bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression-based immune infiltration analyses of renal cancer and their associations with survival outcome
Authors: Chen Lei , Yin Liang , Qi Zilong , Li Jinmin , Wang Xinning , Ma Kun , Liu Xiangyang 
Published: April 2020

Abstract
Renal cancer is a common malignant tumor with an increasing incidence rate. In this study, based on the gene expression profiles, we analyzed the compositions of tumor infiltrating immune cells (TIICs) in renal cancer and paracancerous samples by using CIBERSORT. The proportions of 22 TIICs subsets in 122 paired renal cancer and paracancerous samples, and 224 Wilms tumor (WT) samples varied between intragroup and intergroup. After analyzed the difference in TIICs composition between renal cancer and paired paracancerous samples, we found that compared with paracancerous samples, M0 macrophages and CD8 T cells were significantly elevated, while naive B cells were significantly decreased in renal cancer samples. Survival analysis showed that high overall TIICs proportion, low proportion of resting mast cells and high proportion of activated memory CD4 T cells were associated with poor prognosis of renal cancer patients. In addition, 3 clusters were identified by hierarchical clustering analysis and they presented distinct prognosis. Cluster 1 had superior survival outcome, while cluster 2 had inferior survival outcome. In summary, our study indicated that overall TIICs proportion, certain TIICs subset proportion, and distinct cluster patterns were associated with the prognosis of renal cancer, which was significant for the clinical surveillance and treatment of renal cancer.
Molecular markers in the CSF proteome differentiate neuroinflammatory diseases
Authors: Elkjaer Maria Louise , Nawrocki Arkadiusz , Kacprowski Tim , Lassen Pernille , Simonsen Anja Hviid , Marignier Romain , Sejbaek Tobias , Nielsen Helle Hvisted , Wermuth Lene , Rashid Alyaa , Hogh Peter , Sellebjerg Finn , Reynolds Richard , Baumbach Jan , Larssen Martin R , Illes Zsolt 
Published: April 2020

Abstract
Background: Multiple sclerosis (MS) is characterized by different degree of inflammatory and neurodegenerative features in the early relapsing vs. progressive subtypes. By using controls with different extent of inflammation vs. neurodegeneration, we examined the CSF proteome to identify molecular markers that differentiate between subtypes of MS. Gene expression of specific proteins were explored in MS brain lesions with diverse pathological background. Methods: (i) First, we compared the proteome by LC-MS/MS in 169 pooled CSF from MS subtypes to inflammatory/degenerative controls: AQP4-IgG-positive and AQP4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD), Alzheimer’s disease (AD), and healthy controls. F-test based feature selection was used to cluster diseases and MS subtypes. (ii) Next, we selected 299 molecules by comprehensive statistics, and quantified them in the individual CSF samples. (iii) We also screened the genes of MS-specific CSF proteins in transcriptomes of 73 MS brain lesions with different pathology. Results: We identified 11 proteins that separated diseases, and 8 proteins that clustered MS subtypes. Secondary progressive (SP)MS had the most unique proteome characterized by upregulation of intrinsic pathway proteins of the coagulation pathway. SPMS also clustered far from NMOSD indicating less inflammatory pathways. Primary progressive (PP)MS was more similar to relapsing-remitting (RR)MS than SPMS. Quantification of 299 proteins in 170 individual CSF samples identified 5 molecules uniquely upregulated in MS subtypes and in AQP4-IgG-positive NMOSD, respectively. Chitinase-3-like protein 1 (CHI3L1) was upregulated in part of PPMS and remission CSF samples, and it was expressed by astrocytes in chronic active lesions. GFAP was upregulated in 70% of AQP4-IgG-positive NMOSD but only in 40% of AQP4-IgG-negative NMOSD. Conclusions: By the combination of untargeted and targeted quantitative analysis, we identified CSF molecular markers of axonal growth inhibition, lipid binding, and protein/lipid transport that differentiated between neuroinflammatory and neurodegenerative diseases, and also MS subtypes. The majority of them were expressed in MS brain lesions suggesting their origin from the brain tissue and not from the systemic compartment. Data suggest that the CSF proteome of SPMS is different from PPMS, and astrocyte damage may not be major pathology in part of the AQP4-IgG seronegative NMOSD.
Mental disorder and PTSD in Syria during wartime: a national-wide crisis
Authors: Kakaje Ameer , Zohbi Ragheed Al , Aldeen Osama Hosam , Makki Leen , Alyousbashi Ayham , Alhaffar Bahaa Aldin 
Published: April 2020

