bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and internal validation of a predictive risk model for anxiety after completion of treatment for early stage breast cancer
Authors: Harris Jenny , Purssell Edward , Cornelius Victoria , Ream Emma , Jones Anne , Armes Jo 
Published: December 2020

Abstract
Objective
To develop a predictive risk model (PRM) for patient-reported anxiety after treatment completion for early stage breast cancer suitable for use in practice and underpinned by advances in data science and risk prediction.

Methods
Secondary analysis of a prospective survey of > 800 women at the end of treatment and again 6 months later using patient reported outcome (PRO) the hospital anxiety and depression scale-anxiety (HADS-A) and > 20 candidate predictors. Multiple imputation using chained equations (for missing data) and least absolute shrinkage and selection operator (LASSO) were used to select predictors. Final multivariable linear model performance was assessed (R2) and bootstrapped for internal validation.

Results
Five predictors of anxiety selected by LASSO were HADS-A (Beta 0.73; 95% CI 0.681, 0.785); HAD-depression (Beta 0.095; 95% CI 0.020, 0.182) and having caring responsibilities (Beta 0.488; 95% CI 0.084, 0.866) increased risk, whereas being older (Beta − 0.010; 95% CI -0.028, 0.004) and owning a home (Beta 0.432; 95% CI -0.954, 0.078) reduced the risk. The final model explained 60% of variance and bias was low (− 0.006 to 0.002).

Conclusions
Different modelling approaches are needed to predict rather than explain patient reported outcomes. We developed a parsimonious and pragmatic PRM. External validation is required prior to translation to digital tool and evaluation of clinical implementation. The routine use of PROs and data driven PRM in practice provides a new opportunity to target supportive care and specialist interventions for cancer patients.
Prostate Radiotherapy With Adjuvant Androgen Deprivation Therapy (ADT) Improves Metastasis-Free Survival Compared to Neoadjuvant ADT: An Individual Patient Meta-Analysis
Authors: Spratt Daniel E. , Malone Shawn , Roy Soumyajit , Grimes Scott , Eapen Libni , Morgan Scott C. , Malone Julia , Craig Julia , Dess Robert T. , Jackson William C. , Hartman Holly E. , Kishan Amar U. , Mehra Rohit , Kaffenberger Samuel , Morgan Todd M. , Reichert Zachery R. , Alumkal Joshi J. , Michalski Jeff , Lee W. Robert , Pisansky Thomas M. , Feng Felix Y. , Shipley William , Sandler Howard M. , Schipper Mathew J. , Roach Mack , Sun Yilun , Lawton Colleen A. F. 
Published: December 2020

PURPOSEThere remains a lack of clarity regarding the influence of sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) on outcomes in prostate cancer (PCa). Herein, we evaluate the optimal sequencing of ADT with prostate-directed RT in localized PCa.METHODSMEDLINE (1966-2018), Embase (1982-2018), ClinicalTrials.gov, and conference proceedings (1990-2018) were searched to identify randomized trials evaluating the sequencing, but not duration, of ADT with RT. Two randomized phase III trials were identified, and individual patient data were obtained: Ottawa 0101 and NRG Oncology's Radiation Therapy Oncology Group 9413. Ottawa 0101 randomly assigned patients to neoadjuvant or concurrent versus concurrent or adjuvant short-term ADT. Radiation Therapy Oncology Group 9413, a 2 × 2 factorial trial, included a random assignment of neoadjuvant or concurrent versus adjuvant short-term ADT. The neoadjuvant or concurrent ADT arms of both trials were combined into the neoadjuvant group, and the arms receiving adjuvant ADT were combined into the adjuvant group. The primary end point of this meta-analysis was progression-free survival (PFS).RESULTSThe median follow-up was 14.9 years. Overall, 1,065 patients were included (531 neoadjuvant and 534 adjuvant). PFS was significantly improved in the adjuvant group (15-year PFS, 29% v 36%, hazard ratio [HR], 1.25 [95% CI, 1.07 to 1.47], P = .01). Biochemical failure (subdistribution HR [sHR], 1.37 [95% CI, 1.12 to 1.68], P = .002), distant metastasis (sHR, 1.40 [95% CI, 1.00 to 1.95], P = .04), and metastasis-free survival (HR, 1.17 [95% CI, 1.00 to 1.37], P = .050) were all significantly improved in the adjuvant group. There were no differences in late grade ≥ 3 gastrointestinal (2% v 3%, P = .33) or genitourinary toxicity (5% v 5%, P = .76) between groups.CONCLUSIONThe sequencing of ADT with prostate-directed RT has significant association with long-term PFS and MFS in localized PCa. Our findings favor use of an adjuvant over a neoadjuvant approach, without any increase in long-term toxicity.
Effects of Thyroid Status on Regional Brain Volumes: A Diagnostic and Genetic Imaging Study in UK Biobank
Authors: Chambers Tom , Anney Richard , Taylor Peter N , Teumer Alexander , Peeters Robin P , Medici Marco , Caseras Xavier , Rees D Aled 
Published: December 2020

