bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short or Long Antibiotic Regimes in Orthopaedics (SOLARIO): a randomised controlled open-label non-inferiority trial of duration of systemic antibiotics in adults with orthopaedic infection treated operatively with local antibiotic therapy
Authors: Dudareva Maria , Kümin Michelle , Vach Werner , Kaier Klaus , Ferguson Jamie , McNally Martin , Scarborough Matthew 
Published: December 2019

AbstractBackgroundOrthopaedic infections, such as osteomyelitis, diabetic foot infection and prosthetic joint infection, are most commonly treated by a combination of surgical debridement and a prolonged course of systemic antibiotics, usually for at least 4–6 weeks. Use of local antibiotics, implanted directly into the site of infection at the time of surgery, may improve antibiotic delivery and allow us to shorten the duration of systemic antibiotic therapy, thereby limiting the frequency of side effects, cost and selection pressure for antimicrobial resistance.MethodsSOLARIO is a multicentre open-label randomised controlled non-inferiority trial comparing short and long systemic antibiotic therapy alongside local antibiotic therapy. Adult patients with orthopaedic infection, who have given informed consent, will be eligible to participate in the study provided that no micro-organisms identified from deep tissue samples are resistant to locally implanted antibiotics. Participants will be randomised in a 1:1 ratio to receive either a short course (≤ 7 days) or currently recommended long course (≥ 4 weeks) of systemic antibiotics. The primary outcome will be treatment failure by 12 months after surgery, as ascertained by an independent Endpoint Committee blinded to treatment allocation. An absolute non-inferiority margin of 10% will be used for both per-protocol and intention-to-treat populations. Secondary outcomes will include probable and definite treatment failure, serious adverse events, treatment side effects, quality of life scores and cost analysis.DiscussionThis study aims to assess a treatment strategy that may enable the reduction of systemic antibiotic use for patients with orthopaedic infection. If this strategy is non-inferior, this will be to the advantage of patients and contribute to antimicrobial stewardship.Trial registrationClinicaltrials.gov,NCT03806166. Registered on 11 November 2019.
Cognitive-behavioral intervention via interactive multimedia online video game for active aging: study protocol for a randomized controlled trial
Authors: Vázquez Fernando L. , Torres Ángela J. , Otero Patricia , Blanco Vanessa , López Lara , García-Casal Antonio , Arrojo Manuel 
Published: December 2019

AbstractBackgroundDue to the progressive aging of the population, programs to promote active aging have been recommended. However, older adults have difficulty accessing them. Interventions administered through online video games may increase their accessibility, and complementing these with a smartphone app will likely increase adherence and allow for ongoing professional monitoring. The objective of this study is to evaluate the efficacy of a cognitive-behavioral intervention for active aging administered through an online interactive multimedia video game that includes a smartphone app companion. The secondary objectives are to analyze the moderators and mediators of the change in the outcome variables and to evaluate the adherence to the intervention.Methods/designA randomized controlled clinical trial will be conducted. Adults 45 years and older will be randomly assigned to a cognitive-behavioral intervention administered through an online multimedia video game that includes a smartphone app companion or to a control group that will receive online information on active aging (274 participants per group). The intervention will be administered in eight weekly 45-min modules. An investigator-blinded evaluation will be conducted using online self-administered tests at baseline, post-intervention, and 6- and 12-month follow-ups. The primary outcome will be mental health status as evaluated using the 36-item Short-Form Health Survey (SF-36) at post-intervention. Secondary outcomes will be emotional well-being, depressive symptoms, reinforcement, negative thoughts, self-reported memory, cognitive task performance, sleep hygiene behaviors, physical activity, eating habits, body mass index, social support, dropout, treatment adherence, and satisfaction with the intervention.DiscussionIf the results are favorable, this study would involve the development of the first evidence-based active aging promotion intervention based on a video game that includes a smartphone app companion, providing evidence on its efficacy, accessibility, and clinical utility.Trial registrationClinicalTrials.gov,NCT03643237. Registered 27 August 2018.
Psychosomatic therapy for patients frequently attending primary care with medically unexplained symptoms, the CORPUS trial: study protocol for a randomised controlled trial
Authors: Wortman Margreet S. H. , van der Wouden Johannes C. , Grutters Janneke P. C. , Visser Bart , Assendelft Willem J. J. , van der Horst Henriëtte E. , olde Hartman Tim C. 
Published: December 2019

Abstract
Background
Medically unexplained symptoms (MUS) are highly prevalent and pose a burden both on patients and on health care. In a pilot study psychosomatic therapy delivered by specialised therapists for patients with MUS showed promising results with regard to patient’s acceptability, feasibility and effects on symptoms. The aim of this study is to establish whether psychosomatic therapy by specialised psychosomatic exercise therapists is cost- effective in decreasing symptoms and improving functioning in patients who frequently consult their general practitioner (GP) with MUS.

