bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neferine suppresses osteoclast differentiation through suppressing NF‐κB signal pathway but not MAPKs and promote osteogenesis
Authors: Chen Shenao , Chu Bingxiang , Chen Yao , Cheng Xun , Guo Di , Chen Lihua , Wang Jiacheng , Li Zhiyan , Hong Zhenghua , Hong Dun 
Published: May 2019

AbstractOsteoporosis is an ageing disease characterized by elevated osteoclastic bone resorption resulting in bone loss, decrease bone strength, and elevated incidence of fractures. Neferine, a natural compound isolated from the traditional Chinese medicine Nelumbo nucifera (Lotus), has been reported exhibit anti‐inflammatory, antioxidant, and anticancer properties. However, its effect on bone remains to be determined. Here we showed that Neferine inhibits RANKL‐induced osteoclast formation in a dose‐ and time‐dependent manner. Furthermore, Neferine also demonstrated antiresorptive properties by effectively ameliorating the bone resorptive activity of mature osteoclasts. Mechanistically, Neferine suppressed RANKL‐induced activation of NF‐κB signaling pathway. This in turn hindered the induction and activation of NFATc1 resulting in downregulation of osteoclast marker genes closely related to differentiation, fusion as well as bone resorption. Interestingly, we found Neferine enhanced the differentiation and bone mineralization activity of MC3T3‐E1 preosteoblast cells. Finally, mice treated with Neferine was protected against ovariectomy (OVX)‐induced bone loss. The Neferine treatment improved bone volume following ovariectomy and also exhibited less TRAP‐positive osteoclasts on bone surface. Collectively our data provide promising evidence that Neferine could be a potential therapeutic application for against osteolytic bone conditions such as osteoporosis.
HAO2 inhibits malignancy of clear cell renal cell carcinoma by promoting lipid catabolic process
Authors: Xiao Wen , Wang Xuegang , Wang Tao , chen Bin , Xing Jinchun 
Published: May 2019

AbstractHydroxy acid oxidase 2 (HAO2) has been reported to inhibit tumor progression through metabolic pathway. The current study was designed to evaluate the prognostic significance and probable mechanism of HAO2 in patients with clear cell renal cell carcinoma (ccRCC). The study screened The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA‐KIRC) database for patients with ccRCC having complete clinical information and HAO2 expression. Low HAO2 was associated with shorter overall survival (OS) and shorter disease‐free survival (DFS). Gene set enrichment analysis (GSEA) showed HAO2 was associated with neutral lipid catabolic process, metabolic process, lipid oxidation, epithelial–mesenchymal transition (EMT), and Kirsten rat sarcoma viral oncogene signaling (KRAS). Western blot analysis and immunohistochemistry analysis checked HAO2 expression in ccRCC cancer tissues, normal tissues, and renal cancer cell lines. HAO2 was downregulated in ccRCC cancer tissues and ccRCC cell lines when compared with their control group. Overexpression of HAO2 by plasmid promoted lipid catabolic process, eliminated lipid accumulation, inhibited KRAS expression, controlled the proliferation, migration, and invasion activity of ccRCC tumor cells. Our results indicated that HAO2 inhibits malignancy ccRCC by promoting lipid catabolic process, HAO2 could be an effective molecular marker and treatment for ccRCC.
Comparative evaluation of morphology and osteogenic behavior of human Wharton's jelly mesenchymal stem cells on 2D culture plate and 3D biomimetic scaffold
Authors: Jamalpoor Zahra , Soleimani Mansoureh , Taromi Nafise , Asgari Alireza 
Published: May 2019

