bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cost-effectiveness of icosapent ethyl in combination with statin therapy compared with statin alone for cardiovascular risk reduction
Authors: Ademi Zanfina , Ofori-Asenso Richard , Zomer Ella , Owen Alice , Liew Danny 
Published: January 2020

AbstractAimsThe aim of this study was to estimate the cost-effectiveness, from the perspective of the Australian public healthcare system, of icosapent ethyl in combination with statin therapy compared with statin alone for the prevention of cardiovascular disease.Methods and resultsA Markov model populated with data from the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial was designed to predict the effectiveness and costs of icosapent ethyl in combination with statins compared with statins alone over a 20-year time horizon. Data inputs for costs and utilities were sourced from published sources. The annual costs of icosapent ethyl were assumed to be AUD1637 (USD2907) per person. All future costs and outcomes were discounted annually by 5%. The main outcome of interest was incremental cost-effectiveness ratios in terms of cost per quality adjusted life year (QALY) gained and per year of life saved (YoLS). Over a 20-year time horizon, compared with statin alone, icosapent ethyl in combination with statin was estimated to cost an additional AUD$13,022 per person, but led to 0.338 YoLS and 0.289 QALYs gained (all discounted). These equated to incremental cost-effectiveness ratios of AUD45,036 per QALY gained and AUD38,480 per YoLS. Sub-analyses for primary and secondary prevention were AUD96,136 and AUD35,935 per QALY gained, respectively. The results were sensitive to time-horizon, age related trends and the acquisition price of icosapent ethyl.ConclusionCompared with statin alone, icosapent ethyl in combination with statin therapy is likely to be cost-effective in the prevention of cardiovascular disease assuming a willingness-to-pay threshold of AUD50,000 per QALY gained, especially in the secondary preventive setting.
INTERnational Project for the Evaluation of “activE Rehabilitation” (inter-PEER) – a protocol for a prospective cohort study of community peer-based training programmes for people with spinal cord injury
Authors: Divanoglou Anestis , Tasiemski Tomasz , Jörgensen Sophie 
Published: January 2020

Abstract
Background
Active Rehabilitation (AR) is a community peer-based concept for people with spinal cord injury (SCI) that is primarily delivered through brief residential training programmes. Despite a plethora of positive anecdotal evidence of AR programmes as life-changing experiences, the effects of AR-programmes have not been evaluated scientifically. Here, we present the protocol of the INTERnational Project for the Evaluation of “activE Rehabilitation” (inter-PEER) aiming to evaluate the effects of AR training programmes on community-dwelling individuals with SCI.

Methods
International prospective cohort study that recruits consecutive participants in AR training programmes. Evaluation is conducted through a web-based survey at 3 time-points: at the commencement and completion of the training programme, and 3 months after the end of the training programme. Evaluation also includes a practical wheelchair skills test at the first two time-points.
The primary outcome measures are the Spinal Cord Independence Measure Self-report (SCIM-SR), the Queensland Evaluation of Wheelchair Skills test (QEWS), the Wheelchair Skills Test Questionnaire (WST-Q) and the Moorong Self-Efficacy Scale (MSES). The secondary outcome measures are the 11-item Life Satisfaction Questionnaire (LiSat-11), the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-Participation), the Leisure Time Physical Activity Questionnaire for people with SCI (LTPAQ-SCI) and the 10-item Connor-Davidson Resilience Scale (CD-RISC-10).
We piloted the implementation of the protocol in Sweden in 7 participants with diverse SCI and sociodemographic characteristics and collected feedback from participants and peer-mentors about study procedures through interviews, a workshop and field observations.

Discussion
Inter-PEER is the first initiative to propose a systematic evaluation of the effects of AR training programmes among individuals with SCI. The project is a collaborative work of multiple stakeholders, including researchers, clinicians, peer mentors with SCI, and administrators of organisations providing AR programmes. The inter-PEER uses standardised outcome measures relevant to the AR context, it will facilitate quality evaluations of community peer-based programmes, stimulate international collaborations, and inform the design of randomised controlled trials on the effects of AR training programmes.
Pain in children and adolescents with cerebral palsy – a cross-sectional register study of 3545 individuals
Authors: Eriksson Elsa , Hägglund Gunnar , Alriksson-Schmidt Ann I. 
Published: January 2020

Abstract
Background
Pain is a common problem for individuals with cerebral palsy (CP). In Sweden, 95% of children and adolescents with CP are followed in a national follow-up programme (CPUP), which includes data on pain. The purpose of this study was to investigate the prevalence of pain based on age, sex, gross motor function and source of report (self or proxy). Pain intensity, pain site, and how much pain disturbed sleep and daily activities were also studied.

