bluuebunny/crossref_metadata_2025 huggingface dataset:
The feasibility of using dielectrophoresis for isolation of glioblastoma subpopulations with increased stemness
Authors: Alinezhadbalalami Nastaran , Douglas Temple A. , Balani Nikita , Verbridge Scott S. , Davalos Rafael V.
Published: May 2019

Cancer stem cells (CSCs) are aggressive subpopulations with increased stem‐like properties. CSCs are usually resistant to most standard therapies and are responsible for tumor repropagation. Similar to normal stem cells, isolation of CSCs is challenging due to the lack of reliable markers. Antigen‐based sorting of CSCs usually requires staining with multiple markers, making the experiments complicated, expensive, and sometimes unreliable. Here, we study the feasibility of using dielectrophoresis (DEP) for isolation of glioblastoma cells with increased stemness. We culture a glioblastoma cell line in the form of neurospheres as an in vitro model for glioblastoma stem cells. We demonstrate that spheroid forming cells have higher expression of stem cell marker, nestin. Next, we show that dielectric properties of neurospheres change as a result of changing culture conditions. Our results indicate that spheroid forming cells need higher voltages to experience the same DEP force magnitude compared to normal monolayer cultures of glioblastoma cell line. This study confirms the possibility of using DEP to isolate glioblastoma stem cells.
Baseline separation of α and β‐acids homologues and isomers in hop (Humulus lupulus L.) by CD‐MEKC‐UV
Authors: Duarte Lucas M. , Amorim Tatiane L. , Adriano Luiz H. C. , de Oliveira Marcone A. L.
Published: May 2019

An alternative method for simultaneous baseline separation of α and β‐acids homologues and isomers in hop by CD‐MEKC with UV detection was proposed. The optimized background electrolyte was composed of 30 mmol/L sodium tetraborate solution, 45 mmol/L sodium dodecyl sulfate, 20 mmol/L β‐cyclodextrin and 10% v/v acetonitrile. The instrumental conditions were evaluated by using a 33 Box‐Benhken experimental design. In order to demonstrate the applicability of the method, 21 hop samples from different varieties were analyzed. The repeatability intra‐ and interday tests were performed and relative standard deviations lower than 7% for area and migration times were observed. The present method comprehended 8 min analysis time and revealed to be faster and more efficient when compared to previous reports from literature.
Capillary electrophoresis‐based enzyme assays for β‐lactamase enzymes
Authors: Chen Chunyang , Kramer Jan S. , Brunst Steffen , Proschak Ewgenij , Scriba Gerhard K.E.
Published: May 2019

Generic in‐capillary as well as offline CE‐based enzyme assays were developed for serine‐β‐lactamases and metallo‐β‐lactamases. The hydrolysis of benzylpenicillin to benzylpenicilloic acid was analyzed using 100 mM sodium phosphate solution, pH 6.0, as a background electrolyte. In‐capillary assays employed an uncoated as well as a polyethylene oxide‐coated capillary, while the offline assays employing long end and short end injection were performed in an uncoated capillary. Using procaine hydrochloride or 4‐hydroxybenzoic acid as internal standard, the respective assays were validated with regard to linearity, LOD and LOQ, repeatability, precision, and accuracy. The assays were applied to the determination of the Michaelis‐Menten parameters Km and Vmax of Bacillus cereus penicillinase as well as New Delhi metallo‐β‐lactamase 1 and Verona integrin‐encoded metallo‐β‐lactamase 2. Furthermore, the inhibition of the enzymes by irreversible and competitive inhibitors was evaluated. Comparable data were obtained with all assays. The use of a simple substrate ensured broad applicability to the various types of β‐lactamases.
Flow resistance and hydraulic geometry in bedrock rivers with multiple roughness length scales
Authors: Ferguson Robert I. , Hardy Richard J. , Hodge Rebecca A.
Published: May 2019

