bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of CXCR4 as a Prognostic Biomarker Associated With the Tumor Immune Microenvironment in Gastric Cancer
Authors: Gu Yuyang , Gu Wenyue , Xie Rongrong , Chen Zhi , Xu Tongpeng , Fei Zhenghua 
Published: September 2021

Background:Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide, accounting for high rates of morbidity and mortality in the population. The tumor microenvironment (TME), which plays a crucial role in GC progression, may serve as an optimal prognostic predictor of GC. In this study, we identified CXC motif chemokine receptor 4 (CXCR4) as a TME-related gene among thousands of differentially expressed genes (DEGs). We showed thatCXCR4can be used to predict the effect of immunotherapy in patients with GC.Methods:GC samples obtained from The Cancer Genome Atlas (TCGA) were analyzed for the presence of stroma (stromal score), the infiltration of immune cells (immune score) in tumor tissues, and the tumor purity (estimate score) using the ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm. DEGs were sorted based on differences in the values of the three scores. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the biological processes and pathways enriched in these DEGs. The correlations of scores with clinicopathological features and overall survival (OS) of patients with GC were assessed by the Kaplan–Meier survival and Cox regression analyses. Through subsequent protein–protein interaction (PPI) network and univariate Cox regression analyses, CXCR4 was identified as a TME-related gene. Gene Set Enrichment Analysis (GSEA) was performed to assess the role of CXCR4 in the TME of GC. The CIBERSORT algorithm was used to further explore the correlation between tumor-infiltrating immune cells (TIICs) and CXCR4. Finally, the TISIDB database was used to predict the efficacy of immunotherapy in patients with GC.Results:We extracted 1231 TME-related DEGs and by an overlapping screening of PPI network and univariate Cox regression, CXCR4 was identified as a biomarker of TME, which deeply engaged in immune-related biological processes of gastric cancer and have close association with several immunocompetent cells.Conclusion:CXCR4 may be a useful biomarker of prognosis and an indicator of the TME in GC.
Impact of Age, Sex, and Renal Function on the Efficacy and Safety of Direct Oral Anticoagulants vs. Vitamin K Antagonists for the Treatment of Acute Venous Thromboembolism: A Meta-Analysis of 22,040 Patients
Authors: Zhou Bo , Wu Haoyu , Wang Chen , Lou Bowen , She Jianqing 
Published: September 2021

Objective: In this study, we conducted a meta-analysis to assess the impact of age, sex, and renal function on the efficacy and safety of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) for the treatment of acute venous thromboembolism (VTE).Methods: Electronic databases (accessed till June 2021) were systematically searched to investigate randomized clinical trials evaluating apixaban, dabigatran, edoxaban, and rivaroxaban vs. VKAs for the treatment of acute VTE. Results were presented as odds ratio (OR) and 95% CIs.Results: Direct oral anticoagulants were associated with a borderline higher efficacy in women (OR: 0.79, 95% CI: 0.62–1.02), a significantly higher efficacy in patients with age more than 75 years (OR: 0.51, 95% CI: 0.32–0.80), and creatinine clearance &lt;50 ml/min (OR: 0.57, 95% CI: 0.32–0.99). The primary safety endpoint of major or clinically relevant non-major bleeding was significantly reduced in DOACs as compared to VKAs in both patients with age &lt;75 years (OR: 0.79, 95% CI: 0.70–0.89) and patients with age more than 75 years (OR: 0.75, 95% CI: 0.59–0.96). DOACs also show an advantage in terms of major or clinically relevant non-major bleeding in men (OR: 0.72, 95% CI: 0.60–0.86) and patients with creatinine clearance of more than 50 ml/min (OR: 0.75, 95% CI: 0.67–0.84).Conclusions: Direct oral anticoagulants have exhibited clinical preference among patients with acute VTE with decreased thrombosis and bleeding events, especially in patients with age more than 75 years and creatinine clearance &lt;50 ml/min.
MicroRNA-183-3p Is a Predictor of Worsening Heart Failure in Adult Patients With Transposition of the Great Arteries and a Systemic Right Ventricle
Authors: Abu-Halima Masood , Meese Eckart , Abdul-Khaliq Hashim , Raedle-Hurst Tanja 
Published: September 2021

