bluuebunny/crossref_metadata_2025_split huggingface dataset:
USP7 Inhibition Induces Apoptosis in Glioblastoma by Stabilizing ARF4
Authors: Pan Tingzheng , Li Xuetao , Tao Zhennan , Yao Hui , Wu Yue , Chen Guangliang , Zhang Kai , Zhou Youxin , Huang Yulun 
Published: June 2021

Abstract
Background: Glioblastomas (GBMs) are grade IV central nervous system tumors characterized by a poor prognosis and a median overall survival of 15 months. The glioblastoma cell population is more genetically unstable, resistant to chemotherapy, more angiogenic, and more malignant. Because ubiquitin-specific proteases (USPs) remove ubiquitin from oncogenic protein substrates, effective inhibition of ubiquitin-specific protease 7 (USP7), which is highly expressed in GBMs, is a potentially critical therapeutic approach. Methods: Immunohistochemistry and Western blotting were used to detect high expression of USP7 in GBM. in vitro studies were performed by Western blotting, immunofluorescence, and flow cytometry to detect apoptosis following inhibition of USP7. Anti-apoptotic substrates of USP7 were defined by Co-IP and TMT proteomics. Nude mouse intracranial xenograft models were constructed to verify whether inhibition of USP7 inhibited the proliferation rate of tumours.Results: USP7 is significantly upregulated in glioblastoma samples. Interfering with USP7 in GBMs induced significant apoptosis, which also occurred after treatment with P5091, a novel small molecule inhibitor of USP7. Mechanistically, apoptosis of GBMs after interference with USP7 function is achieved by stabilizing a key anti-apoptotic protein, ADP-ribosylation factor 4 (ARF4).Furthermore, USP7 interacts directly with ARF4 and catalyzes the removal of the K48-linked polyubiquitinated chain that binds to ARF4, thereby stabilizing the protein. In in vivo experiments, P5091 significantly inhibited tumor growth and promoted the expression of apoptotic genes. Conclusion: Targeted inhibition of USP7 enhances the ubiquitination of ARF4 and ultimately mediates the apoptosis of GBM cells. In a clinical sense, P5091 as a specific inhibitor of USP7 may be an effective approach for the treatment of GBM.
Differentiating ability of haematological indicators: comparative blood test of sympatric rodent species of the subfamily Arvicolinae (Clethrionomys glareolus, Clethrionomys rutilus, and Craseomys rufocanus)
Authors: Orekhova Natali , Davydova Yu A. , Smirnov G. Yu. 
Published: June 2021

Abstract
Among the representatives of the subfamily Arvicolinae the interspecific differences (Clethrionomys glareolus, Clethrionomys rutilus, and Craseomys rufocanus) in the respiratory capacity of red blood and the immune status are presented in conjunction with the basal metabolic rate, the level of sociality and eurybionism, and thermoregulatory function. The degree of differentiation of voles in terms of haematological parameters has corresponded to the level of phylogenetic relationships between species. Correct conduct of interspecific comparisons of haematological parameters of voles is possible only within the same reproductive-age groups.
What is the Value and Impact of the Adaptation Process on Quality Indicators for Local Use? A Scoping Review
Authors: Zhu Siyi , Wu Tao , Leese Jenny , Li Linda C. , He Chengqi , Yang Lin 
Published: June 2021

