bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel tumor suppressor ASMTL-AS1 regulates the miR-1228-3p/SOX17/β-catenin axis in triple‐negative breast cancer
Authors: Sun Jie , Li Xiaohua , Yu Enqiao , Liu Jianxia , Sun Liang , He Qin , Lu Qiran 
Published: May 2021

Abstract
Background
Triple-negative breast cancer (TNBC) is a special type of breast cancer that lacks effective therapeutic targets. There is a significant need to clarify its pathogenesis, so as to bring new targeted approaches for TNBC management. Here, we identified a long-non coding RNA (lncRNA) ASMTL-AS1 that linked to TNBC development and progression.

Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays were used to test gene and protein levels, respectively. The regulatory axis of miR-1228-3p/SOX17/β-catenin was determined by luciferase reporter and RNA pull-down assays. In vivo assay was conducted by using the nude mice model via subcutaneous transplantation of tumor cells.

Results
ASMTL-AS1 was significantly downregulated in TNBC tissues compared to normal tissues, which was closely associated with aggressive clinical features and unfavorable prognosis. Lentivirus-mediated ASMTL-AS1 overexpression evidently reduced the ability of TNBC cell colony formation, activity and invasion by more than 2.5 times. RNA pull-down and luciferase reporter assays revealed that miR-1228-3p directly bound to ASMTL-AS1, ASMTL-AS1 increased SOX17 expression via sponging and repressing miR-1228-3p. Subsequently, the upregulated SOX17 trans-suppressed β-catenin expression, resulting in the inactivation of carcinogenic Wnt/β-catenin signaling, thereby restraining TNBC cell growth and dissemination. Importantly, the xenograft tumor model showed that the ASMTL-AS1 overexpression significantly retarded tumor growth, and negatively regulated Wnt/β-catenin pathway.

Conclusions
Our data characterize a novel tumor suppressor in TNBC, restoration of ASMTL-AS1 may be a candidate therapeutic intervention for TNBC patients.
Biomarkers as therapy monitoring for postmenopausal osteoporosis: a systematic review
Authors: Migliorini Filippo , Maffulli Nicola , Spiezia Filippo , Tingart Markus , Maria Peretti Giuseppe , Riccardo Giorgino 
Published: May 2021

Abstract
Background
Biochemical markers of bone turnover (BTMs), such as bone alkaline phosphatase (bALP), procollagen type I N propeptide (PINP), serum cross-linked C-telopeptides of type I collagen (bCTx), and urinary cross-linked N-telopeptides of type I collagen (NTx), are commonly used for therapy monitoring purposes for osteoporotic patients. The present study evaluated the potential role of BTMs as therapy monitoring.

Methods
All randomized clinical trials (RCTs) comparing two or more pharmacological treatments for postmenopausal osteoporosis were accessed. Only studies that reported the value of bALP, PINP, bCTx, and NTx at last follow-up were included. A multivariate analysis was performed to assess associations between these biomarkers and clinical outcomes and rate of adverse events in patients with postmenopausal osteoporosis. A multiple linear model regression analysis through the Pearson product-moment correlation coefficient was used.

Results
A total of 16 RCTs (14,446 patients) were included. The median age was 67 years, and the median BMI 25.4 kg/m2. The median vertebral BMD was 0.82, hip BMD 0.79, and femur BMD 0.64 g/cm2. The ANOVA test found optimal within-group variance concerning mean age, body mass index, and BMD. Greater bALP was associated with lower femoral BMD (P = 0.01). Greater NTx was associated with a greater number of non-vertebral fractures (P = 0.02). Greater NTx was associated with greater rate of therapy discontinuation (P = 0.04). No other statistically significant associations were detected.

Conclusion
Our analysis supports the adoption of BTMs in therapy monitoring of osteoporotic patients.

Level of evidence
Level I, systematic review of RCTs.
Subjective cognitive complaints in patients with stress-related exhaustion disorder: a cross sectional study
Authors: Nelson Andreas , Gavelin Hanna Malmberg , Boraxbekk Carl-Johan , Eskilsson Therese , Josefsson Maria , Slunga Järvholm Lisbeth , Neely Anna Stigsdotter 
Published: May 2021

Abstract
Background
Stress-related exhaustion is associated with cognitive impairment as measured by both subjective cognitive complaints (SCCs) and objective cognitive test performance. This study aimed to examine how patients diagnosed with exhaustion disorder differ from healthy control participants in regard to levels and type of SCCs, and if SCCs are associated with cognitive test performance and psychological distress.

