bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing pleiotropy and mediation in genetic loci associated with chronic obstructive pulmonary disease
Authors: Parker Margaret M. , Lutz Sharon M. , Hobbs Brian D. , Busch Robert , McDonald MerryLynn N. , Castaldi Peter J. , Beaty Terri H. , Hokanson John E. , Silverman Edwin K. , Cho Michael H. 
Published: February 2019

AbstractGenetic association studies have increasingly recognized variant effects on multiple phenotypes. Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with environmental and genetic causes. Multiple genetic variants have been associated with COPD, many of which show significant associations to additional phenotypes. However, it is unknown if these associations represent biological pleiotropy or if they exist through correlation of related phenotypes (“mediated pleiotropy”). Using 6,670 subjects from the COPDGene study, we describe the association of known COPD susceptibility loci with other COPD‐related phenotypes and distinguish if these act directly on the phenotypes (i.e., biological pleiotropy) or if the association is due to correlation (i.e., mediated pleiotropy). We identified additional associated phenotypes for 13 of 25 known COPD loci. Tests for pleiotropy between genotype and associated outcomes were significant for all loci. In cases of significant pleiotropy, we performed mediation analysis to test if SNPs had a direct association to phenotype. Most loci showed a mediated effect through the hypothesized causal pathway. However, many loci also had direct associations, suggesting causal explanations (i.e., emphysema leading to reduced lung function) are incomplete. Our results highlight the high degree of pleiotropy in complex disease‐associated loci and provide novel insights into the mechanisms underlying COPD.
Evaluation of neotectonic variability along major Himalayan thrusts within the Kali River basin using geomorphic markers, Central Kumaun Himalaya, India
Authors: Talukdar Riyanka , Kothyari Girish Ch. , Pant Charu C. 
Published: February 2019

We have analysed the geomorphic signatures in aggregation with the geomorphic indices with respect to hinterland and foreland neotectonic variability across the major Himalayan thrust system along the Kali River valley of eastern Kumaun Himalaya. The valley floor morphology in the vicinity of the major thrust gave rise to the accommodation space for the aggradation of the recent fluvial sediments. For a longitudinal distance of 212 km between the South Tibet Detachment (STD) and Himalayan Frontal Thrust (HFT), the valley has preserved significant aggradational landforms. These landforms have been physically examined to explain the spatial and temporal variability in phases of aggradation/incision in response to the tectonic activity during the late Quaternary. Fossil valleys and associated epigenetic gorges, cut‐and‐fill terraces with thick alluvial cover, debris‐flow terraces, bedrock strath terraces, and alluvial fan terraces are the significant aggradational landforms observed within the valley. They provide signatures of tectonic activity and past climatic records. We have analysed various geomorphic indices, namely, stream‐gradient index (SL), steepness index (Ks), hypsometric curve and index (HI), and asymmetric factor (AF) to map the spatial variability in tectonic processes across the major thrusts. The channel morphology (depth and width) of a river becomes adjusted in geological time because of long‐term tectonic and erosional processes. However, the channel geometry and deviations can be highly adjustable in a tectonically disturbed mountainous region. The deviations along the river course can be attributed to active tectonic movement along thrusts/faults or because of erosion/sedimentation processes. We applied a novel method called the river Gradient Length Anomaly (GLA) for 37 subbasins of the Kali River to deduce active deformation (uplift/subsidence) corresponding to the increased sedimentation and erosional rates, both from the upstream and downstream parts of the thrusted blocks, from where river flows through. The results of basin‐wise morphometric indices were corroborated with GLA anomaly and field observations, which suggests that the area has undergone active deformation between the Main Central Thrust (MCT) and Himalayan Frontal Thrust (HFT), which is attributed to the regional compression. The results of geomorphic and morphometric data are validated with the focal mechanisms of moderate earthquakes. The geomorphic analysis suggests that the hinterland part of eastern Kumaun is more active than the foreland region.
Nicotine induces cell survival and chemoresistance by stimulating Mcl‐1 phosphorylation and its interaction with Bak in lung cancer
Authors: Liu Ling , Shi Xiaqing , Zhao Huandong , Yang Manyi , Wang Chengzhi , Liao Mingmei , Zhao Jinfeng 
Published: February 2019

