bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of genetic variation in DGKK on moderate and severe hypospadias
Authors: Richard Melissa A. , Sok Pagna , Canon Stephen , Brown Austin L. , Peckham‐Gregory Erin C. , Nembhard Wendy N. , Carmichael Suzan L. , Ehli Erik A. , Kallsen Noah A. , Peyton Shanna A. , Davies Gareth E. , Patel Ashay , Zamilpa Ismael , Wyatt Richard A. , Hobbs Charlotte A. , Scheurer Michael E. , Lupo Philip J. 
Published: May 2019

AbstractBackgroundRecent genome‐wide association studies of hypospadias have implicated the role of genetic variants in or near the diacylglycerol kinase kappa (DGKK) gene. However, these variants are largely identified among samples of mild and moderate hypospadias cases. Therefore, we evaluated previously identified DGKK variants among second‐ and third‐degree hypospadias cases and controls recruited in Arkansas, a state characterized by a high birth prevalence of hypospadias.MethodsSecond‐ and third‐degree hypospadias non‐Hispanic white cases (n = 36 and n = 9, respectively) and controls (n = 45) were recruited at Arkansas Children's Hospital. Preputial tissue was collected on cases and controls between 2013 and 2017. Cases and controls were genotyped using the Illumina Infinium Global Screening Array. We used logistic regression models to assess the association of genotyped and imputed genetic variants mapped to the DGKK region with second‐ and third‐degree hypospadias.ResultsAll families self‐reported as non‐Hispanic white and genetic principal component analyses did not demonstrate evidence of population stratification. Five DGKK variants previously reported as associated with hypospadias were identified in the genotype data. None of the variants were associated with second‐ or third‐degree hypospadias (range of odds ratios = 0.7–0.9, all p > .05).ConclusionsIn our analyses, genetic variation in DGKK does not play a role in the development of moderate and severe hypospadias. Our findings provide support to the etiologic heterogeneity of hypospadias by all classifications of severity.
Universal tumor screening for Lynch syndrome: Perceptions of Canadian pathologists and genetic counselors of barriers and facilitators
Authors: Dicks Elizabeth , Pullman Daryl , Kao Ken , MacMillan Andrée , Logan Gabrielle S. , Simmonds Charlene , Etchegary Holly 
Published: May 2019

AbstractBackgroundPeople at risk of developing hereditary cancers associated with Lynch Syndrome (LS) can be identified through universal screening of colorectal tumors. However, tumor screening practices are variable across Canada and few studies explore the perspectives of genetic counselors and pathologists about tumor screening. This study was conducted to better understand the barriers and facilitators of implementing universal tumor screening in health centers across Canada.MethodsAn online survey about tumor screening programs was administered to genetic counselors and pathologists across Canada through communication channels of professional organizations. It was hosted on SurveyMonkey and accessible from October 2016 to March 2017.ResultsBarriers to tumor screening included a lack of sustainable resources, including funding and genetic counselors. Respondents strongly identified the need for a coordinated, interdisciplinary approach to program planning with the “right people at the table.” Respondents currently with a screening program provided advice such as carefully designing the program structure, developing patient and family follow‐up protocols, and ensuring adequate resources (funding, staff, training for providers) were available prior to program initiation.ConclusionThere is no national approach to universal tumor screening in Canada. However, future efforts can be informed by the experiences of those centers that have already created a universal tumor screening program for LS. These data suggest the need for an interdisciplinary approach, initial and sustained funding, and careful advanced planning of program structures and policies.
Towards Light‐Activated Ruthenium–Arene (RAPTA‐Type) Prodrug Candidates
Authors: Renfrew Anna K. , Karges Johannes , Scopelliti Rosario , Bobbink Felix D. , Nowak‐Sliwinska Patrycja , Gasser Gilles , Dyson Paul J. 
Published: May 2019