Methods
This was a cross-sectional register study based on all participants in CPUP, 4–18-years of age, with data reported in 2017–2018. Gross motor function was classified using the Gross Motor Function Classification System (GMFCS). Logistic regression was used to analyse prevalence of pain and how much pain had disturbed sleep and daily activities in the last four weeks.

Results
In total, 3545 participants (2065 boys) were included. The overall prevalence of pain was 44%. Older age and female sex were associated with higher risk of pain with odds ratios of 1.07 (95% confidence interval (CI) 1.06–1.09) and 1.28 (CI 1.12–1.47), respectively. Pain was most common in the lower extremities. There was no statistically significant difference in prevalence of pain related to source of report. Pain intensity was higher at older ages and higher GMFCS-levels. Hip/thigh pain and abdominal pain were associated with the most intense pain.
Of those who reported pain, pain disturbed sleep for 36% and daily activities for 61%.

Conclusions
Both pain frequency and pain intensity were higher at higher age. Pain intensity increased with increasing GMFCS-level. Two-thirds of all children and adolescents with CP reported that their pain disturbed their daily activities, and one-third reported that pain disturbed their sleep.
Are parental dietary patterns associated with children’s overweight and obesity in China?
Authors: Tang Daisheng , Bu Tao , Dong Xuefan 
Published: January 2020

Abstract
Background
It is believed that parents have a great influence on their children’s dietary behaviours. However, it is not clear whether parental food patterns are associated with children’s nutritional status in China, which includes a vast territory with rich, diverse cultures. The goal of this project is to systematically study the associations between parental food intake and children’s overweight and obesity in China, according to children’s ages and regional differences.

Methods
Based on individual food consumption data from the China Health and Nutrition Survey (CHNS) package in 2011, cross-sectional studies have previously been conducted to analyse the association between different categories of food intake of parents and children. The current study extends this research by directly.

Results
Our analysis results show that parental food intake is highly correlated with children’s food intake, with the estimated coefficients of most food intake categories being greater than 0.5. Furthermore, this association between parental food intake and children’s overweight and obesity is most significant in young children, but it begins to weaken in relation to children aged between 13 and 18. Additionally, the associations between parental food intake and children’s overnutrition are more significant in rural areas than they are in urban areas.

Conclusions
The association between parental food intake and childhood overweight and obesity is significant, although it varies considerably according to food categories, children’s ages and area differences. These results show promise for intervening in the overnutrition of children by controlling household dietary patterns according to children’s developmental stages and regional differences.
In vitro effects of alendronate on fibroblasts of the human rotator cuff tendon
Authors: Sung Chang-Meen , Kim Ra Jeong , Hah Young-Sool , Gwark Ji-Yong , Park Hyung Bin 
Published: January 2020

Abstract
Background
Bone mineral density of the humeral head is an independent determining factor for postoperative rotator cuff tendon healing. Bisphosphonates, which are commonly used to treat osteoporosis, have raised concerns regarding their relationships to osteonecrosis of the jaw and to atypical fracture of the femur. In view of the prevalence of rotator cuff tear in osteoporotic elderly people, it is important to determine whether bisphosphonates affect rotator cuff tendon healing. However, no studies have investigated bisphosphonates’ cytotoxicity to human rotator cuff tendon fibroblasts (HRFs) or bisphosphonates’ effects on rotator cuff tendon healing. The purpose of this study was to evaluate the cytotoxicity of alendronate (Ald), a bisphosphonate, and its effects on HRF wound healing.

