bluuebunny/crossref_metadata_2025_split huggingface dataset:
Policy options to increase motivation for improving evidence-informed health policy-making in Iran
Authors: Sajadi Haniye Sadat , Majdzadeh Reza , Ehsani-Chimeh Elham , Yazdizadeh Bahareh , Nikooee Sima , Pourabbasi Ata , Lavis John 
Published: June 2021

Abstract
Background
Current incentive programmes are not sufficient to motivate researchers and policy-makers to use research evidence in policy-making. We conducted a mixed-methods design to identify context-based policy options for strengthening motivations among health researchers and policy-makers to support evidence-informed health policy-making (EIHP) in Iran.

Methods
This study was conducted in 2019 in two phases. In the first phase, we conducted a scoping review to extract interventions implemented or proposed to strengthen motivations to support EIHP. Additionally, we employed a comparative case study design for reviewing the performance evaluation (PE) processes in Iran and other selected countries to determine the current individual and organizational incentives to encourage EIHP. In the second phase, we developed two policy briefs and then convened two policy dialogues, with 12 and 8 key informants, respectively, where the briefs were discussed. Data were analysed using manifest content analysis in order to propose contextualized policy options.

Results
The policy options identified to motivate health researchers and policy-makers to support EIHP in Iran were: revising the criteria of academic PE; designing appropriate incentive programmes for nonacademic researchers; developing an indicator for the evaluation of research impact on policy-making or health outcomes; revising the current policies of scientific journals; revising existing funding mechanisms; presenting the knowledge translation plan when submitting a research proposal, as a mandatory condition; encouraging and supporting mechanisms for increasing interactions between policy-makers and researchers; and revising some administrative processes (e.g. managers and staff PEs; selection, appointment, and changing managers and reward mechanisms).

Conclusions
The current individual or organizational incentives are mainly focused on publications, rather than encouraging researchers and policy-makers to support EIHP. Relying more on incentives that consider the other impacts of research (e.g. impacts on health system and policy, or health outcomes) is recommended. These incentives may encourage individuals and organizations to be more involved in conducting research evidence, resulting in promoting EIHP.

Trial registration
NA.
Determining the sex-specific distributions of average daily alcohol consumption using cluster analysis: is there a separate distribution for people with alcohol dependence?
Authors: Jiang Huan , Lange Shannon , Tran Alexander , Imtiaz Sameer , Rehm Jürgen 
Published: June 2021

AbstractBackgroundIt remains unclear whether alcohol use disorders (AUDs) can be characterized by specific levels of average daily alcohol consumption. The aim of the current study was to model the distributions of average daily alcohol consumption among those who consume alcohol and those with alcohol dependence, the most severe AUD, using various clustering techniques.MethodsData from Wave 1 and Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions were used in the current analyses. Clustering algorithms were applied in order to group a set of data points that represent the average daily amount of alcohol consumed. Gaussian Mixture Models (GMMs) were then used to estimate the likelihood of a data point belonging to one of the mixture distributions. Individuals were assigned to the clusters which had the highest posterior probabilities from the GMMs, and their treatment utilization rate was examined for each of the clusters.ResultsModeling alcohol consumption via clustering techniques was feasible. The clusters identified did not point to alcohol dependence as a separate cluster characterized by a higher level of alcohol consumption. Among both females and males with alcohol dependence, daily alcohol consumption was relatively low.ConclusionsOverall, we found little evidence for clusters of people with the same drinking distribution, which could be characterized as clinically relevant for people with alcohol use disorders as currently defined.
Generating age-specific mortality statistics from incomplete death registration data: two applications of the empirical completeness method
Authors: Adair Tim , Lopez Alan D 
Published: June 2021

Abstract
Background
The study aims to assess two approaches that apply the empirical completeness method to generate age-specific mortality statistics from incomplete death registration systems.

Methods
We use the empirical completeness method to calculate all-age death registration completeness, which is used with a model life table to generate mortality statistics and age-specific completeness using (1) the conventional method and (2) the equivalent deaths method. The results are compared with a capture-recapture (C-RC) study and three alternative mortality estimates for Brazilian states, and C-RC studies in Thailand, Oman and Vietnam, which independently estimate the level and age pattern of mortality or completeness.