Abstract
Background: Syria has experienced war over the past seven years, leaving a high percentage of the population below the poverty line. This has significantly impacted Syrians which is reflected in the psychiatric aspect. This study evaluates the severity of the mental disorder caused by war and other factors, and evaluates the post-traumatic stress disorder (PTSD) in addition to support provided to Syrians. Methods: Online surveys including the Kessler 10 (K10) survey, the Screen for Posttraumatic Stress Symptoms (SPTSS) tool, the Multidimensional Scale of Perceived Social Support (MSPSS) and demographic and war-related questions were used for this study. Results: Our study included 1951 participants, comprising 527 (27.0%) males and 1538 (78.8%) aged (19-25) years. Of all the participants in the study, 44% had severe mental disorder, 27% had severe mental disorder with full PTSD symptoms, 36.9% had full PTSD symptoms, 79% had at least one PTSD symptom, and 10.8% had neither PTSD symptoms nor mental disorder. Only 23.2% had low overall support. Half of the responders were internally displaced and 27.6% of these participants were forced to move three times or more due to war. Only 13.4% of the responders did not believe that the crisis was the reason for their distress. Those with high SPTSS and K10 scores were found to take more days off of work or school due to negative feelings and have somatic symptoms. Moreover, low levels of education, low socioeconomic status, chronic medical conditions, war variables for example distress caused by war noises, changing place of living due to war were all associated with high distress and the presence of PTSD symptoms in this study. Strong significant correlation (r=0.623) was found between SPTSS and k10 score. Conclusion: The conflict in Syria has left the country’s population at great risk of psychological and mental distress. Drastic measures are required to save an entire population from permanent psychological suffering.
Identification of ALDH3A2 as novel prognostic biomarker in gastric adenocarcinoma by integrated bioinformatics analysis
Authors: Yin Zhenhua , Wu Dejun , Wei Xiyi , Shi Jianping , Jin Nuyun , Lu Xiaolan , Ren Xiaohan 
Published: April 2020

Abstract
Extensive experiments and researches have elucidated that genes plays a pivotal role in tumorigenesis and development. Nonetheless, its latent involvement in gastric carcinoma (GC) remains to be further investigated. In this study, we identified overlapping differentially expressed genes (DEGs) by comparing the tumor tissue and adjacent normal tissue from Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database, which included 79 up-regulated and 10 down-regulated genes. Based on these genes, functional enrichment analysis, protein-protein interaction (PPI) and prognosis analysis were conducted, and thus the gene ALDH3A2 was chosen for further analysis. Then, we performed Gene Set Enrichment Analysis (GSEA) and immunocorrelation analysis (infiltration, copy number alterations and checkpoints) to comprehend the in-deep mechanism of ALDH3A2. In a word, ALDH3A2 might have potential reference value for the relief and immunotherapy, and become an independent predictive marker for the prognosis of GC.
Dysbiosis of Gut Microbiota with Increased Trimethylamine N-oxide Level in Patients with Large Artery Atherosclerotic and Cardioembolic Strokes
Authors: Xu Dong-Juan , Wang Kai Cheng , Yuan Lin-Bo , Lin Qiong-Qiong , Li Hong-Fei , Xu Yun-Yun , Wei Lian-Yan , Chen Li , Jin Ke-Ke 
Published: April 2020

Abstract
Background — With the establishment of the concept of the gut–brain axis, increasing evidence has shown that the gut microbiome plays an important role in the pathogenesis of cardiovascular diseases. Gut bacteria can transform dietary choline, L-carnitine, and trimethylamine N -oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver and participate in atherogenesis. However, only few studies have described alterations in the gut microbiota composition and function in cardioembolic (CE) and large artery atherosclerotic (LAA) strokes. Methods and Results — A case–control study was performed on patients with LAA and CE strokes. TMAO was determined via liquid chromatography tandem mass spectrometry. Gut microbiome was profiled through Illumina sequencing of the 16S ribosomal RNA gene (V4–V5 regions). The TMAO levels in the plasma of patients with LAA and CE strokes were significantly increased (TMAO: LAA stroke, 2931±456.4 ng/mL vs. CE stroke, 4220±577.6 ng/mL vs. control, 1663±117.8 ng/mL; P < 0.05). The TMAO level in patients with LAA stroke was positively correlated with the carotid plaque area (rho = 0.333, 95% confidence interval = 0.08 to 0.55, and P = 0.0093). The composition and function of gut microbiomes in the LAA and CE stroke groups were significantly different from those of the asymptomatic control. In addition to the significantly increased α and β diversities, the gut microbiome composition and function showed that the LAA group had more microorganisms than the asymptomatic control group; such microorganisms convert dietary source choline, TMAO to TMA. Parabacteroides and Streptococcus exhibited the strongest association with LAA and CE strokes. Conclusions — This study established the compositional and functional alterations of gut microbiomes in patients with LAA and CE strokes and the relationship between plasma TMAO and gut microbiota. The findings suggest the potential of using gut microbiota as a biomarker for patients with LAA and CE strokes.
Albumin-to-alkaline phosphatase ratio serves as a prognostic indicator in unresectable pancreatic ductal adenocarcinoma: a propensity score matching analysis
Authors: Zhang Ke , Dong Shu , Jing Yan Hua , Gao Hui Feng , Chen Lian Yu , Hua Yong Qiang , Chen Hao , Chen Zhen 
Published: April 2020

