bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDK5 Regulatory Subunit-Associated Protein 1-Like 1 Gene Polymorphisms and Gestational Diabetes Mellitus Risk: A Trial Sequential Meta-Analysis of 13,306 Subjects
Authors: Yu Xiang-yuan , Song Li-ping , Wei Shu-dan , Wen Xiao-lan , Liu Da-bin 
Published: October 2021

ObjectivesThe CDK5 regulatory subunit-associated protein 1-like 1 (CDKAL1) contributes to islet β-cell function and insulin secretion by inhibiting the activation of CDK5. The current studies on the relationship between CDKAL1 polymorphisms rs7756992 A&gt;G and rs7754840 C&gt;G and the risk of gestational diabetes mellitus (GDM) have drawn contradictory conclusions.Materials and MethodsA meta-analysis with a fixed- or random-effects model was conducted to estimate the correlation between studied CDKAL1 polymorphisms and GDM risk with the summary odds ratio (OR) and 95% confidence interval (CI). In addition, trial sequential analysis (TSA) and false-positive report probability (FPRP) analysis were performed to confirm the study findings.ResultsA total of 13,306 subjects were included in the present study. Meta-analysis results showed that the variant heterozygous and homozygous genotypes of the two polymorphisms were associated with increased GDM risk in comparison with the wild-type AA genotype (AG vs. AA: OR = 1.23, 95% CI = 1.08, 1.41, p = 0.002; GG vs. AA: OR = 1.47, 95% CI = 1.05, 2.05, p = 0.024 for rs7756992; and CG vs. GG: OR = 1.36, 95% CI = 1.13, 1.65, p = 0.002; CC vs. GG: OR = 1.76, 95% CI = 1.37, 2.26, p &lt; 0.001 for rs7754840). The TSA confirmed a significant association between rs7754840 and the susceptibility to GDM because the cumulative Z-curve crossed both the conventional cutoff value and the TSA boundaries under the heterozygote and homozygote models.ConclusionsThis study supported the finding that rs7756992 and rs7754840 are associated with susceptibility to GDM. However, further functional studies are warranted to clarify the mechanism.
Associations Between Sleep Duration, Wake-Up Time, Bedtime, and Abdominal Obesity: Results From 9559 Chinese Children Aged 7–18 Years
Authors: Liu Meijuan , Cao Bingyan , Luo Qipeng , Wang Qiao , Liu Min , Liang Xuejun , Wu Di , Li Wenjing , Su Chang , Chen Jiajia , Gong Chunxiu 
Published: October 2021

ObjectiveTo investigate the associations of sleep duration, wake-up time, bedtime, and childhood abdominal obesity, and to test whether there is a weekday/weekend difference and the potential modifying role of sex.MethodsThis cross-sectional study was based on the Students’ Constitution and Health Survey and included 9559 students (4840 boys and 4719 girls) aged 7–18 years (7227 aged 7–12 years, 2332 aged 13–18 years). They were divided into two groups (control group and group with abdominal obesity). The physical measurements included children and youth body height, body weight, and waist circumference (WC). A parent-report questionnaire was used to collect the information about parent characteristics as well as lifestyle and sleep patterns (sleep duration, bedtime, and wake-up time of weekdays and weekends) of children and youth.ResultsThe prevalence of abdominal obesity was 30.57% and the percentages of sleep duration &lt;9 hours/day, wake-up time before 07:00 am on weekdays and weekends, bedtime after 10:00 pm on weekends were significantly higher in the group with abdominal obesity. After adjusting for confounders, sleep duration &lt;9 hours/day on weekends was inversely related to abdominal obesity in the overall subjects, regardless of their sex and age, while bedtime after 10:00 pm on weekends was inversely related to abdominal obesity only in the overall subjects, boys, and children aged 7–12 years. Logistic regression models in all subjects showed that shorter hours of weekends sleep duration were associated with greater risks of abdominal obesity, even after adjusting for all confounders, including wake-up time and bedtime. The adjusted odds ratios and 95% confidence intervals of abdominal obesity (with ≥10 hours/day as the reference group) for children with 9–10 hours/day, 8–9 hours/day, and &lt;8 hours/day of weekend sleep duration were 1.23 (1.04–1.46), 1.59 (1.32–1.91) and 1.83 (1.42–2.36), respectively. Specifically, after stratification by sex and age, this phenomenon was only observed in boys and children aged 7–12 years.ConclusionsSleep duration and bedtime on weekends were independently associated with the risk of childhood abdominal obesity, particularly in boys and children aged 7–12 years.
GnRH Antagonist Protocol With Cessation of Cetrorelix on Trigger Day Improves Embryological Outcomes for Patients With Sufficient Ovarian Reserve
Authors: Xu Huihui , Zhao Shen , Gao Xinxing , Wu Xian , Xia Lan , Zhang Dan , Li Jian , Zhang Aijun , Xu Bufang 
Published: October 2021

