bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Impact of Risk Gene Variants on the Autoimmune Responses in Type 1 Diabetes
Authors: Gootjes Chelsea , Zwaginga Jaap Jan , Roep Bart O. , Nikolic Tatjana 
Published: May 2022

Type 1 diabetes (T1D) is an autoimmune disease that develops in the interplay between genetic and environmental factors. A majority of individuals who develop T1D have a HLA make up, that accounts for 50% of the genetic risk of disease. Besides these HLA haplotypes and the insulin region that importantly contribute to the heritable component, genome-wide association studies have identified many polymorphisms in over 60 non-HLA gene regions that also contribute to T1D susceptibility.Combining the risk genes in a score (T1D-GRS), significantly improved the prediction of disease progression in autoantibody positive individuals. Many of these minor-risk SNPs are associated with immune genes but how they influence the gene and protein expression and whether they cause functional changes on a cellular level remains a subject of investigation. A positive correlation between the genetic risk and the intensity of the peripheral autoimmune response was demonstrated both for HLA and non-HLA genetic risk variants. We also observed epigenetic and genetic modulation of several of these T1D susceptibility genes in dendritic cells (DCs) treated with vitamin D3 and dexamethasone to acquire tolerogenic properties as compared to immune activating DCs (mDC) illustrating the interaction between genes and environment that collectively determines risk for T1D. A notion that targeting such genes for therapeutic modulation could be compatible with correction of the impaired immune response, inspired us to review the current knowledge on the immune-related minor risk genes, their expression and function in immune cells, and how they may contribute to activation of autoreactive T cells, Treg function or β-cell apoptosis, thus contributing to development of the autoimmune disease.
Dynamic Changes of Cytokine Profiles and Virological Markers Associated With HBsAg Loss During Peginterferon Alpha-2a Treatment in HBeAg-Positive Chronic Hepatitis B Patients
Authors: Li Minghui , Zhang Luxue , Xie Si , Sun Fangfang , Zeng Zhan , Deng Wen , Jiang Tingting , Bi Xiaoyue , Lin Yanjie , Yang Liu , Lu Yao , Shen Ge , Liu Ruyu , Wu Shuling , Chang Min , Hu Leiping , Dong Jianping , Yi Wei , Xie Yao 
Published: May 2022

ObjectiveTo explore dynamic changes of cytokines and virological markers associated with hepatitis B surface antigen (HBsAg) loss during peginterferon alpha-2a (PEG-IFN α-2a) treatment in hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients.MethodsIt was a single-center prospective cohort study. HBeAg-positive CHB patients were prospectively and consecutively enrolled. Cytokines were detected at baseline, week 12 and 24 of PEG-IFN treatment. HBsAg disappearance rate was the primary evaluation index at 48 weeks of PEG-IFN treatment.ResultsAmong 100 patients who completed the 48-week PEG-IFN α-2a treatment, 38 patients achieved serum HBeAg disappearance, 25 patients achieved HBeAg seroconversion, 9 patients achieved functional cure, 37 patients had HBsAg decline of ≥1 log IU/ml, and 8 patients produced hepatitis B surface antibody (HBsAb). Albumin (ALB), fms-like tyrosine kinase 3 ligand (FLT3-L) and interferon-alpha2 (IFN-α2) in the clinical cure group were significantly lower than those in the non-clinical-cure group at baseline. After 12 weeks of treatment, HBsAg in the clinical cure group was significantly lower than that in the non-clinical-cure group (median 1.14 vs. 3.45 log10IU/ml, Z=-4.355, P &lt; 0.001). The decrease of HBsAg and hepatitis B virus desoxyribose nucleic acid (HBV DNA) in the clinical cure group was significantly higher than that in non-clinical-cure group (median: HBsAg 1.96 vs. 0.33 log10IU/ml, Z=-4.703, P&lt; 0.001; HBV DNA 4.49 vs.3.13 log10IU/ml, Z=-3.053, P=0.002). The increase of IFN-α2 in the cure group was significantly higher than that in the non-clinical-cure group (497.89 vs. 344.74, Z=-2.126, P=0.034). After 24 weeks of treatment, HBsAg, HBeAg, Flt3-L, and IL-10 in the clinical cure group were significantly lower than those in the non-clinical-cure group (median: HBsAg 0.70 vs. 3.15 log10IU/ml, Z=-4.535, P&lt; 0.001; HBeAg 1.48 vs. 13.72 S/CO, Z = 2.512, P = 0.012; Flt3-l 0.00 vs 2.24 pg/ml, Z = 3.137, P=0.002; IL-10 0.70 vs. 2.71 pg/ml, Z=-4.067, P &lt; 0.001). HBsAg decreased significantly in the clinical cure group compared with non-clinical-cure group (median 3.27 vs. 0.45, Z=-4.463, P &lt; 0.001).ConclusionDynamic changes of cytokines and virology markers during early PEG IFN α-2a treatment were associated with HBsAg loss in HBeAg-positive CHB patients.
Identification of Ferroptosis-Related Prognostic Signature and Subtypes Related to the Immune Microenvironment for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
Authors: Xu Yuhao , Du Yaoqiang , Zheng Qinghui , Zhou Tao , Ye Buyun , Wu Yihao , Xu Qiuran , Meng Xuli 
Published: May 2022

