bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein Disulfide-Isomerase A3 Is a Robust Prognostic Biomarker for Cancers and Predicts the Immunotherapy Response Effectively
Authors: Tu Zewei , Ouyang Qin , Long Xiaoyan , Wu Lei , Li Jingying , Zhu Xingen , Huang Kai 
Published: March 2022

BackgroundProtein disulfide isomerase A3 (PDIA3) is a member of the protein disulfide isomerase (PDI) family that participates in protein folding through its protein disulfide isomerase function. It has been reported to regulate the progression of several cancers, but its function in cancer immunotherapy is unknown.MethodsThe RNA-seq data of cancer and normal tissues were downloaded from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. The Cbioportal dataset was used to explore the genomic alteration information of PDIA3 in pan-cancer. Human Protein Atlas (HPA) and ComPPI websites were employed to mine the protein information of PDIA3, and western blot assay was performed to monitor the upregulated PDIA3 expression in clinical GBM samples. The univariate Cox regression and the Kaplan–Meier method were utilized to appraise the prognostic role of PDIA3 in pan-cancer. Gene Set Enrichment Analysis (GSEA) was applied to search the associated cancer hallmarks with PDIA3 expression. TIMER2.0 was the main platform to investigate the immune cell infiltrations related to PDIA3 in pan-cancer. The associations between PDIA3 and immunotherapy biomarkers were performed by Spearman correlation analysis. The immunoblot was used to quantify the PDIA3 expression levels, and the proliferative and invasive ability of glioma cells was determined by colony formation and transwell assays.FindingsPDIA3 is overexpressed in most cancer types and exhibits prognosis predictive ability in various cancers, and it is especially expressed in the malignant cells and monocytes/macrophages. In addition, PDIA3 is significantly correlated with immune-activated hallmarks, cancer immune cell infiltrations, and immunoregulators, and the most interesting finding is that PDIA3 could significantly predict anti-PDL1 therapy response. Besides, specific inhibitors that correlated with PDIA3 expression in different cancer types were also screened by using Connectivity Map (CMap). Finally, knockdown of PDIA3 significantly weakened the proliferative and invasive ability of glioma cells.InterpretationThe results revealed that PDIA3 acts as a robust tumor biomarker. Its function in protein disulfide linkage regulation could influence protein synthesis, degradation, and secretion, and then shapes the tumor microenvironment, which might be further applied to develop novel anticancer inhibitors.
Prevalence and Risk for Bundle Branch Block, Atrioventricular Block and Pacemaker Implantation in Spondyloarthritis. A Systematic Review of the Literature
Authors: Park Hye Sang , Laiz Ana , Díaz del Campo Petra , Martín Martínez María A. , Guerra-Rodriguez M. , Alonso-Martin Concepcion , Sanchez-Vega Jesus , Corominas Hector 
Published: March 2022

