bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reflex Decay Test Can Reveal Ear Involvement in Fabry Disease
Authors: Kiykim Ertugrul , Kaya Melda , Dincer Mevlut Tamer , Bakir Alev , Alagoz Selma , Aktuglu Zeybek Ayse , Gulcicek Sibel , Seyahi Nurhan , Trabulus Sinan , Atas Ahmet 
Published: March 2021

Objectives:
Fabry disease (FD) is an X-linked lysosomal storage disorder that causes multisystem involvement, including ear disease. In this study, we aimed to investigate the nature of auditory issues in FD using a wide spectrum of audiological tests.

Design:
This cross-sectional study was conducted between June 2017 and December 2018. We collected the clinical and laboratory data of 40 eligible FD patients, 45 healthy subjects, and 26 diabetic controls. All patients and controls completed audiologic evaluations that included tympanometry, acoustic reflex threshold test, reflex decay test, pure-tone audiometry, speech audiometry, transient otoacoustic emissions (TEOAEs), high-frequency audiometry, and distortion product otoacoustic emission (DPOAE).

Results:
In our study population, hearing was reduced at higher frequencies starting at 4 kHz in both the FD and diabetic groups. Regarding the acoustic reflex threshold test, FD and diabetic patients had similar results. In all frequencies, positive decay was significantly more frequent in FD patients when compared with the diabetic patients and healthy controls (p < 0.001 for each ear). The FD patients and healthy controls had similar results for DPOAE testing.

Conclusions:
We showed that FD patients had a higher rate of reflex decay, indicating retrocochlear involvement. Thus, further investigation of factors associated with retrocochlear involvement could be investigated, such as ABR and speech in noise tests.
Circular RNA circ_0010729 Knockdown Attenuates Oxygen–Glucose Deprivation-Induced Human Cardiac Myocytes Injury by miR-338-3p/CALM2 Axis
Authors: Ma Bocong , Zhao Ming , Guo Zhihao 
Published: March 2021

Abstract:
Circular RNAs have pivotal roles in cardiovascular disease. The injury of cardiac myocytes is associated with occurrence of cardiovascular disease. Circular RNA hsa_circ_0010729 (circ_0010729) is associated with cardiac myocytes injury. However, the mechanism of circ_0010729 in cardiac myocytes injury remains largely unclear. In our study, cardiac myocytes were treated by oxygen–glucose deprivation (OGD). The abundances of circ_0010729, microRNA-338-3p (miR-338-3p), and calmodulin 2 (CALM2) were detected by quantitative reverse transcription polymerase chain reaction or Western blot. OGD-induced damage in AC16 cells was assessed by cell viability, apoptosis, and autophagy using Cell Counting Kit-8, flow cytometry, and Western blot analyses. The target relationship of miR-338-3p and circ_0010729 or CALM2 was explored by starBase and dual-luciferase reporter analysis. Our results showed that the circ_0010729 level was enhanced in OGD-treated AC16 cells and murine primary cardiac myocytes. circ_0010729 silence weakened OGD-induced viability inhibition and promotion of apoptosis and autophagy in AC16 cells and murine primary cardiac myocytes. miR-338-3p was sponged by circ_0010729 and miR-338-3p knockdown alleviated the effect of circ_0010729 silence on OGD-induced damage. miR-338-3p directly targeted CALM2 to inhibit OGD-induced damage in AC16 cells. circ_0010729 could regulate CALM2 expression by sponging miR-338-3p. Collectively, circ_0010729 interference mitigated OGD-induced damage in cardiac myocytes through increasing cell viability and inhibiting apoptosis and autophagy by regulating miR-338-3p/CALM2 axis. This study indicated circ_0010729 might act as a target for treatment of cardiovascular disease.
Chrysin Ameliorates Sepsis-Induced Cardiac Dysfunction Through Upregulating Nfr2/Heme Oxygenase 1 Pathway
Authors: Xingyue Li , Shuang Li , Qiang Wang , Jinjuan Fu , Yongjian Yang 
Published: March 2021

