bluuebunny/crossref_metadata_2025_split huggingface dataset:
Down-Regulated CLDN10 Predicts Favorable Prognosis and Correlates With Immune Infiltration in Gastric Cancer
Authors: Rao XiongHui , Jiang JianLong , Liang ZhiHao , Zhang JianBao , Zhuang ZheHong , Qiu HuaiYu , Luo Huixing , Weng Nuoqing , Wu Xiaobin 
Published: October 2021

Background: CLDN10, an important component of the tight junctions of epithelial cells, plays a crucial role in a variety of tumors. The effect of CLDN10 expression in gastric cancer, however, has yet to be elucidated.Methods: Differential expression of CLDN10 at the mRNA and protein levels was evaluated using Oncomine, ULCAN, HPA and TIMER2.0 databases. Real-time polymerase chain reaction (RT-PCR) was utilized to further verify the expression of CLDN10 in vitro. Correlations between CLDN10 expression and clinical outcomes of gastric cancer were explored by Kaplan-Meier Plotter. Gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) were performed via LinkedOmics and GeneMANIA. The correlations between CLDN10 expression and immune cell infiltration and somatic copy number alternations (SCNA) in gastric cancer were explored by TIMER2.0 and GEPIA2.0.Results: CLDN10 expression was lower in gastric cancer compared to adjacent normal tissues, and associated with better prognosis. CLDN10 also showed significant differences at different T stages, Lauren classification, treatments and HER2 status. PPI and GSEA analysis showed that CLDN10 might be involved in signal transmission, transmembrane transport and metabolism. In some major immune cells, low expression of CLDN10 was associated with increased levels of immune cell infiltration. In addition, it was found that different SCNA status in CLDN10 might affect the level of immune cell infiltration. Furthermore, the expression of CLDN10 was significantly associated with the expression of several immune cell markers, especially B cell markers, follicular helper T cell (Tfh) markers and T cell exhaustion markers.Conclusion: Down-regulated CLDN10 was associated with better overall survival (OS) in gastric cancer. And CLDN10 may serve as a potential prognostic biomarker and correlate to immune infiltration levels in gastric cancer.
Using Citizen Science Within an Integrated Knowledge Translation (IKT) Approach to Explore Cardiovascular Disease Risk Perception in Rwanda
Authors: Niyibizi Jean Berchmans , Nganabashaka Jean Pierre , Ntawuyirushintege Seleman , Tumusiime David , Umwali Ghislaine , Rulisa Stephen , Nyandwi Alypio , Okop Kufre Joseph , Ntaganda Evariste , Sell Kerstin , Levitt Naomi , Jessani Nasreen S. , Bavuma Charlotte M. 
Published: October 2021

BackgroundCollaborative approaches to generating knowledge between knowledge users (KUs) and researchers as a means of enhancing evidence-informed decision making have been gaining ground over the last few years. The principal study targeted rural and urban communities within the catchment areas of Cyanika health centre (Burera district, Northern Province) and Kacyiru health centre (Gasabo district, in City of Kigali), respectively to understand perceptions and preferences of communication with respect to cardiovascular disease (CVD) risk in Rwanda. This paper describes the integration of citizen science within an integrated knowledge translation (IKT) approach for this study.MethodsThe citizen science approach included deliberate, selective and targeted engagement of KUs at various steps throughout the study. It incorporated national and district levels stakeholders, primary health care stakeholders, local community leaders and influencers, and local community members (selected and trained to be termed citizen scientists) in the process of implementation. Data for this paper included minutes, reports and notes from meetings and workshops which were perused to report the immediate outcomes and challenges of citizen science within an IKT approach for a study such as described for Rwanda.ResultsAs a result of a deliberate IKT strategy, key national stakeholders attended and contributed to all phases of citizen science implementation. Project-based and relationship-based immediate outcomes were documented. In line with local community health issues reported by the citizen scientists, the local community stakeholders pledged home grown solutions. These included enhancement of compliance to implement the “kitchen garden per household” policy, teaching local residents on preparation of healthy diet from locally available food items, organizing collective physical activity, fighting against locally made substandard beverages and teaching local residents on CVD (risk factors). As an indicator of the probable uptake of research evidence, district officials appreciated citizen scientists’ work and decided to consider presented results in their next fiscal year action plan.ConclusionCitizen science proved to be an important strategy for research co-production in Rwanda. While this strategy falls within the remit of a larger IKT approach it focuses on the role and ownership of research by local community residents. This study demonstrated that to improve the relevance and impact of research in local community a deliberate IKT approach that incorporates citizen science can be invaluable.
Case Report: Severe Immune-Related Cholestatic Hepatitis and Subsequent Pneumonia After Pembrolizumab Therapy in a Geriatic Patient With Metastic Gastric Cancer
Authors: Yang Hui , Zhou Chenfei , Yuan Fei , Guo Liting , Yang Liu , Shi Yan , Zhang Jun 
Published: October 2021

