bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of Longitudinal Fetal Growth Patterns With Cardiometabolic Factors at Birth
Authors: Huang Jia-Shuan , Chen Qiao-Zhu , Zheng Si-Yu , Ramakrishnan Rema , Zeng Ji-Yuan , Zhuo Can-Peng , Lai Yu-Mian , Kuang Ya-Shu , Lu Jin-Hua , He Jian-Rong , Qiu Xiu 
Published: December 2021

BackgroundBirth weight is associated with cardiometabolic factors at birth. However, it is unclear when these associations occur in fetal life. We aimed to investigate the associations between fetal growth in different gestational periods and cord blood cardiometabolic factors.MethodsWe included 1,458 newborns from the Born in Guangzhou Cohort Study, China. Z-scores of fetal size parameters [weight, abdominal circumference (AC), and femur length (FL)] at 22 weeks and growth at 22–27, 28–36, and ≥37 weeks were calculated from multilevel linear spline models. Multiple linear regression was used to examine the associations between fetal growth variables and z-scores of cord blood cardiometabolic factors.ResultsFetal weight at each period was positively associated with insulin levels, with stronger association at 28–36 weeks (β, 0.31; 95% CI, 0.23 to 0.39) and ≥37 weeks (β, 0.15; 95% CI, 0.10 to 0.20) compared with earlier gestational periods. Fetal weight at 28–36 (β, −0.32; 95% CI, −0.39 to −0.24) and ≥37 weeks (β, −0.26; 95% CI, −0.31 to −0.21) was negatively associated with triglyceride levels, whereas weight at 28–36 weeks was positively associated with HDL levels (β, 0.12; 95% CI, 0.04 to 0.20). Similar results were observed for AC. Fetal FL at 22 and 22–27 weeks was associated with increased levels of insulin, glucose, and HDL.ConclusionsFetal growth at different gestational periods was associated with cardiometabolic factors at birth, suggesting that an interplay between fetal growth and cardiometabolic factors might exist early in pregnancy.
Gradual, but Not Sudden, Dose-Dependent Increase of ONJ Risk With Bisphosphonate Exposure: A Nationwide Cohort Study in Women With Osteoporosis
Authors: Park Jung-Hyun , Kwoen Min-Jeong , Lee Jae-Ryun , Kim Keun-Suh , Lee Hyo-Jung , Kim Jin-Woo , Lee Hyejin 
Published: December 2021

BackgroundA causal relationship of bisphosphonate (BP) exposure with osteonecrosis of the jaw (ONJ) has been reported; however, a definite dose-dependent risk remains to be elucidated beyond current vague recommendations of 4-year oral BP for ONJ risk increase.ObjectiveTo identify the effect of bisphosphonate cumulative dose on ONJ development in women with osteoporosis.MethodsA retrospective cohort study was designed using the National Health Insurance Service—National Health Screening database of Korea. Females over the age of 50 were diagnosed with osteoporosis based on the International Classification of Diseases 10th revision (ICD-10) codes (M80, M81, and M82) with bisphosphonate prescriptions. The cumulative dose of bisphosphonate was calculated using defined daily doses (DDD) to provide an accurate BP cumulative effect on ONJ occurrence. Osteonecrosis of the jaw was identified using both ICD-10 codes and related procedure codes. The incidence rates of ONJ and hazard ratios were estimated according to the bisphosphonate cumulative dose.ResultsAmong 74,491 included subjects, 190 cases of ONJ were identified. The incidence rate substantially increased after BP cumulative dose over 1 year (25.75 for DDD &lt; 365, which increased to 53.43 for 365 ≤ DDD &lt; 730). Compared to subjects with a cumulative dose of DDD &lt; 365, subjects with a cumulative dose of 365 ≤ DDD &lt; 730 had 2.36-fold hazard for developing ONJ (p &lt; 0.001).ConclusionA bisphosphonate cumulative dose of more than 1 year had an increased risk of ONJ development. A gradual, but not sudden, dose-dependent increase in ONJ risk with BP exposure needs to be considered in providing the optimal BP treatment duration.
Functional Characterization of a Novel Heterozygous Mutation in the Glucokinase Gene That Causes MODY2 in Chinese Pedigrees
Authors: Jiang Feng , Yan Jing , Zhang Rong , Ma Xiaojing , Bao Yuqian , Gu Yujuan , Hu Cheng 
Published: December 2021

