bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normative values of the retinal macular thickness in a middle eastern population
Authors: AlSaad Mouna M. , Shatarat Amjad T. , AlRyalat Saif Aldeen S. 
Published: April 2020

Abstract
Background
Since the normative value of the retinal macular thickness is undocumented in the Middle East, the aim of this work is to assess the normative values of the macular thickness in healthy eyes in a Middle Eastern population and its relationship with age, sex, and laterality.

Methods
One hundred sixteen individuals were randomly selected from volunteers visiting the Jordan University Hospital in Amman, Jordan. Measurements were obtained using the Fourier domain optical coherence tomography (OCT). Multivariate regression models were developed to obtain predicted normative values with adjustment to candidate variables. In addition, the effect of age, sex and laterality were evaluated.

Results
The average central fovea macular thickness was 229.5 (±30.85) um. The quadratic value of the retinal macular thickness decreased from the superior value of 299.71 (±23.67) um (P = .001) to the inferior value of 296.46 (±28.85) um(P = .001) and a nasal figure of 93.63 (±26.86) um(P = .001). The temporal area has the thinnest value of 293.43 (±30.78) um (P = 0.001). Central thickness was higher in males with a mean variation of 11.67 um (95% CI, 2.41 to 20.93) (p = 0.003). The thickness was highest within 3 mm diameter from the center and decreased towards the periphery Eye sidedness didn’t contribute to variability of the macular thickness. Furthermore, we found a significant difference between age and central macular thickness (p = 0.001), as age was a positive predictor for macular thickness.

Conclusion
Our set of predicted normative data may be used to interrupt measurement of the macular thickness in Middle Eastern population. The average fovea macular thickness among Jordanians is consistent with previously reported values. Normative values from additional Middle Eastern. Population are required to appraise our model.
The effect of health on social capital; a longitudinal observation study of the UK
Authors: Downward Paul , Rasciute Simona , Kumar Harish 
Published: April 2020

Abstract
Background
UK health policy increasingly focusses on health as an asset. This represents a shift of focus away from specific risk factors towards the more holistic capacity by which integrated care assets in the community support improvements in both health and the wider flourishing of individuals. Though the social determinants of health are well known, relatively little research has focussed on the impact of an individual’s health on their social outcomes. This research investigates how improved health can deliver a social return through the development of social capital.

Methods
An observational study is undertaken on 25 years of longitudinal data, from 1991, drawn from the harmonised British Household Panel Survey (BHPS) and Understanding Society Survey (USS). Fixed effects instrumental variable panel data regression analysis is undertaken on individuals. The number of memberships of social organisations, as a measure of structural social capital, is regressed on subjectively measured general health and GHQ12 (Likert) scores. Distinction is drawn between males and females.

Results
Improved general health increases social capital though differences exist between males and females. Interaction effects, that identify the impacts of health for different age groups, reveal that the effect of increased health on social capital is enhanced for males as they age. However, in the case of females increases in general health increase social capital only in connection with their age group. In contrast mental illness generally reduces social capital for males and females, and these effects are reduced through aging.

Conclusions
Investing in health as an asset can improve the social outcomes of individuals. Increasing the outcomes requires tailoring integrated care systems to ensure that opportunities for social engagement are available to individuals and reflect age groups. Targeting improvements in mental health is required, particularly for younger age groups, to promote social capital. The results suggest the importance of ensuring that opportunity for engagement in social and civic organisation be linked to general and mental health care support.
Association between sarcopenia and levels of growth hormone and insulin-like growth factor-1 in the elderly
Authors: Bian Ailin , Ma Yue , Zhou Xinzi , Guo Ying , Wang Wenyi , Zhang Yiran , Wang Xiaofei 
Published: April 2020

Abstract
Background
Age-related sarcopenia is a serious global health issue in elderly individuals and for the community as it induces disability and significant economic burden. The purpose of the study is to understand the factors associated with sarcopenia and the role of growth hormone (GH) and insulin-like growth factor (IGF-1) in the occurrence of sarcopenia.

Methods
Elderly patients (n = 3276) were included in this cross-sectional study. Survey and measurement of body composition (bioelectrical impedance), grip strength, and step speed were performed according to the Asian Working Group on Sarcopenia (AWGS) diagnostic criteria. Hematological and hormonal indicators were compared between patients with and without sarcopenia in order to identify the associated factors.

