bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roles of m5C RNA Modification Patterns in Biochemical Recurrence and Tumor Microenvironment Characterization of Prostate Adenocarcinoma
Authors: Xu Zhipeng , Chen Shuqiu , Zhang Yuxi , Liu Ruiji , Chen Ming 
Published: May 2022

BackgroundProstate cancer is the second most common cancer with a high risk of biochemical recurrence (BCR) among men. Recently, 5-methylcytosine (m5C) modification has attracted more attention as a new layer of RNA post-transcriptional regulation. Hence, we aimed at investigating the potential roles of m5C modification regulators in the BCR of prostate adenocarcinoma (PRAD).MethodsCNV data, mutation annotation data, mRNA expression profiles, and clinical data were downloaded from TCGA and GEO databases. Kaplan-Meier curves analysis, log-rank test, univariate and multivariate Cox regression, and time-dependent ROC curves analysis were performed to evaluate the prognostic factors. Principal components analysis (PCA) was applied to validate the distinction between subgroups. Gene set variation analysis (GSVA) was used to investigate the underlying pathways associated with m5C modification patterns. Single sample gene set enrichment analysis (ssGSEA) was utilized to assess the infiltration of distinct immune cells. Tumor Immune Dysfunction and Exclusion (TIDE) prediction was carried out to assess the potential response to immune checkpoint blockade (ICB) therapy. The m5C modification signature was constructed via LASSO Cox’s proportional hazards regression method.ResultsAfter comprehensively analyzing various types of data from TCGA dataset, and exploring the differential expression and prognostic value of each m5C regulator, we identified m5C modification patterns based on 17 m5C regulators. Two patterns presented a significant difference in the risk of BCR, the tumor microenvironment (TME), and immunotherapy response in PRAD. We found that TET2, which was highly expressed in adjacent normal tissues compared to tumor tissues, was closely associated with many infiltrating immune cells. The m5C modification signature was constructed for the clinical application. Risk score calculated by m5C signature was associated with T stage, N stage, Gleason score, and the possibility of BCR (HR, 4.197; 95% CI, 3.016-5.842; p &lt; 0.001). A higher risk score also represented the possibility of immunotherapy response. Finally, the potential roles of m5C modification signature were validated in the testing dataset.ConclusionsOur study revealed the potential roles of m5C modification in the PRAD BCR and TME diversity, which may provide new insight into the field of prostate cancer in future research.
Immunotherapeutic Effects of Different Doses of Mycobacterium tuberculosis ag85a/b DNA Vaccine Delivered by Electroporation
Authors: Liang Yan , Cui Lei , Xiao Li , Liu Xiao , Yang Yourong , Ling Yanbo , Wang Tong , Wang Lan , Wang Jie , Wu Xueqiong 
Published: May 2022

BackgroundTuberculosis (TB) is a major global public health problem. New treatment methods on TB are urgently demanded.MethodsNinety-six female BALB/c mice were challenged with 2×104 colony-forming units (CFUs) of MTB H37Rv through tail vein injection, then was treated with 10μg, 50μg, 100μg, and 200μg of Mycobacterium tuberculosis (MTB) ag85a/b chimeric DNA vaccine delivered by intramuscular injection (IM) and electroporation (EP), respectively. The immunotherapeutic effects were evaluated immunologically, bacteriologically, and pathologically.ResultsCompared with the phosphate-buffered saline (PBS) group, the CD4+IFN-γ+ T cells% in whole blood from 200 µg DNA IM group and four DNA EP groups increased significantly (P&lt;0.05), CD8+IFN-γ+ T cells% (in 200 μg DNA EP group), CD4+IL-4+ T cells% (50 μg DNA IM group) and CD8+IL-4+ T cells% (50 μg and 100 μg DNA IM group, 100 μg and 200 μg DNA EP group) increased significantly only in a few DNA groups (P&lt; 0.05). The CD4+CD25+ Treg cells% decreased significantly in all DNA vaccine groups (P&lt;0.01). Except for the 10 μg DNA IM group, the lung and spleen colony-forming units (CFUs) of the other seven DNA immunization groups decreased significantly (P&lt;0.001, P&lt;0.01), especially the 100 μg DNA IM group and 50 μg DNA EP group significantly reduced the pulmonary bacterial loads and lung lesions than the other DNA groups.ConclusionsAn MTB ag85a/b chimeric DNA vaccine could induce Th1-type cellular immune reactions. DNA immunization by EP could improve the immunogenicity of the low-dose DNA vaccine, reduce DNA dose, and produce good immunotherapeutic effects on the mouse TB model, to provide the basis for the future human clinical trial of MTB ag85a/b chimeric DNA vaccine.
Identification of CD4+ Conventional T Cells-Related lncRNA Signature to Improve the Prediction of Prognosis and Immunotherapy Response in Breast Cancer
Authors: Ning Shipeng , Wu Jianbin , Pan You , Qiao Kun , Li Lei , Huang Qinghua 
Published: May 2022

