bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of COVID-19 Lockdown With Gestational Diabetes Mellitus
Authors: He Zhongrong , Lv Yanyun , Zheng Suijin , Pu Yudong , Lin Qingmei , Zhou He , Dong Moran , Wang Jiaqi , Fan Jingjie , Ye Yufeng , Chen Hanwei , Qian Rui , Jin Juan , Chen Yumeng , Chen Guimin , He Guanhao , Cheng Shouzhen , Hu Jianxiong , Xiao Jianpeng , Ma Wenjun , Su Xi , Liu Tao 
Published: March 2022

ImportanceThe ongoing pandemic of COVID-19 is still affecting our life, but the effects of lockdown measures on gestational diabetes mellitus (GDM) in pregnant women remain unclear.AimTo investigate the association between COVID-19 lockdown and GDM.Subjects and MethodsMedical records of 140844 pregnant women during 2015-2020 were extracted from 5 hospitals in Guangdong Province, China. Pregnant women who underwent the COVID-19 Level I lockdown (1/23 - 2/24/2020) during pregnancy were defined as the exposed group (N=20472) and pregnant women who underwent the same calendar months during 2015-2019 (1/23 - 2/24) were defined as the unexposed group (N=120372). Subgroup analyses were used to explore the potential susceptible exposure window of COVID-19 lockdown on GDM. Cumulative exposure is quantitatively estimated by assigning different weights to response periods with different exposure intensities. A logistic regression model was used to estimate the association between COVID-19 lockdown exposure and GDM.ResultsThe rates of GDM in the exposed and unexposed groups were 15.2% and 12.4%, respectively. The overall analyses showed positive associations (odds ratio, OR=1.22, 95%CI: 1.17, 1.27) between lockdown exposure and GDM risk in all pregnant women. More pronounced associations were found in women who underwent the COVID-19 lockdown in their first four months of pregnancy, and the adjusted OR values ranged from 1.24 (95%CI: 1.10, 1.39) in women with 5-8 gestational weeks (GWs) to 1.35 (95%CI: 1.20, 1.52) with &lt; 5 GWs. In addition, we found a positive exposure-response association of cumulative lockdown exposure with the risk of GDM.ConclusionsThe COVID-19 lockdown was associated with an increased risk of GDM, and the first four months of pregnancy may be the window for sensitive exposure.
Construction Immune Related Feed-Forward Loop Network Reveals Angiotensin II Receptor Blocker as Potential Neuroprotective Drug for Ischemic Stroke
Authors: Bo Chunrui , Cao Yuze , Li Shuang , Zhang Huixue , Lu Xiaoyu , Kong Xiaotong , Zhang Shuai , Gao Hongyu , Wang Jianjian , Wang Lihua 
Published: March 2022

Ischemic stroke (IS) accounts for the leading cause of disability and mortality in China. Increasing researchers are studying the effects of neuroprotective agents on IS. However, the molecular mechanisms of feed-forward loops (FFLs) associated with neuroprotection in the pathogenesis of IS need to be further studied. A protein-protein interaction (PPI) network of IS immune genes was constructed to decipher the characters and excavate 3 hub genes (PI3K, IL6, and TNF) of immunity. Then, we identified two hub clusters of IS immune genes, and the cytokine-cytokine receptor interaction pathway was discovered on the pathway enrichment results of both clusters. Combined with GO enrichment analysis, the cytokines participate in the inflammatory response in the extracellular space of IS patients. Next, a transcription factor (TF)–miRNA–immune gene network (TMIGN) was established by extracting four regulatory pairs (TF–miRNA, TF–gene, miRNA–gene, and miRNA–TF). Then, we detected 3-node regulatory motif types in the TMIGN network. According to the criteria we set for defining 3-node motifs, the motif with the highest Z-score (3-node composite FFL) was picked as the statistically evident motif, which was merged to construct an immune-associated composite FFL motif-specific sub-network (IA-CFMSN), which contained 21 3-node FFLs composed of 13 miRNAs, 4 TFs, 9 immune genes, and 1 TF&amp; immune gene, among which TP53 and VEGFA were prominent TF and immune gene, respectively. In addition, the immune genes in IA-CFMSN were used for identifying associated pathways and drugs to further clarify the immune regulation mechanism and neuroprotection after IS. As a result, 5 immune genes targeted by 20 drugs were identified and the Angiotensin II Receptor Blockers (ARBs) target AGTR1 was found to be a neuroprotective drug for IS. In the present study, the construction of IA-CFMSN provides IS immune-associated FFLs for further experimental studies, providing new prospects for the discovery of new biomarkers and potential drugs for IS.
Case Report: Exome and RNA Sequencing Identify a Novel de novo Missense Variant in HNRNPK in a Chinese Patient With Au-Kline Syndrome
Authors: Pan Xin , Liu Sihan , Liu Li , Zhang Xu , Yao Hong , Tan Bo 
Published: March 2022

