bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Fiber Diet or Combined With Acarbose Alleviates Heterogeneous Phenotypes of Polycystic Ovary Syndrome by Regulating Gut Microbiota
Authors: Wang Xuejiao , Xu Ting , Liu Rui , Wu Guojun , Gu Liping , Zhang Yahui , Zhang Feng , Fu Huaqing , Ling Yunxia , Wei Xiaohui , Luo Yunchen , Shen Jian , Zhao Liping , Peng Yongde , Zhang Chenhong , Ding Xiaoying 
Published: February 2022

ObjectiveGut microbial dysbiosis is associated with high heterogeneity of polycystic ovary syndrome (PCOS); however, studies about gut microbiota targeted clinical intervention in PCOS are limited. Our study aimed to evaluate the effects of high-fiber diet or combined with acarbose on the clinical phenotypes of PCOS, focusing on the possible influence of gut microbiota in this process.MethodsTwenty-five patients with PCOS were recruited and randomly divided into two groups, W group (n = 14) received the WTP diet (a high-fiber diet composed of whole grains, traditional Chinese medicinal foods, and prebiotics), and A group (n = 11) received the WTP diet combined with acarbose. The follow-up time was 12 weeks. The sex hormonal and glycolipid metabolic parameters, inflammatory factors, brain–gut peptides, and alteration of gut microbiota were evaluated.ResultsThe PCOS clinical phenotypes, inflammatory state, and brain–gut peptides secretion were all alleviated in both groups, while the hyperandrogenism, insulin resistance, and brain–gut peptides secretion were better improved in the A group. Alpha and beta diversities were altered more significantly in the A group. Amplicon sequence variants (ASVs) were clustered into 14 co-abundant groups (CAGs) as potential functional groups that may respond to the intervention. The CAGs predominantly comprised of Bifidobacterium and Lactobacillus were more enriched, while the CAGs predominantly comprised of Bacteroides vulgatus, Alistipes, Blautia, Lachnospira, and Roseburia were more inhibited in the A group than in W group. Moreover, the CAGs enriched in the A group had a stronger negative correlation with the luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, testosterone, homeostasis model assessment-insulin resistance (HOMA-IR), α-1-acid glycoprotein (α-AGP), and leptin, and positive correlation with adiponectin and spexin, while the CAGs inhibited showed an opposite trend.ConclusionsHigh-fiber diet could alleviate the chronic metabolic inflammation, reproductive function, and brain–gut peptides secretion of patients with PCOS, and high-fiber diet combined with acarbose could better improve the PCOS clinical phenotypes. The remodeling of gut microbiota by our intervention may play an important role in these improvements.Clinical Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=4500, ChiCTR-TRC-14005075
Elevated Glycated Hemoglobin Levels Are Associated With Poor Outcome in Acute Ischemic Stroke
Authors: Dong Nan , Shen Xiaozhu , Wu Xuan , Guo Xianghong , Fang Qi 
Published: February 2022

ObjectiveAdmission hyperglycemia is an established risk factor for functional outcome in patients with acute ischemic stroke. However, the association between glycated hemoglobin (HbA1c) and prognosis in patients with acute anterior circulation ischemic stroke (AACIS) remains controversial. This study aimed to explore whether elevated HbA1c levels are associated with functional outcome in AACIS patients.Participants and MethodsWe enrolled patients with AACIS hospitalized in the First Hospital Affiliated to Soochow University from March 2018 to January 2021. Patients were categorized into three groups based on baseline HbA1c: HbA1c ≤ 6.5%, 6.5% &lt; HbA1c ≤ 8.0%, and HbA1c &gt; 8.0%. Ninety-day modified Rankin Scale scores of 0–1 and 0–2 were defined as excellent and favorable functional outcome, respectively. Early neurological improvement was regarded as a reduction in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points compared with that on admission, or an NIHSS score of 0–1 at discharge. The association between HbA1c and clinical outcome in acute ischemic patients was assessed by logistic regression and adjusted for confounding factors. Subgroup analyses by TOAST classification were also conducted.ResultsThe study included 326 patients. The proportion with favorable outcome was significantly lower in the HbA1c &gt; 8.0% group than the HbA1c ≤ 6.5% group (30.4 vs. 55.2%; p &lt; 0.01). Binary logistic regression analysis demonstrated that increasing HbA1c levels (as a continuous variable) were associated with reduced functional independence (adjusted OR = 0.739; 95% CI: 0.605–0.904; p = 0.003). In subgroup analyses, higher HbA1c was also associated with favorable outcome in large-artery atherosclerosis (LAA)-type patients (adjusted OR = 0.776; 95% CI: 0.614–0.981; p = 0.034), but not in LAA group.ConclusionsHbA1c level was an independent predictor of worse functional outcome in patients with AACIS, particularly in those with LAA. For patients with anterior circulation atherosclerosis, strict adherence to a target HbA1c &lt; 6.5% may be required.
Physician-Confirmed and Administrative Definitions of Stroke in UK Biobank Reflect the Same Underlying Genetic Trait
Authors: Rannikmäe Kristiina , Rawlik Konrad , Ferguson Amy C. , Avramidis Nikos , Jiang Muchen , Pirastu Nicola , Shen Xia , Davidson Emma , Woodfield Rebecca , Malik Rainer , Dichgans Martin , Tenesa Albert , Sudlow Cathie 
Published: February 2022

