bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of a Six-Gene Prognostic Risk Model Related to Hypoxia and Angiogenesis for Cervical Cancer
Authors: Liu Lili , Zhu Hongcang , Wang Pei , Wu Suzhen 
Published: June 2022

Background: The prognosis of cervical cancer (CC) is poor and not accurately reflected by the primary tumor node metastasis staging system. Our study aimed to develop a novel survival-prediction model.Methods: Hallmarks of CC were quantified using single-sample gene set enrichment analysis and univariate Cox proportional hazards analysis. We linked gene expression, hypoxia, and angiogenesis using weighted gene co-expression network analysis (WGCNA). Univariate and multivariate Cox regression was combined with the random forest algorithm to construct a prognostic model. We further evaluated the survival predictive power of the gene signature using Kaplan-Meier analysis and receiver operating characteristic (ROC) curves.Results: Hypoxia and angiogenesis were the leading risk factors contributing to poor overall survival (OS) of patients with CC. We identified 109 candidate genes using WGCNA and univariate Cox regression. Our established prognostic model contained six genes (MOCSI, PPP1R14A, ESM1, DES, ITGA5, and SERPINF1). Kaplan-Meier analysis indicated that high-risk patients had worse OS (hazard ratio = 4.63, p &lt; 0.001). Our model had high predictive power according to the ROC curve. The C-index indicated that the risk score was a better predictor of survival than other clinicopathological variables. Additionally, univariate and multivariate Cox regressions indicated that the risk score was the only independent risk factor for poor OS. The risk score was also an independent predictor in the validation set (GSE52903). Bivariate survival prediction suggested that patients exhibited poor prognosis if they had high z-scores for hypoxia or angiogenesis and high risk scores.Conclusions: We established a six-gene survival prediction model associated with hypoxia and angiogenesis. This novel model accurately predicts survival and also provides potential therapeutic targets.
Causal Effects of Circulating Cytokines on the Risk of Psoriasis Vulgaris: A Mendelian Randomization Study
Authors: Zhao Pan , Zhang Jing , Liu Biyong , Tang Yufei , Wang Lei , Wang Guifeng , Wu Huihui , Yang Chengwei , Li Xuemei , Li Bo 
Published: June 2022

Background: Psoriasis vulgaris is an inflammatory skin disease. Observational studies have shown associations between circulating cytokine levels and psoriasis vulgaris. But the causal relationship between circulating cytokine and psoriasis vulgaris remains elusive.Methods: To assess the causal effects of cytokine levels on the risk of psoriasis vulgaris and vice versa, we performed a two-sample Mendelian randomization (MR) study by using the inverse-variance weighted (IVW), weighted median, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) in genome-wide association summary statistics of 41 circulating cytokines in up to 8,293 individuals and psoriasis vulgaris in 399,883 individuals.Results: We identified that increasing RANTES level induced an elevated risk of psoriasis vulgaris in IVW (β = 0.33, S.E. = 0.12, p = 0.006). This causal effect showed consistency across the weighted median (β = 0.35, S.E. = 0.15, p = 0.022) and MR-PRESSO method (β = 0.33, S.E. = 0.11, p = 0.028).Conclusions: Our results suggest a potential causal effect of elevated RANTES concentration on the increased risk of psoriasis vulgaris.
Stunting Status and Exposure to Infection and Inflammation in Early Life Shape Antibacterial Immune Cell Function Among Zimbabwean Children
Authors: Mutasa Kuda , Tome Joice , Rukobo Sandra , Govha Margaret , Mushayanembwa Patience , Matimba Farai S. , Chiorera Courage K. , Majo Florence D. , Tavengwa Naume V. , Mutasa Batsirai , Chasekwa Bernard , Humphrey Jean H. , Ntozini Robert , Prendergast Andrew J. , Bourke Claire D. 
Published: June 2022

