bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated DNA Methylation and Gene Expression Analysis Identified S100A8 and S100A9 in the Pathogenesis of Obesity
Authors: Chen Ningyuan , Miao Liu , Lin Wei , Zou Donghua , Huang Ling , Huang Jia , Shi Wanxin , Li Lilin , Luo Yuxing , Liang Hao , Pan Shangling , Peng Junhua 
Published: May 2021

Background: To explore the association of DNA methylation and gene expression in the pathology of obesity.Methods: (1) Genomic DNA methylation and mRNA expression profile of visceral adipose tissue (VAT) were performed in a comprehensive database of gene expression in obese and normal subjects. (2) Functional enrichment analysis and construction of differential methylation gene regulatory networks were performed. (3) Validation of the two different methylation sites and corresponding gene expression was done in a separate microarray dataset. (4) Correlation analysis was performed on DNA methylation and mRNA expression data.Results: A total of 77 differentially expressed mRNAs matched with differentially methylated genes. Analysis revealed two different methylation sites corresponding to two unique genes—s100a8-cg09174555 and s100a9-cg03165378. Through the verification test of two interesting different expression positions [differentially methylated positions (DMPs)] and their corresponding gene expression, we found that methylation in these genes was negatively correlated to gene expression in the obesity group. Higher S100A8 and S100A9 expressions in obese subjects were validated in a separate microarray dataset.Conclusion: This study confirmed the relationship between DNA methylation and gene expression and emphasized the important role of S100A8 and S100A9 in the pathogenesis of obesity.
Visualizing Water Desaturation in Frozen Gas Diffusion Layers With Flow Field Segmentation via Synchrotron X-Ray Radiography
Authors: Zhang Yuzhou , Anderson Ryan , Zhu Ning , Zhang Lifeng 
Published: May 2021

Synchrotron X-ray tomography images were used to study dynamic, regional water transfer behavior in the gas diffusion layer (GDL) during thawing and desaturation processes. Initially saturated, frozen GDLs were thawed and desaturated with air in a serpentine gas flow channel. On-the-fly (OTF) high speed CT scans via synchrotron X-ray allowed the capture of consecutive water transfer inside the GDL under the cold start-up gas purging condition. Desaturation data of Sigracet 35AA GDLs with three superficial gas velocities (2.88–5.98 m/s) were selected for analysis. Multiple spatial segmentation levels based on the flow field geometry, including channel vs. rib, individual channels and ribs, and smaller sections in each channel and rib, were applied to the in-plane direction to study the GDL regional thawing and desaturation behaviors. Each segmentation volume had a similar desaturation pattern in general; however, water distribution and desaturation show heterogeneity over the GDL domain, as well as relation with factors including the flow field geometry, air traveling distance, and initial saturation level. These data from the segmentation analysis expand the knowledge of localized water transfer behavior during the cold start thawing process. These data can also provide valuable information for future cold start modeling and help in optimizing the PEM fuel cell flow field design.
Immune Landscape of Gastric Carcinoma Tumor Microenvironment Identifies a Peritoneal Relapse Relevant Immune Signature
Authors: Zhang Chuang , Li Danni , Yu Ruoxi , Li Ce , Song Yujia , Chen Xi , Fan Yibo , Liu Yunpeng , Qu Xiujuan 
Published: May 2021

