bluuebunny/crossref_metadata_2025_split huggingface dataset:
Folic Acid Attenuates High-Fat Diet-Induced Osteoporosis Through the AMPK Signaling Pathway
Authors: He Haiting , Zhang Yaxi , Sun Yue , Zhang Yanwei , Xu Jingjing , Yang Yuzhen , Chen Jihua 
Published: January 2022

Objective: Obesity caused by a high-fat diet (HFD) will expand adipose tissue and cause chronic low-grade systemic inflammation, leading to osteoporosis. Folic acid (FA) is a water-soluble vitamin that plays an essential role in regulating blood lipids and antioxidants. However, the effects and underlying mechanisms of FA in osteoporosis induced by an HFD remain poorly understood. This study aimed to investigate the effect of FA on bone health by using HFD-induced osteoporosis mice.Materials and Methods: Mice were fed a normal diet, HFD or an HFD supplemented with FA (20 μg/ml in drinking water) for 16 weeks. Throughout the 16 weeks study period, the rats were weighed once every week. GTT, ITT and lipid indexes were detected to evaluate the effects of FA on lipid metabolism in the HFD-fed mice. Morphological and structural changes of the femur and tibial bone were observed using micro-CT, HE staining and bone conversion parameters. The expression of MDA, SOD and inflammatory factors were detected to evaluate the effects of FA on oxidative stress and inflammatory response in the HFD-fed mice. Quantitative real-time PCR and Western blot (WB) were used to investigate the AMPK signaling pathway.Results: After the intervention of FA, the body fat rate of obese mice was reduced, and related metabolic disorders such as insulin resistance, hyperlipidemia, and systemic inflammation were alleviated. In correlation with those modifications, FA attenuated bone loss and improved bone microarchitecture, accompanied the number of osteoclasts and adipocytes decreased. Furthermore, FA promoted the phosphorylation of AMPK, thereby promoting the expression of Carnitine palmitoyltransferase 1 (CPT1), nuclear factor erythroid-2 related factor 2 (Nrf2) and antioxidant enzymes.Conclusion: These findings suggest that FA may modulate lipid metabolism and oxidative stress responses activating the AMPK signaling pathway, thereby alleviating HFD-induced osteoporosis. The results from our study provide experimental evidence to prevent HFD-induced osteoporosis.
Clinical Performance of the Xpert® CT/NG Test for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae: A Multicenter Evaluation in Chinese Urban Hospitals
Authors: Han Yan , Shi Mei-Qin , Jiang Qing-Ping , Le Wen-Jing , Qin Xiao-Lin , Xiong Han-Zhen , Zheng He-Ping , Tenover Fred C. , Tang Yi-Wei , Yin Yue-Ping 
Published: January 2022

BackgroundWe aimed to evaluate the clinical performance of the GeneXpert® (Xpert) CT/NG assay for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) using urine and cervical swabs collected from patients in China.MethodsThis study was conducted from September 2016 to September 2018 in three Chinese urban hospitals. The results from the Xpert CT/NG test were compared to those from the Roche cobas® 4800 CT/NG test. Discordant results were confirmed by DNA sequence analysis.ResultsIn this study, 619 first void urine (FVU) specimens and 1,042 cervical swab specimens were included in the final dataset. There were no statistical differences between the results of the two tests for the detection of CT/NG in urine samples (p &gt; 0.05), while a statistical difference was found in cervical swabs (p &lt; 0.05). For CT detection, the sensitivity and specificity of the Xpert test were 100.0% (95%CI = 96.8–99.9) and 98.3% (95%CI = 96.6–99.2) for urine samples and 99.4% (95%CI = 96.5–100.0) and 98.6% (95%CI 97.5–99.2) for cervical swabs, respectively. For NG detection, the sensitivity and specificity of the Xpert test were 99.2% (95%CI = 94.9–100.0) and 100.0% (95%CI = 99.0–100.0) for urine and 100% (95%CI = 92.8–100.0) and 99.7% (95%CI = 99.0–99.9) for cervical swabs, respectively.ConclusionThe Xpert CT/NG test exhibited high sensitivity and specificity in the detection of CT and NG in both urine and cervical samples when compared to the reference results. The 90-min turnaround time for CT and NG detection at the point of care using Xpert may enable patients to receive treatment promptly.
Prognosis Between ST-Elevation and Non-ST-elevation Myocardial Infarction in Older Adult Patients
Authors: Chang Shih-Sheng , Lu Chiung-Ray , Chen Ke-Wei , Kuo Zhe-Wei , Yu Shao-Hua , Lin Shih-Yi , Shi Hong-Mo , Yip Hei-Tung , Kao Chia-Hung 
Published: January 2022