ObjectiveTo evaluate the evidence regarding the prevalence and risk of bundle branch block (BBB), atrioventricular block (AVB) and pacemaker implantation (PMI) in patients with spondyloarthritis compared to a control group without spondyloarthritis.MethodsA systematic review of the literature was performed using Pubmed (Medline), EMBASE (Elsevier) and Cochrane Library (Wiley) databases until December 2021. The prevalence and risk for AVB, BBB and PMI were analyzed. Cohort, case control and cross-sectional studies in patients ≥18 years meeting the classification criteria for spondyloarthritis were included. The Odds ratio (OR), risk ratio (RR), or Hazard ratio (HR) and prevalence difference were considered as outcomes. Data was synthesized in a previously defined extraction form which included a risk of bias assessment using the Newcastle-Ottawa Scale.ResultsIn total, eight out of 374 studies were included. None of the studies provided results regarding the risk of low grade AVB and BBB in SpA patients. Only indirect results comparing prevalences from low to medium quality studies were found. According to population based registries, the sex and age adjusted HR of AVB was 2.3 (95% CI 1.6–3.3) in ankylosing spondylitis, 2.9 (95% CI 1.8–4.7) in undifferentiated spondyloarthritis and 1.5 (95% CI 1.1 a 1.9) in psoriatic arthritis. The absolute risk for AVB was 0.4% (moderate to high; 95% CI 0.34%-0.69%) for AS, 0.33% (moderate to high; 95% CI 0.21%-0.53%) for uSpA and 0.34% (moderate to high; 95% CI 0.26%-0.45%) for PsA.The RR for PMI in AS patients was 1.3 (95% CI 1.16–1.46) for groups aged between 65 and 69 years, 1.33 (95% CI 1.22–1.44) for 70–75 years, 1.24 (95% CI 1.55–1.33) for 75–79 years and 1.11 (95% CI 1.06–1.17) for groups older than 80 years. The absolute risk for PMI in AS patients was 0.7% (moderate to high risk; 95% CI 0.6–0.8%) for groups aged between 65–69, 1.44% (high risk; 95% CI 1.33–1.6%) for 70–75 years, 2.09% (high risk; 95% CI 2.0–2.2%) for 75–79 years and 4.15% (high risk; 95% CI 4.0–4.3%) for groups older than 80 yearsConclusionsVery few cases of low grade AVB and BBB were observed in observational studies. No study evaluated association measures for low grade AVB and BBB but the differences of prevalence were similar in SpA and control groups even though studies lacked the power to detect statistical differences. According to population based registries there was an approximately two fold-increased risk of high grade AVB in SpA patients. RR for PMI was higher in younger age groups.
Cronkhite-Canada Syndrome Associated With Superficial Esophageal Carcinoma: A Case Report and Literature Review
Authors: Zhao Yan , Lv Fujing , Yang Xun , Wang Yongjun , Zhang Shutian , Li Peng 
Published: March 2022

IntroductionCronkhite-Canada syndrome is a rare disease characterized by generalized gastrointestinal polyposis, alopecia, skin pigmentation, and onychotrophia with no generally recognized mechanism of pathogenesis. There is a tendency of malignant transformation or coexistence of gastrointestinal malignancies in patients with Cronkhite-Canada syndrome.Case DescriptionThe patient was a 67-year-old man who complained of dyspepsia, hair loss, skin hyperpigmentation, and pedal edema. Lab tests showed hypoalbuminemia. Endoscopic findings included superficial esophageal carcinoma and numerous polyps in the stomach, duodenum, and colon. The patient was treated with endoscopic submucosal dissection for the esophagus lesion, endoscopic mucosal resection for colon polyps, and glucocorticoids for Cronkhite-Canada syndrome.ConclusionEsophagus cancer is a rare comorbidity of Cronkhite-Canada syndrome. Endoscopic examination and surveillance are critical for patients with Cronkhite-Canada syndrome for malignant gastrointestinal tumors.
The Effects of CPAP Treatment on Resting-State Network Centrality in Obstructive Sleep Apnea Patients
Authors: Li Panmei , Shu Yongqiang , Liu Xiang , Kong Linghong , Li Kunyao , Xie Wei , Zeng Yaping , Li Haijun , Peng Dechang 
Published: March 2022

Background and ObjectivesObstructive sleep apnea (OSA) is the most common sleep disorder and previous studies have shown that OSA patients suffer from brain network impairments associated with cognitive deficits, and continuous positive airway pressure (CPAP) treatment can improve clinical symptoms. However, the relationship between CPAP treatment and brain network changes remains unclear. This study explored the characteristics of brain network changes in OSA patients before (pre-CPAP) and after one month of CPAP treatment (post-CPAP).MethodsWe collected data, including sleep monitoring, clinical assessment, and magnetic resonance imaging scans, from 21 OSA patients and 21 age-matched healthy controls (HCs). Voxel-level degree centrality (DC) was used to assess whole-brain network connectivity characteristics, a two-sample t-test was used to compare network differences between pre-CPAP OSA patients and HCs, and a paired sample t-test was used to compare the characteristics of brain network changes in OSA patients before and after treatment. The correlations between the DC value and each of the clinical variables were analyzed in the OSA patients.ResultsCompared with HCs, pre-CPAP OSA patients showed increased DC values in the bilateral cerebellar posterior lobes (CPLs) and decreased DC values in the right superior temporal gyrus, left superior frontal gyrus and right middle frontal gyrus. Compared with pre-CPAP OSA patients, post-CPAP OSA patients showed reduced DC values in the bilateral CPL and increased DC values in several brain regions in the frontal, temporal, and insular lobes after CPAP treatment. The Montreal Cognitive Assessment MoCA (MoCA) scores were positively correlated with the DC value of the bilateral cerebellum posterior lobe, right middle temporal gyrus, left superior temporal gyrus, left paracentral lobule and left paracentral lobule. Also, Pittsburgh Sleep Quality Index (PSQI) scores were negatively correlated with the DC value of the right middle temporal gyrus in post-CPAP OSA patients.ConclusionCPAP treatment can effectively reverse the compensatory response of the bilateral CPL and functional network damage brought about by OSA, which may provide potential neuroimaging biomarkers for CPAP treatment evaluation.
Prognostic Evaluation of Metastasis-Related Lymphocyte/Monocyte Ratio in Stage Ⅰ-Ⅲ Breast Cancer Receiving Chemotherapy
Authors: Zhang Zihan , Lin Qian , Chen Yi , Su Chenlin , Lin Wuye , Wei Daoyu , Zhang Litu , Liu Haizhou 
Published: March 2022