Abstract
Background Recent evidence suggests that albumin-to-Alkaline Phosphatase Ratio (AAPR) functions as a novel prognostic marker in several malignancies. However, whether it can predict the prognosis of unresectable pancreatic ductal adenocarcinoma (PDAC) remains unclear. Herein, we seek to investigate this possibility by a propensity score matching (PSM) analysis.Methods This was a retrospective cohort study in which 419 patients diagnosed with unresectable PDAC and receiving chemotherapy were recruited. Patients were stratified based on the cutoff value of AAPR. The PSM analysis was performed to identify 156 well-balanced patients in each group for overall survival (OS) comparison and subgroup analysis. Univariate and multivariate analyses were carried out to examine the potential of AAPR to indicate the prognosis of unresectable PDAC. The prediction performance of conventional model and combined model including AAPR was compared using the Akaike Information Criterion (AIC) and concordance index (C-index).Results We identified an AAPR of 0.4 to be the optimal cutoff for OS prediction. Patients with AAPR≤0.4 had significantly shorter OS compared with patients with AAPR>0.4 (6.4 versus 9.3 months; P<0.001). Based on the PSM cohort and entire cohort, multivariate Cox analysis revealed that high pretreatment for AAPR was an independent marker predicting favorable survival in unresectable PDAC (hazard ratio, 0.556; 95% confidence interval, 0.408 to 0.757; P<0.001). Significant differences in OS were observed in all subgroups except for the group of patients age≤60. Combined prognostic model including AAPR had lower AIC and higher C-index than conventional prognostic model.Conclusions Pretreatment AAPR servers as an independent prognostic indicator for patients with unresectable PDAC. Inclusion of AAPR improved the prediction performance of conventional prognostic model, potentially helping clinicians to identify patients at high risk and guide individualized treatment.
Administration of Saccharomyces boulardii mafic-1701 improves growth performance, promotes antioxidant capacity, alleviates intestinal inflammation and modulates gut microbiota in weaned piglets
Authors: Zhang Wenxiu , Bao Chengling , Wang Jian , Zang Jianjun , Cao Yunhe 
Published: April 2020

Abstract
Background: Probiotics seem to be an alternative to antibiotics for improving animal's health and intestinal development. Saccharomyces boulardii ( S. boulardii ) is a well-known probiotic. However, only few studies have been performed examining the effects of S. boulardii on weaned piglets . Therefore, this study was conducted to investigate the effects of dietary S. boulardii mafic-1701 on growth performance, antioxidant parameters, inflammation and intestinal microbiota in weaned piglets, using aureomycin as positive control. One hundred and eight piglets were randomly divided into three dietary treatment groups: (1) basal diet (CON); (2) basal diet supplemented with 75 mg/kg aureomycin (ANT); (3) basal diet supplemented with 1 × 10 8 CFU/kg S. boulardii mafic-1701 (SB). Results: Compared to CON, the supplementation with S. boulardii mafic-1701 improved feed efficiency over the entire 28 days ( P < 0.01) and decreased the rate of diarrhea during the first week ( P < 0.05). Total superoxide dismutase concentration was markedly increased in piglets with S. boulardii mafic-1701 ( P < 0.01). Moreover, compared with CON, SB increased the concentration of interleukin-4 in ileum ( P < 0.05), while the level of pro-inflammatory cytokines interleukin-6 ( P < 0.01) and tumor necrosis factor ( P < 0.01) were decreased in jejunum. SB increased the abundance of Bacillus and Ruminococcaceae ( P < 0.05), whereas the population of Clostridiaceae were decreased ( P < 0.05). Furthermore, the analysis of microbiota metabolites showed that S. boulardii mafic-1701 administration increased the concentration of formate and isobutyrate in cecum to maintain a stable microbiota and gut health ( P < 0.05). Conclusion: This study indicated that S. boulardii mafic-1701 supplementation could improve growth performance, alleviate the severity of diarrhea in weaned piglets, which may be associated with S. boulardii mafic-1701 promoted antioxidant activity, anti-inflammatory responses and microbi al ecology of piglets.
The association between length of stay in the emergency department and short term mortality
Authors: Wessman Torgny , Ärnlöv Johan , Carlsson Axel , Ekelund Ulf , Melander Olle , Ruge Thoralph 
Published: April 2020