Methods
A randomised effectiveness trial with an economic evaluation in primary care with 158 patients aged 18 years and older who are frequently consulting their GP with MUS. Patients will be assigned to psychosomatic therapy in addition to usual care or usual care only. Psychosomatic therapy is a multi-component and tailored intervention, aiming to empower patients by applying psycho-education, relaxation techniques, mindfulness, cognitive approaches and/or graded activity. Patients assigned to the psychosomatic therapy receive 6 to 12 sessions of psychosomatic therapy, of 30–45 min each, delivered by a specialised exercise or physical therapist.
Primary outcome measure is patient-specific functioning and disability, measured with the Patient-Specific Functional Scale (PSFS). Secondary outcome measures are symptom severity, consultation frequency and referrals to secondary care, patient satisfaction, quality of life and costs. Assessments will be carried out at baseline, and after 4 and 12 months.
An economic evaluation alongside the trial will be conducted from a societal perspective, with quality-adjusted life years (QALYs) as outcome measure. Furthermore, a mixed-methods process evaluation will be conducted.

Discussion
We expect that psychosomatic therapy in primary care for patients who frequently attend the GP for MUS will improve symptoms and daily functioning and disability, while reducing consultation frequency and referrals to secondary care. We expect that the psychosomatic therapy provides value for money for patients with MUS.

Trial registration
Netherlands Trial Register, ID: NL7157 (NTR7356). Registered 13 July 2018.
Long non-coding XIST raises methylation of TIMP-3 promoter to regulate collagen degradation in osteoarthritic chondrocytes after tibial plateau fracture
Authors: Chen Hongwei , Yang Shengdi , Shao Ruyi 
Published: December 2019

Abstract
Background
Hypermethylation of gene promoters has been regarded as an epigenetic regulator for gene inactivation in the development of several diseases. In the current study, we aimed to explore how long noncoding RNA X-inactive specific transcript (lncRNA XIST) function in collagen degradation in chondrocytes of osteoarthritis (OA) after tibial plateau fracture by regulating tissue inhibitor of metalloproteinase-3 (TIMP-3) promoter methylation.

Methods
In silico analysis was used to screen differentially expressed lncRNAs in cartilage tissues of OA. Chondrocytes were then successfully isolated from normal and OA cartilage tissues and identified, with the expressions of lncRNA XIST and TIMP-3 examined. The methylation levels of TIMP-3 promoter were determined by MS-PCR. The binding of lncRNA XIST to DNA methyltransferase and the binding of TIMP-3 promoter to DNA methyltransferase were determined by a series of experiments, including RIP, RNA pull-down, and ChIP assays.

Results
The differentially expressed lncRNA XIST was determined in OA. In addition, cartilage tissues of OA showed upregulation of lncRNA XIST and downregulation of TIMP-3. LncRNA XIST was primarily localized in the nucleus and was capable of binding to the promoter of TIMP-3. The silencing of lncRNA XIST decreased the methylation levels of TIMP-3 promoter and increased the expressions of TIMP-3, which consequently inhibited collagen degradation in OA chondrocytes. Furthermore, TIMP-3 over-expression reversed the effect of lncRNA XIST on collagen degradation in OA chondrocytes.

Conclusion
Collectively, lncRNA XIST raises collagen degradation in OA chondrocytes after tibial plateau fracture by accelerating the methylation of TIMP-3 promoter by recruiting DNA methyltransferase.
Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT
Authors: Strand Vibeke , Pope Janet , Tundia Namita , Friedman Alan , Camp Heidi S. , Pangan Aileen , Ganguli Arijit , Fuldeore Mahesh , Goldschmidt Debbie , Schiff Michael 
Published: December 2019

Abstract
Background
To evaluate the effect of upadacitinib on patient-reported outcomes (PROs) in patients with RA who had an inadequate response to csDMARDs.

Methods
Patients in SELECT-NEXT, a randomised controlled trial, were on a background of csDMARDs and received upadacitinib 15 mg and 30 mg or placebo daily for 12 weeks. PROs included Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), duration and severity of morning (AM) joint stiffness, Short Form 36 Health Survey (SF-36), and Work Instability Scale for RA (RA-WIS). Least squares mean (LSM) changes were based on mixed-effect repeated measure models. Percentages of patients reporting improvements ≥ minimum clinically important differences (MCIDs) and scores ≥ normative values and number needed to treat (NNT) were determined; group comparisons used chi-square tests.