Background: Immune checkpoint inhibitors have provided significant clinical benefits to many patients with advanced cancer; however, severe immune-related adverse events (irAEs) have occurred. Detecting and treating irAEs early could improve patient prognoses. Therefore, clinicians and patients should understand that these irAEs exist, especially those that are rare and serious.Case Presentation: In this report, an 86-year-old male patient, diagnosed with metastatic gastric cancer involving the peritoneum and retroperitoneal lymph nodes was treated with 5-cycle pembrolizumab therapy (100 mg q 2 weeks), achieving a partial response. However, the patient developed Grade 3 cholestatic hepatitis and delayed pneumonia 10 days and 2 months after the final pembrolizumab dose, respectively. After discontinuing the pembrolizumab therapy and excluding obstructive jaundice with imaging studies, the patient received steroid therapy, with a gradual symptom improvement. However, the patient developed delayed pneumonia with type 1 respiratory failure 1-month post-discharge. Several microbiologic tests were negative, and immune-associated pneumonia was suspected, but we could not exclude an opportunistic infection. The patient recovered with steroids and antibiotics and remained in partial remission 5 months after pembrolizumab withdrawal.Conclusions: Cholestatic hepatitis is a rarely reported toxicity of immune checkpoint inhibitors, which should be suspected and addressed once obstructive jaundice is ruled out. In addition, clinicians should be aware that irAEs can occur at any time in patients treated with immune checkpoint inhibitors and that a timely diagnosis should be made.
Effect of Poor Nutritional Status and Comorbidities on the Occurrence and Outcome of Pneumonia in Elderly Adults
Authors: Chen Bo , Liu Wen , Chen Yanbing , She Quan , Li Min , Zhao HongYe , Zhao Weihong , Peng Zhihang , Wu Jianqing 
Published: October 2021

Background: Malnutrition and comorbidity are two common geriatric syndromes. The pathology of pneumonia is multifactorial, making its diagnosis and management a great challenge. Hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP) are two main types of pneumonia. However, the effect of geriatric syndromes on pneumonia and its prognosis have not been clearly explored.Methods: We collected the relevant electronic data of inpatients aged over 65 years and diagnosed with pneumonia in the Geriatrics Department Building of the First Affiliated Hospital with Nanjing Medical University between December 2018 and December 2019, and further divided them into HAP group and CAP group. The correlations of age, age-adjusted Charlson Comorbidity Index (aCCI), basic diseases and nutritional indexes (i.e., albumin, electrolyte, hemoglobin) with pneumonia and prognosis were analyzed. We analyzed the associations between infection prognosis/infection level and age, nutritional status, aCCI and underlying diseases, using linear regression model. The box plot was applied to present infection outcome, and the nomogram was built for predicting infection outcomes. We utilized the heat map to show the associations between nutritional status and infection level/outcome in all infected patients, HAP, and CAP.Results: The final study comprised samples of 669 pneumonia patients divided into HAP group (n = 517) and CAP group (n = 152). In all patients, the infection outcome was negatively correlated with age (P = 0.013). The level of albumin was negatively correlated with infection prognosis in all patients (P = 0.03), and negatively correlated with neutrophil count and CRP (P = 0.008, P &lt; 0.001). ACCI was positively correlated with CRP (P = 0.003). The prognosis was negatively associated with age and albumin level. In the patients with basic dementia/Alzheimer's disease and chronic obstructive pulmonary disease/asthma, the prognosis was worse.Conclusion: There was a correlation between poor nutritional status-related indexes and inflammatory indexes. A poor nutritional status might predict a high risk of pneumonia in elderly adults. Advanced age and comorbidities were risk factors for the occurrence and poor prognosis of pneumonia. Therefore, comorbidities should be well-treated in the elderly with pneumonia.
Efficacy and Safety of 12-week Monotherapy With Once Daily 5 mg Tadalafil for Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia: Evidence-based Analysis
Authors: Cui Jianwei , Cao Dehong , Bai Yunjin , Wang Jiahao , Yin Shan , Wei Wuran , Xiao Yunfei , Wang Jia , Wei Qiang 
Published: October 2021

