bluuebunny/crossref_metadata_2025_split huggingface dataset:
Canagliflozin combined with metformin versus metformin monotherapy for endocrine and metabolic profiles in overweight and obese women with polycystic ovary syndrome: A single-center, open-labeled prospective randomized controlled trial
Authors: Zhang Jiaqi , Xing Chuan , Cheng Xiangyi , He Bing 
Published: September 2022

ObjectivesCanagliflozin (CANA), a kind of sodium-glucose cotransporter-2 (SGLT-2) inhibition, study in which the role of CANA monotherapy in polycystic ovary syndrome (PCOS) has been investigated, and it could become a novel option in the PCOS treatment. Nevertheless, trials focused on SGLT-2 combination therapy’s efficacy, and safety in PCOS patients are limited. This randomized controlled trial compared the efficacy and safety of CANA and metformin (MET) combination therapy and MET monotherapy in endocrine and metabolic profiles of overweight and obese women with polycystic ovary syndrome (PCOS).MethodsFifty-one overweight or obese non-diabetic PCOS women between 18 and 40 years old were enrolled. Patients were randomly allocated to receive either CANA/MET or MET treatment. The CANA/MET group received CANA 100 mg once daily plus MET 1000 mg twice daily, while the MET group received MET 1000 mg twice daily for three months. Changes in menstrual pattern, anthropometric parameters, gonadal parameters, glucose and lipid homeostasis, and adverse events (AEs) were evaluated.ResultsCompared with the MET group, women have a significantly lower level of total testosterone (TT), area under the curve for glucose (AUCGlu), and area under the curve for insulin (AUCIns) to AUCGlu ratio in the combination group. There were no significant differences in menstrual frequency, body weight, body mass index, follicle-stimulating hormone, luteinizing hormone, free androgen index, sex hormone-binding globulin, androstenedione, fasting blood glucose, fasting insulin, AUCIns, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), and APO B/A1 ratio. AEs were seen in 57.70% (15/26) and 68.00% (17/25) of patients in the CANA/MET and MET groups, respectively.ConclusionsIn overweight and obese women with PCOS, CANA and MET combination therapy may be similar to MET monotherapy in improving menstrual frequency, weight control, hyperandrogenemia, and relieving insulin resistance. CANA/MET may have more benefits in reducing TT, AUCGlu, and the AUCIns/AUCGlu ratio within three months than MET monotherapy.Trial registrationClinicalTrials.gov, NCT04973891.
Exploration of differentially expressed mRNAs and miRNAs for pediatric acute myeloid leukemia
Authors: Wang Qing , Yue Chao , Liu Qin , Che Xuchun 
Published: September 2022

Background: To establish a comprehensive differential gene profile for pediatric acute myeloid leukemia patients (pAML) based on two independent databases and verify the differentially expressed genes using in vitro and in vivo analyses.Methods: The mRNA and miRNA sequencing information of GSE2191 and GSE35320, clinically recruited pAML individuals, and human AML cell line (NB4 cells) were utilized in the study.Results: Compared with the control sample, pAML patients demonstrated a total of 778 differentially expressed genes, including 565 upregulated genes and 213 downregulated genes. The genes including ZC3H15, BCLAF1, PPIG, DNTTIP2, SRSF11, KTN1, UBE3A, PRPF40A, TMED5, and GNL2 were the top 10 potential hub genes. At the same time, 12 miRNAs demonstrated remarkable differential expressions in pAML individuals compared with control individuals, as five upregulated and seven downregulated miRNAs. The hsa-miR-133, hsa-miR-181, and hsa-miR-195 were significantly downregulated. Building a miRNA–mRNA regulatory network, hsa-miR-133 regulated ZC3H15, BCLAF1, SRSF11, KTN1, PRPF40A, and GNL2. Using the NB4 cell model, hsa-miR-133 treatment inhibited cell proliferation capacity, which could be attenuated by a single mRNA transfection or a combination of ZC3H15 and BCLAF1. At the same time, hsa-miR-133 mimic treatment could significantly accelerate cell apoptosis in NB4 cells, which was also ZC3H15- and BCLAF1-dependent. The concentrations of ZC3H15 and BCLAF1 were investigated in peripheral blood using the ELISA method for the clinical control and pAML samples. In pAML samples, the expression levels of ZC3H15 and BCLAF1 were significantly enhanced (p &lt; 0.01), regardless of the classification.Conclusion: Collectively, this study hypothesized several promising candidates for pAML formation.
Establishment of an endoplasmic reticulum stress-related signature predicting outcomes of gastric adenocarcinoma patients
Authors: Gong Meiyuan , Wang Jingtao , Gao Wenfang , Liu Qian , Chen Jiaxing , Wang Guojun , Zhang Qi 
Published: September 2022