ObjectiveTo evaluate the efficiency and validity of cessation of cetrorelix on trigger day during gonadotropin releasing hormone antagonist (GnRH-ant)-controlled ovarian stimulation of in vitro fertilization (IVF) cycles.MethodsIn this retrospective study, a total of 1271 patients undergoing initial IVF cycles following the GnRH-ant protocol were enrolled; 832 patients received cetrorelix on trigger day (Group A) and 439 patients ceased cetrorelix on trigger day (Group B). We compared demographic characteristics, embryological and clinical outcomes between the two groups. A Poisson regression model was used to identify factors that significantly affected embryological outcomes. Patients were further divided into subgroups according to anti-Mullerian hormone (AMH) and age, to assess associations between ceasing cetrorelix on trigger day and embryological outcomes.ResultsThere was a significant improvement on embryological outcomes in patients who ceased cetrorelix on trigger day, and there were no significant differences in clinical outcomes or preovulation rates between the two groups. Furthermore, for patients with 1.1 ≤ AMH ≤ 4.7 ng/ml, all embryological outcomes were significantly higher in Group B compared with Group A. For patients with AMH &gt; 4.7 ng/ml, the number of oocytes retrieved, fertilization rate (2PN) of IVF cycles and proportion of day 3 good quality embryos were all significantly higher in Group B. For patients with age &lt; 35 years, all the embryological outcomes, besides the number of available embryos, were significantly higher in Group B than in Group A. There were no differences in embryological outcomes between the two groups when patients were stratified based on age &gt; 35 years or AMH &lt; 1.1 ng/ml.ConclusionGnRH-ant protocol with cessation of cetrorelix on trigger day improved embryological outcomes for young patients or patients with sufficient ovarian reserve, and was effective at preventing preovulation.
SMRT Sequencing of the Full-Length Transcriptome of the Coelomactra antiquata
Authors: Deng Aiping , Li Jinpeng , Yao Zebin , Afriyie Gyamfua , Chen Ziyang , Guo Yusong , Luo Jie , Wang Zhongduo 
Published: October 2021

Coelomactra antiquata is an important aquatic economic shellfish with high medicinal value. However, because C. antiquata has no reference genome, a lot of molecular biology research cannot be carried out, so the analysis of its transcripts is an important step to study the regulatory genes of various substances in C. antiquata. In the present study, we conducted the first full-length transcriptome analysis of C. antiquata by using PacBio single-molecule real-time (SMRT) sequencing technology. The results identified a total of 39,209 unigenes with an average length of 2,732 bp, 23,338 CDSs, 251 AS events, 9,881 lncRNAs, 20,106 SSRs, and 2,316 TFs. Subsequently, 59.22% (23,220) of the unigenes were successfully annotated, of which 23,164, 18,711, 15,840, 13,534, and 13,474 unigenes could be annotated using NR, Swiss-prot, KOG, GO, and KEGG databases, respectively. This study lays the foundation for the follow-up research of molecular biology and provides a reference for studying the more medicinal value of C. antiquata.
Efficacy and Safety of Dupilumab in Moderate-to-Severe Bullous Pemphigoid
Authors: Zhang Yihua , Xu Qiuyun , Chen Lihong , Chen Jiawen , Zhang Jing , Zou Ying , Gong Ting , Ji Chao 
Published: October 2021

