bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Level of Serum and Cerebrospinal Fluid of Heparan Sulfate and Hyaluronic Acid Might Be a Biomarker of Severity of Neuromyelitis Optica
Authors: Zhang Qi , Pei Shanshan , Zhou Zheyi , Wang Zhanhang , Peng Yu , Chen Jinyu , Wang Honghao 
Published: July 2021

BackgroundNeuromyelitis optica (NMO), multiple sclerosis (MS) and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy are idiopathic inflammatory demyelinating diseases (IIDDs) that mainly present as encephalomyelitis. Heparan sulfate (HS) and hyaluronic acid (HA) are two components of glycocalyx, a carbohydrate-rich layer on the surface of blood vessels that mediates interaction with blood. Degradation of glycocalyx in NMO is poorly understood.PurposeTo detect the serum and cerebrospinal fluid (CSF) levels of shed HS and HA and to correlate these levels with disease severity to determine their diagnostic value.MethodsWe obtained serum and CSF samples from 24 NMO patients, 15 MS patients, 10 autoimmune GFAP astrocytopathy patients, and 18 controls without non-inflammatory neurological diseases. Soluble HS and HA, and IFNγ, IL17A, and matrix metalloproteinase (MMP) 1 were detected via ELISA.ResultsSerum and CSF levels of HS, HA and related cytokines but not of plasma MMP1 were significantly elevated in these diseases. Notably, HS and HA levels were positively correlated with Expanded Disability Status Scale scores.ConclusionsOur results indicate glycocalyx degradation and inflammation in NMO, MS and autoimmune GFAP astrocytopathy. Moreover, increased shedding of HS or HA may indicate a worse clinical situation. Furthermore, therapeutic strategies that protect glycocalyx may be effective in these diseases.
Janus Kinase Inhibition Ameliorates Ischemic Stroke Injury and Neuroinflammation Through Reducing NLRP3 Inflammasome Activation via JAK2/STAT3 Pathway Inhibition
Authors: Zhu Hua , Jian Zhihong , Zhong Yi , Ye Yingze , Zhang Yonggang , Hu Xinyao , Pu Bei , Gu Lijuan , Xiong Xiaoxing 
Published: July 2021

BackgroundInflammatory responses play a multiphase role in the pathogenesis of cerebral ischemic stroke (IS). Ruxolitinib (Rux), a selective oral JAK 1/2 inhibitor, reduces inflammatory responses via the JAK2/STAT3 pathway. Based on its anti-inflammatory and immunosuppressive effects, we hypothesized that it may have a protective effect against stroke. The aim of this study was to investigate whether inhibition of JAK2 has a neuroprotective effect on ischemic stroke and to explore the potential molecular mechanisms.MethodsRux, MCC950 or vehicle was applied to middle cerebral artery occlusion (MCAO) mice in vivo and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. After 3 days of reperfusion, neurological deficit scores, infarct volume and brain water content were assessed. Immunofluorescence staining and western blots were used to measure the expression of NLRP3 inflammasome components. The infiltrating cells were investigated by flow cytometry. Proinflammatory cytokines were assessed by RT-qPCR. The expression of the JAK2/STAT3 pathway was measured by western blots. Local STAT3 deficiency in brain tissue was established with a lentiviral vector carrying STAT3 shRNA, and chromatin immunoprecipitation (ChIP) assays were used to investigate the interplay between NLRP3 and STAT3 signaling.ResultsRux treatment improved neurological scores, decreased the infarct size and ameliorated cerebral edema 3 days after stroke. In addition, immunofluorescence staining and western blots showed that Rux application inhibited the expression of proteins related to the NLRP3 inflammasome and phosphorylated STAT3 (P-STAT3) in neurons and microglia/macrophages. Furthermore, Rux administration inhibited the expression of proinflammatory cytokines, including TNF-α, IFN-γ, HMGB1, IL-1β, IL-2, and IL-6, suggesting that Rux may alleviate IS injury by inhibiting proinflammatory reactions via JAK2/STAT3 signaling pathway regulation. Infiltrating macrophages, B, T, cells were also reduced by Rux. Local STAT3 deficiency in brain tissue decreased histone H3 and H4 acetylation on the NLRP3 promoter and NLRP3 inflammasome component expression, indicating that the NLRP3 inflammasome may be directly regulated by STAT3 signaling. Rux application suppressed lipopolysaccharide (LPS)-induced NLRP3 inflammasome secretion and JAK2/STAT3 pathway activation in the OGD/R model in vitro.ConclusionJAK2 inhibition by Rux in MCAO mice decreased STAT3 phosphorylation, thus inhibiting the expression of downstream proinflammatory cytokines and the acetylation of histones H3 and H4 on the NLRP3 promoter, resulting in the downregulation of NLRP3 inflammasome expression.
Risks of Placenta Previa and Hypertensive Disorders of Pregnancy Are Associated With Endometrial Preparation Methods in Frozen-Thawed Embryo Transfers
Authors: Tao Yu , Kuang Yanping , Wang Ningling 
Published: July 2021