BackgroundChildren who are stunted (length-for-age Z-score&lt;-2) are at greater risk of infectious morbidity and mortality. Previous studies suggest that stunted children have elevated inflammatory biomarkers, but no studies have characterised their capacity to respond to new infections (i.e., their immune function). We hypothesised that antibacterial immune function would differ between stunted and non-stunted children and relate to their health and environment during early life.MethodsWe enrolled a cross-sectional cohort of 113 HIV-negative children nested within a longitudinal cluster-randomised controlled trial of household-level infant and young child feeding (IYCF) and water, sanitation and hygiene (WASH) interventions in rural Zimbabwe (SHINE; Clinical trials registration: NCT01824940). Venous blood was collected at 18 months of age and cultured for 24 h without antigen or with bacterial antigens: heat-killed Salmonella typhimurium (HKST) or Escherichia coli lipopolysaccharide (LPS). TNFα, IL-6, IL-8, IL-12p70, hepcidin, soluble (s)CD163, myeloperoxidase (MPO) and IFNβ were quantified in culture supernatants by ELISA to determine antigen-specific immune function. The effect of stunting status and early-life exposures (anthropometry, inflammation at 18 months, maternal health during pregnancy, household WASH) on immune function was tested in logit and censored log-normal (tobit) regression models.ResultsChildren who were stunted (n = 44) had higher proportions (86.4% vs. 65.2%; 88.6% vs. 73.4%) and concentrations of LPS-specific IL-6 (geometric mean difference (95% CI): 3.46 pg/mL (1.09, 10.80), p = 0.035) and IL-8 (3.52 pg/mL (1.20, 10.38), p = 0.022) than non-stunted children (n = 69). Bacterial antigen-specific pro-inflammatory cytokine concentrations were associated with biomarkers of child enteropathy at 18 months and biomarkers of systemic inflammation and enteropathy in their mothers during pregnancy. Children exposed to the WASH intervention (n = 33) produced higher LPS- (GMD (95% CI): 10.48 pg/mL (1.84, 60.31), p = 0.008) and HKST-specific MPO (5.10 pg/mL (1.77, 14.88), p = 0.003) than children in the no WASH group (n = 80). There was no difference in antigen-specific immune function between the IYCF (n = 55) and no IYCF groups (n = 58).ConclusionsAntibacterial immune function among 18-month-old children in a low-income setting was shaped by their stunting status and prior exposure to maternal inflammation and household WASH. Heterogeneity in immune function due to adverse exposures in early life could plausibly contribute to infection susceptibility.
Differentiation of T Helper 17 Cells May Mediate the Abnormal Humoral Immunity in IgA Nephropathy and Inflammatory Bowel Disease Based on Shared Genetic Effects
Authors: Qing Jianbo , Li Changqun , Hu Xueli , Song Wenzhu , Tirichen Hasna , Yaigoub Hasnaa , Li Yafeng 
Published: June 2022

BackgroundIgA nephropathy (IgAN) is the most frequent glomerulonephritis in inflammatory bowel disease (IBD). However, the inter-relational mechanisms between them are still unclear. This study aimed to explore the shared gene effects and potential immune mechanisms in IgAN and IBD.MethodsThe microarray data of IgAN and IBD in the Gene Expression Omnibus (GEO) database were downloaded. The differential expression analysis was used to identify the shared differentially expressed genes (SDEGs). Besides, the shared transcription factors (TFs) and microRNAs (miRNAs) in IgAN and IBD were screened using humanTFDB, HMDD, ENCODE, JASPAR, and ChEA databases. Moreover, weighted gene co-expression network analysis (WGCNA) was used to identify the shared immune-related genes (SIRGs) related to IgAN and IBD, and R software package org.hs.eg.db (Version3.1.0) were used to identify common immune pathways in IgAN and IBD.ResultsIn this study, 64 SDEGs and 28 SIRGs were identified, and the area under the receiver operating characteristic curve (ROC) of 64 SDEGs was calculated and two genes (MVP, PDXK) with high area under the curve (AUC) in both IgAN and IBD were screened out as potential diagnostic biomarkers. We then screened 3 shared TFs (SRY, MEF2D and SREBF1) and 3 miRNAs (hsa-miR-146, hsa-miR-21 and hsa-miR-320), and further found that the immune pathways of 64SDEGs, 28SIRGs and 3miRNAs were mainly including B cell receptor signaling pathway, FcγR-mediated phagocytosis, IL-17 signaling pathway, toll-like receptor signaling pathway, TNF signaling pathway, TRP channels, T cell receptor signaling pathway, Th17 cell differentiation, and cytokine-cytokine receptor interaction.ConclusionOur work revealed the differentiation of Th17 cells may mediate the abnormal humoral immunity in IgAN and IBD patients and identified novel gene candidates that could be used as biomarkers or potential therapeutic targets.
Metastasis Related Epithelial-Mesenchymal Transition Signature Predicts Prognosis and Response to Immunotherapy in Gastric Cancer
Authors: Song Junquan , Wei Rongyuan , Huo Shiying , Gao Jianpeng , Liu Xiaowen 
Published: June 2022

