bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA sequencing analysis reveals differential gene expression of CXCL2 in ACPA-positive and ACPA-negative rheumatoid arthritis
Authors: Sun Lin , Wang Xinyu , He Ning , An Zhuo , Yu Ruohan , Li Yanming , Li Yongjun , Liu Xiangyuan , Fang Xiangdong , Zhao Jinxia 
Published: April 2020

Abstract
Background. Anti-citrullinated protein/peptide antibodies (ACPA) play important roles in the pathogenesis of rheumatoid arthritis (RA), and are associated with RA severity. It has been suggested that ACPA-positive (ACPA+) and ACPA-negative (ACPA-) RA are different disease subsets with distinct differences in genetic variation and clinical outcomes. The aims of the present study were to compare gene expression profiles in ACPA + and ACPA- RA and identify novel candidate gene signatures that might serve as therapeutic targets. Methods. Comprehensive transcriptome analysis of peripheral blood mononuclear cells (PBMCs) from ACPA + and ACPA- RA patients, and healthy controls was performed via RNA sequencing. Genes with significantly different expressions were analyzed by cluster analysis, Gene Ontology analysis and Ingenuity Pathway analysis. A validation cohort was used to further investigate differentially expressed genes via real-time PCR and enzyme-linked immunosorbent assay. Spearman's correlation test was used to evaluate the correlation of differentially expressed genes and the clinical and laboratory data of the patients. The role of differentially expressed genes in osteoclastogenesis was further investigated. Results. There were significant differences in the expression levels of both genes and gene isoforms between ACPA + and ACPA- RA samples. Expression of C-X-C motif chemokine ligand 2 (CXCL2) was significantly increased in ACPA + RA patients than in ACPA- RA patients and healthy controls. Validation of candidate genes expression showed that CXCL2 levels in PBMCs and serum were higher in ACPA + RA patients than in ACPA- RA patients and healthy controls. CXCL2 promoted the migration of CD14 + monocytes and increased osteoclast differentiation in RA patients. RAW264.7 macrophages were used to investigate specific mechanisms, and the results suggested that CXCL2 stimulated osteoclastogenesis via ERK MAPK and NFκB pathways. Conclusion. Novel pathways associated with ACPA + RA were identified via RNA sequencing, and CXCL2 was highly expressed in ACPA + RA than in ACPA- RA. These results reveal a previously unreported role of CXCL2 during osteoclastogenesis in RA, and suggest that the blockade of CXCL2 might be a novel strategy for the treatment of RA.
World Health Organization Grading Classification for Pancreatic Neuroendocrine Neoplasms: A Comprehensive Analysis from a Large Chinese Institution
Authors: Yang Min , Zeng Lin , Ke Neng-wen , Tan Chun-lu , Tian Bo-le , Liu Xu-bao , Xiang Bo , Zhang Yi 
Published: April 2020

Abstract
Background Pancreatic neuroendocrine neoplasms (p-NENs) are a group of highly heterogeneous tumors with distinct clinicopathological features and long-term prognosis. In 2017, in order to better stratify patients into prognostic groups and predicting their outcomes, World Health Organization (WHO) officially updated its grading system for p-NENs which distinguished these neoplasms among Grading 1 (G1) pancreatic neuroendocrine tumors (p-NETs), G2 p-NETs, G3 p-NETs and G3 pancreatic neuroendocrine carcinomas (p-NECs). However, this new grading classification for p-NENs has not yet been rigorously validated.Methods Data of patients who were surgically treated and histopathologically diagnosed as p-NENs at West China Hospital of Sichuan University from January 2002 to December 2018 were retrospectively collected and analyzed according the novel WHO 2017 grading classification.Results We eventually enrolled 480 eligible patients with p-NENs in our present study, in which 150 patients with WHO 2017 G1 p-NETs, 158 with G2 p-NETs, 64 with G3 p-NETs and 108 with G3 p-NECs were identified. The estimated 5-year overall survival for patients with G1 p-NETs, G2 p-NETs, G3 p-NETs and G3 p-NECs was 75.8%, 58.4%, 35.1% and 11.1%, with a median survival time of 85.3mons, 67.4mons, 51.3mons and 26.8mons, respectively. Patients with G2 p-NETs present notably worse survival than those with G1 p-NETs (P = 0.03). Survival of G3 p-NETs were significantly worse than that of G1 p-NETs or G2 p-NETs (P < 0.001, P = 0.023, respectively), as well as that when comparing G3 p-NECs with G1 p-NETs or G2 p-NETs (P < 0.001, P < 0.001, respectively). Patients with G3 p-NECs showed statistically shorter survival than those with G3 p-NETs (P < 0.001). Both WHO 2017 and 2010 grading criteria could be independent predictor for the OS of p-NENs (P = 0.016, P = 0.022; respectively). The 95% confidence intervals of WHO 2017 grading classification (0.983–9.454) was slightly smaller than that of WHO 2010 criteria (0.201–13.374), indicating a relatively more accurate predicting ability for the prognosis of p-NENs.Conclusion The WHO 2017 grading classification for p-NENs could successfully allocate patients into four groups with distinct clinical features and significant survival differences, which might be superior to the WHO 2010 criteria for its better prognostic stratification and more accurate predicting ability.
SHP2 inhibitor PHPS1 ameliorates acute kidney injury by Erk1/2-STAT3 signaling in a hemorrhage followed CLP mice model
Authors: Jiang Jihong , Hu Baoji , Chung Chun-Shiang , Chen Yaping , Zhang Yunhe , Li Jinbao , Ayala Alfred 
Published: April 2020

