bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomised clinical trial: a leucine‐metformin‐sildenafil combination (NS‐0200) vs placebo in patients with non‐alcoholic fatty liver disease
Authors: Chalasani N. , Vuppalanchi R. , Rinella M. , Middleton M. S. , Siddiqui M. S. , Barritt A. S. , Kolterman O. , Flores O. , Alonso C. , Iruarrizaga‐Lejarreta M. , Gil‐Redondo R. , Sirlin C. B. , Zemel M. B. 
Published: April 2018

SummaryBackgroundSirtuin 1 (Sirt1) is suppressed in non‐alcoholic fatty liver disease (NAFLD), while its’ stimulation or overexpression results in reduced disease severity in pre‐clinical NAFLD models. Leucine allosterically activates Sirt1 and synergise with other Sirt/AMPK/NO pathway activators. We developed a triple combination of leucine, metformin and sildenafil (NS‐0200), which was effective in a mouse model of non‐alcoholic steatohepatitis (NASH).AimTo report the results from a Phase 2, randomised clinical trial of of NS‐0200 in 91 subjects with NAFLD (liver fat ≥15% by magnetic resonance imaging‐proton‐density fat fraction (MRI‐PDFF)).MethodsSubjects were randomised to placebo, low‐dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil) or high‐dose NS‐0200 (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) b.d. for 16 weeks; change in hepatic fat was assessed via MRI‐PDFF, and lipid metabolism was assessed via changes in the lipidomic signature. Seventy subjects completed the trial and met a priori compliance criteria. Analyses were conducted on the full cohort and on those with alanine aminotransferase (ALT) values above median (50 U/L; n = 35).ResultsIn the full cohort, active treatments did not separate from placebo. High dose NS‐0200 reduced hepatic fat by 15.7% (relative change from baseline) in the high ALT group (P < 0.005) while low dose NS‐0200 and placebo did not significantly change hepatic fat. Lipidomic analysis showed dose‐responsive treatment effects in both overall and high ALT cohorts, with significant decreases in metabolically active lipids and up‐regulation of fatty acid oxidation.ConclusionThese data support further evaluation of high‐dose NS‐0200 for treating NASH, especially in those with elevated ALT (NCT 02546609).
A pilot single arm observational study of sofosbuvir/ledipasvir (200 + 45 mg) in 6‐ to 12‐ year old children
Authors: El‐Shabrawi M. H. F. , Kamal N. M. , El‐Khayat H. R. , Kamal E. M. , AbdElgawad M. M. A. H. , Yakoot M. 
Published: April 2018

SummaryBackgroundNo available data on the use of sofosbuvir/ledipasvir combination in treatment of hepatitis C virus (HCV) infection in children 6‐ to 12‐ year old.AimTo assess the safety and efficacy of sofosbuvir plus ledipasvir in children 6‐ to 12‐ year old with chronic HCV genotype 4 infection.MethodsThis is a pilot prospective single arm observational open‐label multicentre study. A total of 20 consecutive eligible chronic HCV infected children, aged from 6‐ to 12‐ years were included in this study and treated with a fixed sofosbuvir/ledipasvir combination in half the adult dose (200/45 mg) once daily for 12 weeks. Laboratory tests including virological markers were measured at baseline, 2, 4, 8 and 12 weeks (end of treatment [EOT]), and 12 weeks after end of treatment for sustained virological response 12 (SVR12).ResultsThe intention‐to‐treat (ITT) SVR12 rate was 19/20 (95%; 95% CI: 76.4%‐99.1%). SVR12 was not assessed in one patient who was lost to follow‐up after showing viral negativity at the EOT12. All the remaining 19 patients (100%, 95% CI: 83.18%‐100%) who completed the full protocol and follow‐up visits achieved SVR12 with normal liver, haematological, and renal function tests and no side effects or fatalities.ConclusionsThis pilot study demonstrated that the fixed dose sofosbuvir/ledipasvir combination could be safe and effective treatment in children 6‐ to 12‐ years with chronic hepatitis C genotype 4 infection. Our pilot results might encourage larger and multicentre studies in this age group.
Does the Reporting Location of Other Comprehensive Income Matter? The Investor's Perspective
Authors: Wang Xin , Jiang Haiyan , Lu Meiting 
Published: April 2018

