bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overcoming insomnia: protocol for a large-scale randomised controlled trial of online cognitive behaviour therapy for insomnia compared with online patient education about sleep
Authors: Kallestad Håvard , Vedaa Øystein , Scott Jan , Morken Gunnar , Pallesen Ståle , Harvey Allison G , Gehrman Phil , Thorndike Frances , Ritterband Lee , Stiles Tore Charles , Sivertsen Børge 
Published: August 2018

IntroductionInsomnia is a major public health concern. While cognitive behaviour therapy for insomnia (CBT-I) is acknowledged as the best available intervention, there are unanswered questions about its wider dissemination, socioeconomic benefits and its impact on health resource utilisation. The aim of this randomised controlled trial (RCT) is to investigate the effectiveness of a fully automated online version of CBT-I compared with online patient education about sleep (PE). Outcome measures comprise changes in symptoms of insomnia, time off work due to sick leave as well as medication and health resource utilisation. Also, we will examine (i) putative mediators of the effects of CBT-I on insomnia severity and (ii) selected potential psycho-bio-social moderators of the effects of the interventions.Methods and analysisA parallel-group RCT will be conducted in a target sample of about 1500 adults recruited across Norway. Participants will complete an online screening and consent process. Those who meet eligibility criteria will be randomised to receive direct access to fully automated online CBT-I or to an online PE programme. The primary outcome is change in insomnia severity immediately postintervention; secondary outcomes are change in daytime functioning and other sleep measures postintervention and at 6-month and 24-month follow-up. Objective data from national registries will be obtained at two time points (1 year and 2 years post-treatment), allowing a mirror image study of preintervention and postintervention rates of sick leave, and of medication and healthcare utilisation by condition.Ethics and disseminationThe study protocol was approved by the Regional Committee for Medical and Health Research Ethics in South East Norway (2015/134). Findings from the RCT will be disseminated in peer-reviewed publications and conference presentations. Exploratory analyses of potential mediators and moderators will be reported separately. User-friendly outputs will be disseminated to patient advocacy and other relevant organisations.Trial registration numberNCT02558647; Pre-results.
‘Take a Mental Break!’ study: Role of mental aspects in running-related injuries using a randomised controlled trial
Authors: de Jonge Jan , van Iperen Luuk , Gevers Josette , Vos Steven 
Published: August 2018

BackgroundRunning-related injuries (RRIs) can be considered the primary enemy of runners. Most literature on injury prediction and prevention overlooks the mental aspects of overtraining and under-recovery, despite their potential role in injury prediction and prevention. Consequently, knowledge on the role of mental aspects in RRIs is lacking.ObjectiveTo investigate mental aspects of overtraining and under-recovery by means of an online injury prevention programme.Methods and analysisThe ‘Take a Mental Break!’ study is a randomised controlled trial with a 12 month follow-up. After completing a web-based baseline survey, half and full marathon runners were randomly assigned to the intervention group or the control group. Participants of the intervention group obtained access to an online injury prevention programme, consisting of a running-related smartphone application. This app provided the participants of the intervention group with information on how to prevent overtraining and RRIs with special attention to mental aspects. The primary outcome measure is any self-reported RRI over the past 12 months. Secondary outcome measures include vigour, fatigue, sleep and perceived running performance. Regression analysis will be conducted to investigate whether the injury prevention programme has led to a lower prevalence of RRIs, better health and improved perceived running performance.Ethics and disseminationThe Medical Ethics Committee of the University Medical Center Utrecht, the Netherlands, has exempted the current study from ethical approval (reference number: NL64342.041.17). Results of the study will be communicated through scientific articles in peer-reviewed journals, scientific reports and presentations on scientific conferences.
Y-configuration stenting for coiling of wide-neck bifurcation aneurysms using Low-profile Visualized Intraluminal Support Junior
Authors: Park Keun Young , Kim Byung Moon , Kim Dong Joon , Chung Joonho , Lee Jae Whan 
Published: August 2018