AbstractNicotine is a major carcinogen in cigarettes, which can enhance cell proliferation and metastasis and increase the chemoresistance of cancer cells. Our previous data found that nicotine promotes cell survival in lung cancer by affecting the expression of antiapoptotic protein Mcl‐1, suggesting that the Mcl‐1 may be a therapeutic target for patients with lung cancer. In this study, we found that the effects of drug resistance on nicotine‐induced lung cancer cell lines were shown to influence the phosphorylation of Mcl‐1. Moreover, nicotine induces Mcl‐1 phosphorylation exclusively at the T163 site, which results in enhancement of the antiapoptotic activity of Mcl‐1 and increased cell survival. Meanwhile, nicotine can reduce the sensitivity of H1299 cells to CDDP via enhancement of the binding of Mcl‐1 to Bak, which inhibits the proapoptotic effect of Bak and ultimately leads to increased survival and drug resistance of lung cancer cells. Thus, nicotine‐induced cell survival and chemoresistance may occur in a mechanism by stimulating Mcl‐1 phosphorylation and its interaction with Bak, which may contribute to improving the efficacy of chemotherapy in the treatment of human lung cancer.
miR‐142‐3p is a tumor suppressor that inhibits estrogen receptor expression in ER‐positive breast cancer
Authors: Mansoori Behzad , Mohammadi Ali , Gjerstorff Morten F. , Shirjang Solmaz , Asadzadeh Zahra , Khaze Vahid , Holmskov Uffe , Kazemi Tohid , Duijf Pascal H. G. , Baradaran Behzad 
Published: February 2019

AbstractEstrogen receptors (ERs) are involved in the development of many types of malignant tumors, in particular, breast cancer. Among others, ERs affect cell growth, proliferation, and differentiation. The microRNA (miRNA) miR‐142‐3p has been shown to inhibit carcinogenesis by regulating various cellular processes, including cell cycle progression, cell migration, apoptosis, and invasion. It does so via targeting molecules involved in a range of signaling pathways. We surgically collected 20 ER‐positive breast cancer samples, each with matched adjacent normal breast tissue, and measured the expression of miR‐142‐3p via quantitative real‐time polymerase chain reaction (qRT‐PCR). Bioinformatics methods, luciferase reporter assay, qRT‐PCR, and western blot analysis were used to assess whether miR‐142‐3p could target ESR1, which encodes the estrogen receptor, in ER‐positive breast cancer cells and patient samples. We also restored miRNA expression and performed cell viability, cytotoxicity, and colony formation assays. Western blot analysis and qRT‐PCR were used to study the expression of apoptosis and stemness markers. We found that miR‐142‐3p is downregulated in ER‐positive breast cancers. Restoration of miR‐142‐3p expression in ER‐positive breast cancer cells reduced cell viability, induced apoptosis via the intrinsic pathway and decreased both colony formation and the expression of stem cell markers. Bioinformatic analysis predicted miR‐142‐3p could bind to 3′‐untranslated region ESR1 messenger RNA (mRNA). Consistently, we demonstrated that miR‐142‐3p reduced luciferase activity in ER‐positive breast cancer cells, and decreased ESR1 expression in both mRNA and protein levels. The results revealed miR‐142‐3p and ESR1 expression correlated negatively in ER‐positive breast cancer samples. The results suggest miR‐142‐3p acts as a tumor suppressor via multiple mechanisms. Thus, restoration of miR‐142‐3p expression, for example, via miRNA replacement therapy, may represent an effective strategy for the treatment of ER‐positive breast cancer patients.
Synergistic activity of chlorhexidine and synoeca‐MP peptide against Pseudomonas aeruginosa
Authors: Dantas Elaine M. G. L. , Lima Stella M. F. , Cantuária Ana Paula C. , Amorim Ingrid A. , Almeida Jeeser A. , Cunha Tássio F. , Franco Octávio L. , Rezende Taia M. B. 
Published: February 2019

