bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-429 inhibits neuroblastoma cell proliferation, migration and invasion via the NF-κB pathway
Authors: Zhou Xianjun , Lu Hongting , Li Fujiang , Hao Xiwei , Han Lulu , Dong Qian , Chen Xin 
Published: February 2020

Abstract
Background
MicroRNAs (miRNAs or miRs) can participate in the development and progression of neuroblastoma. Many studies have indicated that miR-429 can participate in tumor development. However, the mechanism underlying miR-429-mediated progression of neuroblastoma remains largely unclear.

Methods
Colony formation and apoptosis assays were used to determine the effect of miR-429 on cell proliferation. Its impact on cell migration was determined using the wound-healing and Transwell assays. The target gene of miR-429 was confirmed via western blotting and luciferase reporter assays. A nude mouse xenograft model with miR-429 overexpression was used to assess the effect on tumor growth.

Results
Our findings indicate that miR-429 is downregulated in neuroblastoma cell lines. We also found that it can induce apoptosis and inhibit proliferation in cells of those lines. MiR-429 can bind to the 3′-UTR of IKKβ mRNA and overexpression of IKKβ can reverse cell proliferation, blocking the effect of miR-429. Furthermore, miR-429 overexpression inhibited neuroblastoma growth in our nude mouse xenograft model.

Conclusion
We provide important insight into miR-429 as a tumor suppressor through interaction with IKKβ, which is a catalytic subunit of the IKK complex that activates NF-κB nuclear transport. Our results demonstrate that miR-429 may be a new target for the treatment of neuroblastoma.
A systematic review of approaches to improve practice, detection and treatment of unhealthy alcohol use in primary health care: a role for continuous quality improvement
Authors: Dzidowska Monika , Lee K. S. Kylie , Wylie Claire , Bailie Jodie , Percival Nikki , Conigrave James H. , Hayman Noel , Conigrave Katherine M. 
Published: February 2020

AbstractBackgroundUnhealthy alcohol use involves a spectrum from hazardous use (exceeding guidelines but no harms) through to alcohol dependence. Evidence-based management of unhealthy alcohol use in primary health care has been recommended since 1979. However, sustained and systematic implementation has proven challenging. The Continuing Quality Improvement (CQI) process is designed to enable services to detect barriers, then devise and implement changes, resulting in service improvements.MethodsWe conducted a systematic review of literature reporting on strategies to improve implementation of screening and interventions for unhealthy alcohol use in primary care (MEDLINE EMBASE, PsycINFO, CINAHL, the Australian Indigenous Health InfoNet). Additional inclusion criteria were: (1) pragmatic setting; (2) reporting original data; (3) quantitative outcomes related to provision of service or change in practice. We investigate the extent to which the three essential elements of CQI are being used (data-guided activities, considering local conditions; iterative development). We compare characteristics of programs that include these three elements with those that do not. We describe the types, organizational levels (e.g. health service, practice, clinician), duration of strategies, and their outcomes.ResultsFifty-six papers representing 45 projects were included. Of these, 24 papers were randomized controlled trials, 12 controlled studies and 20 before/after and other designs. Most reported on strategies for improving implementation of screening and brief intervention. Only six addressed relapse prevention pharmacotherapies. Only five reported on patient outcomes and none showed significant improvement. The three essential CQI elements were clearly identifiable in 12 reports. More studies with three essential CQI elements had implementation and follow-up durations above the median; utilised multifaceted designs; targeted both practice and health system levels; improved screening and brief intervention than studies without the CQI elements.ConclusionUtilizing CQI methods in implementation research would appear to be well-suited to drive improvements in service delivery for unhealthy alcohol use. However, the body of literature describing such studies is still small. More well-designed research, including hybrid studies of both implementation and patient outcomes, will be needed to draw clearer conclusions on the optimal approach for implementing screening and treatment for unhealthy alcohol use. (PROSPERO registration ID: CRD42018110475).
Design for a multicenter, randomized, sham-controlled study to evaluate safety and efficacy after treatment with the Nuvaira® lung denervation system in subjects with chronic obstructive pulmonary disease (AIRFLOW-3)
Authors:   on behalf of the AIRFLOW-3 Trial Study Group, Slebos Dirk-Jan , Degano Bruno , Valipour Arschang , Shah Pallav L. , Deslée Gaetan , Sciurba Frank C. 
Published: February 2020

