bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of sacubitril/valsartan on heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials
Authors: Yu Wanqian , Zhang Hongzhou , Shen Wen , Luo Fan , Yang Shuai , Gan Lujin , Zhao Yuanbin , Yang Pingping , Wu Qinghua 
Published: September 2022

AimsThe efficacy and safety of sacubitril/valsartan for patients with heart failure with preserved ejection fraction (HFpEF) are controversial. Hence, the primary objective of the study was to evaluate the efficacy and safety of sacubitril/valsartan treatment for patients with HFpEF.Methods and resultsWe used the PubMed, Embase, and Web of Science databases to search for randomized controlled trials of sacubitril–valsartan in patients with HFpEF. Three studies, involving a total of 7,663 patients, were eligible for inclusion. Sacubitril–valsartan reduced the risk of hospitalization for heart failure (HF) [odds ratio (OR): 0.78; 95% CI: 0.70–0.88; p &lt; 0.0001] and the incidence of worsening renal function [risk ratio (RR): 0.79, p = 0.002] among patients with HFpEF in the three trials, but there was no significant reduction in all-cause mortality (0.99, 95% CI: 0.84–1.15; p = 0.86) or cardiovascular mortality (0.95, 95% CI: 0.78–1.15; p = 0.16). Moreover, sacubitril/valsartan was associated with an increased risk of symptomatic hypotension (RR: 1.44; p &lt; 0.00001) and angioedema (RR: 2.66; p &lt; 0.04); there was no difference for decreasing the incidence of hyperkalemia (RR: 0.89; p = 0.11).ConclusionCompared with valsartan or individualized medical therapy (IMT), sacubitril/valsartan significantly decreased the risk of hospitalization for HF and reduced the incidence of renal dysfunction.
Comparison of bicuspidization and Ross procedure in the treatment of unicuspid aortic valve disease in adults – Insight from the AVIATOR registry
Authors: Gofus Ján , Karalko Mikita , Fila Petr , Ondrášek Jiří , Schäfers Hans-Joachim , Kolesár Adrian , Lansac Emmanuel , El-Hamamsy Ismail , de Kerchove Laurent , Dinges Christian , Hlubocký Jaroslav , Němec Petr , Tuna Martin , Vojáček Jan 
Published: September 2022

BackgroundUnicuspid aortic valve (UAV) is the second most common underlying cause of aortic valve dysfunction in young adults after the bicuspid valve. The valve may be replaced (for example by pulmonary autograft) or repaired using the bicuspidization technique. The aim of our study was to compare short- and mid-term outcomes of Ross procedure with bicuspidization in patients with severe UAV dysfunction.MethodsThis was a multi-center retrospective observational cohort study comparing data from two dedicated Ross centers in the Czech Republic with bicuspidization outcomes provided by AVIATOR registry. As for the Ross group, only the patients with UAV were included. Primary endpoint was mid-term freedom from reintervention. Secondary endpoints were mid-term freedom from major adverse events, endocarditis and pacemaker implantation.ResultsThroughout the study period, 114 patients underwent the Ross procedure (years 2009-2020) and 126 patients underwent bicuspidization (years 2006-2019). The bicuspidization group was significantly younger and presented with a higher degree of dyspnea, a lower degree of aortic valve stenosis and more often with pure regurgitation. The primary endpoint occurred more frequently in the bicuspidization group than in the Ross group – 77.9 vs. 97.9 % at 5 years and 68.4 vs. 75.2 % at 10 years (p &lt; 0.001). There was no difference in secondary endpoints.ConclusionRoss procedure might offer a significantly lower mid-term risk of reintervention than bicuspidization in patients with UAV. Both procedures have comparable survival and risk of other short- and mid-term complications postoperatively.
Placental pathologic lesions associated with stroke in term neonates
Authors: Leon Rachel L. , Kalvacherla Vinay , Andrews Michelle Machie , Thomas Jennifer M. , Mir Imran N. , Chalak Lina F. 
Published: September 2022