BackgroundLittle has been reported about the feasibility and durability of a Low-profile Visualized Intraluminal Support Junior (LVIS Jr) Y-stenting device for wide-neck bifurcation aneurysms.PurposeTo evaluate the feasibility and durability of LVIS Jr Y-stenting for coiling of unruptured wide-neck bifurcation aneurysms.MethodsWe identified patients in whom LVIS Jr Y-stenting was attempted for unruptured wide-neck bifurcation aneurysms from a prospectively maintained registry of a referral hospital. Procedural success rate, treatment-related morbidity, and clinical and angiographic outcomes were retrospectively assessed.ResultsLVIS Jr Y-stenting was attempted for a total of 21 aneurysms in 21 patients (mean age 60±8.9 years; M:F=6:15): nine basilar artery, six anterior communicating artery, four middle cerebral artery, one internal carotid artery, and one vertebrobasilar fenestration aneurysms. The mean dome and neck size were 7.9±2.7 mm and 5.7±1.8 mm, respectively. All attempts were successful. Treatment-related morbidity occurred in one individual with a modified Rankin Scale (mRS) score of 2. Immediate postprocedural angiograms showed complete occlusion in 15 (71.4%) and neck remnant in 6 (28.6%) patients. All 21 patients had good outcomes (mRS score 0–2) for a mean of 12 months' follow-up (range 6–27 months); mRS score 0 in 20 patients and mRS score 2 in one patient, respectively. Follow-up imaging over a mean of 11 months (range 6–18 months) was available in 18 patients (85.7%). All aneurysms showed complete occlusion at follow-up.ConclusionsLVIS Jr Y-stenting and coiling for wide-neck bifurcation aneurysms seems to be feasible with acceptable safety and to provide durable aneurysm occlusion for wide-neck bifurcation aneurysms.
Presentation and outcomes of patients with thoracic and lumbosacral spinal epidural arteriovenous fistulas: a systematic review and meta-analysis
Authors: Byun Jun-Soo , Tsang Anderson Chun On , Hilditch Christopher Alan , Nicholson Patrick , Fang Yi-Bin , Krings Timo , Pereira Vitor Mendes , Lanzino Giuseppe , Brinjikji Waleed 
Published: August 2018

Background and purposeThoracolumbar and sacral spinal epidural arteriovenous fistulas (SEDAVFs) are an increasingly recognized form of spinal vascular malformation. The purpose of this study was to perform a systematic review of the demographics, clinical presentation and treatment results of thoracolumbar SEDAVFs.Materials and methodsPubmed, Scopus and Web of Science databases were searched from January 2000 to January 2018 for articles on treatment of SEDAVFs. Pooled data of individual patients were analyzed for demographic and clinical features of SEDAVFs as well as treatment outcomes.ResultsThere were 125 patients from 11 studies included. Mean age was 63.5 years. There was a male sex predilection (69.6%). Sensory symptoms including pain or numbness were the most frequently presenting symptoms. Fistula location was the lumbosacral spine in 79.2% and the thoracic spine in 20.8%. Involvement of intradural venous drainage was more common than extradural venous drainage only (89.6% vs 10.4%). Of the 123 treated patients, endovascular therapy was performed in 67.5% of patients, microsurgery in 23.6%, and combined treatment in 8.9%. The overall complete obliteration rate was 83.5% and did not differ between groups. Clinical symptoms improved in 70.7% of patients, were stable in 25%, and worsened in 1.7% with no difference between treatment modalities.ConclusionsThoracic and lumbosacral SEDAVFs often present with symptoms secondary to congestive myelopathy or compressive symptoms. Both endovascular and microsurgical treatments were associated with high obliteration rates and good clinical outcomes.
Open questions concerning antiautomorphisms of division rings with quasi-generalized Engel conditions
Authors: Chacron M. , Lee T.-K. 
Published: August 2018

