bluuebunny/crossref_metadata_2025_split huggingface dataset:
R269C variant of ESR1: high prevalence and differential function in a subset of pancreatic cancers
Authors: Boldes Tomer , Merenbakh-Lamin Keren , Journo Shani , Shachar Eliya , Lipson Doron , Yeheskel Adva , Pasmanik-Chor Metsada , Rubinek Tami , Wolf Ido 
Published: June 2020

Abstract
Background
Estrogen receptor α (ESR1) plays a critical role in promoting growth of various cancers. Yet, its role in the development of pancreatic cancer is not well-defined. A less studied region of ESR1 is the hinge region, connecting the ligand binding and DNA domains. rs142712646 is a rare SNP in ESR1, which leads to a substitution of arginine to cysteine at amino acid 269 (R269C). The mutation is positioned in the hinge region of ESR1, hence may affect the receptor structure and function. We aimed to characterize the activity of R269C-ESR1 and study its role in the development of pancreatic cancer.

Methods
Transcriptional activity was evaluated by E2-response element (ERE) and AP1 –luciferase reporter assays and qRT-PCR. Proliferation and migration were assessed using MTT and wound healing assays. Gene-expression analysis was performed using RNAseq.

Results
We examined the presence of this SNP in various malignancies, using the entire database of FoundationOne and noted enrichment of it in a subset of pancreatic non-ductal adenocarcinoma (n = 2800) compared to pancreatic ductal adenocarcinoma (PDAC) as well as other tumor types (0.53% vs 0.29%, p = 0.02). Studies in breast and pancreatic cancer cells indicated cell type-dependent activity of ESR1 harboring R269C. Thus, expression of R269C-ESR1 enhanced proliferation and migration of PANC-1 and COLO-357 pancreatic cancer cells but not of MCF-7 breast cancer cells. Moreover, R269C-ESR1 enhanced E2-response elements (ERE) and AP1-dependent transcriptional activity and increased mRNA levels of ERE and AP1-regulated genes in pancreatic cancer cell lines, but had a modest effect on MCF-7 breast cancer cells. Accordingly, whole transcriptome analysis indicated alterations of genes associated with tumorigenicity in pancreatic cancer cells and upregulation of genes associated with cell metabolism and hormone biosynthesis in breast cancer cells.

Conclusions
Our study shed new light on the role of the hinge region in regulating transcriptional activity of the ER and indicates cell-type specific activity, namely increased activity in pancreatic cancer cells but reduced activity in breast cancer cells. While rare, the presence of rs142712646 may serve as a novel genetic risk factor, and a possible target for therapy in a subset of non-ductal pancreatic cancers.
A prognostic nomogram for the cancer-specific survival of patients with upper-tract urothelial carcinoma based on the Surveillance, Epidemiology, and End Results Database
Authors: Li Chengzhuo , Yang Jin , Xu Fengshuo , Han Didi , Zheng Shuai , Kaaya Rahel Elishilia , Wang Shengpeng , Lyu Jun 
Published: June 2020

Abstract
Background
The aim of this study was to establish a comprehensive nomogram for the cancer-specific survival (CSS) of patients with upper-tract urothelial carcinoma (UTUC) and compare it with the traditional American Joint Committee on Cancer (AJCC) staging system in order to determine its reliability.

Methods
This study analyzed 9505 patients with UTUC in the Surveillance, Epidemiology, and End Results (SEER) database. R software was used to randomly divided the patients in a 7-to-3 ratio to form a training cohort (n = 6653) and a validation cohort (n = 2852). Multivariable Cox regression was used to identify predictive variables. The new survival model was compared with the AJCC prognosis model using the concordance index (C-index), the area under the time-dependent receiver operating characteristics curve (AUC), the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA).

