bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a high-throughput screen to identify small molecule enhancers of sarcospan for the treatment of Duchenne muscular dystrophy
Authors: Shu Cynthia , Kaxon-Rupp Ariana N. , Collado Judd R. , Damoiseaux Robert , Crosbie Rachelle H. 
Published: December 2019

AbstractBackgroundDuchenne muscular dystrophy (DMD) is caused by loss of sarcolemma connection to the extracellular matrix. Transgenic overexpression of the transmembrane protein sarcospan (SSPN) in the DMDmdxmouse model significantly reduces disease pathology by restoring membrane adhesion. Identifying SSPN-based therapies has the potential to benefit patients with DMD and other forms of muscular dystrophies caused by deficits in muscle cell adhesion.MethodsStandard cloning methods were used to generate C2C12 myoblasts stably transfected with a fluorescence reporter for human SSPN promoter activity. Assay development and screening were performed in a core facility using liquid handlers and imaging systems specialized for use with a 384-well microplate format. Drug-treated cells were analyzed for target gene expression using quantitative PCR and target protein expression using immunoblotting.ResultsWe investigated the gene expression profiles of SSPN and its associated proteins during myoblast differentiation into myotubes, revealing an increase in expression after 3 days of differentiation. We created C2C12 muscle cells expressing an EGFP reporter for SSPN promoter activity and observed a comparable increase in reporter levels during differentiation. Assay conditions for high-throughput screening were optimized for a 384-well microplate format and a high-content imager for the visualization of reporter levels. We conducted a screen of 3200 compounds and identified seven hits, which include an overrepresentation of L-type calcium channel antagonists, suggesting that SSPN gene activity is sensitive to calcium. Further validation of a select hit revealed that the calcium channel inhibitor felodipine increased SSPN transcript and protein levels in both wild-type and dystrophin-deficient myotubes, without increasing differentiation.ConclusionsWe developed a stable muscle cell line containing the promoter region of the human SSPN protein fused to a fluorescent reporter. Using the reporter cells, we created and validated a scalable, cell-based assay that is able to identify compounds that increase SSPN promoter reporter, transcript, and protein levels in wild-type and dystrophin-deficient muscle cells.
Changes in cerebral glucose metabolism caused by morphologic features of prodromal idiopathic normal pressure hydrocephalus
Authors: Miyazaki Koichi , Hanaoka Kohei , Kaida Hayato , Chiba Yasutaka , Ishii Kazunari 
Published: December 2019

Abstract
Background
Decreased cerebral glucose metabolism has been reported in idiopathic normal pressure hydrocephalus (iNPH). However, the timing of appearance in the preclinical stage of iNPH remains unknown. Herein, we evaluated the changes in regional cerebral glucose metabolism with respect to the characteristic morphologic features of iNPH.

Methods
We performed a cross-sectional study in > 2000 elderly patients who received a whole body 18F-fluorodeoxyglucose-positron emission tomography/computed tomography scanning and recruited subjects with clinical and preclinical iNPH. We included 12 subjects with iNPH, 32 subjects with asymptomatic ventriculomegaly with features of iNPH on magnetic resonance imaging (AVIM), and 33 subjects with preclinical morphologic features of DESH (PMD). We previously reported that iNPH develops in the order of PMD (asymptomatic subjects with incomplete DESH), AVIM (asymptomatic subjects with DESH), and iNPH (symptomatic subjects with DESH). We measured the median regional standardized uptake value ratio (SUVR) on 18F-fluorodeoxyglucose-positron emission tomography/computed tomography images between the three groups and compared them with background-matched normal controls in the frontal lobes, temporal lobes, medial parietal lobes, striata, and thalami.

Results
In the frontal and temporal lobes, the SUVR distributions of the PMD, AVIM, and PMD groups were significantly lower than for each NC (p < 0.05 for all). In the medial parietal lobes, the SUVR distributions were significantly higher in PMD and AVIM groups (p < 0.05 for all). In the thalami and striata, the SUVR distributions were significantly lower in the iNPH group (p < 0.05 for all).