Aim: MicroRNAs (miRNAs) have been shown to play an important role in the progression of heart failure (HF). The aim of our study was to analyze miRNAs in the blood of patients with transposition of the great arteries and a systemic right ventricle (TGA-RV) in order to identify those that predict worsening HF.Materials and Methods: In 36 patients with TGA-RV, SurePrint™ 8 × 60K Human v21 miRNA microarrays were used to determine the miRNA abundance profiles and compared to 35 age- and gender-matched healthy volunteers (HVs). MiRNAs that were most significantly abundant or best related to worsening HF were further validated by RT-qPCR.Results: Using miRNA array analysis, a total of 50 down-regulated and 56 up-regulated miRNAs were found to be differentially abundant in TGA-RV patients compared to HVs. Six of these 106 miRNAs were significantly related to worsening HF. After validation by RT-qPCR, four miRNAs turned out to be significantly associated with worsening HF, namely miR-150-5p, miR-1255b-5p, miR-423-3p, and miR-183-3p. In the stepwise multivariable Cox regression analysis, ejection fraction of the systemic RV, high sensitive TNT and miR-183-3p were found to be independent predictors of worsening HF (P = 0.001, P = 0.002, and P = 0.001, respectively).Conclusions: In patients with TGA-RV, miR-183-3p is an independent predictor of worsening HF and thus may be used as additional biomarker in the risk assessment of these patients.
Estimation of Pubertal Growth Spurt Parameters in Children and Adolescents Living at Moderate Altitude in Colombia
Authors: Cossio-Bolaños Marco Antonio , Vidal-Espinoza Ruben , Minango-Negrete Juan , Olivares Pedro R. , Urzua-Alul Luis , de Campos Luis Felipe Castelli Correia , Fuentes-López Jose , Sanchez-Macedo Lucila , Diaz-Bonilla Edilberto , Torres-Galvis Claudia , Gomez-Campos Rossana 
Published: September 2021

ObjectiveKnowledge of the biological parameters of pubertal growth spurt allows verification of secular changes and exploration of the timing of puberty. The aim of the study was to estimate final height, age at peak height velocity (APHV), and peak height velocity PHV (cm/y) in children and adolescents living at moderate altitude in Colombia.MethodsA cross-sectional study was designed in 2.295 schoolchildren from Bogotá (Colombia) with an age range from 5.0 to 18.9 years. Height (cm) was assessed. Preece–Baines model 1 (1PB) was used to make inferences about mathematical and biological parameters.ResultsThe five mathematical parameters estimated in general have reflected quality in the fit to the model, reflecting a small residual error. Final height was reached in boys at 170.8 ± 0.4 cm and in girls at 157.9 ± 0.2 cm. APHV was estimated at 12.71 ± 0.1 years in boys and 10.4 ± 0.2 years in girls. Girls reached APHV 2.2 years earlier than boys. In relation to PHV (cm/y), boys reached higher growth speed in height (7.4 ± 0.4 cm/y), and in girls it was (7.0 ± 0.2 cm/y).ConclusionIt was determined that final height was reached at 170.8 ± 0.4 cm in boys and 157.9 ± 0.2 cm in girls, and APHV (years) and PHV (cm/ye) were reached relatively early and with average peak velocity similar to Asian and Western populations. A large-scale longitudinal study is needed to confirm these findings.
Degenerate CD8 Epitopes Mapping to Structurally Constrained Regions of the Spike Protein: A T Cell-Based Way-Out From the SARS-CoV-2 Variants Storm
Authors: Boni Carolina , Cavazzini Davide , Bolchi Angelo , Rossi Marzia , Vecchi Andrea , Tiezzi Camilla , Barili Valeria , Fisicaro Paola , Ferrari Carlo , Ottonello Simone 
Published: September 2021

There is an urgent need for new generation anti-SARS-Cov-2 vaccines in order to increase the efficacy of immunization and its broadness of protection against viral variants that are continuously arising and spreading. The effect of variants on protective immunity afforded by vaccination has been mostly analyzed with regard to B cell responses. This analysis revealed variable levels of cross-neutralization capacity for presently available SARS-Cov-2 vaccines. Despite the dampened immune responses documented for some SARS-Cov-2 mutations, available vaccines appear to maintain an overall satisfactory protective activity against most variants of concern (VoC). This may be attributed, at least in part, to cell-mediated immunity. Indeed, the widely multi-specific nature of CD8 T cell responses should allow to avoid VoC-mediated viral escape, because mutational inactivation of a given CD8 T cell epitope is expected to be compensated by the persistent responses directed against unchanged co-existing CD8 epitopes. This is particularly relevant because some immunodominant CD8 T cell epitopes are located within highly conserved SARS-Cov-2 regions that cannot mutate without impairing SARS-Cov-2 functionality. Importantly, some of these conserved epitopes are degenerate, meaning that they are able to associate with different HLA class I molecules and to be simultaneously presented to CD8 T cell populations of different HLA restriction. Based on these concepts, vaccination strategies aimed at potentiating the stimulatory effect on SARS-Cov-2-specific CD8 T cells should greatly enhance the efficacy of immunization against SARS-Cov-2 variants. Our review recollects, discusses and puts into a translational perspective all available experimental data supporting these “hot” concepts, with special emphasis on the structural constraints that limit SARS-CoV-2 S-protein evolution and on potentially invariant and degenerate CD8 epitopes that lend themselves as excellent candidates for the rational development of next-generation, CD8 T-cell response-reinforced, COVID-19 vaccines.
A Five-Gene-Based Prognostic Signature for Hepatocellular Carcinoma
Authors: Tian Dazhi , Yu Yang , Zhang Li , Sun Jisan , Jiang Wentao 
Published: September 2021