BackgroundBreast cancer (BC) is one of the most common malignancies in women, and long non-coding RNAs (lncRNAs) are key regulators of its development. T cells can recognize and kill cancer cells, and CD4+ T conventional (Tconv) cells are the main orchestrators of cancer immune function. However, research on CD4+ Tconv-related lncRNAs (CD4TLAs) prognostic signature in patients with BC is still lacking.MethodA TCGA database and a GEO database were used to collect the BC patients. Through LASSO Cox regression analysis CD4TLAs-related prognostic models were further constructed, and risk scores (RS) were generated and developed a nomogram based on CD4TLAs. The accuracy of this model was validated in randomized cohorts and different clinical subgroups. Gene set enrichment analysis (GSEA) was used to explore potential signature-based functions. The role of RS has been further explored in the tumor microenvironment (TME), immunotherapy, and chemotherapy.ResultA prognostic model based on 16 CD4TLAs was identified. High-RS was significantly associated with a poorer prognosis. RS was shown to be an independent prognostic indicator in BC patients. The low-RS group had a significant expression of immune infiltrating cells and significantly enriched immune-related functional pathways. In addition, the results of immunotherapy prediction indicated that patients with low-RS were more sensitive to immunotherapy.ConclusionsOur signature has potential predictive value for BC prognosis and immunotherapy response. The findings of this work have greatly increased our understanding of CD4TLA in BC.
Factors Facilitating and Hindering the Use of Newly Acquired Positioning Skills in Clinical Practice: A Longitudinal Survey
Authors: Ludwig Vera U. , Pickenbrock Heidrun , Döppner Daniel A. 
Published: May 2022

BackgroundAfter learning new skills, healthcare professionals do not always apply them in practice, despite being motivated. This may be referred to as an intention-behavior gap. One example is the positioning of immobilized and disabled patients in hospitals, nursing homes, or neurorehabilitation clinics. Positioning is crucial to prevent complications such as pressure sores, pneumonia, and deep vein thrombosis. However, it is often not carried out optimally even when professionals have completed education programs. The LiN-method is a positioning procedure involving a special focus on aligning and stabilizing body parts, which has been shown to have advantages over conventional positioning. We assess which factors may facilitate or hinder the use of LiN in clinical practice after participants complete training.MethodsA longitudinal survey with 101 LiN-course participants was conducted in Germany. Each participant completed a questionnaire directly after the course and 12 weeks later, including a report of the frequency of use in practice. They also completed a questionnaire which surveyed 23 aspects that might facilitate or hinder use of the new skills, covering the workplace, socio-collegial factors, motivation, self-confidence, and mindset.ResultsMost assessed aspects were associated with LiN-use, with the highest correlations found for confidence with the method, perceived ease of application, sufficient time, assessing one's skills as sufficient, remembering the relevant steps, and a work environment open to advanced therapeutic concepts. To reduce data complexity, the questionnaire was subjected to a factor analysis, revealing six factors. A regression analysis showed that four factors predicted use 12 weeks after course completion, in the following order of importance: (1) subjective aspects/confidence, (2) access to materials, (3) work context, and (4) competent support in the workplace.ConclusionNumerous aspects are associated with the use of recently acquired clinical or nursing skills, such as LiN. Many of these can be improved by appropriately setting up the workplace. The aspects most associated with use, however, are confidence with the method and self-perceived competence of healthcare professionals. While causality still needs to be demonstrated, this suggests that education programs should support participants in developing confidence and foster a mindset of continuous learning.
Associations of Parity With Change in Global Cognition and Incident Cognitive Impairment in Older Women
Authors: Zhou Rui , Liu Hua-Min , Zou Lian-Wu , Wei Hong-Xia , Huang Yi-Ning , Zhong Qi , Gu Shan-Yuan , Chen Ming-Feng , Wang Shao-Li , Sun Hai-Xia , Wu Xian-Bo 
Published: May 2022