Many models of incision by bedrock rivers predict water depth and shear stress from discharge; conversely, palaeoflood discharge is sometimes reconstructed from flow depth markers in rock gorges. In both cases, assumptions are made about flow resistance. The depth–discharge relation in a bedrock river must depend on at least two roughness length scales (exposed rock and sediment cover) and possibly a third (sidewalls). A conceptually attractive way to model the depth–discharge relation in such situations is to partition the total shear stress and friction factor, but it is not obvious how to quantify the friction factor for rough walls in a way that can be used in incision process models. We show that a single flow resistance calculation using a spatially averaged roughness length scale closely approximates the partitioning of stress between sediment and rock, and between bed and walls, in idealized scenarios. Both approaches give closer fits to the measured depth–discharge relations in two small bedrock reaches than can be achieved using a fixed value of Manning's n or the Chézy friction factor. Sidewalls that are substantially rougher or smoother than the bed have a significant effect on the partitioning of shear stress between bed and sidewalls. More research is needed on how best to estimate roughness length scales from observable or measurable channel characteristics. © 2019 John Wiley & Sons, Ltd.
Building and Applying Quantitative Adverse Outcome Pathway Models for Chemical Hazard and Risk Assessment
Authors: Perkins Edward J. , Ashauer Roman , Burgoon Lyle , Conolly Rory , Landesmann Brigitte , Mackay Cameron , Murphy Cheryl A. , Pollesch Nathan , Wheeler James R. , Zupanic Anze , Scholz Stefan
Published: May 2019

An important goal in toxicology is the development of new ways to increase the speed, accuracy, and applicability of chemical hazard and risk assessment approaches. A promising route is the integration of in vitro assays with biological pathway information. We examined how the adverse outcome pathway (AOP) framework can be used to develop pathway-based quantitative models useful for regulatory chemical safety assessment. By using AOPs as initial conceptual models and the AOP knowledge base as a source of data on key event relationships, different methods can be applied to develop computational quantitative AOP models (qAOPs) relevant for decision making. A qAOP model may not necessarily have the same structure as the AOP it is based on. Useful AOP modeling methods range from statistical, Bayesian networks, regression, and ordinary differential equations to individual-based models and should be chosen according to the questions being asked and the data available. We discuss the need for toxicokinetic models to provide linkages between exposure and qAOPs, to extrapolate from in vitro to in vivo, and to extrapolate across species. Finally, we identify best practices for modeling and model building and the necessity for transparent and comprehensive documentation to gain confidence in the use of qAOP models and ultimately their use in regulatory applications. Environ Toxicol Chem 2019;38:1850–1865. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

Abstract

Quantitative adverse outcome pathway (AOP) model development.
Survival of Salmonids from an Experimental Commercial Fish Trap
Authors: Tuohy Adrian M , Skalski John R , Gayeski Nick J
Published: May 2019

Conventional harvest techniques used in mixed-stock commercial salmon fisheries frequently result in bycatch mortality, thereby impeding salmonid recovery and constraining fishing opportunities in the U.S. Pacific Northwest. To address the problem, a postrelease survival study was conducted in the Columbia River to evaluate the potential of an experimental salmon trap for stock-selective commercial harvest. A modified fish trap was constructed and operated in 2017, from August through September, with the goal of minimizing entanglement, air exposure, crowding, and handling of all captured fishes. Postrelease survival from the trap was estimated through a paired release–recapture study. Results demonstrate that the trap effectively targeted commercially viable quantities of hatchery-origin Chinook Salmon Oncorhynchus tshawytscha and Coho Salmon O. kisutch while reducing bycatch mortality rates relative to conventional commercial fishing gears. During the study, 7,129 salmonids were captured. The postrelease survival effect over a 400-km migration ranged from 0.944 (SE¯ = 0.046) for steelhead O. mykiss to 0.995 (SE¯ = 0.078) for Chinook Salmon, supporting the potential application of traps for stock-selective commercial harvest.
Ablation of Hepatocyte Smad1, Smad5, and Smad8 Causes Severe Tissue Iron Loading and Liver Fibrosis in Mice
Authors: Wang Chia‐Yu , Xiao Xia , Bayer Abraham , Xu Yang , Dev Som , Canali Susanna , Nair Anil V. , Masia Ricard , Babitt Jodie L.
Published: May 2019