PurposeThis study aims to clarify the prognostic significance of metastasis-related indicators in peripheral blood in stage I-III breast cancer (BC).MethodsThe clinicopathological data of 938 breast cancer patients and 509 benign breast disease patients were retrospectively analyzed, and fasting blood samples were collected before treatment. Univariate and multivariate regression analyses were used to evaluate factors related to metastasis risk and prognosis. The Kaplan-Meier method was used to generate survival curves, and the log-rank test was used to measure differences in survival between groups.ResultsUse the cut-off value (3.433) of LMR, the logistic regression analysis revealed that high carbohydrate antigen 153 (CA153), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), killer T cell level, and low lymphocyte to monocyte ratio (LMR) level were significantly associated with BC distant metastasis. In contrast, LMR&gt;=3.433 (HR: 0.409, 95%CI: 0.193–0.867, P = 0.020), Th/Tc ratio &gt;=1.946 (HR: 0.378, 95% CI: 0.158–0.904, P =0.029) is regarded as a protective factor in the multivariate cox analyses. LMR is an independent prognostic factor for DFS in HER2-negative BC patients.ConclusionPeripheral blood parameters play an important role in predicting distant metastasis and prognosis of BC patients. As a potential marker, LMR can predict the metastasis and prognosis of patients with stage I-III BC.
Construction and Validation of Convenient Clinicopathologic Signatures for Predicting the Prognosis of Stage I-III Gastric Cancer
Authors: You Weiqiang , Cai Zerong , Sheng Nengquan , Yan Li , Wan Huihui , Wang Yongkun , Ouyang Jian , Xie Lu , Wu Xiaojian , Wang Zhigang 
Published: March 2022

BackgroundPatients with stage I-III gastric cancer (GC) undergoing R0 radical resection display extremely different prognoses. How to discriminate high-risk patients with poor survival conveniently is a clinical conundrum to be solved urgently.MethodsPatients with stage I-III GC from 2010 to 2016 were included in our study. The associations of clinicopathological features with disease-free survival (DFS) and overall survival (OS) were examined via Cox proportional hazard model. Nomograms were developed which systematically integrated prognosis-related features. Kaplan–Meier survival analysis was performed to compare DFS and OS among groups. The results were then externally validated by The Sixth Affiliated Hospital, Sun Yat-sen University.ResultsA total of 585 and 410 patients were included in the discovery cohort and the validation cohort, respectively. T stage, N stage, lymphatic/vascular/nerve infiltration, preoperative CEA, and CA19-9 were independent prognostic factors (P &lt; 0.05). Two prognostic signatures with a concordance index (C-index) of 0.7502 for DFS and 0.7341 for OS were developed based on the nomograms. The 3-year and 5-year calibration curves showed a perfect correlation between predicted and observed outcomes. Patients were divided into three risk groups (low, intermediate, high), and distinct differences were noticed (p &lt; 0.001). Similar results were achieved in the validation cohort. Notably, a free website was constructed based on our signatures to predict the recurrence risk and survival time of patients with stage I-III GC.ConclusionsThe signatures demonstrate the powerful ability to conveniently identify distinct subpopulations, which may provide significant suggestions for individual follow-up and adjuvant therapy.
Dosimetric Evaluation and Clinical Application of Radioactive Iodine-125 Brachytherapy Stent in the Treatment of Malignant Esophageal Obstruction
Authors: Ji Zhe , Yuan Qianqian , Lin Lei , Xing Chao , Zhang Xusheng , Yang Sen , Jiang Yuliang , Sun Haitao , Zhang Kaixian , Wang Junjie 
Published: March 2022