Abstract‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬This study aims to evaluate the in vitro antimicrobial and immunomodulatory activities and cytotoxicity of chlorhexidine (CHX) and synoeca‐MP peptide alone or in combination against Pseudomonas aeruginosa. The antimicrobial property was evaluated by the determination of minimal inhibitory concentration, minimum bactericidal concentration, and planktonic bacteria and biofilm inhibition. Immunomodulatory activity was determined by enzyme‐linked immunosorbent assay and nitric oxide production by the Griess reaction method. According to the results, synoeca‐MP combined with CHX demonstrated antimicrobial effectiveness compared with its isolated use, in addition to immunomodulatory activity (upregulating MPC‐1 and tumor necrosis factor‐α and downregulating nitric oxide and interleukin‐10). In this context, it is expected that the substances, together, could be capable of controlling bacterial infection and dissemination, besides potentiating macrophages’ immune response against the studied microorganism. Moreover, reducing the CHX concentration by the addition of synoeca‐MP peptide may, in a beneficial way, minimize the undesirable effects of both, CHX and synoeca‐MP in a clinical setting.
LncRNA CRNDE regulates the proliferation and migration of vascular smooth muscle cells
Authors: Zhou Yu , He Xuyu , Liu Ruiming , Qin Yuansen , Wang Shenming , Yao Xi , Li Chunying , Hu Zuojun 
Published: February 2019

AbstractRestenosis after angioplasty or stent is a major clinical problem. While long noncoding RNAs (lncRNAs) are implicated in a variety of diseases, their role in restenosis is not well understood. This study aims to investigate how dysregulated lncRNAs and messenger RNAs (mRNAs) contribute to restenosis. By microarray analysis, we identified 202 lncRNAs and 625 mRNAs (fold change > 2.0, p < 0.05) differentially expressed between the balloon‐injured carotid artery and uninjured carotid artery in the rats. Among differentially expressed lncRNAs, LncRNA CRNDE had the highest fold change and the change was validated by reverse transcription polymerase chain reaction. We found that LncRNA CRNDE was significantly upregulated in injured rat carotid artery and vascular smooth muscle cells (VSMCs) stimulated by platelet‐derived growth factor‐BB (PDGF‐BB). Knockdown of LncRNA CRNDE by small interference RNA significantly inhibited PDGF‐BB stimulated proliferation and migration of VSMCs. Moreover, knockdown of LncRNA CRNDE attenuated PDGF‐BB‐induced phenotypic change of VSMCs. Taken together, our study reveals a novel mechanoresponsive LncRNA CRNDE which may be a therapeutic target for restenosis.
Microcosm evaluation of bioaugmentation and biostimulation efficacy on diesel‐contaminated soil
Authors: Bosco Francesca , Casale Annalisa , Mazzarino Italo , Godio Alberto , Ruffino Barbara , Mollea Chiara , Chiampo Fulvia 
Published: February 2019

AbstractBACKGROUNDDiesel oil broad utilization has led to its dispersion in the environment. In this work, biostimulation and biostimulation coupled with autochthonous bioaugmentation were investigated for the bioremediation of soil artificially contaminated with diesel oil.RESULTSSoil microcosms were prepared and monitored. The most effective strategy and the influence of glucose addition, both in soil or during the biomass ‘enrichment’ phase, were evaluated by means of respirometric analyses, microbial counts and residual contaminant concentration measurements. The respirometric activity was always higher in all microcosms contaminated with diesel oil than in the biotic controls. The presence of the contaminant did not inhibit the microbial activity. The microbial counts performed on diesel oil medium showed that the contaminant was prevalently biodegraded by the indigenous bacterial species. In terms of diesel oil degradation, similar results were obtained in biostimulated and bioaugmented microcosms; a degradation percentage in the range 65–70% after 34 days was achieved. The addition of glucose in soil, though favoring the growth of microorganisms, did not improve the degradation of contaminant.CONCLUSIONIn this work, biostimulation, with no addition of a primary substrate, was the simplest and most cost‐effective strategy for the biodegradation of diesel oil. © 2019 Society of Chemical Industry
An effective and accurate identification system of Mycobacterium tuberculosis using convolution neural networks
Authors: Kuok Chan‐Pang , Horng Ming‐Huwi , Liao Yu‐Ming , Chow Nan‐Haw , Sun Yung‐Nien 
Published: February 2019