A failure of iron to appropriately regulate liver hepcidin production is central to the pathogenesis of hereditary hemochromatosis. SMAD1/5 transcription factors, activated by bone morphogenetic protein (BMP) signaling, are major regulators of hepcidin production in response to iron; however, the role of SMAD8 and the contribution of SMADs to hepcidin production by other systemic cues remain uncertain. Here, we generated hepatocyte Smad8 single (Smad8fl/fl;Alb‐Cre+
), Smad1/5/8 triple (Smad158;Alb‐Cre+
), and littermate Smad1/5 double (Smad15;Alb‐Cre+
) knockout mice to investigate the role of SMAD8 in hepcidin and iron homeostasis regulation and liver injury. We found that Smad8;Alb‐Cre+
mice exhibited no iron phenotype, whereas Smad158;Alb‐Cre+
mice had greater iron overload than Smad15;Alb‐Cre+
mice. In contrast to the sexual dimorphism reported for wild‐type mice and other hemochromatosis models, hepcidin deficiency and extrahepatic iron loading were similarly severe in Smad15;Alb‐Cre+
and Smad158;Alb‐Cre+
female compared with male mice. Moreover, epidermal growth factor (EGF) failed to suppress hepcidin in Smad15;Alb‐Cre+
hepatocytes. Conversely, hepcidin was still increased by lipopolysaccharide in Smad158;Alb‐Cre+
mice, although lower basal hepcidin resulted in lower maximal hepcidin. Finally, unlike most mouse hemochromatosis models, Smad158;Alb‐Cre+
developed liver injury and fibrosis at 8 weeks. Liver injury and fibrosis were prevented in Smad158;Alb‐Cre+
mice by a low‐iron diet and were minimal in iron‐loaded Cre–
mice. Conclusion: Hepatocyte Smad1/5/8 knockout mice are a model of hemochromatosis that encompasses liver injury and fibrosis seen in human disease. These mice reveal the redundant but critical role of SMAD8 in hepcidin and iron homeostasis regulation, establish a requirement for SMAD1/5/8 in hepcidin regulation by testosterone and EGF but not inflammation, and suggest a pathogenic role for both iron loading and SMAD1/5/8 deficiency in liver injury and fibrosis.
Vaginal bleeding in early pregnancy and risk of occult cancer
Authors: Dudukina Elena , Farkas Dóra K. , Horváth‐Puhó Erzsébet , Prandoni Paolo , Sørensen Henrik T. , Ehrenstein Vera
Published: May 2019

Vaginal bleeding in early pregnancy is not associated with a higher cancer risk compared with pregnancies in women from the general population of similar age.
Case of acute respiratory distress syndrome in a patient with an extragonadal germ cell tumor without lung metastasis in which choriocarcinoma syndrome was suspected
Authors: Kobayashi Kota , Tsutsumi Sohgo , Noguchi Go , Umemoto Susumu , Osaka Kimito , Kisida Takeshi
Published: May 2019

Introduction

Choriocarcinoma syndrome is caused by bleeding from metastatic germ cell tumors with choriocarcinoma components. Here, we report a case of acute respiratory distress syndrome, which arose after first‐line chemotherapy for an extragonadal germ cell tumor without lung metastasis.

Case presentation

A 41‐year‐old male visited our institution with chief complaints of back pain and weight loss. Computed tomography showed multiple lymph node metastases in the retroperitoneal cavity. There were no lung metastases. A lymph node biopsy resulted in a diagnosis of choriocarcinoma. Bleomycin etoposide cisplatin therapy was started as induction chemotherapy. On the first day, he was diagnosed with acute respiratory distress syndrome due to choriocarcinoma syndrome. We administered high‐dose hydrocortisone therapy for 3 days. The patient's respiratory status improved.

Conclusion

In patients who are at high risk of developing choriocarcinoma syndrome, induction chemotherapy might lead to the development of acute respiratory distress syndrome due to the release of cytokines despite the absence of lung metastasis.
Measuring mortgage credit availability: A frontier estimation approach
Authors: Anenberg Elliot , Hizmo Aurel , Kung Edward , Molloy Raven
Published: May 2019

We construct a new measure of mortgage credit availability using a technique developed for production frontier estimation. The resulting “loan frontier” describes the maximum amount obtainable by a borrower of given characteristics. We estimate this frontier using mortgage originations data from 2001 to 2014. We find a substantial expansion of mortgage credit for all borrowers during the housing boom, not only for low‐score or low‐income borrowers. The subsequent contraction in credit was most pronounced for low‐score borrowers. Using variation in the frontier across metropolitan areas over time, we show that borrowing constraints played an important role in the recent housing cycle.
Neuroprotection by glucose‐6‐phosphate dehydrogenase and the pentose phosphate pathway
Authors: Tang Bor Luen
Published: May 2019

