bluuebunny/crossref_metadata_2025_split huggingface dataset:
Family, school and individual characteristics associated with adolescents’ physical activity at school in Hong Kong: the iHealt(H) study
Authors: Carver Alison , Akram Muhammad , Barnett Anthony , Huang Wendy Yajun , Gao Gemma Yang , Mellecker Robin R. , Cerin Ester 
Published: January 2021

Abstract
Background
Adolescents (11–18-year-olds) are at risk of physical inactivity. There is limited knowledge of physical activity (PA) levels among adolescents in the school setting in Hong Kong. We developed and tested a novel theoretical model of how household/family characteristics, school-level social and physical environmental factors and individual adolescent’s characteristics impact on their school-based PA during and after school hours.

Methods
Cross-sectional study participants were Hong Kong adolescents attending secondary school, paired with their parent/caregiver (n = 1299 dyads). Parents survey-reported on household/family characteristics, parental PA and rules related to PA. Adolescents survey-reported on school PA-friendly policy, PA equipment at school (combined to create PA-friendly index), social support for PA from peers, athletic ability, attitude to and enjoyment of PA. Adolescents self-reported their school-based PA during school hours (physical education; recess) and after school (sports teams/classes). Objectively-measured moderate-to-vigorous PA (MVPA) was measured using accelerometers for a sub-sample of adolescents (n = 588). Generalized additive mixed models were used to estimate how household/family-level and school-level factors, and adolescents’ individual characteristics were related to adolescents’ school-based PA in Hong Kong, and to identify potential mediators of these associations.

Results
A complex network of potential pathways of influence on adolescents’ school-based PA was identified. Overall, most of the significant effects were indirect ones. However, there were far fewer significant pathways between household/family characteristics and objectively-measured MVPA at school than there were for self-reported PA at school. In fact, there were no indirect pathways between these variables and MVPA at school. Gender disparities among pathways were identified. For example, school PA-friendly index was significantly associated with MVPA after school only among girls (eb = 1.06, 95%CI (1.02,1.12)).

Conclusions
Key points of intervention identified by our study may be in the re-design of PE classes so that adolescents spend more time being physically active during these classes, and promotion of active play during recess. Further research measuring amount, intensity and location of adolescents’ PA using accelerometer and Global Positioning Systems is required in Hong Kong, as well as observational studies of PA during PE classes and in the schoolyard during recess, to guide the design of PA interventions.
Determinants of low breastfeeding self-efficacy amongst mothers of children aged less than six months: results from the BADUTA study in East Java, Indonesia
Authors: Titaley Christiana Rialine , Dibley Michael J. , Ariawan Iwan , Mu’asyaroh Anifatun , Alam Ashraful , Damayanti Rita , Do Tran Thanh , Ferguson Elaine , Htet Kyaw , Li Mu , Sutrisna Aang , Fahmida Umi 
Published: January 2021

Abstract
Background
Despite the increasing rate of exclusive breastfeeding in Indonesia, there is still a need for supportive interventions. The breastfeeding self-efficacy of mothers is a key factor positively associated with optimum breastfeeding practices. Our analysis aims to assess the determinants of low breastfeeding self-efficacy amongst a sample of women with children aged under 6 months in Malang and Sidoarjo Districts, East Java, Indonesia.

Methods
We used information from 1210 mothers of children aged < 6 months recruited in the BADUTA study conducted in 2015–2016 in Malang and Sidoarjo Districts. The outcome variable in this analysis was mothers’ self-efficacy for breastfeeding using the 14 statements in the Breastfeeding Self-Efficacy-Short Form. We evaluated 17 potential predictors of breastfeeding self-efficacy, organized into six sub-groups of variables: (1) context/demographic; (2) household factors; (3) maternal characteristics; (4) child characteristics; (5) breastfeeding practices; and (6) antenatal and delivery care. Logistic regression analyses were employed to examine factors associated with mothers’ self-efficacy with breastfeeding.