Results
We have established a nomogram for determining the 3-, 5-, and 8-year CSS probabilities of UTUC patients. The nomogram indicates that the AJCC stage has the greatest influence on CSS in UTUC, followed by the age at diagnosis, surgery status, tumor size, radiotherapy status, histological grade, marital status, chemotherapy status, race, and finally sex. The C-index was higher for the nomogram than the AJCC staging system in both the training cohort (0.785 versus 0.747) and the validation cohort (0.779 versus 0.739). Calibration plotting demonstrated that the model has good calibration ability. The AUC, NRI, IDI, and DCA of the nomogram showed that it performs better than the AJCC staging system alone.

Conclusions
This study is the first to establish a comprehensive UTUC nomogram based on the SEER database and evaluate it using a series of indicators. Our novel nomogram can help clinical staff to predict the 3-, 5-, and 8-year CSS probabilities of UTUC patients more accurately than using the AJCC staging system.
Immunization coverage and its determinant factors among children aged 12–23 months in Ethiopia: a systematic review, and Meta- analysis of cross-sectional studies
Authors: Eshete Akine , Shewasinad Sisay , Hailemeskel Solomon 
Published: June 2020

Abstract
Background
Immunization is the process by which a person is made immune or resistant to an infectious disease, typically by the administration of vaccine. Vaccination coverage for other single vaccines ranged from 49.1% for PCV to 69.2% for BCG vaccine. The vaccination coverage for basic vaccinations was 39.7% in Ethiopia. There have been epidemiological studies available on immunization in Ethiopia. Yet, these studies revealed a wide variation over time and across geographical areas. This systematic review and Meta-analysis aim to estimate the overall immunization coverage among 12–23 months children in Ethiopia.

Methods
Cross-sectional studies that reported on immunization coverage from 2003 to August 2019 were systematically searched. Searches were conducted using PubMed, Google Scholar, Cochrane library, and gray literature. Information was extracted using a standardized form of Joanna Briggs Institute. The search was updated 20 Jan 2020 to decrease time-lag bias. The quality of studies assessed using Joanna Briggs Institute cross-sectional study quality assessment criteria. I-squared statistics applied to check the heterogeneity of studies. A funnel plot, Begg’s test, and Egger’s regression test was used to check for publication bias.

Results
Out of 206 studies, 30 studies with 21,672 children with mothers were included in the Meta-analysis. The pooled full immunization coverage using the random-effect model in Ethiopia was 58.92% (95% CI: 51.26–66.58%). The trend of immunization coverage was improved from time to time, but there were great disparities among different regions. Amhara region had the highest pooled fully immunized coverage, 72.48 (95%CI: 62.81–82.16). The I2 statistics was I2 = 99.4% (p = 0.0001). A subgroup meta-analysis showed that region and study years were not the sources of heterogeneity.

Conclusion
This review showed that full immunization coverage in Ethiopia was 58.92% (95% CI: 51.26–66.58%). The study suggests that the child routine immunization program needs to discuss this low immunization coverage and the current practice needs revision.
Hotspots of unimproved sources of drinking water in Ethiopia: mapping and spatial analysis of Ethiopia demographic and health survey Data 2016
Authors: Bogale Getahun Gebre 
Published: June 2020

Abstract
Background
More than 35% of the Ethiopian population are using drinking water from unimproved sources. As per the United Nations’ Sustainable Development Goals, Ethiopia is aspiring to achieve universal and equitable access to safe and affordable drinking water for all by 2030. For these goals to be accomplished, it is important to map the country’s hotspot areas of unimproved source of drinking-water so that resource allocation and disease control can be optimized there. Therefore, the objective of this study is to map and identify hotspot areas of unimproved sources of drinking water in Ethiopia.

Methods
A population based cross-sectional study was conducted in Ethiopia from January 18 to June 27, 2016. Data were collected from 10,064 households using a pretested and structured questionnaire. A stratified two-stage cluster sampling was employed where the enumeration areas were primary sampling units and households were secondary sampling units. Systematic sampling with probability proportional to size was employed to select samples. Datasets were cleaned and entered into SaTScan and ArcGIS software for mapping and analysis. The Global Moran’s I and spatial scan statistical tests (Bernoulli model) were done to explore the presence of clustering in the study area and local spatial clusters (hotspots) of unimproved sources of drinking water using ArcGIS version 10.3 and Kuldorff’s SaTScan version 9.4 software, respectively.