Background: Gastric adenocarcinoma (GAC) is a common clinical malignancy with a poor prognosis. Endoplasmic reticulum (ER) stress plays important roles in the progression, immune filtration, and chemoresistance of cancers. However, whether ER stress-related gene signatures can predict the prognosis of GAC patients remains unknown.Methods: GAC patient RNA-seq data downloaded from The Cancer Genome Atlas and gastric cancer patient microarray data from Gene Expression Omnibus datasets were analyzed using LASSO regression to construct an ER stress-related signature. Survival analysis, time-dependent receiver operating characteristic (ROC) curves, and Cox regression analysis were used to verify the efficacy of the signature. Immune infiltration, somatic mutation, immune checkpoint, and copy number variation analyses were utilized to explore the potential biological significance of the signature.Results: In the present study, eight ER stress-related gene signatures were constructed. Survival analysis showed that patients in the high-risk group had a significantly worse prognosis. The area under the time-dependent ROC curves was 0.65, 0.70, and 0.63 at 1, 3, and 5 years, respectively, in the training cohort. Cox regression analysis showed that the signature is an independent prognostic factor. To predict GAC patients’ prognosis meeting individual needs, a nomogram was constructed with good accuracy. In addition, gene set enrichment and immune infiltration analyses showed that the ER stress-related signature is associated with cancer-related pathway activation and an immunosuppressive tumor microenvironment in GAC.Conclusion: In the current study, we established an ER stress-related signature. This prognostic signature has good predictive power and could facilitate the development of novel strategies for the clinical treatment of GAC.
A comprehensively prognostic and immunological analysis of actin-related protein 2/3 complex subunit 5 in pan-cancer and identification in hepatocellular carcinoma
Authors: Huang Shenglan , Sun Liying , Hou Ping , Liu Kan , Wu Jianbing 
Published: September 2022

BackgroundActin-related protein 2/3 complex subunit 5 (ARPC5) is one of the members of actin-related protein 2/3 complex and plays an important role in cell migration and invasion. However, little is known about the expression pattern, prognosis value, and biological function of ARPC5 in pan-cancer. Thus, we focus on ARPC5 as cut point to explore a novel prognostic and immunological biomarker for cancers.MethodsThe public databases, including TCGA, GTEx, and UCEC, were used to analyze ARPC5 expression in pan-cancer. The Human Protein Atlas website was applied to obtain the expression of ARPC5 in different tissues, cell lines, and single-cell types. Univariate Cox regression analysis and Kaplan–Meier analysis were used to explore the prognosis value of ARPC5 in various cancers. Spearman’s correlation analysis was performed to investigate the association between ARPC5 expression and tumor microenvironment scores, immune cell infiltration, immune-related genes, TMB, MSI, RNA modification genes, DNA methyltransferases, and tumor stemness. Moreover, qPCR, Western blot, and immunohistochemistry were carried out to examine the differential expression of ARPC5 in HCC tissues and cell lines. CCK8, EdU, flow cytometry, wound-healing assays, and transwell assays were conducted to explore its role in tumor proliferation, apoptosis, migration, and invasion among HCC cells.ResultsARPC5 expression was upregulated in most cancer types and significantly associated with worse prognosis in KIRC, KIRP, LGG, and LIHC. mRNA expression of ARPC5 showed low tissue and cell specificity in normal tissues, cell lines, and single-cell types. ARPC5 expression was positively correlated with the tumor microenvironment scores, immune infiltrating cells, immune checkpoint–related genes in most cancers. ARPC5 in STAD and BRCA was positively associated with TMB, MSI, and neoantigens. We also discovered that ARPC5 was correlated with the expression of m1A-related genes, m5C-related genes, m6A-related genes, and DNA methyltransferases. In experiment analyses, we found that ARPC5 was significantly highly expressed in HCC tissues and HCC cells. Functionally, silencing ARPC5 dramatically decreased proliferation, migration, and invasion ability of HCC cells.ConclusionsARPC5 expression affects the prognosis of multiple tumors and is closely correlated to tumor immune infiltration and immunotherapy. Furthermore, ARPC5 may function as an oncogene and promote tumor progression in HCC.
Montelukast induces beneficial behavioral outcomes and reduces inflammation in male and female rats
Authors: Rostevanov Ira S. , Betesh-Abay Batya , Nassar Ahmad , Rubin Elina , Uzzan Sarit , Kaplanski Jacob , Biton Linoy , Azab Abed N. 
Published: September 2022

