bluuebunny/crossref_metadata_2025_split huggingface dataset:
What Is the Optimal Timing of Transplantation of Neural Stem Cells in Spinal Cord Injury? A Systematic Review and Network Meta-Analysis Based on Animal Studies
Authors: Shang Zhizhong , Li Dongliang , Chen Jinlei , Wang RuiRui , Wang Mingchuan , Zhang Baolin , Wang Xin , Wanyan Pingping 
Published: March 2022

ObjectiveThe optimal transplantation timing of neural stem cells in spinal cord injury is fully explored in animal studies to reduce the risk of transformation to clinical practice and to provide valuable reference for future animal studies and clinical research.MethodSeven electronic databases, namely, PubMed, Web of Science, Embase, Wanfang, Chinese Scientific Journal Database (CSJD-VIP), China Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI), were searched. The studies were retrieved from inception to November 2021. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality based on the inclusion criteria.Results and DiscussionThirty-nine studies were incorporated into the final analyses. Based on the subgroup of animal models and transplantation dose, the results of network meta-analysis showed that the effect of transplantation in the subacute phase might be the best. However, the results of traditional meta-analysis were inconsistent. In the moderate-dose group of moderate spinal cord injury model and the low-dose group of severe spinal cord injury model, transplantation in the subacute phase did not significantly improve motor function. Given the lack of evidence for direct comparison between different transplantation phases, the indirectness of our network meta-analysis, and the low quality of evidence in current animal studies, our confidence in recommending cell transplantation in the subacute phase is limited. In the future, more high-quality, direct comparative studies are needed to explore this issue in depth.
CASE REPORT: Serial Cases of False-Positive Flow-Cytometry T Cell Crossmatch Associated With Anti–Blood Type Antibodies in Patients Undergoing ABO-Incompatible Kidney Transplantation
Authors: Hayashi Ayaka , Yamamoto Izumi , Kawabe Mayuko , Kobayashi Akimitsu , Ito Makoto , Hotta Kiyohiko , Shinohara Nobuo , Tasaki Tetsunori , Yokoo Takashi , Iwami Daiki 
Published: March 2022

BackgroundA positive flow-cytometry T cell crossmatch (FTXM) has important prognostic implications, even when the complement-dependent cytotoxicity crossmatch is negative. Recent studies have shown that ABO incompatibility is associated with positive FTXM, but the underlying mechanism remains poorly understood.CasesIn five ABO blood type O recipients of kidneys from wives with type B, FTXM was positive but complement-dependent cytotoxicity crossmatch was negative. Application of a solid-phase technique (LABScreen) revealed no case with antibodies to donor-specific human leukocyte antigen. After removal of type B antibodies from patient sera, FTXM was negative for all five patients. In one tested case, the eluate prepared from the donor’s T lymphocyte agglutinated only type B red blood cells, implying the existence of blood type B substances on donor T lymphocytes.DiscussionFalse-positive FTXM reflects blood type B substrates bound to T lymphocytes. Repeat FTXM after incubation with donor-type red blood cells (to adsorb anti-ABO antibodies) was negative. This phenomenon explains the discrepancy between FTXM and solid-phase bead assays. Demonstration of type B substances on donor T lymphocytes is necessary before absolute test validity is confirmed.ConclusionFalse-positive FTXM may be associated with type B antibodies bound to T lymphocytes when a blood type O recipient receives tissue from a type B donor. This phenomenon explains the false-positive FTXM observed in the setting of ABO-incompatible kidney transplantation.
Case Report: Challenges in the Diagnosis of a Case of Mal de Meleda and a Therapeutic Attempt of Ixekizumab and Adalimumab
Authors: Dai Yuwei , Zheng Xiaodong , Zhang Qi , Hu Xia , Wang Peiguang , Yang Sen 
Published: March 2022

BackgroundMal de Meleda (MDM, OMIM 248300) is an autosomal recessive disease characterized by symmetrical and progressive palmoplantar hyperkeratosis soon after birth. Mutations in SLURP1 gene could lead to MDM. Clinically, MDM is easily misdiagnosed as other types of keratoderma due to phenotypic variation and overlap.Objective and MethodsA patient with suspected MDM was confirmed by the combination of next-generation sequencing and Exomiser, and the patient was attempted with the treatment of Ixekizumab and Adalimumab.ResultsA homozygous mutation c.256G&gt;A (p.Gly86Arg) in the SLURP1 gene was identified in the patient. The inflammatory erythemas on his hands, feet and buttocks were mildly relieved after the treatment of high dose of Ixekizumab.ConclusionsOur findings helps to enhance the understanding of MDM. Ixekizumab may be a potential strategy to treat MDM.
Comparison of SARS-CoV-2 Variants of Concern Alpha (B.1.1.7) vs. Beta (B.1.351) in Critically Ill Patients: A Multicenter Cohort Study
Authors: Louis Guillaume , Belveyre Thibaut , Goetz Christophe , Gibot Sébastien , Dunand Paul , Conrad Marie , Gaci Rostane , Gette Sébastien , Ouamara Nadia , Perez Pascale , Cadoz Cyril , Picard Yoann , Mellati Nouchan 
Published: March 2022