Abstract
Background
Targeted lung denervation (TLD) is a bronchoscopically delivered ablation therapy that selectively interrupts pulmonary parasympathetic nerve signaling. The procedure has the potential to alter airway smooth muscle tone and reactivity, decrease mucous secretion, and reduce airway inflammation and reflex airway hyperresponsiveness. Secondary outcome analysis of a previous randomized, sham-controlled trial showed a reduction in moderate-to-severe exacerbations in patients with COPD after TLD treatment. A pivotal trial, AIRFLOW-3 has been designed to evaluate the safety and efficacy of TLD combined with optimal medical therapy to reduce moderate or severe exacerbations throughout 1 year, compared with optimal medical therapy alone.

Methods
The study design is a multicenter, randomized, full sham bronchoscopy controlled, double-blind trial that will enroll 400 patients (1:1 randomization). Key inclusion criteria are FEV1/FVC < 0.7, FEV1 30 to 60% of predicted, post-bronchodilator, ≥ 2 moderate or 1 severe COPD exacerbations in the prior year, and COPD assessment test (CAT) ≥ 10. Primary objective will be the comparison of moderate or severe COPD exacerbations through 12 months of TLD therapy with optimal medical therapy versus optimal medical therapy alone. The sham group will be allowed to cross over at 1 year. Patients will be followed for up to 5 years.

Discussion
The multicenter, randomized, full sham bronchoscopy controlled, double-blind AIRFLOW-3 trial will evaluate the efficacy of TLD to reduce moderate or severe COPD exacerbations beyond optimal medical therapy alone. The target population are patients with COPD, who suffer persistent symptoms and exacerbations despite optimal treatment, defining an unmet medical need requiring novel therapeutic solutions. This trial is registered at clinicaltrials.gov: NCT03639051.
Frequent mutation of hypoxia-related genes in persistent pulmonary hypertension of the newborn
Authors: Wang Mingbang , Zhuang Deyi , Mei Mei , Ma Haiyan , Li Zixiu , He Fusheng , Cheng Guoqiang , Lin Guang , Zhou Wenhao 
Published: February 2020

Abstract
Aims
Persistent pulmonary hypertension of the newborn (PPHN) is characterized by sustained high levels of pulmonary vascular resistance after birth with etiology unclear; Arterial blood oxygen saturation of Tibetan newborns at high latitudes is higher than that of Han newborns at low latitudes, suggesting that genetic adaptation may allow sufficient oxygen to confer Tibetan populations with resistance to pulmonary hypertension; We have previously identified genetic factors related to PPHN through candidate gene sequencing; In this study, we first performed whole exome sequencing in PPHN patients to screen for genetic-related factors.

Methods and results
In this two-phase genetic study, we first sequenced the whole exome of 20 Tibetan PPHN patients and compared it with the published genome sequences of 50 healthy high-altitude Tibetanshypoxia-related genes, a total of 166 PPHN-related variants were found, of which 49% were from 43 hypoxia-related genes; considering many studies have shown that the differences in the genetic background between Tibet and Han are characterized by hypoxia-related genetic polymorphisms, so it is necessary to further verify whether the association between hypoxia-related variants and PPHN is independent of high-altitude life. During the validation phase, 237 hypoxia-related genes were sequenced in another 80 Han PPHN patients living in low altitude areas, including genes at the discovery stage and known hypoxia tolerance, of which 413 variants from 127 of these genes were shown to be significantly associated with PPHN.hypoxia-related genes.

