bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct Target Network of the Neurospora crassa Plant Cell Wall Deconstruction Regulators CLR-1, CLR-2, and XLR-1
Authors: Craig James P. , Coradetti Samuel T. , Starr Trevor L. , Glass N. Louise 
Published: October 2015

ABSTRACT

Fungal deconstruction of the plant cell requires a complex orchestration of a wide array of intracellular and extracellular enzymes. In
Neurospora crassa
, CLR-1, CLR-2, and XLR-1 have been identified as key transcription factors regulating plant cell wall degradation in response to soluble sugars. The XLR-1 regulon was defined using a constitutively active mutant allele, resulting in hemicellulase gene expression and secretion under noninducing conditions. To define genes directly regulated by CLR-1, CLR-2, and XLR-1, we performed chromatin immunoprecipitation and next-generation sequencing (ChIPseq) on epitope-tagged constructs of these three transcription factors. When
N. crassa
is exposed to plant cell wall material, CLR-1, CLR-2, and XLR-1 individually bind to the promoters of the most strongly induced genes in their respective regulons. These include promoters of genes encoding cellulases for CLR-1 and CLR-2 (CLR-1/CLR-2) and promoters of genes encoding hemicellulases for XLR-1. CLR-1 bound to its regulon under noninducing conditions; however, this binding alone did not translate into gene expression and enzyme secretion. Motif analysis of the bound genes revealed conserved DNA binding motifs, with the CLR-2 motif matching that of its closest paralog in
Saccharomyces cerevisiae
, Gal4p. Coimmunoprecipitation studies showed that CLR-1 and CLR-2 act in a homocomplex but not as a CLR-1/CLR-2 heterocomplex.

IMPORTANCE
Understanding fungal regulation of complex plant cell wall deconstruction pathways in response to multiple environmental signals via interconnected transcriptional circuits provides insight into fungus/plant interactions and eukaryotic nutrient sensing. Coordinated optimization of these regulatory networks is likely required for optimal microbial enzyme production.
Impacted Science: Impact Is Not Importance
Authors: Casadevall Arturo , Fang Ferric C. 
Published: October 2015

ABSTRACT
The journal impact factor (IF) exerts a tremendous influence on the conduct of scientists. The obsession with IF has been compared to a medical condition, sometimes referred to as “IF mania” or “impactitis.” Here, we analyze the difference between impact and importance, using examples from the history of science to show that these are not equivalent. If impact does not necessarily equal importance, but scientists are focused on high-impact work, there is a danger that misuse of the IF may adversely affect scientific progress. We suggest five measures to fight this malady: (i) diversify journal club selections, (ii) do not judge science on the publication venue, (iii) reduce the reliance on journal citation metrics for employment and advancement, (iv) discuss the misuse of the IF in ethics courses, and (v) cite the most appropriate sources. If IF mania is indeed a medical condition, the most appropriate course of action may be disimpaction.
Blockade of the Brachial Plexus Abolishes Activation of Specific Brain Regions by Electroacupuncture at Li4: A Functional Mri Study
Authors: Gu Weidong , Jiang Wei , He Jingwei , Liu Songbin , Wang Zhaoxin 
Published: October 2015

Objective Our aim was to test the hypothesis that electroacupuncture (EA) at acupuncture point LI4 activates specific brain regions by nerve stimulation that is mediatied through a pathway involving the brachial plexus. Methods Twelve acupuncture naive right-handed volunteers were allocated to receive three sessions of EA at LI4 in a random different order (crossover): (1) EA alone (EA); EA after injection of local anaesthetics into the deltoid muscle (EA+LA); and (3) EA after blockade of the brachial plexus (EA+NB). During each session, participants were imaged in a 3 T MRI scanner. Brain regions showing change in blood oxygen level-dependent (BOLD) signal (activation) were identified. Subjective acupuncture sensation was quantified after functional MRI scanning was completed. Results were compared between the three sessions for each individual, and averaged. Results Blockade of the brachial plexus inhibited acupuncture sensation during EA. EA and EA+LA activated the bilateral thalamus, basal ganglia, cerebellum and left putamen, whilst no significant activation was observed during EA+NB. The BOLD signal of the thalamus correlated significantly with acupuncture sensation score during EA. Conclusions Blockade of the brachial plexus completely abolishes patterns of brain activation induced by EA at LI4. The results suggest that EA activates specific brain regions through stimulation of the local nerves supplying the tissues at LI4, which transmit sensory information via the brachial plexus. Trial Registration Number ChiCTR-OO-13003389.
Application of two versions of the WHO/international society of hypertension absolute cardiovascular risk assessment tools in a rural Bangladeshi population
Authors: Fatema Kaniz , Zwar Nicholas Arnold , Milton Abul Hasnat , Rahman Bayzidur , Ali Liaquat 
Published: October 2015