PurposeTo identify molecular clusters associated with ferroptosis and to develop a ferroptosis-related signature for providing novel potential targets for the recurrence-free survival and treatment of breast cancer.MethodsFerroptosis-related gene (FRG) signature was constructed by univariate and multivariate Cox regression and least absolute shrinkage and selection operator (LASSO). Receiver operating characteristic curves, Kaplan–Meier survival analysis, principal component analysis, and univariate and multivariate Cox regression analyses in the training and test cohorts were used to evaluate the application of this signature. Quantitative reverse transcriptase–PCR (qRT-PCR) was employed to detect the expression of FRGs in the model. Furthermore, the correlations between the signature and immune microenvironment, somatic mutation, and chemotherapeutic drugs sensitivity were explored.ResultsInternal and external validations affirmed that relapse-free survival differed significantly between the high-risk and low-risk groups. Univariate and multivariate Cox regression analyses indicated that the riskScore was an independent prognostic factor for BRCA. The areas under the curve (AUCs) for predicting 1-, 2-, and 3-year survival in the training and test cohorts were satisfactory. Significant differences were also found in the immune microenvironment and IC50 of chemotherapeutic drugs between different risk groups. Furthermore, we divided patients into three clusters based on 18 FRGs to ameliorate the situation of immunotherapy failure in BRCA.ConclusionsThe FRG signature functions as a robust prognostic predictor of the immune microenvironment and therapeutic response, with great potential to guide individualized treatment strategies in the future.
Neuropilin-1 Identifies a New Subpopulation of TGF-β-Induced Foxp3+ Regulatory T Cells With Potent Suppressive Function and Enhanced Stability During Inflammation
Authors: Chen Weiqian , Huang Weishan , Xue Youqiu , Chen Ye , Qian Wenbin , Ma Jilin , August Avery , Wang Julie , Zheng Song Guo , Lin Jin 
Published: May 2022