ObjectiveTo determine the birth prevalence of perinatal stroke in term born infants at our high-volume delivery center and assess the frequency of both gross and histologic placental pathologies associated with perinatal stroke using the Amsterdam Placental Workshop Group Consensus Statement guidelines and definitions.Study DesignA single-center retrospective cohort study spanning 2010-2020.ResultsThere were 129,759 live births at Parkland Hospital during the study period and a total of 18 term born infants leading to a birth prevalence of 1 in 6,829 infants. Perinatal risk factors were found in all but one patient, and 74% presented with seizures. Pathologic placental examination was available in 56% of the cohort and only one patient had normal placental examination. Acute histologic chorioamnionitis was described in five placentas (50%) and an additional two had isolated umbilical and/or chorionic plate vasculitis with or without funisitis compared to a rate of 28% with acute inflammation in a Control group. Chronic inflammation in the form of villitis of unknown etiology was described in three of the acutely inflamed placentas and was high-grade in each of those while none of the placentas from our Control group showed evidence of any chronic lesion.ConclusionBoth acute and chronic placental inflammation are common in perinatal stroke; placental examination should be considered an essential component to the diagnostic workup.
Network Pharmacology and Bioinformatics Analysis Identifies Potential Therapeutic Targets of Paxlovid Against LUAD/COVID-19
Authors: Zhang Wentao , Yang Zhe , Zhou Fengge , Wei Yanjun , Ma Xiaoqing 
Published: September 2022

BackgroundCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a pandemic in many countries around the world. The virus is highly contagious and has a high fatality rate. Lung adenocarcinoma (LUAD) patients may have higher susceptibility and mortality to COVID-19. While Paxlovid is the first oral drug approved by the U.S. Food and Drug Administration (FDA) for COVID-19, its specific drug mechanism for lung cancer patients infected with COVID-19 remains to be further studied.MethodsCOVID-19 related genes were obtained from NCBI, GeneCards, and KEGG, and then the transcriptome data for LUAD was downloaded from TCGA. The drug targets of Paxlovid were revealed through BATMAN-TCM, DrugBank, SwissTargetPrediction, and TargetNet. The genes related to susceptibility to COVID-19 in LUAD patients were obtained through differential analysis. The interaction of LUAD/COVID-19 related genes was evaluated and displayed by STRING, and a COX risk regression model was established to screen and evaluate the correlation between genes and clinical characteristics. The Venn diagram was drawn to select the candidate targets of Paxlovid against LUAD/COVID-19, and the functional analysis of the target genes was performed using KEGG and GO enrichment analysis. Finally, Cytoscape was used to screen and visualize the Hub Gene, and Autodock was used for molecular docking between the drug and the target.ResultBioinformatics analysis was performed by combining COVID-19-related genes with the gene expression and clinical data of LUAD, including analysis of prognosis-related genes, survival rate, and hub genes screened out by the prognosis model. The key targets of Paxlovid against LUAD/COVID-19 were obtained through network pharmacology, the most important targets include IL6, IL12B, LBP. Furthermore, pathway analysis showed that Paxlovid modulates the IL-17 signaling pathway, the cytokine-cytokine receptor interaction, during LUAD/COVID-19 treatment.ConclusionsBased on bioinformatics and network pharmacology, the prognostic signature of LUAD/COVID-19 patients was screened. And identified the potential therapeutic targets and molecular pathways of Paxlovid Paxlovid in the treatment of LUAD/COVID. As promising features, prognostic signatures and therapeutic targets shed light on improving the personalized management of patients with LUAD.
Lipocalin-2 is associated with FGF23 in WNT1 and PLS3 osteoporosis
Authors: Loid Petra , Hauta-alus Helena , Mäkitie Outi , Magnusson Per , Mäkitie Riikka E. 
Published: September 2022