ObjectivesTo estimate the absolute cardiovascular disease (CVD) risk burden in a remote rural Bangladeshi population using the ‘With’ and ‘Without’ Cholesterol versions of the WHO/International Society of Hypertension (WHO/ISH) CVD risk assessment chart (particularly suitable for low and middle-income countries due to less reliance on laboratory testing) and to evaluate the agreement between the two approaches.DesignCross-sectional study using data from a large prospective cohort of the North Bengal Non-Communicable Disease Programme (NB-NCDP) of Bangladesh.SettingGeneral rural population from Thakurgaon district of Bangladesh.Participants563 individuals who were categorised as having ‘no CVDs’ on screening by a questionnaire-based survey using the ‘WHO CVD-Risk Management Package’ developed in 2002.Main outcome measuresAbsolute CVD risk burden assessed using two versions of the WHO/ISH risk assessment charts for the South-East Asian Region-D.Results10-year risk (moderate, high and very high) positivity was present among 21.5% and 20.2% of participants, respectively, using with and without cholesterol versions of the tool. The overall concordance rate for the two versions was 89.5% and they did not differ significantly in estimating the proportion of overall participants having higher levels of CVD. The projected drug requirement, however, showed a significant overestimation in the proportion of participants at both the threshold levels (p<0.002) on using ‘without’ as compared to ‘with’ cholesterol versions.ConclusionsAbout one-fifth of the adult population in Bangladesh, even in a remote rural area, seem to be at risk of developing CVDs (25% of them at high risk and 25% at very high risk) within 10 years with males and females being almost equally vulnerable.
Increasing incidence of recent hepatitis C virus infection among persons seeking voluntary counselling and testing for HIV and sexually transmitted infections in Taiwan
Authors: Tsai Jen-Chih , Hung Chien-Ching , Chang Sui-Yuan , Liu Wen-Chun , Wu Cheng-Hsin , Su Yi-Ching , Wu Pei-Ying , Luo Yu-Zhen , Chang Lan-Hsin , Sun Hsin-Yun , Chang Shan-Chwen 
Published: October 2015

ObjectivesThe incidence of hepatitis C virus (HCV) infection among HIV-negative men who have sex with men (MSM) is rarely investigated in the Asia-Pacific region. We aimed to estimate the incidence rate of and factors associated with recent HCV infection among the clients seeking voluntary counselling and testing (VCT) services for HIV in Taiwan.MethodsDuring 2006–2013, 12 143 clients sought VCT services for HIV. Clients with subsequent follow-up tests at an interval of 6 months or longer were included to estimate the incidence rate of HCV seroconversion. Phylogenetic analysis of HCV sequences from VCT clients and HIV-positive patients was performed.ResultsThe overall HCV seroprevalence at baseline was 0.3%. Of 2150 clients testing negative for anti-HCV antibody at baseline with a total of 5074.99 person-years of follow-up (PYFU), 17 (0.8%) developed HCV seroconversion, leading to an overall incidence rate of 3.35 per 1000 PYFU (95% CI 1.76 to 4.94), which increased from 2.28 (95% CI 0.05 to 4.51) in 2006–2009, to 3.33 (95% CI 0.86 to 5.80) in 2010 to 2011 and 4.94 per 1000 PYFU (95% CI 0.99 to 8.99) in 2012–2013; the incidence of early syphilis increased from 11.91 to 13.28 and 31.78 per 1000 PYFU in the three corresponding periods. In multivariate analysis, having HIV-positive partners (adjusted HR (AHR) =3.756; 95%CI 1.180 to 11.955) and developing a rapid plasma reagin titre of 4 or greater (AHR=9.978; 95% CI 1.550 to 64.233) were significantly associated with HCV seroconversion.ConclusionsAn increasing trend of recent HCV infection occurs among individuals seeking VCT services in Taiwan. Having HIV-positive partners and having syphilis are independently associated with recent HCV seroconversion.
Understanding burn injuries in Aboriginal and Torres Strait Islander children: protocol for a prospective cohort study
Authors: Ivers Rebecca Q , Hunter Kate , Clapham Kathleen , Coombes Julieann , Fraser Sarah , Lo Serigne , Gabbe Belinda , Hendrie Delia , Read David , Kimble Roy , Sparnon Anthony , Stockton Kellie , Simpson Renee , Quinn Linda , Towers Kurt , Potokar Tom , Mackean Tamara , Grant Julian , Lyons Ronan A , Jones Lindsey , Eades Sandra , Daniels John , Holland Andrew J A 
Published: October 2015