Conclusions
Changes in brain glucose metabolism in the cortices are observed in preclinical iNPH, while metabolic decline in the basal ganglia is only detected in clinical iNPH.
Mapping evidence on access to healthcare information by women of reproductive age in low-and-middle-income countries: scoping review protocol
Authors: Shatilwe Joyce T. , Mashamba-Thompson Tivani P. 
Published: December 2019

Abstract
Background
Research shows that there are inadequate interventions in resource-limited settings that could enable women of reproductive age to access and use health services in those settings. The main objective of this scoping review is to map the evidence on access to healthcare information by women of reproductive age in LMICs.

Method and analysis
The primary search will include Google Scholar, Science Direct, PubMed, EBSCOhost (Academic search complete, CINAHL with full text, MEDLINE with full text, MEDLINE), Emerald, Embase, CDSR, PsycINFO, published and peer review journals, organisational projects, conference papers, reference list, grey literature sources, as well as reports related to this objective will be included in the study. Identified keywords will be used to search articles from the studies. The articles and abstracts will be screened by two independent reviewers (JS and TPMT). Inclusion and exclusion criteria will be considered to guide the screening. A thematic content analysis will be used to present the narrative account of the reviews, using NVivo computer software (version 11).

Discussions
The scoping review will focus on women of reproductive age in LMICs. We anticipate finding relevant literature on the interventions aimed at accessing health care services in LMICs. The study findings will help reveal research gaps to guide future research.

Scoping review registration
Not registered with PROSPERO (not needed).

Protocol and registration
This scoping review was not registered.
Prevalence of lifetime substances use among students in Ethiopia: a systematic review and meta-analysis
Authors: Roba Hirbo Shore , Beyene Addisu Shunu , Irenso Asnake Ararsa , Gebremichael Berhe 
Published: December 2019

AbstractBackgroundThe use of substances is a growing concern in Ethiopia, and their impacts on younger generation have been a concern of different professionals. Even though students are at high-risk of substance abuse, there is lack of comprehensive evidence for policy decision on substance use among students. Therefore, the aim of this systematic review and meta-analysis was to estimate the prevalence of common substances among students in Ethiopia.MethodA comprehensive literature searches were done from biomedical databases: PubMed/Medline, African Journal Online, HINARI, Science Direct, and Google Scholar for article published until Dcember 31, 2017, and Addis Ababa Uiversity’s electronic library search of unpublished thesis and dissertations. Two authors autonomously selected studies, extracted data, and evaluated quality of studies. The prevalence of lifetime substances use was estimated using the random effects model.QandI2statistics were computed to measure the extents of heterogeneity.ResultsA total 676 study articles were identified from electronic databases, and 28 of them were included in meta-analysis. The analysis revealed that the lifetime prevalence of any substance use was 52.5% (95% CI 42.4–62.4%), khat 24.7% (95% CI 21.8–27.7%), alcohol 46.2% (95% CI 40.3–52.2%), and smoking cigarette 14.7% (95% CI 11.3–18.5%). Significant heterogeneity was observed but there was no significant publication bias. The lifetime prevalence of khat, alcohol, and cigarette smoking among high school vs university students was 22.5% (95% CI 15.2–30.7%) vs 25.1% (95% CI 21.9–28.5%), 41.4% (95% CI 22.1–62.1%) vs 47.8% (95% CI 39.9–55.7%), and 21.5% (95% CI 12.6–32.1%) vs 12.9% (95% CI 10.1–16.0%), respectively.ConclusionThis meta-analysis highlighted the extent of lifetime prevalence of any substance, khat, alcohol, and cigarettes smoking among students in Ethiopia. Significant percent of high school students have exposed to substances. Policy makers should devise and implement strictly binding regulation to curb widespread of substances around educational institution premises at national level. Priority should be given to intervention strategies that help delay first use of substance to prevent problems later in life. Besides, the problem warrants regular national-level educational institutions based studies focusing on the magnitude, trajectory, and consequences of substance use among students.Systematic review registration: PROSPEROCRD42018082635
Assessing ecotoxicological effects of 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, and 2,3,4,7,8-PeCDF in soil using Allivibrio fischeri
Authors: Lee Sung Jong , Ha Hong Joo , Jho Eun Hea 
Published: December 2019