BackgroundIncreasing evidence has revealed the effect of epithelial-mesenchymal transition (EMT) on tumor microenvironment and cancer treatment. However, an EMT-based signature to predict the prognosis and therapeutic effect in gastric cancer (GC) has rarely been established.MethodsDifferentially expressed genes (DEGs) between paired primary gastric and ovarian metastatic tumors were identified through comparative RNA-seq analysis, followed by the construction of metastasis-related EMT signature (MEMTS) based on DEGs and EMT gene set. Then, both The Cancer Genome Atlas (TCGA) cohort and the Asian Cancer Research Group (ACRG) cohort were analyzed to explore the potential association between MEMTS and prognosis in GC. Samsung Medical Center (SMC) cohort and two individual immunotherapy treatment cohorts, including Kim cohort and Hugo cohort, were utilized to evaluate the predictive value of MEMTS on the response to adjuvant therapy and immunotherapy, respectively. Finally, the potential association of MEMTS with tumor environment and immune escape mechanisms was investigated.ResultsHigh MEMTS predicted a poor prognosis in patients with GC. Patients with low MEMTS potentially gained more benefits from adjuvant chemoradiotherapy than those with high MEMTS. MEMTS reliably predicted the response to immunotherapy in GC (area under the curve = 0.896). MEMTS was significantly associated with cancer-associated fibroblasts and stromal score in the aspect of the tumor microenvironment.ConclusionMEMTS serves as a potential biomarker to predict the prognosis and response to adjuvant therapy and immunotherapy in GC. MEMTS-based evaluation of individual tumors enables personalized treatment for GC patients in the future.
UV-B Protective and Antioxidant Activities of Protein Hydrolysate From Sea Cucumber (Holothuria scabra) Using Enzymatic Hydrolysis
Authors: Doungapai Chitpon , Siriwoharn Thanyaporn , Malila Yuwares , Autsavapromporn Narongchai , Makkhun Sakunkhun , Yarnpakdee Suthasinee , Jantanasakulwong Kittisak , Regenstein Joe M. , Wangtueai Sutee 
Published: June 2022

Sea cucumber is rich in protein that can be used to prepare a potential derived bioactive peptide for antioxidant and protective effect against UV-B induced skin cell damage. This study aimed to optimize preparation of sea cucumber hydrolysate with both UV-B protective and antioxidant activities using three commercial enzymes using response surface methodology (RSM) with a face-centered central composite design (face- centered CCD). Hydrolysis time and concentration of enzyme effects on the degree of hydrolysis (DH), yield, antioxidant and UV-B protective activities of sea cucumber hydrolysates were determined. The optimum conditions for sea cucumber hydrolysis using papain (SCP), alcalase (SCA), or flavourzyme (SCF) were 3.6, 5.0, and 4.1% (w/w protein), respectively, and a hydrolysis time of 360 min. The resulting hydrolysates had a DH of 81-91%, yield of 13-14%, IC50 for DPPH radical scavenging activity of 0.3-4.1 mg/mL, FRAP of 0.5-0.6 mmol FeSO4/mL, and IC50 for ABTS radical scavenging activity of 1.3-1.6 mg/mL. The UV-B protective activity was reported as the HaCaT cell viability percentage after UV-B treatment. The SCP, SCA, and SCF hydrolysates showed 72.4, 74.5, and 71.3% cell viability, respectively. The concentration of hydrolysates with 80% survival of HaCaT cells was 0.21, 0.15 and 0.20 mg/mL for SCP, SCA and SCF, respectively. Thus, the SCP was selected for bioactive peptide isolation and characterization. The SCP contained hydrophilic and hydrophobic amino acids of 42.4 and 57.6%, respectively. The ultrafiltration and Sephadex G-25 gel filtration chromatography were done for peptide isolation from the SCP. Six potential peptides were identified using LC-MS/MS as Leu-Val-Asn-Glu-Leu-Thr-Glu-Phe-Ala-Gln (1163 Da), Leu-Val-Asn-Glu-Val-Thr-Glu-Phe-Ala-Gln (1149 Da), Phe-Val-Asp-Ser-Ser-Ala-Thr-Thr (826 Da), Phe-Asn-Asp-Leu-Gly-Ala-Trp (821 Da), Phe-Pro-Asp-Thr-Thr-Thr-Leu (793 Da), and Lys-Phe-Gly-Glu-Gly-Lys (664).
Factors Associated With the Decay of Anti-SARS-CoV-2 S1 IgG Antibodies Among Recipients of an Adenoviral Vector-Based AZD1222 and a Whole-Virion Inactivated BBV152 Vaccine
Authors: Selvavinayagam Sivaprakasam T. , Yong Yean Kong , Tan Hong Yien , Zhang Ying , Subramanian Gurunathan , Rajeshkumar Manivannan , Vasudevan Kalaivani , Jayapal Priyanka , Narayanasamy Krishnasamy , Ramesh Dinesh , Palani Sampath , Larsson Marie , Shankar Esaki M. , Raju Sivadoss 
Published: June 2022