CD4+Foxp3+ regulatory T cells (Tregs) play a crucial role in preventing autoimmunity and inflammation. There are naturally-derived in the thymus (tTreg), generated extrathymically in the periphery (pTreg), and induced in vitro culture (iTreg) with different characteristics of suppressiveness, stability, and plasticity. There is an abundance of published data on neuropilin-1 (Nrp-1) as a tTreg marker, but little data exist on iTreg. The fidelity of Nrp-1 as a tTreg marker and its role in iTreg remains to be explored. This study found that Nrp-1 was expressed by a subset of Foxp3+CD4+T cells in the central and peripheral lymphoid organs in intact mice, as well as in iTreg. Nrp-1+iTreg and Nrp-1-iTreg were adoptively transferred into a T cell-mediated colitis model to determine their ability to suppress inflammation. Differences in gene expression between Nrp-1+ and Nrp-1-iTreg were analyzed by RNA sequencing. We demonstrated that the Nrp-1+ subset of the iTreg exhibited enhanced suppressive function and stability compared to the Nrp-1- counterpart both in vivo and in vitro, partly depending on IL-10. We found that Nrp-1 is not an exclusive marker of tTreg, however, it is a biomarker identifying a new subset of iTreg with enhanced suppressive function, implicating a potential for Nrp-1+iTreg cell therapy for autoimmune and inflammatory diseases.
A Nationwide Multicenter Study on 1-Year Outcomes of Posterior Chamber Phakic Intraocular Lens Implantation for Low Myopia
Authors: Kamiya Kazutaka , Shimizu Kimiya , Igarashi Akihito , Kitazawa Yoshihiro , Kojima Takashi , Nakamura Tomoaki , Ichikawa Kazuo , Fukuoka Sachiko , Fujimoto Kahoko ,   The Japan ICL Study Group
Published: May 2022

PurposeTo assess the nationwide multicenter outcomes of posterior chamber phakic intraocular lens implantation with a central hole (EVO-ICL, STAAR Surgical) for patients with low myopia.MethodsThis multicenter study comprised 172 eyes of 111 consecutive patients undergoing hole ICL implantation to correct low myopia and myopic astigmatism [manifest spherical equivalent (MSE);−3 diopters (D) or less] at seven nationwide major surgical facilities. We retrospectively determined safety, efficacy, predictability, stability, and adverse events at 1 week, 1, 3, 6, and 12 months postoperatively, and at the final visit.ResultsThe mean follow-up period was 1.4 ± 1.0 years. Uncorrected and corrected visual acuities at 1 year postoperatively were −0.17 ± 0.12 and −0.24 ± 0.07 logarithm of the minimal angle of resolution (logMAR), respectively. At 1 year postoperatively, 91% and 100% of eyes were within 0.5 and 1.0 D of the target correction, respectively. No significant manifest refraction changes of −0.07 ± 0.26 D occurred from 1 week to 1 year. No vision-threatening complications occurred at any time in this series.ConclusionsAccording to our experience, the EVO-ICL performed well without significant complications throughout the 1-year observation period, even for the correction of low myopia. It is suggested that current ICL implantation is one of the viable surgical options for correcting low myopia.
Parent Joint AB Blood Group Is Associated With Clinical Outcomes of in vitro Fertilization and Intracytoplasmic Sperm Injection Treatment in Chinese Women
Authors: Bao Xiao , Zhao Feifei , Shi Hao , Bu Zhiqin , Liang Yuling , Sun Yingpu 
Published: May 2022

BackgroundA number of publications have examined the relation between blood group and female infertility including ovarian reserve, recurrent miscarriage, and live birth. However, there is a lack of literature investigating joint mother/father ABO blood type in a large cohort. This study aimed to investigate the association between couple combinations for ABO blood groups and assisted reproductive technology (ART) outcomes in patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).MethodsThis retrospective cohort study included 30,717 couples who underwent IVF cycles between 2010 and 2019. The clinical outcomes of IVF treatment were the primary outcome. History of spontaneous miscarriage, embryo quality, and birth sex, weights, defects rate were also studied.ResultsThere was no difference in the baseline demographics between the blood type groups. There was a statistically significant positive association between the combination of female blood type AB and male blood type AB with biochemical pregnancy, clinical pregnancy, and live birth rate (OR 1.36; 95% CI, 1.05–1.78; P = 0.02 and OR 1.31; 95% CI, 1.0–1.68; P = 0.031 and OR 1.28; 95% CI, 1.01–1.63; P = 0.041 respectively). No statistically significant difference was observed between joint mother/father ABO blood types and high-quality embryo rate, early abortion rate, birth sex, birth weights, and birth defect rate.ConclusionsOur findings suggest that the success rate of IVF/ICSI cycles in parent mating AB blood type is higher than that in other blood type combination groups.
Covered TIPS Procedure-Related Major Complications: Incidence, Management and Outcome From a Single Center
Authors: Yin Xiaochun , Gu Lihong , Zhang Ming , Yin Qin , Xiao Jiangqiang , Wang Yi , Zou Xiaoping , Zhang Feng , Zhuge Yuzheng 
Published: May 2022

