tbuckley/cabot-search huggingface dataset:
Abstract 17334: Effects of Alcohol Consumption on Fiver-Year Change in Cardiac Structure and Function: In the Echocardiographic Study of Latinos
Authors: Cristian Zamora, Un Jung Lee, Mayank M Kansal, Barry E Hurwitz, Mario J Garcia, Greg Talavera, Robert Kaplan, Carlos J Rodriguez
Journal: Circulation (2020)

Background: The relationship between alcohol consumption and clinical heart failure has been extensively studied. There have been little longitudinal data documenting alcohol effects on cardiac structure and function in a community-based population. Methods: The second Echocardiographic Study of Latinos (ECHO-SOL2) was designed to provide echocardiographic parameters that characterized longitudinal cardiac structure and function in a random and representative sample of 1,818 participants ≥45 years old. Participants underwent to serial echocardiograms at 2011-2014 (exam 1) and ~5-6 years later at 2016-2019 (exam 2). Quantification of alcohol was created on a gender-specific basis. Multiple linear regression models were adjusted for age and sex. Results: The mean age at enrollment was 56.4 years old, 57% were women. At baseline, impaired left ventricular (LV) systolic function and increased right ventricular (RV) function were associated with binge drinkers (P = 0.01). At 5-6 years later, heavy drinkers had a significant decrease in LV ejection fraction (P = 0.01). Moderate and binge drinkers demonstrated worsening diastolic function over time (P ≤ 0.01). Binge drinkers demonstrated a progressive decrease in LV mass index (P = 0.02), decrease in LV stroke volume (P = 0.01) and further reduction in RV function (P &lt; 0.01). Conclusion: Alcohol consumption was associated with longitudinal changes in cardiac structure and function, mostly among binge drinkers, which can lead to impaired myocardial contractility compared to nondrinkers.
Platelets orchestrate the resolution of pulmonary inflammation in mice by T reg cell repositioning and macrophage education
Authors: Jan Rossaint, Katharina Thomas, Sina Mersmann, Jennifer Skupski, Andreas Margraf, Tobias Tekath, Charlotte C. Jouvene, Jesmond Dalli, Andres Hidalgo, Sven G. Meuth, Oliver Soehnlein, Alexander Zarbock
Journal: The Journal of Experimental Medicine (2021)

Beyond hemostasis, platelets actively participate in immune cell recruitment and host defense, yet their potential in the resolution of inflammatory processes remains unknown. Here, we demonstrate that platelets are recruited into the lung together with neutrophils during the onset of inflammation and alongside regulatory T (T reg) cells during the resolution phase. This partnering dichotomy is regulated by differential adhesion molecule expression during resolution. Mechanistically, intravascular platelets form aggregates with T reg cells, a prerequisite for their recruitment into the lung. This interaction relies on platelet activation by sCD40L and platelet P-selectin binding to PSGL-1 on T reg cells. Physical platelet–T reg cell interactions are necessary to modulate the transcriptome and instruct T reg cells to release the anti-inflammatory mediators IL-10 and TGFβ. Notably, the presence of platelet–T reg cell aggregates in the lung was also required for macrophage transcriptional reprogramming, polarization toward an anti-inflammatory phenotype, and effective resolution of pulmonary inflammation. Thus, platelets partner with successive immune cell subsets to orchestrate both the initiation and resolution of inflammation.
Xenogeneic Silencing and Bacterial Genome Evolution: Mechanisms for DNA Recognition Imply Multifaceted Roles of Xenogeneic Silencers
Authors: Bo Duan, Pengfei Ding, William Wiley Navarre, Jun Liu, Bin Xia
Journal: Molecular Biology and Evolution (2021)