BackgroundThe magnitude of protection conferred following recovery from COVID-19 or by vaccine administration, and the duration of protective immunity developed, remains ambiguous.MethodsWe investigated the factors associated with anti-SARS-CoV-2 S1 IgG decay in 519 individuals who recovered from COVID-19 illness or received COVID-19 vaccination with two commercial vaccines, viz., an adenoviral vector-based (AZD1222) and a whole-virion-based inactivated (BBV152) vaccine in Chennai, India from March to December 2021. Blood samples collected during regular follow-up post-infection/-vaccination were examined for anti-SARS-CoV-2 S1 IgG by a commercial automated chemiluminescent immunoassay (CLIA).ResultsAge and underlying comorbidities were the two variables that were independently associated with the development of a breakthrough infection. Individuals who were &gt;60 years of age with underlying comorbid conditions (viz., hypertension, diabetes mellitus and cardiovascular disease) had a ~15 times and ~10 times greater odds for developing a breakthrough infection and hospitalization, respectively. The time elapsed since the first booster dose was associated with attrition in anti-SARS-CoV-2 IgG, where each month passed was associated with an ebb in the anti-SARS-CoV-2 IgG antibody levels by a coefficient of −6 units.ConclusionsOur findings advocate that the elderly with underlying comorbidities be administered with appropriate number of booster doses with AZD1222 and BBV152 against COVID-19.
Risk of Autoimmune Diseases Following Optic Neuritis: A Nationwide Population-Based Cohort Study
Authors: Ma Kevin Sheng-Kai , Lee Chee-Ming , Chen Po-Hung , Yang Yan , Dong Yi Wei , Wang Yu-Hsun , Wei James Cheng-Chung , Zheng Wen Jie 
Published: June 2022

ObjectivesOptic neuritis is (ON) is believed to be an immune-mediated disease; however, the association between optic neuritis and autoimmune diseases remains unclear. This study aimed to identify the incidence rate and adjusted hazard ratio (aHR) of autoimmune diseases in patients with optic neuritis.MethodsThis nationwide, population-based, retrospective cohort study collected patients’ data between 1999 and 2013 from the National Health Insurance Research Database in Taiwan. A total of 9,235 patients were included. Using 1:4 propensity scoring, 1,847 patients were enrolled in the optic neuritis group and 7,388 in the non-optic neuritis group according to age, sex, comorbidities, and corticosteroid use. Follow-up was started from the index date and the endpoint was a diagnosis of new-onset autoimmune diseases including, myasthenia gravis (MG), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and ankylosing spondylitis (AS).ResultsThe Kaplan-Meier curves depicted that patients with optic neuritis had a higher cumulative incidence of autoimmune diseases than patients without optic neuritis. Cox proportional hazard regression showed that patients with optic neuritis were at a high risk of autoimmune diseases (aHR: 1.40; 95% C.I., 1.05–1.87), including MG (aHR: 4.16, 95% C.I.: 1.33–12.94), SLE (aHR: 3.33, 95% C.I.: 1.24–8.97), and AS (aHR: 2.86, 95% C.I.: 1.54–5.31). Subgroup analysis provided that patients with optic neuritis aged below 65 years (aHR: 1.42, 95% C.I.: 1.03–1.96) or who were females (aHR: 1.59, 95% C.I.: 1.11–2.27) had a significantly increased risk of autoimmune diseases compared to respective controls. The use of corticosteroids reduced the risk of autoimmune diseases in patients with optic neuritis (aHR for corticosteroids non-users: 1.46, 95% C.I.: 1.03–2.07).ConclusionPatients with optic neuritis presented with a high risk of autoimmune diseases such as MG, SLE, and AS, especially patients with optic neuritis who were young or females. Corticosteroids attenuated the link between optic neuritis and subsequent autoimmune diseases.
An Outlook on the Complexity of Protein Morphogenesis in Health and Disease
Authors: Brunori Maurizio , Gianni Stefano 
Published: June 2022

The study of the mechanisms whereby proteins achieve their native functionally competent conformation has been a key issue in molecular biosciences over the last 6 decades. Nevertheless, there are several debated issues and open problems concerning some aspects of this fundamental problem. By considering the emerging complexity of the so-called “native state,” we attempt hereby to propose a personal account on some of the key topics in the field, ranging from the relationships between misfolding and diseases to the significance of protein disorder. Finally, we briefly describe the recent and exciting advances in predicting protein structures from their amino acid sequence.
Effect of Cerebral Small Vessel Disease Burden on Outcomes in Patients With Acute Ischemic Stroke Receiving Endovascular Treatment
Authors: Huang Hao , Zong Weifeng , Tong Xu , Tian Xue , Wang Anxin , Jia Baixue , Zhao Jing , Wu Lingshan , Zhou Xirui , Guo Yinping , Zhang Yi , Yu Zhiyuan , Wang Yilong , Wang Yongjun , Luo Xiang , Miao Zhongrong 
Published: June 2022

