bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chaperone-Mediated Autophagy Ablation in Pericytes Reveals New Glioblastoma Prognostic Markers and Efficient Treatment Against Tumor Progression
Authors: Molina María Luisa , García-Bernal David , Salinas María Dolores , Rubio Gonzalo , Aparicio Pedro , Moraleda José M. , Martínez Salvador , Valdor Rut 
Published: March 2022

Background: The lack of knowledge of the progression mechanisms of glioblastoma (GB), the most aggressive brain tumor, contributes to the absence of successful therapeutic strategies. Our team has recently demonstrated a crucial new role for chaperone-mediated autophagy (CMA) in pericytes (PC)-acquired immunosuppressive function, which prevents anti-tumor immune responses and facilitates GB progression. The possible impact that GB-induced CMA in PC has on other functions that might be useful for future GB prognosis/treatment, has not been explored yet. Thus, we proposed to analyze the contribution of CMA to other GB-induced changes in PC biology and determine if CMA ablation in PC is a key target mechanism for GB treatment.Methods: Studies of RNA-seq and secretome analysis were done in GB-conditioned PC with and without CMA (from knockout mice for LAMP-2A) and compared to control PC. Different therapeutic strategies in a GB mouse model were compared.Results: We found several gene expression pathways enriched in LAMP2A-KO PC and affected by GB-induced CMA in PC that correlate with our previous findings. Phagosome formation, cellular senescence, focal adhesion and the effector function to promote anti-tumor immune responses were the most affected pathways, revealing a transcriptomic profiling of specific target functions useful for future therapies. In addition, several molecules associated with tumor mechanisms and related to tumor immune responses such as gelsolin, periostin, osteopontin, lumican and vitamin D, were identified in the PC secretome dependent on GB-induced CMA. The CMA ablation in PC with GB cells showed an expected immunogenic phenotype able to phagocyte GB cells and a key strategy to develop future therapeutic strategies against GB tumor progression. A novel intravenous therapy using exofucosylated CMA-deficient PC was efficient to make PC reach the tumor niche and facilitate tumor elimination.Conclusion: Our results corroborate previous findings on the impaired immunogenic function of PC with GB-induced CMA, driving to other altered PC functions and the identifications of new target markers related to the tumor immune responses and useful for GB prognosis/therapy. Our work demonstrates CMA ablation in PC as a key target mechanism to develop a successful therapy against GB progression.
A Left Ventricular Mechanical Dyssynchrony-Based Nomogram for Predicting Major Adverse Cardiac Events Risk in Patients With Ischemia and No Obstructive Coronary Artery Disease
Authors: Zhang Han , Shi Kuangyu , Fei Mengyu , Fan Xin , Liu Lu , Xu Chong , Qin Shanshan , Zhang Jiajia , Wang Junpeng , Zhang Yu , Lv Zhongwei , Che Wenliang , Yu Fei 
Published: March 2022

BackgroundThe risk stratification of patients with ischemia and no obstructive coronary artery disease (INOCA) remains suboptimal. This study aims to establish a left ventricular mechanical dyssynchrony (LVMD)-based nomogram to improve the present situation.MethodsPatients with suspected coronary artery disease (CAD) were retrospectively enrolled and divided into three groups: normal (stenosis &lt;50%, without myocardial ischemia), INOCA (stenosis &lt;50%, summed stress score &gt;4, summed difference score ≥2), and obstructive CAD (stenosis ≥50%). LVMD was defined by ROC analysis. INOCA group were followed up for the occurrence of major adverse cardiac events (MACEs: cardiovascular death, non-fatal myocardial infarction, revascularization, stroke, heart failure, and hospitalization for unstable angina). Nomogram was established using multivariate Cox regression analysis.ResultsAmong 334 patients (118 [35.3%] INOCA), LVMD parameters were significantly higher in INOCA group versus normal group but they did not differ between obstructive CAD groups. In INOCA group, 27 (22.9%) MACEs occurred during a 26-month median follow-up. Proportion of LVMD was significantly higher with MACEs under both stress (63.0% vs. 22.0%, P &lt; 0.001) and rest (51.9% vs. 20.9%, P = 0.002). Kaplan–Meier analysis revealed significantly higher rate of MACEs (stress log-rank: P = 0.002; rest log-rank: P &lt; 0.001) in LVMD patients. Multivariate Cox regression analysis showed that stress LVMD (HR: 3.82; 95% CI: 1.30–11.20; P = 0.015) was an independent predictor of MACEs. The internal bootstrap resampling approach indicates that the C-index of nomogram was 0.80 (95% CI: 0.71–0.89) and the AUC values for 1 and 3 years of risk prediction were 0.68 (95% CI: 0.46–0.89) and 0.84 (95% CI: 0.72–0.95), respectively.ConclusionLVMD-based nomogram might provide incremental prognostic value and improve the risk stratification in INOCA patients.
A Meta-Analysis of Teachers’ Job Burnout and Big Five Personality Traits
Authors: Liu Ziyan , Li Yingnan , Zhu Wenying , He Yuanping , Li Dongbin 
Published: March 2022