Abstract:
The incidence of myocardial dysfunction caused by sepsis is high, and the mortality of patients with sepsis can be significantly increased. During sepsis, oxidative stress and inflammation can lead to severe organ dysfunction. Flavone chrysin is one of the indispensable biological active ingredients for different fruits and vegetables and has antioxidant and anti-inflammatory properties. However, it is not clear whether chrysin is an effective treatment for heart dysfunction caused by sepsis. We found that it had protective effects against the harmful effects caused by LPS, manifested in improved survival, normalized cardiac function, improved partial pathological scores of myocardial tissue, and remission of apoptosis, as well as reduced oxidative stress and inflammation. Mechanism studies have found that chrysin is an important antioxidant protein, a key regulator of heme oxygenase 1 (HO-1). We found that HO-1 levels were increased after LPS intervention, and chrysin further increased HO-1 levels, along with the addition of Nrf2, a regulator of antioxidant proteins. Pretreatment with PD98059, an extracellular signal-regulated kinase-specific inhibitor, blocked chrysin-mediated phosphorylation of Nrf2 and the nuclear translocation of Nrf2. The protective effect of chrysin on sepsis-induced cardiac dysfunction was blocked by ZnPP, which is a HO-1 blocker. Chrysin increased antioxidant activity and reduced markers of oxidative stress (SOD and MDA) and inflammation (MPO and IL-1β), all of which were blocked by ZnPP. This indicates that HO-1 is the upstream molecule regulating the protective effect of chrysin. Thus, by upregulation of HO-1, chrysin protects against LPS-induced cardiac dysfunction and inflammation by inhibiting oxidative stress.
MiR-129-5p Protects H9c2 Cardiac Myoblasts From Hypoxia/Reoxygenation Injury by Targeting TRPM7 and Inhibiting NLRP3 Inflammasome Activation
Authors: Liu Shuke , Liao Qingchi , Xu Wei , Zhang Zhen , Yin Minming , Cao Xiaohu 
Published: March 2021

Abstract:
As a biomarker for heart failure, miR-129-5p is abnormally expressed during myocardial I/R, but its specific functions and mechanisms remain largely unclear. Thus, this study explored the roles and possible mechanisms of miR-129-5p in hypoxia/reoxygenation (H/R)-insulted H9c2 cardiac myoblasts. After H/R insult, miR-129-5p expression levels were decreased, along with reduced cell viability and enhanced lactate dehydrogenase release in H9c2 cells. Overexpression of miR-129-5p through transfection of miR-129-5p mimics effectively improved cell viability and reduced lactate dehydrogenase release in H9c2 cells exposed to H/R, along with decreased apoptosis and caspase-3 activities. Moreover, miR-129-5p mimics inhibited reactive oxygen species production and upsurged superoxide dismutase activity in H9c2 cells exposed to H/R, and suppressed H/R-caused massive release of proinflammatory cytokines TNF-α and IL-1β. TRPM7 was identified as the target of miR-129-5p and was negatively regulated by miR-129-5p. TRPM7 overexpression counteracted the antagonistic effect of miR-129-5p on H/R-induced increase in intracellular calcium levels. TRPM7 overexpression also abolished miR-129-5p-induced elevation on cell viability and reduction on apoptosis as well as attenuated miR-129-5p-induced inhibition on reactive oxygen species and IL-1β production. Besides, H/R-induced NLRP3 inflammasome activation was inhibited by miR-129-5p mimic but reactivated by TRPM7. In conclusion, miR-129-5p alleviates H/R injury of H9c2 cardiomyocytes by targeting TRPM7 and inhibiting NLRP3 inflammasome activation, suggesting that miR-129-5p and TRPM7 may be potential therapeutic targets for myocardial I/R injury.
Circulating PGLYRP1 Levels as a Potential Biomarker for Coronary Artery Disease and Heart Failure
Authors: Han Yanxin , Hua Sha , Chen Yanjia , Yang Wenbo , Zhao Weilin , Huang Fanyi , Qiu Zeping , Yang Chendie , Jiang Jie , Su Xiuxiu , Yang Ke , Jin Wei 
Published: March 2021