Methods
HRFs were obtained from human supraspinatus tendons, using primary cell cultures. The experimental groups were control, 0.1 μM Ald, 1 μM Ald, 10 μM Ald, and 100 μM Ald. Alendronate exposure was for 48 h, except during a cell viability analysis with durations from 1 day to 6 days. The experimental groups were evaluated for cell viability, cell cycle and cell proliferation, type of cell death, caspase activity, and wound-healing ability.

Results
The following findings regarding the 100 μM Ald group contrasted with those for all the other experimental groups: a significantly lower rate of live cells (p < 0.01), a higher rate of subG1 population, a lower rate of Ki-67 positive cells, higher rates of apoptosis and necrosis, a higher number of cells with DNA fragmentation, higher caspase-3/7 activity (p < 0.001), and a higher number of caspase-3 positive staining cells. In scratch-wound healing analyses of all the experimental groups, all the wounds healed within 48 h, except in the 100 μM Ald group (p < 0.001).

Conclusions
Low concentrations of alendronate appear to have little effect on HRF viability, proliferation, migration, and wound healing. However, high concentrations are significantly cytotoxic, impairing cellular proliferation, cellular migration, and wound healing in vitro.
A sense of security in palliative homecare in a Norwegian municipality; dyadic comparisons of the perceptions of patients and relatives - a quantitative study
Authors: Hov Reidun , Bjørsland Bente , Kjøs Bente Ødegård , Wilde-Larsson Bodil 
Published: January 2020

Abstract
Background
As palliative care increasingly takes place in patients’ homes, perceptions of security among patients in the late palliative phase and their relatives are important.

Aim
To describe and compare patient-relative dyads regarding their perceptions of security in palliative homecare, including the perceived security of the actual care given to the patients, as well as the subjective importance of that care.

Methods
A cross sectional questionnaire study including 32 patient-relative dyads was conducted in an urban municipality in Norway. Patients were in a late palliative phase and received palliative homecare. Each patient proposed one relative. Data were collected using a modified version of the Quality from the Patients’ Perspective instrument (QPP), which focuses on security and comprises three dimensions: medical-technical competence, identity-orientation approach and physical-technical conditions. Context-specific scales containing four aspects (competence, continuity, coordination/cooperation, availability) were added. The instrument contains two response scales; perceived reality (PR) and subjective importance (SI). Data were analysed by descriptive statistics, Chi-squared test, T-test and Wilcoxon’s signed rank test.

Results
Patients had high mean scores on the PR-scale for the sense of security in palliative homecare in the dimensions of medical-technical competence and physical-technical conditions. There were three low mean scores on the PR-scale: the aspect of continuity from patients and the aspects of continuity and coordination/cooperation from relatives.
The patients scored the SI scale statistically significantly higher than the PR scale in the identity-orientation approach dimension and in the aspect of continuity, while relatives did so in all dimensions and aspects.
The intra-dyadic patient-relative comparisons show statistically significant lower scores from relatives on the PR-scale in the dimensions of medical-technical competence, physical-technical conditions, identity-orientation approach and the aspect coordination/cooperation.

Conclusions
There are several statistically significant differences between patients and relatives’ perceptions of security in the palliative homecare received (PR) compared with the subjective importance of the care (SI) and statistically significant differences in the patient-relative dyads in PR. A relatively mutual sense of security in palliative homecare is important for patient-relative dyads, as relatives often provide care and act as patients’ spokespersons. What they assess as important can guide the development of palliative homecare.
Downregulation of MYPT1 increases tumor resistance in ovarian cancer by targeting the Hippo pathway and increasing the stemness
Authors: Muñoz-Galván Sandra , Felipe-Abrio Blanca , Verdugo-Sivianes Eva M. , Perez Marco , Jiménez-García Manuel P. , Suarez-Martinez Elisa , Estevez-Garcia Purificacion , Carnero Amancio 
Published: January 2020

Abstract
Background
Ovarian cancer is one of the most common and malignant cancers, partly due to its late diagnosis and high recurrence. Chemotherapy resistance has been linked to poor prognosis and is believed to be linked to the cancer stem cell (CSC) pool. Therefore, elucidating the molecular mechanisms mediating therapy resistance is essential to finding new targets for therapy-resistant tumors.