BackgroundGastric cancer (GC) still represents the third leading cause of cancer-related death worldwide. Peritoneal relapse (PR) is the most frequent metastasis occurring among patients with advanced gastric cancer. Increasingly more evidence have clarified the tumor immune microenvironment (TIME) may predict survival and have clinical significance in GC. However, tumor-transcriptomics based immune signatures derived from immune profiling have not been established for predicting the peritoneal recurrence of the advanced GC.MethodsIn this study, we depict the immune landscape of GC by using transcriptome profiling and clinical characteristics retrieved from GSE62254 of Gene Expression Omnibus (GEO). Immune cell infiltration score was evaluated via single-sample gene set enrichment (ssGSEA) analysis algorithm. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used to select the valuable immune cells and construct the final model for the prediction of PR. The receiver operating characteristic (ROC) curve and the Kaplan-Meier curve were used to check the accuracy of PRIs. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to explore the molecular pathways associated with PRIs.ResultsA peritoneal recurrence related immune score (PRIs) with 10 immune cells was constructed. Compared to the low-PRIs group, the high-PRIs group had a greater risk. The upregulation of the focal adhesion signaling was observed in the high-PRIs subtype by GSEA and KEGG. Multivariate analysis found that both in the internal training cohort and the internal validation cohort, PRIs was a stable and independent predictor for PR. A nomogram that integrated clinicopathological features and PRIs to predict peritoneal relapse was constructed. Subgroup analysis indicated that the PRIs could obviously distinguish peritoneal recurrence in different molecular subtypes, pathological stages and Lauren subtypes, in which PRIs of Epithelial-Mesenchymal Transitions (EMT) subtype, III-IV stage and diffuse subtype are higher respectively.ConclusionOverall, we performed a comprehensive evaluation of the immune landscape of GC and constructed a predictive PR model based on the immune cell infiltration. The PRIs represents novel promising feature of predicting peritoneal recurrence of GC and sheds light on the improvement of the personalized management of GC patients after surgery.
Therapeutic Liposomal Vaccines for Dendritic Cell Activation or Tolerance
Authors: Nagy Noémi Anna , de Haas Aram M. , Geijtenbeek Teunis B. H. , van Ree Ronald , Tas Sander W. , van Kooyk Yvette , de Jong Esther C. 
Published: May 2021

Dendritic cells (DCs) are paramount in initiating and guiding immunity towards a state of activation or tolerance. This bidirectional capacity of DCs sets them at the center stage for treatment of cancer and autoimmune or allergic conditions. Accordingly, many clinical studies use ex vivo DC vaccination as a strategy to boost anti-tumor immunity or to suppress immunity by including vitamin D3, NF-κB inhibitors or retinoic acid to create tolerogenic DCs. As harvesting DCs from patients and differentiating these cells in vitro is a costly and cumbersome process, in vivo targeting of DCs has huge potential as nanoparticulate platforms equipped with activating or tolerogenic adjuvants can modulate DCs in their natural environment. There is a rapid expansion of the choices of nanoparticles and activation- or tolerance-promoting adjuvants for a therapeutic vaccine platform. In this review we highlight the most recent nanomedical approaches aimed at inducing immune activation or tolerance via targeting DCs, together with novel fundamental insights into the mechanisms inherent to fostering anti-tumor or tolerogenic immunity.
Antibodies Against Angiotensin II Receptor Type 1 and Endothelin A Receptor Are Associated With an Unfavorable COVID19 Disease Course
Authors: Miedema Jelle , Schreurs Marco , van der Sar – van der Brugge Simone , Paats Marthe , Baart Sara , Bakker Marleen , Hoek Rogier , Dik Willem Arnout , Endeman Henrik , Van Der Velden Vincent , van Gammeren Adriaan , Ermens Antonius , Aerts Joachim G. , Thüsen Jan Von Der 
Published: May 2021

BackgroundLung histopathology demonstrates vasculopathy in a subset of deceased COVID19 patients, which resembles histopathology observed in antibody-mediated lung transplant rejection. Autoantibodies against angiotensin II type 1 receptor (AT1R) and Endothelin receptor Type A (ETAR) have been demonstrated in antibody-mediated rejection and may also be associated with severe COVID19 infection. Objective To assess AT1R and ETAR auto-antibodies in COVID19 patients and controls, and explore their association with disease course.Methods65 hospitalized patients with COVID19 infection were included. Clinical and laboratory findings were retrospectively assessed. Patients with unfavorable disease course, admitted at the intensive care unit and/or deceased during hospital admission (n=33) were compared to admitted COVID19 patients with favorable disease course (n=32). The presence of antinuclear antibodies (ANA) and auto-antibodies against AT1R or ETAR in peripheral blood were compared between COVID19 with unfavorable and favorable disease course and age matched controls (n=20).ResultsThe presence of ANA was not significantly different between COVID19 patients with unfavorable (n=7/33; 21%) and favorable disease course (n=6/32; 19%) (p= 0.804) and controls (n=3/20; 15%). Auto-antibodies against AT1R were significantly increased in unfavorable disease course (median 14.59 U/mL, IQR 11.28 – 19.89) compared to favorable disease course (median 10.67 U/mL, IQR 8.55 – 13.0, p&lt; 0.01). ETAR antibody titers were also significantly increased in unfavorable disease course (median 7.21, IQR 5.0 – 10.45) as compared to favorable disease course (median 4.0, IQR 3.0 – 6.0, p &lt;0.05).ConclusionAuto-antibodies against AT1R and ETAR are significantly increased in COVID19 patients with an unfavorable disease course.
Factors Associated With Working in Remote Indonesia: A National Cross-Sectional Study of Early-Career Doctors
Authors: Putri Likke Prawidya , Russell Deborah Jane , O'Sullivan Belinda Gabrielle , Kippen Rebecca 
Published: May 2021