BackgroundThe pathogenic mechanisms of early-onset osteoporosis caused by WNT1 and PLS3 mutations are incompletely understood and diagnostic biomarkers of these disorders are limited. Recently, lipocalin-2 has been recognized as an osteokine involved in bone development and homeostasis. However, the role of lipocalin-2 in WNT1 and PLS3 osteoporosis is unknown.ObjectiveWe aimed to investigate if plasma lipocalin-2 could be utilized as a biomarker for WNT1 and PLS3 osteoporosis and to evaluate the association between lipocalin-2 and other parameters of bone metabolism.MethodsWe measured plasma lipocalin-2 in 17 WNT1 and 14 PLS3 mutation-positive patients and compared them to those of 34 mutation-negative (MN) healthy subjects. We investigated possible associations between lipocalin-2 and several bone biomarkers including collagen type I cross-linked C-telopeptide (CTX), alkaline phosphatase (ALP), type I procollagen intact N-terminal propeptide (PINP), intact and C-terminal fibroblast growth factor 23 (FGF23), dickkopf-1 (DKK1) and sclerostin as well as parameters of iron metabolism (iron, transferrin, transferrin saturation, soluble transferrin receptor and ferritin).ResultsWe found no differences in plasma lipocalin-2 levels in WNT1 or PLS3 patients compared with MN subjects. However, lipocalin-2 was associated with C-terminal FGF23 in WNT1 patients (r=0.62; p=0.008) and PLS3 patients (r=0.63, p=0.017), and with intact FGF23 in PLS3 patients (r=0.80; p&lt;0.001). In addition, lipocalin-2 correlated with serum transferrin in WNT1 patients (r=0.72; p=0.001).ConclusionWe conclude that plasma lipocalin-2 is not altered in WNT1 or PLS3 mutation-positive subjects but is associated with FGF23 in abnormal WNT1 or PLS3 signaling and with iron status in abnormal WNT1 signaling.
Association of amino acids related to urea cycle with risk of diabetic nephropathy in two independent cross-sectional studies of Chinese adults
Authors: Cao Penglong , Huang Bing , Hong Mo , Jiang Yuxin , Cao Ran , Chi Chen , Cao Yunfeng , Li Shijun 
Published: September 2022

ObjectiveTo investigate the association between amino acids related to the urea cycle and diabetic nephropathy (DN) in two independent cross-sectional studies.MethodsWe obtained the medical records of 145 individuals with DN and 596 individuals without DN who attended an annual health examination at Liaoning Medical University First Affiliated Hospital (LMUFAH), China, from May 2015 to August 2016. From April 2018 to April 2019, we collected medical records of another 741 individuals: 338 individuals with DN and 403 individuals without DN from the Second Affiliated Hospital of Dalian Medical University (DALIAN), China. Binary logistic regression was used to obtain the odds ratio (OR) and 95% confidence interval (CI).ResultsIn two independent cross-sectional studies, we observed that citrulline was consistently associated with DN risk [OR (95% CI) of per standard deviation (SD) increase for citrulline in the LMUFAH population: 1.200 (1.006, 1.432); OR (95% CI) of per SD increase for citrulline in the DALIAN population: 1.189 (1.012, 1.396); pooled effect size for citrulline: 1.194 (1.060, 1.345)]. However, ornithine, arginine, and the ratio of arginine to ornithine were consistently unrelated to DN risk, and the ratios of other amino acids in the urea cycle were inconsistently associated with DN risk. ConclusionsCitrulline was consistently associated with DN risk in two independent cross-sectional studies in Chinese adults.
A higher TyG index is related with a higher prevalence of erectile dysfunction in males between the ages 20-70 in the United States, according to a cross-sectional research
Authors: Li Lin , Yao Hui , Dai Wei , Chen Yan , Liu Heqian , Ding Wei , Liu Yingqing , Tao Lingsong , Wang Jiawei , Chen Mingwei 
Published: September 2022

ObjectiveThis study aims to investigate the relationship between triglyceride glucose index (TyG) and erectile dysfunction (ED) among United States (US) adult males.MethodsA logistic regression analysis, subgroup analysis, and the computation of the dose-response curve were used to investigate the relationship between TyG index and ED prevalence among participants from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) database.ResultsAfter adjusting for all confounders, each unit increase in TyR index was associated with a 25 percent increase in ED prevalence (OR=1.25, 95%CI:1.03, 1.52), and stratified analysis showed that elevated TyG index was associated with increased ED prevalence in the 50-year old group (OR=1.35, 95% CI:1.05, 1.74), the Mexican-American group (OR=1.50, 95% CI:1.00, 2.23) and BMI 25-29.9 kg/m2 (OR=1.48, 95% CI:1.08, 2.01). The dose-response curve demonstrated a positive linear connection between the TyG index and the risk of ED.ConclusionIt has been shown that a higher TyG index is associated with a higher prevalence of erectile dysfunction. Although the causal relationship is not clear, it still deserves clinical attention
A bibliometric analysis of RNA methylation in diabetes mellitus and its complications from 2002 to 2022
Authors: Zhang Wenhua , Zhang Shuwen , Dong Chenlu , Guo Shuaijie , Jia Weiyu , Jiang Yijia , Wang Churan , Zhou Mingxue , Gong Yanbing 
Published: September 2022