Abstract
Background: The detrimental effects of increased length of stay at the emergency department (ED-LOS) for patient outcome have been sparsely studied in the Swedish setting. Our aim was to further explore the association between ED-LOS and short term mortality in patients admitted to the EDs of two large University hospitals in Sweden. Methods: All adult patients (> 18 years) visiting the ED at the Karolinska University Hospital, Sweden, from 1/1/2010 to 1/1/2015 (n=639 385) were retrospectively included. Logistic regression analysis was used to determine association between ED-LOS and 7 and 30-day mortality rates. All patients were triaged according to the RETTS-A into different levels of medical urgency and subsequently separated into five quintiles of ED-LOS. Results: We observed that prolonged ED-LOS was associated with increased mortality for patients with lowest triage priority (risk estimates for 30-day mortality were OR 1.49 (CI 95% 1.20-1.85) for patients with triage priority group 4 and the highest quintile of ED-LOS. No such association was observed in patients with the highest triage priority group and in patients admitted to in-hospital care. Conclusion : Our data suggest that increased ED-LOS could be associated with slightly increased short term mortality in patients with lower clinical urgency and dismissed from the ED but that this does not include patients admitted to in-hospital care.
MiR-21-3p regulation FGFR1/FGF21/PPARγ pathway induces atrial fibrosis by targeting FGFR1 in diabetes
Authors: Gu Jun , Pan Jian-an , Yu Jian-ying , Lin Hao , Zhang Hui-li , Zhang Jun-feng , Wang Chang-qian 
Published: April 2020

Abstract
Background

A relationship between the abundance of epicardial adipose tissue (EAT) and the risk of atrial fibrillation (AF) in diabetes mellitus (DM) has been reported. And browning of EAT might be a novel approach for prevention or treatment in AF by adjusting atrial fibrosis. MicroRNA-21 (miR-21) is one of the most important miRs, and previous studies have shown that it is a regulatory factor in atrial fibrosis and AF. The aim of this study was to examine the role of different subtypes of miR-21 in EAT browning and atrial fibrosis under hyperglycemia conditions.

Methods

The expression of serum hsa-miR-21-3p and hsa-miR-21-5p in patients with DM and/or AF were determined by quantitative reverse transcription-polymerase chain reaction. And normal C57BL/6 wild type (WT) and miR-21 knockout (KO) mice were used to establish the diabetic model by intraperitoneal injection of streptozotocin (STZ). In vitro, The EAT adipocytes from miR-21 KO mice were cultured and transfected with miR-21-3p mimic or miR-21-5p mimic and co-cultured with atrial fibroblasts in both HG or LG conditions. The browning of EAT and the fibrosis of fibroblasts were assessed by western blotting, immunofluorescence, Masson staining, and ELISA. Finally, the gain- and loss-of-function experiments were used to identified fibroblast growth factor receptor 1 (FGFR1) as the target gene of miR-21-3p, and the regulatory pathway of miR-21-3p FGFR1, fibroblast growth factor 21 (FGF21) and peroxisome proliferator-activated receptor gamma (PPARγ) that controlled EAT browning and participates the process of hyperglycemia-induced atrial fibrosis.

Results

In patients with DM and/or AF, serum hsa-miR-21-3p, instead of hsa-miR-21-5p, was significantly up-regulated. And miR-21 KO clearly ameliorated the atrial fibrosis in the diabetic mice. miR-21-3p as a key regulator that controls EAT browning and participates in atrial fibrosis under hyperglycemia conditions. Moreover, our gain- and loss-of-function experiments showed that FGFR1, as a direct target of miR-21-3p identified a regulatory pathway in EAT adipocytes consisting of miR-21-3p, FGFR1, FGF21 and PPARγ.