Results
Data from 661 patients were analysed. Compared with placebo, patients receiving upadacitinib reported statistically significant improvements (both doses, P < 0.05) in PtGA, pain, HAQ-DI, FACIT-F, duration and severity of AM stiffness, SF-36 (PCS and 6/8 domains), and RA-WIS at week 12. Significantly, more upadacitinib-treated patients (both doses, P < 0.05) reported improvements ≥ MCID in PtGA, pain, HAQ-DI, FACIT-F, AM stiffness, SF-36 (PCS and 4 or 7/8 domains), and RA-WIS and scores ≥ normative values in HAQ-DI, FACIT-F, and SF-36 (PCS and 4 or 5/8 domains). For most PROs, the incremental NNT with upadacitinib to report clinically meaningful improvement from baseline ranged from 4 to 8 patients.

Conclusions
Upadacitinib 15 mg or 30 mg daily for 12 weeks resulted in significant and clinically meaningful improvements in global disease activity, pain, physical function, fatigue, duration and severity of AM stiffness, HRQOL, and work instability among csDMARD-IR patients with RA.

Trial registration
Clinicaltrials.gov, NCT02675426. Retrospectively registered 5 February 2016.
Standardization of the Computerized Battery for Neuropsychological Evaluation of Children (BENCI) in an urban setting, in Kenya: a study protocol
Authors: Maina Rachel Wanjiru , Abubakar Amina , Miguel Perez-Garcia , Van De Vijver Fons J. R. , Kumar Manasi 
Published: December 2019

Abstract
Objective
In sub Saharan Africa one of the key challenges in assessment using neuropsychological tools has been the lack of adequately validated and easily implementable measures. This study will translate into English, adapt and standardize the Computerized Battery for Neuropsychological Evaluation of Children (BENCI). The BENCI battery will be adapted using back-translation design, comprehensive cultural adaptation and standardized in a case–control study involving two groups of children: HIV infected and HIV unexposed, uninfected children. The content adaptation will be iteratively carried out using knowledge of English and feedback from pilot testing with children. The proposed study will first involve the cultural adaptation of the BENCI. It will then recruit 544 children aged 8–11 years with half of them being HIV+, while the other half will be HIV unexposed-uninfected. Test–retest reliability will be analyzed using Pearson’s correlation while ANOVA and correlational analyses will be used to calculate discriminant, convergent and construct validity.

Results
This study will result in an open access adequately adapted and standardized measure of neuropsychological functioning for use with children in East Africa. The protocol paper provides an opportunity to share the planned methods and approaches.
Safe regions of miniscrew implantation for distalization of mandibular dentition with CBCT
Authors: Liu Haibo , Wu Xiaoxue , Tan Jun , Li Xiao 
Published: December 2019

AbstractBackgroundTo assess the anatomy of the mandibular buccal shelf (MBS) with cone-beam computed tomography (CBCT) and to identify the region of miniscrew implantation for the distalization of mandibular dentition.Materials and methodsThe MBS was assessed in 80 patients at four regions as follows: (i) between the buccal root of the mandibular second premolar and the mesiobuccal root of the first molar (L5b–L6mb), (ii) between the mesiodistal root of the first molar (L6mb–L6db), (iii) between the distobuccal root of the first molar and the mesiobuccal root of the second molar (L6db–L7mb), and (iv) between the mesiodistal roots of the second molar (L7mb–L7db). The buccal alveolar bone thickness, the narrowest inter-radicular space at the buccal side of the roots, and the distance between the implantation site and the mandibular neural tube were measured at horizontal planes of 3, 5, 7, and 9 mm from the alveolar crest.ResultsThe buccal alveolar bone thickness increased from the premolar to the molar and from the crest edge to the mandibular roots. The L7mb–L7dbregion had the thickest buccal alveolar bone of 7.61 mm at a plane of 9 mm. The buccal inter-radicular spaces were smallest in the L7mb–L7dbregion and greatest in the L6db–L7mbregion. The distances from the implantation site to the mandibular neural tube at planes of 3, 5, 7, and 9 mm were all > 13 mm from the L6 region to the L7 region.ConclusionsThe L6db–L7mbregion should be the first choice for miniscrew implantation in the MBS for the distalization of mandibular dentition.
Evaluation of awarding badges on Student’s engagement in Gamified e-learning systems
Authors: Imran Hazra 
Published: December 2019

AbstractGamification has been gaining increasing acceptability in recent times in educational and commercially related activities, as a tool that encourages and improves the motivation of digital native learners. Since learners can easily engage, educationists have explored gamification as a tool for remediation of engagement, motivation, and collaboration. However, the literature showed that the structural and contextual deployment of game elements is defined only partially in practice. Subsequently, gamification success and failure factors should be explored to identify the required enhancement to achieve improved efficiency in current systems. This research extracts the relevant aspects of gamification that need due consideration to make a guided choice through existing theories. This study is based on an online gamified study that uses well-founded concepts in teaching and evaluation of students in a university. Although badges earned and time spent indicated an increase in engagement, the results show that further work needs to be done by incorporating feedback elements, social interaction, and interactive guidance. The underlying impression is that timely, frequent feedback and personalized guidance, avenues for collaboration and interactivity need to be explored towards the better utility of gamification. Therefore, learning culture in the current learner-centered environment should be further studied to infuse better productivity.
An intervention engine design and development based on learning analytics: the intelligent intervention system (In2S)
Authors: Şahin Muhittin , Yurdugül Halil 
Published: December 2019

