bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roles and Clinical Significances of ATF6, EMC6, and APAF1 in Prognosis of Pancreatic Cancer
Authors: Xiao Wang , Cao Rong-Chang , Yang Wan-Jun , Tan Jie-Hui , Liu Ruo-Qi , Kan He-Ping , Zhou Lei , Zhang Na , Chen Zhi-Ye , Chen Xue-Mei , Xu Jia , Zhang Guo-Wei , Shen Peng 
Published: February 2022

Background: Pancreatic cancer (PC) is prevalent among malignant tumors with poor prognosis and lacks efficient therapeutic strategies. Endoplasmic reticulum (ER) stress and apoptosis are associated with chronic inflammation and cancer progression. However, the prognostic value of ER stress-related, and apoptosis-related genes in PC remains to be further elucidated. Our study aimed at confirming the prognostic values of the ER stress-related genes, ATF6, EMC6, XBP1, and CHOP, and the apoptosis-related gene, APAF1, in PC patients.Methods: Gene Expression Profiling Interactive Analysis 2 (GEPIA2) was used to evaluate prognosis value of ATF6, EMC6, XBP1, CHOP, and APAF1 in PC. Clinical data from 69 PC patients were retrospectively analyzed. Immunohistochemistry, Western blotting, and qRT-PCR were used for the assessment of gene or protein expression. The cell counting kit-8 (CCK-8) and the Transwell invasion assays were, respectively, used for the assessment of the proliferative and invasive abilities of PC cells. The prognostic values of ATF6, XBP1, CHOP, EMC6, and APAF1 in PC patients were evaluated using Kaplan–Meier and Cox regression analyses.Results: XBP1 and CHOP expressions were not associated with PC recurrence-free survival (RFS), overall survival (OS) and disease-specific survival (DSS). ATF6 upregulation and EMC6 and APAF1 downregulations significantly correlated with the poor RFS, OS, and DSS of PC patients. ATF6 promoted PC cell proliferation and invasion, while EMC6 and APAF1 inhibited these events.Conclusion: ATF6 upregulation and EMC6 and APAF1 downregulations may be valid indicators of poor prognosis of PC patients. Moreover, ATF6, EMC6, and APAF1 may constitute potential therapeutic targets in PC patients.
Clinical Features and Surgical Treatment of Subretinal Proliferation in Proliferative Diabetic Retinopathy
Authors: Wu Chan , Dai Rongping , Chen Youxin , Zhang Xiao , Chen Zhe 
Published: February 2022

PurposeTo describe the clinical characteristics, treatments, and prognosis of subretinal proliferation (SRP) in proliferative diabetic retinopathy (PDR) patients.MethodsA total of 184 patients (221 eyes) who received vitrectomy for PDR between 2018 and 2021 were retrospectively reviewed. Patients with SRP were further evaluated. The following data were collected from their medical records: demographics, systemic and ophthalmologic findings, and treatment given specifically for SRP. The main outcome measures included the visual acuity (VA), funduscopic examination, and final anatomic success.ResultsTwelve eyes of eleven patients including seven females and four males with a mean age of 47.64 ± 11.21 years were evaluated. The surgical indication for the patients was mainly tractional retinal detachment (TRD) (100.0%). No retinal break was found preoperatively or intraoperatively. Only one eye (8.3%) had undergone subretinal band removal procedure intraoperatively, and the final anatomical success rate was 100%.ConclusionSubretinal proliferation in PDR was associated with TRD. The retina could reattach successfully after vitrectomy without removal or transection of SRP in most eyes.
Association of Headache Disorders and the Risk of Dementia: Meta-Analysis of Cohort Studies
Authors: Qu Huiling , Yang Shida , Yao Zhicheng , Sun Xiaoyu , Chen Huisheng 
Published: February 2022