Horizontal gene transfer (HGT) is a major driving force for bacterial evolution. To avoid the deleterious effects due to the unregulated expression of newly acquired foreign genes, bacteria have evolved specific proteins named xenogeneic silencers to recognize foreign DNA sequences and suppress their transcription. As there is considerable diversity in genomic base compositions among bacteria, how xenogeneic silencers distinguish self- from nonself DNA in different bacteria remains poorly understood. This review summarizes the progress in studying the DNA binding preferences and the underlying molecular mechanisms of known xenogeneic silencer families, represented by H-NS of Escherichia coli, Lsr2 of Mycobacterium, MvaT of Pseudomonas, and Rok of Bacillus. Comparative analyses of the published data indicate that the differences in DNA recognition mechanisms enable these xenogeneic silencers to have clear characteristics in DNA sequence preferences, which are further correlated with different host genomic features. These correlations provide insights into the mechanisms of how these xenogeneic silencers selectively target foreign DNA in different genomic backgrounds. Furthermore, it is revealed that the genomic AT contents of bacterial species with the same xenogeneic silencer family proteins are distributed in a limited range and are generally lower than those species without any known xenogeneic silencers in the same phylum/class/genus, indicating that xenogeneic silencers have multifaceted roles on bacterial genome evolution. In addition to regulating horizontal gene transfer, xenogeneic silencers also act as a selective force against the GC to AT mutational bias found in bacterial genomes and help the host genomic AT contents maintained at relatively low levels.
Comparison of the Quality of Chronic Disease Management Between Adults With and Without Dementia
Authors: Hiroshi Gotanda, Teryl Nuckols, Kanon Mori, Yusuke Tsugawa
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Adults with dementia may experience poorer quality of chronic disease management because of the difficulty in reporting symptoms and engaging in shared decision-making associated with cognitive impairment. <h3>Objective</h3> To compare the quality of chronic disease management received by adults with and without dementia. <h3>Design, Setting, and Participants</h3> For this cross-sectional study, nationally representative data from noninstitutionalized patients 65 years or older were obtained from the 2002-2015 Medical Expenditure Panel Survey. The control group comprised adults of similarly limited life expectancy without dementia comprised . Data analysis was performed in June 2020. <h3>Exposures</h3> Dementia diagnosis. <h3>Main Outcomes and Measures</h3> Quality of chronic disease management based on 14 individual quality indicators. The association between dementia status and the quality of chronic disease management (3 composite categories: preventive care, diabetes care, and medication treatment) was examined using multivariable linear regression models. Survey weights, sampling strata, and primary sampling unit variables were used to produce national estimates adjusted for nonresponse. <h3>Results</h3> This study included 2506 adults (mean [SD] age, 81.4 [4.7] years; 1259 [49.3%] female; 1243 [50.7%] male), of whom 1335 (53.3%) had a diagnosis of dementia and 1171 (46.7%) did not have a diagnosis of dementia. After adjusting for potential confounders, adults with dementia received lower-quality preventive care compared with adults of similar life expectancy without dementia (adjusted absolute