Background and ObjectiveTransjugular intrahepatic portosystemic shunt (TIPS) is a well-established procedure for treating complications of portal hypertension. Due to the complexity of anatomy and difficulty of the puncture technique, the procedure itself might brought potential complications, such as puncture failure, bleeding, infection, and, rarely, death. The aim of this study is to explore the incidence, management, and outcome of TIPS procedure-related major complications using covered stents.MethodsPatients who underwent TIPS implantation from January 2015 to December 2020 were recruited retrospectively. Major complications after TIPS were screened and analyzed.ResultsNine hundred and forty-eight patients underwent the TIPS procedure with 95.1% (n = 902) technical success in our department. TIPS procedure-related major complications occurred in 30 (3.2%) patients, including hemobilia (n = 13; 1.37%), hemoperitoneum (n = 7; 0.74%), accelerated liver failure (n = 6; 0.63%), and rapidly progressive organ failure (n = 4; 0.42%). Among them, 8 patients died because of hemobilia (n = 1), accelerated liver failure (n = 4), and rapidly progressive organ failure (n = 3).ConclusionThe incidence of major complications related to TIPS procedure is relatively low, and some of them could recover through effective medical intervention. In our cohort, the overall incidence is about 3%, which causes 0.84% death. The most fatal complication is organ failure and hemobilia.
Serum Concentration of Ropivacaine After Repeated Administration to Several Parts of the Head During Awake Craniotomy: A Prospective Cohort Study
Authors: Sato Takehito , Ando Takahiro , Asano Ichiko , Mori Atsushi , Motomura Kazuya , Nishiwaki Kimitoshi 
Published: May 2022

IntroductionDuring awake craniotomy, effective use of local anesthetics, such as ropivacaine, is critical. Blood concentrations of ropivacaine after repeated administration over a short period during awake craniotomy have not been studied.Materials and MethodsIn this prospective cohort study, we evaluated serum concentrations of ropivacaine 15 min after each administration during awake craniotomy at Nagoya University Hospital between April 5, 2018 and August 31, 2019 to determine the safe dose. A total of 30 patients scheduled to undergo elective awake craniotomy were included. Patients were injected with 0.375% ropivacaine before the awake phase at the following points: scalp block (T1), headpin area (T2), skin incision area (T3), temporal muscle (T4), and dura mater (T5). Arterial blood samples were collected 15 min after ropivacaine administration. In addition to the blood concentrations of ropivacaine, complications during the awake phase were evaluated as secondary endpoints.ResultsThe mean total dose of ropivacaine was 5.01 ± 0.68 mg/kg (maximum total dose: 6.30 mg/kg). The mean interval from T1 to T5 was 128.0 ± 17.7 min. The maximum serum concentration did not exceed the toxicity threshold of 4.3 μg/mL in any patient (mean serum concentration: T1, 1.23 ± 0.36 μg/mL; T5, 0.82 ± 0.26 μg/mL). No addiction symptoms were observed during awakening in any case.ConclusionOur results show that, in cases of awake craniotomy with repeated anesthetic administration, a total dose of up to 5.0 mg/kg is safe, without addiction symptoms. Relatively large amounts of ropivacaine can be safely injected during awake craniotomy.
A Preliminary Study on the Relationship Between High-Resolution Computed Tomography and Pulmonary Function in People at Risk of Developing Chronic Obstructive Pulmonary Disease
Authors: Lv Rui , Xie Mengyao , Jin Huaqian , Shu Pingping , Ouyang Mingli , Wang Yanmao , Yao Dan , Yang Lehe , Huang Xiaoying , Wang Yiran 
Published: May 2022