Abstract
Background: Quality indicators (QIs) are designed for improving quality of care, but the development of QIs is resource intensive and time consuming. This study sought to describe and identify the impact and potential attributes of the adaptation process for the local use of existing QIs. Methods: EMBASE, MEDLINE, CINAHL and grey literature were searched for literature operationalizing or implementing QIs that were developed in a different jurisdiction from the place where the QIs were use. Two reviewers independently extracted and mapped data on study and participant characteristics, the adaptation process of QIs, aims and key findings of studies, from which the attributes of the adaptation process was analysed. The quality assessment was done with the SQUIRE tool.Results: Of 7704 citations identified, 10 out of 33 articles were included. All studies were assessed as high quality and most were from Europe. Our results revealed a lack of definition and conceptualization for a systematic adaptation processes in which an existing set of QIs was applied. Four out of ten studies involved a consensus process (e.g., Delphi or RAND process) to determine the suitability of QIs for local use. QIs for chronic conditions in primary and secondary settings were mostly used for adaptation. Of the ones that underwent a consensus process, 56.3 to 85.7% of original QIs were considered valid for local use, and 2 to 21.8% of proposed QIs were newly added. Combining all findings, four attributes should be included in a systematic approach of adaptation: 1) identification of areas/conditions for QIs adaptation and operationalization; 2) intermediate process with considerations of issues risen from adaptation; 3) introduction of a set of proposed QIs for local use; 4) operationalizing QIs and evaluating the applicability.Conclusion: The existing QIs, although serving as a good starting point, were poorly adapted before for use in a different jurisdiction from their origin. Adaptation of QIs under a systematic approach is critical. Therefore, we propose that a systematic adaptation approach including at least four attributes found by this study should be formulated to inform future research planning for QIs adaptation and potentially establishing a new pathway for healthcare improvement. Trial registration: PROSPERO (CRD42018096844).
Assessing Antibiotic Stewardship Program (ASP) Implementation: Psychometric Properties of Survey measures based on the Consolidated Framework for Implementation Research (CFIR)
Authors: Butler Jorie Michaela , Childs Ellen , Barlam Tamar F. , Drainoni Mari-Lynn , Reardon Caitlin , Zhang Yue , Damschroder Laura , Taber Peter , Madaras-Kelly Karl , Goetz Matthew Bidwell , Stenehjem Eddie , Shen Jincheng , Samore Matthew 
Published: June 2021

Abstract
Background: Antibiotic stewardship programs (ASPs) are crucial to prevent the emergence of antibiotic resistance and to improve outcomes for patients. Few measurement instruments examine ASP implementation. A validated instrument rooted in implementation science theory will increase our understanding of ASP implementation and enable comparisons across studies. Methods: We used the Consolidated Framework for Implementation Research (CFIR) to guide development of ASP implementation measures. Survey questions were developed by infectious disease and survey design experts to assess 22 potential determinants of implementation across five domains of the CFIR. Survey items were reviewed by CFIR experts for face and content validity. Antibiotic stewards (infectious disease pharmacists and physicians) were recruited from 154 Veterans Affairs (VA) hospital and Intermountain Healthcare (IH) sites to complete the survey. Survey responses were aggregated by site, and results were determined at the site level. We conducted confirmatory factor analyses (CFA) to assess structural validity of measures and evaluated inter-item consistency. Results: A total of 182 stewards completed the survey (155 VA and 27 IH responses). At least one response was obtained from 126 hospitals (81.8%). CFAs for most CFIR constructs exhibited good fit (CFI > .90; TLI > .90; RMSEA< .05, SRMR < .08). Scale reliabilities ranged from .54-.96 indicating low to strong inter-item consistency. Determinants that were rated highly present at the sites (across site means ³ 4.0 or above) included Self-Efficacy, Engaging, Evidence Strength and Quality and Relative Advantage, indicating stewards found ASP evidence compelling and felt their personal involvement was effective in engendering positive results for the ASP. Conclusions: Psychometric properties measured via CFA indicate validity of our CFIR-based measure of determinants for ASP implementation outcomes. This is the first validated set of measures based on the CFIR for ASP implementation and the first to include measures for 4 out of five CFIR domains. These validated measures will help to provide much needed understanding of barriers and facilitators of ASP implementation. Research and quality improvement teams can use these measures to identify contextual determinants of ASP implementation and use this information to guide selection of strategies and compare results across multiple studies.
Evaluation of Climate Change Impacts and Adaptation Options Using Risk-Based Hydro-Economic Model in Ajichay Basin, Iran
Authors: sani fatemeh , Dashti Ghader , Majnooni Abolfazl , Hosseinzad Javad 
Published: June 2021