Abstract:
Coronary artery disease (CAD) and associated comorbidities such as heart failure (HF) remain the leading cause of morbidity and mortality worldwide attributed to, at least partially, the lack of biomarkers for efficient disease diagnosis. Here, we evaluated the diagnostic potential of serum peptidoglycan recognition protein 1 (PGLYRP1), an important component of the innate immunity and inflammation system, for both CAD and HF. A machine-learning method (random forest) was used to evaluate the clinical utility of circulating PGLYRP1 for diagnosis of CAD and HF in a total of 370 individuals. Causal links of chronic serum PGLYRP1 elevation to both diseases were further explored in ApoE−/− mice. The serum levels of PGLYRP1 were significantly higher in individuals with either chronic CAD or acute coronary syndrome than those in those without coronary artery stenosis (the control group) and even more pronounced in CAD individuals with concomitant HF. Our random forest classifier revealed that this protein performed better than other recommended clinical indicators in distinguishing the CAD from the control individuals. In addition, this protein associates more with the biomarkers of HF including left ventricular ejection fraction than inflammation. Notably, our mice experiment indicated that long-term treatment with recombinant PGLYRP1 could significantly impair the cardiovascular system as reflected from both increased atherogenic lesions and reduced fractional shortening of the left ventricle. Our findings, therefore, supported the circulating levels of PGLYRP1 as a valuable biomarker for both CAD and HF.
The Angiotensin II Type 1(AT1) Receptor and Cardiac Hypertrophy: Did We Have It Wrong All Along?
Authors: Zouein Fouad A. , Altara Raffaele , Massoud Gaelle P. , Booz George W. 
Published: March 2021

Abstract:
An ongoing issue in cardiac pharmacology is whether angiotensin II has direct growth promoting effects on the heart via the angiotensin II type 1 (AT1) receptor. This question has relevance for whether angiotensin-converting enzyme inhibitors and AT1 receptor blockers offer additional benefit in preventing adverse cardiac remodeling in hypertension. In a recent study, 2 strains of mice were infused with angiotensin II. In both, AT1 receptors were deleted in the heart and conduit vessels, but in one, AT1 receptors were also deleted in resistance vessels. Angiotensin II caused hypertrophy and hypertension in the strain lacking AT1 receptors in the heart and conduit vessels, but not in the strain without AT1 receptors in resistance vessels. This finding supports the conclusion that blood pressure is more important in determining cardiac hypertrophy than direct AT1 activation by angiotensin II, when the two are rapidly and simultaneously introduced. Surprisingly, mice with no cardiac AT1 receptor expression developed ventricular dilation and eccentric hypertrophy with pressure overload, in contrast to wild type mice that exhibited concentric hypertrophy, suggesting that cardiac AT1 receptors protect against high blood pressure. This interpretation revives issues related to β–arrestin-biased signaling and mechanosensitivity of AT1 receptors. Synthetic nanobodies, which are based on the variable regions of camelid-derived heavy chain–only antibodies, could be applied to explore the therapeutic potential of exploiting different activation states of AT1 under stress conditions, such as hypertension and heart failure. At the very least, this experimental approach is likely to reveal new facets of AT1 receptor signaling in the heart.
Adverse Effects of Oseltamivir Phosphate Therapy on the Liver of LDLR−/− Mice Without Any Benefit on Atherosclerosis and Thrombosis
Authors: Bocquet Olivier , Wahart Amandine , Sarazin Thomas , Vincent Elise , Schneider Christophe , Fougerat Anne , Gayral Stéphanie , Henry Aubéri , Blaise Sébastien , Romier-Crouzet Béatrice , Boulagnon Camille , Jaisson Stéphane , Gillery Philippe , Bennasroune Amar , Sartelet Hervé , Laffargue Muriel , Martiny Laurent , Duca Laurent , Maurice Pascal 
Published: March 2021

Abstract:
Desialylation, governed by sialidases or neuraminidases, is strongly implicated in a wide range of human disorders, and accumulative data show that inhibition of neuraminidases, such as neuraminidases 1 sialidase, may be useful for managing atherosclerosis. Several studies have reported promising effects of oseltamivir phosphate, a widely used anti-influenza sialidase inhibitor, on human cancer cells, inflammation, and insulin resistance. In this study, we evaluated the effects of oseltamivir phosphate on atherosclerosis and thrombosis and potential liver toxicity in LDLR−/− mice fed with high-fat diet. Our results showed that oseltamivir phosphate significantly decreased plasma levels of LDL cholesterol and elastin fragmentation in aorta. However, no effect was observed on both atherosclerotic plaque size in aortic roots and chemically induced thrombosis in carotid arteries. Importantly, oseltamivir phosphate administration had adverse effects on the liver of mice and significantly increased messenger RNA expression levels of F4/80, interleukin-1β, transforming growth factor-β1, matrix metalloproteinase-12, and collagen. Taken together, our findings suggest that oseltamivir phosphate has limited benefits on atherosclerosis and carotid thrombosis and may lead to adverse side effects on the liver with increased inflammation and fibrosis.
Coronary artery disease prediction based on breast arterial calcification in women undergoing mammography as a screening for breast cancer
Authors: Pudil Jan , Steyerová Petra , Macová Iva , Zemánek David , Král Aleš , Pad’our Michal , Chen Zhi , Daneš Jan , Kovárník Tomáš 
Published: March 2021