ObjectivesPatients with chronic obstructive pulmonary disease (COPD) have high morbidity and mortality, the opportunity to carry out a thoracic high-resolution CT (HRCT) scan may increase the possibility to identify the group at risk of disease. The aim of our study was to explore the differences in HRCT emphysema parameters, air trapping parameters, and lung density parameters between high and low-risk patients of COPD and evaluate their correlation with pulmonary function parameters.MethodsIn this retrospective, single-center cohort study, we enrolled outpatients from the Physical Examination Center and Respiratory Medicine of The First Affiliated Hospital of Wenzhou Medical University. The patients who were ≥ 40 years-old, had chronic cough or sputum production, and/or had exposure to risk factors for the disease and had not reached the diagnostic criteria is considered people at risk of COPD. They were divided into low-risk group and high-risk group according to FEV1/FVC ≥ 80% and 80%&gt;FEV1/FVC ≥ 70%. Data on clinical characteristics, clinical symptom score, pulmonary function, and HRCT were recorded.Results72 COPD high-risk patients and 86 COPD low-risk patients were enrolled in the study, and the air trapping index of left, right, and bilateral lungs of the high-risk group were higher than those of the low-risk group. However, the result of mean expiratory lung density was opposite. The emphysema index of left, right, and bilateral lungs were negatively correlated with FEV1/FVC (correlation coefficients were -0.33, -0.22, -0.26). Consistently, the air trapping index of left and right lungs and bilateral lungs were negatively correlated with FEV1/FVC (correlation coefficients were -0.33, -0.23, -0.28). Additionally, the mean expiratory lung density of left and right lungs and bilateral lungs were positively correlated with FEV1/FVC (correlation coefficients were 0.31, 0.25, 0.29).ConclusionThe emphysema index, air trapping index and the mean expiratory lung density shows significantly positive correlation with FEV1/FVC which can be used to assess the pulmonary function status of people at risk of COPD and provide a useful supplement for the early and comprehensive assessment of the disease.
The Relationship Between Adverse Childhood Experiences and Alzheimer's Disease: A Systematic Review
Authors: Corney Kayla B. , West Emma C. , Quirk Shae E. , Pasco Julie A. , Stuart Amanda L. , Manavi Behnaz Azimi , Kavanagh Bianca E. , Williams Lana J. 
Published: May 2022

BackgroundAlzheimer's disease is a global health concern, and with no present cure, prevention is critical. Exposure to adverse childhood experiences may increase the risk of developing Alzheimer's disease. This systematic review was conducted to synthesize the evidence on the associations between adverse childhood experiences (&lt;18 years) and the risk of Alzheimer's disease in adulthood.MethodsA search strategy was developed and conducted to identify articles investigating the associations between exposure to adverse childhood experiences and the onset of Alzheimer's disease by searching key databases (CINAHL, MEDLINE and PsycInfo). Two reviewers independently determined the eligibility of studies according to pre-determined criteria, and assessed the methodological quality using the US National Heart, Lung and Blood Institute 14-item checklist for observational cohort and cross-sectional studies, respectively. Due to limited studies, a descriptive synthesis was performed. The protocol for this review is published in BMJ Open and registered with PROSPERO (CRD42020191439).ResultsOur search yielded 781 articles, of which three (two separate analyses from the same cohort study and one cross-sectional study) met the predetermined eligibility criteria. The methodological quality assessment yielded an overall mean score of 78.9% (range 66.6 – 84.6%). All studies found adverse childhood experiences were associated with an increased risk of Alzheimer's disease. However, there was a limited number of available studies to inform the synthesis.ConclusionsAdverse childhood experiences appear to be associated with an increased risk of Alzheimer's disease, although, further research is needed.Registration and ProtocolThe protocol for this review is registered with PROSPERO (CRD42020191439) and published with BMJ Open (Corney et al., 2021).
Abnormal Visual Evoked Responses to Emotional Cues Correspond to Diagnosis and Disease Severity in Fibromyalgia
Authors: Goldway Noam , Petro Nathan M. , Ablin Jacob , Keil Andreas , Ben Simon Eti , Zamir Yoav , Weizman Libat , Greental Ayam , Hendler Talma , Sharon Haggai 
Published: May 2022