Results
More than half of the women in this study had a low level of self-efficacy. One of the factors associated with low breastfeeding self-efficacy found in this study was mothers’ problems related to breastfeeding. Mothers who had problems with breastfeeding not related to illness (adjusted odds ratio [aOR] 3.27; 95% CI 2.45, 4.36) or problems related to both illness and non-illness conditions (aOR 3.57; 95% CI 1.37, 9.33) had higher odds of low breastfeeding self-efficacy than those who did not have any problems. Compared to mothers who completed university education, there was a significantly higher odds of low breastfeeding self-efficacy in mothers who completed primary school or lower (aOR 1.88; 95% CI 1.16, 3.05); completed junior high school (aOR 2.27; 95% CI 1.42, 3.63); and completed senior high school (aOR 1.94; 95% CI 1.29, 2.91). Other significant predictors of low breastfeeding self-efficacy were mothers not exposed to any breastfeeding interventions (aOR 1.87; 95% CI 1.09, 3.22); working outside the house (aOR 1.69; 95% CI 1.23, 2.32); not obtaining any advice on breastfeeding (aOR 1.40; 95% CI 1.08, 1.82); with low knowledge of breastfeeding (aOR 1.38; 95% CI 1.03, 1.84); and delivered by Caesarean section (aOR 1.34; 95% CI 1.05, 1.70).

Conclusions
Multipronged breastfeeding education programs and support are required to improve women’s self-efficacy with breastfeeding. Improved access to breastfeeding counselors, active support for mothers following cesarean delivery, and increased supporting facilities at workplaces are essential to improve self-efficacy with breastfeeding.
Difference in the early postoperative change of the joint line convergence angle between opening wedge and closed wedge high tibial osteotomies
Authors: Kumagai Ken , Fujimaki Hiroshi , Yamada Shunsuke , Nejima Shuntaro , Matsubara Joji , Inaba Yutaka 
Published: January 2021

Abstract
Background
The purpose of this study was to investigate the correction error associated with soft tissue balance in high tibial osteotomy (HTO) and the difference between opening wedge HTO (OWHTO) and closed wedge HTO (CWHTO).

Methods
A total of 170 knees of 130 patients (85 knees of 68 patients in OWHTO and 85 knees of 62 patients in CWHTO) were evaluated. Anteroposterior radiographs of the knee and full-length leg were taken preoperatively, immediately under general anesthesia postoperatively, 2 days, and 1 and 12 months postoperatively. The femorotibial angle (FTA), joint line convergence angle (JLCA), and medial proximal tibial angle (MPTA) were measured.

Results
The postoperative FTA was decreased from 170.5 ± 2.1° at 0 day to 168.6 ± 2.2° at 2 days in OWHTO (P < 0.05), whereas it was not changed from 168.7 ± 2.4° at 0 day to 168.1 ± 2.8° at 2 days in CWHTO. The JLCA was 4.8 ± 1.8° preoperatively, 4.2 ± 1.9° at 0 day, 2.2 ± 1.8° at 2 days (P < 0.05 vs 0 day), 2.6 ± 1.7° at 1 month, and 2.7 ± 1.6° at 12 months in OWHTO, and 7.1 ± 3.2° preoperatively, 4.1 ± 2.4° at 0 day (P < 0.05 vs preoperative), 3.4 ± 2.5° at 2 days, 3.9 ± 2.3° at 1 month, and 4.2 ± 2.6° at 12 months in CWHTO. Multiple regression analysis showed that preoperative factors affecting change of the JLCA from preoperative to postoperative 1 month were the correction angle in OWHTO (P = 0.001) and the preoperative standing JLCA in OWHTO (P < 0.001) and CWHTO (P < 0.001).

Conclusions
A significant decrease of the JLCA occurred immediately after osteotomy under anesthesia in CWHTO, whereas in OWHTO there was no decrease under anesthesia, but it decreased several days postoperatively.
RETRACTED ARTICLE: lncRNA HAND2-AS1 is downregulated in osteoarthritis and regulates IL-6 expression in chondrocytes
Authors: Si Zhenxing , Zhou Shifeng , Shen Zilong , Luan Feiyu , Yan Jinglong 
Published: January 2021

Abstract
Background
Osteoarthritis (OA) is a leading cause of disability. The incidence of OA is progressively rising due to the diminishing levels of physical activity and ever-expanding aging population. However, the mainstay for OA treatment only can improve symptoms without delay the progression of this severe disease. This study aimed to explore the biological role and clinical function of lncRNA HAND2-AS1 in OA.