Abstract

Objective:
The aim of the study was to test the potential role of breast arterial calcification (BAC) in the prediction of coronary artery disease (CAD) in women. The criterion standard for CAD diagnostics was coronary angiography.

Methods:
This retrospective study enrolled 163 consecutive women, who underwent digital mammography and coronary angiography in our hospital. We assessed the presence and severity of BAC, and tested whether the presence and/or extent of BAC could be a predictor for CAD, quantified by Gensini score.

Results:
BAC was presented in 34 patients (21%). Neither the presence of CAD (17 patients, 50%, vs 55 42.6%, P = 0.44), nor the Gensini score (20.5 ± 29.7 vs 15.4 ± 24.1, P = 0.3) differed significantly between BAC-present and BAC-absent patients.
A finding of triple-vessel disease, however, more frequently occurred in the BAC-present (seven patients, 20.6%) than in the BAC-absent (nine patients, 7%) group, odds ratio (OR) 3.1, 95% CI 1-9.5, P = 0.049. The presence of BAC did not significantly increase the odds for the presence of CAD (OR = 1.29, P = 0.54). Among the subgroup of patients with CAD, BAC presence was associated with triple vessel disease (OR = 3.34, P = 0.049).

Conclusions:
We did not confirm BAC as a predictor of CAD. However, BAC showed association with more severe forms of coronary atherosclerosis (triple vessel disease).

Video Summary:

http://links.lww.com/MENO/A728.
Demographic and Cultural Differences in the Acceptance and Pursuit of Cosmetic Surgery: A Systematic Literature Review
Authors: Alotaibi Ahmed S. 
Published: March 2021

Background:
Worldwide, the numbers of cosmetic procedures continue to climb. However, cosmetic surgery (CS) continues to be plagued by negative stigmatization. This study reviews the literature to identify how attitudes toward CS vary by sex, age, race, culture, and nationality, and aims to determine how other factors like media exposure interact with demographics to influence how well CS is accepted.

Methods:
A PRISMA-guided systematic review of the literature was conducted to identify all English-language papers reporting on CS or plastic surgery acceptance, attitudes, or stigmatization, specifically examining for data on age, sex, race/ethnicity, culture, and media influence.

Results:
In total, 1515 abstracts were reviewed, of which 94 were deemed pertinent enough to warrant a full-text review. Among the potential demographic predictors of CS acceptance, the one with the most supportive data is sex, with women comprising roughly 90% of all CS patients in virtually all populations studied and consistently exhibiting greater CS knowledge and acceptance. Culturally, the pursuit of beauty through CS is a universal phenomenon, although different countries, races, and cultures differ in how willingly CS is embraced, and in the aesthetic goals of those choosing to have it. In countries with culturally diverse societies like the United States, non-Hispanic Whites continue to predominate among CS patients, but the number of CS patients of other races is rising disproportionately. In this trend, social media is playing a major role.

Conclusion:
Healthcare practitioners performing cosmetic procedures need to consider demographic and cultural differences of the patients in order to enhance their understanding of their patients’ aesthetic goals and expectations.
Payment Discrepancies and Access to Primary Care Physicians for Dual-eligible Medicare-Medicaid Beneficiaries
Authors: Fung Vicki , McCarthy Stephen , Price Mary , Hull Peter , Lê Cook Benjamin , Hsu John , Newhouse Joseph P. 
Published: March 2021

Background:
Physicians often receive lower payments for dual-eligible Medicare-Medicaid beneficiaries versus nondual Medicare beneficiaries because of state reimbursement caps. The Affordable Care Act (ACA) primary care fee bump temporarily eliminated this differential in 2013–2014.

Objective:
To examine how dual payment policy impacts primary care physicians’ (PCP) acceptance of duals.

