bluuebunny/crossref_metadata_2025_split huggingface dataset:
TASCI—transcutaneous tibial nerve stimulation in patients with acute spinal cord injury to prevent neurogenic detrusor overactivity: protocol for a nationwide, randomised, sham-controlled, double-blind clinical trial
Authors: Birkhäuser Veronika , Liechti Martina D , Anderson Collene E , Bachmann Lucas M , Baumann Sarah , Baumberger Michael , Birder Lori A , Botter Sander M , Büeler Silvan , Cruz Célia D , David Gergely , Freund Patrick , Friedl Susanne , Gross Oliver , Hund-Georgiadis Margret , Husmann Knut , Jordan Xavier , Koschorke Miriam , Leitner Lorenz , Luca Eugenia , Mehnert Ulrich , Möhr Sandra , Mohammadzada Freschta , Monastyrskaya Katia , Pfender Nikolai , Pohl Daniel , Sadri Helen , Sartori Andrea M , Schubert Martin , Sprengel Kai , Stalder Stephanie A , Stoyanov Jivko , Stress Cornelia , Tatu Aurora , Tawadros Cécile , van der Lely Stéphanie , Wöllner Jens , Zubler Veronika , Curt Armin , Pannek Jürgen , Brinkhof Martin W G , Kessler Thomas M 
Published: August 2020

IntroductionNeurogenic lower urinary tract dysfunction (NLUTD), including neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia, is one of the most frequent and devastating sequelae of spinal cord injury (SCI), as it can lead to urinary incontinence and secondary damage such as renal failure. Transcutaneous tibial nerve stimulation (TTNS) is a promising, non-invasive neuromodulatory intervention that may prevent the emergence of the C-fibre evoked bladder reflexes that are thought to cause NDO. This paper presents the protocol for TTNS in acute SCI (TASCI), which will evaluate the efficacy of TTNS in preventing NDO. Furthermore, TASCI will provide insight into the mechanisms underlying TTNS, and the course of NLUTD development after SCI.Methods and analysisTASCI is a nationwide, randomised, sham-controlled, double-blind clinical trial, conducted at all four SCI centres in Switzerland. The longitudinal design includes a baseline assessment period 5–39 days after acute SCI and follow-up assessments occurring 3, 6 and 12 months after SCI. A planned 114 participants will be randomised into verum or sham TTNS groups (1:1 ratio), stratified on study centre and lower extremity motor score. TTNS is performed for 30 min/day, 5 days/week, for 6–9 weeks starting within 40 days after SCI. The primary outcome is the occurrence of NDO jeopardising the upper urinary tract at 1 year after SCI, assessed by urodynamic investigation. Secondary outcome measures assess bladder and bowel function and symptoms, sexual function, neurological structure and function, functional independence, quality of life, as well as changes in biomarkers in the urine, blood, stool and bladder tissue. Safety of TTNS is the tertiary outcome.Ethics and disseminationTASCI is approved by the Swiss Ethics Committee for Northwest/Central Switzerland, the Swiss Ethics Committee Vaud and the Swiss Ethics Committee Zürich (#2019-00074). Findings will be disseminated through peer-reviewed publications.Trial registration numberNCT03965299.
Evaluating the validity, reliability and clinical utility of the Music therapy Sensory Instrument for Cognition, Consciousness and Awareness (MuSICCA): protocol of a validation study
Authors: Pool Jonathan Wain , Siegert Richard John , Taylor Steven , Dunford Carolyn , Magee Wendy 
Published: August 2020

IntroductionA growing number of children and young people are surviving severe acquired brain injuries due to advances in healthcare. However, many fail to emerge from coma and continue to live with disorders of consciousness (DOC). Diagnostic, clinical and ethical challenges are prominent in this group. Misdiagnosis can have severe consequences for children and their families, including inadequate care, insufficient access to rehabilitation and stimulation, reduced accessibility to services and inappropriately limited opportunities for participation. The proposed project will develop and validate a diagnostic measure that supports detailed goal-planning—the Music therapy Sensory Instrument for Cognition, Consciousness and Awareness (MuSICCA).Methods and analysisFace validity will be assessed using a short questionnaire and the MuSICCA will be amended if face validity is insufficient. Once face validity is sufficient, 80 participants with suspected DOC will be recruited from multiple sites around the UK, USA and Ireland.Validity will be assessed using external reference standards (Coma Recovery Scale-Revised, Coma Near-Coma Scale and Nociception Coma Scale). Intra-rater reliability will be established using repeated ratings of video recordings from the assessment sessions. Inter-rater reliability will be assessed through video ratings by a second blinded assessor. In addition to these analyses, the clinical utility of the MuSICCA will be evaluated using a questionnaire to be completed by clinicians and relatives of the participants following the completion of the MuSICCA assessment.Ethics and disseminationEthical approval has been obtained for this study from the Research Ethics Committee and Health Research Authority of the National Health Service of the UK (ID: 167534). Results will be presented at national and international conferences, published in scientific journals and disseminated to participant representatives, clinicians, educators and care providers.Trial registration detailsThis study was registered at ClinicalTrials.gov Protocol Registration and Results System on 7th August 2019 (ID: NCT04050995); Pre-results.
Simulation training in non-cancer palliative care for healthcare workers: a systematic review of controlled studies
Authors: Tropea Joanne , Bicknell Ross , Nestel Debra , Brand Caroline A , Johnson Christina E , Paul Sanjoy K , Le Brian H , Lim Wen Kwang 
Published: August 2020