AbstractTuberculosis (TB) remains the leading cause of morbidity and mortality from infectious disease in developing countries. The sputum smear microscopy remains the primary diagnostic laboratory test. However, microscopic examination is always time‐consuming and tedious. Therefore, an effective computer‐aided image identification system is needed to provide timely assistance in diagnosis. The current identification system usually suffers from complex color variations of the images, resulting in plentiful of false object detection. To overcome the dilemma, we propose a two‐stage Mycobacterium tuberculosis identification system, consisting of candidate detection and classification using convolution neural networks (CNNs). The refined Faster region‐based CNN was used to distinguish candidates of M. tuberculosis and the actual ones were classified by utilizing CNN‐based classifier. We first compared three different CNNs, including ensemble CNN, single‐member CNN, and deep CNN. The experimental results showed that both ensemble and deep CNNs were on par with similar identification performance when analyzing more than 19,000 images. A much better recall value was achieved by using our proposed system in comparison with conventional pixel‐based support vector machine method for M. tuberculosis bacilli detection.
Genetic counselors' perceptions of uncertainty in pretest counseling for genomic sequencing: A qualitative study
Authors: Park Jessica , Zayhowski Kimberly , Newson Ainsley J. , Ormond Kelly E. 
Published: February 2019

AbstractIncreased usage of exome and genome sequencing has made uncertainties associated with genomic sequencing methods more prevalent within medicine. Current research focuses on patients' perceptions of uncertainty related to genomic sequencing, but there is limited knowledge of the perspectives of providers. The aim of this study was to explore how professionals in genomics perceive uncertainties involved in genomic sequencing, and if or how this impacts their approach to pretest counseling. We performed 20 semi‐structured interviews with genetic counselors in the United States and Canada who provide pretest genetic counseling for genomic sequencing. Interviews explored participating genetic counselors' views of uncertainty regarding genomic sequencing, how they classify it, how it manifests, and how they manage it during pretest counseling. Thematic analysis showed that genetic counselors acknowledge concepts of uncertainty that map to existing frameworks of uncertainty for genomic sequencing. Genetic counselors also perceived incongruencies between patients' and providers' expectations of genomic sequencing, which prompted them to modify patients' perceptions of uncertainty related to genomic sequencing. All genetic counselors agreed that guidance and strategies for genomic sequencing pretest counseling would be helpful, particularly for novice genetic counselors and non‐genetics providers. These findings highlight the need and potential for conceptual models of uncertainty and uncertainty management strategies to facilitate patient‐centered pretest counseling for genomic sequencing.
Pancreatic parenchymal calcification induced by permanent indwelling transmural stent
Authors: Rana Surinder S , Sharma Ravi , Gupta Rajesh 
Published: February 2019

AbstractLong‐term transmural stent placement is a safe and effective strategy for the prevention of recurrence of pancreatic fluid collection in patients with walled‐off necrosis and disconnected pancreatic duct syndrome. The presence of a stent for an indefinite period has been shown to be safe without any serious adverse effects. We report a rare case of pancreatic parenchymal calcification induced by long‐term transmural stent.
Clinical effectiveness of enzyme replacement therapy with galsulfase in mucopolysaccharidosis type VI treatment: Systematic review
Authors: Gomes Dalila Fernandes , Gallo Luciana Guerra , Leite Betânia Ferreira , Silva Roberta Borges , da Silva Everton Nunes 
Published: February 2019

AbstractIntroductionMucopolysaccharidosis VI is a rare disease characterized by the arylsulfatase B enzyme deficiency, which is responsible for different clinical manifestations. The treatment consists of enzyme replacement therapy with intravenous administration of galsulfase.ObjectiveEvaluate the effectiveness of the enzyme replacement therapy with galsulfase for the mucopolysaccharidosis VI treatment.MethodSystematic review of observational studies. The databases of PubMed, Cochrane Library, Lilacs, and Journal of Inherited Metabolic Disease were reviewed. The selection of studies, data mining, and methodological quality assessment were independently conducted by two authors.ResultsEighteen studies fulfilled the inclusion criteria. Two studies were cohorts, one was longitudinal study, one was cross‐sectional, one was a case–control, eight were case series, and five were case reports. A total of 362 participants with mucopolysaccharidosis type VI were evaluated, and 14 different outcomes related to the treatment effect were identified. Seven outcomes showed positive results, characterized by the patient survival, quality of life, respiratory function, joint mobility, physical resistance, reduction of urinary glycosaminoglycans, and growth. The hearing function and the cognitive development were stable after the treatment. Other outcomes related to the cardiac function, visual acuity, sleep apnea, and the size of the liver and spleen presented inconclusive outcomes. Concerning safety, light adverse reactions of hypersensitivity were reported.ConclusionThis review provided a broader panoramic view of the outcomes related to mucopolysaccharidosis type VI. Regardless of the inherent limitations of observational studies, the outcomes indicate that the enzyme replacement therapy has a positive effect on most of the outcomes associated to the disease.
Influence of implementing a protocol for an intravenously administered ammonia scavenger on the management of acute hyperammonemia in a pediatric intensive care unit
Authors: Brossier David , Goyer Isabelle , Ziani Lydia , Marquis Christopher , Mitchell Grant , Ozanne Bruno , Jouvet Philippe 
Published: February 2019