BackgroundAccumulative data links inflammation and immune dysregulation to the pathophysiology of mental disorders; little is known regarding leukotrienes’ (LTs) involvement in this process. Circumstantial evidence suggests that treatment with leukotriene modifying agents (LTMAs) such as montelukast (MTK) may induce adverse neuropsychiatric events. Further methodic evaluation is warranted.ObjectiveThis study aims to examine behavioral effects, as well as inflammatory mediator levels of chronic MTK treatment in male and female rats.MethodsDepression-like phenotypes were induced by exposing male and female rats to a chronic unpredictable mild stress (CUMS) protocol for four weeks. Thereafter, rats were treated (intraperitoneally) once daily, for two weeks, with either vehicle (dimethyl sulfoxide 0.2 ml/rat) or 20 mg/kg MTK. Following treatment protocols, behavioral tests were conducted and brain regions were evaluated for inflammatory mediators including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and prostaglandin (PG) E2.ResultsOverall, MTK did not invoke negative behavioral phenotypes (except for an aggression-inducing effect in males). Numerous positive behavioral outcomes were observed, including reduction in aggressive behavior in females and reduced manic/hyperactive-like behavior and increased sucrose consumption (suggestive of antidepressant-like effect) in males. Furthermore, in control males, MTK increased IL-6 levels in the hypothalamus and TNF-α in the frontal cortex, while in control females it generated a robust anti-inflammatory effect. In females that were subjected to CUMS, MTK caused a prominent reduction in TNF-α and IL-6 in brain regions, whereas in CUMS-subjected males its effects were inconsistent.ConclusionContrary to prior postulations, MTK may be associated with select beneficial behavioral outcomes. Additionally, MTK differentially affects male vs. female rats in respect to brain inflammatory mediators, plausibly explaining the dissimilar behavioral phenotypes of sexes under MTK treatment.
Effect of acupuncture at the sphenopalatine ganglion for the treatment of moderate to severe seasonal allergic rhinitis: Study protocol for a three-armed randomized controlled trial
Authors: Wang Weiming , Chen Hui , Gao Ning , Yu Shudan , Liao Jiahua , Wang Shijie , Gao Ziqi , Liu Zhishun 
Published: September 2022

IntroductionSeasonal allergic rhinitis (SAR) is a major health problem with a relatively high worldwide prevalence that severely limits the quality of life for sufferers. Acupuncture is widely used for SAR treatment in China; however, the evidence on the efficacy of acupuncture at the sphenopalatine ganglion (SPG) for SAR is inconclusive. Therefore, this study aims to investigate the efficacy and safety of acupuncture at the SPG acupoint for the treatment of SAR.Methods and analysisA total of 120 participants with SAR will be recruited and randomly assigned to the acupuncture group, placebo acupuncture (PA) group, or rescue medication (RM) group with a 1:1:1 allocation ratio. Participants in the acupuncture group and PA group will receive 8 sessions of acupuncture stimulus at the SPG plus RM or 8 sessions of shallow needling at the SPG acupoint plus RM for 4 weeks with a 4-week follow-up in the first year and a 1-week follow-up in the second year. Participants in the RM group will only receive RM throughout the study. The primary outcome is the change from baseline in the average daily combined symptoms and medication score (CSMS) over weeks 1–4. All analysis will be based on an intention-to-treat principle. All statistical tests will be two-sided and a p-value &lt; 0.05 will be considered to be statistically significant.
Prospective association between sleep duration and cognitive impairment: Findings from the China Health and Retirement Longitudinal Study (CHARLS)
Authors: Liu Wenhua , Wu Qingsong , Wang Minghuan , Wang Peng , Shen Na 
Published: September 2022