Results
The empirical completeness method produces similar estimates of all-age completeness of registration to the C-RC studies. Compared with C-RC studies, at 15-59 years, the conventional method’s estimates of mortality and completeness are more concordant, while at 60-84 years the equivalent death method’s estimates are closer. Estimates of life expectancy from the two approaches each have similar concordance with the C-RC studies. For male adult mortality in Brazilian states, there is relatively strong average correlation of this study's estimates with three alternative estimates.

Conclusions
The two approaches produce mortality statistics from incomplete data that are mostly concordant with C-RC studies, and can be most usefully applied to subnational populations.
Physical activity and 4-year changes in body weight in 52,498 non-obese people: the Lifelines cohort
Authors: Byambasukh Oyuntugs , Vinke Petra , Kromhout Daan , Navis Gerjan , Corpeleijn Eva 
Published: June 2021

Abstract
Objectives
We investigated associations between leisure-time physical activity (LTPA) at different intensities (moderate and vigorous or moderate-to-vigorous) and prospective weight gain in non-obese people. We also examined whether these associations were independent of other lifestyle factors and changes in muscle mass and whether they were age-dependent and changed over a person’s life course.

Methods
The data were extracted from the Lifelines cohort study (N = 52,498; 43.5% men) and excluded obese individuals (BMI > 30 kg/m2). We used the validated SQUASH questionnaire to estimate moderate-to-vigorous (MVPA; MET≥4), moderate (MPA; MET between 4 and 6.5) and vigorous PA (VPA; MET≥6.5). Body weight was objectively measured, and changes were standardized to a 4-year period. Separate analyses, adjusted for age, educational level, diet, smoking, alcohol consumption and changes in creatinine excretion (a marker of muscle mass), were performed for men and women.

Results
The average weight gain was + 0.45 ± 0.03 kg in women. Relative to each reference groups (No-MVPA, No-MPA and No-VPA), MVPA (Beta (95%CI): − 0.34 kg (− 0.56;-0.13)), MPA (− 0.32 kg (− 0.54;-0.10)) and VPA (− 0.30 kg (− 0.43;-0.18)) were associated with less gain in body weight in women after adjusting for potential confounders, described above. These associations were dose-dependent when physically active individuals were divided in tertiles. Beta-coefficients (95%CI) for the lowest, middle, and highest MVPA tertiles relative to the ‘No-MVPA’ were, respectively, − 0.24 (− 0.47;-0.02), − 0.31 (− 0.53;-0.08), and − 0.38 (− 0.61;-0.16) kg. The average weight gain in men was + 0.13 ± 0.03 kg, and only VPA, not MPA was associated with less body weight gain. Beta-coefficients (95%CI) for the VPA tertiles relative to the ‘No-VPA’ group were, respectively, − 0.25 (− 0.42;-0.09), − 0.19 (− 0.38;-0.01) and − 0.20 (− 0.38;-0.02) kg. However, after adjusting for potential confounders, the association was no longer significant in men. The potential benefits of leisure-time PA were age-stratified and mainly observed in younger adults (men < 35 years) or stronger with younger age (women < 55 years).

Conclusion
Higher leisure-time MVPA, MPA, and VPA were associated with less weight gain in women < 55 years. In younger men (< 35 years), only VPA was associated with less weight gain.
Underestimated health risks: polystyrene micro- and nanoplastics jointly induce intestinal barrier dysfunction by ROS-mediated epithelial cell apoptosis
Authors: Liang Boxuan , Zhong Yizhou , Huang Yuji , Lin Xi , Liu Jun , Lin Li , Hu Manjiang , Jiang Junying , Dai Mingzhu , Wang Bo , Zhang Bingli , Meng Hao , Lelaka Jesse Justin J. , Sui Haixia , Yang Xingfen , Huang Zhenlie 
Published: June 2021

Abstract
Background
Micro- and nanoplastic pollution has become a global environmental problem. Nanoplastics in the environment are still hard to detect because of analysis technology limitations. It is believed that when microplastics are found in the environment, more undetected nanoplastics are around. The current “microplastic exposure” is in fact the mixture of micro- and nanoplastic exposures. Therefore, the biological interaction between organisms among different sizes of micro- and nanoplastics should not be neglected.