AbstractThe purpose of the study was to evaluate the influence of establishing a protocol for the use of combined sodium benzoate and sodium phenylacetate (SBSP) (Ammonul®) to treat acute hyperammonemia. This was a retrospective, single‐center study in a 24‐bed medical and surgical pediatric intensive care unit (PICU) in a tertiary care teaching maternal–child hospital in Canada. Inclusion criteria were age < 18 years, PICU admission between 1 January 2000 and 30 June 2016, and SBSP treatment. An SBSP delivery protocol was implemented in our hospital on 30 August 2008 in order to improve management of acute hyperammonemia. Patients were assigned to one of the two groups, without or with protocol, depending on date of admission. SBSP was ordered 34 times during the study period, and 23 orders were considered for analysis (14 with and 9 without protocol). Patient characteristics were similar between groups. The median time from diagnosis to prescription was significantly shorter in the protocol group [40 min (21–82) vs 100 min (70–150), p = 0.03)] but the median time from diagnosis to administration of the treatment was equivalent [144 min (90–220) vs 195 (143–274), (p = 0.2)]. Other clinical outcomes did not differ. This study is the first to compare two SBSP delivery strategies in the treatment of acute hyperammonemia in this PICU setting. Implementation of a delivery protocol shortened the time from diagnosis of hyperammonemia to prescription of SBSP and helped us identify other parameters that can be improved to optimize treatment delivery.
Combined malonic and methylmalonic aciduria due to ACSF3 mutations: Benign clinical course in an unselected cohort
Authors: Levtova Alina , Waters Paula J. , Buhas Daniela , Lévesque Sébastien , Auray‐Blais Christiane , Clarke Joe T.R. , Laframboise Rachel , Maranda Bruno , Mitchell Grant A. , Brunel‐Guitton Catherine , Braverman Nancy E. 
Published: February 2019

AbstractBackgroundThe clinical significance of combined malonic and methylmalonic aciduria due to ACSF3 deficiency (CMAMMA) is controversial. In most publications, affected patients were identified during the investigation of various complaints.MethodsUsing a cross‐sectional multicenter retrospective natural history study, we describe the course of all known CMAMMA individuals in the province of Quebec.ResultsWe identified 25 CMAMMA patients (6 months to 30 years old) with a favorable outcome regardless of treatment. All but one came to clinical attention through the Provincial Neonatal Urine Screening Program (screening on day 21 of life). Median methylmalonic acid (MMA) levels ranged from 107 to 857 mmol/mol creatinine in urine (<10) and from 8 to 42 μmol/L in plasma (<0.4); median urine malonic acid (MA) levels ranged from 9 to 280 mmol/mol creatinine (<5). MMA was consistently higher than MA. These findings are comparable to those previously reported in CMAMMA. Causal ACSF3 mutations were identified in all patients for whom genotyping was performed (76% of cases). The most common ACSF3 mutations in our cohort were c.1075G > A (p.E359K) and c.1672C > T (p.R558W), representing 38.2 and 20.6% of alleles in genotyped families, respectively; we also report several novel mutations.ConclusionBecause our province still performs urine newborn screening, our patient cohort is the only one free of selection bias. Therefore, the favorable clinical course observed suggests that CMAMMA is probably a benign condition, although we cannot exclude the possibility that a small minority of patients may present symptoms attributable to CMAMMA, perhaps as a result of interactions with other genetic or environmental factors.