Abstract
Climate change is one of the main issues in the 21st century and has been felt in many regions of world such as the Ajichay basin. The greatest impact of climate change is on the water resource sector. Projected changes in precipitation, temperature and river runoff will largely affect the water cycle and hydrological systems with important results for economic sector. Therefore, the current study aims to investigate the impact of climate and water management scenarios on water resources, cropping patterns, yields, and profits of farmers using a hydro-economic model. Quadratic risk programming was used for economic modeling, and WEAP-MABIA was applied for hydrological modeling. The necessary data were collected from questionnaires completed by 210 farmers selected by stratified random sampling during 2018. The HadCM3 model and LARS-WG downscaling were used to generate daily climatic data under the emissions of A2, B1, and A1B scenarios. The results showed that climate change could reduce the profit and employment rate in the agricultural sector and cause a shift in cropping patterns to crops with low water requirements. In addition to the efficient use of allocated water, the application of increasing irrigation efficiency scenario could raise farmers' profits, providing them with a better situation than the agricultural water reduction scenario. Overall, the findings of the current study revealed that without changing the management strategies there will be a considerable reduction in water resource and crop yield in near future.
The Landscape of Immune Cell Infiltration in the Glomerulus of Diabetic Nephropathy: Evidence Based on Bioinformatics
Authors: ZHOU Wei , LIU Yaoyu , HU Qinghong , ZHOU Jiuyao , LIN Hua 
Published: June 2021

Abstract
BackgroundIncreasing evidence suggests that immune cell infiltration contributes to the pathogenesis and progression of diabetic nephropathy (DN). We aim to unveil the immune infiltration pattern in the glomerulus of DN and provide potential targets for immunotherapy. MethodsInfiltrating percentage of 22 types of immune cell in the glomerulus tissues were estimated by the CIBERSORT algorithm based on three transcriptome datasets mined from the GEO database. Differentially expressed genes (DEGs) were identified by the “limma” package. Then immune-related DEGs were identified by intersecting DEGs with immune-related genes (downloaded from Immport database). The protein-protein interactions of Immune-related DEGs were explored using the STRING database and visualized by Cytoscape. The enrichment analyses for KEGG pathways and GO terms were carried out by the gene set enrichment analysis (GSEA) method. Results9 types of immune cell were revealed to be significantly altered in the glomerulus tissues of DN (Up: B cells memory, T cells CD4 naive, Macrophages M2, Dendritic cells resting, Mast cells resting, Mast cells activated; Down: NK cells resting, Monocytes, Neutrophils). Correlation analysis revealed that immune infiltration act as a complicated and tightly regulated network, among which T cells gamma delta and T cells CD4 naive show the most synergistic effect (r = 0.58, p ＜ 0.001); meanwhile, T cells CD8 and T cells CD4 memory resting show the most competitive effect (r = - 0.67, p ＜ 0.001). Several pathways related to immune were significantly activated. Moreover, 6 hub genes with a medium to strong correlation with renal function (eGFR) were identified (ALB, EGF, FOS, CXCR1, CXCR2, CCL2). ConclusionIn the glomerulus of DN, the immune infiltration pattern changed significantly. A complicated and tightly regulated network of immune cells exists in the pathological of DN. The hub genes identified here will facilitate the development of immunotherapy.
A Combined Prediction Model for Biliary Tract Cancer using the Prognostic Nutritional Index and Pathological Findings: A Single-center Retrospective Study
Authors: Kitada Koji , Tokunaga Naoyuki , Kato Takamitsu , Narusaka Toru , Hamano Ryosuke , Miyasou Hideaki , Tsunemitsu Yousuke , Otsuka Shinya , Inagaki Masaru , Utsumi Masashi 
Published: June 2021