Results
Unimproved sources of drinking water were spatially clustered in the study area (Moran’s I: 0.35, p < 0.05). A total of 143 significant clusters was identified. Of which, eight were most likely (primary) clusters and the other 135 were secondary clusters. The first spatial window which contains primary clusters was located in Amhara and Afar regions (LLR: 78.89, at p < 0.001). The other 33 spatial windows which contain secondary clusters were found in all regions, except Gambela region and Addis Abeba city administration (with a range of LLR: 10.09–78.89, p < 0.001).

Conclusions
This study allowed the identification of important non-random clusters and hotspots of unimproved sources of drinking water. Therefore, these results will be determinant to help decision makers in their geographical interventions to combat problems related to drinking water quality.
The influence of corruption and governance in the delivery of frontline health care services in the public sector: a scoping review of current and future prospects in low and middle-income countries of south and south-east Asia
Authors: Naher Nahitun , Hoque Roksana , Hassan Muhammad Shaikh , Balabanova Dina , Adams Alayne M. , Ahmed Syed Masud 
Published: June 2020

AbstractBackgroundThe dynamic intersection of a pluralistic health system, large informal sector, and poor regulatory environment have provided conditions favourable for ‘corruption’ in the LMICs of south and south-east Asia region. ‘Corruption’ works to undermine the UHC goals of achieving equity, quality, and responsiveness including financial protection, especially while delivering frontline health care services. This scoping review examines current situation regarding health sector corruption at frontlines of service delivery in this region, related policy perspectives, and alternative strategies currently being tested to address this pervasive phenomenon.MethodsA scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was conducted, using three search engines i.e.,PubMed, SCOPUS and Google Scholar. A total of 15 articles and documents on corruption and 18 on governance were selected for analysis. A PRISMA extension for Scoping Reviews (PRISMA-ScR) checklist was filled-in to complete this report. Data were extracted using a pre-designed template and analysed by ‘mixed studies review’ method.ResultsCommon types of corruption like informal payments, bribery and absenteeism identified in the review have largely financial factors as the underlying cause. Poor salary and benefits, poor incentives and motivation, and poor governance have a damaging impact on health outcomes and the quality of health care services. These result in high out-of-pocket expenditure, erosion of trust in the system, and reduced service utilization. Implementing regulations remain constrained not only due to lack of institutional capacity but also political commitment. Lack of good governance encourage frontline health care providers to bend the rules of law and make centrally designed anti-corruption measures largely in-effective. Alternatively, a few bottom-up community-engaged interventions have been tested showing promising results. The challenge is to scale up the successful ones for measurable impact.ConclusionsCorruption and lack of good governance in these countries undermine the delivery of quality essential health care services in an equitable manner, make it costly for the poor and disadvantaged, and results in poor health outcomes. Traditional measures to combat corruption have largely been ineffective, necessitating the need for innovative thinking if UHC is to be achieved by 2030.
Evaluating dose delivered of a behavioral intervention for childhood obesity prevention: a secondary analysis
Authors: Heerman William J. , Sommer Evan C. , Qi Ally , Burgess Laura E. , Mitchell Stephanie J. , Samuels Lauren R. , Martin Nina C. , Barkin Shari L. 
Published: June 2020

Abstract
Background
Current recommendations for intensive behavioral interventions for childhood obesity treatment do not account for variable participant attendance, optimal duration of the intervention, mode of delivery (phone vs. face-to-face), or address obesity prevention among young children. A secondary analysis of an active one-year behavioral intervention for childhood obesity prevention was conducted to test how “dose delivered” was associated with body mass index z-score (BMI-Z) across 3 years of follow-up.