BackgroundThe evidence of the association between parity and risk of mild cognitive impairment (MCI) or dementia is mixed, and the relationship between parity and longitudinal cognitive changes is less clear. We investigated these issues in a large population of older women who were carefully monitored for development of MCI and probable dementia.MethodsUsing the Women’s Health Initiative Memory Study, 7,100 postmenopausal women (mean age 70.1 ± 3.8 years) with information on baseline parity (defined as the number of term pregnancies), measures of global cognition (Modified Mini-Mental State Examination score) from 1996–2007, and cognitive impairment (centrally adjudicated diagnoses of MCI and dementia) from 1996–2016 were included. Multivariable linear mixed-effects models were used to analyze the rate of changes in global cognition. Cox regression models were used to evaluate the risk of MCI/dementia across parity groups.ResultsOver an average of 10.5 years, 465 new cases of MCI/dementia were identified. Compared with nulliparous women, those with a parity of 1–3 and ≥4 had a lower MCI/dementia risk. The HRs were 0.75 (0.56–0.99) and 0.71 (0.53–0.96), respectively (P &lt; 0.01). Similarly, a parity of 1–3 and ≥4 was related to slower cognitive decline (β = 0.164, 0.292, respectively, P &lt; 0.05).ConclusionHigher parity attenuated the future risk for MCI/dementia and slowed the rates of cognitive decline in elderly women. Future studies are needed to determine how parity affects late-life cognitive function in women.
Dietary Antioxidant Indices in Relation to All-Cause and Cause-Specific Mortality Among Adults With Diabetes: A Prospective Cohort Study
Authors: Wang Wenjie , Wang Xiaoyan , Cao Shiling , Duan Yiting , Xu Chengquan , Gan Da , He Wei 
Published: May 2022

BackgroundThe potential beneficial effect of individual antioxidants on mortality has been reported. However, the association of overall intakes of dietary antioxidants with all-cause and cause-specific mortality among adults with diabetes remained unclear.MethodsA total of 4,699 US adults with diabetes were enrolled in 2003–2014 in the National Health and Nutrition Examination Survey (NHANES) and followed for mortality until 31 December 2015. The Dietary Antioxidant Quality Score (DAQS) and the Dietary Antioxidant Index (DAI), which indicate the total antioxidant properties, were calculated based on the intakes of vitamins A, C, E, zinc, selenium, and magnesium. The Cox proportional hazards regression models were used to investigate the associations of the DAQS or the DAI with all-cause and cause-specific mortality.ResultsA total of 913 deaths occurred during 27,735 person-years of follow-up, including 215 deaths due to cardiovascular disease (CVD) and 173 deaths due to cancer. The higher intakes of antioxidant vitamins A, E, magnesium, and selenium were associated with lower all-cause mortality. The adjusted hazard ratios (HRs) (95% CIs) comparing the highest DAQS (5–6) to the lowest DAQS (0–2) were 0.70 (0.53–0.92) for all-cause mortality, 0.56 (0.35–0.90) for CVD mortality, and 0.59 (0.33–1.04) for cancer mortality. Consistent inverse associations were found between the DAI and mortality.ConclusionHigher intake of overall dietary antioxidants was associated with lower risk of death from all-cause and CVD in adults with diabetes. Future dietary intervention studies are needed to determine whether increasing overall antioxidant micronutrients intake could prevent premature death among adults with diabetes.
A Novel Clinically Prognostic Stratification Based on Prognostic Nutritional Index Status and Histological Grade in Patients With Gallbladder Cancer After Radical Surgery
Authors: Cao Peng , Hong Haijie , Yu Zijian , Chen Guodong , Qi Shuo 
Published: May 2022