Background: Whether there is a difference in prognosis between elderly patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) remains mysterious.Methods: We conducted a retrospective cohort study by analyzing the data in the Longitudinal Health Insurance Database (LHID) in Taiwan to explore differences between STEMI and NSTEMI with respect to in-hospital and long-term (3-year) outcomes among older adult patients (aged ≥65 years). Patients were further stratified based on whether they received coronary revascularization.Results: In total, 5,902 patients aged ≥65 years with acute myocardial infarction (AMI) who underwent revascularization (2,254) or medical therapy alone (3,648) were included. In the revascularized group, no difference was observed in cardiovascular (CV) and all-cause mortality during hospitalization or at 3-year follow-up between the two AMIs. Conversely, in the non-revascularized group, patients with NSTEMI had higher crude odds ratio (cOR) for all-cause death during hospitalization [cOR: 1.33, 95% confidence interval (CI) = 1.07–1.65] and at 3-year follow-up (cOR: 1.47, 95% CI = 1.21–1.91) relative to patients with STEMI. However, after multivariable adjustments, only NSTEMI indicated fewer in-hospital CV death [adjusted odds ratio (aOR): 0.75, 95% CI = 0.58–0.98] than STEMI in non-revascularized group. Moreover, major bleeding was not different between patients with STEMI or NSTEMI aged ≥65 years old.Conclusion: Classification of AMI is not associated with the difference of in-hospital or 3-year CV and all-cause death in older adult patients received revascularization. In a 3-year follow-up period, STEMI was an independent predictor of a higher incidence of revascularization after the index event. Non-ST-elevation myocardial infarction had more incidence of MACE than patients with STEMI did in both treatment groups.
Favorable Cardiovascular Health Is Associated With Lower Hepatocyte Growth Factor Levels in the Multi-Ethnic Study of Atherosclerosis
Authors: Osibogun Olatokunbo , Ogunmoroti Oluseye , Ferraro Richard A. , Ndumele Chiadi E. , Burke Gregory L. , Larson Nicholas B. , Bielinski Suzette J. , Michos Erin D. 
Published: January 2022

Introduction: Hepatocyte growth factor (HGF) is a cytokine released in response to endothelial injury and a potential biomarker of cardiovascular disease (CVD) risk. We examined the association between cardiovascular health (CVH) and HGF in a multi-ethnic cohort of adults free from CVD at baseline.Methods: This cross-sectional study conducted between 2020 and 2021 used MESA baseline examination data (2000–2002) from 6,490 US adults aged 45–84 years. The independent variable was CVH measured by the CVH score and number of ideal metrics. The score was derived from seven metrics: smoking, body mass index, physical activity, diet, total cholesterol, blood pressure and blood glucose. Each metric was scored 0 points (poor), 1 point (intermediate) and 2 points (ideal). The total CVH score ranged from 0 to 14. An inadequate score was 0–8, average, 9–10 and optimal, 11–14. The dependent variable was logarithmically transformed HGF. We used regression analyses to estimate associations between CVH and HGF adjusting for sociodemographic factors.Results: Participants' mean (SD) age was 62 (10) years. Fifty-three percent were female. A one-unit increment in the CVH score was significantly associated with 3% lower HGF levels. Average and optimal CVH scores were significantly associated with 8% and 12% lower HGF levels, respectively, compared to inadequate scores. Additionally, a greater number of ideal metrics was associated with lower HGF levels.Conclusion: Favorable CVH was significantly associated with lower HGF levels in this ethnically diverse cohort. Interventions aimed at promoting and preserving favorable CVH may reduce the risk of endothelial injury as indicated by lower serum HGF levels.
Arrhythmia Patterns in Patients on Ibrutinib
Authors: Fazal Muhammad , Kapoor Ridhima , Cheng Paul , Rogers Albert J. , Narayan Sanjiv M. , Wang Paul , Witteles Ronald M. , Perino Alexander C. , Baykaner Tina , Rhee June-Wha 
Published: January 2022