Let [Formula: see text] be a noncommutative division ring with center [Formula: see text], which is algebraic, that is, [Formula: see text] is an algebraic algebra over the field [Formula: see text]. Let [Formula: see text] be an antiautomorphism of [Formula: see text] such that (i) [Formula: see text], all [Formula: see text], where [Formula: see text] and [Formula: see text] are positive integers depending on [Formula: see text]. If, further, [Formula: see text] has finite order, it was shown in [M. Chacron, Antiautomorphisms with quasi-generalised Engel condition, J. Algebra Appl. 17(8) (2018) 1850145 (19 pages)] that [Formula: see text] is commuting, that is, [Formula: see text], all [Formula: see text]. Posed in [M. Chacron, Antiautomorphisms with quasi-generalised Engel condition, J. Algebra Appl. 17(8) (2018) 1850145 (19 pages)] is the question which asks as to whether the finite order requirement on [Formula: see text] can be dropped. We provide here an affirmative answer to the question. The second major result of this paper is concerned with a nonnecessarily algebraic division ring [Formula: see text] with an antiautomorphism [Formula: see text] satisfying the stronger condition (ii) [Formula: see text], all [Formula: see text], where [Formula: see text] and [Formula: see text] are fixed positive integers. It was shown in [T.-K. Lee, Anti-automorphisms satisfying an Engel condition, Comm. Algebra 45(9) (2017) 4030–4036] that if, further, [Formula: see text] has finite order then [Formula: see text] is commuting. We show here, that again the finite order assumption on [Formula: see text] can be lifted answering thus in the affirmative the open question (see Question 2.11 in [T.-K. Lee, Anti-automorphisms satisfying an Engel condition, Comm. Algebra 45(9) (2017) 4030–4036]).
Ontology-Mediated Queries
Authors: Bienvenu Meghyn , Kikot Stanislav , Kontchakov Roman , Podolskii Vladimir V. , Zakharyaschev Michael 
Published: August 2018

We give solutions to two fundamental computational problems in ontology-based data access with the W3C standard ontology language
OWL 2 QL
: the succinctness problem for first-order rewritings of ontology-mediated queries (OMQs) and the complexity problem for OMQ answering. We classify OMQs according to the shape of their conjunctive queries (treewidth, the number of leaves) and the existential depth of their ontologies. For each of these classes, we determine the combined complexity of OMQ answering and whether all OMQs in the class have polynomial-size first-order, positive existential, and nonrecursive datalog rewritings. We obtain the succinctness results using hypergraph programs, a new computational model for Boolean functions, which makes it possible to connect the size of OMQ rewritings and circuit complexity.
Intestinal bile acid sequestration improves glucose control by stimulating hepatic miR-182-5p in type 2 diabetes
Authors: Sedgeman Leslie R. , Beysen Carine , Allen Ryan M. , Ramirez Solano Marisol A. , Turner Scott M. , Vickers Kasey C. 
Published: August 2018

Colesevelam is a bile acid sequestrant approved to treat both hyperlipidemia and type 2 diabetes, but the mechanism for its glucose-lowering effects is not fully understood. The aim of this study was to investigate the role of hepatic microRNAs (miRNAs) as regulators of metabolic disease and to investigate the link between the cholesterol and glucose-lowering effects of colesevelam. To quantify the impact of colesevelam treatment in rodent models of diabetes, metabolic studies were performed in Zucker diabetic fatty (ZDF) rats and db/db mice. Colesevelam treatments significantly decreased plasma glucose levels and increased glycolysis in the absence of changes to insulin levels in ZDF rats and db/db mice. High-throughput sequencing and real-time PCR were used to quantify hepatic miRNA and mRNA changes, and the cholesterol-sensitive miR-96/182/183 cluster was found to be significantly increased in livers from ZDF rats treated with colesevelam compared with vehicle controls. Inhibition of miR-182 in vivo attenuated colesevelam-mediated improvements to glycemic control in db/db mice. Hepatic expression of mediator complex subunit 1 (MED1), a nuclear receptor coactivator, was significantly decreased with colesevelam treatments in db/db mice, and MED1 was experimentally validated to be a direct target of miR-96/182/183 in humans and mice. In summary, these results support that colesevelam likely improves glycemic control through hepatic miR-182–5p, a mechanism that directly links cholesterol and glucose metabolism. NEW & NOTEWORTHY Colesevelam lowers systemic glucose levels in Zucker diabetic fatty rats and db/db mice and increases hepatic levels of the sterol response element binding protein 2-responsive microRNA cluster miR-96/182/183. Inhibition of miR-182 in vivo reverses the glucose-lowering effects of colesevelam in db/db mice. Mediator complex subunit 1 (MED1) is a novel, direct target of the miR-96/182/183 cluster in mice and humans.
Measuring length-tension function of the anal sphincters and puborectalis muscle using the functional luminal imaging probe
Authors: Tuttle Lori J. , Zifan Ali , Sun Catherine , Swartz Jessica , Roalkvam Sophia , Mittal Ravinder K. 
Published: August 2018