AbstractThe toxic effect of dioxins and dioxin-like compounds have largely been studied using in vivo techniques; however, in vivo studies can be limited when rapid screening is required. Microtox® can be used as a rapid ecotoxicity assessment tool for dioxins in the environment, but studies on the assessment of dioxins and dioxin-like compounds using bioluminescent bacteria Allivibrio fischeri are limited. This study investigated the potential of using A. fischeri for assessing different dioxins and dioxin-like compounds, and the toxic effects of soils contaminated with dioxins and dioxin-like compounds were tested using different fractions of dioxins in soil to determine the appropriate way of assessing the toxic effects of contaminated soils. The results show that A. fischeri can potentially be used as a test species for rapidly evaluating toxic effects of dioxins and dioxin-like compounds in the environment. With the soil used in this study, the toxic effects of the water extracts (i.e., mobile fraction of dioxins) and the soil slurries (i.e., bioavailable fraction of dioxins) were similar to that of the controls. This suggests that the toxicity assessment of the organic extracts (i.e., total amount of dioxins) can be inappropriate in a managerial perspective, as the mobile or bioavailable fraction of contaminants in soils is often more of concern than the total amount of contaminants present in soils. Overall, when A. fischeri are to be used for a rapid toxicity assessment of dioxins-contaminated soils, different fractions of dioxins need to be assessed for better management of the contaminated soils.
The trade policy effect in international trade: case of Pakistan
Authors: Yeo Alassane D. , Deng Aimin 
Published: December 2019

AbstractThe debate on free trade and protectionism is ravaging in recent years. The industrialized countries are losing more and more market to the benefit of emerging countries. Liberals worry about new tariff barriers, while protectionists fear that unevenly distributed losses and gains will lead to significant economic dislocation of workers in import-competing industries. The economic policy of restricting imports and the economic policy of opening exports remain two critical measures of international trade. This study uses the gravity model to investigate the impacts of trade policy measures on trade flows between Pakistan and its dominant trading pattern for the period 2006 to 2015. The findings revealed the statistically significant correlation of trade policy variables on exports and imports. The study extended the analysis by examining four specificities groups of trade policy and continuing the analysis by estimating different country groups according to geographical or organizational clusters. The findings indicated that the specificities of trade policy have a statistically significant effect on exports and imports. Moreover, the signs of the coefficients are opposite in both models. The main political implication is that the proliferation of free trade agreements can have a positive impact on international trade.
THE impact of remittance inflows on poverty in Botswana: an ARDL approach
Authors: Musakwa Mercy. T. , Odhiambo N. M. 
Published: December 2019

AbstractThe growing pressure on governments to reduce poverty among other Sustainable Development Goals (SDGs) through harnessing domestic and foreign sources has motivated studies on the relationship between poverty and different economic variables in many developing countries. This study investigates the impact of remittance on poverty in Botswana, employing time-series data from 1980 to 2017. The study employs two poverty proxies—household consumption expenditure and infant mortality rate to capture poverty in its multidimensional form and improve the robustness of the results. Using the autoregressive distributed lag (ARDL) approach, the study finds that remittance inflows reduce poverty in Botswana—both in the short run and in the long run when infant mortality rate is used as a proxy. However, when poverty is measured by household consumption expenditure, remittance was found to have no impact on poverty in the short run and in the long run. The study, therefore, concludes that remittance inflows play a crucial role in reducing poverty and that Botswana can benefit immensely from the surge in remittance inflows by putting in place policies and structures that support remittance inflow.
Fine mapping of genomic regions associated with female fertility in Nellore beef cattle based on sequence variants from segregating sires
Authors: Oliveira Júnior Gerson A. , Santos Daniel J. A. , Cesar Aline S. M. , Boison Solomon A. , Ventura Ricardo V. , Perez Bruno C. , Garcia José F. , Ferraz José Bento S. , Garrick Dorian J. 
Published: December 2019

Abstract
Background
Impaired fertility in cattle limits the efficiency of livestock production systems. Unraveling the genetic architecture of fertility traits would facilitate their improvement by selection. In this study, we characterized SNP chip haplotypes at QTL blocks then used whole-genome sequencing to fine map genomic regions associated with reproduction in a population of Nellore (Bos indicus) heifers.