Background: Doctor shortages in remote areas of Indonesia are amongst challenges to provide equitable healthcare access. Understanding factors associated with doctors' work location is essential to overcome geographic maldistribution. Focused analyses of doctors' early-career years can provide evidence to strengthen home-grown remote workforce development.Method: This is a cross-sectional study of early-career (post-internship years 1–5) Indonesian doctors, involving an online self-administered survey on demographic characteristics, and; locations of upbringing, medical clerkship (placement during medical school), internship, and current work. Multivariate logistic regression was used to test factors associated with current work in remote districts.Results: Of 3,176 doctors actively working as clinicians, 8.9% were practicing in remote districts. Compared with their non-remote counterparts, doctors working in remote districts were more likely to be male (OR 1.5,CI 1.1–2.1) or unmarried (OR 1.9,CI 1.3–3.0), have spent more than half of their childhood in a remote district (OR 19.9,CI 12.3–32.3), have completed a remote clerkship (OR 2.2,CI 1.1–4.4) or internship (OR 2.0,CI 1.3–3.0), currently participate in rural incentive programs (OR 18.6,CI 12.8–26.8) or have previously participated in these (OR 2.0,CI 1.3–3.0), be a government employee (OR 3.2,CI 2.1–4.9), or have worked rurally or remotely post-internship but prior to current position (OR 1.9,CI 1.2–3.0).Conclusion: Our results indicate that building the Indonesian medical workforce in remote regions could be facilitated by investing in strategies to select medical students with a remote background, delivering more remote clerkships during the medical course, deploying more doctors in remote internships and providing financial incentives. Additional considerations include expanding government employment opportunities in rural areas to achieve a more equitable geographic distribution of doctors in Indonesia.
Increased Plasma Level of 24S-Hydroxycholesterol and Polymorphism of CYP46A1 SNP (rs754203) Are Associated With Mild Cognitive Impairment in Patients With Type 2 Diabetes
Authors: Shi Jijing , Jia Jianhong , Tian Sai , Zhang Haoqiang , An Ke , Zhu Wenwen , Cao Wuyou , Yuan Yang , Wang Shaohua 
Published: May 2021

BackgroundAbnormal cholesterol metabolism is common in type 2 diabetes mellitus (T2DM) and causes dementia. Cholesterol 24S-hydroxylase (CYP46A1) converts cholesterol into 24S-hydroxycholesterol (24-OHC) and maintains cholesterol homeostasis in the brain.ObjectiveThis study aimed to investigate the roles of 24-OHC and the CYP46A1 (rs754203) polymorphism in patients with T2DM and mild cognitive impairment (MCI).MethodsA total of 193 Chinese patients with T2DM were recruited into two groups according to the Montreal Cognitive Assessment (MoCA). Demographic and clinical data were collected, and neuropsychological tests were conducted. Enzyme-linked immunosorbent assay (ELISA) and Seqnome method were used to detect the concentration of plasma 24-OHC and the CYP46A1 rs754203 genotype, respectively.ResultsCompared with 118 healthy cognition participants, patients with MCI (n = 75) displayed a higher plasma level of 24-OHC and total cholesterol concentration (all p = 0.031), while no correlation was found between them. In the overall diabetes population, the plasma level of 24-OHC was negatively correlated with MoCA (r = −0.150, p = 0.039), and it was further proved to be an independent risk factor of diabetic MCI (OR = 1.848, p = 0.001). Additionally, patients with MCI and the CC genotype of CYP46A1 rs754203 showed the highest plasma level of 24-OHC even though the difference was not statistically significant, and they obtained low scores in both the verbal fluency test and Stroop color and word test A (p = 0.008 and p = 0.029, respectively).ConclusionIn patients with T2DM, high plasma level of 24-OHC and the CC genotype carrier of CYP46A1 rs754203 may portend a high risk of developing early cognitive impairment, including attention and executive deficits.
A Rapid Motor Task-Based Screening Tool for Parkinsonism in Community-Based Studies
Authors: Dlamini Wendy W. , Nielsen Searles , Ushe Mwiza , Nelson Gill , Racette Brad A. 
Published: May 2021