Results
We measured the biodistribution of three polystyrene (PS) particles (50 nm PS, PS50; 500 nm PS, PS500; 5000 nm PS, PS5000) under single and co-exposure conditions in mice. We explored the underlying mechanisms by investigating the effects on three major components of the intestinal barrier (the mucus layer, tight junctions and the epithelial cells) in four intestine segments (duodenum, jejunum, ileum and colon) of mice. We found that the amounts of both PS500 and PS5000 increased when they were co-exposed with PS50 for 24 h in the mice. These increased amounts were due primarily to the increased permeability in the mouse intestines. We also confirmed there was a combined toxicity of PS50 and PS500 in the mouse intestines. This manifested as the mixture of PS50 and PS500 causing more severe dysfunction of the intestinal barrier than that caused by PS50 or PS500 alone. We found that the combined toxicity of PS micro- and nanoplastics on intestinal barrier dysfunction was caused primarily by reactive oxygen species (ROS)-mediated epithelial cell apoptosis in the mice. These findings were further confirmed by an oxidants or antioxidants pretreatment study. In addition, the combined toxicity of PS micro- and nanoplastics was also found in the mice after a 28-day repeated dose exposure.

Conclusions
There is a combined toxicity of PS50 and PS500 in the mouse intestines, which was caused primarily by ROS-mediated epithelial cell apoptosis in the mice. Considering that most recent studies on PS micro- and nanoplastics have been conducted using a single particle size, the health risks of exposure to PS micro- and nanoplastics on organisms may be underestimated.
Associations between parental alcohol problems in childhood and adversities during childhood and later adulthood: a cross-sectional study of 28047 adults from the general population
Authors: Haugland Siri Håvås , Carvalho Barbara , Stea Tonje Holte , Strandheim Arve , Vederhus John-Kåre 
Published: June 2021

Abstract
Background
Adverse childhood experiences (ACE) are related to adverse physical and mental health outcomes. However, few larger studies based on a general population sample with age groups ranging from young adults to elderly have investigated whether parental alcohol problems increase the risk of offspring subjective reports of ACE both during childhood and current adult adversities. The purpose of this study was to examine the associations between parental alcohol problems and adversities during childhood and later in adulthood.

Methods
The 28,047 respondents were adults (> 18 years old) from the general population who participated in the Norwegian Counties Public Health Survey. The study had a cross-sectional design and included respondents’ evaluations of childhood experiences and current adult adversities. The short version of the Children of Alcoholics Screening Test (CAST-6, cut-off ≥3) measured parental alcohol problems. Multivariable logistic regression was adjusted for gender, age, and education.

Results
Growing up with parental alcohol problems strongly increased the risk of experiencing a dysfunctional family environment during childhood (odds ratio [OR] 6.84; 95% confidence interval [CI] 6.36–7.36), perceiving childhood as difficult (OR 5.01; 95% CI 4.58–5.49), and reporting a lack of support from a trusted adult (OR 3.07; 95% CI 2.86–3.29). Parental alcohol problems were associated with a modestly increased risk of harmful alcohol use (OR 1.38; 95% CI 1.29–1.48), but the association with struggling with bad memories was strong (OR 4.56; 95% CI 4.17–4.98).

Conclusions
Parental alcohol problems increased the risk of offspring experiencing adversities during both childhood and adulthood. Providing supportive services to these children and their families and addressing this issue as part of treatment is important to prevent alcohol related harm.
The effect of aqueous extract of Prunus dulcis on tibial bone healing in the rabbit
Authors: Anaraki Nima , Beyraghi Amir Hossein , Raisi Abbas , Davoodi Farshid , Farjanikish Ghasem , Sadegh Amin Bigham 
Published: June 2021

Abstract
Background
Bone fractures are medical emergencies that require prompt intervention to help return bone to its normal function. Various methods and treatments have been utilized to increase the speed and efficiency of bone repair. This study aimed to investigate the treatment effects of Prunus dulcis aqueous extract on tibial bone healing in rabbits.

Methods
All animals were distributed in five groups with six rats in each group, including the sham group, the control group in which tibial lesion was made and received distilled water, treatment groups with 150 mg kg−1, 300 mg kg−1 doses of Prunus dulcis extract, and osteocare treated group. Biochemical blood factors including calcium, phosphorus, and alkaline phosphatase (on days 0, 10, 30, and 50), biomarkers of oxidative stress such as GPx, CAT, and MDA (on days 10 and 30), radiological evaluation, histopathological parameters, and osteocalcin immunohistochemical expression were assessed.