BackgroundBullous pemphigoid (BP) is an autoimmune blistering disorder that predominantly affects the elderly. As the main treatment for BP, systemic corticosteroids are often limited by their side effects. Safer treatment modalities are therefore needed. Dupilumab is a biologic agent used to treat BP in recent years.MethodsMedical records of patients with moderate-to-severe BP were retrospectively reviewed. Twenty-four patients were included (follow-up period: 32 weeks), eight of whom received dupilumab in combination with methylprednisolone and azathioprine (dupilumab group) while the other 16 patients received methylprednisolone and azathioprine (conventional group). Response to dupilumab was evaluated by comparison of several parameters (time to stop new blister formation, time to reduce the systemic glucocorticoids to minimal dose, and total amount of methylprednisolone).ResultsThe median age of patients in the dupilumab and conventional groups were 64.50 years (range: 22–90 years) and 64.50 years (range: 17–86 years), respectively. The median duration of disease before admission in the dupilumab group was 2 months (range: 1–240 months) and 2.5 months (range: 1–60 months) in the conventional group. The median time to stop new blister formation was 8 days (range: 1–13 days) and 12 days (range: 5–21 days) in patients of the dupilumab and conventional groups, respectively (p = 0.028 by Kaplan-Meier analysis). In addition, the median time to reduce the systemic glucocorticoids to minimal dose (methylprednisolone 0.08 mg/kg/day) was 121.5 and 148.5 days for the dupilumab and conventional therapy groups, respectively (p = 0.0053 by Kaplan-Meier analysis). The median total amount of methylprednisolone (at the time of reaching the minimal dose) used in the dupilumab group was 1,898 mg (range: 1,624–2,932 mg) while the cumulative dose of conventional group was 2,344 mg (range: 1,708–4,744 mg) (p = 0.036 by Mann-Whitney U test). The median total amount of azathioprine (at the time of reaching the minimal dose) used in dupilumab group was 8,300 mg (range: 7,100–10,400 mg) while the total dose of conventional group was 10,300 mg (range: 8,900–14,400 mg) (p = 0.0048 by Mann-Whitney U test). No adverse event related to dupilumab was recorded.ConclusionsDupilumab in addition to methylprednisolone and azathioprine seems superior to methylprednisolone/azathioprine alone in controlling disease progression and accelerating the tapering of glucocorticoids.
Decreased miR-4512 Levels in Monocytes and Macrophages of Individuals With Systemic Lupus Erythematosus Contribute to Innate Immune Activation and Neutrsophil NETosis by Targeting TLR4 and CXCL2
Authors: Yang Binbin , Huang Xinwei , Xu Shuangyan , Li Li , Wu Wei , Dai Yunjia , Ge Ming-Xia , Yuan Limei , Cao Wenting , Yang Meng , Wu Yongzhuo , Deng Danqi 
Published: October 2021

ObjectiveSystemic lupus erythematosus (SLE) is an autoimmune disease with complex etiology that is not yet entirely understood. We aimed to elucidate the mechanisms and therapeutic potential of microRNAs (miRNAs) in SLE in a Tibetan population.MethodsPeripheral blood mononuclear cells from SLE patients (n = 5) and healthy controls (n = 5) were used for miRNA–mRNA co-sequencing to detect miRNAs related to immune abnormalities associated with SLE. Luciferase reporter assay was used to identify potential targets of candidate miRNA. The target genes were verified in miRNA-agomir/antagomir transfection assays with multiple cells lines and by expression analysis. The effects of candidate miRNA on monocyte and macrophage activation were evaluated by multiple cytokine profiling. Neutrophil extracellular traps (NETs) formation was analyzed in vitro by cell stimulation with supernatants of monocytes and macrophages transfected with candidate miRNA. The rodent MRL/lpr lupus model was used to evaluate the therapeutic effect of CXCL2Ab on SLE and the regulation effect of immune disorders.ResultsIntegrated miRNA and mRNA expression profiling identified miRNA-4512 as a candidate miRNA involved in the regulation of neutrophil activation and chemokine-related pathways. MiR-4512 expression was significantly reduced in monocytes and macrophages from SLE patients. MiR-4512 suppressed the TLR4 pathway by targeting TLR4 and CXCL2. Decreased monocyte and macrophage miR-4512 levels led to the expression of multiple proinflammatory cytokines in vitro. Supernatants of miR-4512 antagomir-transfected monocytes and macrophages significantly promoted NETs formation (P &lt; 0.05). Blocking of CXCL2 alleviated various pathogenic manifestations in MRL/lpr mice, including kidney damage and expression of immunological markers of SLE.ConclusionsWe here demonstrated the role of miR-4512 in innate immunity regulation in SLE. The effect of miR-4512 involves the regulation of monocytes, macrophages, and NETs formation by direct targeting of TLR4 and CXCL2, indicating the miR-4512-TLR4-CXCL2 axis as a potential novel therapeutic target in SLE.
Construction and Identification of a Novel 5-Gene Signature for Predicting the Prognosis in Breast Cancer
Authors: Guo Lingling , Jing Yu 
Published: October 2021