ObjectiveTo evaluate the dosimetric characteristics and the clinical application of radioactive iodine-125 brachytherapy stent (RIBS) in malignant esophageal obstruction.MethodsThe dose distribution of RIBS with different seed spacing, diameter and length was studied by treatment planning system (TPS) calculation, thermoluminescence dosimeter (TLD) measurement and Monte Carlo (MC) data fitting. And the data of esophageal cancer patients who were treat with this type of RIBS was analyzed retrospectively.ResultsDoses around the RIBS calculated by the TPS lay between those measured by the TLDs and those simulated by the MC, and the differences between the three methods were significant (p&lt;0.05), the overall absolute dose differences among the three methods were small. Dose coverage at 1.5 cm from the center was comprehensive when the activity reached 0.6 mCi. Both the conformability and the uniformity of isodose lines produced by a seed spacing of 1.0 cm were superior to those produced by a seed spacing of 1.5 cm. The data of 50 patients treated with RIBS was analyzed. They were followed up until February 2020 when all of the patients died. The overall improvement rate of dysphagia after RIBS implant was 90%. Moderate and severe complications with an incidence of more than 10% were hematemesis (28%), pain (20%), and lung infection (10%). Stent restenosis occurred in 4 patients at a median interval of 108 days from the procedure. The overall incidence of fatal complications was 38% (including hematemesis, infection and asphyxia). The median survival time of patients with and without a history of radiotherapy were 3.4 months and 6 months, respectively, the difference of which was significant (p=0.021). No other factors affecting survival were identified. For patients with and without a history of radiotherapy, the incidences of fatal complications were 51.7% and 19%, respectively (p=0.019). No correlation between dose and stent restenosis was found.ConclusionTPS calculations are suitable for clinical applications. RIBS can effectively alleviate obstructive symptoms for patients with malignant esophageal obstruction, but the incidence of fatal complications was high, care should be taken when choosing this treatment.
Immersive Virtual Reality in Alleviating Pain and Anxiety in Children During Immunization in Primary Care: A Pilot Randomized Controlled Trial
Authors: Chang Zi Ying , Kang Gary Chun-Yun , Koh Eileen Yi Ling , Fong Rodney Jin Kai , Tang Jiasheng , Goh Chi Keong , Tan Ngiap Chuan 
Published: March 2022

BackgroundPediatric immunization is often associated with significant fear and anxiety among the children and their parents. Their distress may potentially affect their adherence to the childhood immunization schedule and the acceptance of other recommended vaccines by physicians.ObjectiveThe study primarily aimed to assess the feasibility of using immersive virtual reality (VR) during immunization in children in primary care. The secondary aim was to determine the effectiveness of immersive VR in alleviating pain and anxiety among children, reduction of anxiety of their parents and attending nurses during immunization compared to usual care without VR.MethodsA pilot open-label randomized control trial was conducted at a public primary care clinic in Singapore. Thirty children, aged 4–10 years were randomized to an intervention group (n = 15) using VR and a control group (n = 15) without VR during immunization. Feasibility was assessed by the response rate to the use of VR. The Faces Pain Scale-Revised (FPS-R) and the Children’s Fear Scale (CFS) were used to determine their pain and anxiety, respectively. The anxiety level of their accompanying parents and attending nurses were evaluated using Visual Analog Scale (VAS) prior and post-immunization of these children. The FPS-R and CFS scores, and anxiety assessment for parents and nurses were assessed using Mann-Whitney U test. Wilcoxon signed rank test was used to assess the difference in the nurses’ experience of using the VR application.ResultsOne child refused to use the VR equipment, constituting a rejection rate of 6.7% (1/15) but no adverse event occurred in the intervention arm. The overall response rate of 88% (30/34) when the parents were approached to participate in the study, indicating feasibility of using VR in childhood immunization. In the intervention group compared to the control group, the change in scores for CFS (median −1, IQR −2 to 0; P = 0.04), parental VAS (median −4, IQR −5 to −1; P = 0.04) were significantly decreased. After immunization, nurses scored favorably for VR, in terms of simplicity (median 9.5, IQR 5.72 to 10; P = 0.01), acceptability (median 10, IQR 5 to 10; P = 0.005) and willingness to use VR in the future (median 10, IQR 5 to 10; P = 0.02).ConclusionImmersive VR is feasible, safe and effective in alleviating anxiety among the children and parents. Nurses viewed the application of VR in childhood immunization favorably.Clinical Trial Registration[https://clinicaltrials.gov/ct2/show/NCT04748367], identifier [NCT04748367].
Case Report: Zellweger Syndrome and Humoral Immunodeficiency: The Relevance of Newborn Screening for Primary Immunodeficiency
Authors: Fazi C. , Lodi L. , Magi L. , Canessa C. , Giovannini M. , Pelosi C. , Pochiero F. , Procopio E. , Donati M. A. , Azzari C. , Ricci S. 
Published: March 2022

