucleus, improved gut pathology, inflammation, and permeability were also observed in the SHR following exercise. Interestingly, short-term detraining did not abolish these exercise-mediated improvements. Finally, fecal microbiota transplantation from exercised SHR into sedentary SHR resulted in attenuated SBP and an improved gut-brain axis. These observations support our concept that an impaired gut-brain axis is linked to HTN and exercise ameliorates this impairment to induce antihypertensive effects.
Titanium mesh for bone augmentation in oral implantology: current application and progress
Authors: Yu Xie, Songhang Li, Tianxu Zhang, Chao Wang, Xiaoxiao Cai
Journal: International Journal of Oral Science (2020)

Guided bone regeneration (GBR) is an effective and simple method for bone augmentation, which is often used to reconstruct the alveolar ridge when the bone defect occurs in the implant area. Titanium mesh has expanded the indications of GBR technology due to its excellent mechanical properties and biocompatibility, so that the GBR technology can be used to repair alveolar ridges with larger bone defects, and can obtain excellent and stable bone augmentation results. Currently, GBR with titanium mesh has various clinical applications, including different clinical procedures. Bone graft materials, titanium mesh covering methods, and titanium mesh fixing methods are also optional. Moreover, the research of GBR with titanium mesh has led to multifarious progresses in digitalization and material modification. This article reviews the properties of titanium mesh and the difference of titanium mesh with other barrier membranes; the current clinical application of titanium mesh in bone augmentation; common complications and management and prevention methods in the application of titanium mesh; and research progress of titanium mesh in digitization and material modification. Hoping to provide a reference for further improvement of titanium mesh in clinical application and related research of titanium mesh.
Unraveling the Mysteries of PAX8 in Reproductive Tract Cancers
Authors: Daniele Chaves-Moreira, Patrice J. Morin, Ronny Drapkin
Journal: Cancer Research (2020)

Abstract Paired Box 8 (PAX8) is a lineage-specific transcription factor that has essential roles during embryogenesis and tumorigenesis. The importance of PAX8 in the development of the reproductive system is highlighted by abnormalities observed upon the loss or mutation of this PAX family member. In cancer, PAX8 expression is deregulated in a key set of neoplasms, including those arising from the Müllerian ducts. The roles of PAX8 in oncogenesis are diverse and include epigenetic remodeling, stimulation of proliferation, inhibition of apoptosis, and regulation of angiogenesis. PAX8 can interact with different protein partners during cancer progression and may exhibit significant function-altering alternative splicing. Moreover, expression of PAX8 in cancer can also serve as a biomarker for diagnostic and prognostic purposes. In this review, we focus on the roles of PAX8 in cancers of the reproductive system. Understanding the diverse mechanisms of action of PAX8 in development and oncogenesis may identify new vulnerabilities in malignancies that currently lack effective therapies.
Overexpression of schizophrenia susceptibility factor human complement C4A promotes excessive synaptic loss and behavioral changes in mice
Authors: Melis Yilmaz, Esra Yalcin, Jessy Presumey, Ernest Aw, Minghe Ma, Christopher W. Whelan, Beth Stevens, Steven A. McCarroll, Michael C. Carroll
Journal: Nature Neuroscience (2020)

The complement component 4 (C4) gene is linked to schizophrenia and synaptic refinement. In humans, greater expression of C4A in the brain is associated with an increased risk of schizophrenia. To investigate this genetic finding and address how C4A shapes brain circuits in vivo, here, we generated a mouse model with primate-lineage-specific isoforms of C4, human C4A and/or C4B. Human C4A bound synapses more efficiently than C4B. C4A (but not C4B) rescued the visual system synaptic refinement deficits of C4 knockout mice. Intriguingly, mice without C4 had normal numbers of cortical synapses, which suggests that complement is not required for normal developmental synaptic pruning. However, overexpressing C4A in mice reduced cortical synapse density, increased microglial engulfment of synapses and altered mouse behavior. These results suggest that increased C4A-mediated synaptic elimination results in abnormal brain circuits and behavior. Understanding pathological overpruning mechanisms has important therapeutic implications in disease conditions such as schizophrenia.
Abstract 11669: Cor-triatriatum Dextrum and Patent Foramen Ovale: A Rare Co-occurrence Leading to Recurrent Strokes
Authors: Sohaib S Roomi, Zain Ali, Waqas Ullah, Artem Minalyan, Shujaul Haq, Mahnoor Shirazi
Journal: Circulation (2019)