BackgroundCerebral small vessel disease (SVD) is common in the aging population. The study aimed to evaluate the effect of SVD on functional outcomes in patients with acute ischemic stroke (AIS) receiving endovascular treatment (EVT).MethodsFrom a prospective registry, we selected patients with AIS receiving EVT. SVD features, including white matter hyperintensities (WMH), lacunes and brain atrophy, were assessed on MRI and a validated SVD score was calculated to reflect the total SVD burden.ResultsAmong 137 patients included, 106 had none-mild SVD burden and 31 had moderate-severe SVD burden. The moderate-severe SVD burden group showed a significantly higher modified Rankin Scale score at 90 d (median, 4 versus 1 points, adjusted common odds ratio 0.32 [95% CI, 0.14–0.69], P &lt; 0.01) and a significantly smaller improvement of NIHSS at 24 h (median, –3 versus –3 points, adjusted β coefficient 4.02 [95% CI, 0.57–7.48], P = 0.02) and 7 days (median, –4 versus –6 points, adjusted β coefficient 4.71 [95% CI, 1.06–8.36], P = 0.01) than the none-mild group. There was no significant difference in successful recanalization, death within 90 days, symptomatic intracranial hemorrhage within 24 h between two groups (all P &gt; 0.05). Additionally, for each single SVD feature, brain atrophy and WMH, but not lacunes, were associated with the functional outcome.ConclusionModerate-severe SVD burden was associated with poor early and late functional outcomes in patients with AIS receiving EVT. Our results suggest that SVD score may act as a good predictor of outcomes in these patients.
Multiple Pipeline Embolization Devices for the Treatment of Complex Intracranial Aneurysm: A Multi-Center Study
Authors: Fan Feng , Fu Yu , Liu Jianmin , Yang Xinjian , Zhang Hongqi , Li Tianxiao , Shi Huaizhang , Wan Jieqing , Zhao Yuanli , Wang Yunyan , Feng Wenfeng , Song Donglei , Wang Yang , Mao Guohua , Maimaitili Aisha , Guan Sheng 
Published: June 2022

BackgroundThe Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial primarily demonstrated the safety and efficacy of the implantation of multiple pipeline embolization devices (multi-PEDs) for large/giant intracranial aneurysms. However, no study has focused on when, why, or how to apply multi-PEDs.ObjectiveThe purpose of this study was to investigate the indications and strategies of using multi-PEDs for complex intracranial aneurysms.MethodsPatients who had been treated with two or more PEDs were included in the post-market multicenter registry study from 2014 to 2019, across 14 centers in China. Indications, strategies, perioperative safety, and clinical outcomes were retrospectively analyzed. The modified Rankin scale (mRS) score was used to evaluate clinical outcomes comprehensively, and the O’Kelly–Marotta (OKM) grading scale was used to evaluate aneurysm healing results.ResultsA total of 55 intracranial aneurysms were treated with multi-PEDs. There were 20 fusiform aneurysms with a large range, 25 large/giant saccular aneurysms, six aneurysms with failed treatment, and four aneurysms with greatly varied diameters of the parent artery. The strategies included telescope techniques in 40 patients and overlap techniques in 15 patients. In total, 120 stents were deployed in 55 patients. The operation styles included 25 patients (55.6%) with two PEDs, 21 patients (38.2%) with two PEDs combined with coiling, four patients (7.3%) with three PEDs, four patients (7.3%) with three PEDs combined with coiling, and one patient (1.8%) with four PEDs. Angiography revealed OKM D in two, OKM C in seven, and OKM A and B in 46 cases after surgery. During the perioperative period, eight patients developed neurological dysfunction, three of whom died. A total of thirty-four patients were followed up with digital subtraction angiography for 2–45 (8.2 ± 8.0) months. Angiography revealed OKM D in 26, OKM C in five, and OKM B in three. At the last follow-up, the mRS score was 0–1 in 52 patients.ConclusionThe treatment of anterior circulation aneurysms with multi-PEDs is safe and effective. The implantation of multi-PEDs could be considered for large-scale fusiform aneurysms, large/giant saccular aneurysms with a jet-sign, salvage of failed PED treatments, and in cases where the diameter of the parent artery varies greatly.