AbstractIn the context of changes mandated by the Chinese Ministry of Finance in January 2009 regarding the location in which other comprehensive income (OCI) is reported, this paper finds that reporting OCI on the performance statement significantly improves its value relevance. The improvement is driven by two OCI items: unrealised holding gains/losses on available‐for‐sale securities and the share of other comprehensive income of investees under the equity method. Our results show that the OCI reporting location matters, which supports the psychological perspective that investors pay more attention to salient information. Our findings lend strong support to the approach of standard setters in reporting OCI on the performance statement.
The Value Relevance of Operating Lease Liabilities: Economic Effects of IFRS 16
Authors: Giner Begoña , Pardo Francisca 
Published: April 2018

AbstractThe new IASB and FASB models for leases aim to improve the quality of financial reporting. To this end, both standard setters impose the recognition of assets and liabilities for operating leases. Meanwhile, preparers have been strongly lobbying against these changes, as in their view the new treatment will lead to negative economic consequences. We undertake a value‐relevance study to examine whether as‐if capitalised operating leases are priced by market users in a relatively unexplored setting. We consider Spanish listed firms, and employ hand‐collected data on operating leases disclosed in the notes to the financial statements to constructively capitalise the assets and liabilities. Our analysis suggests that investors in code‐law countries with less developed markets and low enforcement quality do not behave any differently to those in common‐law countries that have more developed markets and stricter enforcement policies. Investors equally value recognised debts and operating lease liabilities resulting from information in the notes in retail sectors. In our view, these results could provide some comfort to managers in the most affected industries, as they suggest the change will not have a major impact on the stock exchange.
Current use of monoclonal antibodies in the treatment of multiple myeloma
Authors: Varga Cindy , Maglio Michelle , Ghobrial Irene M. , Richardson Paul G. 
Published: April 2018

SummaryMultiple myeloma (MM) is the second most common haematological malignancy after non‐Hodgkin lymphoma. Despite the improvement in outcomes over the last decade with the introduction of novel therapies, such as immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs), MM remains an incurable disease. Patients who are both refractory to IMiDs and PIs carry a particularly dismal prognosis. The development of targeted therapy in the form of monoclonal antibodies has shifted the treatment paradigm of this disease, resulting in unprecedented response rates, even among the highest‐risk patients. In this review, we will summarize the mechanism of action and provide an overview of the clinical trials that have led to the US Food and Drug Administration approval of Daratumumab and Elotuzumab, and their current use in the treatment of MM.
National implementation of multi‐parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting
Authors: Brizmohun Appayya Mrishta , Adshead Jim , Ahmed Hashim U. , Allen Clare , Bainbridge Alan , Barrett Tristan , Giganti Francesco , Graham John , Haslam Phil , Johnston Edward W. , Kastner Christof , Kirkham Alexander P.S. , Lipton Alexandra , McNeill Alan , Moniz Larissa , Moore Caroline M. , Nabi Ghulam , Padhani Anwar R. , Parker Chris , Patel Amit , Pursey Jacqueline , Richenberg Jonathan , Staffurth John , van der Meulen Jan , Walls Darren , Punwani Shonit 
Published: April 2018

ObjectivesTo identify areas of agreement and disagreement in the implementation of multi‐parametric magnetic resonance imaging (mpMRI) of the prostate in the diagnostic pathway.Materials and MethodsFifteen UK experts in prostate mpMRI and/or prostate cancer management across the UK (involving nine NHS centres to provide for geographical spread) participated in a consensus meeting following the Research and Development Corporation and University of California‐Los Angeles (UCLA‐RAND) Appropriateness Method, and were moderated by an independent chair. The experts considered 354 items pertaining to who can request an mpMRI, prostate mpMRI protocol, reporting guidelines, training, quality assurance (QA) and patient management based on mpMRI levels of suspicion for cancer. Each item was rated for agreement on a 9‐point scale. A panel median score of ≥7 constituted ‘agreement’ for an item; for an item to reach ‘consensus’, a panel majority scoring was required.ResultsConsensus was reached on 59% of items (208/354); these were used to provide recommendations for the implementation of prostate mpMRI in the UK. Key findings include prostate mpMRI requests should be made in consultation with the urological team; mpMRI scanners should undergo QA checks to guarantee consistently high diagnostic quality scans; scans should only be reported by trained and experienced radiologists to ensure that men with unsuspicious prostate mpMRI might consider avoiding an immediate biopsy.ConclusionsOur consensus statements demonstrate a set of criteria that are required for the practical dissemination of consistently high‐quality prostate mpMRI as a diagnostic test before biopsy in men at risk.
Family caregivers of people who have intellectual/developmental disabilities and asthma: Caregiver knowledge of asthma self‐management concepts—A pilot study
Authors: Erickson Steven R. , Juncaj Sophia , Buckley Charlotte 
Published: April 2018

Accessible Summary

Asthma is a problem for many people.

