bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mocha tyrosinase variant: a new flavour of cat coat coloration
Authors: Yu Y. , Grahn R. A. , Lyons L. A. 
Published: February 2019

SummaryA novel coloration named ‘mocha’ has been identified in the Burmese cat breed from Thailand. Tyrosinase (TYR) mutations are known to be associated with coat coloration in cats, such as the sable Burmese, the points of the Siamese and albino cats. Additionally, sable Burmese that produced mocha‐colored cats had unexpected genotypes for TYR. Therefore, TYR was considered a candidate gene for mocha in cats. Sanger sequencing for genomic DNA revealed NC_018732.3:chromosome D1:45 898 609_45 898 771dup in exon 2 and intron 2 of TYR. Transcription analysis using cDNA detected c.820_936delinsAATCTC (p.I274_L312delinsNL), which caused a 111‐bp (37 amino acid) deletion in the reading frame of TYR. The identified variant was concordant with the phenotype and segregated with TYR variants in a pedigree of 12 Burmese cats. This findings of this study suggest that TYR is associated with the mocha coloration in cats. The new color variant adds to the allelic series for TYR (C > cb = cs > c, c2) and is recessive to full color (C); however, interactions with the cb and cs alleles are unclear due to the temperature‐sensitivity of the alleles.
Identifying support needs to improve rural dementia services for people with dementia and their carers: A consultation study in Victoria, Australia
Authors: Bauer Michael , Fetherstonhaugh Deirdre , Blackberry Irene , Farmer Jane , Wilding Clare 
Published: February 2019

AbstractObjectiveThe support and service needs of people with dementia and their carers are not always addressed in rural regions, yet family carers play an important role in supporting the person living with dementia to remain living in their own home. This study sought to identify and prioritise service and support needs of people with dementia and carers.DesignA two‐phase mixed methods study involving qualitative focus groups and a survey.SettingA rural region in Victoria, Australia.ParticipantsPeople living with dementia, carers and health professionals.ResultsFocus groups identified 12 areas of need. A follow‐up survey reached consensus on the priority areas for service improvement. These included diagnosis and information access, dementia training, community understanding and carer support.ConclusionLiving in a rural region imposes significant challenges on people with dementia and carers. We need to find ways to address gaps in service provision for carers and people with dementia in rural settings and examine their applicability in other rural regions more broadly.
Building a medical workforce in Tasmania: A profile of medical student intake
Authors: Cheek Colleen , Hays Richard , Allen Penny , Walker Gary , Shires Lizzi 
Published: February 2019

AbstractObjectiveTo identify under‐represented groups in a medical school intake.DesignDescriptive analysis of student demographic characteristics.SettingOne state‐wide medical school.ParticipantsAll students enrolled between 2010 and 2016.Main outcome measure(s)Proportion of students from regional and rural areas, state versus independent schools, highest parental qualification, Aboriginal or Torres Strait Islander students.ResultsOf 819 students, 472 (57.6%) were from Tasmania, five (1.1%) identified as Aboriginal or Torres Strait Islanders, 335 (71.0%) completed their secondary education at independent schools and 137 (29.0%) at government schools. The overall median Modified Monash Model was 2 (range 1–6) and median Australia Statistical Geography Standard Remoteness Area was 2 (inner regional: range 1–4), reflecting that a majority came from one of the two main cities. Over two‐thirds (69.5%) had a parent with a Bachelor degree or higher qualification, regardless of the school attended. Just under half (225, 47.7%) of all Tasmanian students attended a secondary school with a parental contribution of ≥$5000 per annum. These students attended a small number of independent schools, with the proportion relatively stable over the period from 2010 to 2016.ConclusionWidening participation and widening access initiatives to graduate doctors who understand and want to work in communities in need might not be working as well in Tasmania as elsewhere in Australia. Social accountability might be improved by adapting a rural classification that reflects the demographic profile of Tasmania.
Prevalence and practice characteristics of urban and rural or remote Australian chiropractors: Analysis of a nationally representative sample of 1830 chiropractors
Authors: Adams Jon , de Luca Katie , Swain Michael , Funabashi Martha , Wong Arnold , Pagé Isabelle , Sibbritt David , Peng Wenbo 
Published: February 2019