PurposeGallbladder carcinoma (GBC) is the most common malignancy of the biliary tract, with a 5-year survival rate of 5%. The prognostic models to predict the prognosis of patients with GBC remain controversial. Therefore, to construct a prognosis prediction of GBC, a retrospective cohort study was carried out to investigate the prognostic nutritional index and histological grade in the long-term outcome of patients with GBC after radical surgery (RS).MethodsA retrospective study of a total of 198 patients with GBC who underwent surgical treatment were enrolled. The hematological indicators, imageological data, and perioperative clinical data were acquired for statistical analysis and poor prognosis model construction.ResultsPrognostic nutrition index (PNI) &lt; 45.88, maximum tumor diameter (MTD) &gt; 2.24 cm, and jaundice (JD) were all associated with a poor prognosis in multivariate logistic regression analysis. The prognosis prediction model was based on the three risk factors, which indicated a superior predictive ability in the primary cohort [area under the curve (AUC) = 0.951] and validation cohort (AUC = 0.888). In multivariate Cox regression analysis, poorly differentiation (PD) was associated with poor 3-year survival. In addition, Kaplan–Meier (KM) survival analysis suggested that GBC patients with high-risk scores and PD had a better prognosis after RS (p &lt; 0.05), but there was no significant difference in prognosis for patients with non-poorly differentiation (NPD) or low-risk scores after RS (p &gt; 0.05).ConclusionOur prediction model for GBC patients with prognosis evaluation is accurate and effective. For patients with PD and high-risk scores, RS is highly recommended; a simple cholecystectomy can also be considered for acceptance for patients with NPD or low-risk score. The significant findings provide a new therapeutic strategy for the clinical treatment of GBC.
Association Between Systemic Lupus Erythematosus and Cancer Morbidity and Mortality: Findings From Cohort Studies
Authors: Zhang Min , Wang Yizhou , Wang Yutong , Bai Ye , Gu Dongqing 
Published: May 2022

BackgroundObservational studies suggested that systemic lupus erythematosus (SLE) might be associated with increased cancer incidence and cancer-related death, however, the results are inconsistent. We aim to comprehensively estimate the causal relationships between SLE and cancer morbidity and mortality using a meta-analysis of cohort studies and Mendelian randomization.MethodsA systematic search was conducted using PubMed to identify cohort studies published before January 21, 2021. Meta-analysis was performed to calculate relative risk (RR) and corresponding 95% confidence intervals (CI). In addition, we further evaluated the potentially causal relationships identified by cohort studies using two-sample Mendelian randomization.ResultsA total of 48 cohort studies involving 247,575 patients were included. We performed 31 main meta-analysis to assess the cancer risk and three meta-analyses to evaluate cancer mortality in SLE patients. Through meta-analyses, we observed an increased risk of overall cancer (RR=1.62, 95%CI, 1.47-1.79, P&lt;0.001) and cancer-related death (RR=1.52, 95%CI, 1.36-1.70, P&lt;0.001) in patients with SLE. Subgroup analysis by site-specific cancer showed that SLE was a risk factor for 17 site-specific cancers, including six digestive cancers (esophagus, colon, anus, hepatobiliary, liver, pancreatic), five hematologic cancers (lymphoma, Hodgkin’s lymphoma, non-Hodgkin lymphoma, leukemia, multiple myeloma), as well as cancer in lung, larynx, cervical, vagina/vulva, renal, bladder, skin, and thyroid. In addition, further mendelian randomization analysis verified a weakly association between genetically predisposed SLE and lymphoma risk (odds ratio=1.0004, P=0.0035).ConclusionsFindings from our study suggest an important role of SLE in carcinogenesis, especially for lymphoma.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, CRD42021243635.
Identification by Bioinformatics Analysis of Potential Key Genes Related to the Progression and Prognosis of Gastric Cancer
Authors: Gao Wencang , Yang Min 
Published: May 2022

ObjectiveDespite increasingly sophisticated medical technology, the prognosis of patients with advanced gastric cancer is still not objectively certain. Therefore, it is urgent to identify new diagnostic and prognostic biomarkers. To identify potential critical genes related to gastric cancer’s staging mechanism and to the prognosis of gastric cancer.MethodsDynamic trend analysis was conducted to find genes with similar trends in gastric cancer staging in order to explore the differentially expressed genes in gastric cancer and identify the intersection of the results of the dynamic trend analysis. Functional predictive analysis were performed on the obtained genes to observe the expression of prognostic genes in gastric cancer and in gastric cancer stages as well as the correlation with tumor immune cell infiltration. Gastric cancer samples were collected and sequenced for follow-up analysis based on the results of the Cancer Genome Atlas (TCGA) database analysis.ResultsThe expression of genes enriched in module 0 had a similar trend in gastric cancer staging. 3213 differential genes were screened. A total of 50 intersection genes were obtained among genes with similar trends, of which only 10 genes have prognostic significance in gastric cancer. These 10 genes were correlated with macrophage infiltration in varying degrees. In addition, we found that AGT was significantly abnormally expressed in the results of sample sequencing. AGT was related to the occurrence of gastric cancer and interacted with brd9, golph3, nom1, klhl25, and psmd11.ConclusionAGT has prominent abnormal expression in gastric cancer and may promote gastric cancer progression. This study provides a new direction for further exploring potential biomarkers and molecular targeted gastric cancer therapy.
Differences in Characteristics and Outcomes Between Large-Cell Neuroendocrine Carcinoma of the Ovary and High-Grade Serous Ovarian Cancer: A Retrospective Observational Cohort Study
Authors: Pang Li , Guo Zhiqiang 
Published: May 2022