Some people need help with their medicines for asthma.

People who help with medicines should know how medicines work and how they are used.

This study found that many helpers need more education about asthma medicines.

AbstractBackgroundPeople who have an intellectual or developmental disability (IDD) and asthma are at greater risk of poor health outcomes. They often require assistance from caregivers when managing their medicines. The objective of this pilot study was to assess the level of understanding of asthma self‐management concepts of family caregivers who provide assistance to people who IDD and asthma. Results will inform future needs assessment and intervention studies.Materials and MethodsNineteen caregivers of people who have asthma and IDD completed a mailed survey. The survey included scales to measure asthma self‐management concepts, inhaler technique knowledge, medication adherence and control of asthma. The caregivers were instructed to complete most of the scales with reference to the person with IDD.ResultsMost caregivers had acceptable health literacy, but had low scores on the asthma self‐management and inhaler technique tests. The most frequently cited barriers to controlling asthma were inadequate caregiver and patient education about the illness as well as knowing and avoiding asthma triggers. The most frequently cited barriers to medication management were knowing inhaler technique, knowledge of medication and forgetting to use medication. Asthma was controlled in 63.2% of patients, while almost 75% of patients were considered nonadherent to controller therapy.ConclusionsMost caregivers had inadequate understanding of asthma self‐management as well as inhaler technique despite having high health literacy. Improving caregiver and patient knowledge and skills may lead to better asthma control.
Components of responsibility in estimating relative value units: How do dentists value their work?
Authors: Brennan DS , Ju X , Teusner DN 
Published: April 2018

AbstractObjectivesResponsibility weights can translate services into a common scale of work effort (relative value units). The aims were to describe the responsibility weights for main areas of dental services and assess associations of ratings of the importance of the components of responsibility with responsibility weights.MethodsMailed questionnaires were used to collect responsibility weights and components of responsibility from a random sample of Australian dentists who were randomly assigned into panels. Across the panels, weights were elicited for 299 service items from 9 service areas. Data were weighted to the age and sex distribution of the workforce. Ordered logit regression models assessed differences in weights by ratings of importance of the 8 components of responsibility.ResultsResponses were collected from 846 dentists (response rate = 37%). Adjusted models showed that, with the exception of general/miscellaneous services, all remaining service areas were associated with between 3 and 7 components. Preventive weights were associated with dexterity and mental effort but negatively with perception. Diagnostic weights were associated with knowledge, judgement, experience, perception, physical and mental effort, and negatively with dexterity. Ratings of components of responsibility were associated with responsibility weights and showed varying patterns across service areas. Mental effort, invasiveness, dexterity, experience and knowledge were associated with responsibility weights in the majority of service areas.ConclusionsThe observed variation in weights across service areas showed that dentists discriminated between services in a systematic and cognizant manner and so provided broad validation of weights assigned by dentists.
Short‐term effect of outdoor mould spore exposure on prescribed allergy medication sales in Central France
Authors: Caillaud D. , Cheriaux M. , Martin S. , Ségala C. , Dupuy N. , Evrard B. , Thibaudon M. 
Published: April 2018

