bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid Profile in Patients With Primary Ovarian Insufficiency: A Systematic Review and Meta-Analysis
Authors: Huang Ling , Wang Hanfeng , Shi Minglu , Kong Weizheng , Jiang Mei 
Published: June 2022

BackgroundsA large number of studies have investigated the effect of early menopause on cardiovascular disease (CVD) outcomes and the relationship between the levels of lipid profile and primary ovarian insufficiency (POI). However, the results are inconsistent. The aim of this meta-analysis was to assess whether the levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) changed in women with POI relative to healthy controls.MethodsTo identify eligible studies, references published prior to December 2021 were searched in the PubMed, Embase, Cochrane Library and Web of Science databases. DerSimonian-Laird random-effects model was used to estimate the overall standard mean difference (SMD) between POI and healthy control subjects. Subgroup analysis and sensitivity analysis were preformed, and publication bias was assessed.ResultsA total of 12 studies featuring 846 women with primary ovarian insufficiency and 959 healthy women were selected for analysis. The meta-analysis showed that the levels of TC (SMD: 0.60; 95% CI: 0.32 to 0.89; P&lt;0.0001), TG (SMD: 0.36; 95% CI: 0.12 to 0.60; P=0.003), LDL (SMD: 0.46; 95% CI: 0.16 to 0.76; P=0.003) were significantly increased in women with POI. There was no significant change in the level of HDL (SMD: 0.25; 95% CI: -0.12 to 0.61; P=0.19). Subgroup analysis showed that the heterogeneity in this meta-analysis of the correlation between lipid profile and POI might come from by region, sample size, number of cases, mean body mass index (BMI) value of cases and mean age of cases.ConclusionsScientific evidence suggests that the lipid profile levels were altered in patients with primary ovarian insufficiency compared to healthy controls. Therefore, we recommend that early medical intervention (e.g., hormone replacement therapy) to minimize the risk of CVD morbidity and mortality associated with dyslipidemia in patients with POI.Systematic Review RegistrationPROSPERO, identifier CRD42021297088
Characteristics of Gut Microbiome and Its Metabolites, Short-Chain Fatty Acids, in Children With Idiopathic Short Stature
Authors: Li Lin , Chen Lifen , Yang Yuanyan , Wang Junqi , Guo Li , An Jingjing , Ma Xiaoyu , Lu Wenli , Xiao Yuan , Wang Xinqiong , Dong Zhiya 
Published: June 2022

BackgroundThe gut microbiome is important for host nutrition and metabolism. Whether the gut microbiome under normal diet regulate human height remains to be addressed. Our study explored the possible relationship between gut microbiota, its metabolic products and the pathogenesis of idiopathic short stature disease (ISS) by comparing the gut microbiota between children with ISS and of normal height, and also the short-chain fatty acids (SCFAs) produced by the gut microbiota.MethodsThe subjects of this study were 32 prepubescent children aged 4-8 years. The fecal microbial structure of the subjects was analyzed by 16S rRNA high-throughput sequencing technology. The concentrations of SCFAs in feces were determined by gas chromatography-mass spectrometry.ResultsThe richness of gut microbiota in ISS group was decreased, and the composition of gut microbiota was significantly different between ISS group and control group. The relative abundance of nine species including family Ruminococcaceae and genera Faecalibacterium and Eubacterium, in ISS group was significantly lower than that in control group (P&lt;0.05). The relative abundance of 10 species, such as those belonging to genus Parabacteroides and genus Clostridium, in ISS group was significantly higher than that in control group (P&lt;0.05). The concentration of total SCFAs and butyrate in ISS group was significantly lower than that in control group. The correlation analysis among different species, clinical indicators, and SCFAs showed that the relative abundance of family Ruminococcaceae and genera Faecalibacterium and Eubacterium was positively correlated with the standard deviation score of height. Furthermore, the concentrations of total SCFAs and butyrate were positively correlated with serum insulin-like growth factor 1 (IGF-1)-SDS. Disease prediction model constructed based on the bacteria who abundance differed between healthy children and ISS children exhibited high diagnostic value (AUC: 0.88).ConclusionsThe composition of gut microbiota and the change in its metabolite levels may be related to ISS pathogenesis. Strains with increased or decreased specificity could be used as biomarkers to diagnose ISS.
Follicular-Phase GnRH Agonist Protocol Is Another Choice for Polycystic Ovary Syndrome Patients With Lower LH/FSH and Lower AMH Levels Without Increasing Severe OHSS Risk
Authors: Gao Rui , Liao Xin , Huang Wanrong , Zeng Rujun , Qin Lang , Bai Peng 
Published: June 2022