Methods
shRNA depletion of MYPT1 in ovarian cancer cell lines, miRNA overexpression, RT-qPCR analysis, patient tumor samples, cell line- and tumorsphere-derived xenografts, in vitro and in vivo treatments, analysis of data from ovarian tumors in public transcriptomic patient databases and in-house patient cohorts.

Results
We show that MYPT1 (PPP1R12A), encoding myosin phosphatase target subunit 1, is downregulated in ovarian tumors, leading to reduced survival and increased tumorigenesis, as well as resistance to platinum-based therapy. Similarly, overexpression of miR-30b targeting MYPT1 results in enhanced CSC-like properties in ovarian tumor cells and is connected to the activation of the Hippo pathway. Inhibition of the Hippo pathway transcriptional co-activator YAP suppresses the resistance to platinum-based therapy induced by either low MYPT1 expression or miR-30b overexpression, both in vitro and in vivo.

Conclusions
Our work provides a functional link between the resistance to chemotherapy in ovarian tumors and the increase in the CSC pool that results from the activation of the Hippo pathway target genes upon MYPT1 downregulation. Combination therapy with cisplatin and YAP inhibitors suppresses MYPT1-induced resistance, demonstrating the possibility of using this treatment in patients with low MYPT1 expression, who are likely to be resistant to platinum-based therapy.
Uterine intravenous leiomyomatosis with an isolated large metastasis to the right atrium: a case report
Authors: Yano Mitsutake , Katoh Tomomi , Nakajima Yoshie , Iwanaga Shiro , Kin Rei , Kozawa Eito , Yasuda Masanori 
Published: January 2020

Abstract
Background
An intravenous leiomyomatosis is a special type of uterine leiomyoma characterized by the formation of benign leiomyomatous tissue within the vascular wall. Although histologically benign, intracardiac metastasis can lead to circulatory failure, and death, if untreated. Herein, we report on a case of a uterine intravenous leiomyomatosis with an isolated large adherent metastasis in the right atrium of the heart.

Case Presentation
A 52-year-old Japanese woman sought medical attention at our hospital for lower abdominal pain. A 27-cm uterine mass was detected on clinical imaging, with a 78 × 47-mm mass in the right atrium detected on preoperative echocardiography. Intracardiac mass resection and tricuspid annuloplasty were performed as the first-stage surgery. The pedicle of the tumor was adherent to the wall of the atrium. On histological examination, the tumor was found to consist of spindle-shaped cells with eosinophilic cytoplasm, without atypia, but with a myxoid change, and rich microvascularization of the pedicle. Total abdominal hysterectomy was performed as the second-stage surgery, with confirmation of the diagnosis as uterine intravenous leiomyomatosis with an isolated metastasic lesion to the right atrium. There has been no evidence of tumor recurrence in the 15 months since surgery.

Conclusion
We report a unique case in which a large right atrial leiomyoma was identified following a uterine intravenous leiomyomatosis. Our case exemplifies that intravenous leiomyomatosis metastatic tumors have the potential to grow via their vascularization.
Structure-based directed evolution improves S. cerevisiae growth on xylose by influencing in vivo enzyme performance
Authors: Lee Misun , Rozeboom Henriëtte J. , Keuning Eline , de Waal Paul , Janssen Dick B. 
Published: January 2020

Abstract
Background
Efficient bioethanol production from hemicellulose feedstocks by Saccharomyces cerevisiae requires xylose utilization. Whereas S. cerevisiae does not metabolize xylose, engineered strains that express xylose isomerase can metabolize xylose by converting it to xylulose. For this, the type II xylose isomerase from Piromyces (PirXI) is used but the in vivo activity is rather low and very high levels of the enzyme are needed for xylose metabolism. In this study, we explore the use of protein engineering and in vivo selection to improve the performance of PirXI. Recently solved crystal structures were used to focus mutagenesis efforts.

Results
We constructed focused mutant libraries of Piromyces xylose isomerase by substitution of second shell residues around the substrate- and metal-binding sites. Following library transfer to S. cerevisiae and selection for enhanced xylose-supported growth under aerobic and anaerobic conditions, two novel xylose isomerase mutants were obtained, which were purified and subjected to biochemical and structural analysis. Apart from a small difference in response to metal availability, neither the new mutants nor mutants described earlier showed significant changes in catalytic performance under various in vitro assay conditions. Yet, in vivo performance was clearly improved. The enzymes appeared to function suboptimally in vivo due to enzyme loading with calcium, which gives poor xylose conversion kinetics. The results show that better in vivo enzyme performance is poorly reflected in kinetic parameters for xylose isomerization determined in vitro with a single type of added metal.