Results
There were significant differences in the demographic parameters between the sarcopenia and non-sarcopenia groups (all P < 0.05). There were significant differences between the two groups regarding the blood levels of GH, IGF-1, testosterone (T), and mechanical growth factor (MGF) (all P < 0.001). Correlation analyses showed that the appendicular skeletal muscle mass (ASMI) was positively associated with gender and BMI, and with GH, T, IGF-1, MGF, BUN, Cr, and Hb levels, but negatively associated with HDL-C (all P < 0.05). Logistic multivariable regression analysis showed that IGF-1, MGF, BMI, and gender were independently associated with appendicular skeletal muscle mass (ASMI) (all P < 0.05).

Conclusions
GH and IGF-1 are associated with sarcopenia in the elderly. IGF-1 and MGF are independently associated with the reduction of skeletal muscle mass, along with BMI and gender.
Autoimmune polyglandular syndrome type 2 and autoimmune hepatitis with thymoma-associated myasthenia gravis: case report
Authors: Inaba Hidefumi , Ariyasu Hiroyuki , Iwakura Hiroshi , Kurimoto Chiaki , Ueda Yoko , Uraki Shinsuke , Takeshima Ken , Furukawa Yasushi , Morita Shuhei , Nakayama Yoshiaki , Ohashi Takuya , Ito Hidefumi , Nishimura Yoshiharu , Akamizu Takashi 
Published: April 2020

Abstract
Background
Autoimmune polyglandular syndrome type 2 (APS-2) is a rare and complex clinical entity, and little is known about its etiology and progression.

Case presentation
A 52-year-old woman with autoimmune hepatitis (AIH) and bronchial asthma was diagnosed with APS-2; autoimmune Addison’s disease (AD), and Hashimoto’s thyroiditis (HT), and she underwent prednisolone (PSL) treatment. Five months later, she presented ptosis and was diagnosed with thymoma-associated myasthenia gravis (MG). Thymectomy and PSL treatment with immuno-suppressants appeared to ameliorate MG, AD, AIH, HT, and bronchial asthma. HLA typing analysis revealed that the patient had susceptible HLA alleles to MG, AIH, and HT in a Japanese population.

Conclusions
This case suggests common endocrinological and autoimmune aspects of APS-2 and AIH with thymoma-associated MG, which are considered to be extremely rare complications.
Changes of DNA methylation are associated with changes in lung function during adolescence
Authors: Sunny Shadia Khan , Zhang Hongmei , Rezwan Faisal I. , Relton Caroline L. , Henderson A. John , Merid Simon Kebede , Melén Erik , Hallberg Jenny , Arshad S. Hasan , Ewart Susan , Holloway John W. 
Published: April 2020

AbstractBackgroundAdolescence is a significant period for the gender-dependent development of lung function. Prior studies have shown that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosine-phosphate-guanine dinucleotide sites (CpGs) changes over time. This study examined whether changes of DNA-M at lung-function-related CpGs are associated with changes in lung function during adolescence for each gender, and if so, the biological significance of the detected CpGs.MethodsGenome-scale DNA-M was measured in peripheral blood samples at ages 10 (n = 330) and 18 years (n = 476) from the Isle of Wight (IOW) birth cohort in United Kingdom, using Illumina Infinium arrays (450 K and EPIC). Spirometry was conducted at both ages. A training and testing method was used to screen 402,714 CpGs for their potential associations with lung function. Linear regressions were applied to assess the association of changes in lung function with changes of DNA-M at those CpGs potentially related to lung function. Adolescence-related and personal and family-related confounders were included in the model. The analyses were stratified by gender. Multiple testing was adjusted by controlling false discovery rate of 0.05. Findings were further examined in two independent birth cohorts, the Avon Longitudinal Study of Children and Parents (ALSPAC) and the Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) cohort. Pathway analyses were performed on genes to which the identified CpGs were mapped.ResultsFor females, 42 CpGs showed statistically significant associations with change in FEV1/FVC, but none for change in FEV1or FVC. No CpGs were identified for males. In replication analyses, 16 and 21 of the 42 CpGs showed the same direction of associations among the females in the ALSPAC and BAMSE cohorts, respectively, with 11 CpGs overlapping across all the three cohorts. Through pathway analyses, significant biological processes were identified that have previously been related to lung function development.ConclusionsThe detected 11 CpGs in all three cohorts have the potential to serve as the candidate epigenetic markers for changes in lung function during adolescence in females.
Long non-coding RNA NEAT1/miR-338-3p axis impedes the progression of acute myeloid leukemia via regulating CREBRF
Authors: Feng Song , Liu Na , Chen Xiaoguang , Liu Yufeng , An Jindou 
Published: April 2020