Methods
We compared a group of patients with stress-related exhaustion disorder (n = 103, female = 88) with matched healthy controls (n = 58, female = 47) cross-sectionally, concerning the type and magnitude of self-reported SCCs. We furthermore explored the association between SCCs and cognitive test performance as well as with self-reported depression, anxiety and burnout levels, in the patient and the control group, respectively.

Results
Patients reported considerably more cognitive failures and were more likely than controls to express memory failures in situations providing few external cues and reminders in the environment. In both groups, SCCs were associated with demographic and psychological factors, and not with cognitive test performance.

Conclusion
Our findings underline the high burden of cognitive problems experienced by patients with exhaustion disorder, particularly in executively demanding tasks without external cognitive support. From a clinical perspective, SCCs and objective cognitive test performance may measure different aspects of cognitive functioning, and external cognitive aids could be of value in stress rehabilitation.

Trial registration
Participants were recruited as part of the Rehabilitation for Improved Cognition (RECO) study (ClinicalTrials.gov: NCT03073772). Date of registration: 8 March 2017
Vitamin D receptor gene polymorphisms and its interactions with environmental factors on renal cell carcinoma risk
Authors: Jianhai Tian , Jian Lv , Long Zhang , Wei Wang , Shumao Zhang , Yiming Wang , Xiaojuan Li 
Published: May 2021

Abstract
Aims
We designed a case-control study to investigate the effect of vitamin D receptor gene (VDR) gene single nucleotide polymorphisms (SNPs) and possible gene- environment interaction on the susceptibility of renal cell carcinoma (RCC).

Methods
Generalized multifactor dimensionality reduction (GMDR) was used to find out the interaction combinations between SNPs and environmental factors, including gene- gene synergy and gene environment synergy effect. Logistic regression was used to analyze the correlation between the four SNPs in VDR gene and RCC, and the significant interaction combinations found by GMDR model were analyzed by hierarchical analysis.

Results
The genotype distribution of the control group was in accordance with Hardy- Weinberg equilibrium. Logistic regression analysis showed that the risk of RCC in VDR-rs7975232 A allele carriers was significantly higher than that of CC genotype carriers (CA + AA vs. CC), adjusted OR (95 % CI) = 1.75 (1.26–2.28). We used GMDR model to screen the best synergistic model between the four SNPs of VDR gene and smoking and drinking. We found a significant two locus model (P = 0.0010) involving rs7975232 and smoking. The cross- validation consistency of the two- locus model was 10/ 10, and the accuracy was 60.72 %. Compared with non-smokers with rs7975232 -CA or AA genotype, smokers with rs7975232 -CC genotype had the highest risk of RCC, or (95 % CI) = 2.23 (1.42–3.09), after adjustment for covariates.

Conclusions
We found that the A allele of rs7975232 within VDR gene, interaction between rs7975232 and smoking were all associated with increased RCC risk.
Platelet-rich plasma for tendinopathy and osteoarthritis: a narrative review
Authors: Shala Rilind 
Published: May 2021

Abstract
Background
Musculoskeletal disorders include a wide range of degenerative and inflammatory problems, which can affect any part of the muscular and skeletal system. Platelet-rich plasma (PRP) has been a breakthrough in musculoskeletal medicine, especially with its effects to speed up soft tissue, cartilage, and bone healing. It is now thought that stem cells are able to reverse the degenerative process and promote rapid healing. Platelet-rich plasma (PRP) has received special attention in treating tendinopathy and osteoarthritis. This review aims to do a comprehensive review of the scientific evidence for the efficiency of PRP application in tendinopathy and osteoarthritis.

Main body of the abstract
In osteoarthritis treatment, platelet-rich plasma is thought to influence the whole joint environment by increasing chondrocyte proliferation. The injection of autologous PRP into the joint space and surrounding soft tissues delivers a concentrated dose of these growth factors, which accelerate the healing process and reduce pain.