AbstractCancer is currently one of the deadliest diseases worldwide. Based on the high incidence of this disease, the side effects associated with current chemotherapies and the appearance of drug resistance, considerable efforts have been directed towards the development of new anticancer drugs with new modes of action. Metal‐based compounds are particularly attractive candidates due to their metabolic mechanisms, which differ substantially from those of organic drugs. Of special interest in this context are organometallic ruthenium(II) complexes of the type [Ru(η6‐arene)(pta)Cl2] (arene: p‐cymene, toluene, benzene, etc.; pta: 1,3,5‐triaza‐7‐phosphaadamantane), which are abbreviated to RAPTA. Complementary to chemotherapy, photoactivated chemotherapy is a technique that has received increasing attention towards the development of treatment for numerous kinds of cancer. With this in mind, a photoactive RAPTA‐type complex bearing azide ligands has been designed. The diazide complex, [Ru(η6‐p‐cymene)pta‐(N3)2], is inert in water, but slowly releases the azide ligand upon exposure to light. Consequently, the in vitro cytotoxicity of the complex in the dark and upon light exposure at λ=450 nm in human cervical carcinoma (HeLa) and noncancerous retinal pigment epithelium (RPE‐1) cells was investigated. Although the cytotoxicity of the complex was found to be modest in the dark, an increase in toxicity upon light exposure was observed.
Effect of debranning process on deoxynivalenol content in whole‐wheat flours
Authors: Tibola Casiane Salete , Guarienti Eliana Maria , Dias Alvaro Renato Guerra , Nicolau Marcio , Devos Rafaela Julyana Barboza , Teixeira Daniela Dalbosco 
Published: May 2019

AbstractBackground and objectivesPost‐harvest mitigation strategies are essential to reduce mycotoxin contamination in wheat‐based foods. The study aimed to evaluate the effect of the debranning process on the deoxynivalenol content in whole‐wheat flour naturally contaminated by Fusarium spp. Thirty commercial wheat samples were used and were obtained in Southern Brazil Region in 2015 crop season.FindingsThe highest DON contamination level was found in the no‐debranned samples and the outermost fraction (extraction rate >95%), which corresponds to the debranning time of 15 s. When all debranning times were included in the analysis, only the samples from Paraná State had the DON content significantly reduced after the debranning.ConclusionsThe debranning process reduced the DON content in whole‐wheat flour with lower to moderate levels of contamination, corresponding to DON content of 1.032 and 1.174 µg/kg, obtained in Paraná and Rio Grande do Sul States, respectively.Significance and noveltyThese results are important for wheat supply chain to meet the legislation requirements and to produce safer foods.
Conversion of Carbonyl Compounds to Olefins via Enolate Intermediate
Authors: Cao Zhi‐Chao , Xu Pei‐Lin , Luo Qin‐Yu , Li Xiao‐Lei , Yu Da‐Gang , Fang Huayi , Shi Zhang‐Jie 
Published: May 2019

Summary of main observation and conclusionA general and efficient protocol to synthesize substituted olefins from carbonyl compounds via nickel catalyzed C—O activation of enolates was developed. Besides ketones, aldehydes were also suitable substrates for the presented catalytic system to produce di‐ or tri‐ substituted olefins. It is worth noting that this approach exhibited good tolerance to highly reactive tertiary alcohols, which could not survive in other reported routes for converting carbonyl compounds to olefins. This method also showed good regio‐ and stereo‐selectivity for olefin products. Preliminary mechanistic studies indicated that the reaction was accomplished through nickel catalyzed C—O activation of enolates, thus offering helpful contribution to current enol chemistry.
Single‐Crystalline Organoiridium Complex for Gas‐Triggered Chromogenic Switches and Its Applications on CO Detection and Reversible Scavenging
Authors: Sun Li‐Ying , An Yuan‐Yuan , Ma Li‐Li , Han Ying‐Feng 
Published: May 2019

Summary of main observation and conclusionNonporous molecular single crystals of coordinatively unsaturated 16‐electron metallacycle are found to undergo highly selective – yet reversible – binding of CO over CH4, H2, N2, CO2, various volatile organic compounds and water, through binding of the molecule to its metal centers. Carbon monoxide is taken up by black crystals and subsequently liberated from the corresponding orange CO adduct by reversible metal coordination, the structural evidence obtained from in situ X‐ray diffraction. The single‐crystallinity of the metallacycle is retained even after several cycles. The material, when adsorbed on silica, shows remarkable sensitivity and selectivity for CO, allowing visual CO sensing in the solid state. The metallacycle offer the possibility of serving as readily regenerable scavenger for removing trace CO from gas mixtures with N2.
Optimizing an AltaRica simulator
Authors: Wang Wenru , Xu Xiaojie , Hu Jian , Lu Xinghai , Shi Xiaohua 
Published: May 2019