Background: Endometrial preparation is essential in frozen-thawed embryo transfer (FET) cycles. Recent studies suggested that different endometrial preparation methods may influence obstetrical complications. However, the association between hormone replacement therapy (HRT) and ovarian stimulation (OS) FET endometrial preparation and obstetrical complications remains unknown.Methods: This retrospective cohort study included a total of 79,662 confirmed embryo transfer cycles during the period from January 2003 to December 2019. After exclusion, the remaining cases were categorized into an ovarian stimulation FET group (OS FET group, n = 29,121) and a hormone replacement therapy FET group (HRT FET group, n = 26,776) and subjected to the analyses. The primary outcome was the rate of obstetrical complications included placenta previa, placenta abruption, hypertensive disorders of pregnancy (HDP), placenta accreta, gestational diabetes mellitus (GDM), preterm premature rupture of the membrane (pPROM). The secondary outcome was pregnancy outcomes such as live birth rate, birth weight, pre-term and post-term delivery and cesarean sections. In order to minimize the bias, 10 pregnancy-related factors were adjusted in multiple logistic regression analysis.Results: Placenta previa (0.6 vs. 1.2%, P &lt; 0.001) and HDP (3.5 vs. 5.3%, P &lt; 0.001) were found lower in the OS FET than HRT FET group. Cesarean section was observed lower in the OS than HRT group (76.3 vs. 84.3%, P &lt; 0.001). After adjustment for 10 important pregnancy-related confounding factors, we found that the risk of placenta previa (aOR 0.54, 95% CI 0.39–0.73) and HDP (aOR 0.65, 95% CI 0.57–0.75) and cesarean section (aOR 0.61, 95% CI 0.57–0.66) were still significantly reduced in the OS than HRT group. Furthermore, live birth rates were higher (80.0 vs. 76.0%, P &lt; 0.001), and the miscarriage rate was lower (17.7 vs. 21.3%, P &lt; 0.001) for pregnancies conceived with OS FET than with HRT FET. And the average birth weight was lower in the OS group compared to HRT group (2982.3 ± 636.4 vs. 3025.0 ± 659.0, P &lt; 0.001), as well as the small-for-gestational age (SGA) was higher (8.7 vs. 7.2%, P &lt; 0.001) and the large-for-gestational age (LGA) was lower (7.2 vs. 8.6%, P &lt; 0.001) in the OS group than in the HRT group.Conclusions: The risks of placenta previa and HDP were lower in patients conceiving after OS FET than in those after HRT FET. Further prospective studies are required to further clarify the mechanism underlying the association between endometrium preparation and obstetrical complications.
Serum Metabolic Profile in Patients With Long-Covid (PASC) Syndrome: Clinical Implications
Authors: Pasini Evasio , Corsetti Giovanni , Romano Claudia , Scarabelli Tiziano M. , Chen-Scarabelli Carol , Saravolatz Louis , Dioguardi Francesco S. 
Published: July 2021

Background: Many patients who have been suffering by Covid-19 suffer of long-Covid syndrome, with symptoms of fatigue and muscular weakness that characterize post-acute sequelae SARS-CoV-2 infection (PASC). However, there is limited knowledge about the molecular pathophysiology, and about the serum profile of these patients.Methods: We studied the blood serum profile of 75 selected patients, with previous confirmed Covid-19, 2 months after hospital discharge, who reported new-onset fatigue, muscle weakness and/or dyspnea not present prior to the virus infection and independently from concomitant diseases and/or clinical conditions.Results: All patients had very high serum concentrations of ferritin and D-Dimer. 87 and 72% of patients had clinically significant low levels of hemoglobin and albumin, respectively. Seventy three percentage had elevations in erythrocyte sedimentation rate and CRP. Twenty seven percentage had elevations in LDH.Conclusions: The co-existence of patient symptoms along with blood markers of coagulation, protein disarrangement and inflammation suggests ongoing alterations in the metabolism, promoting an inflammatory/hypercatabolic state which maintains a vicious circles implicated in the persistence of PASC. The persistence of altered D-Dimer levels raises the possibility of long-term risks of thromboembolic disease. All these markers levels should be accurately evaluated in the long-term follow-up, with individualized consideration for prophylactic nutritional, anti-inflammatory and/or anticoagulant therapy if indicated.
Identification of Lymph Node Metastasis–Related Key Genes and Prognostic Risk Model in Bladder Cancer by Co-Expression Analysis
Authors: Luo Cheng , Huang Bin , Wu Yukun , Xu Yadong , Ou Wei , Chen Junxing , Chen Lingwu 
Published: July 2021