Glucose‐6‐phosphate dehydrogenase (G6PD), the rate limiting enzyme that channels glucose catabolism from glycolysis into the pentose phosphate pathway (PPP), is vital for the production of reduced nicotinamide adenine dinucleotide phosphate (NADPH) in cells. NADPH is in turn a substrate for glutathione reductase, which reduces oxidized glutathione disulfide to sulfhydryl glutathione. Best known for inherited deficiencies underlying acute hemolytic anemia due to elevated oxidative stress by food or medication, G6PD, and PPP activation have been associated with neuroprotection. Recent works have now provided more definitive evidence for G6PD's protective role in ischemic brain injury and strengthened its links to neurodegeneration. In Drosophila models, improved proteostasis and lifespan extension result from an increased PPP flux due to G6PD induction, which is phenocopied by transgenic overexpression of G6PD in neurons. Moderate transgenic expression of G6PD was also shown to improve healthspan in mouse. Here, the deciphered and implicated roles of G6PD and PPP in protection against brain injury, neurodegenerative diseases, and in healthspan/lifespan extensions are discussed together with an important caveat, namely NADPH oxidase (NOX) activity and the oxidative stress generated by the latter. Activation of G6PD with selective inhibition of NOX activity could be a viable neuroprotective strategy for brain injury, disease, and aging.
Therapeutic effect of liraglutide on expression of CTGF and BMP‐7 in induced diabetic nephropathy
Authors: Ramzy Maggie M. , Abdalla Ahlam M. , Zenhom Nagwa M. , Okasha Ahmed M. , Abdelkafy Aya E. , Saleh Rabeh K.
Published: May 2019

Introduction

Diabetic nephropathy (DN) is one of the critical complications of diabetes mellitus and the main cause of chronic renal dysfunction. The pathogenic mechanism causing the disease remains unclear and there is a lack of effective treatment methods so novel strategies are needed for DN management. The aim of this study, therefore, is to evaluate the effect of liraglutide as glucagon‐like peptide‐1 analogue and its underlying mechanisms on induced DN in rats

Materials and Methods

Sixty rats were divided into control group, diabetic group, and liraglutide‐treated group. At the end of experiment, renal CTGF and BMP‐7 messeger RNA expression were determined. Blood sugar, serum urea, and creatinine were measured. Also, histopathological changes were studied.

Results

Liraglutide can improve renal alterations associated with diabetes as it reduced CTGF expression and increased BMP‐7 expression. In the same time, it could improve histopathological changes and renal function tests.

Conclusion

These findings influence the beneficial use of liraglutide for the management of DN in patients with diabetes mellitus.
Leukemia‐derived exosomes: Bringing oncogenic signals to blood cells
Authors: Sharifi Hossein , Shafiee Alimohammad , Molavi Ghader , Razi Ebrahim , Mousavi Nousin , Sarvizadeh Mostafa , Taghizadeh Mohsen
Published: May 2019

Leukemia is a cancer, which is derived from leukocytes and precursors of leukocytes in the bone marrow. A large number of pivotal biological processes are linked to leukemia pathogenesis. More insights into these mechanisms can provide a better developing pharmacological platform for patients with leukemia. Among the different players in leukemia pathogenesis, exosomes have appeared as a new biological vehicle, which can transfer oncogenic signals to blood cells. Exosomes are nano‐carriers, which enable transferring numerous cargos such as DNA fragments, RNAs, messenger RNAs, microRNAs, long noncoding RNA, and proteins. Targeting the contents of exosomes leads to the alteration of host cell behavior. Increasing evidence has indicated that leukemia‐derived exosomes could be utilized as prognostic, diagnostic, and therapeutic biomarkers for individuals suffering from leukemia. In this regard, the importance of exosomes in terms of initiation and progression of leukemia was underlined in this study.
HANR promotes lymphangiogenesis of hepatocellular carcinoma via secreting miR‐296 exosome and regulating EAG1/VEGFA signaling in HDLEC cells
Authors: Shi Yang , Yang Xiaohua , Xue Xiaofeng , Sun Ding , Cai Peng , Song Qingwei , Zhang Bin , Qin Lei
Published: May 2019

