bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of DNA methylation in the association of lung function with body mass index: a two-step epigenetic Mendelian randomisation study
Authors: Amaral André F. S. , Imboden Medea , Wielscher Matthias , Rezwan Faisal I. , Minelli Cosetta , Garcia-Aymerich Judith , Peralta Gabriela P. , Auvinen Juha , Jeong Ayoung , Schaffner Emmanuel , Beckmeyer-Borowko Anna , Holloway John W. , Jarvelin Marjo-Riitta , Probst-Hensch Nicole M. , Jarvis Deborah L. ,   for the ALEC consortium
Published: June 2020

Abstract
Background
Low lung function has been associated with increased body mass index (BMI). The aim of this study was to investigate whether the effect of BMI on lung function is mediated by DNA methylation.

Methods
We used individual data from 285,495 participants in four population-based cohorts: the European Community Respiratory Health Survey, the Northern Finland Birth Cohort 1966, the Swiss Study on Air Pollution and Lung Disease in Adults, and the UK Biobank. We carried out Mendelian randomisation (MR) analyses in two steps using a two-sample approach with SNPs as instrumental variables (IVs) in each step. In step 1 MR, we estimated the causal effect of BMI on peripheral blood DNA methylation (measured at genome-wide level) using 95 BMI-associated SNPs as IVs. In step 2 MR, we estimated the causal effect of DNA methylation on FEV1, FVC, and FEV1/FVC using two SNPs acting as methQTLs occurring close (in cis) to CpGs identified in the first step. These analyses were conducted after exclusion of weak IVs (F statistic < 10) and MR estimates were derived using the Wald ratio, with standard error from the delta method. Individuals whose data were used in step 1 were not included in step 2.

Results
In step 1, we found that BMI might have a small causal effect on DNA methylation levels (less than 1% change in methylation per 1 kg/m2 increase in BMI) at two CpGs (cg09046979 and cg12580248). In step 2, we found no evidence of a causal effect of DNA methylation at cg09046979 on lung function. We could not estimate the causal effect of DNA methylation at cg12580248 on lung function as we could not find publicly available data on the association of this CpG with SNPs.

Conclusions
To our knowledge, this is the first paper to report the use of a two-step MR approach to assess the role of DNA methylation in mediating the effect of a non-genetic factor on lung function. Our findings do not support a mediating effect of DNA methylation in the association of lung function with BMI.
Long-term impact of sagittal malalignment on hardware after posterior fixation of the thoracolumbar spine: a retrospective study
Authors: Elshamly Mahmoud , Windhager Reinhard , Toegel Stefan , Grohs Josef Georg 
Published: June 2020

Abstract
Background
The importance of sagittal alignment in healthy individuals and in reconstructive spinal surgery has been studied over the last 15 years. The aim of the present study was to assess the long-term effects of abnormal sagittal alignment on hardware after posterior thoracolumbar spinal fusion.

Methods
Patients who had undergone revision surgery (revision cohort, n = 34) due to breakage of their implants were compared retrospectively with patients who had intact implants at the final follow-up investigation after a long posterior thoracolumbar and/or lumbar spinal fusion (control cohort, n = 22). Clinical data and radiological parameters including the sagittal vertical axis (SVA), pelvic incidence (PI), lordosis gap (LG), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis (TK), and the femoral obliquity angle (FOA) were assessed on full-spine lateral radiographs obtained in regular standing position. Data were analysed using descriptive statistics, parametric and non-parametric inferential statistics.

Results
Patients in the breakage group (female n = 21, male n = 9, mean age 60.9 ± 15.6 years) had a higher anterior shift of the C7 plumb line (SVA) (p = 0.02), retroversion of the pelvis (PT) (p < 0.001), PI-LL mismatch (LG) (p = 0.001), and PI (p = 0.002) than the intact group (female n = 10, male n = 12, mean age 65.7 ± 12.4 years). No significant difference was registered between groups in regard of SS, LL, TK, FOA, and the mean number of comorbidities.

