bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oct4 Cooperates with c-Myc to Improve Mesenchymal-to- Endothelial Transition and Myocardial Repair of Cardiac-Resident Mesenchymal Stem Cells
Authors: Zhao Lan , Deng Zhanyu , Wang Jianshuo , Cui Jin , Huang Weiguang , Zhang Shaoheng 
Published: April 2022

Abstract
BACKGROUND
Cardiac-resident mesenchymal stem cells (cMSCs) can exhibit fibrotic, proinflammatory, and proangiogenic phenotype in response to myocardial ischemia (Isch). How their phenotypic fate decisions are determined remains poorly understood. Here, we demonstrate that the cooperation of Oct4 and c-Myc in cMSCs creates a preferable mesenchymal-to- endothelial transition (MEndoT) to promote angiogenesis and consequent myocardial repair.
METHODS
We collected MSCs from cardiac and peripheral blood of rat with left ventricular Isch (LV Isch) 30 days after myocardial infarction (MI) or sham operation. After a comparison of characterization between cMSCs and peripheral blood MSCs (pbMSCs), we conducted transcriptome analysis and RNA sequencing of cMSCs. Using loss/gain-of-function approaches to understand the cooperation of c-Myc and Oct4 on MEndoT of cMSCs under hypoxic condition, we explored the mechanisms through transcriptome and functional experiment, and chromatin immunoprecipitation. Next, we transplanted male cMSCs with overexpression or inhibition of c-Myc/Oct4 into the infarcted myocardium of female rats and evaluated infarct size, cell retention, inflammation, remodeling, and function after 30 days.
RESULTS
LV Isch switched cMSCs toward both inflammatory and proangiogenic phenotypes, with increased secretion of inflammatory cytokines as well as pro-angiogenic factors. The effect of LV Isch on pbMSCs was less remarkable. Gene expression heatmap showed imbalance in expression of Oct4 and c-Myc regulating genes associated with remodeling of cMSCs. We provided evidence that cMSCs-sepcific c-Myc- versus Oct4-overexpression showed divergent genomic signatures, and their corresponding target genes play an important role in regulating cMSCs phenotypic changes. In particular, Oct4 accelerated angiogenesis induced by c-Myc overexpression in cMSCs, and inhibited their phenotypic transition into inflammatory cells and fibroblast. Mechanistically, exogenous Oct4 caused c-Myc to translocate from the nucleus to the cytoplasm and activated some of its target singalings including VEGF signaling. Although transplantation of cMSCs alone did not improve LV remodeling and function, cMSCs cotransfected with c-Myc and Oct4 promoted a more positive effect in their survival and reparative properties, improved animal survival, reduced infarct size, decreased scar thickness, and attenuated LV remodeling 30 days after MI. Significantly, Oct4 promoted MEndoT (“Rescue me” signal) of cMSCs after both c-Myc stimulation in vitro and transplantation into the infarcted heart.
CONCLUSIONS
Myocardial ischemia drives resident cMSCs toward multiple phenotypes. Oct4 interacts with c-Myc to promote MEndoT capacity of cMSCs and improved their survival and reparative effects through upregulation of angiogenesis-related signaling pathways. These findings may identify novel targets for stem cell therapy.
Design of novel benzylidenecyclohexenones derivatives as potential anti-cancer inhibitors using 3D-QSAR, pharmacokinetics, and molecular docking studies.
Authors: Er-rajy Mohammed , Mrabti Nidal Naceiri , Zarougui Sara , Elhallaoui Menana 
Published: April 2022

Abstract
The 3D-QSAR models were established in this study based on comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA), the optimal CoMFA model established gave \({\text{Q}}^{2}\)= 0.671, \({\text{R}}^{2}\)= 0.925 and \({\text{R}}_{\text{p}\text{r}\text{e}\text{d} }^{2}\)= 0.868, and the best CoMSIA/SEA model gave \({\text{Q}}^{2}\)= 0.627, \({\text{R}}^{2}\)= 0.775, and \({\text{R}}_{\text{p}\text{r}\text{e}\text{d} }^{2}\)= 0.962. The predictive ability of the developed models was evaluated by external and internal validation. In this study, steric, electrostatic, and hydrogen bond acceptor fields played a key role in the anti-cancer activity. Molecular docking results theoretically revealed the importance of residues ARG164 and THR45 in the active site of the TrxR enzyme. Based on these results, we designed several new inhibitors, and their inhibitory activities were predicted by the best model (CoMFA). In addition, these new inhibitors were analyzed for their ADMET properties and their similarity to drugs. These results will be of great help for the optimization of new anti-cancer drug discovery.
Comprehensive analysis of negatively correlated miRNA-mRNA regulatory pairs associated with breast cancer diagnosis
Authors: Xia Tiansong , Li Jiaying , Fan Xingchen , Zou Xuan , Liu Cheng , Wang Tongshan , Peng Shuang , Zhu Wei 
Published: April 2022