IntroductionAlthough Aboriginal and Torres Strait Islander children in Australia have higher risk of burns compared with non-Aboriginal children, their access to burn care, particularly postdischarge care, is poorly understood, including the impact of care on functional outcomes. The objective of this study is to describe the burden of burns, access to care and functional outcomes in Aboriginal and Torres Strait Islander children in Australia, and develop appropriate models of care.Methods and analysisAll Aboriginal and Torres Strait Islander children aged under 16 years of age (and their families) presenting with a burn to a tertiary paediatric burn unit in 4 Australian States (New South Wales (NSW), Queensland, Northern Territory (NT), South Australia (SA)) will be invited to participate. Participants and carers will complete a baseline questionnaire; follow-ups will be completed at 3, 6, 12 and 24 months. Data collected will include sociodemographic information; out of pocket costs; functional outcome; and measures of pain, itch and scarring. Health-related quality of life will be measured using the PedsQL, and impact of injury using the family impact scale. Clinical data and treatment will also be recorded. Around 225 participants will be recruited allowing complete data on around 130 children. Qualitative data collected by in-depth interviews with families, healthcare providers and policymakers will explore the impact of burn injury and outcomes on family life, needs of patients and barriers to healthcare; interviews with families will be conducted by experienced Aboriginal research staff using Indigenous methodologies. Health systems mapping will describe the provision of care.Ethics and disseminationThe study has been approved by ethics committees in NSW, SA, NT and Queensland. Study results will be distributed to community members by study newsletters, meetings and via the website; to policymakers and clinicians via policy fora, presentations and publication in peer-reviewed journals.
Factors influencing long-term outcomes in relapsing–remitting multiple sclerosis: PRISMS-15
Authors: Kappos Ludwig , Kuhle Jens , Multanen Juha , Kremenchutzky Marcelo , Verdun di Cantogno Elisabetta , Cornelisse Peter , Lehr Lorenz , Casset-Semanaz Florence , Issard Delphine , Uitdehaag Bernard M J 
Published: October 2015

AimAn exploratory study of the relationship between cumulative exposure to subcutaneous (sc) interferon (IFN) β-1a treatment and other possible prognostic factors with long-term clinical outcomes in relapsing–remitting multiple sclerosis (RRMS).MethodsPatients in the original PRISMS study were invited to a single follow-up visit 15 years after initial randomisation (PRISMS-15). Outcomes over 15 years were compared in the lowest and highest quartile of the cumulative sc IFN β-1a dose groups, and according to total time receiving sc IFN β-1a as a continuous variable per 5 years of treatment. Potential prognostic factors for outcomes were analysed.ResultsOf 560 patients randomised in PRISMS, 291 returned for PRISMS-15 and 290 (51.8%) were analysed. Higher cumulative dose exposure and longer treatment time appeared to be associated with better outcomes on: annualised relapse rate, number of relapses, time to Expanded Disability Status Scale (EDSS) progression, change in EDSS, proportions of patients with EDSS ≥4 or ≥6, ≤5 relapses and EDSS <4 or <6, and time to conversion to secondary-progressive MS (SPMS). Higher dose exposure was associated with lower proportions of patients with EDSS progression and conversion to SPMS, and longer time on treatment with lower risk of first relapse. Change in EDSS from baseline to 24 months was a strong predictor of evaluated clinical outcomes over 15 years.ConclusionsThese findings suggest that higher cumulative exposure to sc IFN β-1a may be associated with better clinical outcomes, and early change in EDSS score may have prognostic value, over many years, in RRMS.
OCULAR MG IN 101 CASES: TOWARDS A RISK OF GENERALISATION (‘ROG’) SCORE
Authors: Wong Sui , Petrie Aviva , Plant Gordon 
Published: October 2015