AbstractObjectiveTo determine the prevalence and clinical management characteristics of chiropractors practising in urban and rural or remote Australia.DesignA cross‐sectional analysis of the Australian Chiropractic Research Network project data.SettingNationally representative sample of registered chiropractors practising in Australia.ParticipantsChiropractors who participated in the Australian Chiropractic Research Network project and answered a question about practising in urban or rural or remote areas in the practitioner questionnaire.Main outcome measureThe demographics, practice characteristics and clinical management of chiropractors.ResultsThe majority of chiropractors indicated that they practise in urban areas only, while 22.8% (n = 435) practice in rural or remote areas only and 4.0% (n = 77) practice in both urban and rural or remote areas. Statistically significant predictors of chiropractors who practice in rural or remote areas, as compared to urban areas, included more patient visits per week, practising in more than one location, no imaging facilities on site, often treating degenerative spinal conditions or migraine, often treating people aged over 65 years, frequently treating Aboriginal and Torres Strait Islander people and frequently using biomechanical pelvic blocking or the sacro‐occipital technique.ConclusionA substantial number of chiropractors practice in rural or remote Australia and these rural or remote‐based chiropractors are more likely to treat a wide range of musculoskeletal cases and include an Indigenously diverse group of patients than their urban‐located colleagues. Unique practice challenges for rural or remote chiropractors include a higher workload and a lack of diagnostic tools. Chiropractors should be acknowledged and considered within rural or remote health care policy and service provision.
Right ventricular pacing is associated with increased rates of appropriate implantable cardioverter defibrillator shocks
Authors: Arcinas Liane A. , McIntyre William F. , Farag Ashraf , Kushneriuk Dominique , Hiebert Brett , Seifer Colette M. 
Published: February 2019

AbstractBackgroundRight ventricular (RV) pacing has been associated with increased risk of pacemaker‐induced cardiomyopathy, hospitalization and death among patients with implantable cardioverter defibrillators (ICDs). Little is known about its association with ventricular tachyarrhythmias. We hypothesize that RV pacing is associated with increased incidence of appropriate ICD shocks and death.MethodsRetrospective study of consecutive patients with de novo ICD insertion (excluding cardiac resynchronization therapy devices) from a single tertiary care center. Patients were classified into <10% RV pacing (low‐pace group) and ≥10% RV pacing (high‐pace group). Data were compared using two‐tailed t tests and Fisher's exact test. Binomial logistic regression was performed to identify predictors of appropriate ICD therapies.ResultsA total of 178 patients (54 high paced and 124 low paced) were included. Mean follow‐up was 43 ± 11 months. Appropriate shocks occurred in 27 patients (15%) and were significantly higher in the high‐pace group (35% vs. 10%, p = 0.008), as the number of deaths (31% vs. 11%, p = 0.001). Binary logistic regression showed a significantly increased risk of shock (OR 2.99, p = 0.01) and death (OR 3.61, p = 0.002) in high‐paced patients. Multivariable analysis showed no difference in risk of shocks based on age, sex or ejection fraction. Older patients had higher risk of death.ConclusionsIn this population of ICD patients, those with a high prevalence of RV pacing experienced more shocks for VF/VT and had higher mortality. Further studies should be done to determine whether minimizing RV pacing reduces arrhythmias, shock burden and death in patients with ICDs.
Systematic review finds that fever phobia is a worldwide issue among caregivers and healthcare providers
Authors: Clericetti Caterina M , Milani Gregorio P , Bianchetti Mario G , Simonetti Giacomo D , Fossali Emilio F , Balestra Alessandra M , Bozzini Marie‐Ange , Agostoni Carlo , Lava Sebastiano A G 
Published: February 2019

AbstractAimFever phobia describes exaggerated concerns about the consequences of childhood fever and broader awareness is needed in everyday clinical practice. We investigated the factors associated with fever phobia in caregivers and healthcare providers and the geographical distribution of the issue.MethodsThe National Library of Medicine, Excerpta Medica and Google Scholar databases were searched.ResultsWe retrieved 76 papers, published in English from 1985 to 2018, which covered wide areas of Asia, Europe, America, Africa and Australia. The occurrence of fever phobia was confirmed in 65 papers covering 26 521 caregivers. A number of factors were significantly associated with fever phobia, including low educational or socioeconomic levels, a history of febrile seizures in the child and young maternal age. Fever phobia was also more common in Bedouins and in people from Latin America, Southern Italy and Turkey. There were also 15 papers that addressed fever phobia among 4566 healthcare providers. All the reports suggested that a fear of fever and a tendency to over treat was common among physicians and nurses.ConclusionFever phobia was a common world phenomena that affected caregivers and healthcare providers.
DAN plays important compensatory roles in systemic‐to‐pulmonary shunt associated pulmonary arterial hypertension
Authors: Meng Liukun , Liu Xiaoyan , Teng Xiao , Yuan Wen , Duan Lihua , Meng Jian , Li Jun , Zheng Zhe , Wei Yingjie , Hu Shengshou 
Published: February 2019