ObjectivesThe clinical outcomes of the Beta (B.1.351) variant of concern (VOC) of the SARS-CoV-2 virus remain poorly understood. In early 2021, northeastern France experienced an outbreak of Beta that was not observed elsewhere. This outbreak slightly preceded and then overlapped with a second outbreak of the better understood VOC Alpha (B.1.1.7) in the region. This situation allowed us to contemporaneously compare Alpha and Beta in terms of the characteristics, management, and outcomes of critically ill patients.MethodsA multicenter prospective cohort study was conducted on all consecutive adult patients who had laboratory confirmed SARS CoV-2 infection, underwent variant screening, and were admitted to one of four intensive care units (ICU) for acute respiratory failure between January 9th and May 15th, 2021. Primary outcome was 60-day mortality. Differences between Alpha and Beta in terms of other outcomes, patient variables, management, and vaccination characteristics were also explored by univariate analysis. The factors that associated with 60-day death in Alpha- and Beta-infected patients were examined with logistic regression analysis.ResultsIn total, 333 patients (median age, 63 years; 68% male) were enrolled. Of these, 174 and 159 had Alpha and Beta, respectively. The two groups did not differ significantly in terms of 60-day mortality (19 vs. 23%), 28-day mortality (17 vs. 20%), need for mechanical ventilation (60 vs. 61%), mechanical ventilation duration (14 vs. 15 days), other management variables, patient demographic variables, comorbidities, or clinical variables on ICU admission. The vast majority of patients were unvaccinated (94%). The remaining 18 patients had received a partial vaccine course and 2 were fully vaccinated. The vaccinated patients were equally likely to have Alpha and Beta.ConclusionsBeta did not differ from Alpha in terms of patient characteristics, management, or outcomes in critically ill patients.Trial RegistrationClinicalTrials.gov, identifier: NCT04906850.
Incidence Rates of Myomectomy-Related Mortality and Venous Thromboembolism in South Korea: A Population-Based Study
Authors: Yuk Jin-Sung , Kim Myounghwan 
Published: March 2022

BackgroundUterine leiomyomas are the most commonly observed pathologies, with an estimated prevalence of 4. 5–68.6%. We aimed to calculate myomectomy-related mortality and venous thromboembolism incidence rates in the Republic of Korea.MethodsThe data of patients who underwent myomectomy (2009–2018) were obtained from the Health Insurance Review and Assessment Service-National Inpatient Sample. The mortality rate after myomectomy was calculated using the leiomyoma diagnostic codes and myomectomy procedure codes. The incidence rates of venous thromboembolism, deep vein thrombosis, and pulmonary embolism were calculated using their diagnostic codes, with concomitant use of an antithrombotic agent during the same period or within 90 days after myomectomy.ResultsThe data of 23,549 women aged 15–55 years who underwent myomectomy were extracted. The myomectomy rate was 14.6 ± 0.1 per 10,000 patients. The average age was 39.39 ± 0.04 years. One patient who underwent myomectomy died; this patient did not have concomitant venous thromboembolism. The post-myomectomy mortality rate was 1.3 ± 0.8 per 10,000 patients. The incidence rates of venous thromboembolism, deep vein thrombosis, and pulmonary embolism after myomectomy were 5.7 ± 1.6 per 10,000 patients, 4.4 ± 1.4 per 10,000 patients, and 2.5 ± 1 per 10,000 patients, respectively. The conversion rate to hysterectomy was 2.9 ± 1.1 per 10,000 patients.ConclusionThe current mortality rate after myomectomy (0.013%) is substantially lower than that described in previous studies at the turn of the 20th century. The incidence of venous thromboembolism is also considerably lower than that in the general population worldwide.
Modification Patterns of DNA Methylation-Related lncRNAs Regulating Genomic Instability for Improving the Clinical Outcomes and Tumour Microenvironment Characterisation of Lower-Grade Gliomas
Authors: Maimaiti Aierpati , Aili Yirizhati , Turhon Mirzat , Kadeer Kaheerman , Aikelamu Paziliya , Wang Zhitao , Niu Weiwei , Aisha Maimaitili , Kasimu Maimaitijiang , Wang Yongxin , Wang Zengliang 
Published: March 2022