AbstractIn this study, an intervention engine based on learning analytics was designed and developed. The intervention engine is named the Intelligent Intervention System (In2S). Within the scope of this research; In2S system and its components have been introduced, and the system is evaluated based on learners’ views. In2S includes three types of intervention that are instructional, supportive, and motivational intervention. The instructional intervention was structured based on assessment tasks. The supportive and motivational interventions were structured based on the learning experiences of the learners. Signal lights (red, yellow, and green) are presented to the learners for each assessment task as an instructional intervention. Supportive intervention is presented to the learners via the dashboard. In the context of motivational intervention, elements of gamification as a leader board, badges, and notifications have been used. In order to obtain the learner’s views about the In2S, semi-structured interviews were conducted with the learners who had a previous learning experience with the system. The learning environment was evaluated based on their views. Learners had a nine-week learning experience in the e-learning environment. Then, eight students who used the system most actively and eight students who used the system most passively were selected for focus group interviews.. According to the findings, it was seen that the learners who use the intervention engine indicated that the system is useful and want to use it in the context of other courses.
Detection of thioredoxin-1 using ultra-sensitive ELISA with enzyme-encapsulated human serum albumin nanoparticle
Authors: Lee Myeong-Jun , Lee Eun-Sol , Kim Tae-Hwan , Jeon Ju-Won , Kim YongTae , Oh Byung-Keun 
Published: December 2019

AbstractMany methods for early diagnosis of the disease use biomarker tests, which measure indicators of biological state in body fluids or blood. However, a limitation of these methods is their low sensitivity to biomarkers. In this study, human serum albumin (HSA) based nanoparticles capable of encapsulating excess horseradish peroxidase (HRP) are synthesized and applied to the development of enzyme-linked immunosorbent assay (ELISA) kit with ultra-high sensitivity. The size of the nanoparticles and the amount of encapsulated enzyme are controlled by varying the synthesis conditions of pH and protein concentration, and the surface of the nanoparticles is modified with protein A (proA) to immobilize antibodies to the nanoparticles by self-assembly. Using the synthesized nanoparticles, the biomarker of breast cancer, thioredoxin-1, can be measured in the range of 10 fM to 100 pM by direct sandwich ELISA, which is 105 times more sensitive than conventional methods.
Sex-based differences in the prevalence of acute mountain sickness: a meta-analysis
Authors: Hou Yun-Peng , Wu Jia-Lin , Tan Chao , Chen Yu , Guo Rui , Luo Yong-Jun 
Published: December 2019

Abstract
Background
When lowlanders rapidly ascend to altitudes > 2500 m, they may develop acute mountain sickness (AMS). The individual susceptibility, ascending velocity, time spent at altitude, activity levels and altitude reached are considered risk factors for AMS. However, it is not clear whether sex is a risk factor. The results have been inconclusive. We conducted a meta-analysis to test whether there were sex-based differences in the prevalence of AMS using Lake Louise Scoring System.

Methods
Systematic searches were performed in August 2019 in EMBASE, PubMed, and Web of Science for prospective studies with AMS data for men and women. The titles and abstracts were independently checked in the primary screening step, and the selected full-text articles were independently assessed in the secondary screening step by the two authors (YPH and JLW) based on pre-defined inclusion criteria. The meta-analysis was performed using by the STATA 14.1 software program. A random-effects model was employed.

Results
Eighteen eligible prospective studies were included. A total of 7669 participants (2639 [34.4%] women) were tested. The results showed that there was a statistically significant higher prevalence rate of AMS in women than in men (RR = 1.24, 95%CI 1.09–1.41), regardless of age or race. Howerver, the heterogeneity was significant in the analysis (Tau2 = 0.0403, Chi2 = 50.15, df = 17; I2 = 66.1%, P = 0.000), it was main caused by different numbers of subjects among the studies (coefficient = − 2.17, P = 0.049). Besides, the results showed that there was no evidence of significant publication bias in the combined studies on the basis of Egger’s test (bias coefficient = 1.48, P = 0.052) and Begg’s test (P = 0.130).

Conclusions
According to this study, the statistically significant finding emerging from this study was that women have a higher prevalence of AMS. However, the authors could not exclude studies where patients were on acetazolamide. Our analysis provided a direction for future studies of the relationship of sex and the risk of AMS, such as the pathological mechanism and prevention research.