AbstractBackgroundThyroid hormone is essential for optimal human neurodevelopment and may modify the risk of attention-deficit/hyperactivity disorder (ADHD). However, the brain structures involved are unknown and it is unclear if the adult brain is also susceptible to changes in thyroid status.MethodsWe used International Classification of Disease-10 codes, polygenic thyroid scores at different thresholds of association with thyroid traits (PT-values), and image-derived phenotypes in UK Biobank (n = 18 825) to investigate the effects of a recorded diagnosis of thyroid disease and genetic risk for thyroid status on cerebellar and subcortical gray matter volume. Regional genetic pleiotropy between thyroid status and ADHD was explored using the GWAS-pairwise method.ResultsA recorded diagnosis of hypothyroidism (n = 419) was associated with significant reductions in total cerebellar and pallidum gray matter volumes (β [95% CI] = −0.14[−0.23, −0.06], P = 0.0005 and β [95%CI] = −0.12 [−0.20, −0.04], P = 0.0042, respectively), mediated in part by increases in body mass index. While we found no evidence for total cerebellar volume alterations with increased polygenic scores for any thyroid trait, opposing influences of increased polygenic scores for hypo- and hyperthyroidism were found in the pallidum (PT &lt; 1e−3: β [95% CI] = −0.02 [−0.03, −0.01], P = 0.0003 and PT &lt; 1e−7: β [95% CI] = 0.02 [0.01, 0.03], P = 0.0003, respectively). Neither hypo- nor hyperthyroidism showed evidence of regional genetic pleiotropy with ADHD.ConclusionsThyroid status affects gray matter volume in adults, particularly at the level of the cerebellum and pallidum, with potential implications for the regulation of motor, cognitive, and affective function.
Increased lateral tension is sufficient for epithelial folding in Drosophila
Authors: Sui Liyuan , Dahmann Christian 
Published: December 2020

ABSTRACT
The folding of epithelial sheets is important for tissues, organs and embryos to attain their proper shapes. Epithelial folding requires subcellular modulations of mechanical forces in cells. Fold formation has mainly been attributed to mechanical force generation at apical cell sides, but several studies indicate a role of mechanical tension at lateral cell sides in this process. However, whether lateral tension increase is sufficient to drive epithelial folding remains unclear. Here, we have used optogenetics to locally increase mechanical force generation at apical, lateral or basal sides of epithelial Drosophila wing disc cells, an important model for studying morphogenesis. We show that optogenetic recruitment of RhoGEF2 to apical, lateral or basal cell sides leads to local accumulation of F-actin and increase in mechanical tension. Increased lateral tension, but not increased apical or basal tension, results in sizeable fold formation. Our results stress the diversification of folding mechanisms between different tissues and highlight the importance of lateral tension increase for epithelial folding.
Ancestral role of TNF-R pathway in cell differentiation in the basal metazoan Hydra
Authors: Steichele Mona , Sauermann Lara S. , König Ann-Christine , Hauck Stefanie , Böttger Angelika 
Published: December 2020