Au-Kline syndrome is a severe multisystemic syndrome characterized by several congenital defects, including intellectual disability. Loss-of-function and missense variants in the HNRNPK gene are associated with a range of dysmorphic features. This report describes an eleven-year-old Chinese boy with intellectual disability and developmental delays. Family-based whole-exome and Sanger sequencing identified a de novo missense variant in HNRNPK (NM_002140.3: c.143T &gt; A, p. Leu48Val). In silico analysis predicted that this variant would be damaged in a highly conserved residue in the K homology 1 (KH1) domain. Bioinformatic analysis showed that the affinity change (ΔΔG) caused by this variant was -0.033 kcal/mol, indicating that it would have reduced affinity for RNA binding. Transcript analysis of the peripheral blood from this case found 42 aberrantly expressed and 86 aberrantly spliced genes (p-value &lt;0.01). Functional enrichment analysis confirmed that the biological functions of these genes, including protein binding and transcriptional regulation, are associated with HNRNPK. In summary, this study identifies the first Chinese patient with a novel de novo heterozygous HNRNPK gene variant that contributes to Au-Kline syndrome and expands current knowledge of the clinical spectrum of HNRNPK variants.
Bibliometric Analysis of Chimeric Antigen Receptor-Based Immunotherapy in Cancers From 2001 to 2021
Authors: Ou Zhanpeng , Qiu Ling , Rong Haixu , Li Bowen , Ren Siqi , Kuang Shijia , Lan Tianjun , Lin Hsinyu , Li Qunxing , Wu Fan , Cai Tingting , Yan Lingjian , Ye Yushan , Fan Song , Li Jinsong 
Published: March 2022

BackgroundChimeric antigen receptor (CAR)-based immunotherapy has shown great potential for the treatment of both hematopoietic malignancies and solid tumors. Nevertheless, multiple obstacles still block the development of CAR-based immunotherapy in the clinical setting. In this study, we aimed to summarize the research landscape and highlight the front lines and trends of this field.MethodsLiterature published from 2001 to 2021 was searched in the Web of Science Core Collection database. Full records and cited references of all the documents were extracted and screened. Bibliometric analysis and visualization were conducted using CiteSpace, Microsoft Excel 2019, VOSviewer and R software.ResultsA total of 5981 articles and reviews were included. The publication and citation results exhibited increasing trends in the last 20 years. Frontiers in Immunology and Blood were the most productive and most co-cited journals, respectively. The United States was the country with the most productive organizations and publications in the comprehensive worldwide cooperation network, followed by China and Germany. June, C.H. published the most papers with the most citations, while Maude, S.L. ranked first among the co-cited authors. The hotspots in CAR-based therapy research were multiple myeloma, safety and toxicity, solid tumors, CAR-engineered immune cells beyond T cells, and gene editing.ConclusionCAR-based immunotherapy is a promising treatment for cancer patients, and there is an emerging movement toward using advanced gene modification technologies to overcome therapeutic challenges, especially in solid tumors, and to generate safer and more effective universal CAR-engineered cell products.
Intrauterine Perfusion of Autologous Platelet-Rich Plasma Before Frozen-Thawed Embryo Transfer Improves the Clinical Pregnancy Rate of Women With Recurrent Implantation Failure
Authors: Xu Yangying , Hao Cuifang , Fang Jianye , Liu Xiaoqiang , Xue Pingping , Miao Ruichao 
Published: March 2022