BackgroundRNA methylation has emerged as an active research field in diabetes mellitus (DM) and its complications, while few bibliometric analyses have been performed. We aimed to visualize the hotspots and trends using bibliometric analysis to provide a comprehensive and objective overview of the current search state in this field.MethodsThe articles and reviews regarding RNA methylation in DM and its complications were from the Web of Science Core Collection. A retrospective bibliometric analysis and science mapping was performed using the CiteSpace software to plot the knowledge maps and predict the hotspots and trends.ResultsThree hundred seventy-five qualified records were retrieved. The annual publications gradually increased over the past 20 years. These publications mainly came from 66 countries led by Canada and 423 institutions. Leiter and Sievenpiper were the most productive authors, and Jenkins ranked first in the cited authors. Diabetes Care was the most co-cited journal. The most common keywords were “Type 2 diabetes”, “cardiovascular disease”, “diabetes mellitus”, and “n 6 methyladenosine”. The extracted keywords mainly clustered in “beta-cell function”, “type 2 diabetes”, “diabetic nephropathy”, “aging”, and “n6-methyladenosine”. N6-methyladenosine (m6A) in DM and its complications were the developing areas of study.ConclusionStudies on RNA methylation, especially m6A modification, are the current hotspots and the future trends in type 2 diabetes (T2D) and diabetic nephropathy (DN), as well as a frontier field for other complications of DM. Strengthening future cooperation and exchange between countries and institutions is strongly advisable to promote research developments in this field.
Incorporation of Soil-Derived Covariates in Progeny Testing and Line Selection to Enhance Genomic Prediction Accuracy in Soybean Breeding
Authors: Canella Vieira Caio , Persa Reyna , Chen Pengyin , Jarquin Diego 
Published: September 2022

The availability of high-dimensional molecular markers has allowed plant breeding programs to maximize their efficiency through the genomic prediction of a phenotype of interest. Yield is a complex quantitative trait whose expression is sensitive to environmental stimuli. In this research, we investigated the potential of incorporating soil texture information and its interaction with molecular markers via covariance structures for enhancing predictive ability across breeding scenarios. A total of 797 soybean lines derived from 367 unique bi-parental populations were genotyped using the Illumina BARCSoySNP6K and tested for yield during 5 years in Tiptonville silt loam, Sharkey clay, and Malden fine sand environments. Four statistical models were considered, including the GBLUP model (M1), the reaction norm model (M2) including the interaction between molecular markers and the environment (G×E), an extended version of M2 that also includes soil type (S), and the interaction between soil type and molecular markers (G×S) (M3), and a parsimonious version of M3 which discards the G×E term (M4). Four cross-validation scenarios simulating progeny testing and line selection of tested–untested genotypes (TG, UG) in observed–unobserved environments [OE, UE] were implemented (CV2 [TG, OE], CV1 [UG, OE], CV0 [TG, UE], and CV00 [UG, UE]). Across environments, the addition of G×S interaction in M3 decreased the amount of variability captured by the environment (−30.4%) and residual (−39.2%) terms as compared to M1. Within environments, the G×S term in M3 reduced the variability captured by the residual term by 60 and 30% when compared to M1 and M2, respectively. M3 outperformed all the other models in CV2 (0.577), CV1 (0.480), and CV0 (0.488). In addition to the Pearson correlation, other measures were considered to assess predictive ability and these showed that the addition of soil texture seems to structure/dissect the environmental term revealing its components that could enhance or hinder the predictability of a model, especially in the most complex prediction scenario (CV00). Hence, the availability of soil texture information before the growing season could be used to optimize the efficiency of a breeding program by allowing the reconsideration of field experimental design, allocation of resources, reduction of preliminary trials, and shortening of the breeding cycle.
Pan-cancer analysis of prognostic and immunological role of DTYMK in human tumors
Authors: Zhao Huihui , Xie Rongrong , Zhang Chenxi , Lu Guojun , Kong Hui 
Published: September 2022