IntroductionTo explore the relationship between teachers’ job burnout and big five personality traits through meta-analysis.MethodsChinese and foreign databases, such as China Knowledge Network Infrastructure (CNKI), VIP Database, Wanfang database, Chinese excellent master’s degree full text, Science Direct, Web of science, Wiley online library, Springer link, Taylor &amp; Francis, and APA PsycNET, were searched, and the relevant literature was collected and screened for meta-analysis.ResultsA total of 28 literatures were included, and the total sample size was 12,103. Meta-analysis showed that the dimensions of emotional exhaustion and depersonalization were moderately negatively correlated with conscientiousness, openness, extroversion, and agreeableness, and the effect values were −0.20 (−0.26 ∼−0.13), −0.11 (−0.17 ∼−0.05), −0.18 (−0.24 ∼−0.12), −0.14 (−0.22 ∼−0.06), −0.27 (−0.33 ∼−0.22), −0.12 (−0.16 ∼−0.08), −0.19 (−0.24 ∼−0.14), and −0.28 (−0.36 ∼−0.19), respectively. The effect values were 0.30 (0.21 ∼ 0.40) and 0.26 (0.17 ∼ 0.34). The dimension of low sense of achievement was negatively correlated with the five dimensions of conscientiousness, openness, neuroticism, extroversion and agreeableness of the big five personality traits, and the influence values were −0.02 (−0.18 ∼ 0.13), −0.02 (−0.14 ∼ 0.10), −0.03 (−0.16 ∼ 0.10), −0.04 (−0.18 ∼ 0.19), −0.05 (−0.16 ∼ 0.06) respectively. The correlation between each dimension of big five personality traits and each dimension of teachers’ job burnout is adjusted by teaching segment, region, big five personality traits scale, and publication age.ConclusionThe dimensions of emotional exhaustion and depersonalization are negatively correlated with conscientiousness, openness, extroversion, and agreeableness, and positively correlated with neuroticism. The dimension of low personal achievement is negatively correlated with the dimensions of big five personality traits. According to the results of this study, teachers generally have the problem of job burnout, and their personality characteristics have a significant impact on job burnout. School managers should pay attention to this problem and implement necessary interventions. At the same time, the conclusions of this study also provide some guiding significance for teachers’ career development.
WGCNA, LASSO and SVM Algorithm Revealed RAC1 Correlated M0 Macrophage and the Risk Score to Predict the Survival of Hepatocellular Carcinoma Patients
Authors: You Ji-An , Gong Yuhan , Wu Yongzhe , Jin Libo , Chi Qingjia , Sun Da 
Published: March 2022

Background: RAC1 is involved in the progression of HCC as a regulator, but its prognostic performance and the imbalance of immune cell infiltration mediated by it are still unclear. We aim to explore the prognostic and immune properties of RAC1 in HCC.Methods: We separately downloaded the data related to HCC from the Cancer Genome Atlas (TCGA) and GEO database. CIBERSORT deconvolution algorithm, weighted gene co-expression network analysis (WGCNA) and LASSO algorithm participate in identifying IRGs and the construction of prognostic signatures.Results: The study discovered that RAC1 expression was linked to the severity of HCC lesions, and that its high expression was linked to a poor prognosis. Cox analysis confirmed that RAC1 is a clinically independent prognostic marker. M0, M1 and M2 macrophages’ abundance are significantly different in HCC. We found 828 IRGs related to macrophage infiltration, and established a novel 11-gene signature with excellent prognostic performance. RAC1-based risk score and M0 macrophage has a good ability to predict overall survival.Conclusion: The immune state of irregular macrophage infiltration may be one of the precursors to carcinogenesis. The RAC1 correlated with M0 macrophage and the risk score to show a good performance to predict the survival of HCC patients.
Retinoblastoma Protein Paralogs and Tumor Suppression
Authors: Flores Mauricio , Goodrich David W. 
Published: March 2022