The functional luminal imaging probe (FLIP) has been used to measure the distensibility of the anal canal. We hypothesized that with increasing distension of the anal canal with FLIP there will be an increase in length of the anal sphincter muscle allowing measurement of the length-tension function of anal sphincter and puborectalis muscles (PRM). We studied 14 healthy nulliparous women. A custom-designed FLIP bag (30-mm diameter) was placed in the vagina and then in the anal canal, distended in 10-ml steps with volumes ranging from 30 to 90 ml. At each volume, subject performed maximal voluntary squeezes. Length-tension measurements were also made with a manometric probe system. Tension was calculated (pressure × radius) in Newtons per meter using a custom software program. Peak tensions at different FLIP volumes were compared with the manometric data. No change in the luminal CSA was noted at low fluid volumes; the sphincter muscles were able to fully collapse the FLIP bag within the anal canal/vagina even at rest. At larger volumes, with each squeeze there was an increase in the bag pressure and reduction in the cross-sectional area, which represents concentric contraction of the muscle. Both rest and squeeze tension increased with the increase in volume in the anal as well as vaginal canal indicating that the external anal sphincter and puborectalis muscles produce more tension when lengthened. FLIP device, which has been used to describe the distensibility of the anal canal can also provide information on the length-tension function of the anal sphincters and PRM. NEW & NOTEWORTHY The functional luminal imaging probe (FLIP) has been used to describe the distensibility of the anal canal. This report is the first to describe the use of the FLIP in the vaginal canal and the anal canal to provide information on the length-tension function of the anal sphincter and puborectalis muscles, which may provide clinicians with additional information regarding the active components of muscle contraction involved in the anal closure function.
Daytime loop gain is elevated in obstructive sleep apnea but not reduced by CPAP treatment
Authors: Deacon-Diaz Naomi Louise , Sands Scott A. , McEvoy R. Doug , Catcheside Peter G. 
Published: August 2018

Reduced ventilatory control stability (elevated loop gain) is a key nonanatomical, pathological trait contributing to obstructive sleep apnea (OSA), yet the mechanisms responsible remain unclear. We sought to identify the key factors contributing to elevated loop gain in OSA (controller vs. plant contributions) and to examine whether abnormalities in these factors persist after OSA treatment. In 15 males (8 OSA, 7 height, weight- and age -matched controls), we measured loop gain, controller gain, and plant gain using a pseudorandom binary CO2 stimulation method during wakefulness. Factors potentially influencing plant gain were also assessed (supine lung volume via helium dilution and spirometry). Measures were repeated 2 and 6 wk after initiating continuous positive airway pressure treatment. Loop gain (LG) was higher in OSA versus controls (LG at 1 cycle/min 0.28 ± 0.04 vs. 0.16 ± 0.04, P = 0.046, respectively), and the controller exhibited a greater peak response to CO2 and faster roll-off in OSA. OSA patients also exhibited reduced forced expiratory volume in the first second and forced vital capacity compared with controls (92.2 ± 1.7 vs. 102.9 ± 3.5% predicted, P = 0.021; 93.4 ± 3.1 vs. 106.6 ± 3.6% predicted, P = 0.015, respectively). There was no effect of treatment on any variable. These findings confirm loop gain is higher in untreated OSA patients than in matched controls; however, this was not affected by treatment. NEW & NOTEWORTHY Elevated loop gain contributes to obstructive sleep apnea (OSA) pathophysiology. However, whether loop gain is inherently elevated in OSA or induced by OSA itself, whether it is elevated due to increased chemoreflex sensitivity or obesity-dependent reduced lung volume, and whether it is treatment reversible, are all currently uncertain. This study found loop gain was elevated in OSA versus age-, sex-, height-, and weight-matched controls. However, this was not altered by 6-wk continuous positive airway pressure treatment.
Training state and skeletal muscle autophagy in response to 36 h of fasting
Authors: Dethlefsen Maja Munk , Bertholdt Lærke , Gudiksen Anders , Stankiewicz Tomasz , Bangsbo Jens , van Hall Gerrit , Plomgaard Peter , Pilegaard Henriette 
Published: August 2018