AbstractAimProteins mainly expressed in normal lungs and significantly changed in lungs exposed to systemic‐to‐pulmonary shunts might be promising targets for pulmonary arterial hypertension induced by congenital heart diseases (PAH/CHD). This study aimed to investigate the potential role of differential screening‐selected gene aberrative in neuroblastoma (DAN) in PAH/CHD.MethodsPAH was surgically induced by the combined surgery (right pulmonary artery ligation and left cervical systemic‐to‐pulmonary shunt) in Sprague‐Dawley (SD) rats. Exogenous DAN was supplemented by osmotic minipumps.ResultsFirstly, DAN was significantly decreased in patients with severe PAH/CHD and negatively correlated with pulmonary hemodynamic indices derived from right cardiac catheterization. Secondly, pulmonary hypertensive status and apparent pulmonary vasculopathies of PAH/CHD were surgically reproduced in SD rats. Real time‐PCR and Western blot analysis revealed that DAN mRNA and protein levels decreased in lungs exposed to systemic‐to‐pulmonary shunts, and immunofluorescence staining found that DAN was highly expressed in pulmonary arteries of normal lungs but seldom detected in severely remodelling pulmonary arteries, furthermore, plasma levels of DAN in shunted‐rats manifested a time‐depended decrease and negatively correlated with pulmonary hemodynamic indices. Thirdly, DAN specially reversed the anti‐proliferative and pro‐apoptotic effects of bone morphogenetic protein 2/4 (BMP2/4) on pulmonary arterial smooth muscle cells via BMP2/4‐BMPR2‐Smad1/5/8‐Id1 signalling pathway. Furthermore, continuous supplementation of exogenous DAN protein increased the extent of shunt‐associated PAH.ConclusionCompensatory decrease of DAN in hypertensive lungs may retard the deterioration of shunt‐associated PAH, at least in part, by antagonizing BMP signalling pathway. Furthermore, DAN might be a potential biomarker for PAH/CHD.
Design, synthesis and evaluations of spiro‐fused benzoxaborin derivatives as novel boron‐containing compounds
Authors: Natsutani Itaru , Iwata Riyo , Yamai Yu‐suke , Ishida Kyoji , Nagaoka Yasuo , Sumiyoshi Takaaki 
Published: February 2019

AbstractDrug design using boron‐containing heterocycles has attracted a great deal of attention because these compounds are believed to possess high biological activity. However, information on the synthetic methodology and pharmacokinetic profiling of boron‐containing compounds is limited. In this study, we provide a new synthetic route for preparation of spiro‐fused benzoxaborin derivatives and investigate their in vitro pharmacokinetic properties. Our efforts led to the successful construction of a chemical library of spiro‐fused benzoxaborin derivatives with appropriate physicochemical and in vitro pharmacokinetic properties for oral drugs. These results indicate that the synthesized boron‐containing compounds are therefore eligible for classification in a novel chemical library.
In times of tobacco‐free nicotine consumption: The influence of nicotine on vascular calcification
Authors: Babic Milen , Schuchardt Mirjam , Tölle Markus , van der Giet Markus 
Published: February 2019