Abstract
Purpose： MicroRNAs (miRNAs) represent small noncoding RNAs controlling mRNA expression. MiRNA and mRNA amounts in matching specimens were utilized for identifying miRNA–mRNA interactions. Transcriptome, immunophenotype, methylation, mutation, and survival data analyses were integrated to examine the profiles of miRNAs and target mRNAs and their associations with breast cancer (BC) diagnosis.Methods: Based on the mRNA/miRNA expression microarray and RNA-Seq data sets in the GEO database and RNA-Seq data in TCGA, we analyzed differential expression profiles through GEO2R and the R language. Differentially expressed miRNAs and targeted mRNAs were screened from experimentally verified miRNA-target interactions databases by Pearson's correlation analysis. qRT-PCR was used for verification in breast cancer and benign disease samples, and logistic regression analysis was utilized to establish a diagnostic model based on miRNAs and target mRNAs. ROC curve analysis was performed to test the ability to recognize miRNA-mRNA pairs. Then, complex interactions of miRNA-mRNA regulatory pairs and phenotypic hallmarks, including tumor-infiltrating lymphocytes, tumor microenvironment, tumor mutation burden and global methylation, were described.Result: We first identified 27 dysregulated miRNAs and 135 dysregulated mRNAs based on five gene expression and 21 miRNA expression data sets from GEO and RNA-Seq data from TCGA. Utilizing Pearson's correlation analysis, ten negative miRNA-mRNA regulatory pairs were identified after screening in TarBase and miRTarBase databases, and related miRNA and target mRNA amounts were assessed in 40 breast cancer tissue and 40 breast benign disease tissue. Finally, 2 key regulatory pairs (miR-205-5p/HMGB3 and miR-96-5p/FOXO1) were selected to establish a diagnostic model. We next analyzed the functions of these four markers in breast cancer.Conclusions: A diagnostic model including two miRNAs and their respective target mRNAs was established to distinguish BCs and benign breast diseases. These markers play an essential role in the pathogenesis of BC.
Effectiveness of acrylonitrile-co-methallyl sulfonate surface-treated membranes for treating pneumonia: A propensity-score matched retrospective cohort study
Authors: Hayashi Kentaro , Sasabuchi Yusuke , Matsui Hiroki , Nakajima Mikio , Ohbe Hiroyuki , Fushimi Kiyohide , Ono Kazuyuki , Yasunaga Hideo 
Published: April 2022

Abstract
Background: The acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane has cytokine adsorption capacity and is used for treating sepsis. This study aimed to compare the effects of continuous renal replacement therapy (CRRT) using the AN69ST membrane with CRRT using other membranes for patients with pneumonia-associated sepsis.Methods: We conducted a retrospective cohort study using a nationwide Japanese inpatient database. We included data of those adults who were hospitalized with a primary diagnosis of pneumonia and received CRRT using either the AN69ST membrane or another membrane within 2 days of admission and were discharged from the hospitals between September 2014 and March 2017. Propensity-score matching was used to compare in-hospital mortality between the two groups.Results: Eligible patients (N = 2,393) were categorized into an AN69ST group (N = 631) and a non-AN69ST group (N = 1,762). The overall in-hospital mortality rate was 38.9%. Among the 545 propensity-matched patient pairs, the in-hospital mortality rate was significantly lower in the AN69ST group than in the non-AN69ST group (35.8 vs. 41.8%, P = 0.046).Conclusions: Among patients with pneumonia-associated sepsis treated with CRRT, CRRT with the AN69ST membrane was associated with a significantly lower in-hospital mortality than CRRT with standard membranes.
The Hypothalamic-Pituitary-Gonad Axis in Male Cushing’s disease Before and After Curative Surgery
Authors: Zheng Hangping , Wang Qi , Cui Qiaoli , Sun Quanya , Wu Wei , Ji Lijin , He Min , Lu Bin , Zhang Zhaoyun , Ma Zengyi , Shen Ming , Shou Xuefei , Wang Yongfei , Zhao Yao , Li Yiming , Ye Hongying , Zhang Shuo 
Published: April 2022