Research Design:
We assessed differences in the likelihood that PCPs had dual caseloads of ≥10% or 20% in states with lower versus full dual reimbursement using linear probability models adjusted for physician and area-level traits. Using a triple-difference approach, we examined changes in dual caseloads for PCPs versus a control group of specialists in states with fee bumps versus no change during years postbump versus prebump.

Subjects:
PCPs and specialists (cardiologists, orthopedic surgeons, general surgeons) that billed fee-for-service Medicare.

Measures:
State dual payment policies and physicians’ dual caseloads as a percentage of their Medicare patients.

Results:
In 2012, 81% of PCPs had dual caseloads of ≥10% and this was less likely among PCPs in states with lower versus full dual reimbursement (eg, difference=−4.52 percentage points; 95% confidence interval, −6.80 to −2.25). The proportion of PCPs with dual caseloads of ≥10% or 20% decreased significantly between 2012 and 2017 and the fee bump was not consistently associated with increases in dual caseloads.

Conclusions:
Pre-ACA, PCPs’ participation in the dual program appeared to be lower in states with lower reimbursement for duals. Despite the ACA fee bump, dual caseloads declined over time, raising concerns of worsening access to care.
Biomedical Discovery through the integrative Biomedical Knowledge Hub (iBKH)
Authors: Su Chang , Hou Yu , Rajendran Suraj , Maasch Jacqueline R. M. A. , Abedi Zehra , Zhang Haotan , Bai Zilong , Cuturrufo Anthony , Guo Winston , Chaudhry Fayzan F. , Ghahramani Gregory , Tang Jian , Cheng Feixiong , Li Yue , Zhang Rui , Bian Jiang , Wang Fei 
Published: March 2021

SummaryThe massive and continuously increasing volume of biomedical knowledge derived from biological experiments or gained from healthcare practices has become an invaluable treasure for biomedicine. The emerging biomedical knowledge graphs (BKGs) provide an efficient and effective way to manage the abundant knowledge in biomedical and life science. In the present study, we harmonized and integrated data from diverse biomedical resources to curate a comprehensive BKG, named the integrative Biomedical Knowledge Hub (iBKH). To facilitate the usage of iBKH in biomedical research, we developed a web-based, easy-to-use, publicly available graphical portal that allows fast, interactive, and visualized knowledge retrieval in iBKH. Furthermore, an efficient and scalable graph learning pipeline was developed for novel knowledge discovery in iBKH. As a proof of concept, we performed our iBKH-based method for computational in silico drug repurposing for Alzheimer’s disease. The iBKH is publicly available at: http://ibkh.ai/.
Significance testing for small annotations in stratified LD-Score regression
Authors: Tashman Katherine C. , Cui Ran , O’Connor Luke J. , Neale Benjamin M. , Finucane Hilary K. 
Published: March 2021

AbstractS-LDSC is a widely used heritability enrichment method that has helped gain biological insights into numerous complex traits. It has primarily been used to analyze large annotations that contain approximately 0.5% of SNPs or more. Here, we show in simulation that, when applied to small annotations, the block jackknife-based significance testing used in S-LDSC does not always control type 1 error. We show that the inflation of type 1 error for small annotations is due both to the noisiness of the jackknife estimate of the standard error and to the non-normality of the regression coefficient estimates. We use the percent of 0.01 centimorgan blocks in the genome overlapped by the annotation to quantify the size of an annotation and the extent to which the SNPs in the annotation cluster together, and we find thresholds on this value above which type 1 error is controlled. We have implemented a test in the LDSC software that informs users when they compute LD scores for an annotation if the annotation does not pass the threshold for producing controlled type 1 error.Author SummaryGenetics is a rapidly evolving field that allows us to link our genetic code to the physiological manifestations of disease. A key part of this work is finding regions of the genome that contribute disproportionately to the genetic underpinnings of a disease. A commonly used tool to provide such insight is stratified LD score regression (S-LDSC). S-LDSC allows us to estimate how much a set of genomic regions contributes to the overall heritability of a phenotype, and to test whether this is more than we would expect by chance. Here we show that when we apply S-LDSC to a small set of genomic regions, it does not give an accurate test of whether this set of genomic regions contributes more than we would expect by chance to the phenotype. We characterize what it means to be a “small” set of genomic regions, and we set thresholds to restrict which annotations we test to prevent false positive results.This helps to ensure that as we continue to pursue genetic analyses at scale, we report only truly significant results that will help us further understand the etiology of many of the traits we study.