BackgroundThere is no prognostic test to predict generalized myasthenia gravis (GMG) risk in patients with ocular disease. We aimed to create a predictive risk score.MethodMulti-centre retrospective cohort study: OMG for minimum 3 months, untreated with immunosuppression for minimum 2 years or until GMG onset.Results101 (57F) patients included. Median follow-up 8.4 y(2–42) from onset. 31 developed GMG at median 1.31 y (3.5 mo–20.2 y); 19 within 2 y.3 significant predictors from univariable logistic regression analysis (p<0.10); adjusted ORs in multivariable model (Chi-square p=0.001): seropositivity 5.63 (1.42,22.33); presence of ≥1 comorbidity including autoimmune disorders 5.56 (0.66,46.62); thymic hyperplasia 6.66 (0.45,98.01).Prognostic score derived from the coefficients of the logistic model: sum of the points(one point for presence of each of the above predictive factors); classified ‘low risk’ if ≤1, ‘high risk’ if ≥2. Predicted probabilities: 0.07 (SD 0.03) for ‘low risk’, 0.39(SD 0.09) for ‘high risk’. Negative predictive value 91%(79,98), positive predictive value 38% (23,54), area under ROC curve 0.74 (0.64,0.85).ConclusionsWe present one of the few natural history studies on OMG and create the first predictive score to prognosticate the risk of GMG. This approach of risk stratification moves us towards addressing the question of modifying GMG risk in high-risk patients.
SINGLE CENTRE RANDOMISED PILOT STUDY OF TWO REGIMENS (30 MINS DAILY OR 30 MINS WEEKLY FOR 12 WEEKS) OF TRANSCUTANEOUS TIBIAL NERVE STIMULATION USING A NOVEL DEVICE FOR TREATING MULTIPLE SCLEROSIS-RELATED OVERACTIVE BLADDER SYMPTOMS
Authors: Seth Jai , Haslam Collette , Gonzales Gwen , Pakzad Mahreen , Vashisht Arvind , Elneil Sohier , Sahai Arun , Knowles Charles , Tucker Art , Panicker Jalesh 
Published: October 2015

IntroductionPercutaneous tibial nerve stimulation (PTNS) is effective for managing multiple sclerosis (MS)-related overactive bladder (OAB) symptoms. However the need for weekly clinic visits restricts its use. The purpose of this study was to evaluate safety and efficacy of a novel, self-applying device for managing OAB symptoms.Study design, materials and methods48 patients reporting OAB (MS n=24, idiopathic n=24), were randomized (1:1) to either daily or weekly treatments for 12 weeks with geko™, a novel device stimulating the tibial nerve transcutaneously. Efficacy was assessed using validated questionnaires (ICIQ-OAB, ICIQLUTS-QoL) and bladder diaries filled at weeks 4, 8, and 12. Urinary neurotrophins (Nerve growth factor (NGF) and Brain derived neurotrophic factor) were measured.Results34 patients (MS n=19) completed the study. 18 patients responded to treatment (53%); 72% of responders belonged to the MS cohort. Multilevel regression analysis suggested significant improvements in questionnaire scores (ICIQ-OAB –10.2 (–13.5 to –6.9; p=0.001), ICIQLUTS-QOL –40.8 (–57.4 to –24.3; p=0.000)), without differences between weekly and daily-treated arms. No significant adverse effects were reported and patients rated the treatment as easy to use and comfortable. NGF levels at baseline were significantly greater in non-responders (p=0.05).Concluding messageIn this pilot study, a patch device suitable for self-application at home appears to be an effective, safe and convenient alternative for managing MS-related OAB symptoms.
ANTI-JCV TITRES INCREASE OVER TIME WITH NATALIZUMAB TREATMENT
Authors: Raffel Joel , Gafson Arie , Nicholas Richard 
Published: October 2015

ObjectivesThis study sought to evaluate rates of anti-JCV antibody seroconversion and prospective change in antibody titre in a cohort of people with MS receiving natalizumab.MethodsAnti-JCV antibody results (n=1154) from the second-generation STRATIFY JCV™ DxSelect™ test were analysed from an observational cohort of MS patients on natalizumab (n=485; n= 340 with repeat testing).ResultsAt baseline, 59% (287/485) of patients were JCV seropositive; 33% (162/485) had a high anti-JCV antibody index (> 1.5). Baseline titres and rates of seropositivity increased slightly with baseline patient age. With multiple tests repeated over time, 22.3% of seronegative patients converted to seropositive. When comparing pairs of prospective tests, seroconversion rate was greater than seroreversion rate (40/373 (10.7%) vs 18/296 (6.1%); p<0.05). Moreover, anti-JCV antibody titres increased across prospective paired tests (mA-B 0.095; paired t(668)=4.6; p<0.0001) – an effect that was independent of baseline sample titre. This magnitude of antibody level increase far exceeds that expected due to age alone.ConclusionsOur data suggest that natalizumab therapy itself causes anti-JCV antibody titres to increase over time. Future work should investigate the underlying mechanisms, and clinical relevance to risk stratification of this phenomenon.
ANALYSIS OF THE TOPIC STUDY USING 2010 MCDONALD CRITERIA
Authors: Rog David , Wolinsky Jerry , Truffinet Philippe , Thangavelu Karthinathan , Miller Aaron 
Published: October 2015