Abstract
Background
Hypovolemic shock and septic challenge are two major causes of acute kidney injury (AKI) in the clinic course. Src homology 2 domain-containing phosphatase 2 (SHP2) is one of the major phosphatase protein tyrosine phosphatase (PTPs), which play a significant role in maintaining immunological homeostasis by regulating many facets of immune cell signaling. In this study, we explored whether SHP2 signaling contributed to AKI induced by hemorrhage (Hem) followed by cecal ligation and puncture (CLP) (Hem/CLP) and, further, if inactivation of SHP2 with the selective inhibitor, Phenylhydrazonopyrazolone sulfonate 1 (PHPS1), attenuated this injury.
Methods
Male C57BL/6 mice were subjected to Hem (a “priming” insult) followed by CLP or sham-Hem plus sham-CLP (S/S) as controls. Samples of blood and kidney were harvested at 24 h post CLP. The expression of neutrophil gelatinase-associated lipocalin (NGAL), high mobility group box 1 (HMGB1), caspase3 as well as SHP2:phospho-SHP2, extracellular-regulated kinase (Erk1/2):phospho-Erk1/2, and signal transducer and activator of transcription 3 (STAT3):phospho-STAT3 protein in kidney tissues were detected by Western blotting. The levels of creatinine (Cre) and blood urea nitrogen (BUN) in serum were measured according to the manufacturer’s instructions. Blood inflammatory cytokine/chemokine levels were detected by ELISA.
Results
Here we report that indices of kidney injury, such as BUN, Cre, NGAL in renal tissue and histopathologic change, were pronounced after Hem/CLP in comparison with that observed in the S/S group mice. Furthermore, while Hem/CLP elevated serum levels of inflammatory cytokine/ chemokine, and induced increased levels of HMGB1, SHP2:phospho-SHP2, Erk1/2:phospho-Erk1/2, as well asSTAT3:phospho-STAT3 protein expression in the kidney; treatment with PHPS1 markedly attenuated these Hem/CLP induced changes.
Conclusions
In conclusion, our data indicate that SHP2 inhibition attenuates AKI induced by our double-hit/sequential insult model of Hem/CLP and that this protective action may be attributable to its anti-inflammatory property in mitigating activation of the Erk1/2 and STAT3 signaling pathway. This finding we believe has important potential clinical implications and, thus, warrants further investigation.
The difference between steroid diabetes mellitus and type 2 diabetes mellitus: A whole-body 18F-FDG PET/CT study
Authors: Zhao Qingqing , Zhou Jinxin , Pan Yu , Ju Huijun , Zhu Liying , Liu Yang , Zhang Yifan 
Published: April 2020

Abstract
Background
Steroid diabetes mellitus (SDM) is a metabolic syndrome caused by an increase in glucocorticoids, and its pathogenesis is unclear. 18F-FDG PET/CT can reflect the glucose metabolism of tissues and organs under living conditions, and plays an important role in diabetes research. Here, PET/CT imaging of SDM and type 2 diabetes mellitus (T2DM) rats was used to observe the changes of glucose metabolism in major glucose metabolism organs and immunohistochemical analysis to explore the possible pathogenesis of SDM.
Results
The SDM rat model was successfully established, which showed increased FBG and insulin levels; 18F-FDG PET/CT imaging showed increased FDG uptake in skeletal muscle, but no significant increase in liver uptake (15d);Immunohistochemistry showed that islet α-cell and β-cell proliferation, GLUT-4 and IRS-1, PI3Kp85α expression in skeletal muscle increased, and glycogen storage in liver and skeletal muscle increased.T2DM rats showed atrophy of pancreatic islet β cells and decreased insulin levels; Significantly reduced FDG uptake and glycogen storage in skeletal muscle and liver; IRS-1 expression in skeletal muscle decreased, and GLUT-4 and PI3Kp85α did not change significantly.
Conclusion
The pathogenesis of SDM is different from that of T2DM. The increased glucose metabolism of skeletal muscle may be related to the increased compensatory secretion of insulin; glucocorticoids promote the proliferation of islet α cells and cause the increase of gluconeogenesis in the liver may be the cause of its increased blood glucose.
Assessment of medical professionalism: A Delphi study
Authors: FONG Warren , Kwan Yu Heng , Yoon Sungwon , PHANG Jie Kie , THUMBOO Julian , LEUNG Ying Ying , Ng Swee Cheng 
Published: April 2020