Abstract
Background
Acute myeloid leukemia (AML) is a heterogeneous hematological disease. Our purpose of the research was to investigate the regulatory influence of long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1)/microRNA-338-3p (miR-338-3p)/CREB3 regulatory factor (CREBRF) in AML progression.

Methods
The associated RNA and protein levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Cell growth was assessed through colony formation assay and 3-(4,5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Flow cytometry was exploited to determine the apoptosis rate. Cell migration and invasion were detected by transwell assay. The combination of miR-338-3p and NEAT1 or CREBRF was analyzed via the dual-luciferase reporter assay.

Results
NEAT1 and CREBRF were down-regulated in AML tissues and cells. NEAT1 up-regulation suppressed cell growth, migration and invasion but enhanced apoptosis of AML cells. Inhibition of CREBRF reverted the NEAT1-induced effects on AML cells. Moreover, NEAT1 directly targeted miR-338-3p and miR-338-3p targeted CREBRF. NEAT1/miR-338-3p could affect cellular behaviors of AML cells via the modulation of CREBRF.

Conclusion
NEAT1/miR-338-3p axis repressed the AML progression through regulating CREBRF, which might afford a favorable perspective for the AML treatment molecularly.
Prognostic value of long non-coding RNA GHET1 in cancers: a systematic review and meta-analysis
Authors: Wang Dingding , Zhang Hong , Fang Xiaolian , Zhang Xue , Liu Honggang 
Published: April 2020

Abstract
Background
A number of studies have demonstrated the critical role of long non-coding RNA gastric cancer high expressed transcript 1 (GHET1) in many cancers. This meta-analysis provides an evidence-based evaluation of the prognostic role of GHET1 in cancer.

Materials and methods
Literature searches were conducted in several databases including Medline, Cochrane, EMBASE, CNKI, and Wanfang. The pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) were used to evaluate the role of GHET1 in cancer. The study protocol was registered at PROSPERO (ID: CRD42018111252).

Results
Sixteen studies, containing 1315 patients, were analyzed in this meta-analysis. The pooled results indicated that GHET1 overexpression was significantly associated with poor overall survival (OS) and disease-free survival (DFS) in cancer. Moreover, up-regulation of GHET1 expression predicted larger tumor size, positive lymph node metastasis, positive distant metastasis, and advanced TNM (tumor-node-metastases) stage in human cancers.

Conclusion
There is a significant correlation between up-regulation of GHET1 and both poor prognosis and advanced clinicopathological cancer characteristics. GHET1 may be a potential prognostic predictor for human cancers.
Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets
Authors: Belew Sileshi , Suleman Sultan , Duguma Markos , Teshome Henok , Wynendaele Evelien , Duchateau Luc , De Spiegeleer Bart 
Published: April 2020

Abstract
Background
Dissolution of artemether (ART) and lumefantrine (LUM) active pharmaceutical ingredients (APIs) in fixed dose combination (FDC) ART/LUM tablets is one of the critical quality attributes. Thus, the verification of the release profile of ART and LUM from FDC ART/LUM tablets using a robust and discriminatory dissolution method is crucial. Therefore, the aim of this study was to develop and validate an appropriate dissolution method for quality control of FDC ART/LUM tablets.

Methods
The dissolution medium was selected based on saturation solubility data and sink conditions. The effect of agitation speed, pH and surfactant concentration on the release of ART and LUM was evaluated by employing a two-level factorial experiment. The resulting final method was validated for linearity, precision, robustness and API stability. In addition, the discriminatory power of the method was evaluated using expired and unexpired FDC ART/LUM products.