ObjectiveThe association between sleep duration and cognition are inconclusive. Our study aimed to comprehensively investigate the effects of sleep duration on the risk of cognitive impairment in the middle-aged and older Chinese population.MethodsWe used the longitudinal cohort data from waves 1–4 (2011–2018) of the China Health and Retirement Longitudinal Study (CHARLS). Self-reported exposures included total sleep duration, nocturnal sleep duration, post-lunch napping, and changes in sleep duration over time according to face-to-face interviews. Cognitive function was assessed by a Chinese version of the Modified Mini-Mental State Examination (MMSE).ResultsA total of 7,342 eligible participants were included. The mean age was 61.5 ± 6.5 years, and 48.9% (3,588/7,342) were male. We identified a U-shaped association of total sleep duration as well as nocturnal sleep duration with the risk of cognitive impairment. People with 7–8 h of total sleep duration and 6–7 h of nocturnal sleep had the lowest risk of cognitive impairment. Further results showed that post-lunch napping within 2 h was beneficial to cognition and 60 min was optimal. Moreover, analyses of changes in sleep duration further supported that sleeping less or more was harmful to cognition. Notably, those “excessive-change” sleepers (from ≤6 to ≥9 h, or from ≥9 to ≤6 h) had more risks.ConclusionsKeeping 7–8 h per day was related to the lowest risk of cognitive impairment in midlife and late life, and an optimal post-lunch napping was 60 min for these stable sleepers. Especially, excessive changes in sleep duration over time led to poorer cognition. Our work highlights the importance of optimal sleep habits to cognitive function. The self-reported sleep measures limited our findings, and further studies are needed for verification.
Correlation between heart rate variability and polysomnography-derived scores of obstructive sleep apnea
Authors: dos Santos Rafael Rodrigues , da Silva Thais Marques , Silva Luiz Eduardo Virgilio , Eckeli Alan Luiz , Salgado Helio Cesar , Fazan Rubens 
Published: September 2022

Obstructive sleep apnea (OSA) is one of the most common sleep disorders and affects nearly a billion people worldwide. Furthermore, it is estimated that many patients with OSA are underdiagnosed, which contributes to the development of comorbidities, such as cardiac autonomic imbalance, leading to high cardiac risk. Heart rate variability (HRV) is a non-invasive, widely used approach to evaluating neural control of the heart. This study evaluates the relationship between HRV indices and the presence and severity of OSA. We hypothesize that HRV, especially the nonlinear methods, can serve as an easy-to-collect marker for OSA early risk stratification. Polysomnography (PSG) exams of 157 patients were classified into four groups: OSA-free (N = 26), OSA-mild (N = 39), OSA-moderate (N = 37), and OSA-severe (N = 55). The electrocardiogram was extracted from the PSG recordings, and a 15-min beat-by-beat series of RR intervals were generated every hour during the first 6 h of sleep. Linear and nonlinear HRV approaches were employed to calculate 32 indices of HRV. Specifically, time- and frequency-domain, symbolic analysis, entropy measures, heart rate fragmentation, acceleration and deceleration capacities, asymmetry measures, and fractal analysis. Results with indices of sympathovagal balance provided support to reinforce previous knowledge that patients with OSA have sympathetic overactivity. Nonlinear indices showed that HRV dynamics of patients with OSA display a loss of physiologic complexity that could contribute to their higher risk of development of cardiovascular disease. Moreover, many HRV indices were found to be linked with clinical scores of PSG. Therefore, a complete set of HRV indices, especially the ones obtained by the nonlinear approaches, can bring valuable information about the presence and severity of OSA, suggesting that HRV can be helpful for in a quick diagnosis of OSA, and supporting early interventions that could potentially reduce the development of comorbidities.
Prediction of risk factors for intraoperative hypotension during general anesthesia undergoing carotid endarterectomy
Authors: Jia Yitong , Feng Guang , Wang Zheng , Feng Yao , Jiao Liqun , Wang Tian-Long 
Published: September 2022

ObjectiveCarotid endarterectomy (CEA) has been considered as “gold standard” treatment for patients with significant carotid stenosis Intra-operative hypotension was a risk factor for post-operative complications in patients undergoing CEA. This study aimed to investigate the predictors for intra-operative hypotension during CEA.MethodsThis retrospective study included consecutive patients underwent CEA from June 1, 2020 to May 31, 2021 in the neurosurgery department of Xuanwu Hospital, Capital Medical University. The intraoperative hypotension was defined as blood pressure (BP) of 20% below standard value for longer than 5 min. Univariable and multivariable analyses were performed to identify the prediction of risk factors for intraoperative hypotension.ResultsOverall, 367 patients were included, and 143 (39.0%) patients had hypotension during CEA procedure. Univariate analysis indicated Grade 3 hypertension (P = 0.002), peripheral artery disease (P = 0.006) and shunting (P = 0.049) were associated with occurrence of intraoperative hypotension during CEA procedure. On multivariable analysis, Grade 3 hypertension (P = 0.005), peripheral artery disease (P = 0.009), and shunting (P = 0.034) were all found to be independent predicting factors of hypotension during the CEA process.ConclusionIntraoperative hypotension is a dynamic phenomenon may be affected by patients with grade 3 hypertension, peripheral artery disease and intra-operative shunting. It is necessary to pay special attention to these patients, both intraoperatively and postoperatively, to improve the final clinical outcome.
Beef intake and risk of rheumatoid arthritis: Insights from a cross-sectional study and two-sample Mendelian randomization
Authors: Chen Weiwei , Liu Ke , Huang Lin , Mao Yingying , Wen Chengping , Ye Ding , He Zhixing 
Published: September 2022