BackgroundGlucokinase (GCK) plays a central role in glucose regulation. The heterozygous mutations of GCK can cause a monogenic form of diabetes, maturity-onset diabetes of the young (MODY) directly. In our study, we aimed to explore the mechanism of the novel mutation GCK p.Ala259Thr leading to glucokinase deficiency and hyperglycemia.MethodsThirty early-onset diabetes pedigrees were referred to whole exome sequencing for novel mutations identification. Purified wild-type and mutant GCK proteins were obtained from E.coli systems and then subjected to the kinetic and thermal stability analysis to test the effects on GCK activity.ResultsOne novel missense mutation GCK p.Ala259Thr was identified and co-segregated with diabetes in a Chinese MODY2 pedigree. The kinetic analysis showed that this mutation result in a decreased affinity and catalytic capability for glucose. The thermal stability analysis also indicated that the mutant protein presented dramatically decreased activity at the same temperature.ConclusionOur study firstly identified a novel MODY2 mutation p.Ala259Thr in Chinese diabetes pedigrees. The kinetic and thermal stability analysis confirmed that this mutation caused hyperglycemia through severely damaging the enzyme activities and protein stability.
Genomics and Prognosis Analysis of N6-Methyladenosine Regulators in Lung Adenocarcinoma
Authors: Ma Yanpin , Zhang Huping 
Published: December 2021

Objective: N6-methyladenosine (m6A) modification is involved in modulating various biological processes in human cancers. But the implication of m6A modification in lung adenocarcinoma (LUAD) is still unclear. Hence, this study conducted a comprehensive analysis of the expression and clinical implication of m6A regulators in LUAD.Methods: Consensus clustering analysis of 502 LUAD samples in the TCGA dataset was presented based on the expression profiles of 20 m6A regulators using ConsensusClusterPlus package. Overall survival (OS), activation of signaling pathways and tumor immunity (immune/stromal score, tumor purity, expression of HLA and immune checkpoints, and immune cell infiltration) were compared between m6A modification patterns. The m6A-related genes between patterns were identified and prognostic m6A-related genes were imported into LASSO-cox regression analysis. The m6A risk score was developed and its prognostic implication was evaluated and externally verified in the GSE30219 and GSE72094 dataset. Furthermore, a nomogram that contained independent prognostic indicators was established, followed by external verification.Results: Two m6A modification patterns were clustered across LUAD based on the expression similarity of the m6A regulators via consensus clustering analysis, with distinct OS, activation of signaling pathways and tumor immunity. Totally, 213 m6A-related genes that were identified by comparing two patterns were significantly related to LUAD prognosis. By LASSO method, we constructed the m6A risk score that was a reliable and independent prognostic factor for LUAD. Patients with low m6A risk score displayed a prominent survival advantage. After incorporating independent clinical features, we developed the prognostic nomogram that exhibited high predictive accuracy and the best clinical net benefit for OS.Conclusion: Collectively, our study may provide a clinically useful tool for precise prognostic management and optimization of immunotherapeutic strategies for LUAD patients.
KL-6 as an Immunological Biomarker Predicts the Severity, Progression, Acute Exacerbation, and Poor Outcomes of Interstitial Lung Disease: A Systematic Review and Meta-Analysis
Authors: Zhang Tao , Shen Ping , Duan Chunyan , Gao Lingyun 
Published: December 2021

ObjectInterstitial lung disease (ILD) is a specific form of chronic fibrosing interstitial pneumonia with various etiology. The severity and progression of ILD usually predict the poor outcomes of ILD. Otherwise, Krebs von den Lungen-6 (KL-6) is a potential immunological biomarker reflecting the severity and progression of ILD. This meta-analysis is to clarify the predictive value of elevated KL-6 levels in ILD.MethodEBSCO, PubMed, and Cochrane were systematically searched for articles exploring the prognosis of ILD published between January 1980 and April 2021. The Weighted Mean Difference (WMD) and 95% Confidence Interval (CI) were computed as the effect sizes for comparisons between groups. For the relationship between adverse outcome and elevated KL-6 concentration, Hazard Ratio (HR), and its 95%CI were used to estimate the risk factor of ILD.ResultOur result showed that ILD patients in severe and progressive groups had higher KL-6 levels, and the KL-6 level of patients in the severe ILD was 703.41 (U/ml) than in mild ILD. The KL-6 level in progressive ILD group was 325.98 (U/ml) higher than that in the non-progressive ILD group. Secondly, the KL-6 level of patients in acute exacerbation (AE) of ILD was 545.44 (U/ml) higher than stable ILD. Lastly, the higher KL-6 level in ILD patients predicted poor outcomes. The KL-6 level in death of ILD was 383.53 (U/ml) higher than in survivors of ILD. The pooled HR (95%CI) about elevated KL-6 level predicting the mortality of ILD was 2.05 (1.50–2.78), and the HR (95%CI) for progression of ILD was 1.98 (1.07–3.67).ConclusionThe elevated KL-6 level indicated more severe, more progressive, and predicted the higher mortality and poor outcomes of ILD.
SARS-CoV-2 Specific IgG Antibodies Persist Over a 12-Month Period in Oral Mucosal Fluid Collected From Previously Infected Individuals
Authors: Chellamuthu Prithivi , Angel Aaron N. , MacMullan Melanie A. , Denny Nicholas , Mades Aubree , Santacruz Marilisa , Lopez Ronell , Bagos Cedie , Casian Joseph G. , Trettner Kylie , Lopez Lauren , Nirema Nina , Brobeck Matthew , Kojima Noah , Klausner Jeffrey D. , Turner Fred , Slepnev Vladimir , Ibrayeva Albina 
Published: December 2021