The long noncoding RNA HANR has been shown to be involved in the progression of hepatocellular carcinoma (HCC). However, the underlying mechanism of HCC‐associated long noncoding RNA (HANR)–regulated HCC metastasis and lymphangiogenesis has not been elucidated. RT‐qPCR and Western blot methods were utilized to detect the gene expressions. Interaction of HANR with miR‐296 was predicted by a bioinformatic program and validated by a dual‐luciferase reporter assay. For the functional experiment, a transwell invasion assay was utilized to examine the invasion abilities of HepG2 and Huh‐7 cells. The lymphatic vessel formation assay was used to show the HCC‐associated lymphatic vessel formation ability of human dermal lymphatic endothelial cells (HDLEC). HANR was shown to directly bind to miR‐296, and miR‐296 downregulated HANR expression in HepG2 cells. Then, we observed that miR‐296 inhibitor transfection in shHANR HCC cells could promote lymphatic vessel formation and invasion of HDLEC cells compared with shHANR HCC cells. EAG1 or VEGFA overexpression in HDLEC cells rescued lymphatic vessel formation and invasion in HDLEC cells coincubated with the medium of HepG2 cells expressing shHANR or miR‐296 mimic. Ultimately, HANR knockdown and miR‐296 mimic led to a significant decrease in the EAG1 and VEGFA expression levels in HepG2 cells. Here, we reveal a novel molecular mechanism in which the HANR/miR‐296/EAG1/VEGF axis is responsible for the lymphangiogenesis of HCC cells. Our findings provide more insights into developing therapeutical or diagnostic methods by targeting HANR.
Identification and validation of key genes associated with non‐small‐cell lung cancer
Authors: Ma Qiang , Xu Yuan , Liao Hebin , Cai Yan , Xu Lei , Xiao Dan , Liu Chang , Pu Wenjie , Zhong Xiaowu , Guo Xiaolan
Published: May 2019

Non‐small‐cell lung cancer (NSCLC) is one of the main causes of death induced by cancer globally. However, the molecular aberrations in NSCLC patients remain unclearly. In the present study, four messenger RNA microarray datasets (GSE18842, GSE40275, GSE43458, and GSE102287) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between NSCLC tissues and adjacent lung tissues were obtained from GEO2R and the overlapping DEGs were identified. Moreover, functional and pathway enrichment were performed by Funrich, while the protein–protein interaction (PPI) network construction were obtained from STRING and hub genes were visualized and identified by Cytoscape software. Furthermore, validation, overall survival (OS) and tumor staging analysis of selected hub genes were performed by GEPIA. A total of 367 DEGs (95 upregulated and 272 downregulated) were obtained through gene integration analysis. The PPI network consisted of 94 nodes and 1036 edges in the upregulated DEGs and 272 nodes and 464 edges in the downregulated DEGs, respectively. The PPI network identified 46 upregulated and 27 downregulated hub genes among the DEGs, and six (such as CENPE, NCAPH, MYH11, LRRK2, HSD17B6, and A2M) of that have not been identified to be associated with NSCLC so far. Moreover, the expression differences of the mentioned hub genes were consistent with that in lung adenocarcinoma and lung squamous cell carcinoma in the TCGA database. Further analysis showed that all the six hub genes were associated with tumor staging except MYH11, while only the upregulated DEG CENPE was associated with the worse OS of patients with NSCLC. In conclusion, the current study showed that CENPE, NCAPH, MYH11, LRRK2, HSD17B6, and A2M might be the key genes contributed to tumorigenesis or tumor progression in NSCLC, further functional study is needed to explore the involved mechanisms.
Knockdown of periostin attenuates 5/6 nephrectomy‐induced intrarenal renin–angiotensin system activation, fibrosis, and inflammation in rats
Authors: Bian Xiaohui , Bai Yu , Su Xiaoxiao , Zhao Guifeng , Sun Guangping , Li Detian
Published: May 2019