Conclusions

MiR-21-3p regulated EAT browning and participates the process of hyperglycemia-induced atrial fibrosis by targeting FGFR1/FGF21/PPARγ pathway.
An Empirical Approach toward the SLCF reduction targets in Asia for the Mid-term Climate Change Mitigation
Authors: AKIMOTO HAJIME , Nagashima Tatsuya , Tanimoto Hiroshi , Klimont Zbigniew , Amann Markus 
Published: April 2020

Abstract
Although importance of co-control of SLCFs together with the emission reduction of CO 2 has attracted much attention for the mid-term climate change mitigation, their contribution to radiative forcing (RF) are rather complex, and chemical-climate model analysis for the future scenario tends to give black box for the contribution of each species. In order to deliver a more straightforward message on the effect of the reduction of SLCFs to policymakers, we propose “top-down” reduction targets of CH 4 and tropospheric O 3 in reference to the historical levels of their RF. Although the RF increase due to the increasing CO 2 concentration is inevitable in mid-term future (ca. 0.80 W m -2 in 2040), the RF of CH 4 and O 3 is expected to decrease from 0.48 to 0.41, 0.34, 0.27, and 0.22 W m -2 , and from 0.40 to 0.29, 0.23, 0.19, and 0.15 W m -2 , respectively, if their atmospheric concentrations decrease from the level of 2010 to those of 1980, 1970, 1960 and 1950, according to the IPCC 2013 database. Consequently, the sum of -ΔRF x (CH 4 ) and -ΔRF x (O 3 ) (the difference of RF between the target year of x and 2010 as the base year) are 0.18, 0.31, 0.42 and 0.51 W m -2 in 1980, 1970, 1960 and 1950, respectively. This indicates that the increase of ΔRF 2040 (CO 2 ) can be compensated by of 23 to 64%, and the policy target can be selected from the combination of different target years for CH 4 and O 3 . With these global reduction ratio the necessary reductions in CH 4 , NO x, and NMVOC in Asia was estimated and compared with the GAINS model-based cost-beneficial reduction amount proposed by the Solution Report prepared under UN Environment Asia pacific Office. The comparison suggests that the reduction of O 3 to the 1970 level is promising if the emissions of NO x and NMVOC from other parts of the world are reduced coherently, but further efforts would be necessary for the reduction of CH 4 emissions to realize the 1970 concentration level.
Quantitative 166Ho-microspheres SPECT derived from a dual-isotope acquisition with 99mTc-colloid is clinically feasible
Authors: Stella Martina , Braat Arthur J.A.T. , Lam Marnix G.E.H. , de Jong Hugo W.A.M. , Rooij Rob van 
Published: April 2020

Abstract
Background Accurate dosimetry is essential in radioembolization. To this purpose, an automatic protocol for healthy liver dosimetry based on dual isotope (DI) SPECT imaging, combining holmium-166 ( 166 Ho)-microspheres and technetium-99m ( 99m Tc)-colloid, was developed: 166 Ho-microspheres used as scout and therapeutic particles and 99m Tc-colloid to identify the healthy liver. DI SPECT allows for an automatic and accurate estimation of absorbed doses, introducing true personalized dosimetry. However, photon crosstalk between isotopes can compromise image quality. This study investigates the effect of 99m Tc downscatter on 166 Ho dosimetry, by comparing 166 Ho-SPECT reconstructions of patient scans acquired before ( 166 Ho-only) and after additional administration of 99m Tc-colloid ( 166 Ho-DI). Results The 166 Ho-only and 166 Ho-DI scans were performed in short succession by injecting 99m Tc-colloid on the scanner table. To compensate for 99m Tc downscatter, its influence was accounted for in the DI image reconstruction using energy window-based scatter correction methods. The qualitative assessment was performed by independent blinded comparison by two nuclear medicine physicians assessing 65 pairs of SPECT/CT. Inter-observer agreement was tested by Cohen's kappa coefficient. For the quantitative analysis, two volumes of interest within the liver, VOI TUMOR and VOI HEALTHY , were manually delineated on the 166 Ho-only reconstruction and transferred to the co-registered 166 Ho-DI reconstruction. Absorbed dose within the resulting VOIs, and in the lungs (VOI LUNGS ), was calculated based on the administered therapeutic activity. The qualitative assessment showed no distinct clinical preference for either 166 Ho-only or 166 Ho-DI SPECT (kappa=0.093). Quantitative analysis indicated that the mean absorbed dose difference between 166 Ho-DI and 1 66 Ho-only was -2.00±2.84 Gy (median 27 Gy; p-value <0.00001), -5.27±8.99 Gy (median 116 Gy; p-value =0.00035) and 0.80±1.08 Gy (median 3 Gy; p-value <0.00001) for VOI HEALTHY , VOI TUMOR and VOI LUNGS respectively. The corresponding Pearson’s correlation coefficient between 166 Ho-only and 166 Ho-DI for absorbed dose was 0.97, 0.99 and 0.82, respectively. Conclusions The DI protocol enables automatic dosimetry with undiminished image quality and accuracy.