bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supranutritional selenium level minimizes high concentrate diet-induced epithelial injury by alleviating oxidative stress and apoptosis in colon of goat
Authors: Samo Saba Parveen , Malhi Moolchand , Kachiwal Allah Bux , Gadahi Javaid Ali , Parveen Fahmida , Kalhoro Nazeer Hussain , Lei Yan 
Published: November 2020

Abstract
Background
High concentrate (HC) diet-induced oxidative stress causes gut epithelial damages associated with apoptosis. Selenium (Se) being an integral component of glutathione peroxidase (GSH-Px) plays an important role in antioxidant defense system. Therefore, increasing dietary Se level would alleviate HC diet-induced injuries in gut mucosa. The present study investigated eighteen cross-bred goats, randomly divided into three groups (n = 6/group) fed either low concentrate (LC, roughage: concentrate ratio 65:35), high concentrate (HC, 35:65) or HC plus Se (HC-SY) diets for 10 weeks. Se was supplemented at the dose rate of 0.5 mg Se kg− 1 diet in the form of selenium yeast. The background Se level in HC and LC diets were 0.15 and 0.035 mg.kg− 1 diet, respectively. The Se at the dose of 0.115 mg.kg− 1 diet was added in LC diet to make its concentration equivalent to HC diet and with the supplementation of 0.5 mg Se kg− 1, the goats in group HC-SY received total Se by 0.65 mg.kg− 1 diet.

Results
The molar concentrations of individual and total short chain fatty acids (TSCFA) significantly increased (P < 0.05) with simultaneous decrease in pH of colonic fluid in goats of HC and HC-SY groups compared with LC goats. HC diet induced loss of epithelial integrity, inflammation and loss of goblet cells in colonic mucosa associated with higher lipopolysaccharide (LPS) concentrations in colonic fluid whereas, the addition of SY in HC diet alleviated such damaging changes. Compared with LC, the HC diet elevated malondialdehyde (MDA) level with concurrent decrease in GSH-Px and superoxide dismutase (SOD) activities, while SY supplementation attenuated these changes and improved antioxidant status in colonic epithelium. Moreover, epithelial injury and oxidative stress in colon of HC goats were associated with increased apoptosis as evidenced by downregulation of bcl2 and upregulation of bax, caspases 3 and 8 mRNA expressions compared with LC goats. On contrary, addition of SY in HC (HC-SY) diet alleviated these changes by modulating expression of apoptotic genes in colonic epithelium.

Conclusions
Our data suggest that supranutritional level of Se attenuates HC diet-induced oxidative stress and apoptosis and thereby minimizes the epithelial injury in colon of goats.
Marked effects of novel selective peroxisome proliferator-activated receptor α modulator, pemafibrate in severe hypertriglyceridemia: preliminary report
Authors: Iitake Chie , Masuda Daisaku , Koseki Masahiro , Yamashita Shizuya 
Published: November 2020

AbstractBackgroundCurrently available treatments have only been partly successful in patients with severe hypertriglyceridemia, including those with high serum triglycerides above 1,000 mg/dL (11.3 mmol/L), who often suffer from acute pancreatitis. Pemafibrate is a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα) which has been developed as an affordable oral tablet in Japan. We herein report the first three patients with severe hypertriglyceridemia who were successfully treated with pemafibrate.MethodsThree patients with fasting serum triglyceride (TG) levels above 1,000 mg/dL (11.3 mmol/L) were treated with pemafibrate (0.2–0.4 mg/day, 0.1–0.2 mg BID).ResultsSerum TGs decreased from 2,000–3,000 mg/dL (22.6–33.9 mmol/L) to < 250 mg/dL (2.8 mmol/L) without adverse effects in all three patients. Serum TGs in Patient 1 and 2 decreased from 1,326 mg/dL (15.0 mmol/L) to 164 mg/dL (1.9 mmol/L) and from 2,040 mg/dL (23.1 mmol/L) to 234 mg/dL (2.6 mmol/L), respectively. Patient 3 with type 2 diabetes and 12.1% (109 mmol/mol) hemoglobin A1c had a TG level of 2,300 mg/dL (26.0 mmol/L). Even after glycemic control improved, TG remained high. After pemafibrate administration, TG decreased to 200 mg/dL (2.3 mmol/L). All patients showed no serious adverse events.ConclusionsPemafibrate demonstrated potential efficacy and safety for severe hypertriglyceridemia which may contribute to the prevention of acute pancreatitis, in a manner that can be easily prescribed and used as an oral tablet.
SLC39A1 contribute to malignant progression and have clinical prognostic impact in gliomas
Authors: Wang Peng , Zhang Jingjing , He Shuai , Xiao Boan , Peng Xiaobin 
Published: November 2020