Methods
Blood samples and synovial fluid were collected from OA patients and normal subjects. HAND2-AS1 expression was detected by qRT-PCR and IL-6 expression was detected by ELISA. The plasma levels of HAND2-AS1 were also detected in different ages, stages, and gender of OA patients and controls. Furthermore, the ROC curve was used to analyze whether HAND2-AS1 can distinguish OA patients from normal subjects. Also, Pearson correlation coefficient analysis was used to analyze the correlation between lncRNA HAND2-AS1 and IL-6. In addition, Western blot was used to detect the IL-6 level upon HAND2-AS1 over-expression in chondrocytes and qRT-PCR was used to detect the HAND2-AS1 level after endogenous IL-6 treatment.

Results
HAND2-AS1 and IL-6 were dysregulated in plasma and synovial fluid of OA patients. The expression of HAND2-AS1 in plasma of OA patients was decreased with aging and progression. Furthermore, HAND2-AS1 downregulation effectively distinguished OA patients from the healthy controls. Over-expression of HAND2-AS1 inhibited IL-6 expression in chondrocytes, while treatment with exogenous IL-6 did not affect HAND2-AS1 expression.

Conclusion
HAND2-AS1 effectively distinguished OA patients from the healthy controls and regulates IL-6 expression in human chondrocytes.

Trial registration
ChiCTR, ChiCTR2000038635. Registered 11 February 2019
Anti-platelet aggregation of Panax notoginseng triol saponins by regulating GP1BA for ischemic stroke therapy
Authors: Xu Zhi-yi , Xu Yang , Xie Xiao-fang , Tian Yin , Sui Jun-hui , Sun Yong , Lin Da-sheng , Gao Xing , Peng Cheng , Fan Yu-jiang 
Published: January 2021

Abstract
Background
Panax notoginseng triol saponins (PTS) has been used clinically for ischemic stroke therapy (IST) in China for more than 17 years due to its anti-platelet aggregation and neuro-protective effects, but its mechanism of action is not fully understand. In this study, anti-platelet aggregation-related protein analysis and computer simulations of drug-protein binding interactions were performed to explore the mechanism of the effects of PTS against ischemic stroke in an ischemia reperfusion model.

Methods
Three oral doses of PTS were administered in a model of middle cerebral artery occlusion (MCAO) in rats. Panax notoginseng total saponins (PNS) and a combination of PTS and aspirin were chosen for comparison. To evaluate therapeutic effects and explore possible mechanisms of anti-platelet aggregation, we measured cerebral infarct size and water content in brain tissue, histomorphological changes, expression of related factors (such as arachidonic acid metabolites) and platelet receptors in serum, as well as the binding affinity of PTS for platelet adhesion receptors.

Results
Compared with PNS, PTS showed a stronger and more potent anti-platelet aggregation effect in MCAO model rats. The combination of PTS and aspirin could reduce adverse gastrointestinal effects by regulating the TXA2/PGI2 ratio. We demonstrated for the first time that PTS was able to regulate Glycoprotein Ib-α (GP1BA) in a model animal. The binding of ginsenoside Rg1 and GP1BA could form a stable structure. Moreover, PTS could reduce von Willebrand factor (VWF)-mediated platelet adhesion to damaged vascular endothelium, and thus enhance the probability of anti-platelet aggregation and anti-thrombosis under pathological conditions.

Conclusions
Our results showed that GP1BA was closely related to the anti-platelet aggregation action of PTS, which provided new scientific and molecular evidence for its clinical application.
Fibroblasts from idiopathic Parkinson’s disease exhibit deficiency of lysosomal glucocerebrosidase activity associated with reduced levels of the trafficking receptor LIMP2
Authors: Thomas Ria , Moloney Elizabeth B. , Macbain Zachary K. , Hallett Penelope J. , Isacson Ole 
Published: January 2021