Conclusion
Failure of restoration of the SVA and the LG to the acceptable ranges, especially in patients with a high PI, may be regarded as a risk factor for the long-term failure of implants after posterior thoracolumbar spinal fusion.
How group coaching contributes to organisational understanding among newly graduated doctors
Authors: Malling Bente , de Lasson Lydia , Just Eva , Stegeager Nikolaj 
Published: June 2020

Abstract
Background
Practising medicine at an expert level requires skills beyond medical expert knowledge. Research shows that newly appointed consultants feel less prepared to deal with leadership issues compared to issues regarding medical expertice. Newly graduated (NG) doctors and residents in particular struggle with leadership and organisational issues.
The purpose of this study was to explore the impact of group coaching on NG doctors’ approach to organisational and leadership challenges in daily practice during the transition period from medical school to clinical work.

Methods
Newly graduated doctors participated in a group coaching course comprising three full-day sessions and five two-hour sessions. The purpose was to support NG doctors’ professional development regarding organisational issues in the first years after graduation. The coaches were health professionals with certified coaching training. Data from the intervention were collected from open-ended questionnaires and observational notes. A thematic analysis was performed.

Results
Forty-five NG doctors participated in a total of six courses sharing experiences and problems reflected in their professional lives. The following themes emerged: Revelation of the hidden curriculum, importance of professional relations, inter-professional communication, conflict management and emerging leadership skills. Participants’ communication skills improved due to an increased awareness of other peoples’ perspectives and preferences. They realized the importance of good relations, saw how they could become active contributors in their departments and began to practice leadership skills through e.g. involvement of the team, delegation of work and negotiation of own obligations.

Conclusion
Newly graduated doctors seemed to develop a growing awareness of organisational issues and a deeper understanding of the complexity of health care organisations through participation in a group coaching course. The study indicates that participation in a group coaching course probably contributes to improve practice among NG doctors. Further studies are needed to consolidate the findings and explore possible organisational effects.
Stratifying patients using fast multiple kernel learning framework: case studies of Alzheimer’s disease and cancers
Authors: Giang Thanh-Trung , Nguyen Thanh-Phuong , Tran Dang-Hung 
Published: June 2020

Abstract
Background
Predictive patient stratification is greatly emerging, because it allows us to prospectively identify which patients will benefit from what interventions before their condition worsens. In the biomedical research, a number of stratification methods have been successfully applied and have assisted treatment process. Because of heterogeneity and complexity of medical data, it is very challenging to integrate them and make use of them in practical clinic. There are two major challenges of data integration. Firstly, since the biomedical data has a high number of dimensions, combining multiple data leads to the hard problem of vast dimensional space handling. The computation is enormously complex and time-consuming. Secondly, the disparity of different data types causes another critical problem in machine learning for biomedical data. It has a great need to develop an efficient machine learning framework to handle the challenges.

Methods
In this paper, we propose a fast-multiple kernel learning framework, referred to as fMKL-DR, that optimise equations to calculate matrix chain multiplication and reduce dimensions in data space. We applied our framework to two case studies, Alzheimer’s disease (AD) patient stratification and cancer patient stratification. We performed several comparative evaluations on various biomedical datasets.

Results
In the case study of AD patients, we enhanced significantly the multiple-ROIs approach based on MRI image data. The method could successfully classify not only AD patients and non-AD patients but also different phases of AD patients with AUC close to 1. In the case study of cancer patients, the framework was applied to six types of cancers, i.e., glioblastoma multiforme cancer, ovarian cancer, lung cancer, breast cancer, kidney cancer, and liver cancer. We efficiently integrated gene expression, miRNA expression, and DNA methylation. The results showed that the classification model basing on integrated datasets was much more accurate than classification model basing on the single data type.