Introduction: Ibrutinib, a Bruton's tyrosine kinase inhibitor (TKI) used primarily in the treatment of hematologic malignancies, has been associated with increased incidence of atrial fibrillation (AF), with limited data on its association with other tachyarrhythmias. There are limited reports that comprehensively analyze atrial and ventricular arrhythmia (VA) burden in patients on ibrutinib. We hypothesized that long-term event monitors could reveal a high burden of atrial and VAs in patients on ibrutinib.Methods: A retrospective data analysis at a single center using electronic medical records database search tools and individual chart review was conducted to identify consecutive patients who had event monitors while on ibrutinib therapy.Results: Seventy-two patients were included in the analysis with a mean age of 76.9 ± 9.9 years and 13 patients (18%) had a diagnosis of AF prior to the ibrutinib therapy. During ibrutinib therapy, most common arrhythmias documented were non-AF supraventricular tachycardia (n = 32, 44.4%), AF (n = 32, 44%), and non-sustained ventricular tachycardia (n = 31, 43%). Thirteen (18%) patients had &gt;1% premature atrial contraction burden; 16 (22.2%) patients had &gt;1% premature ventricular contraction burden. In 25% of the patients, ibrutinib was held because of arrhythmias. Overall 8.3% of patients were started on antiarrhythmic drugs during ibrutinib therapy to manage these arrhythmias.Conclusions: In this large dataset of ambulatory cardiac monitors on patients treated with ibrutinib, we report a high prevalence of atrial and VAs, with a high incidence of treatment interruption secondary to arrhythmias and related symptoms. Further research is warranted to optimize strategies to diagnose, monitor, and manage ibrutinib-related arrhythmias.
Effect of Coronary Calcification Severity on Measurements and Diagnostic Performance of CT-FFR With Computational Fluid Dynamics: Results From CT-FFR CHINA Trial
Authors: Zhao Na , Gao Yang , Xu Bo , Yang Weixian , Song Lei , Jiang Tao , Xu Li , Hu Hongjie , Li Lin , Chen Wenqiang , Li Dumin , Zhang Feng , Fan Lijuan , Lu Bin 
Published: January 2022