BackgroundStroke in UK Biobank (UKB) is ascertained via linkages to coded administrative datasets and self-report. We studied the accuracy of these codes using genetic validation.MethodsWe compiled stroke-specific and broad cerebrovascular disease (CVD) code lists (Read V2/V3, ICD-9/-10) for medical settings (hospital, death record, primary care) and self-report. Among 408,210 UKB participants, we identified all with a relevant code, creating 12 stroke definitions based on the code type and source. We performed genome-wide association studies (GWASs) for each definition, comparing summary results against the largest published stroke GWAS (MEGASTROKE), assessing genetic correlations, and replicating 32 stroke-associated loci.ResultsThe stroke case numbers identified varied widely from 3,976 (primary care stroke-specific codes) to 19,449 (all codes, all sources). All 12 UKB stroke definitions were significantly correlated with the MEGASTROKE summary GWAS results (rg.81-1) and each other (rg.4-1). However, Bonferroni-corrected confidence intervals were wide, suggesting limited precision of some results. Six previously reported stroke-associated loci were replicated using ≥1 UKB stroke definition.ConclusionsStroke case numbers in UKB depend on the code source and type used, with a 5-fold difference in the maximum case-sample size. All stroke definitions are significantly genetically correlated with the largest stroke GWAS to date.
Adjuvant Chemotherapy Might Be Recommended to Patients With Positive Margin After Gastrectomy: A 20-Year Retrospective Analysis in a Single Center
Authors: Zhang Xiaojie , Zhao Lulu , Niu Penghui , Wang Tongbo , Wang Wanqing , Sun Chongyuan , Li Zefeng , Chen Yingtai , Zhao Dongbing 
Published: February 2022

BackgroundMargin positivity after gastric cancer resection is associated with poorer outcomes. However, the prognostic factors and the choice of postoperative adjuvant treatment of patients with positive margin (PM) after gastrectomy are still being debated.MethodsA single-center, retrospective analysis was conducted for patients with PM after gastrectomy from the China National Cancer Center Gastric Cancer Database (NCCGCDB) from 1998 to 2018. Univariate and multivariate Cox regression analyses were performed to identify prognostic factors of overall survival (OS) and recurrence-free survival (RFS).ResultsA total of 449 patients were included in the study, including 192 (42.8%) in the proximal PM group (PPM), 205 (45.7%) in the distal PM group (DPM), and 52 (11.6%) in the bilateral PM group (BPM). The 3- and 5-year OS rates for the PM patients investigated were 47.5% and 39.3%, respectively, and the 3- and 5-year RFS rates were 60.0% and 53.6%, respectively. Multivariate Cox regression analysis proved total gastrectomy (hazard ratio (HR): 1.783, 95%CI: 1.133–2.805, p = 0.012), pT4 (HR: 5.264, 95%CI: 1.493–18.565, p = 0.01), pN2 (HR: 2.263, 95%CI: 1.164–4.397, p = 0.016), pN3 (HR: 2.327, 95%CI: 1.233–4.393, p = 0.009), and combined resection (HR: 1.952, 95%CI: 1.256–3.034, p = 0.003) to be independent risk factors of OS, and pT3 (HR: 9.257, 95%CI: 1.152–74.386, p = 0.036) and pT4 (HR: 11.361, 95%CI: 1.469–87.847, p = 0.020) to be independent risk factors for RFS. Adjuvant chemotherapy prolonged OS in the PPM group (p = 0.032) and prolonged RFS in the PPM group (p &lt; 0.001) and the DPM group (p = 0.035) compared with surgery alone.ConclusionsAdvanced pathologic stage was associated with poor prognosis, and postoperative adjuvant chemotherapy might be recommended in PM patients after gastrectomy. Still, further prospective trials are warranted to verify and support our conclusions.
YTHDF2 Inhibits the Migration and Invasion of Lung Adenocarcinoma by Negatively Regulating the FAM83D-TGFβ1-SMAD2/3 Pathway
Authors: Zhao Teng , Wang Mingchao , Zhao Xin , Weng Shuang , Qian Kun , Shi Kejian , Gu Yanfei , Ying Wantao , Qian Xiaohong , Zhang Yi 
Published: February 2022