ObjectivesThe purpose of this meta-analysis is to assess whether there is an association between headache disorders and all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD).MethodsPubMed, Cochrane Library, Embase, and Web of Science were searched for cohort studies published from database inception to October 8, 2021, using medical subject headings (MeSH) and keywords. All statistical analyses were performed using Stata statistical software version 14.0. If P &gt; 0.1 and I2 ≤ 50%, a fixed-effects model was adopted. If I2 &gt; 50% (which indicated great heterogeneity), a random-effects model was adopted. The funnel plot and Egger's test were used to evaluate publication bias.ResultsThis meta-analysis included 12 cohort studies covering 465,358 individuals, which were published between 2001 and 2020. The pooling analysis shows that a history of any headache disorder is associated with an increased risk of all-cause dementia (OR = 1.35; 95% CI: 1.21–1.50; I2 = 81.6%, P &lt; 0.001). The history of any headache was associated with an increased risk of AD (OR = 1.49; 95% CI: 1.08–2.05; I2 = 70.0%, P = 0.003) and VaD (OR = 1.72; 95% CI: 1.32–2.25; I2 = 0%, P &lt; 0.001). In the subgroup analysis, females with a history of headache have a slightly higher risk of dementia than males (OR = 1.32; 95% CI: 1.16–1.51; I2 = 88.3%, P &lt; 0.001) and the risk of dementia in the retrospective cohort was slightly higher than in the prospective cohort (OR = 1.38; 95% CI: 1.22–1.56; I2 = 83.4%, P &lt; 0.001).ConclusionsOur meta-analysis shows that any headache disorder increases the risk of all-cause dementia, AD, or VaD. These findings provide evidence that headache should be recognized as an independent risk factor for dementia, AD, or VaD.
Is Immune Suppression Involved in the Ischemic Stroke? A Study Based on Computational Biology
Authors: Wang Xin , Wang Qian , Wang Kun , Ni Qingbin , Li Hu , Su Zhiqiang , Xu Yuzhen 
Published: February 2022

ObjectiveTo identify the genetic mechanisms of immunosuppression-related genes implicated in ischemic stroke.BackgroundA better understanding of immune-related genes (IGs) involved in the pathophysiology of ischemic stroke may help identify drug targets beneficial for immunomodulatory approaches and reducing stroke-induced immunosuppression complications.MethodsTwo datasets related to ischemic stroke were downloaded from the GEO database. Immunosuppression-associated genes were obtained from three databases (i.e., DisGeNET, HisgAtlas, and Drugbank). The CIBERSORT algorithm was used to calculate the mean proportions of 22 immune-infiltrating cells in the stroke samples. Differential gene expression analysis was performed to identify the differentially expressed genes (DEGs) involved in stroke. Immunosuppression-related crosstalk genes were identified as the overlapping genes between ischemic stroke-DEGs and IGs. Feature selection was performed using the Boruta algorithm and a classifier model was constructed to evaluate the prediction accuracy of the obtained immunosuppression-related crosstalk genes. Functional enrichment analysis, gene-transcriptional factor and gene-drug interaction networks were constructed.ResultsTwenty two immune cell subsets were identified in stroke, where resting CD4 T memory cells were significantly downregulated while M0 macrophages were significantly upregulated. By overlapping the 54 crosstalk genes obtained by feature selection with ischemic stroke-related genes obtained from the DisGenet database, 17 potentially most valuable immunosuppression-related crosstalk genes were obtained, ARG1, CD36, FCN1, GRN, IL7R, JAK2, MAFB, MMP9, PTEN, STAT3, STAT5A, THBS1, TLR2, TLR4, TLR7, TNFSF10, and VASP. Regulatory transcriptional factors targeting key immunosuppression-related crosstalk genes in stroke included STAT3, SPI1, CEPBD, SP1, TP53, NFIL3, STAT1, HIF1A, and JUN. In addition, signaling pathways enriched by the crosstalk genes, including PD-L1 expression and PD-1 checkpoint pathway, NF-kappa B signaling, IL-17 signaling, TNF signaling, and NOD-like receptor signaling, were also identified.ConclusionPutative crosstalk genes that link immunosuppression and ischemic stroke were identified using bioinformatics analysis and machine learning approaches. These may be regarded as potential therapeutic targets for ischemic stroke.
Non-invasive Brain Stimulation for Neuropathic Pain After Spinal Cord Injury: A Systematic Review and Network Meta-Analysis
Authors: Li Lingling , Huang Hailiang , Yu Ying , Jia Yuqi , Liu Zhiyao , Shi Xin , Wang Fangqi , Zhang Tingting 
Published: February 2022