Aims: To explore the effect of coronary calcification severity on the measurements and diagnostic performance of computed tomography-derived fractional flow reserve (FFR; CT-FFR).Methods: This study included 305 patients (348 target vessels) with evaluable coronary calcification (CAC) scores from CT-FFR CHINA clinical trial. The enrolled patients all received coronary CT angiography (CCTA), CT-FFR, and invasive FFR examinations within 7 days. On both per-patient and per-vessel levels, the measured values, accuracy, and diagnostic performance of CT-FFR in identifying hemodynamically significant lesions were analyzed in all CAC score groups (CAC = 0, &gt; 0 to &lt;100, ≥ 100 to &lt;400, and ≥ 400), with FFR as reference standard.Results: In total, the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under receiver operating characteristics curve (AUC) of CT-FFR were 85.8, 88.7, 86.9, 87.8, 87.1%, 0.90 on a per-patient level and 88.3, 89.3, 89.5, 88.2, 88.9%, 0.88 on a per-vessel level, respectively. Absolute difference of CT-FFR and FFR values tended to elevate with increased CAC scores (CAC = 0: 0.09 ± 0.10; CAC &gt; 0 to &lt;100: 0.06 ± 0.06; CAC ≥ 100 to &lt;400: 0.09 ± 0.10; CAC ≥ 400: 0.11 ± 0.13; p = 0.246). However, no statistically significant difference was found in patient-based and vessel-based diagnostic performance of CT-FFR among all CAC score groups.Conclusion: This prospective multicenter trial supported CT-FFR as a viable tool in assessing coronary calcified lesions. Although large deviation of CT-FFR has a tendency to correlate with severe calcification, coronary calcification has no significant influence on CT-FFR diagnostic performance using the widely-recognized cut-off value of 0.8.
qPCR Analysis Reveals Association of Differential Expression of SRR, NFKB1, and PDE4B Genes With Type 2 Diabetes Mellitus
Authors: Raza Waseem , Guo Jinlei , Qadir Muhammad Imran , Bai Baogang , Muhammad Syed Aun 
Published: January 2022

BackgroundType 2 diabetes mellitus (T2DM) is a heterogeneous, metabolic, and chronic condition affecting vast numbers of the world’s population. The related variables and T2DM associations have not been fully understood due to their diverse nature. However, functional genomics can facilitate understanding of the disease. This information will be useful in drug design, advanced diagnostic, and prognostic markers.AimTo understand the genetic causes of T2DM, this study was designed to identify the differentially expressed genes (DEGs) of the disease.MethodsWe investigated 20 publicly available disease-specific cDNA datasets from Gene Expression Omnibus (GEO) containing several attributes including gene symbols and clone identifiers, GenBank accession numbers, and phenotypic feature coordinates. We analyzed an integrated system-level framework involving Gene Ontology (GO), protein motifs and co-expression analysis, pathway enrichment, and transcriptional factors to reveal the biological information of genes. A co-expression network was studied to highlight the genes that showed a coordinated expression pattern across a group of samples. The DEGs were validated by quantitative PCR (qPCR) to analyze the expression levels of case and control samples (50 each) using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as the reference gene.ResultsFrom the list of 50 DEGs, we ranked three T2DM-related genes (p &lt; 0.05): SRR, NFKB1, and PDE4B. The enriched terms revealed a significant functional role in amino acid metabolism, signal transduction, transmembrane and intracellular transport, and other vital biological functions. DMBX1, TAL1, ZFP161, NFIC (66.7%), and NR1H4 (33.3%) are transcriptional factors associated with the regulatory mechanism. We found substantial enrichment of insulin signaling and other T2DM-related pathways, such as valine, leucine and isoleucine biosynthesis, serine and threonine metabolism, adipocytokine signaling pathway, P13K/Akt pathway, and Hedgehog signaling pathway. The expression profiles of these DEGs verified by qPCR showed a substantial level of twofold change (FC) expression (2−ΔΔCT) in the genes SRR (FC ≤ 0.12), NFKB1 (FC ≤ 1.09), and PDE4B (FC ≤ 0.9) compared to controls (FC ≥ 1.6). The downregulated expression of these genes is associated with pathophysiological development and metabolic disorders.ConclusionThis study would help to modulate the therapeutic strategies for T2DM and could speed up drug discovery outcomes.
Association Between Serum Furin and Fasting Glucose: A Cross-Sectional Study in Chinese Adults
Authors: He Yan , Zhu Hanyun , Zhang Min , Li Jing , Ma Shengqi , Lu Yin , Chen Linan , Zhang Mingzhi , Peng Hao 
Published: January 2022