Short conclusion
Many studies report some benefits in regard to pain and functionality, especially in tendinopathy, but further investigations are needed to incorporate PRP into clinical practice and be a common form of therapy for tendinopathy and osteoarthritis. Caution should be applied with any treatment we use in clinical practice, especially with PRP and other forms of injections.
Revisiting vitamin D status and supplementation for in-patients with intellectual and developmental disability in the North of England, UK
Authors: Dudley Bethany , Ostrowski Marcin , Ciausu Vlad , Ince Chris , McKinnon Iain 
Published: May 2021

Aims and methodTo re-evaluate vitamin D testing and supplementation among in-patients with intellectual and developmental disability (IDD) and examine any correlates with physical health conditions, including COVID-19. Records of all in-patients between January 2019 and July 2020 (n = 78) were examined for 25-hydroxyvitamin D (25(OH)D) level, ward area, supplementation status, test seasonality, medication and health status.ResultsThe mean 25(OH)D level for supplemented (800 IU/day) patients was 75 nmol/L (s.d. = 20), compared with 40 nmol/L (s.d. = 19) in the non-supplemented group (P < 0.001). Thirty-eight percent of those who were in-patients during the first wave of the COVID-19 pandemic developed symptoms, but the small sample size could not establish vitamin D levels as a predictor of outcome.Clinical implicationsVitamin D (800 IU/day) supplementation is effective but the adequacy of the nationally recommended dose of 400 IU/day is unclear. Links to COVID-19 merit further research.
Psychological distress among people with probable COVID-19 infection: analysis of the UK Household Longitudinal Study
Authors: Niedzwiedz Claire L. , Benzeval Michaela , Hainey Kirsten , Leyland Alastair H. , Katikireddi Srinivasa Vittal 
Published: May 2021

SummaryStudies exploring the longer-term effects of experiencing coronavirus disease-2019 (COVID-19) on mental health are lacking. We explored the relationship between reporting probable COVID-19 symptoms in April 2020 and psychological distress (measured using the General Health Questionnaire) 1, 2, 3, 5 and 7 months later. Data were taken from the UK Household Longitudinal Study, a nationally representative household panel survey of UK adults. Elevated levels of psychological distress were found up to 7 months after probable COVID-19, compared with participants with no likely infection. Associations were stronger among younger age groups and men. Further research into the psychological sequalae of COVID-19 is urgently needed.
Updated Standardized Definitions for Efficacy End Points (STEEP) in Adjuvant Breast Cancer Clinical Trials: STEEP Version 2.0
Authors: Tolaney Sara M. , Garrett-Mayer Elizabeth , White Julia , Blinder Victoria S. , Foster Jared C. , Amiri-Kordestani Laleh , Hwang E. Shelley , Bliss Judith M. , Rakovitch Eileen , Perlmutter Jane , Spears Patricia A. , Frank Elizabeth , Tung Nadine M. , Elias Anthony D. , Cameron David , Denduluri Neelima , Best Ana F. , DiLeo Angelo , Baizer Lawrence , Butler Lynn Pearson , Schwartz Elena , Winer Eric P. , Korde Larissa A. 
Published: May 2021

PURPOSEThe Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007, provide standardized definitions of adjuvant breast cancer clinical trial end points. Given the evolution of breast cancer clinical trials and improvements in outcomes, a panel of experts reviewed the STEEP criteria to determine whether modifications are needed.METHODSWe conducted systematic searches of ClinicalTrials.gov for adjuvant systemic and local-regional therapy trials for breast cancer to investigate if the primary end points reported met STEEP criteria. On the basis of common STEEP deviations, we performed a series of simulations to evaluate the effect of excluding non–breast cancer deaths and new nonbreast primary cancers from the invasive disease–free survival end point.RESULTSAmong 11 phase III breast cancer trials with primary efficacy end points, three had primary end points that followed STEEP criteria, four used STEEP definitions but not the corresponding end point names, and four used end points that were not included in the original STEEP manuscript. Simulation modeling demonstrated that inclusion of second nonbreast primary cancer can increase the probability of incorrect inferences, can decrease power to detect clinically relevant efficacy effects, and may mask differences in recurrence rates, especially when recurrence rates are low.CONCLUSIONWe recommend an additional end point, invasive breast cancer–free survival, which includes all invasive disease–free survival events except second nonbreast primary cancers. This end point should be considered for trials in which the toxicities of agents are well-known and where the risk of second primary cancer is small. Additionally, we provide end point recommendations for local therapy trials, low-risk populations, noninferiority trials, and trials incorporating patient-reported outcomes.
On a contextual model refuting Bell's theorem
Authors: Muchowski Eugen 
Published: May 2021