AbstractExpansion of seeded human Wharton's jelly mesenchymal stem cells (hWJ‐MSCs) on 2D culture plates and 3D nano‐hydroxyapatite/chitosan/gelatin scaffolds, from morphology and osteoactivity points of view, were investigated. Cell attachment and spreading, temporal expression profiles of selected osteogenic gene and protein markers, intracellular alkaline phosphatase enzyme activity (ALP activity), and matrix mineralization were assayed over the course of the experiments. Morphological results demonstrated hWJ‐MSCs had greater affinity to adhere onto the 3D scaffold surface, as the number and thickness of the filopodia were higher in the 3D compared with 2D culture system. Functionally, the intracellular ALP activity and extracellular mineralization in 3D scaffolds were significantly greater, in parallel with elevation of osteogenic markers at the mRNA and protein levels at all‐time point. It is concluded that 3D scaffolds, more so than 2D culture plate, promote morphology and osteogenic behavior of WJ‐MSCs in vitro, a promising system for MSCs expansion without compromising their stemness before clinical transplantation.
Conduct and reporting of citation searching in Cochrane systematic reviews: A cross‐sectional study
Authors: Briscoe Simon , Bethel Alison , Rogers Morwenna 
Published: May 2019

BackgroundThe search for studies for a systematic review should be conducted systematically and reported transparently to facilitate reproduction. This study aimed to report on the conduct and reporting of backward citation searching (ie, checking reference lists) and forward citation searching in a cross section of Cochrane reviews. Citation searching uses the citation network surrounding a source study to identify additional studies.MethodsCochrane reviews were identified by searching the Cochrane Database of Systematic Reviews using the wildcard symbol and date limiting to the 3‐month period November 2016 to January 2017. Cochrane reviews thus identified were screened for mention of citation searching. Descriptive detail on the conduct and reporting of citation searching was captured in data extraction forms and described and evaluated.ResultsTwo hundred fifteen Cochrane reviews were identified. One hundred seventy‐two reviews reported backward citation searching, and 18 reviews reported forward citation searching. Web of Science was the most frequently reported citation index. The studies used for backward citation searching consisted mainly of studies meeting the inclusion criteria. One‐third of reviews that reported forward citation searching used selected studies of importance. Reporting of citation searching was compliant with the Methodological Expectations of Cochrane Intervention Reviews (MECIR) standards, but full transparency requires additional detail that only a minority of reviews reported.ConclusionThe conduct of backward citation searching was more uniform than forward citation searching. This might be due to lack of MECIR guidance for forward citation searching. Reporting was generally compliant with MECIR, but this is not always sufficient to ensure full transparency.
VCF‐Server: A web‐based visualization tool for high‐throughput variant data mining and management
Authors: Jiang Jianping , Gu Jianlei , Zhao Tingting , Lu Hui 
Published: May 2019

AbstractBackgroundNext‐generation sequencing (NGS) has been widely used in both clinics and research. It has become the most powerful tool for diagnosing genetic disorders and investigating disease etiology through the discovery of genetic variants. Variants identified by NGS are stored in variant call format (VCF) files. However, querying and filtering VCF files are extremely difficult for researchers without programming skills. Furthermore, as the mutation data are increasing exponentially, there is an urgent need to develop tools to manage these variant data in a centralized way.MethodsThe VCF‐Server was developed as a web‐based visualization tool to support the interactive analysis of genetic variant data. It allows researchers and medical geneticists to manage, annotate, filter, query, and export variants in a fast and effective way.ResultsIn this study, we developed the VCF‐Server, a powerful and easily accessible tool for researchers and medical geneticists to perform variant analysis. Users can query VCFs, annotate, and filter variants without knowing programming code. Once the VCF file is uploaded, VCF‐Server allows users to annotate the VCF with commonly used databases or user‐defined variant annotations (including variant blacklist and whitelist). Variant information in the VCF is shown visually via the interactive graphical interface. Users can filter the variants with flexible filtering rules, and the prioritized variants can be exported locally for further analysis. As VCF‐Server adopts a web file system, files in the VCF‐Server can be stored and managed in a centralized way. Moreover, VCF‐Server allows direct web‐based analysis (accessible through either desktop computers or mobile devices) as well as local deployment.ConclusionsWith an easy‐to‐use graphical interface, VCF‐Server allows researchers with little bioinformatics background to explore and mine mutation data, which may broaden the application of NGS technology in clinics and research. The tool is freely available for use at https://www.diseasegps.org/VCF-Server?lan = eng.
Inherited glycophosphatidylinositol deficiency variant database and analysis of pathogenic variants
Authors: Baratang Nissan Vida , Jimenez Cruz Daniel Alexander , Ajeawung Norbert Fonya , Nguyen Thi Tuyet Mai , Pacheco‐Cuéllar Guillermo , Campeau Philippe M. 
Published: May 2019