Methods
The dataset comprised of 1337 heifers genotyped using a GeneSeek® Genomic Profiler panel (74677 SNPs), representing the daughters from 78 sires. After performing marker quality control, 64800 SNPs were retained. Haplotypes carried by each sire at six previously identified QTL on BTAs 5, 14 and 18 for heifer pregnancy and BTAs 8, 11 and 22 for antral follicle count were constructed using findhap software. The significance of the contrasts between the effects of every two paternally-inherited haplotype alleles were used to identify sires that were heterozygous at each QTL. Whole-genome sequencing data localized to the haplotypes from six sires and 20 other ancestors were used to identify sequence variants that were concordant with the haplotype contrasts. Enrichment analyses were applied to these variants using KEGG and MeSH libraries.

Results
A total of six (BTA 5), six (BTA 14) and five (BTA 18) sires were heterozygous for heifer pregnancy QTL whereas six (BTA 8), fourteen (BTA 11), and five (BTA 22) sires were heterozygous for number of antral follicles’ QTL. Due to inadequate representation of many haplotype alleles in the sequenced animals, fine mapping analysis could only be reliably performed for the QTL on BTA 5 and 14, which had 641 and 3733 concordant candidate sequence variants, respectively. The KEGG “Circadian rhythm” and “Neurotrophin signaling pathway” were significantly associated with the genes in the QTL on BTA 5 whereas 32 MeSH terms were associated with the QTL on BTA 14. Among the concordant sequence variants, 0.2% and 0.3% were classified as missense variants for BTAs 5 and 14, respectively, highlighting the genes MTERF2, RTMB, ENSBTAG00000037306 (miRNA), ENSBTAG00000040351, PRKDC, and RGS20. The potential causal mutations found in the present study were associated with biological processes such as oocyte maturation, embryo development, placenta development and response to reproductive hormones.

Conclusions
The identification of heterozygous sires by positionally phasing SNP chip data and contrasting haplotype effects for previously detected QTL can be used for fine mapping to identify potential causal mutations and candidate genes. Genomic variants on genes MTERF2, RTBC, miRNA ENSBTAG00000037306, ENSBTAG00000040351, PRKDC, and RGS20, which are known to have influence on reproductive biological processes, were detected.
A community-based comprehensive intervention to reduce syphilis infection among low-fee female sex workers in China: a matched-pair, community-based randomized study
Authors: Dong Wei , Zhou Chu , Rou Ke-Ming , Wu Zun-You , Chen Jun , Scott Sarah Robbins , Jia Man-Hong , Zhou Yue-Jiao , Chen Xi 
Published: December 2019

Abstract
Background
Low-fee female sex workers (FSWs) are at high risk of acquiring and spreading human immunodeficiency virus (HIV)/sexually transmitted diseases (STDs) in China. There is an urgent need to develop comprehensive intervention measures targeted towards low-fee FSWs to reduce HIV/STD infections. Thus, this study aimed to reduce HIV/STD infections among low-fee FSW through a matched-pair, community-based randomized intervention trial carried out in 12 cities in three provinces in China.

Methods
Four cities from Guangxi Zhuang Autonomous Region, four from Yunnan Province, and four from Hunan Province were paired and participants received either the intervention package (including condom promotion, HIV and syphilis testing, reimbursement for syphilis treatment costs, and free anti-retroviral therapy or the current standard of care. Venue-based, convenience sampling was used to recruit FSWs. A face-to-face interview and HIV and syphilis blood testing was conducted at baseline and follow-up intervals of 24 months. Generalized linear mixed models (GLMM) were used to evaluate the effect of the intervention package on reducing HIV/STD infection in the FSWs.

Results
A total of 1024 eligible FSWs were enrolled in the baseline survey and 843 in the follow-up. GLMM results showed that syphilis infection was reduced by 49% in the intervention group compared to the current standard of care group (P = 0.0378, OR = 0.51, 95% CI: 0.27–0.96). FSWs aged 35 years or older were 2.38 times more likely to get syphilis infection compared to those younger than 35 years old (P <  0.0001, OR = 2.38, 95% CI: 1.55–3.65). The risk of syphilis infection among more educated FSWs was 0.43 times less than those with lower levels of education (P <  0.05, OR = 0.43, 95% CI: 0.63–0.93).

Conclusions
This study demonstrates that comprehensive interventions can lead to significant declines in syphilis infection amongst low-tier FSWs. Integrating both behavioral and biomedical intervention measures should be considered when developing programs for low-fee FSWs.