Background: Tadalafil has been approved for the treatment of benign prostatic hyperplasia (BPH) for nearly 10 years. However, there are insufficient evidence-based studies of the efficacy and safety of tadalafil in treating lower urinary tract symptoms of BPH (LUTS/BPH).Objective: To evaluate the therapeutic effect and clinical safety of tadalafil monotherapy (5 mg once daily for 12 weeks) for LUTS/BPH.Methods: A total of 13 studies (15 randomized clinical trials [RCTs]) were extracted from the following databases: PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science for the period up to July 2021. The quality of the included RCTs was evaluated independently by two authors, who, respectively, extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses principles. Conflicts were settled by a discussion with two-third of senior authors. All data analyses were conducted by the Review Manager, version 5.4.Results: Regarding efficacy, 12-week trials indicated that 5 mg once daily tadalafil showed a significantly lower and, consequently, better total International Prostate Symptom Score (IPSS) than the placebo did (mean difference [MD]: −1.97, 95% CI: −2.24 to −1.70; P &lt; 0.00001). In addition, significant differences were found between the tadalafil regimen and the placebo in the IPSS voiding subscore (MD: −1.30, 95% CI: −1.48 to −1.11; P &lt; 0.00001), the IPSS storage subscore (MD: −0.70, 95% CI: −0.82 to −0.58; P &lt; 0.00001), the IPSS quality of life (MD: −0.29, 95% CI: −0.35 to −0.22; P &lt; 0.00001), and BPH impact index (MD: −0.58, 95% CI: −0.76 to −0.40; P &lt; 0.00001). The safety analysis did not show a significant difference in serious adverse events between the two groups (risk ratio: 1.27, 95% CI: 0.80–2.01; P = 0.31), although the adverse events occurred at a higher incidence in the tadalafil group than in the placebo.Conclusions: This study demonstrates that once daily 5 mg tadalafil is a potentially effective and safe treatment choice with excellent tolerability for patients with LUTS/BPH.Systematic Review Registration: Identifier (CRD42021228840).
Early Alterations of Lymphocyte Subsets in Acute Respiratory Distress Syndrome Caused by Acinetobacter baumannii Pneumonia: A Prospective Observational Study
Authors: Cheng Wei , Zhang Jiahui , Li Dongkai , Bai Guangxu , Han Wen , Chen Jianwei , Wang Hao , Cui Na 
Published: October 2021

Background: To prospectively observe the early alterations of lymphocyte subsets in ARDS caused by Acinetobacter baumannii.Methods: ARDS patients admitted to our ICU between January 1, 2017 and May 30, 2020 were selected. We enrolled all the pulmonary ARDS caused by Acinetobacter baumannii pneumonia who required mechanical ventilation or vasopressors. All the available clinical data, follow up information and lymphocyte subsets were recorded.Results: Eighty-seven of all the 576 ARDS patients were enrolled. The 28-day mortality of the enrolled patients was 20.7% (18/87). The T lymphocyte count (452 vs. 729 cells/ul, P = 0.004), especially the CD8+ T lymphocyte count (104 vs. 253 cells/ul, P = 0.002) was significantly lower in non-survivors, as were counts of the activated T cell subsets (CD8+CD28+ and CD8+CD38+). The CD8+ T cell count was an independent risk factor for 28-day mortality, and a cutoff value of 123 cells/ul was a good indicator to predict the prognosis of ARDS caused by Acinetobacter baumannii pneumonia, with sensitivity of 74.6% and specificity of 83.3% (AUC 0.812, P &lt; 0.0001).Conclusions: Lower CD8+ T cell count was associated with higher severity and early mortality in ARDS patients caused by Acinetobacter baumannii pneumonia, which could be valuable for outcome prediction.
Factors Influencing the Degree of Disability in Patients With Multiple Sclerosis
Authors: Xue Huiru , Yang Zhenzhen , Wang Li , Jiang Yayun , Li Jiayang , Wu Minghui , Wang Guilian , Zhang Yuanyuan , Zhang Meini 
Published: October 2021