Abstract
Background
Gliomas are one of the most common primary tumors of the central nervous system, and have an unfavorable prognosis. SLC39A1 is a zinc ion transport protein which inhibits the progression of prostate cancer. By studying the role and mechanism of SLC39A1 in the progression of gliomas, perhaps a new therapeutic target can be provided for their treatment.

Method
The TCGA, CCGA, GSE16011, GSE44971 and GSE11260 data sets were employed to evaluate the expression level of SLC39A1 in paracancerous and glioma tissues. In addition, Kaplan–Meier analysis, Cox analysis, and the ESTIMATE and CIBERSORT algorithms were used to analyze its prognostic value and immune infiltration correlation. A CCK-8 and flow cytometer were used to measure the effects of SLC39A1 on U87 cell proliferation or apoptosis; RT-qPCR and western blot were used to detect its effects on the expression of MMP2\MMP9.

Results
SLC39A1 has up-regulated expression in glioma tissues. High SLC39A1 expression predicted significantly worse survival. Univariate and multivariate analysis show that SLC39A1 independently indicated poor prognosis in patients with gliomas. The expression of SLC39A1 is significantly correlated with clinical pathological parameters such as Grade, IDH mutation status, and 1p19q codeletion status. In vitro experimental results show that SLC39A1 promotes proliferation of glioma cells, inhibits their apoptosis, and promotes expression of MMP2\MMP9. In addition, it may affect infiltration of immune cells into the glioma microenvironment.

Conclusion
SLC39A1 may serve as a new prognostic biomarker and potential target for treatment of gliomas.
Can computed tomography-based radiomics potentially discriminate between anterior mediastinal cysts and type B1 and B2 thymomas?
Authors: Liu Lulu , Lu Fangxiao , Pang Peipei , Shao Guoliang 
Published: November 2020

Abstract
Background
Anterior mediastinal cysts (AMC) are often misdiagnosed as thymomas and undergo surgical resection, which caused unnecessary treatment and medical resource waste. The purpose of this study is to explore potential possibility of computed tomography (CT)-based radiomics for the diagnosis of AMC and type B1 and B2 thymomas.

Methods
A group of 188 patients with pathologically confirmed AMC (106 cases misdiagnosed as thymomas in CT) and thymomas (82 cases) and underwent routine chest CT from January 2010 to December 2018 were retrospectively analyzed. The lesions were manually delineated using ITK-SNAP software, and radiomics features were performed using the artificial intelligence kit (AK) software. A total of 180 tumour texture features were extracted from enhanced CT and unenhanced CT, respectively. The general test, correlation analysis, and LASSO were used to features selection and then the radiomics signature (radscore) was obtained. The combined model including radscore and independent clinical factors was developed. The model performances were evaluated on discrimination, calibration curve.

Results
Two radscore models were constructed from the unenhanced and enhanced phases based on the selected four and three features, respectively. The AUC, sensitivity, and specificity of the enhanced radscore model were 0.928, 89.3%, and 83.8% in the training dataset and 0.899, 84.6%, and 87.5% in the test dataset (higher than the unenhanced radscore model). The combined model of enhanced CT including radiomics features and independent clinical factors yielded an AUC, sensitivity and specificity of 0.941, 82.1%, and 94.6% in the training dataset and 0.938, 92.3%, and 87.5% in the test dataset (higher than the unenhanced combined model and enhanced radscore model).

Conclusions
The study suggested the possibility that the combined model in enhanced CT provided a potential tool to facilitate the differential diagnosis of AMC and type B1 and B2 thymomas.
Coverage determinants of breast cancer screening in Flanders: an evaluation of the past decade
Authors: Ding L. , Jidkova S. , Greuter M. J. W. , Van Herck K. , Goossens M. , Martens P. , de Bock G. H. , Van Hal G. 
Published: November 2020

Abstract
Background
Breast cancer (BC) is the most common cancer in women in the developed world. In order to find developing cancers in an early stage, BC screening is commonly used. In Flanders, screening is performed in and outside an organized breast cancer screening program (BCSP). However, the determinants of BC screening coverage for both screening strategies are yet unknown.