ObjectiveYTH domain family 2 (YTHDF2) is an important N6-methyladenosine (m6A) reader, but its role in lung adenocarcinoma remains elusive. This study assessed its function in lung adenocarcinoma.MethodsYTHDF2 expression in lung adenocarcinoma was explored using public databases, such as The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumour Analysis Consortium (CPTAC). The effect of YTHDF2 on a lung adenocarcinoma cell line was explored by performing cytological and molecular experiments. Molecules downstream of YTHDF2 were identified using proteomics, and the related pathways were verified through cytological and molecular biology experiments.ResultsYTHDF2 expression was upregulated in lung adenocarcinoma, and patients with high YTHDF2 expression experienced prolonged overall survival. In two lung cancer cell lines, YTHDF2 knockdown inhibited proliferation but promoted migration, invasion, and the epithelial-mesenchymal transition. The proteomic analysis identified 142 molecules downstream of YTHDF2, and 11 were closely related to survival. Further experiments revealed that YTHDF2 inhibited expression of the family with sequence similarity 83D (FAM83D)-TGFβ1-SMAD2/3 pathway components. This study is the first to show that YTHDF2 regulated the downstream TGFβ1-SMAD2/3 pathway through FAM83D in lung adenocarcinoma.ConclusionYTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-TGFβ1-pSMAD2/3 pathway, which may play an important role in lung cancer metastasis.
Multi-Center Analysis of Predictive Factors of Enteral Autonomy and Risk Factors of Complications of Pediatric Intestinal Failure in China
Authors: Jiang Weiwei , Chen Guanglin , Wang Ying , Zhong Wei , Zhou Chonggao , Zhang Jie , Lv Xiaofeng , Du Chunxia , Zhu Zhongxian , Geng Qiming , Tang Weibing 
Published: February 2022

ObjectivesThe aim of this study was to identify predictors for enteral autonomy and intestinal failure (IF)-related complications and evaluate the outcomes of a multi-center pediatric cohort in China.MethodsThe medical records of pediatric patients with IF treated at four medical centers in China from January 1, 2012 to November 31, 2020 were retrospectively reviewed. Enteral autonomy was defined as sustained growth and cessation of parenteral nutrition for &gt;90 days. Multivariate logistic regression analysis was used to identify factors predictive of enteral autonomy and the risk factors of complications, such as IF-associated liver disease (IFALD) and catheter-related bloodstream infection (CRBSI).ResultsThe study cohort of 92 pediatric patients with IF included 71 (77%) who underwent surgery and 21 (23%) who received non-surgical treatment. Eventually, 63 (68.5%) patients achieved enteral autonomy by the end of the follow-up period. Multivariate logistic regression analysis indicated that longer duration of parenteral nutrition (PN), sepsis, and non-breastfeeding were risk factors for enteral autonomy. When considering the detailed intraoperative data, the presence of an ileocecal valve (ICV) and greater residual small bowel (RSB) length were reaffirmed as predictors of achieving enteral autonomy. Medium/long-chain (MCT/LCT) lipids or sepsis were identified as negative predictors for IFALD. Univariate analysis revealed that the use of MCT/LCT lipids was associated with a greater likelihood of CRBSI.ConclusionIn this cohort, enteral autonomy was achieved at a percentage of 68.5%, and the risk factors for not achieving enteral autonomy were a longer duration of PN, sepsis, and non-breastfeeding. The presence of an ICV and a greater RSB length were important predictors of achieving enteral autonomy.
Adverse Drug Reactions in Pediatric Oncohematology: A Systematic Review
Authors: Amaro-Hosey Kristopher , Danés Immaculada , Agustí Antònia 
Published: February 2022