Trial registration
CHiCTR-TRC-12002655.
Attenuation of neuroinflammation reverses Adriamycin-induced cognitive impairments
Authors: Allen Barrett D. , Apodaca Lauren A. , Syage Amber R. , Markarian Mineh , Baddour Al Anoud D. , Minasyan Harutyun , Alikhani Leila , Lu Celine , West Brian L. , Giedzinski Erich , Baulch Janet E. , Acharya Munjal M. 
Published: December 2019

AbstractNumerous clinical studies have established the debilitating neurocognitive side effects of chemotherapy in the treatment of breast cancer, often referred as chemobrain. We hypothesize that cognitive impairments are associated with elevated microglial inflammation in the brain. Thus, either elimination of microglia or restoration of microglial function could ameliorate cognitive dysfunction. Using a rodent model of chronic Adriamycin (ADR) treatment, a commonly used breast cancer chemotherapy, we evaluated two strategies to ameliorate chemobrain: 1) microglia depletion using the colony stimulating factor-1 receptor (CSF1R) inhibitor PLX5622 and 2) human induced pluripotent stem cell-derived microglia (iMG)-derived extracellular vesicle (EV) treatment. In strategy 1 mice received ADR once weekly for 4 weeks and were then administered CSF1R inhibitor (PLX5622) starting 72 h post-ADR treatment. ADR-treated animals given a normal diet exhibited significant behavioral deficits and increased microglial activation 4–6 weeks later. PLX5622-treated mice exhibited no ADR-related cognitive deficits and near complete depletion of IBA-1 and CD68+ microglia in the brain. Cytokine and RNA sequencing analysis for inflammation pathways validated these findings. In strategy 2, 1 week after the last ADR treatment, mice received retro-orbital vein injections of iMG-EV (once weekly for 4 weeks) and 1 week later, mice underwent behavior testing. ADR-treated mice receiving EV showed nearly complete restoration of cognitive function and significant reductions in microglial activation as compared to untreated ADR mice. Our data demonstrate that ADR treatment elevates CNS inflammation that is linked to cognitive dysfunction and that attenuation of neuroinflammation reverses the adverse neurocognitive effects of chemotherapy.
A comparative assessment of clinical efficiency between premium heat-activated copper nickel-titanium and superelastic nickel-titanium archwires during initial orthodontic alignment in adolescents: a randomized clinical trial
Authors: Atik Ezgi , Gorucu-Coskuner Hande , Akarsu-Guven Bengisu , Taner Tulin 
Published: December 2019

Abstract
Background
To compare the clinical efficiency of premium heat-activated copper nickel-titanium (Tanzo Cu-NiTi) and NT3 superelastic NiTi during initial orthodontic alignment.

Subject and methods
A total of 50 patients were randomly allocated to 1 of 2 different archwire types (group 1, Tanzo Cu-NiTi; group 2, NT3 superelastic NiTi). Eligibility criteria included Class I or Class II malocclusion, moderate maxillary anterior crowding, and healthy periodontal condition. Impressions of the upper arches were taken before archwire placement (T0) and at every 4 weeks (T1, T2, T3, and T4). For T1 and T2 stages, 0.014-in., and for T3 and T4 stages, 0.018-in. archwires were used. The primary outcome was the alignment efficiency assessed using Little’s irregularity index. The secondary outcomes were arch width and incisor inclination changes. Data were analyzed using independent samples t test, repeated measures ANOVA, and Mann-Whitney U test. Marginal models were established for the estimation of coefficients.

Results
The anterior irregularity index reduction was mostly observed between T0 and T2 periods, which were respectively − 7.40 ± 0.50 mm (p < 0.001; 95% CI, − 8.94, − 5.85) and − 6.80 ± 0.55 mm (p < 0.001; 95% CI, − 8.49, − 5.12) for groups 1 and 2 (p < 0.001). With both wires, Little’s irregularity index decreased over time, and the difference between the groups was not significant (p = 0.581; estimated effect size, 0.011). No statistically significant difference was found between the groups in terms of intercanine and intermolar width and incisor inclination changes.

Conclusion
There were no significant between-group differences in alignment efficiency, arch width, and incisor inclination change. There was an increased alignment with 0.014-in. compared with 0.018-in. diameter archwire.