To simulate clinical features in human chronic kidney disease (CKD), SD rats were subjected to 5/6 nephrectomy in this study. We found that periostin gene was upregulated in the remnant kidneys using Agilent gene microarrays, and further explored its role via in vivo and in vitro experiments. Intrarenal renin–angiotensin system (RAS) was activated in 5/6 nephrectomized rats and partly deactivated by injection of adenoviruses encoding short hairpin RNA against periostin (sh‐periostin). Renal fibrosis in nephrectomized rats and profibrotic transforming growth factor‐β‐induced epithelial–mesenchymal transition (EMT) and ERK1/2 activation in NRK‐52E cells were suppressed by sh‐periostin. Moreover, knockdown of periostin decreased the generation of Interleukin 6 (IL6) and tumor necrosis factor‐α (TNF‐α) and accelerated p62 degradation in the remnant kidneys. Both HK‐2 cells treated with recombinant periostin and NRK‐52E cells infected with adenoviruses expressing periostin produced more IL6 and TNF‐α than control cells and displayed impaired autophagy as evidenced by inhibition of LC3II to LC3I conversion, Beclin 1 expression, and p62 degradation. By treating cells with rapamycin, an inhibitor of mamalian target of rapamycin known to activate autophagy, we noted that periostin‐induced inflammation was inhibited. Additionally, HK‐2 cells transfected with periostin overexpression plasmid generated more CCL2 and CXCL10, two important chemotactic factors, than untransfected cells. Conditioned medium from HK‐2 cells overexpressing periostin augmented chemotaxis of THP‐1 macrophages. Collectively, our work demonstrates that knockdown of periostin attenuates 5/6 nephrectomy‐induced intrarenal RAS activation, fibrosis, and inflammation in rats. These findings advance our understanding of periostin's role in CKD induced by nephron loss.
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

Osteoporosis 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

Hydroxy 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

Expansion 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

Background

The 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.

Methods

Cochrane 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.

Results

Two 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.

Conclusion

The 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

Background

Next‐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.

Methods

The 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.

Results

In 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.

Conclusions

With 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

Background

Glycophosphatidylinositol‐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.

Methods

We 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.

Results

A 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.

Conclusion

We 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

Objective

This 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.

Methods

In 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.

Results

All 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.

Conclusions

Measures 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

Background

Psychological 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?

Methods

In 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.

Results

Patients 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.

Conclusions

PEPRR 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

Objective

The 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.

Methods

Female 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.

Results

Only 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).

Conclusions

The 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.
Polyurethane Prepolymer Modified Cassava Starch Based Poly(butylene adipate‐co‐terephthalate) Composites with Excellent Compatibility and High Toughness
Authors: Meng Wei , Chen Fangping , Zhang Chenhao , Cui Ruihua , Wang Peilei , Liu Changsheng
Published: May 2019

In this study, a high‐efficiency polyurethane prepolymer (PUP) compatibilizer is developed to improve the compatibility between cassava starch and poly(butylene adipate‐co‐terephthalate) with higher molecular weight (MPBAT). Preferentially, modified starch (MS) is prepared by reacting isocyanate groups of PUP with hydroxyl groups of starch in a high‐speed mixer, and then starch‐based MPBAT composites (MSPT) with PUP as a compatibilizer are continuously extruded using twin‐screw extruder. The mechanical properties, water absorption, and thermodynamic properties as well as morphology of MSPT are investigated with different PUP contents and at the same mass ratio of MPBAT to starch (1:1). Samples of MSPT‐2 provide satisfactory mechanical properties comparable to control samples. Addition of 13 wt.% PUP to MSPT, improves tensile strength from 3.8 to 11.9 MPa and increases elongation at break from 93.3 to 580.4% at room temperature compared with control without the PUP. The hydrophobicity and thermostability properties of MSPT‐2 composites are also enhanced. The results further prove that MSPT‐2 composites possess excellent compatibility, not only because of the urethane bonds of the PUP and starch, but also stemming from the physical crosslinking between soft segment of PUP and aliphatic segment of MPBAT. Starch‐based MPBAT composites with excellent compatibility and high toughness will help broaden the application field of biodegradable plastics.
Faculty and international student perceptions of language performance and instructional support: A mismatch of expectations
Authors: Gallagher Colleen , Haan Jennifer , Lovett Sarah
Published: May 2019

With increasingly mobile and global populations in universities worldwide, it is important that faculty and students share common expectations for student and instructor behaviors. This study focused on international student and faculty perceptions of student language performance and faculty instructional techniques in one U.S. university with recent growth in the international student population. Using responses from two questionnaires administered to faculty and matriculated international students at the university, the authors found a mismatch between faculty and student perceptions. Faculty rated students’ linguistic performance poorly, whereas students saw their language skills as adequate for the demands of their classes. In terms of instructional supports for international students, both students and faculty reported using or appreciating visuals, but other strategies such as advance provision of instructional materials or invitations to office hours were appreciated by students but less often used by faculty. The authors discuss the results in terms of developing shared expectations between students and faculty and engaging in intentional language acquisition planning at the institutional level.
Integrated triple-collinear counter-terms for the nested soft-collinear subtraction scheme
Authors: Delto Maximilian , Melnikov Kirill
Published: May 2019