Results
The data showed calcium levels in the treatment groups increased significantly from day 10 to day 50, respectively, and blood phosphorus levels decreased from day 10 to day 50 in the treatment groups. Alkaline phosphatase initially increased and then decreased in treatment groups. In the treatment groups, GPx and CAT levels significantly increased, and the serum amount of MDA reduced. The best antioxidant results were related to the extract-treated group with a higher dose. Radiographic score was significantly higher in the treatment groups than the control group on day 30. Based on the pathological findings, the healing occurred faster in the extract-treated group with a higher dose. Osteocalcin expression was significantly higher in the control group than that in the treatment groups.

Conclusions
Treatment with Prunus dulcis extract with a dosage of 300 mg/kg accelerated tibial bone healing in rabbits.

Graphical abstract
NDRG1 regulates osteosarcoma cells via mediating the mitochondrial function and CSCs differentiation
Authors: Zhao Tong , Meng Ying , Wang Yongping , Wang Wenji 
Published: June 2021

Abstract
Background
Cancer stem cells (CSCs) are mainly contributed to malignancy metastatic potential and resistant therapy of osteosarcoma (OS). The mitochondria-related apoptosis was generally accepted as the target of tumor therapy. However, the effect of N-myc downstream-regulated gene 1 (NDRG1) on CSCs and mitochondrial health in OS is still unknown.

Methods
In OS cells, MG63 and U2OS, the siRNA of NDRG1 were conducted. Transwell, western blot, RT-qPCR, and mitochondria isolation were used to identify the effect of NDRG on OS cells and mitochondria. Moreover, the differentiation-related factors of CSCs were determined.

Results
After downregulation of NDRG1, the cell viability, invasion ability decreased whereas cell apoptosis increased. The expressions profiles of fibronectin, vimentin, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP) 2, MMP9, and MMP13 were downregulated, but E-cadherin expression level was upregulated by NDRG1 siRNA. At the same time, cytochrome (Cyt) C levels were increased in cytosol with the decreasing in mitochondria after siRNA treatment. The mitochondrial membrane potential (MMPs) was declined, and the function of mitochondria was impeded. The expressions of uncoupling proteins (UCP) 2, voltage dependent anion channel (VDAC), peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α, and cyclooxygenase (COX) 2 were downregulated by NDRG1 silencing. Moreover, NDRG performed its function primarily through the Wnt pathway and could regulate the differentiation of osteosarcoma stem cells.

Conclusion
Silencing of NDRG1 could damage the function of mitochondria, promote the CSCs differentiation, alleviating OS progression.
Incidence of valvular regurgitation and leaflet perforation by using automated titanium fasteners (CORKNOT®) in heart valve repair or replacement: less usual than reported
Authors: Sazzad Faizus , Xian Ong Zhi , Ler Ashlynn , Guohao Chang , Swee Kang Giap , Kofidis Theo 
Published: June 2021

Abstract
Background
CORKNOT® facilitates a reduction in cardiopulmonary bypass (CPB) time, aortic cross clamp (ACC) time and operative time, but reported to be associated with other complications. We aim to quantify the incidence of valvular complications related to CORKNOT® and determine the feasibility of its use between different valvular surgeries.

Methods
Patients who underwent heart valve repair or replacement surgery via the use of automated titanium suture fasteners (CORKNOT®) in a tertiary care hospital were included in the study. This single-centre retrospective study was conducted on 132 patients between January 2016 and June 2018.

Results
In our study, the overall mean operative time was 320.0 ± 97.0 min, mean CPB time was 171.4 ± 76.0 min and the calculated mean ACC time was 105.9 ± 54.0 min. Fifty-eight patients (43.9%) underwent minimally invasive valve replacement or repair surgery and 66 patients (50.0%) underwent concomitant procedures. A total of 157 valves were operated on, with 112 (84.8%) single valve surgeries, 15 (11.4%) double valve surgeries and 5 (3.8%) triple valve surgeries. After reviewed by the cardiologist blinded towards the study, we report trivial and/or mild paravalvular leak (PVL) in immediate post-operative echocardiography was found in 1 (1.01%) patients. There were no reported cases of valvular thrombosis, leaflet perforation, device dislodgement or embolization, moderate and/or severe PVL during hospitalization and follow-up echocardiography within 1 year. Single mitral valve and aortic surgeries had comparable incidences of post surgical complications.