Abstract
Bell's theorem is refuted by presenting a counterexample that correctly predicts the expectation values of QM. As Bell only ruled out non-contextual models, a contextual model with hidden variables can refute his theorem. Such a model, which is able to explain the spin measurement results with entangled photons or electrons, is presented herein. It is not ruled out by the Kochen-Specker theorem. A physical justification for the contextual behaviour of entangled systems is provided. Consequences for the feasibility of quantum computers are discussed.
Smokers’ support for the ban on sale of slim cigarettes in six European countries: findings from the EUREST-PLUS ITC Europe surveys
Authors: Mechili Enkeleint A. , Przewoźniak Krzysztof , Driezen Pete , Kyriakos Christina N , Girvalaki Charis , Mons Ute , Quah Anne CK , Fernández Esteve , Trofor Antigona C , Demjén Tibor , Katsaounou Paraskevi A , Zatoński Witold , Fong Geoffrey T , Vardavas Constantine I 
Published: May 2021

Background: Efforts to regulate tobacco products and reduce consumption in the European Union (EU) include the European Tobacco Products Directive (TPD), which went into force in May 2016. Despite the initial discussion to include a ban on sale of slim cigarettes, it was excluded in the final TPD. The main goal of this study was to examine support for a ban on slim cigarettes among smokers in six European Countries. Methods: Data from the 2018 (Wave 2) International Tobacco Control Policy Evaluation Project 6 European Country (ITC 6E) EUREST-PLUS project survey, a cross sectional study of adult smokers (n=5592) from Germany, Greece, Hungary, Poland, Romania, and Spain, was analysed. Descriptive statistics were used to estimate support for a ban on slim cigarettes by sociodemographic characteristics and smoking behaviors. Logistic regression analysis was used to examine factors associated with support for a ban on slim cigarettes and perceptions of harm. Results: Support for a ban on slims varied across countries, with highest support in Romania (33.8%), and lowest in Greece (18.0%). Female smokers (OR=0.77; 95%CI=0.66-0.90, daily smokers (OR=0.59; 95%CI=0.42-0.83), menthol smokers (OR=0.56; 95%CI=0.36-0.87), and smokers who did not have plans to quit within next six months (OR=0.45; 95%CI=0.36-0.57) had significantly lower odds of supporting a ban on slim cigarettes. Overall, 20% of smokers perceived slim cigarettes as less harmful than regular cigarettes. Conclusions: Support for a ban of slim cigarettes was relatively low among smokers, while misperceptions that slim cigarettes are less harmful is high, particularly among countries where slim cigarette use is more prevalent. Findings support a ban on slim cigarettes to reduce misperceptions around slim cigarettes being less harmful.
A tool for assessing the climate change mitigation and health impacts of environmental policies: the Cities Rapid Assessment Framework for Transformation (CRAFT)
Authors: Symonds Phil , Milner James , Mohajeri Nahid , Aplin Juliette , Hale Joanna , J Lloyd Simon , Fremont Henry , Younkin Sam , Shrubsole Clive , Robertson Lawrie , Taylor Jonathon , Zimmermann Nici , Wilkinson Paul , Davies Mike 
Published: May 2021