Introduction: Cor-triatriatum is a sporadic genetic defect representing 0.1% of all congenital cardiac anomalies where either left atrium(cor-triatriatum sinistrum) or very rarely right atrium(cor-...
Treatment and Outcomes of Inpatient Hypertension Among Adults With Noncardiac Admissions
Authors: Radhika Rastogi, Megan M. Sheehan, Bo Hu, Victoria Shaker, Lisa Kojima, Michael B. Rothberg
Journal: JAMA Internal Medicine (2020)

Despite high prevalence of elevated blood pressure (BP) among medical inpatients, BP management guidelines are lacking for this population. The outcomes associated with intensifying BP treatment in the hospital are poorly studied.To characterize clinician response to BP in the hospital and at discharge and to compare short- and long-term outcomes associated with antihypertensive treatment intensification.This cohort study took place from January 1 to December 31, 2017, with 1 year of follow-up at 10 hospitals within the Cleveland Clinic Hospitals health care system. All adults admitted to a medicine service in 2017 were evaluated for inclusion. Patients with cardiovascular diagnoses were excluded. Demographic and BP characteristics were used for propensity matching.Acute hypertension treatment, defined as administration of an intravenous antihypertensive medication or a new class of an oral antihypertensive treatment.The association between acute hypertension treatment and subsequent inpatient acute kidney injury, myocardial injury, and stroke was measured. Postdischarge outcomes included stroke and myocardial infarction within 30 days and BP control up to 1 year.Among 22 834 adults hospitalized for noncardiovascular diagnoses (mean [SD] age, 65.6 [17.9] years; 12 993 women [56.9%]; 15 963 White patients [69.9%]), 17 821 (78%) had at least 1 hypertensive BP recorded during their admission. Of these patients, 5904 (33.1%) were treated. A total of 8692 of 106 097 cases (8.2%) of hypertensive systolic BPs were treated; of these, 5747 (66%) were treated with oral medications. In a propensity-matched sample controlling for patient and BP characteristics, treated patients had higher rates of subsequent acute kidney injury (466 of 4520 [10.3%] vs 357 of 4520 [7.9%]; P < .001) and myocardial injury (53 of 4520 [1.2%] vs 26 of 4520 [0.6%]; P = .003). There was no BP interval in which treated patients had better outcomes than untreated patients. A total of 1645 of 17 821 patients (9%) with hypertension were discharged with an intensified antihypertensive regimen. Medication intensification at discharge was not associated with better BP control in the following year.In this cohort study, hypertension was common among medical inpatients, but antihypertensive treatment intensification was not. Intensification of therapy without signs of end-organ damage was associated with worse outcomes.
Abstract 399: The Roles of NAD <sup>+</sup> -sensitive Protein Acetylation in Diastolic Dysfunction
Authors: Chi Fung Lee, Juan Chavez, Ying Ann Chiao, James Bruce, Michael Regnier, Rong Tian
Journal: Circulation Research (2017)

Half of the heart failure (HF) patients in US have preserved ejection fraction but diastolic dysfunction. Without a specific medication, better understanding on the mechanisms of diastolic dysfunction is urgently needed. NAD + -sensitive lysine acetylation emerges as regulators of HF pathogenesis. We generated mouse models to manipulate NAD + redox states in the heart. We used cardiac Ndufs4-KO mice (cKO) as a model of reduced NAD + /NADH ratio and cardiac NAMPT over expression (cNAMPT), as a model of elevated NAD + levels. Using labelled-free quantitative proteomics, we identified NAD + -sensitive changes of acetylation landscapes in the heart. Muscle contraction is one of the top categories of acetylated proteins identified by gene ontology analysis. Analysis of non-mitochondrial acetylome showed that many proteins regulating SR Ca 2+ homeostasis and myofilament movement were hyperacetylated in cKO hearts. Therefore, we hypothesized that increased acetylation of components of SR Ca 2+ homeostasis and myofilament movement impairs diastolic function. Using Doppler echocardiography, we observed a decline in E’/A’ ratio and increased myocardial performance index in cKO hearts. Systolic function and cardiac geometry were normal in cKO hearts. In addition, elevation NAD + levels by cNAMPT expression (cKO:cNAMPT) normalized protein hyperacetylation and reversed diastolic dysfunction in cKO. These data support that increased acetylation contributes to the decline in diastolic function in cKO hearts. Future experiments using isolated myofibril and cardiomyocytes will determine the roles of protein acetylation to regulate myofilament, SR Ca 2+ homeostasis and thus diastolic dysfunction.
Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection
Authors: Catherine J. Reynolds, Leo Swadling, Joseph M. Gibbons, Corinna Pade, Melanie P. Jensen, Mariana O. Diniz, Nathalie M. Schmidt, David K. Butler, Oliver E. Amin, Sasha N. L. Bailey, Sam M. Murray, Franziska P. Pieper, Stephen Taylor, Jessica Jones, Meleri Jones, Wing-Yiu Jason Lee, Joshua Rosenheim, Aneesh Chandran, George Joy, Cecilia Di Genova, Nigel Temperton, Jonathan Lambourne, Teresa Cutino-Moguel, Mervyn Andiapen, Marianna Fontana, Angelique Smit, Amanda Semper, Ben O’Brien, Benjamin Chain, Tim Brooks, Charlotte Manisty, Thomas Treibel, James C. Moon, Mahdad Noursadeghi, Daniel M. Altmann, Mala K. Maini, Áine McKnight, Rosemary J. Boyton
Journal: Science Immunology (2020)