Conclusions
Our results indicates that the association of hypoxia-related genes with PPHN does not depend on high-altitude life, at the same time, 21 rare mutations associated with PPHN were also found, including three rare variants of the tubulin tyrosine ligase-like family member 3 gene (TTLL3:p.E317K, TTLL3:p.P777S) and the integrin subunit alpha M gene (ITGAM:p.E1071D). These novel findings provide important information on the genetic basis of PPHN.
Endoscopic radial incision method for two strictures of the esophagus after endoscopic submucosal dissection: a case report
Authors: Huang Zhong , Wei Wei , Cheng Fang 
Published: February 2020

Abstract
Background
The development of severe esophageal stricture after endoscopic submucosal dissection (ESD) for early esophageal carcinoma is not uncommon. Dilation by Savary-Gilliard dilators or balloon dilators is the first-line treatment for such complex refractory benign stricture, but it has a high risk of treatment failure. So far, endoscopic radial incision (ERI) as a new technology for the treatment of post-ESD esophageal stricture has been rarely reported. We report a case, which we designed to assess the efficacy and safety of ERI technology for two severe strictures of the esophagus after ESD.

Case presentation
A 67-year-old man had suffered from two complex refractory benign strictures of the esophagus after ESD for early esophageal carcinoma. The patient was refractory to multiple endoscopic balloon dilation (EBD) therapy previously. Thus, the patient underwent ERI successfully and without postoperative complications such as fever, poststernal pain, bleeding, and perforation. During 3 months of follow-up after ERI, the patient had no recurrence of dysphagia.

Conclusions
Refractory strictures of the esophagus after ESD are common. ERI is a safe and efficient strategy for treating such multiple refractory esophageal strictures.
Can-Seq: a PCR and DNA sequencing strategy for identifying new alleles of known and candidate genes
Authors: Cao Jiangling , Gursanscky Nial R. , Fletcher Stephen J. , Sawyer Anne , Wadia Mehershad , McKeough Lachlan , Coleman Marek , Dressel Uwe , Taochy Christelle , Mitter Neena , Vaucheret Hervé , Carroll Bernard J. 
Published: February 2020

Abstract
Background
Forward genetic screens are a powerful approach for identifying the genes contributing to a trait of interest. However, mutants arising in genes already known can obscure the identification of new genes contributing to the trait. Here, we describe a strategy called Candidate gene-Sequencing (Can-Seq) for rapidly identifying and filtering out mutants carrying new alleles of known and candidate genes.

Results
We carried out a forward genetic screen and identified 40 independent Arabidopsis mutants with defects in systemic spreading of RNA interference (RNAi), or more specifically in root-to-shoot transmission of post-transcriptional gene silencing (rtp). To classify the mutants as either representing a new allele of a known or candidate gene versus carrying a mutation in an undiscovered gene, bulk genomic DNA from up to 23 independent mutants was used as template to amplify a collection of 47 known or candidate genes. These amplified sequences were combined into Can-Seq libraries and deep sequenced. Subsequently, mutations in the known and candidate genes were identified using a custom Snakemake script (https://github.com/Carroll-Lab/can_seq), and PCR zygosity tests were then designed and used to identify the individual mutants carrying each mutation. Using this approach, we showed that 28 of the 40 rtp mutants carried homozygous nonsense, missense or splice site mutations in one or more of the 47 known or candidate genes. We conducted complementation tests to demonstrate that several of the candidate mutations were responsible for the rtp defect. Importantly, by exclusion, the Can-Seq pipeline also identified rtp mutants that did not carry a causative mutation in any of the 47 known and candidate genes, and these mutants represent an undiscovered gene(s) required for systemic RNAi.

Conclusions
Can-Seq offers an accurate, cost-effective method for classifying new mutants into known versus unknown genes. It has several advantages over existing genetic and DNA sequencing approaches that are currently being used in forward genetic screens for gene discovery. Using Can-Seq in conjunction with map-based gene cloning is a cost-effective approach towards identifying the full complement of genes contributing to a trait of interest.
GrpClassifierEC: a novel classification approach based on the ensemble clustering space
Authors: Abdallah Loai , Yousef Malik 
Published: February 2020

Abstract
Background
Advances in molecular biology have resulted in big and complicated data sets, therefore a clustering approach that able to capture the actual structure and the hidden patterns of the data is required. Moreover, the geometric space may not reflects the actual similarity between the different objects. As a result, in this research we use clustering-based space that convert the geometric space of the molecular to a categorical space based on clustering results. Then we use this space for developing a new classification algorithm.