Abstract
Objective: Gonadal and sexual disturbances are commonly encountered in patients with Cushing’s disease. Nevertheless, the prevalence of hypogonadism in male Cushing’s disease, the risk factors as well as the recovery time have been scarcely reported. Therefore, we aimed to explore the prevalence of hypogonadism at baseline and its determinants. In addition, the recovery time of hypogonadism and risk factors for unrecovered gonadal axis in male Cushing’s disease with biochemical remission were investigated.Methods: We reviewed medical records of males with Cushing’s disease managed between 2010 and 2020. Fifty-two male patients were enrolled according to the criteria. Each case attained biochemical remission after transsphenoidal surgery. Demographic details, clinical features, 24-hour UFC, hormonal profile [serum PRL, FSH, LH, TT, ACTH, cortisol, TT4/FT4, TT3/ FT3, TSH and IGF-1] were measured at baseline and during follow-up. The maximal tumor diameter on MRI was recorded at diagnosis.Results: Hypogonadotropic hypogonadism was observed in thirty-nine patients (75%) at diagnosis. Total testosterone was negatively correlated with ACTH and 24-hour UFC. Midnight serum ACTH level at diagnosis was significantly associated with hypogonadism after adjusting for confounding factors. Thirty-two (80%) patients achieved eugonadism within 12 months after the surgery, of which twenty-eight (87.5%) achieved eugonadism within 3 months. Seven patients were persistently hypogonadal during the follow-up (>1 year), mainly due to the hypopituitarism as a complication of the therapies such as surgery.Conclusion: Hypogonadotropic hypogonadism is frequent in male Cushing’s disease, but it is reversible in most cases within one-year follow-up after remission.
Assessment of farmers’ socioeconomic and conservation practice towards watershed management in the South West of Ethiopia
Authors: Woldeab Bizuneh , Ambelu Argaw , Beyene Abebe , Efrem Zewdu , Deribe Siyoum , Megersa Moa , Alemu Tibebu , Mereta Seid Tiku 
Published: April 2022

Abstract
Background
Watershed resource conservation is important for the wellbeing of the environment and communities. Understanding farmers’ socioeconomics and watershed conservation practices help in determining necessary interventions to address environmental threats. The study area is important at regional and national level due to the hydroelectric dam of the mega power project. This study deals with the farmers’ socio economic and conservation practices of Gilgel Gibe watershed. The study targeted 305 households in 4 districts of Jimma Zone surrounding the Gilgel Gibe Reservoir I. Semi-structured questionnaire was administered via interviews and focus group discussions led by trained survey interviewers.
Result
The findings of the study indicated that majority of farmers in the watershed have adequate knowledge, positive attitude and bad practice towards watershed conservation. To achieve better means of subsistence and improve their living condition farmers are forced to put stress on natural resource, degrading watershed and increase pollution loads that affect water quality of tributaries and reservoir.
Conclusion
Based on the present scenario, we forwarded stakeholders to establish team from the elders, officials at woreda and zonal level to initiate commitment, coordinate conservation activity and promote households’ income generating activities at homestead level like conservation agriculture.
Preparation and Validation of Ultra-sensitive Aptamers by Computer Simulation and Site- specific Mutation
Authors: Sha Junyi , Lin Hong , Zhang Ziye , Sui Jianxin 
Published: April 2022

Abstract
Aptamers are widely used in the detection field as a new type of probe due to their advantages of easy synthesis and modification. Due to the traditional aptamer screening method, the aptamers which are screened by SELEX technology generally have redundant sequences, which affect the binding affinity and detection sensitivity. In this study, a structural transformation strategy for rationally shortening was established by analyzing the secondary structure, finding the sequence of the binding site by base mutation and double cloning the binding sites. We obtained a 27-mer new aptamer SEQ.A52 with the dissociation constants (Kd) of 10.74 nM which is 21 times higher than the original aptamer. When used to detect enrofloxacin(ENR) with fluorescent method, the sensitivity could reach to 50 ~ 1000 pM and the limit of detections(LOD) was only 41.35 pM which was 88 times higher than the original aptamer. All the results implied that the strategy could be used for structural modification of some other aptamers to increase the affinity and sensitivity.
Preferential substrate use decreases priming effects in contrasting treeline soils
Authors: Michel Jennifer , Hartley Iain P. , Buckeridge Kate M. , Meegen Carmen van , Broyd Rosanne , Reinelt Laura , Quispe Adan J. Ccahuana , Whitaker Jeanette 
Published: April 2022