BackgroundDeveloping an understanding of the antibody response, seroprevalence, and seroconversion from natural infection and vaccination against SARS-CoV-2 will give way to a critical epidemiological tool to predict reinfection rates, identify vulnerable communities, and manage future viral outbreaks. To monitor the antibody response on a larger scale, we need an inexpensive, less invasive, and high throughput method.MethodsHere we investigate the use of oral mucosal fluids from individuals recovered from SARS-CoV-2 infection to monitor antibody response and persistence over a 12-month period. For this cohort study, enzyme-linked immunosorbent assays (ELISAs) were used to quantify anti-Spike(S) protein IgG antibodies in participants who had prior SARS-CoV-2 infection and regularly (every 2-4 weeks) provided both serum and oral fluid mucosal fluid samples for longitudinal antibody titer analysis.ResultsIn our study cohort (n=42) with 17 males and 25 females with an average age of 45.6 +/- 19.3 years, we observed no significant change in oral mucosal fluid IgG levels across the time course of antibody monitoring. In oral mucosal fluids, all the participants who initially had detectable antibodies continued to have detectable antibodies throughout the study.ConclusionsBased on the results presented here, we have shown that oral mucosal fluid-based assays are an effective, less invasive tool for monitoring seroprevalence and seroconversion, which offers an alternative to serum-based assays for understanding the protective ability conferred by the adaptive immune response from viral infection and vaccination against future reinfections.
Changes of Dry Eye Related Markers and Tear Inflammatory Cytokines After Upper Blepharoplasty
Authors: Zhao Songjiao , Song Nan , Gong Lan 
Published: December 2021

Objectives: To investigate the changes of dry eye-related clinical manifestations, ocular surface parameters, and tear inflammatory cytokines after upper blepharoplasty.Methods: Forty eyes of 20 who underwent upper blepharoplasty were divided into either the group with or the group without preexisting dry eye before upper blepharoplasty. Ocular Surface Disease Index (OSDI), Schirmer I test, tear meniscus height, lipid layer thickness, non-invasive tear break-up time (NIKBUT), fluorescein tear film break-up time (FBUT), corneal fluorescein staining, meibum expression, lid margin changes, and tear inflammatory cytokines were assessed preoperatively and at 1, 3, and 6 months postoperatively. Correlations between inflammatory cytokines and dry eye-related parameters were determined.Results: The OSDI scores increased significantly at 1 month (p = 0.040) and subsequently decreased to the preoperative levels at 6 months postoperatively in subjects with dry eye. First (f)-NIKBUT and FBUT were significantly shortened at 1, 3, and 6 months postoperatively in subjects with dry eye (f-NIKBUT: p &lt;0.001, p = 0.010, p = 0.042; FBUT: p = 0.002, p = 0.005, p = 0.037, respectively), but were only shortened at 1 month (p = 0.028, p = 0.005) and returned to baseline levels at 6 months postoperatively in subjects without preexisting dry eye. A significant increasing trend of interleukin (IL)-6 was found in both dry eye and subjects without preexisting dry eye (p = 0.016, p = 0.008), while IL-8 and tumor necrosis factor alpha (TNF-α) were only found to be increased in subjects with dry eye postoperatively (p = 0.031, p = 0.031). The levels of IL-8 and TNF-α were positively correlated with OSDI scores (p = 0.046, p = 0.043, respectively) and negatively correlated with f-NIKBUT and FBUT (p = 0.026, p = 0.006, respectively).Conclusions: Upper blepharoplasty might increase the release of tear inflammatory cytokines and tear film instability that contribute to the development of postoperative dry eye in the early postoperative period and the changes most relieved in 6 months. Preexisting dry eye is a higher risk factor for worse and persistent ocular surface damage after upper blepharoplasty.
Physical Exercise vs. Metformin to Improve Delivery- and Newborn-Related Outcomes Among Pregnant Women With Overweight: A Network Meta-Analysis
Authors: Pascual-Morena Carlos , Cavero-Redondo Iván , Álvarez-Bueno Celia , Martínez-Hortelano José Alberto , Reina-Gutiérrez Sara , Saz-Lara Alicia , Núñez de Arenas-Arroyo Sergio , Martínez-Vizcaíno Vicente 
Published: December 2021