Methods
Parent-child pairs were eligible if they qualified for government assistance and spoke English or Spanish. Children were between three and 5 years old and were at risk for but not yet obese (BMI percentiles ≥50th and < 95th). The intended intervention dose was 18 h over 3-months via 12 face-to-face “intensive sessions” (90 min each) and 6.75 h over the next 9 months via 9 “maintenance phone calls” (45 min each). Ordinary least-squares multivariable regression was utilized to test for associations between dose delivered and child BMI-Z immediately after the 1-year intervention, and at 2-, and 3-year follow-up, including participants who were initially randomized to the control group as having “zero” dose.

Results
Among 610 parent-child pairs (intervention n = 304, control n = 306), mean child age was 4.3 (SD = 0.9) years and 51.8% were female. Mean dose delivered was 10.9 (SD = 2.5) of 12 intensive sessions and 7.7 (SD = 2.4) of 9 maintenance calls. Multivariable linear regression models indicated statistically significant associations of intensive face-to-face contacts (B = -0.011; 95% CI [− 0.021, − 0.001]; p = 0.029) and maintenance calls (B = -0.015; 95% CI [− 0.026, − 0.004]; p = 0.006) with lower BMI-Z immediately following the 1-year intervention. Their interaction was also significant (p = 0.04), such that parent-child pairs who received higher numbers of both face-to-face intensive sessions (> 6) and maintenance calls (> 8) were predicted to have lower BMI-Z. Sustained impacts were not statistically significant at 2- or 3-year follow-up.

Conclusions
In a behavioral intervention for childhood obesity prevention, the combination of a modest dose of face-to-face sessions (> 6 h over 3 months) with sustained maintenance calls (> 8 calls over 9 months) was associated with improved BMI-Z at 1-year for underserved preschool aged children, but sustained impacts were not statistically significant at 2 or 3 year follow-up.

Clinical trial registration
The trial was registered on ClinicalTrials.gov (NCT01316653) on March 16, 2011, which was prior to participant enrollment.
Regret over the delay in childbearing decision negatively associates with life satisfaction among Japanese women and men seeking fertility treatment: a cross-sectional study
Authors: Adachi Tomoko , Endo Masayuki , Ohashi Kazutomo 
Published: June 2020

Abstract
Background
Currently, in developed countries, increasing numbers of women and men are delaying childbearing but begin seeking fertility treatment later in life. Some women undergoing infertility treatment develop negative feelings such as depression associated with low life satisfaction and regret over the delay in childbearing. We therefore examine the association of life satisfaction with regret over the delay in childbearing decision and infertility-related factors among Japanese women and men seeking fertility treatment.

Methods
This cross-sectional study included 253 women and 196 men referred to fertility facilities in Japan from July to December 2018. Participants completed a questionnaire on life satisfaction, regret over the delay in childbearing decision, infertility-related factors and sociodemographic characteristics. Life satisfaction was measured using the Satisfaction with Life Scale (SWLS), and the degree of regret over delay in childbearing decision was measured on a 7-point Likert scale. Multiple linear regressions, conducted separately by sex, were used to analyze the association of life satisfaction with regret over the delay in childbearing decision and infertility-related factors.

Results
Of the 253 women and 196 men, 102 (40.3%) women and 43 (21.9%) men answered “strongly agree” regarding their regret over the delay in childbearing decision. Among women, life satisfaction was negatively associated with regret (β = − 0.155, 95% CI [− 0.938, − 0.093], p = 0.017), use of assisted reproduction technology (ART) (β = − 0.135, 95% CI [− 2.977, − 0.020], p = 0.047). In contrast, previous live birth was positively associated with life satisfaction (β = 0.134, 95% CI [0.122, 3.739], p = 0.037). In men, we found no significant association of life satisfaction with regret over the delay in childbearing decision and infertility-related factors.