BackgroundChronic pain disorders are often associated with cognitive-emotional dysregulation. However, the relations between such dysregulation, underlying brain processes, and clinical symptom constellations, remain unclear. Here, we aimed to characterize the abnormalities in cognitive-emotional processing involved in fibromyalgia syndrome (FMS) and their relation to disease severity.MethodsFifty-eight participants, 39 FMS patients (35F), and 19 healthy control subjects (16F) performed an EEG-based paradigm assessing attention allocation by extracting steady-state visually evoked potentials (ssVEP) in response to affective distractors presented during a cognitive task. Patients were also evaluated for pain severity, sleep quality, depression, and anxiety.ResultsEEG ssVEP measurement indicated that, compared to healthy controls, FMS patients displayed impaired affective discrimination, and sustained attention to negative distractors. Moreover, patients displayed decreased task-related fronto-occipital EEG connectivity. Lack of adaptive attentional discrimination, measured via EEG, was predictive of pain severity, while impairments in fronto-occipital connectivity were predictive of impaired sleep.ConclusionsFMS patients display maladaptive affective attention modulation, which predicts disease symptoms. These findings support the centrality of cognitive-emotional dysregulation in the pathophysiology of chronic pain.
Focal Adhesion-Related Signatures Predict the Treatment Efficacy of Chemotherapy and Prognosis in Patients with Gastric Cancer
Authors: Tang Xiaohuan , Wu Xiaolong , Guo Ting , Jia Fangzhou , Hu Ying , Xing Xiaofang , Gao Xiangyu , Li Ziyu 
Published: May 2022

BackgroundThe current tumor-node-metastasis (TNM) staging system is insufficient for predicting the efficacy of chemotherapy in patients with gastric cancer (GC). This study aimed to analyze the association between the focal adhesion pathway and therapeutic efficacy of chemotherapy in patients with GC.MethodsRNA sequencing was performed on 33 clinical samples from patients who responded or did not respond to treatment prior to neoadjuvant chemotherapy. The validation sets containing 696 GC patients with RNA data from three cohorts (PKUCH, TCGA, and GSE14210) were analyzed. A series of machine learning and bioinformatics approaches was combined to build a focal adhesion-related signature model to predict the treatment efficacy and prognosis of patients with GC.ResultsAmong the various signaling pathways associated with cancer, focal adhesion was identified as a risk factor related to the treatment efficacy of chemotherapy and prognosis in patients with GC. The focal adhesion-related gene model (FAscore) discriminated patients with a high FAscore who are insensitive to neoadjuvant chemotherapy in our training cohort, and the predicted value was further verified in the GSE14210 cohort. Survival analysis also demonstrated that patients with high FAscores had a relatively shorter survival compared to those with low FAscores. In addition, we found that the levels of tumor mutation burden (TMB) and microsatellite instability (MSI) increased with an increase in FAscore, and the tumor microenvironment (TME) also shifted to a pro-tumor immune microenvironment.ConclusionThe FAscore model can be used to predict the treatment efficacy of chemotherapy and select appropriate treatment strategies for patients with GC.