Objective: This study intends to identify potential prognostic marker genes associated with the prognosis of patients suffering from hepatocellular carcinoma (HCC) based on TCGA and GEO analysis.Methods: TCGA-LIHC cohort was downloaded and the data related to HCC were extracted from The Cancer Genome Atlas (TCGA) database and subjected to differential analysis. HCC-related gene expression datasets were retrieved from the GEO database, followed by differential analysis. After intersection of the results of TCGA and GEO databases, gene interaction analysis was performed to obtain the core genes. To identify the genes related to the prognosis of HCC patients, we conducted univariate and multivariate Cox analyses.Results: Based on differential analysis of TCGA database, 854 genes were differentially expressed in HCC, any of which might link to the occurrence and progression of HCC. Meanwhile, joint analysis of HCC-related gene expression datasets in the GEO database screened 214 genes. Five core genes CDC20, TOP2A, RRM2, UBE2C and AOX1 were significantly associated with the prognosis of HCC patients and the risk model based on these five genes effectively predicted the prognosis of HCC patients.Conclusion: Collectively, our data suggest that CDC20, TOP2A, RRM2, UBE2C and AOX1 may be the key genes affecting the prognosis of patients with HCC. The five-gene signature could accurately predict the prognosis of HCC patients.
Predicting Severe/Critical Outcomes in Patients With SARS-CoV2 Pneumonia: Development of the prediCtion seveRe/crItical ouTcome in COVID-19 (CRITIC) Model
Authors: Salaffi Fausto , Carotti Marina , Di Carlo Marco , Ceccarelli Luca , Galli Massimo , Sarzi-Puttini Piercarlo , Giovagnoni Andrea 
Published: September 2021

Objective: To create a prediction model of the risk of severe/critical disease in patients with Coronavirus disease (COVID-19).Methods: Clinical, laboratory, and lung computed tomography (CT) severity score were collected from patients admitted for COVID-19 pneumonia and considered as independent variables for the risk of severe/critical disease in a logistic regression analysis. The discriminative properties of the variables were analyzed through the area under the receiver operating characteristic curve analysis and included in a prediction model based on Fagan's nomogram to calculate the post-test probability of severe/critical disease. All analyses were conducted using Medcalc (version 19.0, MedCalc Software, Ostend, Belgium).Results: One hundred seventy-one patients with COVID-19 pneumonia, including 37 severe/critical cases (21.6%) and 134 mild/moderate cases were evaluated. Among all the analyzed variables, Charlson Comorbidity Index (CCI) was that with the highest relative importance (p = 0.0001), followed by CT severity score (p = 0.0002), and age (p = 0.0009). The optimal cut-off points for the predictive variables resulted: 3 for CCI [sensitivity 83.8%, specificity 69.6%, positive likelihood ratio (+LR) 2.76], 69.9 for age (sensitivity 94.6%, specificity 68.1, +LR 2.97), and 53 for CT severity score (sensitivity 64.9%, specificity 84.4%, +LR 4.17).Conclusion: The nomogram including CCI, age, and CT severity score, may be used to stratify patients with COVID-19 pneumonia.
Admission and Readmission/Death Patterns in Hospitalized and Non-hospitalized First-Ever-in-a-Lifetime Stroke Patients During the First Year: A Population-Based Incidence Study
Authors: Abreu Pedro , Magalhães Rui , Baptista Diana , Azevedo Elsa , Correia Manuel 
Published: September 2021