Results
In this study, we propose a new classification method named GrpClassifierEC that replaces the given data space with categorical space based on ensemble clustering (EC). The EC space is defined by tracking the membership of the points over multiple runs of clustering algorithms. Different points that were included in the same clusters will be represented as a single point. Our algorithm classifies all these points as a single class. The similarity between two objects is defined as the number of times that these objects were not belong to the same cluster. In order to evaluate our suggested method, we compare its results to the k nearest neighbors, Decision tree and Random forest classification algorithms on several benchmark datasets. The results confirm that the suggested new algorithm GrpClassifierEC outperforms the other algorithms.

Conclusions
Our algorithm can be integrated with many other algorithms. In this research, we use only the k-means clustering algorithm with different k values. In future research, we propose several directions: (1) checking the effect of the clustering algorithm to build an ensemble clustering space. (2) Finding poor clustering results based on the training data, (3) reducing the volume of the data by combining similar points based on the EC.

Availability and implementation
The KNIME workflow, implementing GrpClassifierEC, is available at https://malikyousef.com
Nasal Airway Obstruction Study (NAIROS): a phase III, open-label, mixed-methods, multicentre randomised controlled trial of septoplasty versus medical management of a septal deviation with nasal obstruction
Authors:   for the NAIROS Study Group, Rennie Katherine J. , O’Hara James , Rousseau Nikki , Stocken Deborah , Howel Denise , Ternent Laura , Drinnan Mike , Bray Alison , Rooshenas Leila , Hamilton David W. , Steel Alison , Fouweather Tony , Hynes Ann-Marie , Holstein Eva-Maria , Oluboyede Yemi , Abouhajar Alaa , Wilson Janet A. , Carrie Sean 
Published: February 2020

AbstractBackgroundSeptoplasty (surgery to straighten a deviation in the nasal septum) is a frequently performed operation worldwide, with approximately 250,000 performed annually in the US and 22,000 in the UK. Most septoplasties aim to improve diurnal and nocturnal nasal obstruction. The evidence base for septoplasty clinical effectiveness is hitherto very limited.AimsTo establish, and inform guidance for, the best management strategy for individuals with nasal obstruction associated with a deviated septum.Methods/designA multicentre, mixed-methods, open label, randomised controlled trial of septoplasty versus medical management for adults with a deviated septum and a reduced nasal airway. Eligible patients will have septal deflection visible at nasendoscopy and a nasal symptom score ≥ 30 on the NOSE questionnaire. Surgical treatment comprises septoplasty with or without reduction of the inferior nasal turbinate on the anatomically wider side of the nose. Medical management comprises a nasal saline spray followed by a fluorinated steroid spray daily for six months. The recruitment target is 378 patients, recruited from up to 17 sites across Scotland, England and Wales. Randomisation will be on a 1:1 basis, stratified by gender and severity (NOSE score). Participants will be followed up for 12 months post randomisation. The primary outcome measure is the total SNOT-22 score at 6 months. Clinical and economic outcomes will be modelled against baseline severity (NOSE scale) to inform clinical decision-making. The study includes a recruitment enhancement process, and an economic evaluation.DiscussionThe NAIROS trial will evaluate the clinical effectiveness and cost-effectiveness of septoplasty versus medical management for adults with a deviated septum and symptoms of nasal blockage. Identifying those individuals most likely to benefit from surgery should enable more efficient and effective clinical decision-making, and avoid unnecessary operations where there is low likelihood of patient benefit.Trial registrationEudraCT: 2017–000893-12, ISRCTN:16168569. Registered on 24 March 2017.
Evaluation of fluralaner as an oral acaricide to reduce tick infestation in a wild rodent reservoir of Lyme disease
Authors: Pelletier Jérôme , Rocheleau Jean-Philippe , Aenishaenslin Cécile , Beaudry Francis , Dimitri Masson Gabrielle , Lindsay L. Robbin , Ogden Nicholas H. , Bouchard Catherine , Leighton Patrick A. 
Published: February 2020

Abstract
Background
Lyme disease (LD) is an increasing public health threat in temperate zones of the northern hemisphere, yet relatively few methods exist for reducing LD risk in endemic areas. Disrupting the LD transmission cycle in nature is a promising avenue for risk reduction. This experimental study evaluated the efficacy of fluralaner, a recent oral acaricide with a long duration of effect in dogs, for killing Ixodes scapularis ticks in Peromyscus maniculatus mice, a known wildlife reservoir for Borrelia burgdorferi in nature.