The retinoblastoma susceptibility gene (RB1) is the first tumor suppressor gene discovered and a prototype for understanding regulatory networks that function in opposition to oncogenic stimuli. More than 3 decades of research has firmly established a widespread and prominent role for RB1 in human cancer. Yet, this gene encodes but one of three structurally and functionally related proteins that comprise the pocket protein family. A central question in the field is whether the additional genes in this family, RBL1 and RBL2, are important tumor suppressor genes. If so, how does their tumor suppressor activity overlap or differ from RB1. Here we revisit these questions by reviewing relevant data from human cancer genome sequencing studies that have been rapidly accumulating in recent years as well as pertinent functional studies in genetically engineered mice. We conclude that RBL1 and RBL2 do have important tumor suppressor activity in some contexts, but RB1 remains the dominant tumor suppressor in the family. Given their similarities, we speculate on why RB1 tumor suppressor activity is unique.
Follow-Up Comparison of Fluorescence Optical Imaging With Musculoskeletal Ultrasound for Early Detection of Psoriatic Arthritis
Authors: Büttner Juliane , Glimm Anne-Marie , Kokolakis Georgios , Erdmann-Keding Magdalena , Burmester Gerd-Rüdiger , Hoff Paula , Klotsche Jens , Ohrndorf Sarah 
Published: March 2022

ObjectivesEarly diagnosis of psoriatic arthritis (PsA) is crucial for a patient outcome but hampered by heterogenous manifestation and a lack of specific biomarkers. We recently showed that fluorescence optical imaging (FOI) can differentiate between patients with confirmed and suspected PsA. This study aims to follow-up (FU) patients with confirmed and suspected PsA focusing on patients with a change from suspected to confirmed PsA by the use of FOI in comparison with musculoskeletal ultrasound (MSUS).MethodsFollow-up examination of patients included in the study performed by Erdmann-Keding et al. in which FOI of both hands was performed in a standardized manner using three predefined phases (p1–p3) and PrimaVista Mode (PVM). The comparison was drawn to grayscale–power Doppler (GS/PD) MSUS of the clinically dominant hand (wrist, MCP, PIP, DIP 2–5) from dorsal or palmar.ResultsPatients with a change from suspected to diagnosed PsA showed an increased prevalence of joints with pathological enhancement in FOI (p = 0.046) with an unchanged joint distribution pattern, especially with a dominant involvement of DIP joints. Compared to the baseline, these patients were three times more common to show enhancement in FOI p3 at FU. Newly detected pathologic joints by FOI (PVM, p2) and MSUS at FU were positively associated with the change of diagnosis from suspected to confirmed PsA (FOI: AUC 0.78; GSUS: AUC 0.77).ConclusionFluorescence optical imaging appears to be a helpful tool to detect early PsA and to distinguish between acute and chronic disease stages. It could thereby become a suitable tool as a screening method to select psoriasis patients with an indication for further rheumatological evaluation.
Population Diversity of Antibiotic Resistant Enterobacterales in Samples From Wildlife Origin in Senegal: Identification of a Multidrug Resistance Transposon Carrying blaCTX–M–15 in Escherichia coli
Authors: Abdallah Rim , Kuete Yimagou Edmond , Hadjadj Linda , Mediannikov Oleg , Ibrahim Ahmad , Davoust Bernard , Barciela Amanda , Hernandez-Aguilar R. Adriana , Diatta Georges , Sokhna Cheikh , Raoult Didier , Rolain Jean-Marc , Baron Sophie Alexandra 
Published: March 2022