Results
A suitable dissolution profile of FDC ART/LUM tablets was obtained in 900 ml HCl (0.025 N, pH 1.6) with 1%Myrj 52 using paddle method at 100 rpm and 37 °C. ART and LUM were analysed using a HPLC method with UV detection at wavelengths of 210 and 335 nm, respectively. The results from the stability study showed that ART and LUM were sufficiently stable in HCl (0.025 N, pH 1.6) with 1%Myrj 52 at 37 °C. The method was linear (r2 = 0.999) over the concentration range of 6.25–100 μg/ml. The results for precision were within the acceptance limit (%RSD < 2). The percent relative standard deviation (< 2%) and statistically non-significant (p > 0.05) difference in release of ART and LUM observed between deliberately changed dissolution method settings (pH = 1.6 ± 0.2 or agitation speed = 100 ± 2) and optimized dissolution conditions revealed the robustness of the dissolution method. The method was capable to discriminate among different FDC ART/LUM products with different quality.

Conclusions
The developed dissolution method is robust and discriminatory. It can be used in the quality evaluation of FDC ART/LUM tablets.
The circRNA circSEPT9 mediated by E2F1 and EIF4A3 facilitates the carcinogenesis and development of triple-negative breast cancer
Authors: Zheng Xiaying , Huang Mengge , Xing Lei , Yang Rui , Wang Xiaosong , Jiang Rong , Zhang Luyu , Chen Junxia 
Published: April 2020

Abstract
Background
Increasing studies have shown that circRNA is closely related to the carcinogenesis and development of many cancers. However, biological functions and the underlying molecular mechanism of circRNAs in triple-negative breast cancer (TNBC) remain largely unclear so far.

Methods
Here, we investigated the expression pattern of circRNAs in four pairs of TNBC tissues and paracancerous normal tissues using RNA-sequencing. The expression and prognostic significance of circSEPT9 were evaluated with qRT-PCR and in situ hybridization in two TNBC cohorts. The survival curves were drawn by the Kaplan-Meier method, and statistical significance was estimated with the log-rank test. A series of in vitro and in vivo functional experiments were executed to investigate the role of circSEPT9 in the carcinogenesis and development of TNBC. Mechanistically, we explored the potential regulatory effects of E2F1 and EIF4A3 on biogenesis of circSEPT9 with chromatin immunoprecipitation (ChIP), luciferase reporter and RNA immunoprecipitation (RIP) assays. Furthermore, fluorescent in situ hybridization (FISH), luciferase reporter and biotin-coupled RNA pull-down assays were implemented to verify the relationship between the circSEPT9 and miR-637 in TNBC.

Results
Increased expression of circSEPT9 was found in TNBC tissues, which was positively correlated with advanced clinical stage and poor prognosis. Knockdown of circSEPT9 significantly suppressed the proliferation, migration and invasion of TNBC cells, induced apoptosis and autophagy in TNBC cells as well as inhibited tumor growth and metastasis in vivo. Whereas up-regulation of circSEPT9 exerted opposite effects. Further mechanism research demonstrated that circSEPT9 could regulate the expression of Leukemia Inhibitory Factor (LIF) via sponging miR-637 and activate LIF/Stat3 signaling pathway involved in progression of TNBC. More importantly, we discovered that E2F1 and EIF4A3 might promote the biogenesis of circSEPT9.

Conclusions
Our data reveal that the circSEPT9 mediated by E2F1 and EIF4A3 facilitates the carcinogenesis and development of triple-negative breast cancer through circSEPT9/miR-637/LIF axis. Therefore, circSEPT9 could be used as a potential prognostic marker and therapeutical target for TNBC.
The intake assessment of diverse dietary patterns on childhood hypertension: alleviating the blood pressure and lipidemic factors with low-sodium seafood rich in omega-3 fatty acids
Authors: Izadi Anahita , Khedmat Leila , Tavakolizadeh Reza , Mojtahedi Sayed Yousef 
Published: April 2020

Abstract
Background
Childhood hypertension (CH) is related to the dietary intake and diversity of children. The study aimed to assess the critical role of dietary diversity, and seafood long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) in reducing CH among the Iranian community.