Background: DNA methylation is an important epigenetic modification that affects genomic instability and regulates gene expression. Long non-coding RNAs (lncRNAs) modulate gene expression by interacting with chromosomal modifications or remodelling factors. It is urgently needed to evaluate the effects of DNA methylation-related lncRNAs (DMlncRNAs) on genome instability and further investigate the mechanism of action of DMlncRNAs in mediating the progression of lower-grade gliomas (LGGs) and their impact on the immune microenvironment.Methods: LGG transcriptome data, somatic mutation profiles and clinical features analysed in the present study were obtained from the CGGA, GEO and TCGA databases. Univariate, multivariate Cox and Lasso regression analyses were performed to establish a DMlncRNA signature. The KEGG and GO analyses were performed to screen for pathways and biological functions associated with key genes. The ESTIMATE and CIBERSORT algorithms were used to determine the level of immune cells in LGGs and the immune microenvironment fraction. In addition, DMlncRNAs were assessed using survival analysis, ROC curves, correlation analysis, external validation, independent prognostic analysis, clinical stratification analysis and qRT-PCR.Results: We identified five DMlncRNAs with prognostic value for LGGs and established a prognostic signature using them. The Kaplan–Meier analysis revealed 10-years survival rate of 10.10% [95% confidence interval (CI): 3.27–31.40%] in high-risk patients and 57.28% (95% CI: 43.17–76.00%) in low-risk patients. The hazard ratio (HR) and 95% CI of risk scores were 1.013 and 1.009–1.017 (p &lt; 0.001), respectively, based on the univariate Cox regression analysis and 1.009 and 1.004–1.013 (p &lt; 0.001), respectively, based on the multivariate Cox regression analysis. Therefore, the five-lncRNAs were identified as independent prognostic markers for patients with LGGs. Furthermore, GO and KEGG analyses revealed that these lncRNAs are involved in the prognosis and tumorigenesis of LGGs by regulating cancer pathways and DNA methylation.Conclusion: The findings of the study provide key information regarding the functions of lncRNAs in DNA methylation and reveal that DNA methylation can regulate tumour progression through modulation of the immune microenvironment and genomic instability. The identified prognostic lncRNAs have high potential for clinical grouping of patients with LGGs to ensure effective treatment and management.
Highly Expressed Soluble Recombinant Anti-GFP VHHs in Escherichia coli via Optimized Signal Peptides, Strains, and Inducers
Authors: Chao Shuangying , Liu Yuhang , Ding Ning , Lin Yue , Wang Qian , Tan Junwen , Li Wei , Zheng Yang , Hu Xuejun , Li Junming 
Published: March 2022

Antigen-binding variable domains of the H chain of heavy-chain antibodies (VHHs), also known as nanobodies (Nbs), are of great interest in imaging technique, disease prevention, diagnosis, and therapy. High-level expression of soluble Nbs is very important for its industrial production. In this study, we optimized the expression system of anti-green fluorescent protein (GFP) VHHs with three different signal peptides (SPs), outer-membrane protein A (OmpA), pectate lyase B (PelB), and L-asparaginase II SP (L-AsPsII), in different Escherichia coli strains via isopropyl β-D-thiogalactoside (IPTG) induction and auto-induction, respectively. The solubility of recombinant anti-GFP VHHs with PelB or OmpA was significantly enhanced to the same extent by IPTG induction and auto-induction in BL21 (DE3) E. coli strain and the maximum yield of target protein reached approximately 0.4 mg/l in a shake flask. The binding activity of recombinant anti-GFP VHHs was also confirmed to be retained by native-polyacrylamide gel electrophoresis (PAGE). These results suggest that SPs like OmpA and PelB could efficiently improve the recombinant anti-GFP VHH solubility without changing its bioactivity, providing a novel strategy to optimize the E. coli expression system of soluble VHHs, and lay the foundation for the industrial production of soluble recombinant anti-GFP VHHs and the research of other VHHs in the future.
Functional Brain Connectivity in Mild Cognitive Impairment With Sleep Disorders: A Study Based on Resting-State Functional Magnetic Resonance Imaging
Authors: Luo Yuxi , Qiao Mengyuan , Liang Yuqing , Chen Chongli , Zeng Lichuan , Wang Lin , Wu Wenbin 
Published: March 2022