ABSTRACT
Tumour necrosis factor receptors (TNF-Rs) and their ligands, tumour necrosis factors, are highly conserved proteins described in all metazoan phyla. They function as inducers of extrinsic apoptotic signalling and facilitate inflammation, differentiation and cell survival. TNF-Rs use distinct adaptor molecules to activate signalling cascades. Fas-associated protein with death domain (FADD) family adaptors often mediate apoptosis, and TNF-R-associated factor (TRAF) family adaptors mediate cell differentiation and inflammation. Most of these pathway components are conserved in cnidarians, and, here, we investigated the Hydra TNF-R. We report that it is related to the ectodysplasin receptor, which is involved in epithelial cell differentiation in mammals. In Hydra, it is localised in epithelial cells with incorporated nematocytes in tentacles and body column, indicating a similar function. Further experiments suggest that it interacts with the Hydra homologue of a TRAF adaptor, but not with FADD proteins. Hydra FADD proteins colocalised with Hydra caspases in death effector filaments and recruited caspases, suggesting that they are part of an apoptotic signalling pathway. Regulating epithelial cell differentiation via TRAF adaptors therefore seems to be an ancient function of TNF-Rs, whereas FADD–caspase interactions may be part of a separate apoptotic pathway.
Generation of thirst: a critical review of dehydration among older adults living in residential care
Authors: Hart Kirsty , Marsden Rachel , Paxman Jenny 
Published: December 2020

Dehydration is common among older adults and exacerbated in residential care. In this article, the authors summarise the reported prevalence of dehydration in this sub-population group and evaluate the associated risks before reviewing interventions designed to improve hydration. Heterogeneity in methods to assess dehydration inhibits interpretation of both prevalence and intervention studies (primarily small randomised control trials and case-control observational studies). The estimated prevalence of dehydration among older adults in residential care is 20-38%, with further increased prevalence of inadequate fluid intake, leading to increased urological, gastrointestinal, circulatory and neurological disorders or, in extreme cases, death. Multi-component interventions that include changes to drinks, vessels, placement and drinking opportunity, alongside staff training and support, are most effective in tackling dehydration in residential care. The detection and prevention of dehydration is crucial, and a practical, population-specific reference standard for adequate fluid intake is warranted. Future research should prioritise interventions that are individualised to residents' needs, according to dehydration typology. Ongoing investment in the care sector should address staff-to-resident ratios and enhance staff training on the detection and prevention of dehydration.
Clinical outcomes in elective total hip arthroplasty in Parkinson’s disease: a systematic review of the literature
Authors: Fontalis Andreas , Kenanidis Eustathios , Bennett-Brown Katharine , Tsiridis Eleftherios 
Published: December 2020

Parkinson’s disease (PD) poses a significant challenge for the arthroplasty surgeon, owing to excessive muscle tone, higher fracture risk and poor bone quality. Several studies have reported high mortality, early failure and perioperative complications associated with hip fracture surgery in PD; however, no higher-level evidence exists regarding elective hip arthroplasty. The aim of our study was to perform a systematic review to evaluate the evidence basis and clinical outcomes pertaining to patients with underlying Parkinson’s disease undergoing elective total hip arthroplasty (THA). We searched MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials to identify studies evaluating the safety and clinical outcomes of THA in patients suffering from Parkinson’s. Our review conforms to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ten studies encompassing 49,730 patients were included in our systematic review. Qualitative synthesis demonstrated comparable results between PD patients and controls with respect to one-year mortality and surgical site infections. PD patients experienced more medical complications, had a longer hospital stay and worse long-term implant survival. Some studies also reported a higher rate of dislocation, periprosthetic fractures and aseptic loosening. Decisions about the optimal articulation, the utilization of cemented components, dual-mobility cups or constrained liners were not uniform among included studies. THA in patients with Parkinson’s disease can offer significant functional gains and pain relief. Surgical considerations pertain to the approach and ways to address instability, whereas emphasis should be placed on appropriate counselling and exploring whether potential improvement of life quality outweighs the risks.Cite this article: EFORT Open Rev 2020;5:856-865. DOI: 10.1302/2058-5241.5.200034
Sexual assault cases at a tertiary referral hospital in urban Ethiopia: One-year retrospective review
Authors: Tolu Lemi Belay , Gudu Wondimu 
Published: December 2020