BackgroundOwing to its extremely low incidence and the paucity of relevant reports, there is currently no recognized first-line treatment strategy for ovarian large-cell neuroendocrine carcinoma, and there are no statistics related to prognosis derived from large samples. This study aimed to investigate the characteristics, outcomes, and independent predictors of survival for ovarian large-cell neuroendocrine carcinoma and compare them with those of high-grade serous ovarian cancer.MethodsThe Surveillance, Epidemiology, and End Results database was used to identify women diagnosed with ovarian large-cell neuroendocrine carcinoma or high-grade serous ovarian cancer from 1988 to 2015. Clinical, demographic, and treatment characteristics were compared between the groups. Propensity-score matching, Cox risk regression analysis, and Kaplan–Meier survival curves were used to analyze the data.ResultsIn total, 23,917 women, including 23,698 (99.1%) diagnosed with high-grade serous ovarian cancer and 219 (0.9%) diagnosed with ovarian large-cell neuroendocrine carcinoma, were identified. Age &gt;77 years, diagnosis before 2003–2010, and advanced-stage disease were more common in patients with ovarian large-cell neuroendocrine carcinoma than in those with high-grade serous ovarian cancer. Women with ovarian large-cell neuroendocrine carcinoma were less likely to receive adjuvant chemotherapy (54.8% vs. 81.9%) but more likely to receive radiotherapy (3.2% vs. 1.5%; both P&lt;0.001) than women with high-grade serous ovarian cancer. Stage, chemotherapy, and tumor size were independent predictors of overall survival, and the risk of death was greater in the advanced stage than in the early stage (P=0.047). Chemotherapy and tumor size were also independent predictors of cancer-specific survival. Overall and cancer-specific survival rates were significantly low for ovarian large-cell neuroendocrine carcinoma than for more malignant high-grade serous ovarian cancer.ConclusionsCompared to patients with high-grade serous ovarian cancer, those with ovarian large-cell neuroendocrine carcinoma presented more often with advanced-stage disease and had decreased overall and cancer-specific survival rates.
Comparison of Ray Tracing and Monte Carlo Calculation Algorithms for Spine Lesions Treated With CyberKnife
Authors: Li Jun , Zhang Xile , Pan Yuxi , Zhuang Hongqing , Yang Ruijie 
Published: May 2022

PurposeThis study attempts to evaluate Ray Tracing (RT) and Monte Carlo (MC) algorithms for CyberKnife treatments of spine lesions and determine whether the MC algorithm is necessary for all spine treatment and compare the RT algorithm and MC algorithm at various spine lesion sites.MethodsThe CyberKnife is used for stereotactic body radiotherapy for lesions in the cervical spine (30), thoracic spine (50), lumbar spine (30), and sacral spine (15). Dose was calculated using RT and MC algorithms for patients planned with the same beam angles and monitor units. Dose-volume histograms of the target and selected critical structures are evaluated.ResultsThe average target coverage of prescribed dose with MC algorithms was 94.80%, 88.47%, 92.52%, and 93.41%, respectively, in cervical, thoracic, lumbar, and sacral spine. For the thoracic spine, the RT algorithm significantly overestimates the percentage volume of the target covered by the prescribed dose, as well as overestimates doses to organs at risk in most cases, including lung, spinal cord, and esophagus. For cervical, lumbar, and sacral spine, the differences of the target coverage of prescription dose were generally less than 3% between the RT and MC algorithms. The differences of doses to organs at risk varied with lesion sites and surrounding organs.ConclusionsIn the thoracic spine lesions with beams through air cavities, RT algorithm should be limited and verified with MC algorithm, but the RT algorithm is adequate for treatment of cervical, lumbar, and sacral spine lesions without or with a small amount of beams passing through the lungs.