BackgroundThe need for healthcare workers (HCWs) to have skills and knowledge in non-cancer palliative care has been recognised. Simulation is increasingly being used for palliative care training, offering participants the opportunity to learn in a realistic environment and fully interactive way.ObjectiveThe aim of this systematic review was to summarise and critically appraise controlled studies on simulation training in non-cancer palliative care for HCWs.SelectionMedline, CINAHL, PubMed and Cochrane Library databases were searched using palliative care and simulation terms. Randomised controlled trials (RCTs), non-randomised RCTs and controlled before-and-after (CBA) studies were included. Two reviewers independently screened titles and abstracts and undertook full article review using predefined selection criteria. Studies that met the inclusion criteria had data extracted and risk of bias assessed using the Cochrane Effective Practice and Organisation of Care risk of bias criteria.FindingsFive articles were included: three RCTs and two CBA studies. All studies assessed learners’ palliative care communication skills, most studies evaluated learners’ perception of change in skills and one study assessed impact on patient outcomes and learners’ change in behaviour when applied in practice. There was variation in intervention content, intensity and duration, outcome measures and study design, making it difficult to compare and synthesise results.ConclusionThere is a paucity of evidence to support simulation training to improve non-cancer palliative care. This review highlights the need for more robust research, including multicentre studies that use standardised outcome measures to assess clinician skills, changes in clinical practice and patient-related outcomes.
CDK1/2/5 inhibition overcomes IFNG-mediated adaptive immune resistance in pancreatic cancer
Authors: Huang Jin , Chen Pan , Liu Ke , Liu Jiao , Zhou Borong , Wu Runliu , Peng Qiu , Liu Ze-Xian , Li Changfeng , Kroemer Guido , Lotze Michael , Zeh Herbert , Kang Rui , Tang Daolin 
Published: August 2020

ObjectiveAdaptive immune resistance mediated by the cytokine interferon gamma (IFNG) still constitutes a major problem in cancer immunotherapy. We develop strategies for overcoming IFNG-mediated adaptive immune resistance in pancreatic ductal adenocarcinoma cancer (PDAC).DesignWe screened 429 kinase inhibitors for blocking IFNG-induced immune checkpoint (indoleamine 2,3-dioxygenase 1 (IDO1) and CD274) expression in a human PDAC cell line. We evaluated the ability of the cyclin-dependent kinase (CDK) inhibitor dinaciclib to block IFNG-inducedIDO1andCD274expression in 24 human and mouse cancer cell lines as well as in primary cancer cells from patients with PDAC or ovarian carcinoma. We tested the effects of dinaciclib on IFNG-induced signal transducer and activator of transcription 1 activation and immunological cell death, and investigated the potential utility of dinaciclib in combination with IFNG for pancreatic cancer therapy in vivo, and compared gene expression levels between human cancer tissues with patient survival times using the Cancer Genome Atlas datasets.ResultsPharmacological (using dinaciclib) or genetic (using shRNA or siRNA) inactivation of CDK1/2/5 not only blocks JUN-dependent immune checkpoint expression, but also triggers histone-dependent immunogenic cell death in immortalised or primary cancer cells in response to IFNG. This dual mechanism turns an immunologically ‘cold’ tumour microenvironment into a ‘hot’ one, dramatically improving overall survival rates in mouse pancreatic tumour models (subcutaneous, orthotopic and transgenic models). The abnormal expression of CDK1/2/5 and IDO1 was associated with poor patient survival in several cancer types, including PDAC.ConclusionCDK1/2/5 kinase activity is essential for IFNG-mediated cancer immunoevasion. CDK1/2/5 inhibition by dinaciclib provides a novel strategy to overcome IFNG-triggered acquired resistance in pancreatic tumour immunity.
Cost-effectiveness of cardiovascular imaging for stable coronary heart disease
Authors: Walker Simon , Cox Edward , Rothwell Ben , Berry Colin , McCann Gerry P , Bucciarelli-Ducci Chiara , Dall’Armellina Erica , Prasad Abhiram , Foley James Robert John , Mangion Kenneth , Bijsterveld Petra , Everett Colin , Stocken Deborah , Plein Sven , Greenwood John P , Sculpher Mark 
Published: August 2020