Objective
To assess the determinants of BC screening coverage in Flanders.

Methods
Reimbursement data were used to attribute a screening status to each woman in the target population for the years 2008–2016. Yearly coverage data were categorized as screening inside or outside BCSP or no screening. Data were clustered by municipality level. A generalized linear equation model was used to assess the determinants of screening type.

Results
Over all years and municipalities, the median screening coverage rate inside and outside BCSP was 48.40% (IQR: 41.50–54.40%) and 14.10% (IQR: 9.80–19.80%) respectively. A higher coverage rate outside BSCP was statistically significantly (P < 0.001) associated with more crowded households (OR: 3.797, 95% CI: 3.199–4.508), younger age, higher population densities (OR: 2.528, 95% CI: 2.455–2.606), a lower proportion of unemployed job seekers (OR: 0.641, 95% CI: 0.624–0.658) and lower use of dental care (OR: 0.969, 95% CI: 0.967–0.972).

Conclusion
Coverage rate of BC screening is not optimal in Flanders. Women with low SES that are characterized by younger age, living in a high population density area, living in crowded households, or having low dental care are less likely to be screened for BC in Flanders. If screened, they are more likely to be screened outside the BCSP.
Immunological classification of gliomas based on immunogenomic profiling
Authors: Feng Qiushi , Li Lin , Li Mengyuan , Wang Xiaosheng 
Published: November 2020

AbstractBackgroundGliomas are heterogeneous in the tumor immune microenvironment (TIM). However, a classification of gliomas based on immunogenomic profiling remains lacking.MethodsWe hierarchically clustered gliomas based on the enrichment levels of 28 immune cells in the TIM in five datasets and obtained three clusters: immunity-high, immunity-medium, and immunity-low.ResultsGlioblastomas were mainly distributed in immunity-high and immunity-medium, while lower-grade gliomas were distributed in all the three subtypes and predominated in immunity-low. Immunity-low displayed a better survival than other subtypes, indicating a negative correlation between immune infiltration and survival prognosis in gliomas.IDHmutations had a negative correlation with glioma immunity. Immunity-high had higher tumor stemness and epithelial-mesenchymal transition scores and included more high-grade tumors than immunity-low, suggesting that elevated immunity is associated with tumor progression in gliomas. Immunity-high had higher tumor mutation burden and more frequent somatic copy number alterations, suggesting a positive association between tumor immunity and genomic instability in gliomas.ConclusionsThe identification of immune-specific glioma subtypes has potential clinical implications for the immunotherapy of gliomas.
CCL3 contributes to secondary damage after spinal cord injury
Authors: Pelisch Nicolas , Rosas Almanza Jose , Stehlik Kyle E. , Aperi Brandy V. , Kroner Antje 
Published: November 2020

AbstractBackgroundSecondary damage after spinal cord injury (SCI) is characterized by a cascade of events including hemorrhage, apoptosis, oxidative stress, and inflammation which increase the lesion size which can influence the functional impairment. Thus, identifying specific mechanisms attributed to secondary injury is critical in minimizing tissue damage and improving neurological outcome. In this work, we are investigating the role of CCL3 (macrophage inflammatory protein 1-α, MIP-1α), a chemokine involved in the recruitment of inflammatory cells, which plays an important role in inflammatory conditions of the central and peripheral nervous system.MethodsA mouse model of lower thoracic (T11) spinal cord contusion injury was used. We assessed expression levels of CCL3 and its receptors on the mRNA and protein level and analyzed changes in locomotor recovery and the inflammatory response in the injured spinal cord of wild-type andCCL3−/−mice.ResultsThe expression of CCL3 and its receptors was increased after thoracic contusion SCI in mice. We then examined the role of CCL3 after SCI and its direct influence on the inflammatory response, locomotor recovery and lesion size usingCCL3−/−mice.CCL3−/−mice showed mild but significant improvement of locomotor recovery, a smaller lesion size and reduced neuronal damage compared to wild-type controls. In addition, neutrophil numbers as well as the pro-inflammatory cytokines and chemokines, known to play a deleterious role after SCI, were markedly reduced inthe absence of CCL3.ConclusionWe have identified CCL3 as a potential target to modulate the inflammatory response and secondary damage after SCI. Collectively, this study shows that CCL3 contributes to progressive tissue damage and functional impairment during secondary injury after SCI.
Oleanolic acid ameliorates intestinal alterations associated with EAE
Authors: Gutierrez Beatriz , Gallardo Isabel , Ruiz Lorena , Alvarez Yolanda , Cachofeiro Victoria , Margolles Abelardo , Hernandez Marita , Nieto Maria Luisa 
Published: November 2020