SummaryBackgroundOutdoor moulds are classically associated with exacerbations of asthma.ObjectiveThe aim of this paper was to examine nasal allergy morbidity by studying the short‐term relationship between mould spore exposure and daily sales of reimbursable anti‐allergic treatment in central France.MethodsThe relationship between daily changes in mould concentrations and daily sales obtained from the national healthcare database was analysed with generalized additive models, taking into account confounding factors such as air pollution, weather conditions, pollen counts, and days of the week.ResultsDuring the study, the average total yearly number of treated people was around 10 000 over approximately 230 000 surveyed. The relative risk (95% CI confidence interval) of sales of oral antihistamines with topical treatment associated with an interquartile increase in mould concentration was significant for Cladosporium 1.079 [1.019‐1.142] and Aspergillus‐Penicillium (Asp‐Pen) 1.051 [1.021‐1.082] in the whole population. When the influence of age and sex was considered, the relationship was significant only in male children aged 0‐12 years and those aged between 13 and 49 years for Cladosporium: 1.256 [1.081‐1.460] and 1.151 [1.063‐1.245], respectively. The relationship was also significant for Asp‐Pen: 1.038 [1.003‐1.075] for those aged between 13 and 49 years and 1.056 [1.007‐1.108] for adults over 50 years of age.ConclusionThe association between prescribed daily sales of oral antihistamines with topical treatment sales is associated with temporal changes to Cladosporium and Aspergillus‐Penicillium in the whole population. When the influence of age and sex was considered, these two moulds contributed to prescribed medication sales only in the male general population.
Tuftsin–phosphorylcholine (TPC) equally effective to methylprednisolone in ameliorating lupus nephritis in a mice model
Authors: Shemer A , Kivity S , Shovman O , Bashi T , Perry O , Watad A , Ben-Ami Shor D , Volkov A , Barshack I , Bragazzi N L , Krule A , Fridkin M , Amital H , Blank M , Shoenfeld Y 
Published: April 2018

Summary
The role of helminth treatment in autoimmune diseases is growing constantly. Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with challenging treatment options. Tuftsin–phosphorylcholine (TPC) is a novel helminth-based compound that modulates the host immune network. This study was conducted to evaluate the potential value of TPC in ameliorating lupus nephritis in a murine model and specifically to compare the efficacy of TPC to the existing first-line therapy for SLE: corticosteroids (methylprednisolone). Lupus-prone NZBxW/F1mice were treated with TPC (5 µg/mouse), methylprednisolone (MP; 5 mg/body weight) or phosphate-buffered saline (PBS) (control) three times per week once glomerulonephritis, defined as proteinuria of grade &gt; 100 mg/dl, was established. Levels of anti-dsDNA autoantibodies were evaluated by enzyme-linked immunosorbent assay (ELISA), splenic cytokines were measured in vitro and the kidney microscopy was analysed following staining. TPC and MP treatments improved lupus nephritis significantly and prolonged survival in NZBxW/F1 mice. TPC-treated mice showed a significantly decreased level of proteinuria (P &lt; 0·001) and anti-dsDNA antibodies (P &lt; 0·001) compared to PBS-treated mice. Moreover, TPC and MP inhibited the production of the proinflammatory cytokines interferon IFN-γ, interleukin IL-1β and IL-6 (P &lt; 0·001) and enhanced expression of the anti-inflammatory cytokine IL-10 (P &lt; 0·001). Finally, microscopy analysis of the kidneys demonstrated that TPC-treated mice maintained normal structure equally to MP-treated mice. These data indicate that the small molecule named TPC hinders lupus development in genetically lupus-prone mice equally to methylprednisolone in most of the cases. Hence, TCP may be employed as a therapeutic potential for lupus nephritis.
Grandparents matter: Optimizing grandparents' involvement after child safety concerns
Authors: Gair Susan , Zuchowski Ines , Munns Lyn , Thorpe Ros , Henderson Debbie 
Published: April 2018

AbstractAcross Australia and internationally, growing numbers of grandparents are becoming primary carers for grandchildren, both within and outside of formal state care arrangements. Underlying factors include family breakdown, family circumstances where parents are unable to care for their children, or where there are child safety concerns. Some grandparents report a pattern of initially providing care for grandchildren but then experiencing reduced or lost contact that sometimes is not restored, in turn impacting ongoing relationships with grandchildren. A prevailing concern is the disproportional numbers of Aboriginal children in state care in all Australian states. Reported here are findings from a recent partnership research project focused on optimizing grandparent contact and ongoing relationships with grandchildren after child safety concerns. Qualitative in‐depth interviews and focus groups were conducted with 77 participants. Findings revealed grandparents yearned to maintain a significant role in grandchildren's lives after child safety issues emerged, however, they often felt powerless, unsupported, and sidelined from decision‐making in the best interests of their grandchildren. Participants made strong recommendations for more inclusive processes.
Increased Soluble CD137 Levels and CD4+ T‐Cell‐Associated Expression of CD137 in Acute Atherothrombotic Stroke
Authors: He Yang , Ao Dong‐Hui , Li Xiao‐Qing , Zhong Shan‐Shan , A Rong , Wang Yang‐Yang , Xiang Ya‐Juan , Xu Bao‐Lei , Yang Ting‐Ting , Gao Xu‐Guang , Liu Guang‐Zhi 
Published: April 2018