AbstractBackgroundGlycophosphatidylinositol‐anchored proteins (GPI‐APs) mediate several physiological processes such as embryogenesis and neurogenesis. Germline variants in genes involved in their synthesis can disrupt normal development and result in a variety of clinical phenotypes. With the advent of new sequencing technologies, more cases are identified, leading to a rapidly growing number of reported genetic variants. With this number expected to rise with increased accessibility to molecular tests, an accurate and up‐to‐date database is needed to keep track of the information and help interpret results.MethodsWe therefore developed an online resource (www.gpibiosynthesis.org) which compiles all published pathogenic variants in GPI biosynthesis genes which are deposited in the LOVD database. It contains 276 individuals and 192 unique public variants; 92% of which are predicted as damaging by bioinformatics tools.ResultsA significant proportion of recorded variants was substitution variants (81%) and resulted mainly in missense and frameshift alterations. Interestingly, five patients (2%) had deleterious mutations in untranslated regions. CADD score analysis placed 97% of variants in the top 1% of deleterious variants in the human genome. In genome aggregation database, the gene with the highest frequency of reported pathogenic variants is PIGL, with a carrier rate of 1/937.ConclusionWe thus present the GPI biosynthesis database and review the molecular genetics of published variants in GPI‐anchor biosynthesis genes.
Association Between Adiposity and Perceived Physical Fatigability in Mid‐ to Late Life
Authors: Martinez‐Amezcua Pablo , Simonsick Eleanor M. , Wanigatunga Amal A. , Urbanek Jacek K. , Chiles Shaffer Nancy , Ferrucci Luigi , Schrack Jennifer A. 
Published: May 2019

ObjectiveThis study aimed to compare and contrast the associations between measures of adiposity and fat distribution and perceived fatigability among well‐functioning individuals in mid‐ to late life.MethodsIn 1,054 adults (70.4 ± 12.4 years, 52% female), adiposity was measured as BMI, percent fat (dual‐energy x‐ray absorptiometry), waist and hip circumferences, and waist to height ratio. In a subset of 383 participants, visceral fat was measured. Perceived fatigability was evaluated after a 5‐minute treadmill walk (1.5 mph) using the Borg rating of perceived exertion (range, 6‐20). Associations between adiposity measures and perceived fatigability were assessed using regression models adjusting for age, sex, race, smoking, and comorbidities.ResultsAll adiposity measures, except subcutaneous fat, were positively associated with perceived fatigability after adjustment (P < 0.05 for all). Standardized coefficients indicated that BMI, hip circumference, and visceral fat had the strongest associations with fatigability. Associations between BMI and fatigability were present only among those above the threshold for overweight and strongest in those aged ≥ 65 years. Moreover, BMI was associated with fatigability only among participants with higher waist circumference.ConclusionsMeasures of adiposity, particularly central adiposity, are strongly associated with fatigability, suggesting that weight management may be an effective target for curbing fatigability and maintaining quality of life with aging.
A randomized control trial of stress management for caregivers of stem cell transplant patients: Effect on patient quality of life and caregiver distress
Authors: Laudenslager Mark L. , Simoneau Teresa L. , Mikulich‐Gilbertson Susan K. , Natvig Crystal , Brewer Benjamin W. , Sannes Timothy S. , Kilbourn Kristin , Gutman Jon , McSweeney Peter 
Published: May 2019