Background: Hospitalization and readmission rates after a first-ever-in-a-lifetime stroke (FELS) are considered measures of quality of care and, importantly, may give valuable information to better allocate health-related resources. We aimed to investigate the hospitalization pattern and the unplanned readmissions or death of hospitalized (HospS) and non-hospitalized stroke (NHospS) patients 1 year after a FELS, based on a community register.Methods: Data about hospitalization and unplanned readmissions and case fatality 1 year after a FELS were retrieved from the population-based register undertaken in Northern Portugal (ACIN2), comprising all FELS in 2009–2011. We used the Kaplan–Meier method to estimate 1-year readmission/death-free survival and Cox proportional hazard models to identify independent factors for readmission/death.Results: Of the 720 FELS, 35.7% were not hospitalized. Unplanned readmission/death within 1 year occurred in 33.0 and 24.9% of HospS and NHospS patients, respectively. The leading causes of readmission were infections, recurrent stroke, and cardiovascular events. Stroke-related readmissions were observed in more than half of the patients in both groups. Male sex, age, pre- and post-stroke functional status, and diabetes were independent factors of readmission/death within 1 year.Conclusion: About one-third of stroke patients were not hospitalized, and the readmission/death rate was higher in HospS patients. Still, that readmission/death rate difference was likely due to other factors than hospitalization itself. Our research provides novel information that may help implement targeted health-related policies to reduce the burden of stroke and its complications.
Quantifying the Changes of Mechanical and Electrical Properties of Paralyzed Muscle in Survivors With Cervical Spinal Cord Injury
Authors: Hu Huijing , Chen Yingyue , Wang Xiaoyun , Lo Wai Leung Ambrose , Li Le 
Published: September 2021

Background: Survivors with spinal cord injury (SCI) have neuromuscular deficits such as muscle atrophy that lead to functional impairments. This study utilized myotonometry and electrical impedance myography (EIM) to quantitatively evaluate the changes in muscle mechanical properties and compositions after SCI.Methods: This study adopted a cross-sectional design. Eighteen SCI patients and 18 healthy individuals were recruited. The outcome measures were: (1) The myotonometer measured muscle mechanical parameters of oscillation frequency (freq), dynamic stiffness, logarithmic decrement (decr), mechanical stress relaxation time, and indication of creep. (2) The electrical impedance myography measured parameters of resistance (R), reactance (X), and phase angle (θ). (3) muscle strength (maxForce); (4) clinical scales of Manual Muscle Testing (MMT) and modified Ashworth scale (MAS). All outcome measures were compared between the bicep brachii muscle of the weaker side of the SCI group and the non-dominate side of the healthy group. Correlation analysis was performed at quantitative data and clinical scales.Results: Freq, stiffness, and maxForce of the SCI group were significantly lower (p &lt; 0.01) than those of the healthy control. The relaxation time and creep were significantly higher in the SCI group than in the control group. Significant differences of R and Xc were observed between the two groups. Significant correlation was observed between freq, stiffness, and months past injury, and between Xc, creep, and relaxation time.Conclusions: Reduced muscle tone and stiffness might relate to muscle atrophy, and higher relax time and creep may be caused by poor contractile ability. The changes in EIM parameters could indirectly reflect the muscle cell size, and fatty and connective tissue alterations. These findings support the feasibility of myotonometer and EIM to quantify muscle mechanical and intrinsic properties in patients with SCI. The results could facilitate the understanding of neuromuscular changes that are related to functional impairments.
Physical, Emotional, Medical, and Socioeconomic Status of Patients With NMOSD: A Cross-Sectional Survey of 123 Cases From a Single Center in North China
Authors: Jia Zhen , Dong XiuYu , Song Shuang , Guo Ruoyi , Zhang Lu , Liu Jia , Li Bin 
Published: September 2021