ObjectiveTo evaluate whether the intrauterine perfusion of platelet-rich plasma (PRP) before frozen-thawed embryo transfer (FET) improves the pregnancy outcomes of patients with repeated implantation failure (RIF).MethodsThis retrospective study included 288 infertile women with RIF after undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment from October 1, 2019, to January 1, 2021, at Qingdao Women and Children's Hospital. Patients were divided into two groups according to whether they received PRP intrauterine perfusion before embryo transfer in FET cycles. 138 women were in the PRP group, 150 women were in the control group. The primary outcome measure was live birth rates and the secondary outcome were clinical pregnancy, positive β hCG, miscarriage and implantation rates.ResultsNo significant differences in baseline demographic and clinical characteristics were observed between the two groups. Overall, significantly more women in the PRP group than in the control group achieved a live birth rate (41 women; 29.71% vs. 27 women; 18%) and a clinical pregnancy (50 women; 36.23% vs. 37 women; 24.67%). The PRP group had a higher implantation rate and lower spontaneous miscarriage rate than the control group, but these differences were not statistically significant. No pregnancy outcome difference between two groups in PCOS patients with RIF.ConclusionOur results showed that intrauterine perfusion of PRP before embryo transfer in FET cycles can significantly increase the live birth and clinical pregnancy rates in patients with RIF.
Challenges and Opportunities of Real-World Data: Statistical Analysis Plan for the Optimise:MS Multicenter Prospective Cohort Pharmacovigilance Study
Authors: Waddingham Ed , Miller Aleisha , Dobson Ruth , Matthews Paul M. 
Published: March 2022

IntroductionOptimise:MS is an observational pharmacovigilance study aimed at characterizing the safety profile of disease-modifying therapies (DMTs) for multiple sclerosis (MS) in a real world population. The study will categorize and quantify the occurrence of serious adverse events (SAEs) in a cohort of MS patients recruited from clinical sites around the UK. The study was motivated particularly by a need to establish the safety profile of newer DMTs, but will also gather data on outcomes among treatment-eligible but untreated patients and those receiving established DMTs (interferons and glatiramer acetate). It will also explore the impact of treatment switching.MethodsCausal pathway confounding between treatment selection and outcomes, together with the variety and complexity of treatment and disease patterns observed among MS patients in the real world, present statistical challenges to be addressed in the analysis plan. We developed an approach for analysis of the Optimise:MS data that will include disproportionality-based signal detection methods adapted to the longitudinal structure of the data and a longitudinal time-series analysis of a cohort of participants receiving second-generation DMT for the first time. The time-series analyses will use a number of exposure definitions in order to identify temporal patterns, carryover effects and interactions with prior treatments. Time-dependent confounding will be allowed forviainverse-probability-of-treatment weighting (IPTW). Additional analyses will examine rates and outcomes of pregnancies and explore interactions of these with treatment type and duration.ResultsTo date 14 hospitals have joined the study and over 2,000 participants have been recruited. A statistical analysis plan has been developed and is described here.ConclusionOptimise:MS is expected to be a rich source of data on the outcomes of DMTs in real-world conditions over several years of follow-up in an inclusive sample of UK MS patients. Analysis is complicated by the influence of confounding factors including complex treatment histories and a highly variable disease course, but the statistical analysis plan includes measures to mitigate the biases such factors can introduce. It will enable us to address key questions that are beyond the reach of randomized controlled trials.
Altered Spontaneous Brain Activity in Left-Behind Children: A Resting-State Functional MRI Study
Authors: Wang Yu , Lu Yi , Du Meimei , Hussein Nimo Mohamed , Li Lan , Wang Yu , Mao Chuanwan , Chen Tao , Chen Fangfang , Liu Xiaozheng , Yan Zhihan , Fu Yuchuan 
Published: March 2022

BackgroundParental migration has been associated with a higher risk of cognitive and behavioral abnormalities in left-behind children (LBC). This study aimed to explore the spontaneous brain activity in LBC and reveal the mechanisms underlying behavioral and cognitive abnormalities.MethodsInvolved LBC (n= 36) and non-LBC (n= 22) underwent resting-state functional MRI (fMRI) examination and cognitive and behavioral assessment. The fMRI-based amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were assessed to analyze the spontaneous brain activity pattern. The relationships among abnormal spontaneous brain activity, behavioral and cognitive deficits and altered family environment were assessed by partial correlation analysis.ResultsCompared with non-LBC, LBC exhibited increased amplitude of low-frequency fluctuations in the right lingual gyrus (LING), while a decreased ALFF was observed in the bilateral insula and right orbital part of the middle frontal gyrus (ORBmid) (two-tailed voxel-levelp&lt; 0.01 and cluster-levelp&lt;0.05, Gaussian Random Field (GRF) correction). The fALFF in LBC were significantly increased in the left cerebellum 9 (Cbe9) and right cerebellum Crus2 (CbeCru2), while it decreased in the right hippocampus and left superior temporal gyrus (STG) (two-tailed voxel-levelp&lt; 0.01 and cluster-levelp&lt; 0.05, GRF correction). The ALFF and fALFF values in abnormal brain regions were found to be correlated with the learning ability, except for the right insula, while the fALFF values of the left STG were positively correlated with the full-scale IQ scores (p&lt; 0.05). Moreover, the ALFF and fALFF values in all abnormal brain regions correlated with the education level of caregivers (p&lt; 0.05).ConclusionsOur study provided empirical evidence that the lack of direct parental care during early childhood could affect brain function development involving cognition, behavior, and emotion. Our findings emphasized that intellectual and emotional cares are essential for LBC.
Feasibility and Long-Term Compliance to Continuous Positive Airway Pressure Treatment in Adults With Down Syndrome, a Genetic Form of Alzheimer’s Disease
Authors: Giménez Sandra , Farre Ariadna , Morente Fátima , Videla Laura , Gutiérrez Marta , Clos Susana , Fernández Ana , Blanco Marta , Altuna Miren , Pegueroles Jordi , Asensio Amparo , Benejam Bessy , Batista Mar , Barroeta Isabel , Fortuna Ana , Fortea Juan , Mayos Mercedes 
Published: March 2022