Background: Lymph node metastasis (LNM) is an important pathological characteristic of bladder cancer (BCa). However, the molecular mechanism underlying LNM was not thoroughly elaborated. Identification for LNM-related biomarkers may contribute to making suitable therapies. So, the current study was aimed to identify key genes and construct a prognostic signature.Methods: Based on the Cancer Genome Atlas (TCGA) database, gene expression and clinical information were obtained. Then, the weighted gene co-expression network analysis (WGCNA) was performed to identify the key modules and hub genes. A function analysis and a gene set enrichment analysis were applied to explore biological functions and pathways of interested genes. Furthermore, a prognostic model based on LNM-related genes was constructed by using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis.Results: Finally, nine co-expression modules were constructed, and two modules (turquoise and green) were significantly associated with LNM. Three hub genes were identified as DACT3, TNS1, and MSRB3, which were annotated in actin binding, actin cytoskeleton, adaptive immune response, and cell adhesion molecular binding by the GSEA method. Further analysis demonstrated that three hub genes were associated with the overall survival of BCa patients. In addition, we built a prognostic signature based on the genes from LNM-related modules and evaluated the prognostic value of this signature.Conclusion: In general, this study revealed the key genes related to LNM and prognostic signature, which might provide new insights into therapeutic target of BCa.
Motor Responses of Lumbar Erector Spinae Induced by Electrical Vestibular Stimulation in Seated Participants
Authors: Desgagnés Amélie , Desmons Mikaël , Cyr Jean-Philippe , Simoneau Martin , Massé-Alarie Hugo 
Published: July 2021

Introduction: The study of motor responses induced by electrical vestibular stimulation (EVS) may help clarify the role of the vestibular system in postural control. Although back muscles have an important role in postural control, their EVS-induced motor responses were rarely studied. Moreover, the effects of EVS parameters, head position, and vision on EVS-induced back muscles responses remain little explored.Objectives: To explore the effects of EVS parameters, head position, and vision on lumbar erector spinae muscles EVS-induced responses.Design: Exploratory, cross-sectional study.Materials and Methods: Ten healthy participants were recruited. Three head positions (right, left and no head rotation), 4 intensities (2, 3, 4, 5 mA), and 4 EVS durations (5, 20, 100, 200 ms) were tested in sitting position with eyes open or closed. EVS usually induced a body sway toward the anode (placed on the right mastoid). EMG activity of the right lumbar erector spinae was recorded. Variables of interest were amplitude, occurrence, and latency of the EVS-induced modulation of the EMG activity.Results: The short-latency response was inhibitory and the medium-latency response was excitatory. Increased EVS current intensity augmented the occurrence and the amplitude of the short- and medium-latency responses (more inhibition and more excitation, respectively). EVS duration influenced the medium-latency response differently depending on the position of the head. Right head rotation produced larger responses amplitude and occurrence than left head rotation. Opposite head rotation (left vs. right) did not induce a reversal of the short- and medium-latency responses (i.e., the inhibition did not become an excitation), as typically reported in lower legs muscles. The eyes open condition did not modulate muscle responses.Conclusion: Modulation of EVS parameters (current intensity and duration of EVS) affects the amplitude and occurrence of the lumbar erector spinae responses. In contrast, vision did not influence the responses, suggesting its minimal contribution to vestibulomotor control in sitting. The lack of response reversal in sagittal plane may reflect the biomechanical role of lumbar erector spinae to fine-tune the lumbar lordosis during the induced body sway. This hypothesis remains to be further tested.
Expression of HER2 and Mismatch Repair Proteins in Surgically Resected Gallbladder Adenocarcinoma
Authors: Sung You-Na , Kim Sung Joo , Jun Sun-Young , Yoo Changhoon , Kim Kyu-Pyo , Lee Jae Hoon , Hwang Dae Wook , Hwang Shin , Lee Sang Soo , Hong Seung-Mo 
Published: July 2021