Background: Deoxythymidylate kinase (DTYMK) has been reported to correlate with the progression of hepatocellular carcinoma. However, the role of DTYMK in human cancers is not studied. In this study, we studied the prognostic value, functional states, and correlations with immune infiltration of DTYMK in human cancers.Methods: The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UALCAN, Clinical Proteomic Tumor Analysis Consortium (CPTAC), the search tool for the retrieval of interacting genes (STRING), GeneMANIA, cBioPortal, Cancer Single-cell State Atlas (CancerSEA), and Tumor IMmune Estimation Resource (TIMER) databases were utilized to analyze DTYMK in cancers.Results: In general, DTYMK is abnormally expressed between most human cancer and normal tissues from a pan-cancer perspective. DTYMK can be used as a diagnostic biomarker to differentiate tumor tissues from normal tissues in most tumors. Upregulation of DTYMK predicted poor survival status in most cancer types in TCGA. Moreover, DTYMK expression was correlated with the T stage in ACC, BRCA, KIRC, LIHC, and LUAD, with the N stage in BLCA, HNSC, KICH, KIRC, LUAD, LUSC, and THCA, with the M stage in ACC, KIRC, KIRP, and LUAD, with TNM stage in ACC, KIRC, LIHC, LUAD, and LUSC. In addition, based on single-cell sequencing data, we concluded that the expression of DTYMK was correlated with the functional status of the cell cycle, DNA damage, DNA repair, invasion, EMT, and proliferation. Finally, DTYMK expression was correlated with six infiltrating immune cells, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells by investigating TIMER.Conclusion: Our findings suggested that abnormally expressed DTYMK was correlated with poor survival, malignant functional status, and immune infiltrates. DTYMK might be served as a potential biomarker for diagnosis and poor prognosis in various cancer types. DTYMK might act as a potential target for immune therapy.
Identification of clinical prognostic features of esophageal cancer based on m6A regulators
Authors: Wang Huimei , Zhang Yiping , Chen Lin , Liu Yufeng , Xu Chen , Jiang Dongxian , Song Qi , Wang Haixing , Wang Liyan , Lin Yu , Chen Yuanmei , Chen Junqiang , Xu Yuanji , Hou Yingyong 
Published: September 2022

BackgroundEsophageal cancer (ESCA) is a common malignancy with high morbidity and mortality. n6-methyladenosine (m6A) regulators have been widely recognized as one of the major causes of cancer development and progression. However, for ESCA, the role of regulators is unclear. The aim of this study was to investigate the role of m6A RNA methylation regulators in the immune regulation and prognosis of ESCA.MethodsRNA-seq data were downloaded using the Cancer Genome Atlas (TCGA) database, and the expression differences of m6A RNA methylation regulators in ESCA were analyzed. Further m6A methylation regulator markers were constructed, and prognostic and predictive values were assessed using survival analysis and nomograms. Patients were divided into low-risk and high-risk groups. The signature was evaluated in terms of survival, single nucleotide polymorphism (SNP), copy number variation (CNV), tumor mutation burden (TMB), and functional enrichment analysis (TMB). The m6A expression of key genes in clinical specimens was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR).ResultsIn ESCA tissues, most of the 23 regulators were significantly differentially expressed. LASSO regression analysis included 7 m6A-related factors (FMR1, RBMX, IGFBP1, IGFBP2, ALKBH5, RBM15B, METTL14). In addition, this study also identified that the risk model is associated with biological functions, including base metabolism, DNA repair, and mismatch repair. In this study, a nomogram was created to predict the prognosis of ESCA patients. Bioinformatics analysis of human ESCA and normal tissues was performed using qRT-PCR. Finally. Seven genetic features were found to be associated with m6A in ESCA patients. The results of this study suggest that three different clusters of m6A modifications are involved in the immune microenvironment of ESCA, providing important clues for clinical diagnosis and treatment.