Background: The prevalence of parkinsonism in developing countries is largely unknown due to difficulty in ascertainment because access to neurologists is often limited.Objective: Develop and validate a parkinsonism screening tool using objective motor task-based tests that can be administered by non-clinicians.Methods: In a cross-sectional population-based sample from South Africa, we evaluated 315 adults, age &gt;40, from an Mn-exposed (smelter) community, using the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3), Purdue grooved pegboard, and kinematic-UPDRS3-based motor tasks. In 275 participants (training dataset), we constructed a linear regression model to predict UPDRS3. We selected motor task summary measures independently associated with UPDRS3 (p &lt; 0.05). We validated the model internally in the remaining 40 participants from the manganese-exposed community (test dataset) using the area under the receiver operating characteristic curve (AUC), and externally in another population-based sample of 90 participants from another South African community with only background levels of environmental Mn exposure.Results: The mean UPDRS3 score in participants from the Mn-exposed community was 9.1 in both the training and test datasets (standard deviation = 6.4 and 6.1, respectively). Together, 57 (18.1%) participants in this community had a UPDRS3 ≥ 15, including three with Parkinson's disease. In the non-exposed community, the mean UPDRS3 was 3.9 (standard deviation = 4.3). Three (3.3%) had a UPDRS3 ≥ 15. Grooved pegboard time and mean velocity for hand rotation and finger tapping tasks were strongly associated with UPDRS3. Using these motor task summary measures and age, the UPDRS3 predictive model performed very well. In the test dataset, AUCs were 0.81 (95% CI 0.68, 0.94) and 0.91 (95% CI 0.81, 1.00) for cut points for neurologist-assessed UPDRS3 ≥ 10 and UPDRS3 ≥ 15, respectively. In the external validation dataset, the AUC was 0.85 (95% CI 0.73, 0.97) for UPDRS3 ≥ 10. AUCs were 0.76–0.82 when excluding age.Conclusion: A predictive model based on a series of objective motor tasks performs very well in assessing severity of parkinsonism in both Mn-exposed and non-exposed population-based cohorts.
Usefulness of the Neutrophil-to-Lymphocyte Ratio as a Predictor of Pneumonia and Urinary Tract Infection Within the First Week After Acute Ischemic Stroke
Authors: Gens Robin , Ourtani Anissa , De Vos Aurelie , De Keyser Jacques , De Raedt Sylvie 
Published: May 2021