Introduction: Adverse drug reactions (ADR) are an important cause of morbidity and mortality in pediatric patients. Due to the disease severity and chemotherapy safety profile, oncologic patients are at higher risk of ADR. However, there is little evidence on pharmacovigilance studies evaluating drug safety in this specific population.Methods: In order to assess the incidence and characteristics of ADR in pediatric patients with oncohematogical diseases and the methodology used in the studies, a systematic review was carried out using both free search and a combination of MeSH terms. Data extraction and critical appraisal were performed independently using a predefined form.Results: Fourteen studies were included, of which eight were prospective and half focused in inpatients. Sample size and study duration varied widely. Different methods of ADR identification were detected, used alone or combined. Causality and severity were assessed frequently, whereas preventability was lacking in most studies. ADR incidence varied between 14.4 and 67% in inpatients, and 19.6–68.1% in admissions, mainly in the form of hematological, gastrointestinal and skin toxicity. Between 11 and 16.4% ADR were considered severe, and preventability ranged from 0 to 74.5%.Conclusion: ADR in oncohematology pediatric patients are frequent. A high variability in study design and results has been found. The use of methodological standards and preventability assessment should be reinforced in order to allow results comparison between studies and centers, and to detected areas of improvement.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=96513, identifier CRD42018096513.
Network Pharmacology-Based and Experimental Identification of the Effects of Paeoniflorin on Major Depressive Disorder
Authors: Zhang Sha , Jiang Mingchen , Yan Shuxia , Liang Miaomiao , Wang Wei , Yuan Bin , Xu Qiuyue 
Published: February 2022

Objective: Major depressive disorder (MDD) is one of the most common psychiatric disorders, the diagnosis and treatment of MDD are major clinical issues. However, there is a lack of effective biomarkers and drugs diagnosis and therapeutics of MDD. In the present study, bioinformatics analysis combined with an experimental verification strategy was used to identify biomarkers and paeoniflorin targets for MDD diagnosis and treatment.Methods: Based on network pharmacology, we obtained potential targets and pathways of paeoniflorin as an antidepressant through multiple databases. We then constructed a protein-protein interaction network and performed enrichment analyses. According to the results, we performed in vivo and in vitro experimental validation.Results: The results showed that paeoniflorin may exert an antidepressant effect by regulating cell inflammation, synaptic function, NF-κB signaling pathway, and intestinal inflammation.Conclusion: NPM1, HSPA8, HSPA5, HNRNPU, and TNF are the targets of paeoniflorin treatment. In addition, we demonstrated that paeoniflorin inhibits inflammatory cytokine production via the p38MAPK/NF-κB pathway and has neuroprotective effects on the synaptic structure. Our findings provide valuable evidence for the diagnosis and treatment of MDD.
The Association Between Physical Activity and Insulin Level Under Different Levels of Lipid Indices and Serum Uric Acid
Authors: Lin Yajuan , Fan Rui , Hao Zhujing , Li Jiatian , Yang Xiaolei , Zhang Ying , Xia Yunlong 
Published: February 2022