BackgroundDown syndrome (DS) is a genetic form of Alzheimer’s disease (AD) with a high prevalence of obstructive sleep apnea (OSA). These characteristics place the DS population as an optimal model to study the relationship between sleep and AD and to design clinical trials of preventive sleep therapies for AD. Regrettably, OSA treatment with continuous positive airway pressure (CPAP) is often neglected in adults with DS. In both clinical practice and research trials, it is usually presumed that these patients will not adapt to or tolerate the therapy.Study ObjectiveWe aimed to evaluate the feasibility and long-term CPAP compliance in this population and their capacity to be enrolled in CPAP research studies.MethodsWe prospectively compared the CPAP compliance of 17 OSA patients with DS and 19 age and sex matched OSA euploid patients. CPAP management and follow-up schedules were prescribed according to the habitual clinical practice. We compared group differences in tolerance, objective, and subjective hours of nightly CPAP usage at the 1st, 3rd, 6th, 12th, 24th, and 36th month visits. Good compliance was defined as at least 4 h use per night. We also investigated predictive factors of long-term CPAP compliance.ResultsThe percentage of DS subjects with good CPAP compliance (81.2 vs. 78.9%) and the objective CPAP use (5 vs. 6 h, p = 0.92) did not differ from the control group (CG). Subjective CPAP compliance was significantly higher in OSA patients with DS than in controls in all the follow-up visits (8 vs. 6.75 h, p = 0.001). The DS group had a significantly higher number of visits (9 vs. 5; p = 0.021) and mask changes (2.5 vs. 2; p = 0.05) than controls. Objective hours of CPAP use at the first follow-up visit predicted long-term CPAP compliance (p &lt; 0.005).ConclusionCPAP treatment is feasible and has good long-term compliance in OSA patients with DS. It should be recommended to improve health and prevent comorbidities. The DS population is indeed suitable to participate in longitudinal preventive sleep clinical trials for AD.
AFF2 Is Associated With X-Linked Partial (Focal) Epilepsy With Antecedent Febrile Seizures
Authors: Zou Dongfang , Qin Bing , Wang Jie , Shi Yiwu , Zhou Peng , Yi Yonghong , Liao Jianxiang , Lu Xinguo 
Published: March 2022

ObjectiveAFF2 mutations were associated with X-linked intellectual developmental disorder-109 and in males with autism spectrum disorder (ASD). The relationship between AFF2 and epilepsy has not been defined.MethodTrios-based whole-exome sequencing was performed in a cohort of 372 unrelated cases (families) with partial (focal) epilepsy without acquired causes.ResultsFive hemizygous missense AFF2 mutations were identified in five males with partial epilepsy and antecedent febrile seizures without intellectual disability or other developmental abnormalities. The mutations did not present in the controls of general populations with an aggregate frequency significantly higher than that in the control populations. Previously, intellectual disability-associated AFF2 mutations were genomic rearrangements and CCG repeat expansion mutations mostly, whereas the mutations associated with partial epilepsy were all missense. Missense AFF2 mutations associated with epilepsy fell into the regions from N-terminal to the nuclear localization signal 1 (NLS1), while ASD-associated missense mutations fell in the regions from NLS1 to C-terminal.ConclusionAFF2 is potentially a candidate causative gene of X-link partial epilepsy with antecedent febrile seizures. The genotype–phenotype correlation and molecular sub-regional effect of AFF2 help in explaining the mechanisms underlying phenotypic variations.
Probiotic Intake and Inflammation in Patients With Chronic Kidney Disease: An Analysis of the CKD-REIN Cohort
Authors: Wagner Sandra , Merkling Thomas , Metzger Marie , Koppe Laetitia , Laville Maurice , Boutron-Ruault Marie-Christine , Frimat Luc , Combe Christian , Massy Ziad A. , Stengel Bénédicte , Fouque Denis 
Published: March 2022