Conclusions
The results demonstrated that the fMKL-DR remarkably improves computational cost and accuracy for both AD patient and cancer patient stratification. We optimised the data integration, dimension reduction, and kernel fusion. Our framework has great potential for mining large-scale cohort data and aiding personalised prevention.
Out of pocket expenditures of patients with a chronic condition consulting a primary care provider in Tajikistan: a cross-sectional household survey
Authors: Fischer Fabienne B. , Mengliboeva Zulfira , Karimova Gulzira , Abdujabarov Nasrullo , Prytherch Helen , Wyss Kaspar 
Published: June 2020

Abstract
Background
Within its reform efforts, the Government of Tajikistan is embracing the essential role of primary health care (PHC) in decreasing out of pocket (OOP) expenditures and increasing equity in access to health services. In the light of the increasing burden of disease relating to chronic conditions, we investigated OOP expenditures of patients with chronic conditions within a PHC setting; and if and how those expenditures are impacted by several interventions currently being implemented within Tajikistan.

Methods
A cross-sectional survey among 1600 adult patients who had visited a PHC facility was conducted. The data obtained through interviews were descriptively analysed, and logistic regressions and gamma generalized linear models were performed.

Results
The total OOP expenditures related to a patient’s last visit to the PHC facility were 17.2 USD for those with chronic conditions and 13.9 USD for those visiting due to an acute condition. Adjustment for potential confounders reduced the discrepancy from 3.3 USD to 0.5 USD. This convergence of costs was only observed in districts covered by the Basic Benefit Package (BBP), a governmental pilot project, aiming to standardise exemptions for payment and formal co-payments for health care services. Hence, we found the BBP to have a protective impact for patients with chronic conditions. However, considering the demographics of these patients (older in age, with greater dependency on pensions and social aid, and lower socio-economic status) in combination with the 40% higher utilisation rate of PHC and the high rate of onward referrals to specialists; it is clear that patients with chronic conditions continue to face substantial long-term costs and disadvantages.

Conclusions
After accounting for confounders, patients with chronic and acute conditions faced similar costs related to a single visit to a PHC facility in districts covered by the BBP. However, greater efforts are required to ensure that citizens are well informed about their rights to health care, the BBP and the services that should be provided at no cost at the point of delivery. Moreover, the needs of patients with chronic conditions warrant a more integrative approach that takes long-term expenditures and services beyond the level of PHC into account.
Interaction between obstructive sleep apnea and short sleep duration on insulin resistance: a large-scale study
Authors: Xu Huajun , Liang Chen , Zou Jianyin , Yi Hongliang , Guan Jian , Gu Meizhen , Feng Yanhong , Yin Shankai 
Published: June 2020

Abstract
Objectives
Both short sleep duration and obstructive sleep apnea (OSA) seem to be associated with insulin resistance. We aimed to explore whether short sleep duration modifies the relationship between OSA and insulin resistance.

Methods
Participants were consecutively enrolled from our sleep center during the period from 2007 to 2017. The index of homeostasis model assessment insulin resistance (HOMA-IR) was calculated from insulin and glucose. Sleep duration was determined by standard polysomnography. The associations between sleep duration and insulin resistance were estimated by logistic regression analyses.

Results
A total of 5447 participants (4507 OSA and 940 primary snorers) were included in the study. OSA was independently correlated with insulin resistance after adjusting for all potential confounders (OR, 1.319; 95% CI, 1.088–1.599), but not short sleep duration. In stratified analysis by sleep duration, compared with primary snorers, in the OSA group only extremely short sleep duration (< 5 h) was significantly associated with insulin resistance after adjusting for all covariates (OR, 2.229; 95% CI, 1.283–3.874). Rapid eye movement predominant OSA was significantly associated with insulin resistance (OR = 1.355, 95% CI: 1.019–1.802) after adjustment for confounding factors including age, sex and body mass index.