IntroductionSexual assault is an important health and social problem affecting young girls. The aim of the study is therefore to do a one-year retrospective review of documents of alleged sexual assaults managed at Saint Paulo’s Hospital Millennium Medical College (SPHMMC) to determine survivors’ characteristics, circumstances of the assault, and treatment offered.MethodsThis is a hospital-based one-year retrospective review of alleged sexual assault cases. The case records of survivors were retrieved, reviewed and information extracted analyzed using SPSS version 17. Characteristics of victims of the sexual assault, clinical presentation, and management provided were described by frequency and percentage distribution.ResultA total of 170 cases of alleged sexual assault who received care during the study period were identified. Around 96% of the survivors were female while there were 6 male cases. The mean age of the victims was 13 yrs. with a range from 2 to 25 yrs. About 23.6% of the victims were less than 10 years. Half of the victims were assaulted by neighbors (45%) followed by strangers (36.5%). The interval between the incident and presentation to the hospital ranged from 2 hours to 93 days (2224 hours) with an average of 98 hours. Most (93.0%) had one or more physical examination findings at presentation. Serology tests for HIV, Hepatitis B, and Syphilis were done in 97.3%, 88.7%, and 84.5% cases respectively. Urine pregnancy tests were done in 62.5% of the cases. Prophylaxis against HIV and STI prophylaxis was provided to 42% and 45% respectively. Social support/counseling was provided to 61% of the victims and legal evidence (certificate) was provided to 45.5% of the cases.Conclusion and recommendationsAlthough it is largely not reported by the victims, sexual assault is a grievous offense still happening constantly. Children and young girls remain the most vulnerable. There is inadequate forensic evidence collection, legal and medical care. There is also a delay in presentation to hospital by victims. Therefore, there is a need to have standardized protocols for comprehensive evaluation and care of the survivors. It is also imperative that a multidisciplinary approach like a one-stop clinic should be utilized to provide effective and efficient medical, social, psychological, and legal services. Finally, it is very necessary to increase public awareness and preventive interventions are required particularly to protect the vulnerable age group to enhance their safety.
Adipolin/C1q/Tnf-related protein 12 prevents adverse cardiac remodeling after myocardial infarction
Authors: Takikawa Tomonobu , Ohashi Koji , Ogawa Hayato , Otaka Naoya , Kawanishi Hiroshi , Fang Lixin , Ozaki Yuta , Eguchi Shunsuke , Tatsumi Minako , Takefuji Mikito , Murohara Toyoaki , Ouchi Noriyuki 
Published: December 2020

Background
Myocardial infarction (MI) is a leading cause of death worldwide. We previously identified adipolin, also known as C1q/Tnf-related protein 12, as an anti-inflammatory adipokine with protective features against metabolic and vascular disorders. Here, we investigated the effect of adipolin on myocardial remodeling in a mouse model of MI.

Methods
Male adipolin-knockout (APL-KO) and wild-type (WT) mice were subjected to the permanent ligation of the left anterior descending coronary artery to create MI.

Results
APL-KO mice exhibited increased ratios of heart weight/body weight and lung weight/body weight after MI compared with WT mice. APL-KO mice showed increased left ventricular diastolic diameter and decreased fractional shortening after MI compared with WT mice. APL-KO mice exhibited increased expression of pro-inflammatory mediators and enhanced cardiomyocyte apoptosis in the post-MI hearts compared with WT mice. Systemic administration of adenoviral vectors expressing adipolin to WT mice after MI surgery improved left ventricular contractile dysfunction and reduced cardiac expression of pro-inflammatory genes. Treatment of cultured cardiomyocytes with adipolin protein reduced lipopolysaccharide-induced expression of pro-inflammatory mediators and hypoxia-induced apoptosis. Treatment with adipolin protein increased Akt phosphorylation in cardiomyocytes. Inhibition of PI3 kinase/Akt signaling reversed the anti-inflammatory and anti-apoptotic effects of adipolin in cardiomyocytes.

Conclusion
Our data indicate that adipolin ameliorates pathological remodeling of myocardium after MI, at least in part, by its ability to reduce myocardial inflammatory response and apoptosis.
Why women with breast cancer presented late to health care facility in North-west Ethiopia? A qualitative study
Authors: Tesfaw Aragaw , Alebachew Wubet , Tiruneh Mulu 
Published: December 2020

Background
Although early diagnosis is a key determinant factor for breast cancer survival, delay in presentation and advanced stage diagnosis are common challenges in low and middle income countries including Ethiopia. Long patient delays in presentation to health facility and advanced stage diagnosis are common features in breast cancer care in Ethiopia but the reasons for patient delays are not well explored in the country. Therefore we aimed to explore the reasons for patient delay in seeking early medical care for breast cancer in North-west Ethiopia.