SummarySince the AltaRica language has, in fact, become the European industry standard, the AltaRica‐based simulation method is one of the important research contents in the field of safety analysis methods. At the same time, in practical applications, simulations are mostly executed tens of thousands of times. Therefore, it is practical to optimize the execution time of the simulation method. We first analyze the hotspots in the execution of simulation methods and then propose two optimization strategies for two hot issues. The optimization method is designed and implemented by the method of space for time. Finally, the effectiveness and application scenarios of the optimization method are illustrated by experiments with different scale models. Moreover, the experiment data shows that the optimization method is effective in most cases.
Semantic locality‐based approximate knowledge graph query
Authors: Wang Yuxiang , Ge Zhangpeng , Yan Haijiang , Xu Xiaoliang , Xia Yixing 
Published: May 2019

SummaryRDF knowledge graphs (KG) usually contain billions of labeled entities, and how to obtain the desired results efficiently on RDF KG for given SPARQL queries have attracted increasing attentions recently. However, it is difficult for users to write a complex SPARQL query without full knowledge of the underlying KG schema due to the “schema‐free” feature of RDF KG. In this paper, we study the problem of acquiring semantic approximate results for a simple SPARQL query instead of the complex expression. The basic idea behind is to use the real knowledge semantics to extend the query intention of given simplified SPARQL query, and then a semantic based greedy search over is designed to return top‐k similar results. To obtain the knowledge semantics efficiently, we define type similarity to reorganize the original KG as a corpus with semantic locality and then a context aware text embedding model is adopted to achieve the semantic vectors of existing knowledge. Afterwards, an approximate query method over RDF KG is designed to obtain top‐k similar results based on the knowledge semantics above. Extensive experiments over DBpedia dataset and QALD‐4 benchmark confirm our solution's superiority on both effectiveness and efficiency.
Predisposing germline mutations in high hyperdiploid acute lymphoblastic leukemia in children
Authors: de Smith Adam J. , Lavoie Geneviève , Walsh Kyle M. , Aujla Sumeet , Evans Erica , Hansen Helen M. , Smirnov Ivan , Kang Alice Y. , Zenker Martin , Ceremsak John J. , Stieglitz Elliot , Muskens Ivo S. , Roberts William , McKean‐Cowdin Roberta , Metayer Catherine , Roux Philippe P. , Wiemels Joseph L. 
Published: May 2019

AbstractHigh hyperdiploidy (HD) is the most common cytogenetic subtype of childhood acute lymphoblastic leukemia (ALL), and a higher incidence of HD has been reported in ALL patients with congenital cancer syndromes. We assessed the frequency of predisposing germline mutations in 57 HD‐ALL patients from the California Childhood Leukemia Study via targeted sequencing of cancer‐relevant genes. Three out of 57 patients (5.3%) harbored confirmed germline mutations that were likely causal, in NBN, ETV6, and FLT3, with an additional six patients (10.5%) harboring putative predisposing mutations that were rare in unselected individuals (<0.01% allele frequency in the Exome Aggregation Consortium, ExAC) and predicted functional (scaled CADD score ≥ 20) in known or potential ALL predisposition genes (SH2B3, CREBBP, PMS2, MLL, ABL1, and MYH9). Three additional patients carried rare and predicted damaging germline mutations in GAB2, a known activator of the ERK/MAPK and PI3K/AKT pathways and binding partner of PTPN11‐encoded SHP2. The frequency of rare and predicted functional germline GAB2 mutations was significantly higher in our patients (2.6%) than in ExAC (0.28%, P = 4.4 × 10−3), an observation that was replicated in ALL patients from the TARGET project (P = .034). We cloned patient GAB2 mutations and expressed mutant proteins in HEK293 cells and found that frameshift mutation P621fs led to reduced SHP2 binding and ERK1/2 phosphorylation but significantly increased AKT phosphorylation, suggesting possible RAS‐independent leukemogenic effects. Our results support a significant contribution of rare, high penetrance germline mutations to HD‐ALL etiology, and pinpoint GAB2 as a putative novel ALL predisposition gene.
Integrated analysis of genomics, longitudinal metabolomics, and Alzheimer's risk factors among 1,111 cohort participants
Authors: Darst Burcu F. , Lu Qiongshi , Johnson Sterling C. , Engelman Corinne D. 
Published: May 2019