difference [aAD], −6.1 percentage points [pp]; 95% CI, −9.7 to −2.5 pp;<i>P</i> = .001). We found no evidence that the quality of care differed in diabetes care (aAD, 1.7 pp; 95% CI, −4.5 to 7.9 pp;<i>P</i> = .59) and medication treatment (aAD, 1.0 pp; 95% CI, −5.0 to 7.0 pp;<i>P</i> = .75). <h3>Conclusions and Relevance</h3> In this cross-sectional study, the quality of chronic disease management for adults with dementia was not substantially different from that for those without dementia despite potential barriers. Future studies are warranted to gain a better understanding of the underlying mechanism of these findings for preventive care.
Poster Exhibition : Usefulness of Positron Emission Tomography with Fluorine-18-Fluorodeoxyglucose in Predicting Treatment Response in Unresectable Hepatocellular Carcinoma Patients Treated with Localized External Beam Radiotherapy (초)
Authors: Jun Won Kim, Jin Sil Seong, Mi Jin Yun, Woong Sub Koom, Hong In Yoon, Ho Jin Cho, Kwang Hyub Han
Journal: Clinical and Molecular Hepatology (2009)
SAT0699-HPR ASSESSMENT OF HEALTH LITERACY IN A COHORT OF SYSTEMIC SCLEROSIS (SSC) PATIENTS
Authors: Khadija El Aoufy, Silvia Basville, Chiara Lorini, Guglielmo Bonaccorsi, Luca Pietrini, Cosimo Bruni, Marco Matucci-Cerinic, Laura Rasero
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> SSc is a chronic, complex and very debilitating disease, involving all the aspects of physical, mental and social life. Thus, the need of a first assessment of the degree of health literacy (HL) is required to develop useful tools for SSc patients to simplify their access to health care services. HL is defined as the ability to acquire, synthesize and understand health information and services required to make decisions regarding an individual or community's health. Objectives: to assess the HL in SSc patients. <h3>Methods:</h3> 25 SSc patients classified ACR/EULAR criteria (limited and diffuse subsets) were enrolled in September-October 2018 with the support of the local association of patients (ASSMAF). Patients have been evaluated for socio-demographic variables and the HLS-EU-Q16 questionnaire (Italian version). <h3>Results:</h3> Questions 1 to 7 (on health information) are associated with age, educational qualifications and with the number of children; while 8 to 12 (on prevention) are associated with the number of children, but also with the type of employment and marital status; finally, questions 13-16 (on health promotion) are associated with age, educational qualifications and number of children. Moreover, our results show 20% of SSc patients with an inadequate level (0-8) of HL, compared to the 12% of the general population; 40% show a problematic level (9-12) of HL lower than that found in the general population (55%), while 40% of patients show an adequate level (13-16) of HL, higher than the 33% of the general population. <h3>Conclusion:</h3> Health literacy level is an important parameter to consider and assess in SSc patients to facilitate their access to health care services and their understanding of the disease. Future researches with larger sample size are needed. <h3> Disclosure of Interests:</h3> Khadija El Aoufy: None declared, Silvia Basville: None declared, Chiara Lorini: None declared, Guglielmo Bonaccorsi: None declared, Luca Pietrini: None declared, Cosimo Bruni: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Pfizer, BMS, Chemomab, Sanipedia, Speakers bureau: Actelion, BMS; MSD, Janssen, Laura Rasero: None declared
Authors’ reply to Moyle and Ashworth
Authors: Matthew Knight, Trisha Greenhalgh, Naomi J Fulop, Matt Inada-Kim
Journal: BMJ (2021)