AbstractLysosomal dysfunction is a central pathway associated with Parkinson’s disease (PD) pathogenesis. Haploinsufficiency of the lysosomal hydrolase GBA (encoding glucocerebrosidase (GCase)) is one of the largest genetic risk factors for developing PD. Deficiencies in the activity of the GCase enzyme have been observed in human tissues from both genetic (harboring mutations in the GBA gene) and idiopathic forms of the disease. To understand the mechanisms behind the deficits of lysosomal GCase enzyme activity in idiopathic PD, this study utilized a large cohort of fibroblast cells from control subjects and PD patients with and without mutations in the GBA gene (N370S mutation) (control, n = 15; idiopathic PD, n = 31; PD with GBA N370S mutation, n = 6). The current data demonstrates that idiopathic PD fibroblasts devoid of any mutations in the GBA gene also exhibit reduction in lysosomal GCase activity, similar to those with the GBA N370S mutation. This reduced GCase enzyme activity in idiopathic PD cells was accompanied by decreased expression of the GBA trafficking receptor, LIMP2, and increased ER retention of the GBA protein in these cells. Importantly, in idiopathic PD fibroblasts LIMP2 protein levels correlated significantly with GCase activity, which was not the case in control subjects or in genetic PD GBA N370S cells. In conclusion, idiopathic PD fibroblasts have decreased GCase activity primarily driven by altered LIMP2-mediated transport of GBA to lysosome and the reduced GCase activity exhibited by the genetic GBA N370S derived PD fibroblasts occurs through a different mechanism.
Vitamin C sensitizes BRAFV600E thyroid cancer to PLX4032 via inhibiting the feedback activation of MAPK/ERK signal by PLX4032
Authors: Su Xi , Li Peng , Han Bin , Jia Hao , Liang Qingzhuang , Wang Haichao , Gu Mengwei , Cai Jiaxuan , Li Shaolei , Zhou Yaqi , Yi Xin , Wei Wei 
Published: January 2021

Abstract
Background
BRAFV600E mutation is the most common mutation in thyroid cancer. It strongly activates MAPK/ERK pathway and indicates an invasive subtype of thyroid cancer. PLX4032 is a selective oral inhibitor of the BRAFV600 kinase although with limited effect in treating this panel of thyroid cancer, due to the feedback activation of MAPK/ERK as well as PI3K/AKT pathways. It was investigated that Vitamin C plays a positive role in inhibiting these pathways in thyroid cancer. However, whether Vitamin C could enhance the antitumor effect of PLX4032 remains largely unclear.

Methods
The antitumor efficacy of combination therapy with PLX4032 and Vitamin C on BRAFMT thyroid cancer cell was assessed by the MTT assay, EdU assay and colony formation, Chou-Talalay way was employed to analyze the synergistic effect. Flow cytometry were employed to assess cells’ apoptosis and cell cycle arrest in response to combination therapy. Xenograft models were used to test its in vivo antitumor activity. Western blot and IHC were applied to investigate the mechanism underlying synergistic effect.

Results
PLX4032 or Vitamin C monotherapy was mildly effective in treating BRAFMT thyroid cancer cell and xenografts model. The combination therapy significantly inhibited cancer cell proliferation and tumor growth in nude mice, and induced cell apoptosis and cell cycle arrest compared to either monotherapy. PLX4032 monotherapy induced feedback activation of MAPK/ERK as well as PI3K/AKT pathway; while combination therapy significantly relieved this feedback.

Conclusion
Vitamin C promotes the antitumor effect of PLX4032 in BRAFMT thyroid cancer cell and xenografts model via relieving the feedback activation of MAPK/ERK as well as PI3K/AKT pathway. PLX4032/Vitamin C combination may be a potential therapeutic approach to treat BRAFMT thyroid cancer.
Recontacting non-BRCA1/2 breast cancer patients for germline CHEK2 c.1100del pathogenic variant testing: uptake and patient experiences
Authors: Velthuizen Mary E. , van der Luijt Rob B. , de Vries Beja J. , Koudijs Marco J. , Bleiker Eveline M. A. , Ausems Margreet G. E. M. 
Published: January 2021

Abstract
Background
CHEK2 has been recognized as a breast cancer risk gene with moderate effect. Women who have previously tested negative for a BRCA1/2 gene germline pathogenic variant may benefit from additional genetic testing for the CHEK2 c.1100del pathogenic variant. The aims of this study were: 1) to assess the uptake of an active approach by recontacting BRCA1/2-negative women for additional CHEK2 c.1100del testing on stored DNA-samples and 2) to explore patients’ experiences with this approach.

Methods
Between 2015 and 2017, women who had been tested earlier negative for BRCA1/2 germline pathogenic variants, were recontacted for additional CHEK2 c.1100del testing on stored DNA-samples, free-of-charge. They received an information letter about the CHEK2 pathogenic variant and could return an informed consent form when they opted for additional genetic testing. Those in whom the CHEK2 pathogenic variant was absent, received a letter describing this result. Those who tested positive, were invited for a personal counseling at the department of genetics. On average 21 months (range 4–27) after the genetic test result, a questionnaire was sent to all identified carriers and a control group of women who tested negative for the pathogenic variant to explore patients’ experiences with our approach.