PurposeTo explore another choice for a controlled ovarian stimulation (COS) protocol that does not increase severe ovarian hyperstimulation syndrome (OHSS) risk among polycystic ovarian syndrome (PCOS) patients with specific clinical features.MethodsA retrospective study was performed. Two hundred and fifty-nine participants were divided into two groups, group 1 (fixed GnRH antagonist protocol, n = 295) and group 2 (follicular-phase GnRH agonist protocol, n = 69) according to COS protocols. The basic characteristics and laboratory indicators between these two groups were compared. The severe OHSS rate and clinical pregnancy rate were selected as indicators to evaluate the risks and benefits of the two COS protocols. Subgroup analyses for the severe OHSS rate and clinical pregnancy rate were performed based on baseline luteinizing hormone/follicle-stimulating hormone (bLH/FSH) and anti-Mullerian hormone (AMH) levels.ResultsThe severe OHSS rate was statistically higher in group 2 than in group 1 (11.6% vs. 3.7%, p = 0.008), but the biochemical pregnancy rate and clinical pregnancy rate showed no statistical difference between the groups (71.9% vs. 60.3% and 62.5% vs. 54.3%). In the higher bLH/FSH subgroup (≥1.33) and the higher serum AMH level subgroup (&gt;3.4 ng/ml), severe OHSS incidence was statistically higher in group 2 compared to group 1, but this incidence was lower in the bLH/FSH subgroup (&lt;1.33) and the subgroup with lower serum AMH levels (≤3.4 ng/ml); a difference in severe OHSS risk was not observed. There was no statistical difference between the two groups regarding clinical pregnancy rate in any subgroup.ConclusionThe limited evidence from this study indicates that in PCOS patients with lower bLH/FSH levels (&lt;1.33) and lower serum AMH levels (≤3.4 ng/ml), a follicular-phase GnRH agonist protocol may be another choice that does not increase the risk of severe OHSS.
Aberrant IL-17 Levels in Rodent Models of Autism Spectrum Disorder: A Systematic Review
Authors: Thawley Alexandra Jade , Veneziani Luciana Peixoto , Rabelo-da-Ponte Francisco Diego , Riederer Ingo , Mendes-da-Cruz Daniella Areas , Bambini-Junior Victorio 
Published: June 2022

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterised by stereotyped behaviours, specific interests, and impaired communication skills. Elevated levels of pro-inflammatory cytokines, such as interleukin-17A (IL-17A or IL-17), have been implicated as part of immune alterations that may contribute to this outcome. In this context, rodent models have helped elucidate the role of T-cell activation and IL-17 secretion in the pathogenesis of ASD. Regarding the preclinical findings, the data available is contradictory in offspring but not in the pregnant dams, pointing to IL-17 as one of the main drivers of altered behaviour in some models ASD, whilst there are no alterations described in IL-17 levels in others. To address this gap in the literature, a systematic review of altered IL-17 levels in rodent models of ASD was conducted. In total, 28 studies that explored IL-17 levels were included and observed that this cytokine was generally increased among the different models of ASD. The data compiled in this review can help the choice of animal models to study the role of cytokines in the development of ASD, seeking a parallel with immune alterations observed in individuals with this condition.Systematic Review RegistrationPROSPERO, identifier CRD42022306558.
Effect of the Combination of Everolimus and Mesenchymal Stromal Cells on Regulatory T Cells Levels and in a Liver Transplant Rejection Model in Rats
Authors: Vandermeulen Morgan , Erpicum Pauline , Bletard Noella , Poma Laurence , Jouret François , Detry Olivier 
Published: June 2022