The recognised common causes of inaccurate oximetry in the context of home monitoring in virtual wards are listed in our article.1 Readers wanting to explore further can consult the British Thoracic Society’s emergency oxygen guidelines (section 7.1.2)2 or an excellent review on pulse oximetry from Chan and colleagues.3 As with all technologies, oximetry has limitations.

The effects of smoking and other activities on carboxyhaemoglobin (COHb) levels mentioned by Moyle4 are known, but they have not been of marked clinical significance in the context of patients managed in virtual wards. Schimmel and colleagues analysed non-invasively the effect of smoking outdoors on SpCO (an estimation of COHb) in smokers and non-smokers, noting that the mean level of COHb in smokers was 2.7% before smoking a cigarette and 3.1% after, compared with 1.3% in non-smokers.5 This rise was observed in minutes, and 80% of smokers had an SpCO of <5%. A multicentre trial evaluating pulse oximeters against arterial gases found …
Role of the WWOX fragile gene in cancer
Authors: Rami Aqeilan, Louise Fong, Nicola Zanesi, Stefan Costinean, Yuri Pekarsky, Sadiq Hussain, Jane Lian, Gary Stein, Carlo Croce
Journal: Cancer Research (2007)

LB-107  The WW domain-containing oxidoreductase (WWOX) encodes a 46kDa protein that contains two N-terminal WW domains and central short-chain dehydrogenase/reductase (SDR) -like domain. The WWOX gene spans the second most active common fragile site, FRA16D; a region that shows frequent loss-of heterozygosity, and is associated with homozygous deletions in various adenocarcinomas and with chromosomal translocations in multiple myeloma. Indeed, WWOX expression is altered in a large fraction of many cancer types including breast, prostate, lung, stomach and pancreatic carcinomas. Therefore, it has been suggested that loss of WWOX expression in several cancer types is due mainly to its location within FRA16D and might be a secondary event not associated with tumorigenesis. Our recent observations, however, indicate that loss of WWOX expression in human tumors contributes to their pathogenesis. Early evidence that WWOX might be capable of suppressing tumor growth came from overexpression studies. Restoration of WWOX in cancer cells lacking expression of endogenous WWOX results in significant growth inhibition and prevents the development of tumors in athymic nude mice. To provide direct in vivo evidence that WWOX is a tumor suppressor, we generated mice carrying a targeted deletion of the Wwox gene. The murine Wwox locus is similar to its human homolog, spans the Fra8E1 common fragile site, and is highly conserved. We demonstrate that the loss of both alleles of Wwox results in osteosarcomas in some early postnatal mice, while loss of one allele significantly increases the incidence of spontaneous lung papillary carcinomas. In addition, higher incidence and multiplicity of ethyl nitrosourea (ENU) and N-nitrosomethylbenzylamine (NMBA)-induced tumors were formed in Wwoxheterozygous mice compared to wild type mice. Intriguingly, some of these tumors still express Wwox protein, suggesting haploinsuffiency of Wwox itself is cancer predisposing. Our findings indicate that WWOX is a bona fide tumor suppressor and that inactivation of one Wwox allele, a condition that frequently occurs due to the fragility of the WWOX locus and the high incidence of LOH observed in WWOX gene in many human cancer types, is sufficient for tumorigenesis.
Inducible expression quantitative trait locus analysis of the MUC5AC gene in asthma in urban populations of children
Authors: Matthew C. Altman, Kaitlin Flynn, Mario G. Rosasco, Matthew Dapas, Meyer Kattan, Stephanie Lovinsky-Desir, George T. O’Connor, Michelle A. Gill, Rebecca S. Gruchalla, Andrew H. Liu, Jacqueline A. Pongracic, Gurjit K. Khurana Hershey, Edward M. Zoratti, Stephen J. Teach, Deepa Rastrogi, Robert A. Wood, Leonard B. Bacharier, Petra LeBeau, Peter J. Gergen, Alkis Togias, William W. Busse, Scott Presnell, James E. Gern, Carole Ober, Daniel J. Jackson
Journal: Journal of Allergy and Clinical Immunology (2021)
Abstract 10080: Endothelial Function in Healthy Adults is Unaffected by Elevated Serum Trimethylamine N-oxide Levels Following One Month of Dietary Choline Supplementation
Authors: Scott T Chiesa, Marietta Charakida, Alicja Rapala, Devina J Bhowruth, Charles Turner, R N Dalton, John E Deanfield
Journal: Circulation (2019)

Introduction: Trimethylamine N-Oxide (TMAO) - a gut-microbial derived metabolite generated from the conversion of dietary choline - is associated with an increased risk of cardiovascular disease. S...
Assessment of the causal relevance of ECG parameters for risk of atrial fibrillation: A mendelian randomisation study
Authors: Parag Ravindra Gajendragadkar, Adam Von Ende, Maysson Ibrahim, Elsa Valdes-Marquez, Christian Fielder Camm, Federico Murgia, Alexander Stiby, Barbara Casadei, Jemma C. Hopewell
Journal: PLoS Medicine (2021)