Objective: To explore the factors influencing the degree of disability in patients with multiple sclerosis (MS), and to provide evidence for its early diagnosis, prognostic evaluation and clinical intervention.Methods: This retrospective observational study included 72 patients with relapsing-remitting multiple sclerosis (RRMS) at the First Hospital of Shanxi Medical University. All patients completed craniocerebral and spinal cord MRI (with or without Gd enhancement) and were evaluated for Expanded Disability Status Score (EDSS) scores before receiving treatment.Results: Among 72 patients with RRMS, 45 (62.5%) had an EDSS score ≤3; A total of 27 patients (37.5%) had an EDSS score &gt;3 points. Univariate analysis showed that age, annual recurrence rate (ARR), drug use, albumin (ALB), triglycerides (TG), and total number of lesions in groups with EDSS score ≤3 were significantly different from those with an EDSS score &gt; 3 points (P &lt; 0.05). Multivariate logistic regression analysis showed that ALB, total number of lesions, and drug use were independent influencing factors of the degree of disability in patients with MS, and the difference was statistically significant (P &lt; 0.05). An ROC curve was constructed using ALB and the total number of lesions. The AUC of ALB was 0.681, P &lt; 0.05, and the best cut-off value was 44.2 g/L. Its sensitivity to predict the degree of disability in patients with multiple sclerosis was 85.2%, while its specificity was 51.1%. The AUC of the total number of lesions was 0.665 (P &lt; 0.05) and the best cut-off value was 5.5. Its sensitivity to predict the degree of disability in patients with multiple sclerosis was 70.4%, while its specificity was 64.4%. The AUC of the combined ALB, total number of lesions, and drug use was 0.795 (P &lt; 0.05), sensitivity was 77.8, and specificity was 73.3%. The optimal diagnostic cut-off value of the regression equation for the EDSS score of patients with multiple sclerosis was 0.420.Conclusion: Serum ALB, total number of lesions, and drug use in patients with multiple sclerosis were independent factors influencing the degree of disability. These findings provide clinical evidence for the prognostic evaluation and early intervention of patients with multiple sclerosis.
Association Between CST3 Gene Polymorphisms and Large-Artery Atherosclerotic Stroke
Authors: Ding Yarong , Xu Zhe , Pan Yuesong , Meng Xia , Xiang Xianglong , Li Hao , Liu Liping , Wang Yongjun 
Published: October 2021

Objective: Cystatin C, a marker of atherosclerosis, is encoded by CST3. We aimed to evaluate whether two single-nucleotide polymorphisms (SNPs) of CST3 are correlated with large-artery atherosclerotic stroke (LAAS) and prognosis.Methods: This subgroup analysis of the Third China National Stroke Registry (CNSR-III) enrolled acute ischemic stroke (AIS) patients within 7 days from August 2015 to March 2018 in China. rs13038305 and rs911119 of CST3 were selected based on the strong association with cystatin C concentration.Results: Two loci of CST3 (rs13038305 and rs911119) were analyzed in 3,833 ischemic stroke patients. Carriers of T allele in rs13038305 and C allele in rs911119 tend to have lower serum cystatin C levels (p &lt; 0.05). Compared with C/C as a reference in rs13038305, odds ratio (OR) of T/T was 0.486, 95% CI 0.237–0.994, p = 0.048. Per C allele of rs13038305 also showed an increased level of low-density lipoprotein cholesterol (LDL-C), β (95% CI) was 1.335 (1.008–1.250), p = 0.044. No correlation was found between the selected SNPs and stroke prognosis (functional outcome, recurrence, and mortality).Conclusions: Carriers of the T allele in rs13038305 tend to have a lower proportion of LAAS. rs13038305 and rs911119 polymorphisms were likely to affect cystatin C concentration independently of kidney function.
Study of Diffusion Weighted Imaging Derived Diffusion Parameters as Biomarkers for the Microenvironment in Gliomas
Authors: Bai Yan , Liu Taiyuan , Chen Lijuan , Gao Haiyan , Wei Wei , Zhang Ge , Wang Lifu , Kong Lingfei , Liu Siyun , Liu Huan , Roberts Neil , Wang Meiyun 
Published: October 2021