ObjectiveThis study aims to systematically evaluate the effect of non-invasive brain stimulation (NIBS) on neuropathic pain (NP) after spinal cord injury and compare the effects of two different NIBS.MethodsRandomized controlled trials (RCTs) about the effect of NIBS on NP after spinal cord injury (SCI) were retrieved from the databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, and CBM from inception to September 2021. The quality of the trials was assessed, and the data were extracted according to the Cochrane handbook of systematic review. Statistical analysis was conducted with Stata (version 16) and R software (version 4.0.2).ResultsA total of 17 studies involving 507 patients were included. The meta-analysis showed that NIBS could reduce the pain score (SMD = −0.84, 95% CI −1.27 −0.40, P = 0.00) and the pain score during follow-up (SMD = −0.32, 95%CI −0.57 −0.07, P = 0.02), and the depression score of the NIBS group was not statistically significant than that of the control group (SMD = −0.43, 95%CI −0.89–0.02, P = 0.06). The network meta-analysis showed that the best probabilistic ranking of the effects of two different NIBS on the pain score was repetitive transcranial magnetic stimulation (rTMS) (P = 0.62) &gt; transcranial direct current stimulation (tDCS) (P = 0.38).ConclusionNIBS can relieve NP after SCI. The effect of rTMS on NP is superior to that of tDCS. We suggest that the rTMS parameters are 80–120% resting motion threshold and 5–20 Hz, while the tDCS parameters are 2 mA and 20 min. However, it is necessary to carry out more large-scale, multicenter, double-blind, high-quality RCT to explore the efficacy and mechanism of NIBS for NP after SCI.
Two-Year Toxicity and Efficacy of Carbon Ion Radiotherapy in the Treatment of Localized Prostate Cancer: A Single-Centered Study
Authors: Li Ping , Hong Zhengshan , Li Yongqiang , Fu Shen , Zhang Qing 
Published: February 2022

BackgroundWe aimed at determining the safety and feasibility of spot-scanning carbon ion radiotherapy (CIRT) for patients with localized prostate cancer.MethodsWe enrolled 118 patients with localized prostate cancer who underwent treatment with spot-scanning CIRT at the Shanghai Proton and Heavy Ion Center (SPHIC) from January 2016 to December 2020. The dose was gradually increased from relative biological effectiveness (RBE)-weighted dose (DRBE) = 59.2–65.6 Gy in 16 fractions. The primary endpoint was the occurrence of acute and late toxicities, while the secondary endpoints were biochemical relapse-free survival (bRFS), distant metastasis-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS).ResultsThe median follow-up time was 30.2 months (4.8–62.7 months). Acute grade 1 and 2 genitourinary (GU) toxicities were 15.3% and 18.6%, while acute grade 1 and 2 gastrointestinal (GI) toxicities were 2.5% and 0%, respectively. Late grade 1 and 2 GU toxicities were 4.2% and 1.7%, respectively. No late GI toxicity was observed. Moreover, there were no cases of severe acute or late toxicity (≥ grade 3). No significant association were observed between the factors and the acute GU toxicities, except for clinical target volume (CTV) (p = 0.031) on multivariate analysis. The 2-year bRFS, DMFS, PCSS, and OS were 100%, 100%, 100%, and 98.8%, respectively.ConclusionThe 2-year outcomes were encouraging, providing additional and useful information on the feasibility and safety of spot-scanning CIRT for treating prostate cancer. Thus, we recommend long-term follow-up and prospective multicentered studies to reinforce the role of CIRT in the management of localized prostate cancer.
Correlation Between Adjuvant Chemotherapy Regimen, Recurrence Pattern and Prognosis of Cholangiocarcinoma After Radical Surgery
Authors: Rao Le , Ma Na , Liu Yanli , Du Lehui , Qu Baolin 
Published: February 2022