BackgroundGallbladder cancer (GBC) has a poor prognosis. Although complete surgical resection is the only successful approach for improving survival, additional therapeutic modalities are required for recurrent or surgically unresectable GBCs.Materials and MethodsTo determine the expression status of HER2 and the mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, immunohistochemical staining of MMR proteins and HER2 was carried out in 216 surgically resected GBCs. HER2 labeling was scored by adopting a scoring system for gastric carcinomas. Tissues scoring 0 to 2+ were defined as HER2 negative, whereas those scoring 3+ were regarded as HER2-positive. In addition, silver in situ hybridization and microsatellite instability (MSI) analysis were conducted to confirm HER2 amplification and MSI, respectively.ResultsThree of 216 GBCs (1.3%) showed MMR protein deficiency. All three observed MSI cases exhibited dual loss of MSH2 and MSH6 protein expression. However, no cases showed loss of either MLH1 or PMS2 expression. No association was observed between MMR protein deficiency and other clinicopathological factors. HER2 amplification was noted in 30 (13.9%) GBCs and associated with Crohn-like lymphoid reaction (P = 0.023). No survival difference was observed based on HER2 overexpression or HER2 amplification status.ConclusionMMR protein deficiency and HER2 overexpression were observed in a small subset (1.3% and 13.9%, respectively) of GBCs without simultaneous occurrence of deficient MMR protein expression and HER2 overexpression. The presence of Crohn-like lymphoid reaction may help identify cases with HER2 amplification, by using hematoxylin-stained slides. Although the proportion of MMR protein-deficient- and HER2-overexpressing GBCs was small, applying immunotherapy to MMR protein-deficient GBCs and herceptin to HER2-overexpressing GBCs may provide alternative treatment options for patients with GBC.
ADGRG1 Is a Predictor of Chemoresistance and Poor Survival in Cervical Squamous Carcinoma
Authors: Zhang Shuo , Guo Kui , Liang Ying , Wang Kun , Liu Shuyan , Yang Xingsheng 
Published: July 2021

BackgroundCisplatin is the first-line chemotherapy for cervical cancer. Cisplatin resistance has always been one of the most significant barriers to acquiring better outcomes. However, the complex molecular mechanisms accounting for the phenomenon are not completely clear.MethodsConstruction of the cisplatin-resistant cell model of cervical cancer, then performing RNA sequencing and bioinformatic analysis of the differential expression genes. Then Adhesion G protein-coupled receptor G1 (ADGRG1) was screened out as our target gene. Gene Expression Profiling Interactive Analysis (GEPIA) was searched to show the expression level of ADGRG1 in cervical cancer and normal tissue. Kaplan-Meier Plotter (Kmplot) was used to explore the relationship of its expression with survival data. Tissue specimens were used to verify the relationship between the clinicopathological characteristics and ADGRG1 expression. Then we explored the roles of ADGRG1 in tumorigenesis through in vitro and in vivo assays.ResultsWe found the ADGRG1 was significantly overexpressed in cervical cancer tissues compared to corresponding normal tissues. Higher ADGRG1 expression was correlated with poor progress-free survival. Knockdown of ADGRG1 markedly suppressed cell proliferation, migration, and invasion and increased cell sensitivity to cisplatin in vitro. Similarly, the role of ADGRG1 knockdown on tumorigenicity and sensitivity to cisplatin treatment was verified in vivo. The underlying mechanism was explored by western blotting that ADGRG1 knockdown inhibited tumorigenesis by PI3K/Akt/mTOR signaling pathway.ConclusionADGRG1 acts as an oncogene to maintain tumorigenicity, migration, and invasion, and its depressed expression prompts sensitivity to cisplatin. Thus, ADGRG1 may represent a potential prognostic marker and possible therapeutic target for cervical cancer.
Immune Reconstitution-Based Score for Risk Stratification of Chronic Graft-Versus-Host Disease Patients
Authors: Serpenti Fabio , Lorentino Francesca , Marktel Sarah , Milani Raffaella , Messina Carlo , Greco Raffaella , Girlanda Stefania , Clerici Daniela , Giglio Fabio , Liberatore Carmine , Farina Francesca , Mastaglio Sara , Piemontese Simona , Guggiari Elena , Lunghi Francesca , Marcatti Magda , Carrabba Matteo G. , Bernardi Massimo , Bonini Chiara , Assanelli Andrea , Corti Consuelo , Peccatori Jacopo , Ciceri Fabio , Lupo-Stanghellini Maria Teresa 
Published: July 2021