Abstract

We obtain analytic results for integrated triple-collinear splitting functions that emerge as collinear counter-terms in the context of the nested soft-collinear subtraction scheme [1]. With these results, all integrated subtraction terms required for NNLO QCD computations within this scheme are known analytically. In addition to improving efficiency and numerical stability of practical computations, the availability of these results will contribute towards establishing a general NNLO QCD subtraction formula for generic hard scattering processes in hadron collisions, similar to Catani-Seymour and FKS subtractions at NLO.
A revisit to scalar dark matter with radiative corrections
Authors: Banerjee Shankha , Chakrabarty Nabarun
Published: May 2019

Abstract

Extended Higgs sectors have been studied extensively in context of dark matter phenomenology in tandem with other aspects. In this study, we compute radiative corrections to the dark matter-Higgs portal coupling, which is in fact a common feature of all scalar dark matter models irrespective of the hypercharge of the multiplet from which the dark matter candidate emerges. We select the popular inert doublet model (IDM) as a prototype in order to demonstrate the impact of the next-to-leading order corrections, thereby probing the plausibility of extending the allowed parameter space through quantum effects. Given that the tree level portal coupling is a prima facie free parameter, the percentage change from loop effects can be large. This modifies the dark matter phenomenology at a quantitative level. It also encourages one to include loop corrections to all other interactions that are deemed relevant in this context.
Swampland variations on a theme by KKLT
Authors: Blumenhagen Ralph , Kläwer Daniel , Schlechter Lorenz
Published: May 2019

Abstract

The KKLT scenario in a warped throat, if consistent, provides a concrete counterexample to both the AdS scale separation and the dS swampland conjectures. First, we define and analyze the relevant effective field theory for the conifold modulus and the overall Kähler modulus that both have exponentially small masses. The scalar potential still admits KKLT-like AdS and dS minima. Second, we critically analyze the reliability of the employed Wilsonian effective action by evaluating the masses of light modes localized in the warped throat. The resulting mass spectrum is discussed with respect to the swampland distance conjecture. We find the recently observed emergent nature of the latter not only at large distance points but also at the conifold point motivating a general extension of it. In this respect, KKLT and trans-Planckian field distance are on equal footing. It is pointed out that the reliability of the KKLT minimum will depend on how this emergent behavior is interpreted.
VOAs labelled by complex reflection groups and 4d SCFTs
Authors: Bonetti Federico , Meneghelli Carlo , Rastelli Leonardo
Published: May 2019

Abstract

We define and study a class of

$$ \mathcal{N} $$

N

= 2 vertex operator algebras

$$ {\mathcal{W}}_{\mathrm{G}} $$

W
G

labelled by complex reflection groups. They are extensions of the

$$ \mathcal{N} $$

N

= 2 super Virasoro algebra obtained by introducing additional generators, in correspondence with the invariants of the complex reflection group G. If G is a Coxeter group, the

$$ \mathcal{N} $$

N

= 2 super Virasoro algebra enhances to the (small)

$$ \mathcal{N} $$

N

= 4 superconformal algebra. With the exception of G = ℤ2, which corresponds to just the

$$ \mathcal{N} $$

N

= 4 algebra, these are non-deformable VOAs that exist only for a specific negative value of the central charge. We describe a free-field realization of

$$ {\mathcal{W}}_{\mathrm{G}} $$

W
G

in terms of rank(G) βγbc ghost systems, generalizing a construction of Adamovic for the

$$ \mathcal{N} $$

N

= 4 algebra at c = −9. If G is a Weyl group,

$$ {\mathcal{W}}_{\mathrm{G}} $$

W
G

is believed to coincide with the

$$ \mathcal{N} $$

N

= 4 VOA that arises from the four-dimensional super Yang-Mills theory whose gauge algebra has Weyl group G. More generally, if G is a crystallographic complex reflection group,

$$ {\mathcal{W}}_{\mathrm{G}} $$

W
G

is conjecturally associated to an

$$ \mathcal{N} $$

N

= 3 4d superconformal field theory. The free-field realization allows to determine the elusive “R-filtration” of

$$ {\mathcal{W}}_{\mathrm{G}} $$

W
G

, and thus to recover the full Macdonald index of the parent 4d theory.