Conclusion
We conclude the feasibility of CORKNOT® utilisation in mitral and aortic valve surgeries. Additionally, incidence of CORKNOT® related complications in heart valve repair or replacement surgery is less usual in our setting than previously reported. These results motivate the use of CORKNOT® as a valid alternative with complete commitment.
Comparison of the clinical effect between the lower sternal incision and the left parasternal fourth intercostal incision in the transthoracic closure of ventricular septal defect
Authors: Ma Jun , Shangguan Wenlin , Chen Liang-Wan , Liao Dong-shan 
Published: June 2021

Abstract
Background
To analyze the clinical effect of two different ways of minimally invasive transthoracic closure in children with ventricular septal defect (VSD).

Methods
From January 2015 to July 2019, 294 children with VSD were enrolled in the Fujian Medical University Union Hospital. Patients were divided into two groups – those who underwent VSD closure through the left sternal fourth intercostal incision (group A: n = 95) and the lower sternal incision (group B: n = 129).

Results
The operation time, bleeding volume, postoperative mechanical ventilation time, postoperative intensive care unit (ICU) monitoring time, postoperative hospitalization time and complication rate in group A were significantly lower than those in group B (P < 0.05). There was no significant difference between the two groups in the operation success rate, mechanical ventilation time and total hospitalization cost (P > 0.05).

Conclusion
The transthoracic closure of ventricular septal defect through the left sternal fourth intercostal incision is feasible, safe, cosmetic, and worth popularizing.
Analysis of copy number variations of WNT4 gene in a Chinese population with Müllerian anomalies
Authors: Zhu Ying , Wang Ruyi , Cheng Yun , Han Yang , Li Tengyan , Cao Yunxia , Wang Binbin 
Published: June 2021

Abstract
Background
To investigate the genetic contribution of copy number variations (CNVs) in Wingless-type MMTV integration site family, member 4 (WNT4), in a Chinese population with Müllerian anomalies (MA), copy number analysis of WNT4 by Multiplex ligation‐dependent probe amplification (MLPA) was performed on 248 female patients. Some studies have shown that heterozygous missense mutation of WNT4 can lead to MA. However, few studies on the relationship between WNT4 CNVs and MA have been performed.

Results
Among the 248 Chinese women affected by MA in this study, heterozygous deletion of WNT4 was detected in a single patient.

Conclusions
MLPA identified one heterozygous deletion in WNT4 in a single female patient among 248 Chinese women affected by MA. This study firstly reports CNVs of WNT4 in a large sample of MA patients from the Chinese population, which suggests that CNVs of WNT4 cannot be excluded in the occurrence of MA. This provides a genetic basis for precise treatment in the future.
Determinants of resistance to VEGF-TKI and immune checkpoint inhibitors in metastatic renal cell carcinoma
Authors: Sharma Revati , Kadife Elif , Myers Mark , Kannourakis George , Prithviraj Prashanth , Ahmed Nuzhat 
Published: June 2021

AbstractVascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) have been the mainstay of treatment for patients with advanced renal cell carcinoma (RCC). Despite its early promising results in decreasing or delaying the progression of RCC in patients, VEGF-TKIs have provided modest benefits in terms of disease-free progression, as 70% of the patients who initially respond to the treatment later develop drug resistance, with 30% of the patients innately resistant to VEGF-TKIs. In the past decade, several molecular and genetic mechanisms of VEGF-TKI resistance have been reported. One of the mechanisms of VEGF-TKIs is inhibition of the classical angiogenesis pathway. However, recent studies have shown the restoration of an alternative angiogenesis pathway in modulating resistance. Further, in the last 5 years, immune checkpoint inhibitors (ICIs) have revolutionized RCC treatment. Although some patients exhibit potent responses, a non-negligible number of patients are innately resistant or develop resistance within a few months to ICI therapy. Hence, an understanding of the mechanisms of VEGF-TKI and ICI resistance will help in formulating useful knowledge about developing effective treatment strategies for patients with advanced RCC. In this article, we review recent findings on the emerging understanding of RCC pathology, VEGF-TKI and ICI resistance mechanisms, and potential avenues to overcome these resistance mechanisms through rationally designed combination therapies.