Background: Overweight/obesity is associated with the risk of delivery- and newborn-related complications in pregnancy. Interventions such as exercise or metformin could reduce the risk of these complications.Objective: To estimate and compare the effects of different types of exercise interventions (i.e., aerobic, resistance, combined exercise) and metformin on delivery- and newborn-related outcomes among pregnant women with overweight/obesity.Methods: MEDLINE, Scopus, Web of Science, Cochrane Library databases and the gray literature were searched from inception to September 2021. This systematic review was registered in PROSPERO (CDR: 42019121715). Randomized controlled trials (RCTs) of metformin or an exercise intervention aimed at preventing cesarean section, preterm birth, macrosomia, or birth weight among pregnant women with overweight/obesity were included. Random effects meta-analyses and frequentist network meta-analyses (NMA) were conducted for each outcome.Results: Fifteen RCTs were included. In the NMA, metformin reduced the risk of cesarean section (RR = 0.66, 95% CI: 0.46, 0.95), combined exercise reduced the risk of macrosomia (RR = 0.37, 95% CI: 0.14, 0.95), and aerobic exercise reduced birth weight (mean difference = −96.66 g, 95% CI: −192.45, −0.88). In the subgroup among pregnant women with obesity, metformin reduced the risk of cesarean section (RR = 0.66, 95% CI: 0.45, 0.97).Conclusions: Combined exercise could reduce the risk of macrosomia in pregnant women with overweight, whereas metformin could reduce the risk of cesarean section in pregnant women with obesity. However, previous evidence suggests a larger effect of physical exercise in other outcomes for this population group. Therefore, the medicalization of healthy pregnant women with obesity is not justified by the current evidence.Systematic Review Registration: PROSPERO: CRD42019121715; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019121715
Association of the Serum Levels of the Nucleocapsid Antigen of SARS-CoV-2 With the Diagnosis, Disease Severity, and Antibody Titers in Patients With COVID-19: A Retrospective Cross-Sectional Study
Authors: Yokoyama Rin , Kurano Makoto , Nakano Yuki , Morita Yoshifumi , Ohmiya Hiroko , Kishi Yoshiro , Okada Jun , Qian Chungen , Xia Fuzhen , He Fan , Zheng Liang , Yu Yi , Mizoguchi Miyuki , Higurashi Yoshimi , Harada Sohei , Jubishi Daisuke , Okamoto Koh , Moriya Kyoji , Kodama Tatsuhiko , Yatomi Yutaka 
Published: December 2021

Background: Several types of laboratory tests for COVID-19 have been established to date; however, the clinical significance of the serum SARS-CoV-2 nucleocapsid (N) antigen levels remains to be fully elucidated. In the present study, we attempted to elucidate the usefulness and clinical significance of the serum N antigen levels.Methods: We measured the serum N antigen levels in 391 serum samples collected from symptomatic patients with a confirmed diagnosis of COVID-19 and 96 serum samples collected from patients with non-COVID-19, using a fully automated chemiluminescence immunoassay analyzer.Results: Receiver operating characteristic analysis identified the optimal cutoff value of the serum N antigen level (cutoff index, based on Youden’s index) as 0.255, which yielded a sensitivity and specificity for the diagnosis of COVID-19 of 91.0 and 81.3%, respectively. The serum N antigen levels were significantly higher in the patient groups with moderate and severe COVID-19 than with mild disease. Moreover, a significant negative correlation was observed between the serum N antigen levels and the SARS-CoV-2 IgG antibody titers, especially in patients with severe COVID-19.Conclusion: Serum N antigen testing might be useful both for the diagnosis of COVID-19 and for obtaining a better understanding of the clinical features of the disease.
A Case Report: Genetically Distinct Severe Acute Respiratory Syndrome Coronavirus-2 Variant Causing Reinfection
Authors: Hossain Mohammad Enayet , Rahman Md. Mahfuzur , Alam Md. Shaheen , Sarmin Monira , Karim Yeasir , Hasan Mehedi , Hoque Ananya Ferdous , Hasan Md. Mahmudul , Rahman Mohammed Ziaur , Chisti Mohammod Jobayer , Rahman Mustafizur 
Published: December 2021