ObjectiveTo assess the cost-effectiveness of management strategies for patients presenting with chest pain and suspected coronary heart disease (CHD): (1) cardiovascular magnetic resonance (CMR); (2) myocardial perfusion scintigraphy (MPS); and (3) UK National Institute for Health and Care Excellence (NICE) guideline-guided care.MethodsUsing UK data for 1202 patients from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 trial, we conducted an economic evaluation to assess the cost-effectiveness of CMR, MPS and NICE guidelines. Health outcomes were expressed as quality-adjusted life-years (QALYs), and costs reflected UK pound sterling in 2016–2017. Cost-effectiveness results were presented as incremental cost-effectiveness ratios and incremental net health benefits overall and for low, medium and high pretest likelihood of CHD subgroups.ResultsCMR had the highest estimated QALY gain overall (2.21 (95% credible interval 2.15, 2.26) compared with 2.07 (1.92, 2.20) for NICE and 2.11 (2.01, 2.22) for MPS) and incurred comparable costs (overall £1625 (£1431, £1824) compared with £1753 (£1473, £2032) for NICE and £1768 (£1572, £1989) for MPS). Overall, CMR was the cost-effective strategy, being the dominant strategy (more effective, less costly) with incremental net health benefits per patient of 0.146 QALYs (−0.18, 0.406) compared with NICE guidelines at a cost-effectiveness threshold of £15 000 per QALY (93% probability of cost-effectiveness). Results were similar in the pretest likelihood subgroups.ConclusionsCMR-guided care is cost-effective overall and across all pretest likelihood subgroups, compared with MPS and NICE guidelines.
Residual risks of ischaemic stroke and systemic embolism among atrial fibrillation patients with anticoagulation: large-scale real-world data (F-CREATE project)
Authors: Maeda Toshiki , Nishi Takumi , Funakoshi Shunsuke , Tada Kazuhiro , Tsuji Masayoshi , Satoh Atsushi , Kawazoe Miki , Yoshimura Chikara , Arima Hisatomi 
Published: August 2020

ObjectiveAmong patients with atrial fibrillation, the risks of ischaemic stroke and systemic embolism (IS/SE) are high even with effective anticoagulation. Using large-scale, real-world data from Japan, this study aims to clarify residual risks of IS/SE attributable to modifiable risk factors among patients with atrial fibrillation who are taking oral anticoagulants.MethodsThe study design we employed was a retrospective cohort. Health check-ups and insurance claims data of Japanese health insurance companies were accumulated from January 2005 to June 2017. We identified 11 848 participants with atrial fibrillation who were on oral anticoagulants during the study period. We set the modifiable risk factors as hypertension, diabetes and dyslipidaemia. A Cox proportional hazards model was used to obtain the effects of the risk factors for IS/SE.ResultsDuring an average of 3 years’ follow-up, 200 cases of IS/SE occurred (incidence rate 0.57 per 100 person-years). In multivariable analyses, older age (65–74 vs <65 years; adjusted HR 2.02 (95% CI 1.49 to 2.73)), hypertension (adjusted HR 1.41 (1.04 to 1.92)) and dyslipidaemia (adjusted HR 1.46 (1.07 to 1.98)) were significantly associated with increased risk of IS/SE. Percentage of IS/SE risk attributable to modifiable risk factors (hypertension, diabetes and dyslipidaemia) was 30.0% (16.1% to 41.6%).ConclusionAmong patients with atrial fibrillation on anticoagulant therapy, approximately one-third of the residual risks were estimated to be attributable to modifiable risk factors such as hypertension, diabetes and dyslipidaemia.
Ageing trajectories of health—longitudinal opportunities and synergies (ATHLOS) Healthy Ageing Scale in adults from 16 international cohorts representing 38 countries worldwide
Authors: Critselis Elena , Panaretos Dimitris , Sánchez-Niubò Albert , Giné-Vázquez Iago , Ayuso-Mateos José Luis , Caballero Francisco Felix , de la Fuente Javier , Haro Josep Maria , Panagiotakos Demosthenes 
Published: August 2020