Conclusions
OSA, but not short sleep duration, was independently associated with insulin resistance. It is worth noting that OSA combined with extremely short sleep duration showed a greater detrimental effect than OSA itself with regard to insulin resistance.
Circular RNA circ_0000284 plays an oncogenic role in the progression of non-small cell lung cancer through the miR-377-3p-mediated PD-L1 promotion
Authors: Li Li , Zhang Qiaohua , Lian Ke 
Published: June 2020

AbstractBackgroundCircular RNAs (circRNAs), a subgroup of non-coding RNAs, are recognized as pivotal mediators in various types of cancers. CircRNA_0000284 (circ_0000284) was manifested to participate in the development of non-small cell lung cancer (NSCLC). The novel functional mechanism of circ_0000284 in NSCLC was investigated in our current study.MethodsWe exploited quantitative real-time polymerase chain reaction (qRT-PCR) to analyze the relative RNA (circRNA, miRNA and mRNA) expression. The assessment of cell proliferation and colony formation was executed by Cell Counting Kit-8 (CCK-8) and colony formation assay, respectively. Transwell assay was implemented to examine cell migration and invasion. All protein levels were assayed using western blot. The role of circ_0000284 in vivo was evaluated via xenograft model. The target relation was estimated by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.ResultsAs for the biological characterization, circ_0000284 was highly stable and localized in the cytoplasm. Circ_0000284 was up-regulated in NSCLC and could predict poor prognosis of NSCLC patients. Both in vitro and in vivo, down-regulation of circ_0000284 refrained tumorigenesis of NSCLC. Besides, microRNA-377-3p (miR-377-3p) was a miRNA target of circ_0000284, and targeted programmed death-ligand 1 (PD-L1). Circ_0000284 was a cancer-promoting circRNA in NSCLC via regulating the miR-377-3p/PD-L1 axis.ConclusionThus, our results unraveled that circ_0000284 facilitated the progression of NSCLC by up-regulating the PD-L1 expression as a competing endogenous RNA (ceRNA) of miR-377, possibly developing a different perspective in understanding the molecular pathogenesis of NSCLC.
CircHIPK3 promotes proliferation and metastasis and inhibits apoptosis of renal cancer cells by inhibiting MiR-485-3p
Authors: Lai Jinjin , Xin Jun , Fu Changde , Zhang Wei 
Published: June 2020

Abstract
Background
The intervention of circHIPK3 in renal carcinoma (RC) has not been reported, and thus, the current study investigated the intervention and mechanism of circHIPK3 in RC.

Methods
The expression of circHIPK3 in RC tissues and cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Ribonuclease R (RNase R) resistance and distribution of circHIPK3 and HIPK3 were analyzed by RNase R digestion experiments and cytoplasm/nucleus separation experiments. CircHIPK3 was knocked down in ACHN and 769-P cells. Cell counting kit-8 (CCK-8), colony formation assay, scratch assay, and Transwell assay were performed to detect cell proliferation and metastasis. CircInteractome, qRT-PCR and dual-luciferase reporter assay were used to predict the target miRNAs of circHIPK3. Furthermore, a series of rescue experiments were performed to analyze the regulatory relationship between circHIPK3 and miR-485-3p. Epithelial-mesenchymal transition (EMT) and the expressions of apoptosis-associated markers were detected by Western blot and qRT-PCR. The regulatory relationship between circHIPK3 and miR-485-3p in vivo was explored by xenograft experiments, Western blot, qRT-PCR and immunohistochemistry (Ki-67).

Results
CircHIPK3 was mainly overexpressed in the cytoplasm of RC tissues and cells. Knocking down circHIPK3 inhibited the proliferation, migration, and invasion of RC cells. The expression of circHIPK3 was negatively related to that of its target gene miR-485-3p. Results of the rescue experiments showed that circHIPK3 overexpression could partially reverse the anti-carcinoma effect of miR-485-3p mimic. The specific mechanism of circHIPK3 was related to the effect of miR-485-3p on partially reversing the up-regulated expressions of Clever caspase-3, Bax, E-Cadherin and down-regulated expressions of Bcl-2, N-Cadherin and Vimentin. The results of in vivo experiments demonstrated that circHIPK3 promoted tumor growth and the expression of Ki-67 by down-regulating miR-485-3p.