Abstract
In high altitudes and high latitudes climate change manifests in upward and northward shifting treelines. This entails changes to the carbon (C) and nitrogen (N) composition of organic inputs to soils and can increase or decrease microbial mineralisation of native soil organic matter (positive or negative priming effect). It is currently unknown whether the observed treeline shifts will lead to carbon loss or storage in the soils of these ecosystems.
We therefore investigated priming effects in treeline soils from high altitudes (Peruvian Andes) and high latitudes (subarctic Sweden). In a laboratory soil incubation, we added realistic amounts of organic carbon at a constant ratio of 30% substrate-C to each soils’ microbial biomass C. Substrate additions were neutral in pH and covered different C:N ratios, representing naturally occurring substances of the studied ecosystems.
We observed a clear pattern linking the direction of priming (positive or negative) to land cover (boreal or tropical forest, tundra heath, Puna grassland) and soil horizon (organic or mineral). Mechanistically, no support was found for N-mining to induce positive priming, indeed half of all priming effects were negative. Whenever negative priming prevailed, the decrease in SOM-mineralisation was consistently linked to increased microbial substrate utilisation.
In line with other recent studies, our results suggest preferential substrate use is pervasive, linked to negative priming and a promising tool to increase soil carbon storage. Yet, the positive priming observed alerts climate change-induced upwards shifts in high altitudes and deeper rooting plants in high latitudes may cause C-loss via positive priming.
Efficacy of Cholecalciferol rodenticide against Wood Rat, Rattus tiomanicus and its secondary poisoning impact towards Barn Owl, Tyto javanica javanica
Authors: Noh Ariff Ateed Mohd , Ahmad Abu Hassan , Salim Hasber 
Published: April 2022

Abstract
Studies were conducted on the potential use of cholecalciferol as an alternative to anticoagulant rodenticides against common rat pest in oil palm plantations, i.e., wood rats, Rattus tiomanicus, and the secondary poisoning impact of cholecalciferol on barn owls, Tyto javanica javanica. The laboratory efficacy of cholecalciferol was compared with commonly used first-generation anticoagulant rodenticides (FGARs): chlorophacinone (0.005% a.i) and warfarin (0.05% a.i). The results of the study showed cholecalciferol baits recorded high mortality at 71.39% against wild wood rats in six-day feeding laboratory trial. Similarly, the FGAR chlorophacinone recorded a high mortality rate of 74.20%. Warfarin baits recorded the lowest mortality rate at 46.07% against the rat samples. The days-to-death of rat samples was in range of 6-8 days. The highest daily consumption of bait by rat samples was recorded by warfarin at 5.85±0.38 gram per day while the lowest was recorded in rat samples fed with cholecalciferol, i.e., 3.03±0.20 gram per day. Chlorophacinone-treated and control rat samples recorded consumption of about 5 gram per day. A secondary poisoning assessment on barn owls in captivity fed with cholecalciferol-poisoned rats showed after 7 days of alternate feeding, the barn owls appeared to remain healthy. All the barn owls fed with cholecalciferol-poisoned rats survived the 7-day alternate feeding test and throughout the study, up to six months after exposure. All the barn owls did not show any abnormal behavior or physical change. The barn owls were observed to be as healthy as the barn owls from the control group throughout the study.
Comprehensive Analysis of the Expression and Prognosis Value of Claudin Family Members in Clear Cell Renal Cell Carcinoma
Authors: dang qihua , Chen Rui , Xu Jingjing , Jiang Ke , Lin Yun , He Miaoxia 
Published: April 2022

Abstract
Background
Clear cell renal cell carcinoma (ccRCC) accounts for 80% of all renal cancers and has a poor prognosis. The claudin (CLND) family comprises a group of transmembrane proteins associated with tight junctions (TJs). Studies have found that the abnormal expression of CLNDs can influence TJ-function and plays an important role in the occurrence, development, and metastasis of malignant tumors in a variety of epithelial malignant tumors. However, the roles of the different CLND family members in ccRCC are poorly understood.
Results
Using the GEPIA, UALCAN, HPA, Kaplan-Meier Plotter, cBioPortal, String-DB, GeneMANIA, Metascape, and TIMER databases, we found that the expression levels of CLDN7, 8, 10, 11, 14, 16, and 19 were significantly reduced in ccRCC-affected tissues than in healthy kidney tissues. Promoters were hypermethylated in ccRCC cells. ccRCC patients with low expression levels exhibited a strong association with the clinical cancer stage, tumor grade, and poor overall survival. The functions of the differentially expressed CLDNs were primarily associated with epithelial cell differentiation and regulation of cell adhesion. Moreover, differential expression were significantly correlated with the infiltration of diverse immune cells, including six types of CD4 + T cells, macrophages, neutrophils, B cells, CD8 + T cells, and dendritic cells in ccRCC.
Conclusions
CLDN family members are expected to serve as biomarkers for predicting the prognosis of ccRCC patients.
Exercise therapy with multiple myeloma patients: Evaluation of real-life data from an oncologic care structure on feasibility, adherence, and efficacy
Authors: Wefelnberg Michael Mendes , Niels Timo , Holtick Udo , Jundt Franziska , Scheid Christoph , Baumann Freerk T. 
Published: April 2022