Methods
We assigned 87 mice to 3 fluralaner treatment groups (50 mg/kg, 12.5 mg/kg and untreated control) administered as a single oral treatment. Mice were then infested with 20 Ixodes scapularis larvae at 2, 28 and 45 days post-treatment and we measured efficacy as the proportion of infesting larvae that died within 48 h. At each infestation, blood from 3 mice in each treatment group was tested to obtain fluralaner plasma concentrations (Cp).

Results
Treatment with 50 mg/kg and 12.5 mg/kg fluralaner killed 97% and 94% of infesting larvae 2 days post-treatment, but no significant effect of treatment on feeding larvae was observed 28 and 45 days post-treatment. Mouse Cp did not differ significantly between the two tested doses. Mean Cp decreased from 13,000 ng/ml in the 50 mg/kg group and 4000 ng/ml in the 12.5 mg/kg group at Day 2 to < 100 ng/ml in both groups at Day 45.

Conclusions
We provide the first evidence that fluralaner is effective for killing immature ticks in Peromyscus mice, a first step in evaluating its potential for treating wild rodents as a public health intervention to reduce LD risk in endemic areas.
Analysis of the model of HIV-1 infection of $CD4^{+}$ T-cell with a new approach of fractional derivative
Authors: Baleanu Dumitru , Mohammadi Hakimeh , Rezapour Shahram 
Published: February 2020

AbstractBy using the fractional Caputo–Fabrizio derivative, we investigate a new version for the mathematical model of HIV. In this way, we review the existence and uniqueness of the solution for the model by using fixed point theory. We solve the equation by a combination of the Laplace transform and homotopy analysis method. Finally, we provide some numerical analytics and comparisons of the results.
Sex-differences in fine-scale home-range use in an upper-trophic level marine predator
Authors: Lidgard D. C. , Bowen W. D. , Iverson S. J. 
Published: February 2020

Abstract
Background
The distribution of prey in the ocean is spatially and temporally patchy. How predators respond to this prey patchiness may have consequences on their foraging success, and thus physical condition. The recent ability to record fine-scale movements of marine animals combined with novel home-range analyses that incorporate the dimension of time should permit a better understanding of how individuals utilise different regions of space and the consequences on their foraging success.

Methods
Over a six-year study, we used T-LoCoH (Time-Local Convex Hull) home-range software to model archival GPS (Global Positioning System) data from 81 grey seals to investigate the fine-scale spatio-temporal use of space and the distribution of apparent foraging effort. Regions of home-ranges were classified according to the frequency of return visits (site fidelity) and duration of visits (intensity of use). Generalized linear mixed -effects models were used to test hypotheses on seasonal changes in foraging distribution and behaviour and the role of space-use and state on determining foraging success.

Results
Male grey seals had larger home-ranges and core areas than females, and both sexes showed a contraction in home-range and core area in fall leading up to the breeding season compared with summer. Heavier individuals had smaller core areas than lighter ones, suggesting access to higher quality habitat might be limited to those individuals with greater foraging experience and competitive ability. The size of the home-range or core area was not an important predictor of the rate of mass gain. A fine-scale spatio-temporal analysis of habitat use within the home-range provided evidence of intra-annual site fidelity at presumed foraging locations, suggesting predictably in prey distribution. Neither sex nor season were useful predictors for classifying behaviour. Rather, individual identity explained much of the variation in fine-scale behaviour.

Conclusions
Understanding how upper-trophic level marine predators use space provides opportunities to explore the consequences of variation in foraging tactics and their success on fitness. Having knowledge of the drivers that shape this intraspecific variation can contribute toward predicting how these predators may respond to both natural and man-made environmental forcing.