Methods
A qualitative study was conducted from November to December 2019 using in-depth interviews from newly diagnosed breast cancer patients in the two comprehensive specialized hospitals in North West Ethiopia. Verbal informed consent was taken from each participant before interviews. A thematic content analysis was performed using Open Code software version 4.02.

Results
Lack of knowledge and awareness about breast cancer, cultural and religious beliefs, economic hardships, lack of health care and transportation access, fear of surgical procedures and lack of trusts on medical care were the major reasons for late presentation of breast cancer identified from the patient’s narratives.

Conclusions
The reasons for late presentation of patients to seek early medical care for breast cancer had multidimensional nature in Northwest Ethiopia. Health education and promotion programs about breast cancer should be designed to increase public awareness to facilitate early detection of cases before advancement on the existing health care delivery system.
Blocking mitochondrial pyruvate import in brown adipocytes induces energy wasting via lipid cycling
Authors: Veliova Michaela , Ferreira Caroline M , Benador Ilan Y , Jones Anthony E , Mahdaviani Kiana , Brownstein Alexandra J , Desousa Brandon R , Acín‐Pérez Rebeca , Petcherski Anton , Assali Essam A , Stiles Linsey , Divakaruni Ajit S , Prentki Marc , Corkey Barbara E , Liesa Marc , Oliveira Marcus F , Shirihai Orian S 
Published: December 2020

AbstractCombined fatty acid esterification and lipolysis, termed lipid cycling, is an ATP‐consuming process that contributes to energy expenditure. Therefore, interventions that stimulate energy expenditure through lipid cycling are of great interest. Here we find that pharmacological and genetic inhibition of the mitochondrial pyruvate carrier (MPC) in brown adipocytes activates lipid cycling and energy expenditure, even in the absence of adrenergic stimulation. We show that the resulting increase in ATP demand elevates mitochondrial respiration coupled to ATP synthesis and fueled by lipid oxidation. We identify that glutamine consumption and the Malate‐Aspartate Shuttle are required for the increase in Energy Expenditure induced by MPC inhibition in Brown Adipocytes (MAShEEBA). We thus demonstrate that energy expenditure through enhanced lipid cycling can be activated in brown adipocytes by decreasing mitochondrial pyruvate availability. We present a new mechanism to increase energy expenditure and fat oxidation in brown adipocytes, which does not require adrenergic stimulation of mitochondrial uncoupling.
Mechanism of transformation of agricultural enterprises in terms of innovative development
Authors: Shelenko Diana , Balaniuk Ivan , Sas Liudmyla , Matkovskyi Petrо , Kozak-Balaniuk Iryna 
Published: December 2020

The mechanism under study should be aimed at introducing innovative approaches to the modernization of technical l and technological cycles of production and economic processes, strengthening the competitive position of enterprises in the agrarian market and overcoming internal and external institutional barriers to enterprise development by suppressing irrational institutional influences on the functioning. The purpose of this study is to substantiate theoretical and methodological foundations and to develop applied approaches for implementing the mechanism of transformation of agricultural enterprises in a competitive environment. The scientific novelty of the obtained results lies in the substantiation of the mechanism of transformation of agricultural enterprises, which includes such components as: information and analytical tools (monitoring of the economic environment, verification and systematization of information data, establishment of essential laws and relationships, the formation of information bases of decision making, management, design-testing apparatus (designing a perspective plan for the transformation of agricultural enterprises, pilot testing of the target project of the proposed changes in the organizational and legal form of management, adjustment of the project of transformation of enterprises) and implementation-block (formation of innovative structures of agricultural enterprises, ensuring the sequence and consistency of implementation of target changes, minimization of conflict environment in the process of transformation in balancing the duties, process responsibilities and responsibilities in terms of the structural components of the new organizational and legal system). The social and economic effect of this mechanism is achieved through a synergistic effect obtained through the functional interaction of enterprises that are able, however, to work autonomously. The practical significance of the mechanism is manifested in the ability to generate comprehensive management support in the process of transformation of agricultural enterprises, taking into account the specifics of a particular organizational and legal form of management in a competitive environment of their operation.