IntroductionMesenchymal stromal cells (MSCs) have particular properties that are of interest in organ transplantation, including the expansion of regulatory T cells (Tregs), a key factor in transplant tolerance induction. However, the most effective immunosuppressive drug to associate with MSCs has yet to be defined. Additionally, the impact of the association of everolimus with MSCs on Treg expansion, and on the induction of liver graft tolerance, has never been studied. The aim of this study was to evaluate the effects of MSCs in combination, or not, with everolimus on Treg expansion and in a model of rejection after liver transplantation (LT) in the rat.MethodsFirstly, 24 Lewis rats were assigned to 4 groups (n=6 in each group) receiving intravenous MSCs or saline injection at day (D)9 with/without subcutaneous everolimus from D0 to D14. Analysis of circulating Tregs was performed at D0, D14 and D28. In a second set of experiment, 30 Lewis rats were randomized in 3 groups 48hours after LT with a Dark Agouti rat liver: everolimus (subcutaneous for 14 days), MSCs (intravenous injection at post-operative day 2 and 9), or both everolimus and MSCs. Rejection of the liver graft was assessed by liver tests, histology and survival.ResultsIndividually, MSC infusion and everolimus promoted Treg expansion in rats, and everolimus had no negative impact on Treg expansion in combination with MSCs. However, in the LT model, injections of MSCs two and nine days following LT were not effective at preventing acute rejection, and the combination of MSCs with everolimus failed to show any synergistic effect when compared to everolimus alone.ConclusionEverolimus may be used in association with MSCs. However, in our model of LT in the rat, post-transplant MSC injections did not prevent acute rejection, and the association of MSCs with everolimus did not show any synergistic effect.
Case Report: Dual Inhibition of HDAC and BTK for Diffuse Large B-Cell Lymphoma After Failure to CD19-Targeted CAR-T Therapy
Authors: Zhu Weiguo , Tao Shi , Miao Wenchun , Liu Hui , Yuan Xianggui 
Published: June 2022

BackgroundFailure to CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), is an emerging clinical problem. There is no consensus on the treatment for these patients and treatment remains empirical.Case ReportWe reported a case of an elderly R/R DLBCL patient who had TP53 mutation and relapsed 12 months after initial response to CAR T-cell therapy. The patient did not respond to salvage chemotherapy with the GDP regimen and could not tolerate any aggressive chemotherapy. Thereafter, the patient was given chidamide and zanubrutinib. After two months of treatment, the patient achieved sustained complete remission. At the last follow-up, the patient remains in radiographic CR 22 months after CAR-T infusion and 10 months after the initiation of the combination treatment.ConclusionWe report the first successful case of dual inhibition of HDAC and BTK for the treatment of R/R DLBCL after failure to CAR-T cell therapy, which opens a new therapeutic possibility for the future.
Comprehensive Analysis and Reinforcement Learning of Hypoxic Genes Based on Four Machine Learning Algorithms for Estimating the Immune Landscape, Clinical Outcomes, and Therapeutic Implications in Patients With Lung Adenocarcinoma
Authors: Sun Zhaoyang , Zeng Yu , Yuan Ting , Chen Xiaoying , Wang Hua , Ma Xiaowei 
Published: June 2022

BackgroundPatients with lung adenocarcinoma (LUAD) exhibit significant heterogeneity in therapeutic responses and overall survival (OS). In recent years, accumulating research has uncovered the critical roles of hypoxia in a variety of solid tumors, but its role in LUAD is not currently fully elucidated. This study aims to discover novel insights into the mechanistic and therapeutic implications of the hypoxia genes in LUAD cancers by exploring the potential association between hypoxia and LUAD.MethodsFour machine learning approaches were implemented to screen out potential hypoxia-related genes for the prognosis of LUAD based on gene expression profile of LUAD samples obtained from The Cancer Genome Atlas (TCGA), then validated by six cohorts of validation datasets. The risk score derived from the hypoxia-related genes was proven to be an independent factor by using the univariate and multivariate Cox regression analyses and Kaplan–Meier survival analyses. Hypoxia-related mechanisms based on tumor mutational burden (TMB), the immune activity, and therapeutic value were also performed to adequately dig deeper into the clinical value of hypoxia-related genes. Finally, the expression level of hypoxia genes was validated at protein level and clinical samples from LUAD patients at transcript levels.ResultsAll patients in TCGA and GEO-LUAD group were distinctly stratified into low- and high-risk groups based on the risk score. Survival analyses demonstrated that our risk score could serve as a powerful and independent risk factor for OS, and the nomogram also exhibited high accuracy. LUAD patients in high-risk group presented worse OS, lower TMB, and lower immune activity. We found that the model is highly sensitive to immune features. Moreover, we revealed that the hypoxia-related genes had potential therapeutic value for LUAD patients based on the drug sensitivity and chemotherapeutic response prediction. The protein and gene expression levels of 10 selected hypoxia gene also showed significant difference between LUAD tumors tissues and normal tissues. The validation experiment showed that the gene transcript levels of most of their genes were consistent with the levels of their translated proteins.ConclusionsOur study might contribute to the optimization of risk stratification for survival and personalized management of LUAD patients by using the hypoxia genes, which will provide a valuable resource that will guide both mechanistic and therapeutic implications of the hypoxia genes in LUAD cancers.
Causal Association Between Inflammatory Bowel Disease and Psoriasis: A Two-Sample Bidirectional Mendelian Randomization Study
Authors: Li Yajia , Guo Jia , Cao Ziqin , Wu Jianhuang 
Published: June 2022