Abstract
Background The importance of medical professionalism and its assessment has been well documented in the literature. However, there is currently no culturally-adapted tool to assess medical professionalism in Singapore. This study sets out to find consensus on relevance of the items from the Professional Mini Evaluation Exercise (P-MEX) for assessing medical professionalism in Singapore. Methods A two-round Delphi survey was completed by an expert panel consisting of program directors, associate designated institutional officials, and designated institutional official (n=15) from residency programs in Singapore. Round 1 comprised of 23 items from the P-MEX rated on a 5-point scale (1= Definitely include, 2= Possibly include, 3= Neutral, 4= Possibly exclude, 5= Definitely exclude). In round 2, the experts received feedback from the previous round, and were asked to re-rate the items which did not achieve consensus in the previous round. The threshold for consensus in the study was defined as 70% or greater agreement among experts. Results Completed questionnaires for both rounds were received from all 15 experts. In round 1, 18 items (78%) achieved consensus to be included. In round 2, 1 (4%) item achieved consensus to be included. However, none of the remaining item achieved consensus to be removed. A consensual list of 23 items covering four domains of medical professionalism (Doctor-patient relationship skills, Reflective skills, Time management and Inter-professional relationship skills) was obtained during the two-rounds of Delphi survey. Conclusions This 23-item P-MEX has garnered consensus and is suitable for assessing medical professionalism in Singapore. The findings of this study can provide guidance for faculty and institutions who want to assess medical professionalism of their medical trainees.
Altered distribution of NK cell subsets in children with Mycoplasma pneumoniae pneumonia&nbsp;Altered distribution of NK cell subsets in children with Mycoplasma pneumoniae pneumonia
Authors: Zhou Weifang , Zhang Dandan , Cao Xiuling , Li Yuqin , Ding Ying , Fan Yujie , Yu Yixue , Chu Chu , Li Yan 
Published: April 2020

Abstract

Background : Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory illness in children, particularly those with allergic constitutions. NK cells and cytokines are thought to be involved; however, understanding of the immunopathology of MPP is incomplete. Methods : Peripheral blood samples were collected from 51 children hospitalized with with MPP, 26 with an allergic constitution and 25 without, and 29 healthy controls. NK cell subsets were analyzed by flow cytometry and the expression of interleukin (IL)-1 alpha and IL-18 was detected by ELISA. The relationship between NK cell subsets and the expression of IL-18 and IL-1 alpha was determined. Results : The number of CD3 − CD56 + NK cells and CD3 − CD56 dim CD16 bright NK cells in children with MPP was lower than in healthy controls (P < 0.05). The percentage of CD3 − CD56 + NK cells, CD3 − CD56 dim CD16 bright NK cells and the number of CD3 − CD56 dim CD16 bright NK cells in the MPP allergic group were lower than in the non-allergic group (P < 0.05). The expression of IL-18 was significantly increased in the MPP groups (P < 0.05), and the absolute number of CD3 − CD56 dim CD16 bright NK cells negatively correlated with IL-18 levels in the peripheral blood (P < 0.05). Conclusion : Reduced numbers of NK cell subsets were identified in children with MPP and MPP with an allergic predisposition compared with healthy controls. Concomitant increases in IL-18 in children with MPP suggest the involvement of IL-18 in the immunopathogenesis of MPP and may be related to the reduced CD3 − CD56 dim CD16 bright NK cells.
Trends in Shaken Baby Syndrome Diagnoses Among Young Children Hospitalized for Abuse
Authors: Conrad Aislinn , Butcher Brandon , Oral Resmiye , Ronnenberg Megan , Peek-Asa Corinne 
Published: April 2020

Abstract
Objective

To investigate national trends of SBS diagnosis codes and how trends varied among patient and hospital characteristics.