AbstractAlthough Alzheimer's disease (AD) is highly heritable, genetic variants are known to be associated with AD only explain a small proportion of its heritability. Genetic factors may only convey disease risk in individuals with certain environmental exposures, suggesting that a multiomics approach could reveal underlying mechanisms contributing to complex traits, such as AD. We developed an integrated network to investigate relationships between metabolomics, genomics, and AD risk factors using Wisconsin Registry for Alzheimer's Prevention participants. Analyses included 1,111 non‐Hispanic Caucasian participants with whole blood expression for 11,376 genes (imputed from dense genome‐wide genotyping), 1,097 fasting plasma metabolites, and 17 AD risk factors. A subset of 155 individuals also had 364 fastings cerebral spinal fluid (CSF) metabolites. After adjusting each of these 12,854 variables for potential confounders, we developed an undirected graphical network, representing all significant pairwise correlations upon adjusting for multiple testing. There were many instances of genes being indirectly linked to AD risk factors through metabolites, suggesting that genes may influence AD risk through particular metabolites. Follow‐up analyses suggested that glycine mediates the relationship between carbamoyl‐phosphate synthase 1 and measures of cardiovascular and diabetes risk, including body mass index, waist–hip ratio, inflammation, and insulin resistance. Further, 38 CSF metabolites explained more than 60% of the variance of CSF levels of tau, a detrimental protein that accumulates in the brain of AD patients and is necessary for its diagnosis. These results further our understanding of underlying mechanisms contributing to AD risk while demonstrating the utility of generating and integrating multiple omics data types.
Investigation of anti‐inflammatory and toxicity effects of mangrove‐derived Streptomyces rochei strain VITGAP173
Authors: Gomathi Ajitha , Gothandam Kodiveri Muthukalianan 
Published: May 2019

AbstractMangrove ecosystems generate the major biodiversity hotspots of actinobacteria. Among the actinobacteria, Streptomyces species are the prolific producers of bioactive natural products. In this study, with research efforts to discover biopotential compounds from marine actinobacteria, 41 actinobacterial strains were isolated from sediment soil sample of Indian mangrove regions. The phylogeny prediction using the 16S rRNA gene sequences revealed that the isolates were related to Streptomyces. Isolates were further screened based on a two‐step process wherein the first step, around nine strains, unveiled the presence of type 1 polyketide synthase gene and dTDP‐glucose 4,6‐dehydratase gene through polymerase chain reaction. As the second step of the screening process, cell viability assay was performed in RAW264.7 cells to assess the toxicity of extracts. Among all the isolates, Streptomyces rochei strain VITGAP173 was subjected to further analysis. To explore the bioactivities, the organic solvent extraction method was utilized to extract the broth culture of VITGAP173. Inhibition of nitric oxide and cyclooxygenase enzymes upon lipopolysaccharide‐induced inflammation were utilized to evaluate the anti‐inflammatory efficacy, and the results showed the potency of VITGAP173 in a dose‐dependent manner. The extract significantly suppressed the messenger RNA levels of the inflammatory mediators such as tumor necrosis factor‐α and interleukin‐6 induced by lipopolysaccharide in RAW264.7 macrophages. The presence of several chemical constituents was identified through gas chromatography‐mass spectrometry analysis of VITGAP173 extract. To achieve the toxicity analysis, oral administration of VITGAP173 extract in Wistar albino rats was carried out to investigate the biochemical parameters, histopathology which revealed its nontoxic nature.
RNA‐Seq analysis of potential lncRNAs and genes for the anti‐renal fibrotic effect of norcantharidin
Authors: Xiao Hengting , Liao Yingjun , Tang Chengyuan , Xiao Zheng , Luo Hanwen , Li Jun , Liu Hong , Sun Lin , Zeng Dong , Li Ying 
Published: May 2019