Abstract
Purpose: Multiple myeloma (MM) is a severe hemato-oncological disease with high mortality and increasing incidence rate. Since evidence on exercise therapy in MM patients remains limited, this study examines feasibility, adherence, and efficacy based on real-life data from an oncologic care structure.Methods: A data evaluation of MM patients who participated in the oncologic exercise and movement therapy (OTT) at the Cologne University Hospital between 2012 and 2019 was conducted. The patient flow was incrementally reduced to four cohorts, intention-to-treat cohort (ITTC), safety cohort (SC), adherence cohort (AC) and efficacy cohort (EC). Cohorts were evaluated descriptively and by means of correlation analysis as well as group and, time comparisons. Results: 30 patients registered at the OTT between 2012 and 2019 (ITTC). The SC (N = 26) attended exercise therapy on average about one session per week over a period of eight month. One third dropped-out within three months. In the AC (N = 15) BMI at baseline exhibited a strong and very significant negative correlation with exercise adherence. In the EC (N = 8), a significant improvement in physical functioning and a tendency towards significance in fatigue reduction between two measurement points was observed. No adverse events were documented. Conclusions: The present study reveals safety, feasibility and promising findings on adherence and efficacy of exercising MM patients under real-life therapy circumstances. Potential obstacles to exercising such as high BMI might indicate hints for future research. Improvements in physical functioning and tendencies in fatigue reduction should be examined in confirmatory study designs.
Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study
Authors: Pignon Baptiste , Peyre Hugo , Ayrolles Anaël , Kirkbride James , Jamain Stéphane , ferchiou AZIZ , Richard Jean-Romain , Baudin Grégoire , Tosato Sarah , Jongsma Hannah , De Haan Lieuwe , Tarricone Ilaria , Bernardo Miquel , Velthorst Eva , braca mauro , Arango Celso , Arrojo Manuel , Bobes Julio , Del-Ben Cristina , Forti Marta di , Gayer-Anderson Charlotte , Jones Peter , Lasalvia Antonio , Menezes Paulo , Quattrone Diego , Sanjuan Julio , Selten Jean-Paul , Tortelli Andrea , Llorca Pierre Michel , Os Jim van , Rutten Bart , Murray Robin , Morgan Craig , Leboyer Marion , Szoke Andrei , Schurhof Franck 
Published: April 2022

Abstract
Gene x environment (GxE) interactions have not been reliably established regarding etiology of psychotic disorders, while genes-environment (G-E) associations have been displayed. We studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social capital) and the polygenic risk scores for schizophrenia (PRS-SZ) on subclinical psychosis in a population-based sample. Data were drawn from the EU-GEI study, in which subjects without psychotic disorders were included in six countries. The sample was restricted to European descendant subjects (N = 706). Subclinical dimensions of psychosis (positive, negative, and depressive) were measured by the Community Assessment of Psychic Experiences (CAPE) scale. For each dimension, the interactions between genes and environment were assessed comparing explained variances of “Genetic” models (solely fitted with PRS-SZ), “Environmental” models (solely fitted with each environmental stressor), “Independent” models (with PRS-SZ and each environmental factor), and “Interaction” models (with an interaction term between the PRS-SZ and each environmental factor). There were no direct G-E associations. PRS-SZ was associated with positive dimensions (ß = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except for low social capital and positive dimension). Concerning the positive dimension, Independent models fitted better than Environmental and Genetic models. No significant GxE interaction was observed for any dimension. This study in healthy individuals suggests that i) the etiological continuum hypothesis could concern particularly the positive dimension of subclinical psychosis, ii) genetic and environmental factors have independent effects on the level of this positive dimension, iii) and that interactions between genetic and individual environmental factors could not be identified in this sample.