The present study aimed at investigating fasting-induced responses in regulators and markers of autophagy in vastus lateralis muscle from untrained and trained human subjects. Untrained and trained subjects (based on maximum oxygen uptake, muscle citrate synthase activity, and oxidative phosphorylation protein level) fasted for 36 h with vastus lateralis muscle biopsies obtained at 2, 12, 24, and 36 h after a standardized meal. Fasting reduced ( P < 0.05) skeletal muscle microtubule-associated protein-1A/1B light chain 3 (LC3)I, LC3II, and adaptor protein sequestosome 1/p62 protein content in untrained subjects only. Moreover, skeletal muscle RAC-alpha serine/threonine-protein kinase (AKT)Thr308, AMP-activated protein kinase (AMPK)Thr172, and Unc-51-like autophagy-activating kinase-1 (ULK1)Ser555 phosphorylation state, as well as Bcl-2-interacting coiled-coil protein-1 (Beclin1) and ULK1Ser757 phosphorylation, was lower ( P < 0.05) in trained than untrained subjects during fasting. In addition, the plasma concentrations of several amino acids were higher ( P < 0.05) in trained than untrained subjects, and the plasma concentration profile of several amino acids was different in untrained and trained subjects during fasting. Taken together, these findings suggest that 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle and that training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle. NEW & NOTEWORTHY This study showed that skeletal muscle autophagy was only modestly affected in humans by 36 h of fasting. Hence, 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle, and training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle.
ATR Inhibition Is a Promising Radiosensitizing Strategy for Triple-Negative Breast Cancer
Authors: Tu Xinyi , Kahila Mohamed M. , Zhou Qin , Yu Jia , Kalari Krishna R. , Wang Liewei , Harmsen William S. , Yuan Jian , Boughey Judy C. , Goetz Matthew P. , Sarkaria Jann N. , Lou Zhenkun , Mutter Robert W. 
Published: August 2018

Abstract
Triple-negative breast cancer (TNBC) is characterized by elevated locoregional recurrence risk despite aggressive local therapies. New tumor-specific radiosensitizers are needed. We hypothesized that the ATR inhibitor, VX-970 (now known as M6620), would preferentially radiosensitize TNBC. Noncancerous breast epithelial and TNBC cell lines were investigated in clonogenic survival, cell cycle, and DNA damage signaling and repair assays. In addition, patient-derived xenograft (PDX) models generated prospectively as part of a neoadjuvant chemotherapy study from either baseline tumor biopsies or surgical specimens with chemoresistant residual disease were assessed for sensitivity to fractionated radiotherapy, VX-970, or the combination. To explore potential response biomarkers, exome sequencing was assessed for germline and/or somatic alterations in homologous recombination (HR) genes and other alterations associated with ATR inhibitor sensitivity. VX-970 preferentially inhibited ATR-Chk1-CDC25a signaling, abrogated the radiotherapy-induced G2–M checkpoint, delayed resolution of DNA double-strand breaks, and reduced colony formation after radiotherapy in TNBC cells relative to normal-like breast epithelial cells. In vivo, VX-970 did not exhibit significant single-agent activity at the dose administered even in the context of genomic alterations predictive of ATR inhibitor responsiveness, but significantly sensitized TNBC PDXs to radiotherapy. Exome sequencing and functional testing demonstrated that combination therapy was effective in both HR-proficient and -deficient models. PDXs established from patients with chemoresistant TNBC were also highly radiosensitized. In conclusion, VX-970 is a tumor-specific radiosensitizer for TNBC. Patients with residual TNBC after neoadjuvant chemotherapy, a subset at particularly high risk of relapse, may be ideally suited for this treatment intensification strategy. Mol Cancer Ther; 17(11); 2462–72. ©2018 AACR.