BackgroundZellweger syndrome (ZS) is a congenital autosomal recessive disease within the spectrum of peroxisome biogenesis disorders, characterized by the impairment of peroxisome assembly. The presence of peroxisome enzyme deficiencies leads to complex developmental sequelae, progressive disabilities, and multiorgan damage, due to intracellular accumulation of very-long-chain fatty acids (VLCFAs).Case PresentationWe report the case of an infant affected by ZS in which agammaglobulinemia, detected through neonatal screening of congenital immunodeficiencies, appeared as a peculiar trait standing out among all the other classical characteristics of the syndrome. The exome analysis through next-generation sequencing (NGS), which had previously confirmed the diagnostic suspicion of ZS, was repeated, but no mutations causative of inborn error of immunity (humoral defect) were detected.ConclusionIn this case, no genetic variants accountable for the abovementioned agammaglobulinemia were detected. Given that the scientific literature reports the involvement of peroxisomes in the activation of Nuclear Factor κ-light-chain-enhancer of activated B cells (NF-κB) pathway, which is crucial for B-cell survival, with this work, we hypothesize the existence of a link between ZS and humoral immunodeficiencies. Further studies are required to confirm this hypothesis.
The Efficacy of Cognitive Behavioral Therapy for Tic Disorder: A Meta-Analysis and a Literature Review
Authors: Shou Songting , Li Yuanliang , Fan Guohui , Zhang Qiang , Yan Yurou , Lv Tiying , Wang Junhong 
Published: March 2022

BackgroundAt present, tic disorder has attracted the attention of medical researchers in many countries. More clinicians choose non-drug therapy, especially cognitive-behavioral therapy (CBT) because of the cognitive side effects of drug therapy. However, few studies had assessed its efficacy. It is necessary to have a more comprehensive understanding of the literature quality of CBT and its intervention effect.MethodsIn this study, MEDLINE, Embase, and Cochrane were searched from the beginning to June 15, 2021 to study the efficacy of -CBT on tic disorder. Only studies using the Yale Global Tic Severity Scale (YGTSS) and the control group were included.ResultsA total of 12 randomized controlled trials (RCTs), including 536 patients with tic disorders, were identified. The results showed that the effect of CBT was better than that of the control group. The pooled standardized mean difference (SMD) was −0.34 (95% CI: −0.61, −0.07). The effect size of CBT differs from different intervention conditions. In seven studies, the subjects’ motor tic scores were counted. The sample size of the experimental group was 224 and that of the control group was 218. The pooled SMD was −0.43 (95% CI: −0.75, −0.11). Seven studies counted the vocal tic scores of subjects, 224 in the experimental group and 218 in the control group. The pooled SMD was −0.22 (95% CI: −0.54, −0.11). Seven studies counted the tic impairment scores of subjects, 220 in the experimental group and 214 in the control group. The pooled SMD was −0.48 (95% CI: −0.73, −0.23).ConclusionThe literature shows that different CBTs can significantly reduce the total score of tic disorder and the score of motor tic, but cannot significantly reduce the score of vocal tic. In the future, more new interventions were needed to improve the symptoms of different patients, especially vocal tic.