Objective: This study aimed to assess the physical, emotional, medical, and socioeconomic conditions of patients with neuromyelitis optica spectrum disorder (NMOSD) in North China.Methods: A cross-sectional survey of patients with NMOSD was performed, based on an established questionnaire from the Multiple Sclerosis Patient Survival Report 2018. Logistic regression analysis was conducted to define the significant determinants of certain physical or emotional characteristics of patients. A total of 123 patients were included.Results: A total of 63.4% of participants were initially diagnosed with conditions other than NMOSD, with a median delay of 6 months for accurate diagnosis. An aggregate of 72.2% of patients had one or more relapses, corresponding to an annual relapse rate of 0.8. Paresthesia was the most frequent physical symptom among patients both at disease onset (53.7%) and throughout the duration of the disease (86.2%). Onset in elderly (&gt;50 years) patients was associated with an annual Expanded Disability Status Scale increase ≥1, compared with onset in younger (&lt;30 years) patients (P = 0.001, OR = 7.83). A total of 76.4% of patients had received attack-prevention treatments in the remission phase, and 31.7 and 10.6% of patients had ever been administered rituximab and traditional Chinese medicine, respectively. Additionally, 63.4 and 43.1% of patients reported participating in few or no social activities and being out of work because of the disease. To be noted, 76.4% of patients reported suffering from negative emotions, with the most frequent being worry (60.2%), with 20.3% of patients experiencing suicidal thoughts. The inability to work and participating in few or no social activities due to NMOSD were two determinants of experiencing negative emotions (Pwork = 0.03, ORwork = 3.34; Psocialactivities = 0.02, ORsocialactivities = 3.19).Conclusion: This study reported patient perspectives on NMOSD in North China, whereby demonstrating that the inability to work and participating in few or no social activities due to NMOSD rather than the physical impairment caused by the disease, was directly associated with patients experiencing negative emotions. This insight offers potential ways to manage patients' negative emotions by enhancing family and social support and facilitating active employment.
Role of 3D Volumetric and Perfusion Imaging for Detecting Early Changes in Pancreatic Adenocarcinoma
Authors: Rahmanuddin Syed , Korn Ronald , Cridebring Derek , Borazanci Erkut , Brase Jordyn , Boswell William , Jamil Asma , Cai Wenli , Sabir Aqsa , Motarjem Pejman , Koay Eugene , Mitra Anirban , Goel Ajay , Ho Joyce , Chung Vincent , Von Hoff Daniel D. 
Published: September 2021

PurposeThere is a major shortage of reliable early detection methods for pancreatic cancer in high-risk groups. The focus of this preliminary study was to use Time Intensity-Density Curve (TIDC) and Marley Equation analyses, in conjunction with 3D volumetric and perfusion imaging to demonstrate their potential as imaging biomarkers to assist in the early detection of Pancreatic Ductal Adenocarcinoma (PDAC).Experimental DesignsA quantitative retrospective and prospective study was done by analyzing multi-phase Computed Tomography (CT) images of 28 patients undergoing treatment at different stages of pancreatic adenocarcinoma using advanced 3D imaging software to identify the perfusion and radio density of tumors.ResultsTIDC and the Marley Equation proved useful in quantifying tumor aggressiveness. Perfusion delays in the venous phase can be linked to Vascular Endothelial Growth Factor (VEGF)-related activity which represents the active part of the tumor. 3D volume analysis of the multiphase CT scan of the patient showed clear changes in arterial and venous perfusion indicating the aggressive state of the tumor.ConclusionTIDC and 3D volumetric analysis can play a significant role in defining the response of the tumor to treatment and identifying early-stage aggressiveness.
Exploration of Lipid Metabolism in Gastric Cancer: A Novel Prognostic Genes Expression Profile
Authors: Xiong Zhen , Lin Yao , Yu Yan , Zhou Xianghui , Fan Jun , Rog Colin J. , Cai Kailin , Wang Zheng , Chang Zhijie , Wang Guobin , Tao Kaixiong , Cai Ming 
Published: September 2021

BackgroundAlterations in lipid metabolism are increasingly being recognized. However, the application of lipid metabolism in the prognosis of gastric cancer (GC) has not yet been explored.MethodsA total of 204 lipid metabolism relative genes were analyzed in the GC cohort from The Cancer Genome Atlas (TCGA), and four independent cohorts from Gene Expression Omnibus (GEO) and one cohort from Wuhan Union Hospital were applied for external validation. Differential expression and enrichment analyses were performed between GC and normal tissue. The LASSO-Cox proportional hazard regression model was applied to select prognostic genes and to construct a gene expression profile.ResultsOur research indicated that higher expression level of AKR1B1, PLD1, and UGT8 were correlated with worse prognosis of GC patients, while AGPAT3 was correlated with better prognosis. Furthermore, we developed a gene profile composed of AGPAT3, AKR1B1, PLD1, and UGT8 suggested three groups with a significant difference in overall survival (OS). The profile was successfully validated in an independent cohort and performed well in the immunohistochemical cohort. Furthermore, we found that ether lipid metabolism, glycerophospholipid metabolism, and glycerolipid metabolism were upregulated, and fatty acid β-oxidation and other lipid peroxidation processes were reduced in GC.ConclusionCollectively, we found lipid metabolism is reliable and clinically applicable in predicting the prognosis of GC based on a novel gene profile.