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.
Regression of Cardiac Hypertrophy by Cyclic Guanosine Monophosphate-Dependent Protein Kinase Signaling: Are Myocytes Active Sources or Mere Beneficiaries?**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Roger J. Hajjar, Fadi G. Akar
Journal: Journal of the American College of Cardiology (2010)
Words matter: a randomized controlled study evaluating the impact of decision‐framing on treatment preferences in adults with psoriasis and psoriatic arthritis
Authors: A.A. Kassardjian, V.S. Chat, L. Archuleta, J. Hekmatjah, T.J. Sierro, C. Read, A.Y. Chen, I. Singh, A.W. Armstrong
Journal: British Journal of Dermatology (2020)
Readdressing the Needs of Cancer Survivors During COVID-19: A Path Forward
Authors: Jennifer M Jones, Hina Saeed, Matthew S Katz, Maryam B Lustberg, Victoria J Forster, Larissa Nekhlyudov
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract The growing number of cancer survivors and the high prevalence of cancer-related physical and psychosocial effects pose important and pressing challenges to health systems. The coronavirus disease 2019 (COVID-19) pandemic has led to further stressors on cancer survivors and health care systems. As the pandemic continues to have substantial impact on the world, it is critical to focus attention on the health care needs of cancer survivors. In this commentary, we propose an adoption of essential steps that should be part of a continuous adaptive approach to promote effective cancer survivorship care during ongoing COVID-19 waves and beyond.
Association of Frailty and Sex With Wait List Mortality in Liver Transplant Candidates in the Multicenter Functional Assessment in Liver Transplantation (FrAILT) Study
Authors: Jennifer C. Lai, Daniel R. Ganger, Michael L. Volk, Jennifer L. Dodge, Michael A. Dunn, Andres Duarte-Rojo, Matthew R. Kappus, Robert S. Rahimi, Daniela P. Ladner, Brian Boyarsky, Mara McAdams-DeMarco, Dorry L. Segev, Charles E. McCulloch, Elizabeth C. Verna
Journal: JAMA Surgery (2020)