Abstract
Background
Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease affecting the CNS. Recent studies have indicated that intestinal alterations play key pathogenic roles in the development of autoimmune diseases, including MS. The triterpene oleanolic acid (OA), due to its anti-inflammatory properties, has shown to beneficially influence the severity of the experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We herein investigate EAE-associated gut intestinal dysfunction and the effect of OA treatment.

Methods
Mice with MOG35–55-induced EAE were treated with OA or vehicle from immunization day and were daily analyzed for clinical deficit. We performed molecular and histological analysis in serum and intestinal tissues to measure oxidative and inflammatory responses. We used Caco-2 and HT29-MTX-E12 cells to elucidate OA in vitro effects.

Results
We found that OA protected from EAE-induced changes in intestinal permeability and preserved the mucin-containing goblet cells along the intestinal tract.
Serum levels of the markers for intestinal barrier damage iFABP and monocyte activation sCD14 were consistently and significantly reduced in OA-treated EAE mice. Beneficial OA effects also included a decrease of pro-inflammatory mediators both in serum and colonic tissue of treated-EAE mice. Moreover, the levels of some immunoregulatory cytokines, the neurotrophic factor GDNF, and the gastrointestinal hormone motilin were preserved in OA-treated EAE mice. Regarding oxidative stress, OA treatment prevented lipid peroxidation and superoxide anion accumulation in intestinal tissue, while inducing the expression of the ROS scavenger Sestrin-3. Furthermore, short-chain fatty acids (SCFA) quantification in the cecal content showed that OA reduced the high iso-valeric acid concentrations detected in EAE-mice. Lastly, using in vitro cell models which mimic the intestinal epithelium, we verified that OA protected against intestinal barrier dysfunction induced by injurious agents produced in both EAE and MS.

Conclusion
These findings reveal that OA ameliorates the gut dysfunction found in EAE mice. OA normalizes the levels of gut mucosal dysfunction markers, as well as the pro- and anti-inflammatory immune bias during EAE, thus reinforcing the idea that OA is a beneficial compound for treating EAE and suggesting that OA may be an interesting candidate to be explored for the treatment of human MS.
Astrocyte-derived clusterin suppresses amyloid formation in vivo
Authors: Wojtas Aleksandra M. , Sens Jonathon P. , Kang Silvia S. , Baker Kelsey E. , Berry Taylor J. , Kurti Aishe , Daughrity Lillian , Jansen-West Karen R. , Dickson Dennis W. , Petrucelli Leonard , Bu Guojun , Liu Chia-Chen , Fryer John D. 
Published: November 2020

Abstract
Background
Accumulation of amyloid-β (Aβ) peptide in the brain is a pathological hallmark of Alzheimer’s disease (AD). The clusterin (CLU) gene confers a risk for AD and CLU is highly upregulated in AD patients, with the common non-coding, protective CLU variants associated with increased expression. Although there is strong evidence implicating CLU in amyloid metabolism, the exact mechanism underlying the CLU involvement in AD is not fully understood or whether physiologic alterations of CLU levels in the brain would be protective.

Results
We used a gene delivery approach to overexpress CLU in astrocytes, the major source of CLU expression in the brain. We found that CLU overexpression resulted in a significant reduction of total and fibrillar amyloid in both cortex and hippocampus in the APP/PS1 mouse model of AD amyloidosis. CLU overexpression also ameliorated amyloid-associated neurotoxicity and gliosis. To complement these overexpression studies, we also analyzed the effects of haploinsufficiency of Clu using heterozygous (Clu+/−) mice and control littermates in the APP/PS1 model. CLU reduction led to a substantial increase in the amyloid plaque load in both cortex and hippocampus in APP/PS1; Clu+/− mice compared to wild-type (APP/PS1; Clu+/+) littermate controls, with a concomitant increase in neuritic dystrophy and gliosis.