BackgroundPrevious observational studies have found an association between inflammatory bowel disease (IBD) and psoriasis. Using the mendelian randomization (MR) approach, we aim to determine whether there was a causal association between IBD and psoriasis.MethodsWe performed a two-sample MR with the genetic instruments identified for IBD and its main subtypes, Crohn’s disease (CD) and ulcerative colitis (UC), from a genome-wide association study (GWAS) involving 25,042 cases with an IBD diagnosis and 34,915 controls. Summarized data for psoriasis were obtained from different GWAS studies which included 4510 cases and 212,242 controls without psoriasis. Causal estimates are presented as odds ratios (ORs) with 95% confidence intervals (CIs).ResultsThe overall outcome of MR analysis was to demonstrate that genetic predisposition to IBD was associated with an increased risk of psoriasis (OR: 1.1271; 95% CI: 1.0708 to 1.1864). Psoriatic arthritis (PsA) had a significant association with total IBD (OR: 1.1202; 95% CI: 1.0491 to 1.1961). Casual relationship was also identified for CD-psoriasis (OR: 1.1552; 95% CI: 1.0955 to 1.2182) and CD-PsA (OR: 1.1407; 95% CI: 1.0535 to 1.2350). The bidirectional analysis did not demonstrate that a genetic predisposition to psoriasis was associated with total IBD, although psoriasis showed association with CD (OR: 1.2224; 95% CI: 1.1710 to 1.2760) but not with UC. A genetic predisposition to PsA had a borderline association with IBD (OR: 1.0716; 95% CI: 1.0292 to 1.1157) and a suggestive association with CD (OR: 1.0667; 95% CI: 1.0194 to 1.1162).ConclusionThere appears to be a causal relationship between IBD and psoriasis, especially for PsA, but for psoriasis and IBD, only total psoriasis and PsA were associated with CD. Understanding that specific types of psoriasis and IBD constitute mutual risk factors facilitates the clinical management of two diseases.
Polymyxin B/Tigecycline Combination vs. Polymyxin B or Tigecycline Alone for the Treatment of Hospital-Acquired Pneumonia Caused by Carbapenem-Resistant Enterobacteriaceae or Carbapenem-Resistant Acinetobacter baumannii
Authors: Chang Kang , Wang Haibo , Zhao Jianping , Yang Xianghong , Wu Bo , Sun Wenkui , Huang Man , Cheng Zhenshun , Chen Hong , Song Yuanlin , Chen Ping , Chen Xiangqi , Gan Xin , Ma Wanli , Xing Lihua , Wang Yimin , Gu Xiaoying , Zou Xiaohui , Cao Bin 
Published: June 2022