Methods

We examined possible and confirmed SBS diagnoses among children age three and younger who were hospitalized for abuse between 1998 and 2014 using a secondary analysis of the National Inpatient Sample, the largest US all-payer inpatient care database ( N = 52,562). A baseline category logit model was used based on a quasi-likelihood approach (QIC) with an independent working correlation structure.

Results

The rate of confirmed SBS diagnoses increased from 3.8 (± 0.3) in 1998 to 5.1 (± 0.9) in 2005, and decreased to 1.3 (± 0.2) in 2014. Possible SBS diagnoses were 0.6 (± 0.2) in 1998, and increased to 2.4 (± 0.4) in 2014. Confirmed SBS diagnoses have declined since 2002, while possible SBS diagnoses have increased. Possible SBS diagnoses were more common among urban teaching hospitals and small to medium hospitals than for other hospital types.

Conclusions

We investigated seventeen-year trends of SBS diagnoses among young children hospitalized for abuse. The discrepancy between trends in possible and confirmed SBS suggests differences in diagnostic norms for SBS and related conditions. Researchers should examine diagnostic processes for SBS and investigate why cases are diagnosed as SBS or a related diagnosis. We propose that researchers and pediatric medical providers agree to a standardized definition and diagnostic guidelines for SBS, much like the AHT guidelines proposed by CDC, which may help reduce discrepancies in diagnosis and improve options for surveillance.
Lipids monitoring in Scenedesmus obliquus based on Terahertz Technology
Authors: Shao Yongni , Gu Weimin , Qiu Yating , Wang Shengfeng , Peng Yan , Zhu YiMing , Zhuang Songlin 
Published: April 2020

Abstract
Background
Microalgae are considered as a source of low pollution and renewable fuel due to their ability to synthesize an abundance of lipids. Conventional methods for lipid quantification are time consuming and chemically contaminated. Spectroscopic method combined with mathematical model can be used for qualitative and quantitative analysis of material composition.Terahertz technology provides not only timely and nondestructive testing without chemical pollution, but also information about the functional group vibration mode and structure of the measured components. Therefore,terahertz is proposed for microalgae metabolism detection.
Results
The aim of this study was to use Terahertz (THz) spectroscopy to observe lipid content in Scenedesmus obliquus (S. obliquus). We collected the THz spectra of S. obliquus which were cultivated under nitrogen stress and THz spectroscopy was used to analyze changes in substance components (lipids, proteins, carbohydrates and β-carotene). Partial least square was used to establish the prediction model of each stress time point. The correlation coefficient of the prediction results of the model was above 0.991, and the root mean square error was less than 0.020. It indicated that THz technology can be used to discriminate S. obliquus cells under different nitrogen stress culture times effectively. The correlation between the THz characteristic peak (9.3 THz) and the total lipid content determined by gravimetry reaches 0.96. The final results were compared with the commonly used spectroscopic methods for lipid observation (Raman spectroscopy).
Conclusions
The prediction accuracy of model of THz bands is relatively high. It indicated that THz technology can be used to monitor the change of material composition in microalgae under nitrogen stress. THz is more accurate than Raman in total lipid monitoring. For the research of microalgal metabolites, compared with Raman technology, there is more research space for THz technology. THz technology can provide technical supporting for the engineering culture of oil-producing microalgae under environmental control in future.
Limiting factors to Boolean remission differ between autoantibody-positive and -negative patients in early rheumatoid arthritis
Authors: Bugatti Serena , De Stefano Ludovico , Benaglio Francesca , Sakellariou Garifallia , Manzo Antonio , Montecucco Carlomaurizio 
Published: April 2020