AbstractBackgroundPsychological interventions reduce caregiver distress (CG‐distress). Less distress in caregivers may contribute to improved patient quality of life (QoL), but empirical evidence is lacking. Will a caregiver stress management intervention improve patient QoL?MethodsIn this replication study, we randomized 155 allogeneic hematopoietic stem cell transplant (Allo‐HSCT) patients and caregivers to PsychoEducation, Paced Respiration, and Relaxation (PEPRR) or enhanced treatment as usual (eTAU). We provided PEPRR over 3 months following transplant. Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT‐BMT) evaluated patient QoL, and CG‐distress was based on depressive, anxious, and stress symptoms. Hierarchical linear models tested intervention, time, and interactions as fixed effects with participant as random effects.ResultsPatients whose caregivers received PEPRR did not differ on FACT‐BMT between baseline and 6 months (mean = +3.74; 95% CI, −3.54 to 11.02) compared with patients of caregivers in eTAU (mean = +3.16; 95% CI, −2.88 to 9.20) even though CG‐distress was decreased by PEPRR (mean = −0.23; 95% CI, −0.448 to −0.010) compared with those receiving eTAU (mean = +0.27; 95% CI, 0.033‐0.504) at 6 months.ConclusionsPEPRR reduced CG‐distress without affecting their patient's FACT‐BMT score. The FACT‐BMT may not have distinguished unique psychological changes associated with their caregiver receiving PEPRR.
Revisiting the Reproductive Concerns After Cancer (RCAC) scale
Authors: Gorman Jessica R. , Pan‐Weisz Tonya M. , Drizin Julia H. , Su H. Irene , Malcarne Vanessa L. 
Published: May 2019

AbstractObjectiveThe aims of this study were to examine the factor structure and reliability of the multidimensional Reproductive Concerns After Cancer (RCAC) scale in a sample of female cancer survivors during their reproductive years, younger than age 45.MethodsFemale reproductive‐aged survivors (N = 238; current age, 18 to 44 y) with a variety of cancer diagnoses completed a web‐based survey that included the RCAC scale. Three structural models were examined via confirmatory factor analysis: (a) one‐factor, (b) higher‐order with one second‐order factor and six first‐order factors, and (c) oblique six‐factor. Reliability was examined using omega total and Revelle omega total.ResultsOnly the oblique six‐factor model of the RCAC scale fits well. Omega total and Revelle omega total estimates for all of the six three‐item subscales were in the nearly satisfactory to good range (.66 to.87).ConclusionsThe RCAC scale was found to have satisfactory factor structure and reliability when measuring a range of reproductive concerns experienced by female reproductive‐aged survivors. The RCAC scale is a multidimensional measure of varying aspects of reproductive concerns, and results suggest that the scale may be best represented as a profile of subscale scores. The subscale scores would be useful for tailoring recommendations and interventions to more effectively address the diverse reproductive concerns of female reproductive‐aged survivors.
Schizophrenia-spectrum psychopathology in obsessive–compulsive disorder: an empirical study
Authors: Rasmussen Andreas Rosén , Nordgaard Julie , Parnas Josef 
Published: May 2019