PurposeTo investigate the effect of sleep disorder (SD) on the changes of brain network dysfunction in mild cognitive impairment (MCI), we compared network connectivity patterns among MCI, SD, and comorbid MCI and sleep disorders (MCI-SD) patients using resting state functional magnetic resonance imaging (RS-fMRI).Patients and MethodsA total of 60 participants were included in this study, 20 each with MCI, SD, or MCI-SD. And all participants underwent structural and functional MRI scanning. The default-mode network (DMN) was extracted by independent component analysis (ICA), and regional functional connectivity strengths were calculated and compared among groups.ResultsCompared to MCI patients, The DMN of MCI-SD patients demonstrated weaker functional connectivity with left middle frontal gyrus, right superior marginal gyrus, but stronger connectivity with the left parahippocampus, left precuneus and left middle temporal gyrus. Compared to the SD group, MCI-SD patients demonstrated weaker functional connectivity with right transverse temporal gyrus (Heschl’s gyrus), right precentral gyrus, and left insula, but stronger connectivity with posterior cerebellum, right middle occipital gyrus, and left precuneus.ConclusionPatients with MCI-SD show unique changes in brain network connectivity patterns compared to MCI or SD alone, likely reflecting a broader functional disconnection and the need to recruit more brain regions for functional compensation.
Generalized Fast Discharges Along the Genetic Generalized Epilepsy Spectrum: Clinical and Prognostic Significance
Authors: Cerulli Irelli Emanuele , Barone Francesca Antonietta , Mari Luisa , Morano Alessandra , Orlando Biagio , Salamone Enrico Michele , Marchi Angela , Fanella Martina , Fattouch Jinane , Placidi Fabio , Giallonardo Anna Teresa , Izzi Francesca , Di Bonaventura Carlo 
Published: March 2022

ObjectiveTo investigate the electroclinical characteristics and the prognostic impact of generalized fast discharges in a large cohort of genetic generalized epilepsy (GGE) patients studied with 24-h prolonged ambulatory electroencephalography (paEEG).MethodsThis retrospective multicenter cohort study included 202 GGE patients. The occurrence of generalized paroxysmal fast activity (GPFA) and generalized polyspike train (GPT) was reviewed. GGE patients were classified as having idiopathic generalized epilepsy (IGE) or another GGE syndrome (namely perioral myoclonia with absences, eyelid myoclonia with absences, epilepsy with myoclonic absences, generalized epilepsy with febrile seizures plus, or GGE without a specific epilepsy syndrome) according to recent classification proposals.ResultsGPFA/GPT was found in overall 25 (12.4%) patients, though it was significantly less frequent in IGE compared with other GGE syndromes (9.3 vs. 25%,p= 0.007). GPFA/GPT was found independently of seizure type experienced during history, the presence of mild intellectual disability/borderline intellectual functioning, or EEG features. At multivariable analysis, GPFA/GPT was significantly associated with drug resistance (p= 0.04) and with a higher number of antiseizure medications (ASMs) at the time of paEEG (p&lt; 0.001) and at the last medical observation (p&lt; 0.001). Similarly, GPFA/GPT, frequent/abundant generalized spike-wave discharges during sleep, and a higher number of seizure types during history were the only factors independently associated with a lower chance of achieving 2-year seizure remission at the last medical observation. Additionally, a greater number of GPFA/GPT discharges significantly discriminated between patients who achieved 2-year seizure remission at the last medical observation and those who did not (area under the curve = 0.77, 95% confidence interval 0.57–0.97,p= 0.02)ConclusionWe found that generalized fast discharges were more common than expected in GGE patients when considering the entire GGE spectrum. In addition, our study highlighted that GPFA/GPT could be found along the entire GGE continuum, though their occurrence was more common in less benign GGE syndromes. Finally, we confirmed that GPFA/GPT was associated with difficult-to-treat GGE, as evidenced by the multivariable analysis and the higher ASM load during history.
Body Roundness Index and Waist–Hip Ratio Result in Better Cardiovascular Disease Risk Stratification: Results From a Large Chinese Cross-Sectional Study
Authors: Li Ying , He Yongmei , Yang Lin , Liu Qingqi , Li Chao , Wang Yaqin , Yang Pingting , Wang Jiangang , Chen Zhiheng , Huang Xin 
Published: March 2022