Abstract
Background: The prognostic nutritional index, a marker of nutritional status and systemic inflammation, is a known biomarker for various cancers. However, few studies have evaluated the predictive value of the prognostic nutritional index in patients with biliary tract cancer. Therefore, we investigated the prognostic significance of the prognostic nutritional index and developed a risk-stratification system to identify prognostic factors in patients with biliary tract cancer.Methods: Between July 2010 and March 2021, 117 patients with biliary tract cancer were recruited to this single-center retrospective study. The relationship between clinicopathological variables, including the prognostic nutritional index and overall survival, was analyzed using univariate and multivariate analyses. P < 0.05 was considered statistically significant.Results: The median age was 75 (range, 38–92) years. Thirty patients had intrahepatic cholangiocarcinoma; 29, gallbladder carcinoma; 28, distal cholangiocarcinoma; 16, ampullary carcinoma; and 13, perihilar cholangiocarcinoma. R0 resection was achieved in 99 patients. In univariate analysis, the prognostic nutritional index (< 42), lymph node metastasis, carbohydrate antigen 19-9 level (> 20 U/mL), preoperative cholangitis, tumor differentiation, operation time (≥ 360 minutes), and R1–2 resection were significant risk factors for overall survival. The prognostic nutritional index (P = 0.007), lymph node metastasis (P = 0.024), and tumor differentiation (P = 0.008) were independent prognostic factors in the multivariate analysis. A combined score of the prognostic nutritional index and pathological findings outperformed each marker alone, in terms of discriminatory power.Conclusions: The prognostic nutritional index, lymph node metastasis, and tumor differentiation were independent prognostic predictors after surgical resection in patients with biliary tract cancer. A combined prediction model using the prognostic nutritional index and pathological findings accurately predicted prognosis and can be applied as a novel prognostic indicator for patients with biliary tract cancer.
Analysis of Capability, Motivation and Opportunity to Prevent Substance Abuse in Sensation Seeking Students on the Outskirts of a City in Eastern Iran: A Qualitative Study Using a Focus Group Discussion
Authors: Mahmoodabad Seyed Saeed Mazloomy , Majd Hssein Mazhari , Mahmoodabadi Hassan Zareei , Miri Mohammad Reza 
Published: June 2021

Abstract
Background: Usually, substance abuse begins in adolescence. The prevalence of alcohol use among Iranian adolescents (15 to 18 years old) is 15%, opium use is 3.1%, and ecstasy use is 5.6%. Young people who score high on the sensation-seeking trait tend to be more prone to substance abuse and an early experience in using. In this respect, environmental factors also act as a mediator or moderator.According to the COM_B model (Capability (C), Opportunity (O), Motivation (M), Behavior (B)), substance abuse can be observed in situations where a person has the necessary physical and mental abilities, the necessary opportunities, and competing motivations.Methods: To better understand substance abuse preventions' capability, motivation, and opportunities, we conducted a focus group discussion with 18 participants (high school male students) from the outskirts of Birjand, who received a positive score from the Zuckerman Sensation Seeking Questionnaires' summary form. The group discussion was conducted using a guide to semi-structured questions based on COM-B model constructs. Results: Students' knowledge of substance cognition, side effects, and consequences of addiction were incomplete. Some students believed that substance use was a way to control or vent emotions and that smoking was a sedative, and private spaces and uncrowded public places were physical environments that students cited for engaging in substance use.Conclusions: In order to achieve more precise prevention interventions against adolescents' tendency for substance abuse and to have a more significant impact on their behaviors, it is beneficial to study the three identified factors in some of the target individuals before intervention.
Anomalous Origin of the Right Coronary Artery With Interarterial Course: Red Flag or Innocent Bystander?
Authors: Albuquerque Francisco , Gonçalves Pedro De Araújo , Marques Hugo , Ferreira António M. , Freitas Pedro , Lopes Pedro , Gonçalves Mariana , Dores Hélder , Cardim Nuno 
Published: June 2021