IntroductionTOPIC (NCT00622700) was designed to evaluate teriflunomide in patients with a first clinical episode suggestive of multiple sclerosis (MS). Teriflunomide 14 mg reduced risk of relapse determining conversion to clinically definite MS by 42.6%, and of new relapse or magnetic resonance imaging lesion by 34.9% vs placebo. After study initiation, the 2005 McDonald criteria were revised, potentially allowing earlier MS diagnosis.MethodsThe 2010 McDonald criteria were applied retrospectively. Patients who received teriflunomide 14 mg or placebo for ≤108 weeks were grouped according to fulfilment of 2010 criteria at baseline. Time to MS was analysed for those not fulfilling the 2010 criteria at baseline. Additional post hoc analyses will evaluate differences in outcomes based on baseline radiological characteristics of reclassified patients.ResultsPatients receiving teriflunomide 14mg (n=214) or placebo (n=197) were analysed. For those not meeting the 2010 criteria (n=163), probability of conversion to MS was 54.1% (14 mg) and 74.4% (placebo). Teriflunomide 14mg reduced the probability of conversion to MS by 39.1% vs placebo. Data regarding time to MS based upon baseline radiological characteristics will be presented.ConclusionsTeriflunomide demonstrates a consistent treatment effect in patients with MS diagnosed according to differing diagnostic criteria. (Study supported by Genzyme, a Sanofi company).
PSYCHOLOGICAL ATTRIBUTES AND WORK INSTABILITY IN MS
Authors: Wicks C R , Ward Karl , Stroud Amanda , Tennant Alan , Ford Helen 
Published: October 2015

For people with MS (PWMS) the relationship between job retention and psychological factors is unclear. This may lead to psychological interventions to aid job retention. This study aims to investigate relationships between psychological factors, work instability and MS in a longitudinal prospective study of PWMS in paid employment.Participants completed two time point questionnaire packs of validated scales with repeat testing planned. 221 employed PWMS were recruited. Mean age was 40.6; 75.1% were female. 91% had relapsing-remitting MS (RRMS). 213 (96.4%) completed the baseline questionnaire, 199 completed month 8. Disease progression was mostly stable with just 3% transitioning from RRMS. 57.2% were at medium/high risk of job loss, with only marginal changes in work instability at 8 months. 14% reported high physical and psychological impact of MS at baseline which remained unchanged. There was a strong association between risk of job loss and both physical and psychological variables. Some psychological variables fluctuated, e.g. depression fell from 24.6% to 14.5%. No changes were reported in levels of fatigue or pain over this period.Psychological attributes in MS appear to fluctuate but contribute to work instability. Further investigation will clarify this relationship and inform possible intervention strategies.
HEAD JOLTING NYSTAGMUS: HEAD-SHAKING-INDUCED OCCLUSION OF THE HORIZONTAL SEMICIRCULAR CANAL
Authors: Kaski Diego , Bronstein Adolfo , Cutfield Nick , Buckwell David , Banga Rupan , Ray Jaydip , Chavda Swarupsinh , Irving Richard 
Published: October 2015

Background and aimsWe report a new syndrome (head jolting nystagmus, HJN) that expands the differential diagnosis of head-movement induced paroxysmal vertigo.Methods and resultsTwo male patients (65 and 58 yrs) described rotational vertigo after violent and brief (1–2 s) oscillations of the head (head jolting) that triggered intense horizontal nystagmus lasting 45s. Accelerations of the head required to induce these episodes could only be achieved by the patients themselves. In Patient 1 the episodes gradually disappeared over a 6–year period. In Patient 2, 3–Tesla MRI suggested a filling defect in the left horizontal semicircular canal. He underwent surgical canal plugging that resolved the symptoms.Conclusion and relevanceWe attribute HJN to dislodged material within the horizontal semicircular canal, and provide a mechanistic model to explain its origin.