Conclusions
Regret over the delay in childbearing decision is negatively associated with life satisfaction among Japanese women seeking fertility treatment. It may be important for women to make better informed decision regarding the timing of childbearing to not regret later in life. Health professionals should address regret over the delay in childbearing decision during fertility treatment and explore ways to spread information on fertility awareness.
Acceptability of the “MOVEdiabetes” physical activity intervention in diabetes primary care settings in Oman: findings from participants and practitioners
Authors: Alghafri Thamra S. , Al Harthi Saud M. , Al-Ajmi Fatma , Al-Farsi Yahya , Craigie Angela M. , Bannerman Elaine , Anderson Annie S. 
Published: June 2020

Abstract
Background
Adequate physical activity (PA) is considered essential in diabetes management. However, evidence on the best method of promoting PA within diabetes care is inconclusive. The current work identifies perceptions on the acceptability of Intervention Group Participants (IGP) and Project Officers (POs) about the “MOVEdiabetes” intervention programme aimed at increasing PA in adults with type 2 diabetes in Oman (a retrospectively registered trial).

Methods
The “MOVEdiabetes” programme (PA consultations, pedometers and WhatsApp messages) was delivered by the POs (primary health care practitioners) in four primary care centres within a one-year cluster randomised control trial. Recruitment and retention were measured from trial attendance records. Programme satisfaction, appropriateness, and content suitability were assessed using exit surveys for both the IGP (interview based) and POs (self-administered). Open text questions on perceptions to the study programme were also included.

Results
Participants were randomised to an intervention group (IG, n = 122) or comparison group (CG, n = 110). The overall retention rate at three and 12 months was 92.7% [110(90.2%) IG vs 105(95.5%) CG] and 75% [82(67.2%) IG vs 92(83.6%) CG] respectively. Most (n = 14, 87.5%) POs and more than half (n = 49, 59.8%) IGP perceived the programme as very appropriate and many reported that they were “quite/ very satisfied” with the programme (n = 16, 100% PO’s and n = 71, 86.6% IGP). Two thirds (n = 55, 66.0%) of IGP were very/quite likely to recommend the programme to others. PA consultations, use of pedometers and Whatsapp messages were well perceived by all. Participants recommended the inclusion of dietary advice and PA promotion for the general public. Exploring PA facilities within the community was suggested by POs.

Conclusions
The “MOVEdiabetes” programme achieved a high retention rate and was perceived as satisfactory and appropriate. Results from this study suggest that it is worthwhile exploring the use of the “MOVEdiabetes” programme in clinical practice and further community links.

Trial registration
International Standard Randomised Controlled Trials No: ISRCTN14425284. Registered retrospectively on 12th April 2016.
A cross country comparison for the burden of cardiovascular disease attributable to tobacco exposure in China, Japan, USA and world
Authors: Wu Xiaomei , Zhu Bo , Xu Shuang , Bi Yifei , Liu Yong , Shi Jingpu 
Published: June 2020

Abstract
Background
Tobacco exposure (TE) is the major contributor for CVD mortality, but few published studies on CVD mortality attributable to TE have analyzed the potential reasons underlying long-term trends in China. Our studysought to find the potential reasons and compared CVD mortality attributable to TE in China, Japan, the United States of America (USA), and the world between 1990 and 2017.

Methods
The mortality data in China, Japan, the USA, and the world were obtained from Global Burden of Disease Study 2017(GBD 2017). Joinpoint regression was used to assess the trend magnitude and directions over time for CVD mortality, while the age-period-cohort method was used to analyzethe temporal trends of CVD mortality according to age, period, and cohort.

Results
A significant downward trend was found in the age-standardised mortality rate (ASMR) of CVD attributable to smoking in four regions. China had the smallest decline and the Chinese ASMR became the highest in 2017. All the annual net drifts in the four regions were negative and the local drifts were below zero. The longitudinal age curves of CVD mortality attributable to smoking increased in four regions,with China having the largest increase. The period or cohort RRs indicated a decline, and China had the smallest decline. The researchers further analyzed the IHD and stroke trends, finding that the morality and period or cohort RR of IHD in China was always at a high level.

Conclusions
CVD mortality attributable to TE declined in four regions, and was highest in China. The proportion of IHD mortality attributable to TE was similar to stroke, which significantly changed the traditional cognition of CVD composition, but the control measure was not sufficient for IHD in China.