Background: Breast cancer is one of the most common malignancies in women worldwide. The purpose of this study was to identify the hub genes and construct prognostic signature that could predict the survival of patients with breast cancer (BC).Methods: We identified differentially expressed genes between the responder group and non-responder group based on the GEO cohort. Drug-resistance hub genes were identified by weighted gene co-expression network analysis, and a multigene risk model was constructed by univariate and multivariate Cox regression analysis based on the TCGA cohort. Immune cell infiltration and mutation characteristics were analyzed.Results: A 5-gene signature (GP6, MAK, DCTN2, TMEM156, and FKBP14) was constructed as a prognostic risk model. The 5-gene signature demonstrated favorable prediction performance in different cohorts, and it has been confirmed that the signature was an independent risk indicater. The nomogram comprising 5-gene signature showed better performance compared with other clinical features, Further, in the high-risk group, high M2 macrophage scores were related with bad prognosis, and the frequency of TP53 mutations was greater in the high-risk group than in the low-risk group. In the low-risk group, high CD8+ T cell scores were associated with a good prognosis, and the frequency of CDH1 mutations was greater in the low-risk group than that in the high-risk group. At the same time, patients in the low risk group have a good response to immunotherapy in terms of immunotherapy. The results of immunohistochemistry showed that MAK, GP6, and TEMEM156 were significantly highly expressed in tumor tissues, and DCTN2 was highly expressed in normal tissues.Conclusions: Our study may find potential new targets against breast cancer, and provide new insight into the underlying mechanisms.
Feasibility of Noninvasive Diagnosis of Spinal Vascular Diseases Using Time-Resolved Angiography With Stochastic Trajectories
Authors: Wei Xiao-Er , Li Ming-Hua , Qiao Rui-Hua , Yu Wei-Bin , Li Yue-Hua 
Published: October 2021

Background and Purpose: To determine the feasibility of time-resolved angiography with stochastic trajectories (TWIST) in the diagnosis of spinal dural arteriovenous fistula (SDAVF) and perimedullary arteriovenous fistula (PAVF).Methods: A total of 11 negative patients with TWIST examination were retrospective analyzed and then 18 patients with suspected spinal vascular diseases underwent TWIST. For negative patients, Adamkiewicz artery (AKA), great anterior radiculomedullary vein (GARV) and anterior spinal artery (ASA) were retrospective analyzed. In patients, the results of TWIST were compared with those of DSA.Results: The displaying rates of the ASA, AKA and GARV in 11 negative patients were 100, 90.9, and 90.9%, respectively. The AKA and GARV were separated on TWIST. Of 18 patients, 11 and three were diagnosed with SDAVF and PAVF, respectively. The spinal cord vascular malformation diagnosed on TWIST was consistent with DSA with an excellent intermodality agreement (Kappa = 0.92, p &lt; 0.001). The feeding artery and side of all 11 SDAVF patients were displayed on TWIST and the results were consistent with DSA. For PAVF patients, the feeding artery in two patients and the sides as displayed on TWIST were consistent with DSA.Conclusions: TWIST enables the differentiation of the spinal artery and vein and the differential diagnosis of SDAVF and PAVF.
Age-Related Variation in Sympathetic Nerve Distribution in the Human Spleen
Authors: Cleypool Cindy G. J. , Brinkman David J. , Mackaaij Claire , Nikkels Peter G. J. , Nolte Martijn A. , Luyer Misha D. , de Jonge Wouter J. , Bleys Ronald L. A. W. 
Published: October 2021