Background and PurposeAbout 70% of patients with radical surgery Cholangiocarcinoma (CCA) have recurrence and metastasis. There are few studies on the relationship between CCA adjuvant chemotherapy (mono or combined therapy), recurrence pattern (local, regional, distant recurrence) and prognosis [(Disease free survival, DFS), (Overall survival, OS)] after radical surgery. This study focuses on the correlation between CCA adjuvant chemotherapy, recurrence pattern and prognosis.MethodsThe study involved retrospective analysis of data: preoperative hematology, clinical pathology, adjuvant chemotherapy regimens, recurrence pattern, DFS and OS, of 207 patients with CCA. Chi-square test was used to analyze the correlation between related factors and postoperative recurrence. Survival curves were plotted by Kaplan-Meier method, P-values were calculated by Log-rank for univariate analysis, multivariate COX regression method for multivariate analysis.ResultsUsing chi-square test, there were correlations between high carbohydrate antigen 19-9 level(CA19-9≥35), vascular invasion, single-agent adjuvant chemotherapy and postoperative recurrences (p=0.04, p=0.04, p=0.02), COX multivariate regression analysis showed that adjuvant chemotherapy (single vs. doublet drug regimen) was an independent prognostic factor for DFS (11.0 vs. 24.6 months, HR=2.88, P=0.01), whereas recurrence pattern (local vs. distant; regional vs. distant) was an independent prognostic factor for OS (31.2 months vs. 20.4 months, HR=0.58, p=0.01; 32.0 months vs. 20.4 months, HR=0.51, p=0.01).ConclusionAdjuvant chemotherapy regimen was an independent prognostic factor of DFS, whereas recurrence patterns were independent prognostic factors for OS. adjuvant chemotherapy with doublet drug regimen was correlated with longer DFS, and different recurrence modes affect OS.
Aggressive Posterior Retinopathy of Prematurity: Long-Term Outcomes Following Intravitreal Bevacizumab
Authors: Naravane Ameay V. , Belin Peter J. , Rubino Shaina , Quiram Polly A. 
Published: February 2022

PurposeThe purpose of this study is to review the neonatal and early childhood course of children who were treated with intravitreal bevacizumab for APROP and identify any long term limitations these children face years after treatment.MethodsThis retrospective consecutive case series reviewed both ophthalmologic and pediatric medical records to determine ocular and neurologic function following treatment with a single injection of intravitreal bevacizumab (IVB) for APROP. Patient records were reviewed to identify the gestational age, average birth weight, gender, post-menstrual age (PMA) at the time of injection, regression status, rescue therapy events, final visual acuity, final refraction, ophthalmologic diagnoses and complications, neurologic diagnoses, and duration of follow up.ResultsThe study included 43 eyes from 13 male and 9 female children. The average gestational age was 24 weeks and average birth weight was 625.2 grams. The average follow-up was 4.08 years (range: 1.85–7.36 years). The average PMA at time of bevacizumab injection was 35.59 weeks. Thirty-five eyes eventually received laser photocoagulation at an average PMA of 53.17 weeks. All eyes in this study demonstrated regression without progression to retinal detachment. At last follow up, 67% (29/43) of eyes were able to discern letters or shapes, with an average visual acuity of 20/37. 16 (72%) children were diagnosed with perinatal neurological disorders. 59% (n = 13) developed chronic neurological impairment, 77% (n = 10) of whom developed neurodevelopmental delay. Several infants were diagnosed with endocrine disease or genetic syndromes.ConclusionsExtreme prematurity is associated with significant morbidity. Nearly all infants (92%) who developed chronic neurologic disease were diagnosed with neurologic disease during the perinatal period. Intravitreal bevacizumab, often with adjuvant photocoagulation, led to regression without detachment in 100% of eyes, with most verbal children retaining functional vision.
Non-Vitamin K Oral Anticoagulant After Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis
Authors: Li Dongxu , Ma Xiaofang , Zhou Xu , Qian Yongjun 
Published: February 2022

Objective: We aimed to compare non-vitamin K oral anticoagulants (NOACs) with a traditional antithrombotic such as vitamin K antagonist (VKA) and antiplatelet agents in patients after transcatheter aortic valve replacement (TAVR).Methods: We conducted a search in PubMed, EMBASE, and the Cochrane Library until November 2021 for studies involving comparisons of any type of NOACs, including dabigatran, apixaban, rivaroxaban, and edoxaban, with VKA or antiplatelet agents after TAVR. A comparison of NOACs versus VKA was performed in patients with an indication for oral anticoagulation. In addition, we compared NOACs versus antiplatelet in patients without such indication. We calculated the hazard ratios with 95% confidence intervals (CIs) to determine long-term outcomes. The primary outcome was a combined endpoint consisting of all-cause mortality, stroke, major bleeding, or any related clinical adverse events. Secondary outcomes were all-cause mortality, major bleeding, and stroke, respectively.Results: A total of 10 studies including 10,563 patients after TAVR were included in this meta-analysis. There were no significant differences in any of the long-term outcomes between the NOAC and VKA groups. Although there were no significant differences in the combined endpoint, major bleeding, or stroke, a significant difference was observed in the all-cause mortality (HR 1.74, 95% CI 1.25–2.43, p = 0.001) between the NOAC and antiplatelet groups.Conclusion: For patients with an indication for oral anticoagulation after TAVR, NOACs seem to be associated with noninferior outcomes compared with VKA therapy. However, for patients without an indication for oral anticoagulation, NOACs appear to be associated with a higher risk of all-cause death as compared with antiplatelet treatment.Systematic Review Registration:https://clinicaltrials.gov/, identifier CRD42020155122.
Fenestropathy of Voltage-Gated Sodium Channels
Authors: Gamal El-Din Tamer M. , Lenaeus Michael J. 
Published: February 2022