BackgroundThe appropriate optimal anthropometric indices and their thresholds within each BMI category for predicting those at a high risk of cardiovascular disease risk factors (CVDRFs) among the Chinese are still under dispute.ObjectivesWe aimed to identify the best indicators of CVDRFs and the optimal threshold within each BMI category among the Chinese.MethodsBetween 2012 and 2020, a total of 500,090 participants were surveyed in Hunan, China. Six anthropometric indices including waist circumference (WC), a body shape index (ABSI), body roundness index (BRI), waist–hip ratio (WHR), hip circumference (HC), and waist–height ratio (WHtR) were evaluated in the present study. Considered CVDRFs included dyslipidaemia, hypertension, diabetes mellitus (DM), and chronic kidney disease (CKD). The associations of anthropometrics with CVDRFs within each BMI category were evaluated through logistic regression models. The area under the receiver operating characteristic curve (AUROC) was used to assess the predictive abilities.ResultsFor the presence of at least one CVDRFs, the WHR had the highest AUROC in overweight [0.641 (95%CI:0.638, 0.644)] and obese [0.616 (95%CI:0.609, 0.623)] men. BRI had the highest AUROC in underweight [0.649 (95%CI:0.629, 0.670)] and normal weight [0.686 (95%CI:0.683, 0.690)] men. However, the BRI had the highest discrimination ability among women in all the BMI categories, with AUROC ranging from 0.641 to 0.727. In most cases, the discriminatory ability of WHtR was similar to BRI and was easier to calculate; therefore, thresholds of BRI, WHR, and WHtR for CVDRFs identification were all calculated. In men, BRI thresholds of 1.8, 3.0, 3.9, and 5.0, WHtR thresholds of 0.41, 0.48, 0.53, and 0.58, and WHR thresholds of 0.81, 0.88, 0.92, and 0.95 were identified as optimal thresholds across underweight, normal weight, overweight, and obese populations, respectively. The corresponding BRI values in women were 1.9, 2.9, 4.0, and 5.2, respectively, and WHtR were 0.41, 0.48, 0.54, and 0.59, while the WHR values were 0.77, 0.83, 0.88, and 0.90. The recommended BRI, WHtR, or WHR cut-offs could not statistically differentiate high-risk CKD or hypercholesterolemia populations.ConclusionsWe found that BRI and WHR were superior to other indices for predicting CVD risk factors, except CKD or hypercholesterolemia, among the Chinese.
Serum Vitamin D Levels in Relation to Hypertension and Pre-hypertension in Adults: A Systematic Review and Dose–Response Meta-Analysis of Epidemiologic Studies
Authors: Mokhtari Elahe , Hajhashemy Zahra , Saneei Parvane 
Published: March 2022

BackgroundFindings of observational studies that evaluated the association of serum vitamin D status and high blood pressure were contradictory. This meta-analysis of epidemiologic studies assessed the relation of serum vitamin D levels to hypertension (HTN) and pre-hypertension in adults.MethodsWe conducted a systematic search of all published articles up to March 2021, in four electronic databases (MEDLINE (PubMed), Web of Science (ISI), Embase and Scopus), and Google scholar. Seventy epidemiologic studies (10 prospective cohort, one nested case–control, and 59 cross-sectional investigations) that reported relative risks (RRs), odds ratios (ORs), hazard ratios, or prevalence ratios with 95% CIs for HTN or pre-hypertension in relation to serum vitamin D concentrations in adults were included in the analysis.ResultsIn prospective studies, a 16% decrease in risk of hypertension was observed in participants with high levels of serum vitamin D compared to low levels (RR: 0.84; 95%CI: 0.73, 0.96; 12 effect sizes). Dose–response analysis in prospective studies revealed that each 25 nmol/L increase in serum vitamin D concentrations resulted in 5% reduced risk of HTN (RR: 0.95; 95% CI: 0.90, 1.00). Also, a significant nonlinear relationship between serum vitamin D levels and HTN was found (Pnonlinearity&lt; 0.001). In cross-sectional investigations, highest vs. lowest level of serum vitamin D was related to reduced odds of HTN (OR: 0.84; 95%CI: 0.79, 0.90; 66 effect sizes) and pre-hypertension (OR: 0.75; 0.95%CI: 0.68, 0.83; 9 effect sizes). Dose–response analysis in these studies showed that each 25 nmol/L increase in serum vitamin D levels was related to a significant 6% reduction in odds of hypertension in all populations (RR: 0.94; 95%CI: 0.90, 0.99) and 3% in studies with representative populations (RR: 0.97; 95%CI: 0.95, 0.99).ConclusionThis meta-analysis of epidemiologic studies disclosed that serum vitamin D concentrations were inversely related to the risk of HTN in adults, in a dose–response manner in both prospective cohort and cross-sectional studies.Systematic Review Registration:http://www.crd.york.ac.uk/Prospero, identifier: CRD42021251513.