IntroductionThe role of wildlife in the transmission of antimicrobial resistant (AMR) is suspected but scarcely reported in current studies. Therefore, we studied the dynamics and prevalence of antibiotic-resistant Enterobacterales in antibiotic-limited areas of Senegal.Materials and MethodsWe collected fecal samples from monkeys and apes (N = 226) and non-fecal environmental samples (N = 113) from Senegal in 2015 and 2019. We grew the samples on selective media, subsequently isolated AMR Enterobacterales, and then sequenced their genomes.ResultsWe isolated 72 different Enterobacterales among which we obtained a resistance rate of 65% for colistin (N = 47/72) and 29% for third generation-cephalosporin (C3G) (29%, N = 21/72). Interestingly, almost 46% of our isolates, among Enterobacter sp., Citrobacter cronae and Klebsiella aerogenes, belong to 34 new STs. Moreover, the genes blaCTX–M–15, blaTEM1B, sul2, dfrA14, qnrs, aph(3′′), aph(6), tetA, and tetR harbored within a transposon on the IncY plasmid of ST224 Escherichia coli were transferred and inserted into a ST10 E. coli phage coding region.ConclusionWildlife constitutes a rich, unexplored reservoir of natural microbial diversity, AMR genes and international resistant clones pathogenic in humans. The presence of a transposon that carries AMR genes is intriguing since no antibiotics are used in the non-human primates we studied.
Systemic Glycemic Variation Predicts Mortality of Acute Ischemic Stroke After Mechanical Thrombectomy: A Prospective Study Using Continuous Glucose Monitoring
Authors: Deng Jiangshan , Li Ling , Cao Fengya , Wang Feng , Wang Hongmei , Shi Hong , Shen Li , Zhao Fei , Zhao Yuwu 
Published: March 2022

ObjectiveWe investigated the association of glycemic variation with the clinical outcomes of large vessel occlusion (LVO) induced acute ischemic stroke (AIS) after mechanical thrombectomy (MT).MethodsWe recruited consecutive ischemic patients with stroke. Glucose levels were assessed through continuous glucose monitoring in 70 patients with AIS who had undergone MT. Metrics including percentages of time of glucose levels above the range, the hypoglycemic range, and the time within the range, coefficient of variation, standard deviation (SD), mean of daily differences, mean amplitude of glycemic excursion, largest amplitude of glycemic excursion, high blood glucose index, and low blood glucose index. The outcomes of this observational study were in-hospital mortality, neurological improvement during hospitalization, functional independence, and mortality at follow-up (3 months). The associations of the blood glucose metrics with outcomes were analyzed.ResultsThe average period of glucose monitoring was 3.5 days, and serum glucose was recorded 728 times after MT for each person. The glycemic variation expressed in SDs was independently associated with in-hospital mortality [odds ratio (OR): 2.8, 95% confidence interval (CI): 1.276–6.145, p = 0.01] and the 3-month mortality (OR: 2.107, 95% CI: 1.013–4.382, p = 0.046) after adjusting for potential confounders. There was no association of glycemic variation with the 3-month clinical functional independence.ConclusionsIncreased systemic glycemic variation was associated with higher odds of mortality of LVO-AIS after MT.Clinical Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=21016, identifier: ChiCTR-OOC-17012378.
Fucoidan Alleviates Renal Fibrosis in Diabetic Kidney Disease via Inhibition of NLRP3 Inflammasome-Mediated Podocyte Pyroptosis
Authors: Wang Mei-Zi , Wang Jie , Cao Dong-Wei , Tu Yue , Liu Bu-Hui , Yuan Can-Can , Li Huan , Fang Qi-Jun , Chen Jia-Xin , Fu Yan , Wan Bing-Ying , Wan Zi-Yue , Wan Yi-Gang , Wu Guo-Wen 
Published: March 2022