Voltage-gated sodium channels (Nav) are responsible for the initiation and propagation of action potentials in excitable cells. From pain to heartbeat, these integral membrane proteins are the ignition stations for every sensation and action in human bodies. They are large (&gt;200 kDa, 24 transmembrane helices) multi-domain proteins that couple changes in membrane voltage to the gating cycle of the sodium-selective pore. Nav mutations lead to a multitude of diseases - including chronic pain, cardiac arrhythmia, muscle illnesses, and seizure disorders - and a wide variety of currently used therapeutics block Nav. Despite this, the mechanisms of action of Nav blocking drugs are only modestly understood at this time and many questions remain to be answered regarding their state- and voltage-dependence, as well as the role of the hydrophobic membrane access pathways, or fenestrations, in drug ingress or egress. Nav fenestrations, which are pathways that connect the plasma membrane to the central cavity in the pore domain, were discovered through functional studies more than 40 years ago and once thought to be simple pathways. A variety of recent genetic, structural, and pharmacological data, however, shows that these fenestrations are actually key functional regions of Nav that modulate drug binding, lipid binding, and influence gating behaviors. We discovered that some of the disease mutations that cause arrhythmias alter amino acid residues that line the fenestrations of Nav1.5. This indicates that fenestrations may play a critical role in channel’s gating, and that individual genetic variation may also influence drug access through the fenestrations for resting/inactivated state block. In this review, we will discuss the channelopathies associated with these fenestrations, which we collectively name “Fenestropathy,” and how changes in the fenestrations associated with the opening of the intracellular gate could modulate the state-dependent ingress and egress of drugs binding in the central cavity of voltage gated sodium channels.
Exploring Correlates of Loss of Control Eating in a Nonclinical Sample
Authors: Conceição Eva M. , Moreira Célia S. , de Lourdes Marta , Ramalho Sofia , Vaz Ana Rita 
Published: February 2022

ObjectiveLoss of control (LOC) eating has been directly related to the core aspects of the psychopathology of eating disorders and to different dimensions of emotion and behavior regulation and self-criticism. This study investigates a model representing the interplay between these dimensions to understand LOC eating among a nonclinical sample.MethodsA total of 341 participants, recruited in a college campus (mean age 23.21, SD = 6.02), completed a set of self-report measures assessing LOC eating, weight suppression, psychopathology of eating disorders, depression, negative urgency, emotion regulation difficulties, and self-criticism. Path analysis modeling tested a hypothesized model with 3 paths for LOC eating as follows: (1) psychopathology of eating disorders; (2) emotion and behavior regulation; and (3) interplay between these paths.ResultsWe found goodness-of-fit indexes to our data: χ2 = 17.11, df = 10, Comparative Fit Index (CFI) = 0.99, Tucker-Lewis index (TLI) = 0.98, Root Mean Square Error Approximation (RMSEA) = 0.045, Standardized Root Mean Square Residual (SRMR) = 0.041, suggesting that: (1) participants with higher weight suppression showed higher degrees of the psychopathology of eating disorders, which was linked to higher levels of LOC eating; (2) self-criticism was a mediator between emotion regulation and depression/negative urgency; (3) self-criticism was a mediator between emotion regulation and disorder eating, which was significantly associated with LOC eating via increased negative urgency.ConclusionOur model shows that LOC eating occurs for individuals with the psychopathology of higher eating disorders who experience depressive symptoms and act rashly under distress for their inability to cope adequately with negative feelings of self-devaluation. These findings point to the importance of negative self-evaluations and feelings of inadequacy or worthlessness to understand LOC eating among college students.