Background Atrial electrical and structural remodelling in older individuals with cardiovascular risk factors has been associated with changes in surface electrocardiographic (ECG) parameters (e.g., prolongation of the PR interval) and higher risks of atrial fibrillation (AF). However, it has been difficult to establish whether altered ECG parameters are the cause or a consequence of the myocardial substrate leading to AF. This study aimed to examine the potential causal relevance of ECG parameters on risk of AF using mendelian randomisation (MR). Methods and findings Weighted genetic scores explaining lifelong differences in P-wave duration, PR interval, and QT interval were constructed, and associations between these ECG scores and risk of AF were estimated among 278,792 UK Biobank participants (mean age: 57 years at recruitment; 19,132 AF cases). The independent genetic variants contributing to each of the separate ECG scores, and their corresponding weights, were based on published genome-wide association studies. In UK Biobank, genetic scores representing a 5 ms longer P-wave duration or PR interval were significantly associated with lower risks of AF (odds ratio [OR] 0.91; 95% confidence interval [CI]: 0.87–0.96, P = 2 × 10 −4 and OR 0.94; 95% CI: 0.93–0.96, P = 2 × 10 −19 , respectively), while longer QT interval was not significantly associated with AF. These effects were independently replicated among a further 17,931 AF cases from the AFGen Consortium. Investigation of potential mechanistic pathways showed that differences in ECG parameters associated with specific ion channel genes had effects on risk of AF consistent with the overall scores, while the overall scores were not associated with changes in left atrial size. Limitations of the study included the inherent assumptions of MR, restriction to individuals of European ancestry, and possible restriction of results to the normal ECG ranges represented in UK Biobank. Conclusions In UK Biobank, we observed evidence suggesting a causal relationship between lifelong differences in ECG parameters (particularly PR interval) that reflect longer atrial conduction times and a lower risk of AF. These findings, which appear to be independent of atrial size and concomitant cardiovascular comorbidity, support the relevance of varying mechanisms underpinning AF and indicate that more individualised treatment strategies warrant consideration.
춘계학술대회 : 구연 ; 사망 수용체 관련 간세포 자멸사에서 Eupatilin의 항자멸사 효과 및 그 기전 규명
Authors: 윤정환, 곽금연, 김윤준, 이효석, 김정룡
Journal: Clinical and Molecular Hepatology (2005)

배경/목적: 담즙정체성 간질환에서 담즙산은 간세포 자멸사를 유도하여 간손상을 초래하는데, 주로 사망 수용체 관련 자멸사 경로를 활성화시키는 것으로 알려져 있다. 최근 쑥(Artemisia asiatica) 추출물인 Eupatilin (5,7dihydroxy3,4,6trimethoxy flavone)은 항산화 및 항염증 효과와 더불어, 위장관 뿐 아니라 간과 췌장 손상 모델에서도 세포 보호 효과를 나타내는 것이 알려져 있다. 그리하여 본 연구에서는 이러한
British Association of Dermatologists guidelines for the management of people with rosacea 2021*
Authors: P.J. Hampton, J. Berth‐Jones, C.E. Duarte Williamson, R. Hay, T.A. Leslie, I. Porter, S. Rauz, D. Seukeran, R.T. Winn, M. Hashme, L.S. Exton, M.F. Mohd Mustapa, L. Manounah
Journal: British Journal of Dermatology (2021)

Linked Comment: J.S.S. Ho and Y. Asai. Br J Dermatol 2021; 185:689–690. Plain language summary available online
A randomized phase II trial of veliparib, radiotherapy, and temozolomide in patients with unmethylated<i>MGMT</i>glioblastoma: the VERTU study
Authors: Hao-Wen Sim, Kerrie L McDonald, Zarnie Lwin, Elizabeth H Barnes, Mark Rosenthal, Matthew C Foote, Eng-Siew Koh, Michael Back, Helen Wheeler, Erik P Sulman, Michael E Buckland, Lauren Fisher, Robyn Leonard, Merryn Hall, David M Ashley, Sonia Yip, John Simes, Mustafa Khasraw
Journal: Neuro-Oncology (2021)