ObjectivesInsulin resistance (IR) has been shown to play important role in the pathogenesis of type 2 diabetes mellitus (T2DM). There is an intricate interplay between IR, dyslipidemia, and serum uric acid (SUA) in people with and without diabetes. Physical activity has a positive impact on insulin sensitivity in insulin-resistant populations. However, the effect of different intensities of physical activity on insulin levels under different lipid indices and SUA levels is unclear.MethodsTo explore the association between physical activity and insulin, we enrolled 12,982 participants aged above 18 years from the National Health and Nutrition Examination Survey (NHANES) conducted between 2009 and 2018. Next, we conducted multivariate logistic regression analyses, generated fitted smoothing curves, and visualized the data using generalized additive models.ResultsIncreased intensities of physical activity can significantly reduce insulin levels. The association between physical activity and insulin persisted even after adjusting for confounding factors, with β value (95% CI) = −17.10 (−21.64, −12.56) in moderate group, β value (95% CI) = −28.60 (−33.08, −24.11) in high group, respectively. High-intensity physical activity significantly lowered insulin levels in the lower and higher SUA tertiles, and three tertiles of LDL-c, HDL-c, and TG. Moreover, the link between physical activity and insulin was stronger in male individuals.ConclusionThis study shows that physical activity can significantly lower insulin levels, and high-intensity physical activity still has additional potential benefits for insulin levels, even in the condition of dyslipidemia and hyperuricemia.
The Effect of Hyperoxia on Central and Peripheral Factors of Arm Flexor Muscles Fatigue Following Maximal Ergometer Rowing in Men
Authors: Volianitis Stefanos , Rasmussen Peter , Petersen Nicolas C. , Secher Niels H. 
Published: February 2022

PurposeThis study evaluates the effect of hyperoxia on cerebral oxygenation and neuromuscular fatigue mechanisms of the elbow flexor muscles following ergometer rowing.MethodsIn 11 competitive male rowers (age, 30 ± 4 years), we measured near-infrared spectroscopy determined frontal lobe oxygenation (ScO2) and transcranial Doppler ultrasound determined middle cerebral artery mean flow velocity (MCA Vmean) combined with maximal voluntary force (MVC), peak resting twitch force (Ptw) and cortical voluntary activation (VATMS) of the elbow flexor muscles using electrical motor point and magnetic motor cortex stimulation, respectively, before, during, and immediately after 2,000 m all-out effort on rowing ergometer with normoxia and hyperoxia (30% O2).ResultsArterial hemoglobin O2 saturation was reduced to 92.5 ± 0.2% during exercise with normoxia but maintained at 98.9 ± 0.2% with hyperoxia. The MCA Vmean increased by 38% (p &lt; 0.05) with hyperoxia, while only marginally increased with normoxia. Similarly, ScO2 was not affected with hyperoxia but decreased by 7.0 ± 4.8% from rest (p = 0.04) with normoxia. The MVC and Ptw were reduced (7 ± 3% and 31 ± 9%, respectively, p = 0.014), while VATMS was not affected by the rowing effort in normoxia. With hyperoxia, the deficit in MVC and Ptw was attenuated, while VATMS was unchanged.ConclusionThese data indicate that even though hyperoxia restores frontal lobe oxygenation the resultant attenuation of arm muscle fatigue following maximal rowing is peripherally rather than centrally mediated.
Childhood Abuse, Social Support, and Long-Term Pharmacological Treatment Outcomes in Patients With Depressive Disorders
Authors: Lee Ju-Yeon , Stewart Robert , Kang Hee-Ju , Kim Ju-Wan , Jhon Min , Kim Sung-Wan , Shin Il-Seon , Kim Jae-Min 
Published: February 2022

ObjectivesThis study was performed to investigate the roles of childhood abuse and social support in predicting short- and long-term pharmacological treatment outcomes in outpatients with depressive disorders in a naturalistic 1-year prospective design.MethodsPatients were recruited at a university hospital in South Korea between March 2012 and April 2017. Subjects with stepwise pharmacotherapy (switching, augmentation, combination, and mixture of these approaches) included 1246 patients at 12-week points in the acute treatment response and 1,015 patients at 12-months in the long-term treatment response. Remission was defined as Hamilton Depression Rating Scale score ≤ 7. Exposure to three types of childhood abuse (physical, emotional, and sexual) before the age of 16 and perceived social support were assessed at baseline.ResultsIndividual associations of childhood abuse were associated with poorer treatment outcomes in the 12-month long-term phase, and no significant individual associations were found for social support level with any period outcome. In combination, any child abuse, emotional abuse, and physical abuse were significantly associated with long-term 12-month remission rate in the presence of higher level of social support after adjustment with significant interaction terms. However, no significant interactions were found with sexual abuse.ConclusionSynergistic interactive effects of child abuse and social support levels on treatment outcomes in depressive patients were found during long-term pharmacotherapy. Thus, depressed patients with a history of childhood abuse may require specialized clinical approaches, including social support, to enhance the long-term treatment outcomes.