Background: A growing number of cities, including Greater London, have set ambitious targets, including detailed policies and implementation plans, to reach global goals on sustainability, health, and climate change. Here we present a tool for a rapid assessment of the magnitude of impact of specific policy initiatives to reach these targets. The decision-support tool simultaneously quantifies the environmental and health impacts of specified selected policies. Methods: The ‘Cities Rapid Assessment Framework for Transformation (CRAFT)’ tool was applied to Greater London. CRAFT quantifies the effects of ten environmental policies on changes in (1) greenhouse gas (GHG) emissions, (2) exposures to environmental hazards, (3) travel-related physical activity, and (4) mortality (the number of attributable deaths avoided in one typical year). Publicly available data and epidemiological evidence were used to make rapid quantitative estimates of these effects based on proportional reductions in GHG emissions and environmental exposures from current baseline levels and to compute the mortality impacts. Results: The CRAFT tool estimates that, of roughly 50,000 annual deaths in Greater London, the modelled hazards (PM2.5 (from indoor and outdoor sources), outdoor NO2, indoor radon, cold, overheating) and low travel-related physical activity are responsible for approximately 10,000 premature environment-related deaths. Implementing the selected polices could reduce the annual mortality number by about 20% (~1,900 deaths) by 2050. The majority of these deaths (1,700) may be avoided through increased uptake in active travel. Thus, out of ten environmental policies, the ‘active travel’ policy provides the greatest health benefit. Also, implementing the ten policies results in a GHG reduction of around 90%. Conclusions: The CRAFT tool quantifies the effects of city policies on reducing GHG emissions, decreasing environmental health hazards, and improving public health. The tool has potential value for policy makers through providing quantitative estimates of health impacts to support and prioritise policy options.
Multilevel symmetrized Toeplitz structures and spectral distribution results for the related matrix sequences
Authors: Ferrari Paola , Furci Isabella , Serra-Capizzano Stefano 
Published: May 2021

In recent years, motivated by computational purposes, the singular value and spectral features of the symmetrization of Toeplitz matrices generated by a Lebesgue integrable function have been studied. Indeed, under the assumptions that $f$ belongs to $L^1([-\pi,\pi])$ and it has real Fourier coefficients, the spectral and singular value distribution of the matrix-sequence $\{Y_nT_n[f]\}_n$ has been identified, where $n$ is the matrix size, $Y_n$ is the anti-identity matrix, and $T_n[f]$ is the Toeplitz matrix generated by $f$. In this note, the authors consider the multilevel Toeplitz matrix $T_{\bf n}[f]$ generated by $f\in L^1([-\pi,\pi]^k)$, $\bf n$ being a multi-index identifying the matrix-size, and they prove spectral and singular value distribution results for the matrix-sequence $\{Y_{\bf n}T_{\bf n}[f]\}_{\bf n}$ with $Y_{\bf n}$ being the corresponding tensorization of the anti-identity matrix.
Early mortality outcomes of patients with fragility hip fracture and concurrent SARS-CoV-2 infection
Authors: Alcock Harry , Moppett Eleanor Ann , Moppett Iain Keith 
Published: May 2021

Aims Hip fracture is a common condition of the older, frailer person. This population is also at risk from SARS-CoV-2 infection. It is important to understand the impact of coexistent hip fracture and SARS-CoV-2 for informed decision-making at patient and service levels. Methods We undertook a systematic review and meta-analysis of observational studies of older (> 60 years) people with fragility hip fractures and outcomes with and without SARS-CoV-2 infection during the first wave of the COVID-19 pandemic. The primary outcome was early (30-day or in-hospital) mortality. Secondary outcomes included length of hospital stay and key clinical characteristics known to be associated with outcomes after hip fracture. Results A total of 14 cohort and five case series studies were included (692 SARS-CoV-2 positive, 2,585 SARS-CoV-2 negative). SARS-CoV-2 infection was associated with an overall risk ratio (RR) for early mortality of 4.42 (95% confidence interval (CI) 3.42 to 5.82). Early mortality was 34% (95% CI 30% to 38%) and 9% (95% CI 8% to 10%) in the infected and noninfected groups respectively. Length of stay was increased in SARS-CoV-2 infected patients (mean difference (MD) 5.2 days (3.2 to 7.2)). Age (MD 1.6 years (0.3 to 2.9)); female sex (RR 0.83 (95% CI 0.65 to 1.05)); admission from home (RR 0.51 (95% CI 0.26 to 1.00)); presence of dementia (RR 1.13 (95% CI 0.94 to 1.43)); and intracapsular fracture (RR 0.89 (95% CI 0.71 to 1.11)) were not associated with SARS-CoV-2 infection. There were statistically, but not clinically, significantly greater Nottingham Hip Fracture Scores in infected compared with non-infected patients (MD 0.7 (0.4 to 0.9)). Conclusion SARS-CoV-2 infection is associated with worse outcomes after hip fracture. This is not explained by differences in patient characteristics. These data can be used to support informed decision-making and may help track the impact of widespread adoption of system-level and therapeutic changes in management of the COVID-19 pandemic. Cite this article: Bone Jt Open 2021;2(5):314–322.