Abstract Background Temozolomide offers minimal benefit in patients with glioblastoma with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter status, hence, the need for novel therapies. This study evaluated whether veliparib, a brain-penetrant poly(ADP-ribose) polymerase (PARP) inhibitor, acts synergistically with radiation and temozolomide. Methods VERTU was a multicenter 2:1 randomized phase II trial in patients with newly diagnosed glioblastoma and MGMT-unmethylated promotor status. The experimental arm consisted of veliparib and radiotherapy, followed by adjuvant veliparib and temozolomide. The standard arm consisted of concurrent temozolomide and radiotherapy, followed by adjuvant temozolomide. The primary objective was to extend the progression-free survival rate at six months (PFS-6m) in the experimental arm. Results A total of 125 participants were enrolled, with 84 in the experimental arm and 41 in the standard arm. The median age was 61 years, 70% were male, 59% had Eastern Cooperative Oncology Group (ECOG) performance status of 0, and 87% underwent macroscopic resection. PFS-6m was 46% (95% confidence interval [CI]: 36%-57%) in the experimental arm and 31% (95% CI: 18%-46%) in the standard arm. Median overall survival was 12.7 months (95% CI: 11.4-14.5 months) in the experimental arm and 12.8 months (95% CI: 9.5-15.8 months) in the standard arm. The most common grade 3-4 adverse events were thrombocytopenia and neutropenia, with no new safety signals. Conclusion The veliparib-containing regimen was feasible and well tolerated. However, there was insufficient evidence of clinical benefit in this population. Further information from correlative translational work and other trials of PARP inhibitors in glioblastoma are still awaited.
Abstract 15731: Sildenafil Improves Mitochondrial Function in Failing Single Ventricles
Authors: Anastacia M Garcia, Carissa A Miyano, Raleigh Joschner, Matthew Stone, Brian L Stauffer, Carmen C SUCHAROV, Shelley D Miyamoto
Journal: Circulation (2020)

Introduction: Heart failure (HF) remains a leading cause of death and indication for transplant in single ventricle congenital heart disease (SV). However, little is known regarding the molecular mechanisms leading to HF in SV. The purpose of this study was to characterize mitochondrial function in the myocardium of failing (SVHF) and non-failing (SVNF) SV patients compared to biventricular NF controls (BVNF). Furthermore, we investigated the effect of ex vivo treatment with the phosphodiesterase-5 inhibitor (PDE5i) sildenafil on mitochondrial function. Methods: Freshly explanted ventricular tissue was saponin permeabilized and mitochondrial oxygen consumption was measured sequentially throughout the electron transport system using SUbstrate-Inhibitor-Titration (“SUIT”) protocols and an Oroboros O2k high resolution respirometer. Permeabilized ventricular tissue was treated for 40 min with sildenafil [1μM] prior to measurement of oxygen consumption. A Western blot for PDE5 was performed in isolated mitochondrial proteins from SVHF subjects ± PDE5i. Results: Compared to BVNF (n=15) and SVNF (n=6), SVHF (n=8) hearts have decreased function of Complex I and Complex I and II (A, B), and decreased maximal respiration (C), all of which improve with acute ex vivo treatment with sildenafil in SVHF (SVHF+PDE5i, n=6). Importantly, mitochondrial function is impaired in BVNF+PDE5i (n=5) and SVNF+PDE5i hearts (n=5) (A-C, one-way Anova p&lt;0.05). PDE5 protein is expressed in SVHF mitochondria, but expression is not affected by ex vivo PDE5i treatment (D). Conclusions: Our results indicate that mitochondrial function is impaired in SVHF, PDE5 protein is expressed in SVHF mitochondria, and PDE5i improves mitochondrial function in SVHF, but may be detrimental to mitochondrial function in SVNF and BVNF. Together these data suggest that mitochondrial PDE5 is a potential therapeutic target, but that indiscriminate use of PDE5i in SV patients may not be advisable.