Results
In total, 70% (N = 1666) of the N = 2377 women contacted opted for additional testing, and 66 (4%) of them proved to be carriers of the CHEK2 c.1100del pathogenic variant. Regardless of the outcome of the genetic test, women were generally satisfied with our approach and reported that the written information was sufficient to make an informed decision about the additional CHEK2 testing.

Conclusions
The uptake (70%) of our approach was considered satisfactory. Patients considered the benefits more important than the psychosocial burden. Given the rapid developments in DNA-diagnostics, our findings may support future initiatives to recontact patients about additional genetic testing when they previously tested negative for a pathogenic variant in a breast cancer gene.
A rare large duplication of MLH1 identified in Lynch syndrome
Authors: Kumar Abhishek , Paramasivam Nagarajan , Bandapalli Obul Reddy , Schlesner Matthias , Chen Tianhui , Sijmons Rolf , Dymerska Dagmara , Golebiewska Katarzyna , Kuswik Magdalena , Lubinski Jan , Hemminki Kari , Försti Asta 
Published: January 2021

Abstract
Background
The most frequently identified strong cancer predisposition mutations for colorectal cancer (CRC) are those in the mismatch repair (MMR) genes in Lynch syndrome. Laboratory diagnostics include testing tumors for immunohistochemical staining (IHC) of the Lynch syndrome-associated DNA MMR proteins and/or for microsatellite instability (MSI) followed by sequencing or other techniques, such as denaturing high performance liquid chromatography (DHPLC), to identify the mutation.

Methods
In an ongoing project focusing on finding Mendelian cancer syndromes we applied whole-exome/whole-genome sequencing (WES/WGS) to 19 CRC families.

Results
Three families were identified with a pathogenic/likely pathogenic germline variant in a MMR gene that had previously tested negative in DHPLC gene variant screening. All families had a history of CRC in several family members across multiple generations. Tumor analysis showed loss of the MMR protein IHC staining corresponding to the mutated genes, as well as MSI. In family A, a structural variant, a duplication of exons 4 to 13, was identified in MLH1. The duplication was predicted to lead to a frameshift at amino acid 520 and a premature stop codon at amino acid 539. In family B, a 1 base pair deletion was found in MLH1, resulting in a frameshift and a stop codon at amino acid 491. In family C, we identified a splice site variant in MSH2, which was predicted to lead loss of a splice donor site.

Conclusions
We identified altogether three pathogenic/likely pathogenic variants in the MMR genes in three of the 19 sequenced families. The MLH1 variants, a duplication of exons 4 to 13 and a frameshift variant, were novel, based on the InSiGHT and ClinVar databases; the MSH2 splice site variant was reported by a single submitter in ClinVar. As a variant class, duplications have rarely been reported in the MMR gene literature, particularly those covering several exons.
Utilising benefit-risk assessments within clinical trials—a protocol for the BRAINS project
Authors: Totton Nikki , Julious Steven , Hughes Dyfrig , Cook Jonathan , Biggs Katie , Coates Lizzie , Cook Andrew , Hewitt Catherine , Day Simon 
Published: January 2021

Abstract
Background
Depending on the treatment to be investigated, a clinical trial could be designed to assess objectives of superiority, equivalence or non-inferiority. The design of the study is affected by many different elements including the control treatment, the primary outcome and associated relationships.
In some studies, there could be more than one outcome of interest. In these situations, benefit-risk methodologies could be used to assess the outcomes simultaneously and consider the trade-off between the benefits against the risks of a treatment.
Benefit-risk is used within the regulatory industry but seldom included within publicly funded clinical trials within the UK. This project aims to gain an expert consensus on how to select the appropriate trial design (e.g. superiority) and when to consider including benefit-risk methods.

Methods
The project will consist of four work packages:

A web-based survey to elicit current experiences and opinions,

A rapid literature review to assess any current recommendations,

A two-day consensus workshop to gain agreement on the recommendations, and

Production of a guidance document.

Discussion
The aim of the project is to provide a guideline for clinical researchers, grant funding bodies and reviewers for grant bodies for how to select the most appropriate trial design and when it is appropriate to consider using benefit-risk methods. The focus of the guideline will be on publicly funded trials however, the vision is that the work will be applicable across research settings and we will connect with other organisations and committees as appropriate.