Conclusion
CircHIPK3 promotes the proliferation and metastasis and inhibits the apoptosis of RC cells through competitively binding to miR-485-3p.
Development of a consensus statement on the role of the family in the physical activity, sedentary, and sleep behaviours of children and youth
Authors: Rhodes Ryan E. , Guerrero Michelle D. , Vanderloo Leigh M. , Barbeau Kheana , Birken Catherine S. , Chaput Jean-Philippe , Faulkner Guy , Janssen Ian , Madigan Sheri , Mâsse Louise C. , McHugh Tara-Leigh , Perdew Megan , Stone Kelly , Shelley Jacob , Spinks Nora , Tamminen Katherine A. , Tomasone Jennifer R. , Ward Helen , Welsh Frank , Tremblay Mark S. 
Published: June 2020

AbstractBackgroundChildren and youth who meet the physical activity, sedentary, and sleep behaviour recommendations in the Canadian 24-Hour Movement Guidelines are more likely to have desirable physical and psychosocial health outcomes. Yet, few children and youth actually meet the recommendations. The family is a key source of influence that can affect lifestyle behaviours. The purpose of this paper is to describe the process used to develop theConsensus Statement on the Role of the Family in the Physical Activity, Sedentary, and Sleep Behaviours of Children and Youth(0–17 years) and present, explain, substantiate, and discuss the finalConsensus Statement.MethodsThe development of theConsensus Statementincluded the establishment of a multidisciplinary Expert Panel, completion of six reviews (three literature, two scoping, one systematic review of reviews), custom data analyses of Statistics Canada’s Canadian Health Measures Survey, integration of related research identified by Expert Panel members, a stakeholder consultation, establishment of consensus, and the development of a media, public relations, communications and launch plan.ResultsEvidence from the literature reviews provided substantial support for the importance of family on children’s movement behaviours and highlighted the importance of inclusion of the entire family system as a source of influence and promotion of healthy child and youth movement behaviours. The Expert Panel incorporated the collective evidence from all reviews, the custom analyses, other related research identified, and stakeholder survey feedback, to develop a conceptual model and arrive at theConsensus Statement: Families can support children and youth in achieving healthy physical activity, sedentary and sleep behaviours by encouraging, facilitating, modelling, setting expectations and engaging in healthy movement behaviours with them. Other sources of influence are important (e.g., child care, school, health care, community, governments) and can support families in this pursuit.ConclusionFamily is important for the support and promotion of healthy movement behaviours of children and youth. ThisConsensus Statementserves as a comprehensive, credible, and current synopsis of related evidence, recommendations, and resources for multiple stakeholders.
The influence of timing of surgery in the outcome of spinal cord injury without radiographic abnormality (SCIWORA)
Authors: Qi Can , Xia Hehuan , Miao Dechao , Wang Xingui , Li Zengyan 
Published: June 2020

Abstract
Background
Spinal cord injury without radiographic abnormality (SCIWORA) is a rare traumatic myelopathy. Although surgery is one of the most important treatments, the surgery for SCIWORA is controversial, especially the time of surgery is a topic of controversy. Here, we investigate the effects of difference in duration from injury to surgery on the outcome of SCIWORA.

Methods
This retrospective study was performed in all patients with spinal cord injury admitted to the Third Affiliated Hospital of Hebei Medical University from January 2013 to April 2017. Fifty-seven patients who met the study requirements were divided into 3 groups according to the duration from injury to surgery. Group A (surgery within 3 days of injury) had 18 patients, group B (surgery within 3–7 days) had 18 patients, and group C (surgery later than 7 days) had 21 patients. All the groups were compared with Mann–Whitney U test; the functional improvement of spinal cord was compared and analyzed using the ASIA sports score and ASIA Impairment Scale (AIS).

Results
There was a significant improvement in the long-term AIS (final follow-up) in all the 3 groups compared to before surgery. The final follow-up recovery rate of group C was worse than group A and group B. The curative effect of operation within 7 days was significantly better than the surgery done 7 days later. The recovery rate of group C was worse than group A and B. The ASIA sports score showed that recovery was quicker in the early stage and slow in the later stage.

Conclusions
The optimal schedule of surgical treatment was 3–7 days after injury, which can significantly improve the short-term and long-term follow-up effects. Longer the time to surgery from the time of injury, the worse was the prognosis.