Female liver transplant candidates experience higher rates of wait list mortality than male candidates. Frailty is a critical determinant of mortality in patients with cirrhosis, but how frailty differs between women and men is unknown.To determine whether frailty is associated with the gap between women and men in mortality among patients with cirrhosis awaiting liver transplantation.This prospective cohort study enrolled 1405 adults with cirrhosis awaiting liver transplant without hepatocellular carcinoma seen during 3436 ambulatory clinic visits at 9 US liver transplant centers. Data were collected from January 1, 2012, to October 1, 2019, and analyzed from August 30, 2019, to October 30, 2020.At outpatient evaluation, the Liver Frailty Index (LFI) score was calculated (grip strength, chair stands, and balance).The risk of wait list mortality was quantified using Cox proportional hazards regression by frailty. Mediation analysis was used to quantify the contribution of frailty to the gap in wait list mortality between women and men.Of 1405 participants, 578 (41%) were women and 827 (59%) were men (median age, 58 [interquartile range (IQR), 50-63] years). Women and men had similar median scores on the laboratory-based Model for End-stage Liver Disease incorporating sodium levels (MELDNa) (women, 18 [IQR, 14-23]; men, 18 [IQR, 15-22]), but baseline LFI was higher in women (mean [SD], 4.12 [0.85] vs 4.00 [0.82]; P = .005). Women displayed worse balance of less than 30 seconds (145 [25%] vs 149 [18%]; P = .003), worse sex-adjusted grip (mean [SD], -0.31 [1.08] vs -0.16 [1.08] kg; P = .01), and fewer chair stands per second (median, 0.35 [IQR, 0.23-0.46] vs 0.37 [IQR, 0.25-0.49]; P = .04). In unadjusted mixed-effects models, LFI was 0.15 (95% CI, 0.06-0.23) units higher in women than men (P = .001). After adjustment for other variables associated with frailty, LFI was 0.16 (95% CI, 0.08-0.23) units higher in women than men (P < .001). In unadjusted regression, women experienced a 34% (95% CI, 3%-74%) increased risk of wait list mortality than men (P = .03). Sequential covariable adjustment did not alter the association between sex and wait list mortality; however, adjustment for LFI attenuated the mortality gap between women and men. In mediation analysis, an estimated 13.0% (IQR, 0.5%-132.0%) of the gender gap in wait list mortality was mediated by frailty.These findings demonstrate that women with cirrhosis display worse frailty scores than men despite similar MELDNa scores. The higher risk of wait list mortality that women experienced appeared to be explained in part by frailty.
Circadian immune circuits
Authors: Miguel Palomino-Segura, Andrés Hidalgo
Journal: The Journal of Experimental Medicine (2020)

Immune responses are gated to protect the host against specific antigens and microbes, a task that is achieved through antigen- and pattern-specific receptors. Less appreciated is that in order to optimize responses and to avoid collateral damage to the host, immune responses must be additionally gated in intensity and time. An evolutionary solution to this challenge is provided by the circadian clock, an ancient time-keeping mechanism that anticipates environmental changes and represents a fundamental property of immunity. Immune responses, however, are not exclusive to immune cells and demand the coordinated action of nonhematopoietic cells interspersed within the architecture of tissues. Here, we review the circadian features of innate immunity as they encompass effector immune cells as well as structural cells that orchestrate their responses in space and time. We finally propose models in which the central clock, structural elements, and immune cells establish multidirectional circadian circuits that may shape the efficacy and strength of immune responses and other physiological processes.
Balloon Angioplasty Versus New Device Intervention: Clinical Outcomes: A Comparison of the NHLBI PTCA and NACI Registries fn1fn1This study was supported by Grants HL33292 and HL44284 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Authors: Spencer B. King, Wanlin Yeh, Richard Holubkov, Donald S. Baim, George Sopko, Patrice Desvigne-Nickens, David R. Holmes, Michael J. Cowley, Martial G. Bourassa, James Margolis, Katherine M. Detre, Naci Registry Investigators
Journal: Journal of the American College of Cardiology (1998)
Abstract 14426: Incidence, Characteristics and Prognosis of Complete Atrioventricular Block in Fulminant Myocarditis Requiring a Mechanical Support System
Authors: Shozo Konishi, Hitoshi Minamiguchi, Kentaro Ozu, Hiroya Mizuno, Fusako Sera, Isamu Mizote, Tomohito Ohtani, Shungo Hikoso, Yasushi Sakata
Journal: Circulation (2018)

Background: Complete atrioventricular block (CAVB) is sometimes a complication of acute myocarditis. However, its incidence, characteristics, and prognosis in fulminant myocarditis (FM) are not wel...
Deliberations of an International Panel of Experts on OCT Angiography Nomenclature of Neovascular Age-Related Macular Degeneration
Authors: Luísa S.M. Mendonça, Rhianon Perrott-Reynolds, Roy Schwartz, Haifa A. Madi, Nicola Cronbach, Isaac Gendelman, Alyson Muldrew, Finnian Bannon, Konstantinos Balaskas, Chui Ming Gemmy Cheung, Amani Fawzi, Daniela Ferrara, K. Bailey Freund, James Fujimoto, Marion R. Munk, Giuseppe Querques, Ramiro Ribeiro, Philip J. Rosenfeld, SriniVas R. Sadda, Jayashree Sahni, David Sarraf, Richard F. Spaide, Ursula Schmidt-Erfurth, Eric Souied, Giovanni Staurenghi, Ramin Tadayoni, Ruikang K. Wang, Usha Chakravarthy, Nadia K. Waheed
Journal: Ophthalmology (2020)