Conclusion
This study shows that in vivo selection can identify xylose isomerase mutants with only minor changes in catalytic properties measured under standard conditions. Metal loading of xylose isomerase expressed in yeast is suboptimal and strongly influences kinetic properties. Metal uptake, distribution and binding to xylose isomerase are highly relevant for rapid xylose conversion and may be an important target for optimizing yeast xylose metabolism.
Development of a total serum testosterone, androstenedione, 17-hydroxyprogesterone, 11β-hydroxyandrostenedione and 11-ketotestosterone LC-MS/MS assay and its application to evaluate pre-analytical sample stability
Authors: Hawley James M. , Adaway Joanne E. , Owen Laura J. , Keevil Brian G. 
Published: January 2020

Abstract

Background
Classically, serum testosterone (T) and androstenedione (A4) have been the mainstay for the biochemical assessment of hyperandrogenism. However, recent evidence suggests 11β-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT) may also be important. Here, we describe the development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for quantitation of total serum T, A4, 17-hydroxyprogesterone (17OHP), 11OHA4 and 11KT. In addition, we applied the method to assess pre-analytical stability.

Methods
An isotopically labelled internal standard was added to samples prior to supported liquid extraction (SLE). Extracts were analysed using LC-MS/MS to detect T/A4/17OHP/11OHA4 and 11KT along with their corresponding internal standards. Samples (n = 7) were collected from healthy volunteers (n = 14) and left incubated at 20 °C for up to 72 h. Tubes were retrieved at select time points, centrifuged, separated and frozen prior to analysis.

Results
The total run time was 4 min. For all analytes, intra- and inter-assay imprecision did not exceed 7.9% and 5.3%, respectively; matrix effects were negligible and mean recoveries ranged from 95.3 to 111.6%. The limits of quantitation (LOQs) were 0.25 nmol/L for T, A4 and 11OHA4, 0.50 nmol/L for 17OHP, and 0.24 nmol/L for 11KT. No significant change was observed in pre-centrifugation A4 or female T concentrations over 72 h. Significant increases (p < 0.01) in concentrations of 11KT, 17OHP, 11OHA4 and male T were observed after 2, 8, 12 and 24 h, respectively.

Conclusions
We developed a robust LC-MS/MS assay for the quantitation of total serum T/A4/17OHP/11OHA4 and 11KT. Applying the method to determine pre-analytical stability suggests samples requiring 11KT need separating from the cells within 2 h.
Sexual motivation: problem solved and new problems introduced
Authors: Pfaff Donald , Saad Farid 
Published: January 2020

AbstractBackgroundDuring the past 50 years, motivational studies have evolved from the logical inference of logically required “intervening variables” to explain behavioral change, to electrophysiological and molecular analyses of the mechanisms causing such changes.AimThe purpose of this review article is two-fold: first to describe the logic of sexual motivation in a way that applies to laboratory animals as well as humans, and the second is to address some of the problems of sexual motivation experienced by men.ResultsWhen problems of motivational mechanisms are stripped down to their essentials, as performed in the laboratory animal models and are available for reductionistic studies, then the problems can be solved with certainty, as illustrated in the first part of this review. However, with respect to human sexual motivation, the various determinants which include so many behavioral routes and so many brain states come into play, that definite conclusions are harder to come by, as illustrated in the second part of this review.ConclusionsThis review highlights a number of key questions that merit further investigation. These include (a) What mechanisms do cultural and experiential influences interact with androgenic hormone influences on human sexual motivation? (b) How would epigenetic effects in the human brain related to changes in motivation be investigated? (c) What are the effects of unpredictable traumatic and stressful human experiences on sexual motivation; (d) How such mechanisms are activated upon unpredictable traumatic and stressful insults? (e) What are the outstanding differences between sexual motivational drive and motivations driven by homeostatic systems such as hunger and thirst?