AbstractBackgroundAs a common phenotype in chronic kidney disease, renal interstitial fibrosis has been largely studied. Norcantharidin (NCTD), a derivative of naturally occurring cantharidin, has an anti‐renal fibrotic effect. However, its underlying mechanisms of the protective role remain largely unknown. Long noncoding RNAs (lncRNAs) play vital parts in tissue homeostasis modulation under pathophysiological conditions. In this study, we discovered the underlying lncRNAs and genes, which may contribute to the anti‐renal fibrotic effects of NCTD.MethodsRNA‐seq analysis was performed to evaluate profiling of lncRNAs and messenger RNAs (mRNAs) in kidney tissues of sham‐control, and unilateral ureteral obstruction (UUO) mouse models with or without NCTD treatment. Systematic bioinformatic analysis of expression levels was used in lncRNAs and mRNAs of NCTD‐treated UUO kidneys. Altered expression of lncRNAs and mRNAs levels was confirmed by quantitative real‐time polymerase chain reaction analysis.Results467 lncRNAs and 1502 mRNAs were differentially expressed between UUO‐ and sham‐operated kidneys, and notably, these alterations in UUO‐operated kidney were partially reversed following NCTD treatment. Interestingly, the up‐regulation of lncRNA Gm16076, Gm26669, and down‐regulation of Fam120aos were highly correlated with the up‐regulation of mRNA levels of fibrosis‐related gene ITGB1, STAT3 and reduction of Pink1 in UUO kidney, respectively.ConclusionsThe result suggested lncRNAs‐regulated genes may contribute to the anti‐renal fibrotic effect under NCTD treatment, and thus targeting lncRNAs‐controlled genes and their related molecular signaling pathways may serve as a promising therapeutic target in renal fibrosis treatment.
Reasons for smoking and barriers to cessation among adults with serious mental illness: A qualitative study
Authors: Keller‐Hamilton Brittney , Moe Aubrey M. , Breitborde Nicholas J. K. , Lee Angela , Ferketich Amy K. 
Published: May 2019

AbstractAimsMost research into reasons for smoking among adults with serious mental illness (SMI) has focused on reasons related to SMI symptoms. The current study reports reasons for smoking and barriers to cessation that are both related and unrelated to SMI symptoms among adults with SMI.MethodsFour focus groups were conducted among current smokers receiving outpatient care for a psychotic disorder in 2017 (N = 24). Participants were asked why they currently smoke and their barriers to quitting smoking.ResultsSmoking as a coping mechanism and to self‐medicate SMI symptoms were reasons for current smoking and barriers to cessation. Avoidance of other unhealthy behaviors, routine, and enjoyment emerged as reasons for smoking and barriers to cessation that were unrelated to mental illness.ConclusionConsideration of factors that are both related and unrelated to SMI symptoms in smoking cessation interventions and brief cessation counseling may improve cessation success in this population.
Silencing of long noncoding RNA RP11‐476D10.1 enhances apoptosis and autophagy while inhibiting proliferation of papillary thyroid carcinoma cells via microRNA‐138‐5p‐dependent inhibition of LRRK2
Authors: Zhao Yinlong , Zhao Lingzhi , Li Junfeng , Zhong Lili 
Published: May 2019

AbstractThe distant metastasis in papillary thyroid carcinoma (PTC) is a major threat for PTC patients. Moreover, the involvement of long noncoding RNAs (lncRNAs) in the regulation of PTC progression has been extensively investigated. The aim of this study was to underscore whether lncRNA RP11‐476D10.1 affects the proliferation, apoptosis and autophagy of PTC cells. Initially, we determined that lncRNA RP11‐476D10.1 and LRRK2 were highly expressed in PTC cells. Meanwhile, through experimentation, miR‐138‐5p was confirmed to bind with lncRNA RP11‐476D10.1 and LRRK2. It was also revealed that lncRNA RP11‐476D10.1 downregulated the miR‐138‐5p expression, thereby upregulating the LRRK2 expression. After that, PTC cells were transfected with siRNA against RP11‐476D10.1, or inhibitor or mimic of miR‐138‐5p to evaluate the influence of lncRNA RP11‐476D10.1 on the PTC cell proliferation, apoptosis, and autophagy in vitro and on the tumor formation ability in vivo. The results showed that silenced lncRNA RP11‐476D10.1 or overexpressed miR‐138‐5p enhanced the apoptosis and autophagy of PTC cells while reducing cell proliferation, with increased levels of Bax, LC3B, and Beclin1 and decreased Bcl‐2 level were observed. The inhibitory role of silenced lncRNA RP11‐476D10.1 role in the PTC development was further verified by the reduced tumor formation ability in nude mice. Our results demonstrated that lncRNA RP11‐476D10.1 could bind to miR‐138‐5p and promote LRRK2 expression. Moreover, the silencing of lncRNA RP11‐476D10.1 may inhibit the development of PTC, highlighting a novel insight for the development of superior therapeutic targets for PTC treatment.