AbstractAs a proinflammatory cytokine, CD137 (4‐1BB, TNFRSF9) is present in membrane‐bound and soluble forms. Increased expression of CD137 was recently found in T cells in human atherosclerotic plaques. However, the exact role of CD137 in ischemic stroke is not clear. In this study we analyzed the protein levels of soluble CD137 (sCD137) and the expression of CD137 on CD4+ T cells in the peripheral blood of patients with acute atherothrombotic stroke by using the cytometry beads array (CBA) and flow cytometry. Within 24 hours of onset, the stroke patients showed elevated levels of sCD137 (2.7 pg/ml) and CD137 expression on CD4+ T cells (4.9 ± 3.2%) compared with normal controls (1.1 pg/ml, P < 0.01; 1.3 ± 1.0%, P < 0.01). Alterations in CD137 expression may enhance ischemia‐induced inflammatory responses via bidirectional signaling and, consequently, aggravate brain injury in early stages of this disorder.
Perceived stress and well‐being in UK and Australian dental hygiene and dental therapy students
Authors: Harris M. , Wilson J. C. , Hughes S. , Knevel R. J. M. , Radford D. R. 
Published: April 2018

AbstractIntroductionThis study aimed to explore United Kingdom (UK) and Australian (Aus) dental hygiene and dental therapy students’ (DHDTS) perception of stress and well‐being during their undergraduate education. Upon qualification, DHDTS in the UK register as dental therapists (DT), and in Australia, they register as Oral Health Therapists (OHT).Materials and methodsA questionnaire was distributed to years 1, 2 and 3 DHDTS at the University of Portsmouth Dental Academy (UPDA) in the UK and La Trobe Rural Health School in Australia. The questionnaire consisted of 5 well‐used measurement instruments which included the following: Dental Environment Stress questionnaire (DES); Depression Anxiety Stress Scales (DASS‐21); Scales of Psychological Well‐Being (SPWB); Valuing Questionnaire (VQ); and the Adult Hope Scale (AHS) to collect data on students’ perception of levels of stress and well‐being.ResultsA response rate of 58% (UK) and 55% (Australia) was achieved. Clinical factors and academic work were perceived as stressful for DHDTS in both the UK and Australia. The Australian DHDTS‐perceived stress in the educational environment was significantly higher (P < .002) than the UK DHDTS. The majority of respondents reported levels of depression, anxiety and stress to be within the normal‐to‐moderate range. All students reported high levels of positive well‐being, with no significant differences between the 2 groups.ConclusionsDHDTS in the UK and Australia identified sources of stress within their undergraduate education, but also perceived themselves as positively functioning individuals.
Increased cardiac stiffness is associated with autonomic dysfunction in patients with temporal lobe epilepsy
Authors: Fialho Guilherme L. , Wolf Peter , Walz Roger , Lin Katia 
Published: April 2018

SummaryAutonomic dysfunction is linked to sudden death regardless of the presence of structural heart disease. The pathway from autonomic dysfunction to sudden death is not fully understood, but myocardial sympathetic stimulation leading to arrhythmia and/or cardiac fibrosis might play a role. Our goal was to evaluate cardiac stiffness by echocardiography and its association with clinical, structural, and autonomic variables in people with epilepsy (PWE) compared to healthy controls. A 12‐lead electrocardiogram, treadmill testing, and transthoracic echocardiography from 30 patients with temporal lobe epilepsy (TLE) without any known cardiovascular disorders were compared to 30 individuals without epilepsy matched by sex, age, and body mass index. Distribution of cardiovascular risk factors was similar in both groups. PWE had a higher left ventricle stiffness, left ventricle filling pressure, and greater left atrial volume as well as markers of autonomic dysfunction such as impaired chronotropic index and percentage achieved of predicted peak heart rate at effort. In multiple regressions, autonomic dysfunction explained 52% of stiffness and carbamazepine treatment and polytherapy with antiepileptic drugs (AEDs) explained, additionally, 6% each. Stiffness is increased in young patients with TLE and is related to autonomic dysfunction and to a lesser extent, carbamazepine use and polytherapy with AEDs.