AbstractBackgroundSmoking remains the most important avoidable cause of global mortality. Even though the number of cigarette smokers declines in first world countries, the uses of alternative nicotine delivery products increase and may even surpass the sells of cigarettes. In this light, the explicit role of nicotine in the development of cardiovascular diseases should be elucidated.ObjectivesThis narrative review attempts to connect current literature about possible effects of nicotine on the environment of the vasculature to the pathogenesis of vascular calcification, focusing on the tunica media of the vessel wall.MethodsFor this review, papers found on Pubmed and Medline until December 2018 by searching for the keywords nicotine, vascular calcification, oxidative stress, osteoblastic transdifferentiation and matrix degradation were considered.ResultsNicotine creates an environment that probably facilitates and maybe even induces osteogenic transdifferentiation of VSMC by inflammation, endothelial dysfunction and reactive oxygen species. This process is believed to be a key event in calcification of the tunica media of the vessel wall. Furthermore, nicotine could lead to the formation of nucleation sites for hydroxyapatite by facilitating matrix vesicles and extracellular matrix degradation.ConclusionsThere is a growing body of evidence implicating that nicotine alone could impair vascular function and lead to vascular calcification. Further research is necessary to elucidate the explicit influence of nicotine on arteriosclerosis.
Replication, reanalysis, and gene expression: ME2 and genetic generalized epilepsy
Authors: Wang Meng , Greenberg David A. , Stewart William C. L. 
Published: February 2019

SummaryObjectiveGenetic generalized epilepsy (GGE) consists of epileptic syndromes with overlapping symptoms and is considered to be largely genetic. Previous cosegregation and association studies have pointed to malic enzyme 2 (ME2) as a candidate susceptibility gene for adolescent‐onset GGE. In this article, we present new evidence supporting ME2's involvement in GGE.MethodsTo definitively test ME2's influence on GGE, we used 3 different approaches. First, we compared a newly recruited GGE cohort with an ethnically matched reference sample from 1000 Genomes Project, using an efficient test of association (POPFAM+). Second, we used POPFAM+ to reanalyze a previously collected data set, wherein the original controls were replaced with ethnically matched reference samples to minimize the confounding effect of population stratification. Third, in a post hoc analysis of expression data from healthy human prefrontal cortex, we identified single nucleotide polymorphisms (SNPs) influencing ME2 messenger RNA (mRNA) expression; and then we tested those same SNPs for association with GGE in a large case‐control cohort.ResultsFirst, in the analysis of our newly recruited GGE Cohort, we found a strong association between an ME2 SNP and GGE (P = 0.0006 at rs608781). Second, in the reanalysis of previously collected data, we confirmed the Greenberg et al (2005) finding of a GGE‐associated ME2 risk haplotype. Third, in the post hoc ME2 expression analysis, we found evidence for a possible link between GGE and ME2 gene expression in human brain.SignificanceOverall, our research, and the research of others, provides compelling evidence that ME2 influences susceptibility to adolescent‐onset GGE.
Fenfluramine, a serotonin‐releasing drug, prevents seizure‐induced respiratory arrest and is anticonvulsant in the DBA/1 mouse model of SUDEP
Authors: Tupal Srinivasan , Faingold Carl L. 
Published: February 2019

SummaryObjectivePrevention of sudden unexpected death in epilepsy (SUDEP) is a critical goal for epilepsy therapy. The DBA/1 mouse model of SUDEP exhibits an elevated susceptibility to seizure‐induced death in response to electroconvulsive shock, hyperthermia, convulsant drug, and acoustic stimulation. The serotonin hypothesis of SUDEP is based on findings that treatments which modify serotonergic function significantly alter susceptibility to seizure‐induced sudden death in several epilepsy models, including DBA/1 mice. Serotonergic abnormalities have also recently been observed in human SUDEP. Fenfluramine is a drug that enhances serotonin release in the brain. Recent studies have found that the addition of fenfluramine improved seizure control in patients with Dravet syndrome, which has a high incidence of SUDEP. Therefore, we investigated the effects of fenfluramine on seizures and seizure‐induced respiratory arrest (S‐IRA) in DBA/1 mice.MethodsThe dose and time course of the effects of fenfluramine (i.p.) on audiogenic seizures (Sz) induced by an electric bell in DBA/1 mice were determined. Videos of Sz‐induced behaviors were recorded for analysis. Statistical significance (P < 0.05) was evaluated using the chi‐square test.ResultsSixteen hours after administration of 15 mg/kg of fenfluramine, a high incidence of selective block of S‐IRA susceptibility (P < 0.001) occurred in DBA/1 mice without blocking any convulsive behavior. Thirty minutes after 20‐40 mg/kg of fenfluramine, significant reductions of seizure incidence and severity, as well as S‐IRA susceptibility occurred, which were long‐lasting (≥48 hours). The median effective dose (ED50) of fenfluramine for significantly reducing Sz at 30 minutes was 21 mg/kg.SignificanceThis study presents the first evidence for the effectiveness of fenfluramine in reducing seizure incidence, severity, and S‐IRA susceptibility in a mammalian SUDEP model. The ability of fenfluramine to block S‐IRA selectively suggests the potential usefulness of fenfluramine in prophylaxis of SUDEP. These results further confirm and extend the serotonin hypothesis of SUDEP.
Risk factors for injury in a community‐treated cohort of patients with epilepsy in Australia
Authors: Tan Michael , Boston Ray , Cook Mark J. , D'Souza Wendyl J. 
Published: February 2019