Background: A high Neutrophil-to-Lymphocyte ratio (NLR) in patients with acute ischemic stroke (AIS) has been associated with post-stroke infections, but it's role as an early predictive biomarker for post-stroke pneumonia (PSP) and urinary tract infection (UTI) is not clear.Aim: To investigate the usefulness of NLR obtained within 24 h after AIS for predicting PSP and UTI in the first week.Methods: Clinical and laboratory data were retrieved from the University Hospital Brussels stroke database/electronic record system. Patients were divided into those who developed PSP or UTI within the first week after stroke onset and those who didn't. Receiver operating characteristics (ROC) curves and logistic regression analysis were used to identify independent predictors.Results: Five hundred and fourteen patients were included, of which 15.4% (n = 79) developed PSP and 22% (n = 115) UTI. In univariate analysis, NLR was significantly higher in patients who developed PSP (4.1 vs. 2.8, p &lt; 0.001) but not in those who developed UTI (3.3 vs. 2.9, p = 0.074). Multiple logistic regression analysis for PSP showed that NLR, male gender, dysphagia, and stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), were independent predictors of PSP. For NLR alone, the area under the curve (AUC) in the ROC curve was 0.66 (95% CI = 0.59–0.73). When combining NLR ≥ 4.7 with age &gt;75 years, male gender, NIHSS &gt; 7, and dysphagia, the AUC increased to 0.84 (95% CI = 0.79–0.89).Conclusion: The NLR within 24 h after AIS appears to have no predictive value for post-stroke UTI, and is only a weak predictor for identifying patients at high risk for PSP. Its predictive value for PSP appears to be much stronger when incorporated in a prediction model including age, gender, NIHSS score, and dysphagia.
An Improvement of Survival Stratification in Glioblastoma Patients via Combining Subregional Radiomics Signatures
Authors: Yang Yang , Han Yu , Hu Xintao , Wang Wen , Cui Guangbin , Guo Lei , Zhang Xin 
Published: May 2021

PurposeTo investigate whether combining multiple radiomics signatures derived from the subregions of glioblastoma (GBM) can improve survival prediction of patients with GBM.MethodsIn total, 129 patients were included in this study and split into training (n = 99) and test (n = 30) cohorts. Radiomics features were extracted from each tumor region then radiomics scores were obtained separately using least absolute shrinkage and selection operator (LASSO) COX regression. A clinical nomogram was also constructed using various clinical risk factors. Radiomics nomograms were constructed by combing a single radiomics signature from the whole tumor region with clinical risk factors or combining three radiomics signatures from three tumor subregions with clinical risk factors. The performance of these models was assessed by the discrimination, calibration and clinical usefulness metrics, and was compared with that of the clinical nomogram.ResultsIncorporating the three radiomics signatures, i.e., Radscores for ET, NET, and ED, into the radiomics-based nomogram improved the performance in estimating survival (C-index: training/test cohort: 0.717/0.655) compared with that of the clinical nomogram (C-index: training/test cohort: 0.633/0.560) and that of the radiomics nomogram based on single region radiomics signatures (C-index: training/test cohort: 0.656/0.535).ConclusionThe multiregional radiomics nomogram exhibited a favorable survival stratification accuracy.
Age-Associated Changes in Adverse Events Arising From Anti-PD-(L)1 Therapy
Authors: Huang Xinyi , Tian Tiantian , Zhang Yan , Zhou Shengjian , Hu Pingping , Zhang Jiandong 
Published: May 2021

BackgroundImmune-related adverse events (irAEs) may complicate the immune checkpoint inhibition (ICI) therapy. The effect of age on these irAEs is not elucidated. The aim of the study was to compare the occurrence of irAEs in different age groups.MethodsPatients with lung cancer receiving anti-programmed death- (ligand)1 (PD-(L)1) were selected from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Immune cell infiltration data set was obtained from TIMER 2.0 web server. The patients were stratified for age as follows: &lt;65 year-old (young patients, YP), 65 to 75 year-old (middle aged patients, MP), ≥75 year-old (old patients, OP). The severity of irAEs was compared using logistic binary regression model. The distribution differences of immune cell infiltration were estimated using non-parametric tests.ResultsOf all the 17,006 patients treated by anti-PD-(L)1, 7,355 were &lt;65 (YP), 6,706 were 65–75 (MP), and 2,945 were ≥75 (OP). In general, we analyzed a total of 16 irAEs in this article and found that pulmonary toxicity was more frequent in OP (OP vs. YP: OR = 1.45, 95% CI: 1.28–1.64) and MP (MP vs. YP: OR = 1.38, 95% CI: 1.24–1.52), but hepatitis was less frequent in OP (OP vs. YP: OR = 0.56, 95% CI: 0.32–0.97) and MP (MP vs. YP: OR = 0.57, 95%CI: 0.38–0.85). Further analysis demonstrated that older patients showed less B cell, CD8+ T cell and myeloid dendritic cell infiltration than younger patients.ConclusionsElderly patients exhibited higher incidences of pulmonary toxicity, while hepatitis was found at low incidence. Therefore, clinicians should carefully monitor comorbidities in elderly patients.