Background: Fucoidan (FPS) has been widely used to treat renal fibrosis (RF) in patients with diabetic kidney disease (DKD); however, the precise therapeutic mechanisms remain unclear. Recently, research focusing on inflammation-derived podocyte pyroptosis in DKD has attracted increasing attention. This phenomenon is mediated by the activation of the nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to RF during DKD progression. Therefore, we designed a series of experiments to investigate the ameliorative effects of FPS on RF in DKD and the mechanisms that are responsible for its effect on NLRP3 inflammasome-mediated podocyte pyroptosis in the diabetic kidney.Methods: The modified DKD rat models were subjected to uninephrectomy, intraperitoneal injection of streptozotocin, and a high-fat diet. Following induction of renal injury, the animals received either FPS, rapamycin (RAP), or a vehicle for 4 weeks. For in vitro research, we exposed murine podocytes to high glucose and MCC950, an NLRP3 inflammasome inhibitor, with or without FPS or RAP. Changes in the parameters related to RF and inflammatory podocyte injury were analyzed in vivo. Changes in podocyte pyroptosis, NLRP3 inflammasome activation, and activation of the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (mTORC1)/NLRP3 signaling axis involved in these changes were analyzed in vivo and in vitro.Results: FPS and RAP ameliorated RF and inflammatory podocyte injury in the DKD model rats. Moreover, FPS and RAP attenuated podocyte pyroptosis, inhibited NLRP3 inflammasome activation, and regulated the AMPK/mTORC1/NLRP3 signaling axis in vivo and in vitro. Notably, our data showed that the regulative effects of FPS, both in vivo and in vitro, on the key signaling molecules, such as p-AMPK and p-raptor, in the AMPK/mTORC1/NLRP3 signaling axis were superior to those of RAP, but similar to those of metformin, an AMPK agonist, in vitro.Conclusion: We confirmed that FPS, similar to RAP, can alleviate RF in DKD by inhibiting NLRP3 inflammasome-mediated podocyte pyroptosis via regulation of the AMPK/mTORC1/NLRP3 signaling axis in the diabetic kidney. Our findings provide an in-depth understanding of the pathogenesis of RF, which will aid in identifying precise targets that can be used for DKD treatment.
Genetic Polymorphisms and the Clinical Response to Systemic Lupus Erythematosus Treatment Towards Personalized Medicine
Authors: Barliana Melisa Intan , Afifah Nadiya Nurul , Amalia Riezki , Hamijoyo Laniyati , Abdulah Rizky 
Published: March 2022

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a broad spectrum of clinical manifestations, an aberrant autoimmune response to self-antigens, which affect organs and tissues. There are several immune-pathogenic pathways, but the exact one is still not well known unless it is related to genetics. SLE and other autoimmune diseases are known to be inseparable from genetic factors, not only pathogenesis but also regarding the response to therapy. Seventy-one human studies published in the last 10 years were collected. Research communications, thesis publication, reviews, expert opinions, and unrelated studies were excluded. Finally, 32 articles were included. A polymorphism that occurs on the genes related to drugs pharmacokinetic, such as CYP, OATP, ABC Transporter, UGT, GST or drug-target pharmacodynamics, such as FCGR, TLR, and BAFF, can change the level of gene expression or its activity, thereby causing a variation on the clinical response of the drugs. A study that summarizes gene polymorphisms influencing the response to SLE therapy is urgently needed for personalized medicine practices. Personalized medicine is an effort to provide individual therapy based on genetic profiles, and it gives better and more effective treatments for SLE and other autoimmune disease patients.
Therapeutic Drug Monitoring of Anti-Thymocyte Globulin in Allogeneic Stem Cell Transplantation: Proof of Concept
Authors: Meesters-Ensing J.I. , Admiraal R. , Ebskamp L. , Lacna A. , Boelens J. J. , Lindemans C. A. , Nierkens S. 
Published: March 2022

Anti-thymocyte globulin (ATG), a polyclonal antibody, is used in allogeneic hematopoietic cell transplantation (HCT) to prevent graft-vs.-host-disease (GvHD) and graft failure (GF). Overexposure to ATG leads to poor early T-cell recovery, which is associated with viral infections and poor survival. Patients with severe inflammation are at high risk for GF and GvHD, and may have active infections warranting swift T-cell recovery. As ATG exposure may be critical in these patients, individualized dosing combined with therapeutic drug monitoring (TDM) may improve outcomes. We describe the individualized dosing approach, an optimal sampling scheme, the assay to measure the active fraction of ATG, and the workflow to perform TDM. Using a previously published population pharmacokinetic (PK) model, we determine the dose to reach optimal exposures associated with low GvHD and rejection, and at the same time promote T-cell recovery. Based on an optimal sampling scheme, peak and trough samples are taken during the first 3 days of once-daily dosing. The fraction of ATG able to bind to T-cells (active ATG) is analyzed using a bio-assay in which Jurkat cells are co-cultured with patient’s plasma and the binding is quantified using flow cytometry. TDM is performed based on these ATG concentrations on the third day of dosing; subsequent doses can be adjusted based on the expected area under the curve. We show that individualized ATG dosing with TDM is feasible. This approach is unique in the setting of antibody treatment and may result in better immune reconstitution post-HCT and subsequently better survival chances.