Background and AimsLittle is known about the effects of probiotics on inflammation in the context of chronic kidney disease (CKD). We investigated the association between probiotic intake and inflammation in patients with moderate-to-advanced CKD.MethodsWe performed a cross-sectional study of 888 patients with stage 3–5 CKD and data on serum C-reactive protein (CRP) levels and a concomitant food frequency questionnaire. We estimated the odds ratios (ORs) [95% confidence interval (CI)] for various CRP thresholds (&gt;3, &gt;4, &gt;5, &gt;6, and &gt;7 mg/L) associated with three intake categories (no yoghurt, ordinary yoghurt, and probiotics from yoghurts or dietary supplements) and two frequency categories (daily or less than daily).ResultsThe 888 study participants (median age: 70; men: 65%) had a median estimated glomerular filtration rate of 28.6 mL/min/1.73 m2 and a median [interquartile range] CRP level of 3.0 [1.6, 7.0] mg/L. Fifty-seven percent consumed ordinary yoghurt and 30% consumed probiotic yoghurt. The median intake frequency for yoghurt and probiotics was 7 per week. Relative to participants not consuming yoghurt, the ORs [95% CI] for CRP &gt; 6 or &gt;7 mg/L were significantly lower for participants consuming ordinary yoghurt (0.58 [0.37, 0.93] and 0.57 [0.35, 0.91], respectively) and for participants consuming probiotics (0.54 [0.33, 0.9] and 0.48 [0.28, 0.81], respectively), independently of age, sex, body mass index, CKD stage, cardiovascular disease, and fibre, protein and total energy intakes. The ORs were not significantly lower for CRP thresholds &gt;3, &gt;4, and &gt;5 mg/L and were not significantly greater in daily consumers than in occasional consumers.ConclusionWe observed independent associations between the consumption of yoghurt or probiotics and lower levels of inflammation in patients with CKD. There was no evidence of a dose-effect relationship.Clinical Trial Registration[https://www.clinicaltrials.gov/ct2/show/NCT03381950], identifier [NCT03381950].
Serum Homocysteine Level Is Positively Correlated With Serum Uric Acid Level in U.S. Adolescents: A Cross Sectional Study
Authors: Shi Yumeng , Wu Zuxiang , Wu Ji , Chen Zhiqiang , Li Ping 
Published: March 2022

BackgroundPhysiologically, the levels of homocysteine (Hcy) and serum uric acid (SUA) are closely related; however, clinical studies on the relationship between Hcy and SUA have drawn different conclusions and have not analyzed this association among adolescents. This study therefore aimed to evaluate the relationship between Hcy and SUA levels among adolescents.MethodsIn this study, we performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey for the period 1999–2006, which included 5,404 adolescents aged 12–19 years. An elevated SUA level was defined as ≥5.5 mg/dL. Multivariate logistic regression and multivariate linear regression models were also applied in this study.ResultsThe mean concentrations of Hcy and SUA were 6.0 μmol/L and 5.0 mg/dL, respectively, and 33.6% of the participants had SUA levels of ≥5.5 mg/dL. There was a dose–response relationship between Hcy and SUA, and Hcy was linearly positively correlated with SUA. The β value [95% confidence interval (CI)] for SUA in the fully adjusted model was1.43 (95% CI: 1.18, 1.68). The multivariate logistic regression model showed that per 1 increment in log-transformed Hcy, the risk of elevated SUA levels increased by 8.80 times (odds ratio, 8.80, 95% CI: 4.25, 18.20). Subgroup analyses showed that the relationship between Hcy and SUA was significantly different according to sex, age, body mass index (BMI), and estimated glomerular filtration rate (eGFR) stratification (P for interaction &lt;0.05).ConclusionHcy levels were positively correlated with SUA levels and elevated SUA levels among U.S. teenagers, and this effect was more significant among boys aged ≥17 years and among people with lower BMI and eGFR.