BackgroundBeef is common in daily diet, but its association with the risk of rheumatoid arthritis (RA) remains uncertain. The objective of this study is to explore the relationship between beef intake and the risk of RA.Materials and methodsWe investigated the association between beef intake and risk of RA by multivariate logistic regression, based on the National Health and Nutrition Examination Survey (NHANES) 1999–2016 involving 9,618 participants. The dose–response relationship between beef intake and RA was explored as well. Furthermore, we performed Mendelian randomization (MR) analysis to examine the causal effect of beef intake on RA. Genetic instruments for beef intake were selected from a genome-wide association study (GWAS) including 335,576 individuals from the UK Biobank study, and summary statistics relating to RA were obtained from a GWAS meta-analysis of 14,361 RA patients and 43,923 controls. The inverse-variance weighted (IVW) approach was used to estimate the causal association, and MR-Egger regression and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test were applied to evaluate the pleiotropy and outliers.ResultsCompared with the lowest quintile (0 to ≤33.50 g/d), beef intake was found to be significantly associated with the risk of RA [odds ratio (OR): 1.94; 95% confidence interval (CI): 1.20–3.12] in the third quintile (50.26 to ≤76.50 g/d). Moreover, a reversed “U” dose–response relationship between beef and RA (Pnon–linearity = 0.023) was found. In the MR analysis, beef intake was associated with an increased risk of RA (OR: 3.05; 95% CI: 1.11–8.35; P = 0.030) by the IVW method. The results from MR-Egger regression and MR-PRESSO test showed that there were no pleiotropic variations and outliers.ConclusionThis study indicated that there is suggestive evidence to support the causal effect of beef intake on the risk of RA, while further studies are warranted to elucidate the exact association.
Nutrient patterns and non-alcoholic fatty liver disease in Iranian Adul: A case-control study
Authors: Salehi-sahlabadi Ammar , Teymoori Farshad , Ahmadirad Hamid , Mokhtari Ebrahim , Azadi Mina , Seraj Shaikh Sanjid , Hekmatdoost Azita 
Published: September 2022

BackgroundsThe current literature boasts the importance of diet in preventing or managing liver complications. However, there is limited evidence on the association of nutrient patterns (NP) with these complications. In this case-control study, we aimed to examine the possible relationship between nutrient patterns and the risk of non-alcoholic fatty liver disease (NAFLD) amongst the adult Iranian population.MethodsThis case-control study is being conducted at the Metabolic Liver Disease Research Center at Isfahan University of Medical Sciences in 2019. The study included 225 newly diagnosed cases of NAFLD and 450 controls. A validated semi-quantitative food frequency questionnaire (FFQ) assessed dietary intake. Principal component analysis using Varimax rotation obtained nutrient patterns. Logistic regression was performed to estimate NAFLD risk.ResultsWe identified four major nutrient patterns. The first nutrient pattern was high in consumption of lactose, animal protein, vitamin D, riboflavin, pantothenic acid, vitamin B12, calcium, phosphorus, zinc, and potassium. The second nutrient pattern included fiber, plant protein, vitamin A, thiamine, niacin, copper, and selenium, while the third featured plant protein, zinc, copper, magnesium, manganese, chromium, and selenium. The fourth was characterized by fructose, vitamin A, pyridoxine, vitamin C, and potassium. After adjusting for confounders, individuals in the highest tertile of NP4 had lower odds of NAFLD (OR: 0.56, 95% CI: 0.32–0.98, P_trend = 0.042); compared to those who were in the lowest tertile.ConclusionHigh compliance to a nutrient pattern characterized by fructose, vitamin C, vitamin A, pyridoxine, and potassium mainly supplied from fruits, vegetables, and nuts is inversely proportional to the odds of NAFLD. Also our findings indicate a very high fiber intake, a relatively optimal dietary fat profile, and a pretty low sugar intake for cases and controls, unseen in western countries. However, these initial findings need to be approved with further studies to confirm the relationship between nutrient patterns and NAFLD.