IntroductionAllogeneic stem cell transplantation survivors are at a relevant risk of developing chronic GvHD (cGvHD), which importantly affects quality of life and increases morbidity and mortality. Early identification of patients at risk of cGvHD-related morbidity could represent a relevant tool to tailor preventive strategies. The aim of this study was to evaluate the prognostic power of immune reconstitution (IR) at cGvHD onset through an IR-based score.MethodsWe analyzed data from 411 adult patients consecutively transplanted between January 2011 and December 2016 at our Institution: 151 patients developed cGvHD (median follow-up 4 years). A first set of 111 consecutive patients with cGvHD entered the test cohort while an additional consecutive 40 patients represented the validation cohort. A Cox multivariate model for OS (overall survival) in patients with cGvHD of any severity allowed the identification of six variables independently predicting OS and TRM (transplant-related mortality). A formula for a prognostic risk index using the β coefficients derived from the model was designed. Each patient was assigned a score defining three groups of risk (low, intermediate, and high).ResultsOur multivariate model defined the variables independently predicting OS at cGvHD onset: CD4+ &gt;233 cells/mm3, NK &lt;115 cells/mm3, IgA &lt;0.43g/L, IgM &lt;0.45g/L, Karnofsky PS &lt;80%, platelets &lt;100x103/mm3. Low-risk patients were defined as having a score ≤3.09, intermediate-risk patients &gt;3.09 and ≤6.9, and high-risk patients &gt;6.9. By ROC analysis, we identified a cut-off of 6.310 for both TRM and overall mortality.In the training cohort, the 6-year OS and TRM from cGvHD occurrence were 85% (95% CI, 70-92) and 13% (95% CI, 5-25) for low-risk, 64% (95% CI, 44-89) and 30% (95% CI, 15-47) for intermediate-risk, 26% (95% CI, 10-47), and 42% (95% CI, 19-63) for high-risk patients (OS p&lt;0.0001; TRM p = 0.015).The validation cohort confirmed the model with a 6-year OS and TRM of 83% (95% CI, 48-96) and 8% (95% CI, 1-32) for low-risk, 78% (95% CI, 37-94) and 11% (95% CI, 1-41) for intermediate-risk, 37% (95% CI, 17-58), and 63% (95% CI, 36-81) for high-risk patients (OS p = 0.0075; TRM p = 0.0009).ConclusionsIR score at diagnosis of cGvHD predicts GvHD severity and overall survival. IR score may contribute to the risk stratification of patients. If confirmed in a larger and multicenter-based study, IR score could be adopted to identify patients at high risk and modulate cGvHD treatments accordingly in the context of clinical trial.
Systematic Review and Meta-Analysis of Rituximab for Steroid-Dependent or Frequently Relapsing Nephrotic Syndrome in Children
Authors: Gao Xia , Wang Yan , Xu Zichuan , Deng Huiying , Yang Huabin , Zhong Fu 
Published: July 2021

Objective: To explore the effectiveness and safety of rituximab (RTX) for steroid-dependent or frequently relapsing nephrotic syndrome via a systematic review and meta-analysis.Methods: All the literature about RTX therapy for childhood nephrotic syndrome (NS) on PubMed, Web of Science, Cochrane Library, EMBASE, and Chinese biomedical literature database published before November 1, 2019, were conducted and selected according to the preset criteria. The Cochrane bias risk assessment tool was used to evaluate the quality of the literature included. The outcome data were analyzed by RevMan 5.3 software.Results: There were six RCT studies that met the inclusion criteria with a moderate quality after evaluation. At the end of the treatment, the relapse rate of NS in the RTX group reduced significantly when compared with that in the control group [odds ratio (OR) = 0.11, 95% confidence interval (CI) (0.03, 0.43), p = 0.001]. The number of patients in the RTX group used less steroid or/and calcineurin inhibitors significantly than that in the control group [OR = 0.05, 95% CI (0.01, 0.28), p = 0.0007]. For children who were steroid-dependent, RTX treatment significantly reduced the dosage of the steroid, compared with that in control [standardized mean difference (SMD) = −1.49, 95% CI (−2.00, −0.99), p &lt; 0.00001]. There was no significant reduction in protein excretion between the two groups [SMD = −0.33, 95% CI (−0.71, 0.04), p = 0.08]. Fewer serious adverse reactions of RTX in the six studies were reported and most adverse events were mild.Conclusion: RTX is effective and safe for children with steroid-dependent or frequently relapsing nephrotic syndrome.Systematic Review Registration: Identifier: CRD 42020150933. https://www.crd.york.ac.uk/prospero/. This review has been registered to the PROSPERO on 27 Feb 2020.