Introduction: The cholinergic anti-inflammatory pathway (CAIP) has been proposed as an efferent neural pathway dampening the systemic inflammatory response via the spleen. The CAIP activates the splenic neural plexus and a subsequent series of intrasplenic events, which at least require a close association between sympathetic nerves and T cells. Knowledge on this pathway has mostly been derived from rodent studies and only scarce information is available on the innervation of the human spleen. This study aimed to investigate the sympathetic innervation of different structures of the human spleen, the topographical association of nerves with T cells and age-related variations in nerve distribution.Materials and Methods: Spleen samples were retrieved from a diagnostic archive and were allocated to three age groups; neonates, 10–25 and 25–70 years of age. Sympathetic nerves and T cells were identified by immunohistochemistry for tyrosine hydroxylase (TH) and the membrane marker CD3, respectively. The overall presence of sympathetic nerves and T cells was semi-automatically quantified and expressed as total area percentage. A predefined scoring system was used to analyze the distribution of nerves within different splenic structures.Results: Sympathetic nerves were observed in all spleens and their number appeared to slightly increase from birth to adulthood and to decrease afterward. Irrespective to age, more than halve of the periarteriolar lymphatic sheaths (PALSs) contained sympathetic nerves in close association with T cells. Furthermore, discrete sympathetic nerves were observed in the capsule, trabeculae and red pulp and comparable to the total amount of sympathetic nerves, showed a tendency to decrease with age. No correlation was found between the number of T cells and sympathetic nerves.Conclusion: The presence of discrete sympathetic nerves in the splenic parenchyma, capsule and trabecular of human spleens could suggest a role in functions other than vasoregulation. In the PALS, sympathetic nerves were observed to be in proximity to T cells and is suggestive for the existence of the CAIP in humans. Since sympathetic nerve distribution shows interspecies and age-related variation, and our general understanding of the relative and spatial contribution of splenic innervation in immune regulation is incomplete, it remains difficult to estimate the anti-inflammatory potential of targeting splenic nerves in patients.
Parkinson's Disease Risk and Alcohol Intake: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies
Authors: Shao Chuan , Wang Xiaoya , Wang Pan , Tang Hui , He Jiaquan , Wu Nan 
Published: October 2021

Background: The association between Parkinson's disease (PD) risk and alcohol intake is a controversial topic.Objectives: To systematically assess the association between PD risk and alcohol intake.Methods: PubMed and Embase databases were searched for eligible studies with prospective design on PD risk and alcohol intake. A meta-analysis with a random-effects model and dose-response analysis was performed. Relative risk ratios (RRs) with 95% CIs were calculated.Results: Eleven prospective studies were included. Overall, a higher intake of alcohol was inversely associated with PD risk (RR: 0.81, 95% CI: 0.70–0.95, I2 = 73.7%). Significant differences existed between the specific types of alcoholic beverages and geographic area. Specifically, a significant association existed for beer (RR: 0.78, 95% CI: 0.65–0.94, I2 = 0.0%) and studies conducted in Asia (RR: 0.66, 95% CI: 0.55–0.80, I2 = 37.3%). Dose-response analysis indicated a nonlinear relationship between PD risk and alcohol exposure. No evidence for publication bias was detected.Conclusions: In summary, our meta-analysis suggests that alcohol consumption was associated with a decreased risk of PD, with a nearly U-shaped association. Future studies are warranted to clarify the question of a specific type of alcoholic beverage-dependent association, geographic area effect, and possible threshold effects regarding both the adverse and beneficial effects of alcohol.
US Older Adults That Consume Avocado or Guacamole Have Better Cognition Than Non-consumers: National Health and Nutrition Examination Survey 2011–2014
Authors: Cheng Feon W. , Ford Nikki A. , Taylor Matthew K. 
Published: October 2021

Purpose: The goal of this study is to examine how avocado relates to cognitive function among older adults.Methods: A total of 2,886 National Health and Nutrition Examination Survey 2011–2014 participants aged 60 or older met the eligibility criteria and were included of our cross-sectional study. Participants were binarily classified as avocado consumers (i.e., reported consuming any avocado/guacamole in either 24-h dietary recalls) or non-consumers. Cognitive performance was evaluated with: Consortium to Establish a Registry for Alzheimer's disease (CERAD)—immediate and delayed recall (IWR/DWR), the Animal Fluency test, and the Digit Symbol Substitution Test. We calculated the education-dependent z-scores for each subject because education level can impact cognitive function. Global cognitive score, an average of the z-scores for each cognitive test, was calculated in participants who had completed all four tests. To account for relevant covariates, we tested for mean differences in cognition between consumers and non-consumers using independent sample t-tests and ANCOVA, special cases of ordinary least squares regression.Results: Avocado consumers had significantly better cognitive scores across all cognitive tests and the global cognition score (p &lt; 0.05) in the unadjusted model. Some mean differences attenuated after adjusting for potential confounders, but others remained significant. Compared to non-consumers, avocado consumers had significantly higher z-scores of 0.15, 0.15, and 0.11 for CERAD IWR and DWR, and global cognition score, respectively (all p &lt; 0.05 in adjusted models).Conclusion: Avocado consumption was associated with significantly better IWR, DWR, and the overall global cognition score, which remained significant when controlling for all relevant confounders.