ObjectivesTo explore the efficacy of diffusion weighted imaging (DWI)-derived metrics under different models as surrogate indicators for molecular biomarkers and tumor microenvironment in gliomas.MethodsA retrospective study was performed for 41 patients with gliomas. The standard apparent diffusion coefficient (ADCst) and ADC under ultra-high b values (ADCuh) (b values: 2500 to 5000 s/mm2) were calculated based on monoexponential model. The fraction of fast diffusion (f), pseudo ADC (ADCfast) and true ADC (ADCslow) were calculated by bi-exponential model (b values: 0 to 2000 s/mm2). The apparent diffusional kurtosis (Kapp) was derived from the simplified diffusion kurtosis imaging (DKI) model (b values: 200 to 3000 s/mm2). Potential correlations between DWI parameters and immunohistological indices (i.e. Aquaporin (AQP)1, AQP4, AQP9 and Ki-67) were investigated and DWI parameters were compared between high- and low-grade gliomas, and between tumor center and peritumor. Receiver operator characteristic (ROC) curve and area under the curve (AUC) were calculated to determine the performance of independent or combined DWI parameters in grading gliomas.ResultsThe ADCslow and ADCuh at tumor center showed a stronger correlation with Ki-67 than other DWI metrics. The ADCst, ADCslow and ADCuh at tumor center presented correlations with AQP1 and AQP4 while AQP9 did not correlate with any DWI metric. Kapp showed a correlation with Ki-67 while no significant correlation with AQPs. ADCst (p &lt; 0.001) and ADCslow (p = 0.001) were significantly lower while the ADCuh (p = 0.006) and Kapp (p = 0.005) were significantly higher in the high-grade than in the low-grade gliomas. ADCst, f, ADCfast, ADCslow, ADCuh, Kapp at the tumor center had significant differences with those in peritumor when the gliomas grade became high (p &lt; 0.05). Involving ADCuh and Kapp simultaneously into an independent ADCst model (AUC = 0.833) could further improve the grading performance (ADCst+ADCuh+Kapp: AUC = 0.923).ConclusionDifferent DWI metrics fitted within different b-value ranges (low to ultra-high b values) have different efficacies as a surrogate indicator for molecular expression or microstructural complexity in gliomas. Further studies are needed to better explain the biological meanings of these DWI parameters in gliomas.
Peritumoral Brain Edema in Metastases May Be Related to Glymphatic Dysfunction
Authors: Toh Cheng Hong , Siow Tiing Yee , Castillo Mauricio 
Published: October 2021

ObjectivesThe proliferation of microvessels with increased permeability is thought to be the cause of peritumoral brain edema (PTBE) in metastases. The contribution of the glymphatic system to the formation of PTBE in brain metastases remains unexplored. We aimed to investigate if the PTBE volume of brain metastases is related to glymphatic dysfunction.Materials and MethodsA total of 56 patients with brain metastases who had preoperative dynamic susceptibility contrast-enhanced perfusion-weighted imaging for calculation of tumor cerebral blood volume (CBV) and diffusion tensor imaging for calculations of tumor apparent diffusion coefficient (ADC), tumor fractional anisotropy (FA), and analysis along perivascular space (ALPS) index were analyzed. The volumes of PTBE, whole tumor, enhancing tumor, and necrotic and hemorrhagic portions were manually measured. Additional information collected for each patient included age, sex, primary cancer, metastasis location and number, and the presence of concurrent infratentorial tumors. Linear regression analyses were performed to identify factors associated with PTBE volume.ResultsAmong 56 patients, 45 had solitary metastasis, 24 had right cerebral metastasis, 21 had left cerebral metastasis, 11 had bilateral cerebral metastases, and 11 had concurrent infratentorial metastases. On univariable linear regression analysis, PTBE volume correlated with whole tumor volume (β = -0.348, P = 0.009), hemorrhagic portion volume (β = -0.327, P = 0.014), tumor ADC (β = 0.530, P &lt;.001), and ALPS index (β = -0.750, P &lt;.001). The associations of PTBE volume with age, sex, tumor location, number of tumors, concurrent infratentorial tumor, enhancing tumor volume, necrotic portion volume, tumor FA, and tumor CBV were not significant. On multivariable linear regression analysis, tumor ADC (β = 0.303; P = 0.004) and ALPS index (β = -0.624; P &lt; 0.001) were the two independent factors associated with PTBE volume.ConclusionMetastases with higher tumor ADC and lower ALPS index were associated with larger peritumoral brain edema volumes. The higher tumor ADC may be related to increased periarterial water influx into the tumor interstitium, while the lower ALPS index may indicate insufficient fluid clearance. The changes in both tumor ADC and ALPS index may imply glymphatic dysfunction, which is, at least, partially responsible for peritumoral brain edema formation.