Abstract
Purpose: Anomalous origin of the right coronary artery from the opposite sinus (right-ACAOS) with interarterial course (IAC) has been associated with increased risk of sudden cardiac death (SCD). Widespread use of coronary computed tomography angiography (CCTA) has led to increasing recognition of this condition, even among healthy individuals. Our study sought to examine the prevalence, anatomical characteristics and outcomes of right-ACAOS with IAC in patients undergoing CCTA for suspected coronary artery disease (CAD).Methods: We conducted a retrospective analysis of consecutive patients referred for CCTA at one tertiary hospital from January 2012 to December 2020. Right-ACAOS with IAC patients were analyzed for cardiac symptoms and long-term occurrence of first MACE (SCD, non-fatal myocardial infarction (MI) or revascularization of the anomalous vessel). CCTAs were reviewed for anatomical high-risk features and concomitant CAD. Results: Among 10928 patients referred for CCTA, 28 patients with right-ACAOS with IAC were identified. Mean age was 55 ± 17 years, 64% were male and 11 (39.3%) presented with stable cardiac symptoms. Most patients had at least one high risk anatomical feature. During follow-up, there were no CV deaths or aborted SCD episodes and only 1 patient underwent surgical revascularization of the anomalous vessel.Conclusions: Right-ACAOS with IAC is an uncommon finding (prevalence of 0.26%). In a contemporary population of predominantly asymptomatic patients who survived this condition well into adulthood, most patients were managed conservatively with a low event rate. Additional studies are needed to support medical follow-up as the preferred option in this setting.
Micro-CT Mineral Density Profile as Reference Standard for Early Carious Lesion Activity Assessment.
Authors: Hoxie Adam Michael , Neves Aline de Almeida , Moss Kevin , de Vasconcellos Adalberto Bastos , Ferreira-Zandona Andrea , Ribeiro Apoena Aguiar 
Published: June 2021

Abstract
A challenging and crucial component to clinical caries diagnosis is diagnosing the activity of early lesions because it may have a significant impact on treatment decisions. This study aims to utilize microtomographic (micro-CT) scans of the enamel smooth surface layer to serve as a reference standard for future ex vivo caries activity assessment validation studies. Sound and non-cavitated (ICDAS 1-3) smooth surfaces (n=59) of extracted permanent teeth were examined for caries activity by calibrated individuals via visual-tactile examination. Each surface was scanned via micro-CT and line plot analysis generated plots of the mineral density against lesion depth, where the AUC was calculated. AUC thresholds were established to classify sound, remineralized, and demineralized surfaces against the gold standard examiner’s ICCMS assessment of sound, inactive, and active lesions, respectively. Diagnostic thresholds were associated with caries ICCMS activity classification using AUC mineral density values of the most external 96 μm of enamel. The established thresholds demonstrated 76.3% agreement with the ICCMS assessment in identifying demineralized lesions (k=0.45), with high sensitivity (0.73) and specificity (0.77). This study demonstrates quantifiable differences among demineralized, remineralized lesions, and sound surfaces, which contributes to the establishment of micro-CT as a reference standard for caries activity that may be used to improve clinical and technological caries examinations.
Investigation of Job Satisfaction Amongst Voluntary, Counseling and Testing Centers and Health centers in Iran
Authors: Heydari Mohammadreza , faghih Marjan , Karimzadeh Yasaman , Joulaei Hassan , SeyedAlinaghi SeyedAhmad , Miri Mohammad Reza , Pirmadah Farzane , Amini Wali , Meshkati Marjan , Kazerooni Parvin Afsar , Mehraeen Morteza , Qhiasi Fariba , Dadmanesh Negin , Hosseini Farzane , Yeilaghi Soloman 
Published: June 2021

Abstract
Background: Job satisfaction is the persons’ feeling about their job and if personnel haven't good feel to his work, can destroy all plans, intentionally or unintentionally. The present research aims to investigate and compare job satisfaction in the employees and therapists of Voluntary, Counseling and Testing Centers vs. Health centers in 9 provinces of Iran. Methods: All employees of Voluntary, Counseling and Testing Centers were included from Fars, Bushehr, Tehran, Isfahan, South Khorasan, Kurdistan, Kermanshah, Kerman, and Yazd provinces as case group and 103 staffs of similar Health centers selected with the same ratio as the staffs of Voluntary, Counseling and Testing Centers as control samples and answered to Minnesota Satisfaction Questionnaire (MSQ). Results: 50.5% of Health centers employees and 54% of Voluntary, Counseling and Testing Centers employees had high job satisfaction. Other than age and subscale management style no one of data had significant difference between 2 groups. Conclusion: According to the findings, in the Iranian treatment centers, the employees’ satisfaction will be at the same level regardless of their position and workplace. Also, the eastern and western regions of the country reported higher satisfaction than the southern and central regions.