BackgroundUniform international measurement tools for assessing healthy ageing are currently lacking.ObjectivesThe study assessed the novel comprehensive global Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) Healthy Ageing Scale, using an Item Response Theory approach, for evaluating healthy ageing across populations.DesignPooled analysis of 16 international longitudinal studies.Setting38 countries in five continents.SubjectsInternational cohort (n=355 314), including 44.4% (n=153 597) males, aged (mean±SD) 61.7±11.5 years old.MethodsThe ATHLOS Healthy Ageing Scale (including 41 items related to intrinsic capacity and functional ability) was evaluated in a pooled international cohort (n=355 314 from 16 studies) according to gender, country of residence and age group. It was also assessed in a subset of eight cohorts with ≥3 waves of follow-up assessment. The independent samples t-test and Mann–Whitney test were applied for comparing normally and skewed continuous variables between groups, respectively.ResultsThe ATHLOS Scale (range: 12.49–68.84) had a mean (±SD) value of 50.2±10.0, with males and individuals >65 years old exhibiting higher and lower mean scores, respectively. Highest mean scores were detected in Switzerland, Japan and Denmark, while lowest in Ghana, India and Russia. When the ATHLOS Scale was evaluated in a subset of cohorts with ≥3 study waves, mean scores were significantly higher than those of the baseline cohort (mean scores in ≥3 study waves vs baseline: 51.6±9.4 vs 50.2±10.0; p<0.01).ConclusionsThe ATHLOS Healthy Ageing Scale may be adequately applied for assessing healthy ageing across populations.
Differential quantities of immune checkpoint-expressing CD8 T cells in soft tissue sarcoma subtypes
Authors: Klaver Yarne , Rijnders Maud , Oostvogels Astrid , Wijers Rebecca , Smid Marcel , Grünhagen Dirk , Verhoef Cornelis , Sleijfer Stefan , Lamers Cor , Debets Reno 
Published: August 2020

IntroductionLocal T-cell immunity is recognized for its contribution to the evolution and therapy response of various carcinomas. Here, we investigated characteristics of tumor-infiltrating lymphocytes (TILs), as well as T-cell evasive mechanisms in different soft tissue sarcoma (STS) subtypes.MethodsLiposarcoma, gastrointestinal stromal tumor (GIST), leiomyosarcoma, myxofibrosarcoma and pleomorphic sarcomas were assessed for T-cell numbers and phenotypes using flow cytometry. Next-generation sequencing was used to analyze T-cell receptor repertoire, mutational load, immune cell frequencies, and expression of immune-related genes.ResultsGIST, myxofibrosarcoma and pleomorphic sarcoma showed high numbers of CD8+ TILs, with GIST having the lowest fraction of effector memory T cells. These TILs coexpress the immune checkpoints PD1, TIM3, and LAG3 in myxofibrosarcoma and pleomorphic sarcoma, yet TILs coexpressing these checkpoints were near negligible in GIST. Fractions of dominant T-cell clones among STS subtypes were lowest in GIST and liposarcoma, whereas mutational load was relatively low in all STS subtypes. Furthermore, myeloid-derived cells and expression of the costimulatory ligands CD86, ICOS-L and 41BB-L were lowest in GIST when compared with other STS subtypes.ConclusionSTS subtypes differ with respect to number and phenotypical signs of antitumor responsiveness of CD8+ TILs. Notably, GIST, myxofibrosarcoma and pleomorphic sarcoma harbor high numbers of CD8+ T cells, yet in the GIST microenvironment, these T cells are less differentiated and non-exhausted, which is accompanied with a relatively low expression of costimulatory ligands.
Morbidity and mortality associated with sequential flow reduction embolization technique of cerebral arteriovenous malformations using n-butyl cyanoacrylate
Authors: See Alfred P , Mohammaden Mahmoud H , Rizko Mark , Stapleton Christopher J , Amin-Hanjani Sepideh , Charbel Fady T , Aletich Victor , Alaraj Ali 
Published: August 2020