Conclusions
Thus, both physiologic ~ 30% overexpression or ~ 50% reduction in CLU have substantial impacts on amyloid load and associated pathologies. Our results demonstrate that CLU plays a major role in Aβ accumulation in the brain and suggest that efforts aimed at CLU upregulation via pharmacological or gene delivery approaches offer a promising therapeutic strategy to regulate amyloid pathology.
Determinants of postnatal care utilization in sub-Saharan Africa: a meta and multilevel analysis of data from 36 sub-Saharan countries
Authors: Tessema Zemenu Tadesse , Yazachew Lake , Tesema Getayeneh Antehunegn , Teshale Achamyeleh Birhanu 
Published: November 2020

Abstract
Introduction
Globally, over 65% of maternal deaths occur during the first 42 days of postpartum while the same proportion of neonatal deaths occur during the first 7 days of life. In sab- Saharan Africa, 4.7 million mothers, newborns, and children die on annual basis. As to our knowledge, there is no study on postnatal care utilization that incorporates all sub-Saharan Africa countries that had DHS data. Therefore, this study aimed at identifying pooled magnitude and determinants of postnatal care utilization in sub-Saharan Africa.

Method
A population-based cross-sectional study from the most recent Demographic and Health Surveys data from the period of 2006 to 2018 of 36 SSA countries were used. A total weighted sample of 286,255 reproductive-age women who gave birth 5 years preceding the survey were included in the study. A meta-analysis of DHS data of each Sub-Saharan countries was conducted to generate pooled magnitude and a forest plot was used to present it. A multilevel logistic regression model was fitted to identify determinants of postnatal care utilization. The AOR (Adjusted Odds Ratio) with their 95% CI and p-value ≤0.05 was used to declare that determinates associated with postnatal care utilization.

Result
The pooled magnitude of postnatal care utilization in sub-Saharan Africa countries was 52.48% [95% CI: 52.33, 52.63], with the highest postnatal care utilization in the Central Region of Africa (73.51%) and the low postnatal care utilization in Eastern Regions of Africa (31.71%). In the multilevel logistic regression model region, residence, age group, maternal education, maternal occupation, media exposure, ANC visit, place of delivery, and accessing health care were determinants of postnatal care utilization in Sub-Saharan Africa.

Conclusion
The coverage of postnatal care service utilization was low with high disparities among the region. Being in rural residence, young age group, low education level, had no occupation, not exposed to media, a big problem to access health care, not had ANC visit, and home delivery was associated with low postnatal care service utilization. This study evidenced that there is a wide gap in postnatal care utilization between SSA countries. Special attention is required to improve health accessibility, utilization, and quality of maternal health services to increase postnatal care service utilization in the region.
Designing process evaluations using case study to explore the context of complex interventions evaluated in trials
Authors: Grant Aileen , Bugge Carol , Wells Mary 
Published: November 2020

AbstractBackgroundProcess evaluations are an important component of an effectiveness evaluation as they focus on understanding the relationship between interventions and context to explain how and why interventions work or fail, and whether they can be transferred to other settings and populations. However, historically, context has not been sufficiently explored and reported resulting in the poor uptake of trial results. Therefore, suitable methodologies are needed to guide the investigation of context. Case study is one appropriate methodology, but there is little guidance about what case study design can offer the study of context in trials. We address this gap in the literature by presenting a number of important considerations for process evaluation using a case study design.Main textIn this paper, we define context, the relationship between complex interventions and context, and describe case study design methodology. A well-designed process evaluation using case study should consider the following core components: the purpose; definition of the intervention; the trial design, the case, the theories or logic models underpinning the intervention, the sampling approach and the conceptual or theoretical framework. We describe each of these in detail and highlight with examples from recently published process evaluations.ConclusionsThere are a number of approaches to process evaluation design in the literature; however, there is a paucity of research on what case study design can offer process evaluations. We argue that case study is one of the best research designs to underpin process evaluations, to capture the dynamic and complex relationship between intervention and context during implementation. We provide a comprehensive overview of the issues for process evaluation design to consider when using a case study design.Trial registrationDQIP - ClinicalTrials.gov number,NCT01425502- OPAL -ISRCTN57746448