BackgroundFurin has been associated with glucose metabolic phenotypes in small sampled clinical studies. However, this association has not yet been studied in Chinese. Here, we aimed to examine the association between serum furin and fasting glucose in Chinese adults.MethodsSerum furin and fasting plasma glucose were assayed for 2,172 participants (mean aged 53 years, 38% men) in the Gusu cohort. A median regression model was applied to examine the association between serum furin and fasting glucose, adjusting for age, sex, education level, cigarette smoking, alcohol drinking, obesity, blood pressure, and lipids. To facilitate data interpretation, the association between serum furin and prevalent diabetes was also examined.ResultsSerum furin was negatively associated with fasting glucose (β=-0.18, P&lt;0.001 for log-furin). In participants with diabetes, serum furin was significantly lower than those with normal glucose (median: 0.90 ng/mL vs. 1.05 ng/mL, P=0.001). Compared with participants in the highest quartile of serum furin, those in the lowest quartile had 42% and 80% increased risk of prevalent prediabetes (OR=1.42, 95%CI: 1.05-1.92, P=0.023) and diabetes (OR=1.80, 95%CI: 1.13-2.91, P=0.015), respectively.ConclusionsSerum furin was negatively associated with prediabetes and diabetes in Chinese adults. Our findings suggest that serum furin may be a risk factor or a biomarker of diabetes.
Hybrid Solar Geothermal Heat Pump System Model Demonstration Study
Authors: Kim Yu-Jin , Yang Libing , Entchev Evgueniy , Cho Soolyeon , Kang Eun-Chul , Lee Euy-Joon 
Published: January 2022

In this paper, the development and demonstration of a hybrid solar geothermal heat pump polygeneration system is presented. The poly-generation system has been designed, modeled, and simulated in TRNSYS software environment. Its performance was assessed followed by installation and demonstration at a demo site in Cheongju, Korea. The space heating and cooling load of the building is 13.8 kW in heating mode at an ambient temperature of −10.3°C and 10.6 kW in cooling mode at an ambient temperature of 32.3°C. The simulation data were compared with the field demo data using ISO 13256. The results showed that the model data compare well with the demo data both in heating and cooling modes of operation. At a source temperature of 16.7°C, the heat pump lab performance data-based COPc shows 9.9, while demonstration COPc shows 10.3, thus, representing 4.3% relative error. The heat pump source temperature decreased by 4.0°C from 20.9°C to 16.9°C due to ground heat exchanger coupling and resulted in a COPc increase by 13.3% from 8.5 to 9.8. When compared at the design conditions (outside temperature of 32.3°C), the TRSNYS model overestimated the demonstration site data by 12%, 9.3 vs. 8.1 kW with power consumption of 3.1 vs. 2.2 kW. The hybrid polygeneration system power consumption decreased by 1.2 kW when ambient temperature decreased from 35°C to 25°C.
Genetic Variation of Migration Inhibitory Factor Gene rs2070766 Is Associated With Acute Coronary Syndromes in Chinese Population
Authors: Zhang Jin-Yu , Zhao Qian , Liu Fen , Li De-Yang , Men Li , Luo Jun-Yi , Zhao Ling , Li Xiao-Mei , Gao Xiao-Ming , Yang Yi-Ning 
Published: January 2022