BackgroundEndovascular embolization of cerebral arteriovenous malformations (AVM) with liquid n-butyl cyanoacrylate (n-BCA) serves multiple purposes including AVM occlusion and flow reduction in preparation for other treatment modalities. The objective was to study the clinical, structural, and angiographic factors affecting complications associated with AVM treatment by sequential n-BCA embolizations for nidal occlusion versus quantitative flow reduction in preparation for surgical resection or radiosurgery.MethodsWe performed a retrospective review of all patients who underwent endovascular embolization of cerebral AVM at our institution between 1998 and 2019, during which time the technique of traditional embolization evolved to a strategy of targeted sequential flow reduction guided by serial flow imaging based on quantitative magnetic resonance angiography, in conjunction with a shift away from nidal penetration.ResultsAmong 251 patients, 47.8% of patients presented with ruptured AVM. On average, each patient underwent 2.4 embolizations, for a total of 613 sessions. Major morbidity related to embolization occurred in 18 (7.2%) patients, but this occurred disproportionately in the traditional embolization strategy (n=16, 8%) in contrast with the flow-targeting strategy (n=2, 3.8%). Four patients (1.6%) died in the overall group, and these all occurred with the traditional embolization strategy (2% of 199 patients); no deaths occurred in the flow-targeting strategy (n=52).ConclusionEmbolization with n-BCA targeted to sequential flow reduction and feeder occlusion with limited nidal penetration prior to definitive surgical or radiosurgical treatment can be safely performed with low overall morbidity and mortality.
Cardiovascular drug treatment, statins and biopsy-confirmed giant cell arteritis: a population-based case–control study
Authors: Turkiewicz Aleksandra , Stamatis Pavlos , Mohammad Aladdin J 
Published: August 2020

ObjectiveTo determine whether exposure to cardiovascular medications and statins is associated with increased risk of giant cell arteritis (GCA).DesignThe population-based case–control study comprised a cohort of patients with biopsy-confirmed GCA linked to the Swedish Prescribed Drug Register to identify all exposure to drugs prior to diagnosis of GCA. Ten controls per GCA case, matched for age, sex and residential area, were included. Using corresponding Anatomical Therapeutic Chemical codes, ACE inhibitors, angiotensin II receptor blockers, beta-blocking agents, calcium antagonists, diuretics, statins and cardiac therapy drugs were investigated from July 1, 2005 to the diagnosis/index date. A conditional logistic regression model was fitted adjusted for income, education level and marital status. We repeated the analyses including only new drug users excluding those with any prescription during the year from July 1, 2005 to July 1, 2006.Results574 cases (29% men) of diagnosed GCA and 5740 controls (29% men) were included. The mean age at diagnosis is 75 years (SD 8). Of the GCA cases, 71% had at least one dispensation of a cardiovascular drug prior to the index date, compared to 74% of controls. The ORs for the association of target drug exposure with GCA were <1 for most drugs, but close to 1 in the analysis of new users. Statins were consistently associated with lower risk of GCA, OR 0.74 (95% CI 0.61 to 0.90).ConclusionStatins may be associated with lower risk of incident biopsy-confirmed GCA. No association was evident for other studied drugs.
Differences in atheroma between Caucasian and Asian subjects with anterior stroke: A vessel wall MRI study
Authors: Watase Hiroko , Shen Mi , Sui Binbin , Gao Peiyi , Zhang Dong , Sun Jie , Balu Niranjan , Hippe Daniel S , Jarvik Gail P , Zhao Xihai , Li Rui , Chen Shuo , Yuan Chun , Hatsukami Thomas S 
Published: August 2020

Background and purposeWhile extracranial carotid artery stenosis is more common among Caucasians and intracranial artery stenosis is more common among Asians, the differences in atherosclerotic plaque characteristics have not yet been extensively examined. We sought to investigate plaque location and characteristics within extracranial carotid and intracranial arteries in symptomatic Caucasians and Chinese using vessel wall MRI.MethodsSubjects with recent anterior circulation ischaemic stroke were recruited and imaged at two sites in the USA and China using similar protocols. Both extracranial carotid and intracranial arteries were reviewed to determine plaque location and characteristics.ResultsThe prevalence of extracranial carotid plaque in Caucasians and Chinese was 73.1% and 49.1%, respectively (p=0.055). Prevalence of intracranial plaque was 38.5% and 69.1% in Caucasians and Chinese, respectively (p=0.02). Furthermore, 42% of Caucasians and 16% of Chinese had high-risk plaque (HRP) features (intraplaque haemorrhage, luminal surface disruption) in the extracranial carotid artery (p=0.03). The prevalence of HRP features in intracranial arteries was not significantly different between the two cohorts (4% vs 11%; p=0.42).ConclusionsDifferences in the location and characteristics of cerebrovascular atherosclerosis were identified by vessel wall MRI in US Caucasian and Chinese subjects with recent anterior circulation ischaemic stroke. Extracranial carotid plaques with HRP features were more common in Caucasians. Intracranial plaques were more common in Chinese subjects, but no significant difference between the two cohorts in intracranial HRP prevalence was found. Larger studies using vessel wall imaging to investigate racial differences in cerebrovascular disease may inform underlying mechanisms of HRP development and may ultimately help guide appropriate therapy.