Abstract
Background: Patients with established rheumatoid arthritis (RA) frequently miss Boolean remission solely because of the patient global assessment of disease activity (PGA) exceeding the cut-off of 1. Here, we investigated the frequency and the limiting variables to disease remission in patients with early RA treated with conventional synthetic disease modifying anti-rheumatic drugs according to a treat-to-target strategy, depending on the autoantibody status. Methods: Data were retrieved from 535 early RA patients (<12 months of symptoms), treatment-naïve at inclusion, with an observation period of 6 to 12 months upon initiation of therapy with methotrexate aimed at the achievement of low disease activity based on the 28-joints disease activity score. Near-remission was defined as any of the 4 core items of Boolean remission exceeding the cut-off of 1 with the remaining 3 all ≤1. Reasons for missing Boolean remission and predictors of near-remission subcategories were analysed in relation to baseline disease variables. Results: After 6 and 12 months from treatment start, near-remission was two-times more frequent than Boolean remission (25.6% and 26.9% at the two time-points). A 28-swollen joint count (SJC28) >1 was responsible for the majority of near-misses (56.2% and 57.6% at 6 and 12 months, respectively), and PGA >1 accounted for approximatively 35% of the cases. None of the variables of disease activity neither patient reported outcomes at baseline could discriminate SJC28 from PGA near-misses. Rather, autoantibody-positivity independently predicted the risk of missing remission because of SJC28 >1 with an adjusted OR [95% CI] of 3.62 [1.89-6.93] at 6 months and 2.36 [1.25-4.47] at 12 months, whilst autoantibody-negativity was an independent predictor of PGA near-miss (adjusted OR [95% CI] 2.71 [1.31-5.64] at 6 months and 6.50 [2.47-17.12] at 12 months). Conclusions: In patients with early RA, Boolean remission is more frequently missed because of persistent swollen joints. However, barriers to full-remission vary in relation to the autoantibody status. Autoantibody-positive patients more commonly experience residual swollen joints, whilst the PGA more frequently impairs the achievement of remission in autoantibody-negative patients. These findings indicate that efforts to target full-remission in early RA may require different treatment strategies according to the autoantibody profile.
Clinical findings of 35 cases with novel coronavirus pneumonia outside of Wuhan
Authors: Luo Wen , Lin Yihua , Yao Xiangyang , Shi Yonghong , Lu Fang , Wang Zhanxiang , Wu Dinghui 
Published: April 2020

Abstract
Objective: We sought to investigate the clinical characteristics of patients with novel coronavirus pneumonia in Xiamen, which is a city in Fujian Province, China. Methods: From January 20, 2020, to March 4, 2020, the clinical characteristics of all patients confirmed with novel coronavirus pneumonia admitted to the First Affiliated Hospital of Xiamen University, which was the only designated hospital for cases of novel coronavirus pneumonia in Xiamen, were analyzed. Results: A total of 35 cases of novel coronavirus pneumonia were confirmed. Patients were divided into the general-ward admission group and the intensive-care-unit (ICU) admission group. The most commonly observed symptoms were fever (80%), cough (51%), expectoration (28%), and fatigue (23%). Compared with patients in the general-ward group, patients in the ICU group had a higher maximum body temperature, a longer duration of fever after admission, and more symptoms of systemic pain. Considering the laboratory findings, patients in the ICU group exhibited lower peripheral blood lymphocyte ratios and lymphocyte counts but higher C-reactive protein and lactate dehydrogenase levels. All patients were discharged without death, and no patients required invasive ventilation, continuous renal replacement therapy, or extracorporeal membrane oxygenation. Conclusion: Relative to patients with novel coronavirus pneumonia in Wuhan, the cases in Xiamen were less severe.
Tim-3 protein expression with MGMT methylation status in glioblastoma and association with survival
Authors: zhang ji , Wang Xiaoli , Ye Shengquan , Liang Lijiao , Zhou Yi , Chen Zhijie , Hu Wanming , Liu Jianmin 
Published: April 2020

Abstract
Background Understanding the molecular landscape of glioblastoma (GBM) is increasingly crucial for its therapy. Immune checkpoint molecules motivated the emergence of immune checkpoint-targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecule T cell immunoglobulin mucin-3 (Tim-3) on tumor-infiltrating immune cells (TIICs) and O-6-Methylguanine-DNA methyltransferase (MGMT) methylation status remains to be fully elucidated. We aimed to develop an MGMT methylation status-associated immune prognostic signature for predicting prognosis in GBMs.Patients and Methods: A total of 84 patients with newly diagnosed GBM were involved. MGMT methylation status was retrospectively analyzed and the expression level of Tim-3 protein was investigated using immunohistochemistry (IHC). The correlation between Tim-3 protein expression and MGMT methylation status, and the prognosis was explored.Results The obtained data showed that Tim-3 protein was expressed at different levels in GBMs. Mesenchymal expression of Tim-3 protein in these tissues was 73.81% (62/84), including low 15.48% (13/84), moderate 7.14% (6/84) and strong expression 51.19% (43/84), respectively. Of the 48 patients whose tumors tested positive for MGMT methylation, the remaining 36 patients was negative.Conclusions We profiled the immune status in GBM with MGMT promoter methylation and established a local immune signature for GBM, which could independently identify patients with a favorable prognosis, indicating the relationship between prognosis and immune. MGMT promoter methylation with lower Tim-3 protein expression was statistically significantly associated with better survival.