IntroductionIt is not clear whether polymyxin B/tigecycline (PMB/TGC) combination is better than PMB or TGC alone in the treatment of hospital-acquired pneumonia (HAP) caused by carbapenem-resistant organisms (CROs).MethodsWe conducted a multicenter, retrospective cohort study in patients with HAP caused by CROs. The primary outcome was 28-day mortality, and the secondary outcomes included clinical success and the incidence of acute kidney injury (AKI). Multivariate Cox regression analysis was performed to examine the relationship between antimicrobial treatments and 28-day mortality by adjusting other potential confounding factors.ResultsA total of 364 eligible patients were included in the final analysis, i.e., 99 in the PMB group, 173 in the TGC group, and 92 in the PMB/TGC combination group. The 28-day mortality rate was 28.3% (28/99) in the PMB group, 39.3% (68/173) in the TGC group, and 48.9% (45/92) in the PMB/TGC combination group (p= 0.014). The multivariate Cox regression model showed that there was a statistically significant lower risk of 28-day mortality among participants in the PMB group when compared with the PMB/TGC combination group [hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31–0.81,p= 0.004] and that participants in the TGC group had a lower risk of 28-day mortality than in the PMB/TGC combination group but without statistical significance. The incidence of AKI in the PMB group (52.5%) and the PMB/TGC combination group (53.3%) was significantly higher than that in the TGC group (33.5%,p= 0.001).ConclusionThe appropriate PMB/TGC combination was not superior to appropriate PMB therapy in the treatment of HAP caused by carbapenem-resistantEnterobacteriaceae/carbapenem-resistantAcinetobacter baumannii(CRE/CRAB) in terms of 28-day mortality.
Classification-Based Approaches to Myopia Control in a Taiwanese Cohort
Authors: Hsieh Meng-Wei , Chang Hsu-Chieh , Chen Yi-Hao , Chien Ke-Hung 
Published: June 2022

PurposeMyopia is a disorder of growing prevalence in school-aged children worldwide, especially in Asia. Although low-dose atropine is recognized as an effective treatment to slow myopia progression, different studies have reported varying efficacies of treatment, and the optimal concentration of low-dose atropine remains an open question.MethodsA two-stage approach was conducted in this study. First, an observational study was conducted to plot the axial length growth curve for Taiwanese children. Second, an interventional 2-year study was performed in which different concentrations of low-dose atropine were applied based upon the risk-level status from the first stage.ResultsA total of 4,091 subjects, consisting of 2,105 boys (51.5%) and 1,986 girls (48.5%), were enrolled in the first stage to plot the axial growth curve for Taiwanese children aged between 3 and 16 years. The percentage of children with myopia increased from 2.3% in 4-year-olds to 88.0% in 16-year-olds. At the second stage, a total of 886 subjects [307 (34.65%) at low risk, 358 (40.41%) at moderate risk and 221 (24.94%) at high risk] were enrolled to receive low-dose atropine based upon the risk level (0.02, 0.03, and 0.05%, respectively). With this approach, the mean annual myopia progression was −0.33, −0.57, and −0.82 D in the low-risk, moderate-risk and high-risk groups, respectively. Applying annual myopic progression &lt; -1.0 D as a criterion for responder, the responder rates were 95.77, 83.52, and 70.59% in the low-risk, moderate-risk, and high-risk groups, respectively.ConclusionsWe proposed a classification-based approach involving different concentrations of low-dose atropine based upon an individual's risk-level status. With this approach, myopic progression can be effectively controlled in patients without exposure to atropine side effects due to exposure to a higher dose than actually needed.
Operationalization of the Clinical Frailty Scale in Korean Community-Dwelling Older People
Authors: Jung Hee-Won , Baek Ji Yeon , Jang Il-Young , Lee Eunju 
Published: June 2022

BackgroundThe Clinical Frailty Scale (CFS) is a simple measure of global fitness validated in various populations in real-world settings. In this study, we aimed to assess the characteristics and validities of the CFS in community-dwelling older people in Korea, with the original classification tree (oCFS) and a culturally modified tree (mCFS).MethodsThe comprehensive geriatric assessment records of 1,064 individuals of the Aging Study of the Pyeongchang Rural Area were used for this study. For mCFS, we considered the dependency of the food preparations and household chores not to be deficits in the male population. The frailty index was used as a reference for construct validity. We used a composite outcome of death and institutionalization for outcome validity.ResultsThe correlation coefficients with frailty index were higher in mCFS (.535) than in oCFS (.468). The mean frailty index was lower in individuals reclassified by mCFS (5 to 4) than people who stayed in mCFS 5. The classification coefficient of mCFS was significantly higher than that of oCFS (p &lt;0.001) in determining people with frailty (frailty index.25 or higher). Trends of a higher incidence of the composite outcome were observed in both higher oCFS and mCFS, in which oCFS and mCFS did not differ significantly in predicting the risk of the outcome.ConclusionThe classification tree of CFS could be culturally adopted in a community-dwelling population of Korea and considered valid in detecting the vulnerable population.