Methods
A cross-sectional two-phase study with 7–12-year-old Iranian students was designed. In the initial phase, the socio-demographic characteristics, and blood pressure status (normal, pre-hypertension, and hypertension) based on systolic (SBP) and diastolic (DBP) blood pressure data were assessed. The 24-h dietary recall questionnaire was used to generate the dietary diversity score (DDS, count of consumed food groups) and dietary variety score (DVS, the cumulative number of daily consumed food items). In the second phase, the association between CH reduction and changes in serum 25-hydroxyvitamin D (25OHD), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TG) levels of schoolchildren intervened by a seafood diet rich in omega-3 fatty acids were assessed using the regression analyses.

Results
The pre-hypertension and hypertension prevalence rates were 7.8 and 9.15%, respectively. CH was significantly associated with age, gender, and DDS. A significant inverse association was found between the high intake of seafood and CH (P = 0.032). The gas-chromatography analysis showed the high presence of α-linolenic (ALA, 6.72%), eicosapentaenoic (EPA, 7.62%), docosapentaenoic (DPA, 5.88%), and docosahexaenoic (DHA, 18.52%) acids in the seafood-based diet (p <  0.05). The low blood pressure levels with regular consumption of this healthy-functional diet were significantly associated with a reduction in BMI, LDL, TC, and TG, and a remarkable increase in 25OHD and HDL levels. The multiple linear regression showed that the SBP was highly associated with the TC (p <  0.001; β = 0.464).

Conclusions
The age and DDS were efficient predictors for the different CH status. A regular seafood-rich dietary pattern due to the high LC n-3 PUFAs contents could significantly reduce the obesity-related cardiovascular risk factors.
Preoperative adjuvant therapy for locally advanced and recurrent/metastatic gastrointestinal stromal tumors: a retrospective study
Authors: Qi Jing , Liu He-Li , Ren Feng , Liu Sheng , Shi Wei , Liu Wei-Hang , Cai Gao-Qiang , Liao Guo-Qing 
Published: April 2020

Abstract
Background
Preoperative imatinib mesylate therapy for gastrointestinal stromal tumors (GISTs) is controversial. This study aimed to explore the clinical efficacy and optimal duration of preoperative imatinib mesylate (IM) therapy in patients with locally advanced and recurrent/metastatic GISTs.

Methods
We retrospectively examined patients who received preoperative imatinib mesylate therapy from January 2013 to December 2018 at Xiangya Hospital, Central South University and the Second Xiangya Hospital of Central South University, China. Clinical data, including the results of tests for mutations in KIT and PDGFR, findings from regularly conducted re-examinations, abdominal-enhanced computed tomography/magnetic resonance imaging data, responses to imatinib, progression-free survival, and overall cancer-specific survival, were recorded.

Results
A total of 25 patients were enrolled in our study, including 18 with a locally advanced GIST and 7 with recurrent or metastatic GISTs. Their ages ranged from 22 to 70 years (M:F = 1.6:0.9), with a mean age of 50.48 ± 12.51 years. The tumor locations included the stomach (56.0%), rectum (16.0%), enterocoelic/retroperitoneal sites (12.0%), and the small intestine (12.0%). Based on testing for mutations in KIT and PDGFR, 22 patients received 400 mg/day KIT, and 3 patients received 600 mg/day PDGFR. The median duration of preoperative IM therapy was 8.96 ± 4.81 months, ranging from 3 to 26 months. According to the Choi criteria, 24 patients achieved a partial response (PR), and 1 patient had stable disease (SD). All patients underwent surgery after preoperative IM therapy, and no postoperative complications appeared. The 2-year PFS and 5-year PFS were 92% and 60%, respectively, and the total 5-year cancer-specific survival (CSS) was 92%.

Conclusion
Preoperative imatinib therapy is feasible for locally advanced and recurrent/metastatic GISTs and can effectively shrink the tumor size, allow organ sparing, and avoid extensive organ resection. Moreover, the optimal duration of preoperative IM therapy in patients with locally advanced and recurrent/metastatic GISTs was 8.96 ± 4.81 months, ranging from 3 to 26 months, and gastric GISTs had a better response to preoperative IM therapy than did non-gastric GISTs.