AbstractThe differential diagnosis of obsessive–compulsive disorder (OCD) and schizophrenia-spectrum disorders can be difficult. In the current diagnostic criteria, basic concepts such as obsession and delusion overlap. This study examined lifetime schizophrenia-spectrum psychopathology, including subtle schizotypal symptomatology and subjective anomalies such as self-disorders, in a sample diagnosed with OCD in a specialized setting. The study also examined the differential diagnostic potential of the classic psychopathological notions of true obsession (‘with resistance’) and pseudo-obsession. The study involved 42 outpatients diagnosed with OCD at two clinics specialized in the treatment of OCD. The patients underwent semi-structured, narrative interviews assessing a comprehensive battery of psychopathological instruments. The final lifetime research-diagnosis was based on a consensus between a senior clinical psychiatrist and an experienced research clinician. The study found that 29% of the patients fulfilled criteria of schizophrenia or another non-affective psychosis as main, lifetime DSM-5 research-diagnosis. Another 33% received a research-diagnosis of schizotypal personality disorder, 10% a research-diagnosis of major depression and 29% a main research-diagnosis of OCD. Self-disorders aggregated in the schizophrenia-spectrum groups. True obsessions had a specificity of 93% and a sensitivity of 58% for a main diagnosis of OCD. In conclusion, a high proportion of clinically diagnosed OCD patients fulfilled diagnostic criteria of a schizophrenia-spectrum disorder. The conspicuous obsessive–compulsive symptomatology may have resulted in a disregard of psychotic symptoms and other psychopathology. Furthermore, the differentiation of obsessions from related psychopathological phenomena is insufficient and a conceptual and empirical effort in this domain is required in the future.
Scheduling approach for on-site jobs of service providers
Authors: Holczinger Tibor , Ősz Olivér , Hegyháti Máté 
Published: May 2019

AbstractNowadays the successful operation of a company is unimaginable without fast and reliable communication. As a result, so-called Communication Service Providers play an important role in today’s business life. Their orders have to be carried out promptly and dependably, let them be requests for new installations, modifications, or maintenance tasks. These orders have to be performed at different locations and they often have deadlines or strict starting times. Violating such a timing requirement usually implies penalties. In this paper, scheduling problems arising at a Hungarian service provider are examined. At this company, orders are decomposed into smaller tasks, which can be performed by specially trained personnel. Transportation of these specialists contributes a lot to the costs and to the complexity of their scheduling, as well. The goal is to minimize the overall cost of satisfying all orders within the given time horizon with the available assets of the company. The proposed approach relies on the S-graph framework, which has been applied to various production scheduling problems in the literature. In addition to an unambiguous and sound S-graph model of the examined problem, slight modifications of the scheduling algorithms for cost minimization, and new bounding methods have been developed. Several of such bounds have been provided and tested for performance and scalability over a large number of generated examples. The sensitivity of the approach for certain problem features has also been examined.
Perspective-Based Generic Questions as a Tool to Promote Student Biology Teacher Questioning
Authors: de Boer Eveline , Janssen Fred J. J. M. , van Driel Jan H. , Dam Michiel 
Published: May 2019

AbstractIn biological research, generic questions that are derived from perspectives (ways of looking at and thinking about life processes) help in generating specific questions. In this study, we used perspective-based generic questions as scaffolds to support student teachers in increasing the quality and quantity of their questions about biological topics. Fifteen student biology teachers were given an intervention to individually generate, in 15 min, as many questions as possible that they might ask in class about standards from the national syllabus for biology on a particular biological topic, first without using, and then using a set of perspective-based generic questions. The results of this study show that, using perspective-based generic questions, student teachers generated significantly more and higher quality questions. The formulated questions can be applied in two different contexts: during practicum, when student teachers actually teach biology, or when they plan future lessons, as the basis of challenging tasks or assignments, with the aim of getting students interested in finding the answers.
Taxes, the tax administrative burden and the entrepreneurial life cycle
Authors: Braunerhjelm Pontus , Eklund Johan E. , Thulin Per 
Published: May 2019

AbstractWe present a modified version of the entrepreneurial choice model, where it is shown that the expected utility of becoming an entrepreneur is decreasing in both the levels of taxes and the tax administrative burden. We extend previous empirical findings by examining how these variables influence entrepreneurs at different stages in the entrepreneurial life cycle. Our findings imply that the effect of the tax administrative burden varies over the entrepreneurial life cycle from strongly negative to insignificant. The most pronounced negative effects appear in the early stages of entrepreneurship. We conclude that a 10% reduction in the tax administrative burden increases the propensity for new business establishments by 4%. Our findings support the idea that tax simplification is one way to encourage entrepreneurship, without any reduction in tax revenues.