SummaryObjectiveThere remains a paucity of knowledge regarding specific epilepsy‐related risk factors for accidents and injuries in people with epilepsy. Injury studies in people with epilepsy are overrepresented, with tertiary based populations that are prone to bias from severe disease. This study aims to assess the contribution of epilepsy‐related risk factors to injuries in a community‐based cohort.MethodsWe performed a retrospective nested case‐control study on patients recruited into the Tasmanian Epilepsy Register (TER) from July 1, 2001 to June 30, 2002. TheTERis a community‐based cohort of patients with epilepsy in Tasmania, Australia, recruited from the national prescription database and interviewed for epilepsy diagnosis, injuries, and risk factors using validated questionnaires with diagnosis made by an epilepsy specialist. The primary outcome measures were lifetime and recent 12‐month injury. Multivariate logistic regression with multiple imputation modeling responder nondisclosure was performed, adjusting for age, gender, region, socioeconomic status, seizure frequency, and epilepsy duration.ResultsA total of 819 patients with epilepsy were included in this study. Ten percent of patients experienced an injury in the preceding year. Before adjusting for seizure frequency, any seizure over the past 12 months was associated with recent injury (adjusted odds ratio [OR] = 7.90, 95% confidence interval [CI] = 4.17‐14.96). Impaired awareness, cluster seizures, sleep‐only seizures, and convulsive seizure were characteristics found to significantly influence injuries irrespective of seizure frequency. Although a warning appeared initially protective for recent injuries (OR= 0.39, 95%CI= 0.22‐0.69), this was entirely explained by seizure frequency, with the effect becoming nonsignificant.SignificanceLikely due to their unpredictable nature, seizures expose patients with epilepsy to a high risk of life‐threatening injury. These findings emphasize the importance of seizure freedom for maximizing the safety of patients with epilepsy.
Phylogenetic diversity in freshwater‐dwelling Isochrysidales haptophytes with implications for alkenone production
Authors: Richter Nora , Longo William M. , George Sarabeth , Shipunova Anna , Huang Yongsong , Amaral‐Zettler Linda 
Published: February 2019

AbstractMembers of the order Isochrysidales are unique among haptophyte lineages in being the exclusive producers of alkenones, long‐chain ketones that are commonly used for paleotemperature reconstructions. Alkenone‐producing haptophytes are divided into three major groups based largely on molecular ecological data: Group I is found in freshwater lakes, Group II commonly occurs in brackish and coastal marine environments, and Group III consists of open ocean species. Each group has distinct alkenone distributions; however, only Groups II and III Isochrysidales currently have cultured representatives. The uncultured Group I Isochrysidales are distinguished geochemically by the presence of tri‐unsaturated alkenone isomers (C37:3b Me, C38:3b Et, C38:3b Me, C39:3b Et) present in water column and sediment samples, yet their genetic diversity, morphology, and environmental controls are largely unknown. Using small‐subunit (SSU) ribosomal RNA (rRNA) marker gene amplicon high‐throughput sequencing of environmental water column and sediment samples, we show that Group I is monophyletic with high phylogenetic diversity and contains a well‐supported clade separating the previously described “EV” clade from the “Greenland” clade. We infer the first partial large‐subunit (LSU) rRNA gene Group I sequence phylogeny, which uncovered additional well‐supported clades embedded within Group I. Relative to Group II, Group I revealed higher levels of genetic diversity despite conservation of alkenone signatures and a closer evolutionary relationship with Group III. In Group I, the presence of the tri‐unsaturated alkenone isomers appears to be conserved, which is not the case for Group II. This suggests differing environmental influences on Group I and II and perhaps uncovers evolutionary constraints on alkenone biosynthesis.