Background: The emergence of novel variants has been a great deal of international concern since the recently published data suggest that previous infections with SARS-CoV-2 may not protect an individual from new variants. We report a patient had two distinct episodes of COVID-19 with different variants of SARS-CoV-2.Methods: The nasopharyngeal samples collected from the two episodes were subjected to whole-genome sequencing and comparative genome analysis.Results: The first infection presented with mild symptoms, while the second infection presented with severe outcomes which occurred 74 days after the patient recovered from the first episode. He had elevated C-reactive protein, ferritin, and bilateral consolidation as a sign of acute infection. Genome analysis revealed that the strains from the first and second episodes belonged to two distinct Nexstrain clades 20B and 20I and Pangolin lineages B.1.1.25 and B.1.1.7, respectively. A total of 36 mutations were observed in the episode-2 strain when compared with the reference strain Wuhan-Hu-1. Among them, eight mutations were identified in the receptor-binding domain (RBD).Conclusion: Our findings concern whether the immunity acquired by natural infection or mass vaccination could confer adequate protection against the constantly evolving SARS-CoV-2. Therefore, continuous monitoring of genetic variations of SARS-CoV-2 strains is crucial for interventions such as vaccine and drug designs, treatment using monoclonal antibodies, and patient management.
Efficacy of Scalp Acupuncture in Patients With Post-stroke Hemiparesis: Meta-Analysis of Randomized Controlled Trials
Authors: Huang Yuan-Ju , Huang Chih-Shan , Leng Kuo-Feng , Sung Jia-Ying , Cheng Sheng-Wei 
Published: December 2021

Objectives:To conduct a meta-analysis to assess the efficacy of scalp acupuncture (SA) in patients with stroke and consequent hemiparesis regardless of brain infarction or intracerebral hemorrhage.Methods:A literature search of randomized controlled trials (RCTs) on SA for stroke was performed in five databases up to May 10, 2021. We investigated three types of outcome: motor function, sequelae of poststroke hemiparesis, and adverse effects. Methodological quality was assessed using the revised Cochrane risk of bias tool version 2.0.Results:Of 1,063 papers, 30 RCTs involving Fugl–Meyer Assessment were selected, among which 10 and four RCTs were selected for evaluation of courses lasting of 1 and 3 months, respectively. The meta-analysis of 1- and 3-month courses revealed significant differences in the motor function of the SA plus Western standard treatment group vs. Western standard treatment only (medication plus rehabilitation;P&lt; 0.001). A 3-month course tended to result in better outcomes than a 1-month course.Conclusions:Our meta-analysis results reveal that SA improves motor function in patients with acute to chronic stroke, regardless of brain infarction or intracerebral hemorrhage. However, because of a lack of methodological quality, thoroughly planned clinical studies are still required.
Kinematic Changes in the Uninjured Limb After a Traumatic Brachial Plexus Injury
Authors: Souza Lidiane , Lustosa Luiggi , Silva Ana Elisa Lemos , Martins José Vicente , Pozzo Thierry , Vargas Claudia D. 
Published: December 2021

Background: Traumatic brachial plexus injury (TBPI) typically causes sensory, motor and autonomic deficits of the affected upper limb. Recent studies have suggested that a unilateral TBPI can also affect the cortical representations associated to the uninjured limb.Objective: To investigate the kinematic features of the uninjured upper limb in participants with TBPI.Methods: Eleven participants with unilateral TBPI and twelve healthy controls matched in gender, age and anthropometric characteristics were recruited. Kinematic parameters collected from the index finger marker were measured while participants performed a free-endpoint whole-body reaching task and a cup-to-mouth task with the uninjured upper limb in a standing position.Results: For the whole-body reaching task, lower time to peak velocity (p = 0.01), lower peak of velocity (p = 0.003), greater movement duration (p = 0.04) and shorter trajectory length (p = 0.01) were observed in the TBPI group compared to the control group. For the cup-to-mouth task, only a lower time to peak velocity was found for the TBPI group compared to the control group (p = 0.02). Interestingly, no differences between groups were observed for the finger endpoint height parameter in either of the tasks. Taken together, these results suggest that TBPI leads to a higher cost for motor planning when it comes to movements of the uninjured limb as compared to healthy participants. This cost is even higher in a task with a greater postural balance challenge.Conclusion: This study expands the current knowledge on bilateral sensorimotor alterations after unilateral TBPI and should guide rehabilitation after a peripheral injury.