Genetic variation of macrophage migration inhibitory factor (MIF) gene has been linked to coronary artery disease. We investigated an association between the polymorphism of MIF gene rs2070766 and acute coronary syndromes (ACS) and the predictive value of MIF gene variation in clinical outcomes. This study involved in 963 ACS patients and 932 control subjects from a Chinese population. All participants were genotyped for the single nucleotide polymorphism (SNP) of MIF gene rs2070766 using SNPscan™. A nomogram model using MIF genetic variation and clinical variables was established to predict risk of ACS. Major adverse cardiovascular events (MACE) were monitored during a follow-up period. The frequency of rs2070766 GG genotype was higher in ACS patients than in control subjects (6.2 vs 3.8%, p = 0.034). Multivariate logistic regression analysis revealed that individuals with mutant GG genotype had a 1.7-fold higher risk of ACS compared with individuals with CC or CG genotypes. Using MIF rs2070766 genotypes and clinical factors, we developed a nomogram model to predict risk of ACS. The nomogram model had a good discrimination with an area under the curve of 0.781 (95% CI: 0.759–0.804), concordance index of 0.784 (95% CI: 0.762–0.806) and well-fitted calibration. During the follow-up period of 25 months, Kaplan-Meier curves demonstrated that ACS patients carrying GG phenotype developed more MACE compared to CC or CG carriers (p &lt; 0.05). GG genotype of MIF gene rs2070766 was associated with a higher risk of ACS in a Chinese population. The GG genotype carriers in ACS patients had worse clinical outcomes compared with those carrying CC or CG genotype. Together with rs2070766 genetic variant of MIF gene, we established a novel nomogram model that can provide individualized prediction for ACS.
Analysis of N6-Methyladenosine Modification Patterns and Tumor Immune Microenvironment in Pancreatic Adenocarcinoma
Authors: Liu Yong , Li Guangbing , Yang Yang , Lu Ziwen , Wang Tao , Wang Xiaoyu , Liu Jun 
Published: January 2022

Background: Pancreatic adenocarcinoma (PAAD) is a rare cancer with a poor prognosis. N6-methyladenosine (m6A) is the most common mRNA modification. However, little is known about the relationship between m6A modification and the tumor immune microenvironment (TIME) in PAAD.Methods: Based on 22 m6A regulators, m6A modification patterns of PAAD samples extracted from public databases were systematically evaluated and correlated with the tumor immune and prognosis characteristics. An integrated model called the “m6Ascore” was constructed, and its prognostic role was evaluated.Results: Three different m6Aclusters and gene clusters were successively identified; these clusters were characterized by differences in prognosis, immune cell infiltration, and pathway signatures. The m6Ascore was constructed to quantify the m6A modifications of individual patients. Subsequent analysis revealed that m6Ascore was an independent prognostic factor of PAAD and could be a potential indicator to predict the response to immunotherapy.Conclusion: This study comprehensively evaluated the features of m6A modification patterns in PAAD. m6A modification patterns play a non-negligible role in the TIME of PAAD. m6Ascore provides a more holistic understanding of m6A modification in PAAD, and will help clinicians predict the prognosis and response to immunotherapy.
Classification of CHD7 Rare Variants in Chinese Congenital Hypogonadotropic Hypogonadism Patients and Analysis of Their Clinical Characteristics
Authors: Sun Bang , Wang Xi , Mao Jiangfeng , Zhao Zhiyuan , Zhang Wei , Nie Min , Wu Xueyan 
Published: January 2022

Purpose:CHD7 rare variants can cause congenital hypogonadotropic hypogonadism (CHH) and CHARGE syndrome. We aimed to summarize the genotype and phenotype characteristics of CHH patients with CHD7 rare variants.Methods: Rare sequencing variants (RSVs) were detected by Sanger sequencing in a series of 327 CHH patients and were interpreted and grouped according to the American College of Medical Genetics and Genomics (ACMG) guideline. Detailed phenotyping and genotype-phenotype correlation were analyzed.Results: The RSV detection rate was 11.01% (36/327) in the CHH patients. We identified 30 RSVs and 19 of them were novel. Following ACMG criteria, three variants were pathogenic (P), 4 were likely pathogenic (LP), 3 were of uncertain significance with paradoxical evidence (US1), and 20 were of uncertain significance without enough evidence (US2). All patients (4/4, 100%) with P or LP variants manifested extragonadal symptoms.Conclusion: Addition of 19 novel CHD7 variants expanded the spectrum of variants, and pathogenic or likely pathogenic RSVs were more likely to cause syndromic CHH. For CHH patients carrying CHD7 RSVs, detailed genotyping and phenotyping can facilitate clinical diagnosis and therapy.