bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive ascertainment of bleeding in patients prescribed different combinations of dual antiplatelet therapy (DAPT) and triple therapy (TT) in the UK: study protocol for three population-based cohort studies emulating ‘target trials’ (the ADAPTT Study)
Authors: Pufulete Maria , Harris Jessica , Sterne Jonathan A C , Johnson Thomas W , Lasserson Daniel , Mumford Andrew , Doble Brett , Wordsworth Sarah , Benedetto Umberto , Rogers Chris A , Loke Yoon , Pithara Christalla , Redwood Sabi , Reeves Barnaby C 
Published: June 2019

Introduction‘Real world’ bleeding in patients exposed to different regimens of dual antiplatelet therapy (DAPT) and triple therapy (TT, DAPT plus an anticoagulant) have a clinical and economic impact but have not been previously quantified.Methods and analysisWe will use linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) data to assemble populations eligible for three ‘target trials’ in patient groups: percutaneous coronary intervention (PCI); coronary artery bypass grafting (CABG); conservatively managed (medication only) acute coronary syndrome (ACS). Patients ≥18 years old will be eligible if, in CPRD records, they have: ≥1 year of data before the index event; no prescription for DAPT or anticoagulants in the preceding 3 months; a prescription for aspirin or DAPT within 2 months after discharge from the index event. The primary outcome will be any bleeding event (CPRD or HES) up to 12 months after the index event. We will estimate adjusted HR for time to first bleeding event comparing: aspirin and clopidogrel (reference) versus aspirin and prasugrel or aspirin and ticagrelor after PCI; and aspirin (reference) versus aspirin and clopidogrel after CABG and ACS. We will describe rates of bleeding in patients prescribed TT (DAPT plus an anticoagulant). Potential confounders will be identified systematically using literature review, semistructured interviews with clinicians and a short survey of clinicians. We will conduct sensitivity analyses addressing the robustness of results to the study’s main limitation—that we will not be able to identify the intervention group for patients whose bleeding event occurs before a DAPT prescription in CPRD.Ethics and disseminationThis protocol was approved by the Independent Scientific Advisory Committee for the UK Medicines and Healthcare Products Regulatory Agency Database Research (protocol 16_126R) and the South West Cornwall and Plymouth Research Ethics Committee (17/SW/0092). The findings will be presented in peer-reviewed journals, lay summaries and briefing papers to commissioners/other stakeholders.Trial registration number76607611; Pre-results.
Expanding the spectrum of genes responsible for hereditary motor neuropathies
Authors: Previtali Stefano C. , Zhao Edward , Lazarevic Dejan , Pipitone Giovanni Battista , Fabrizi Gian Maria , Manganelli Fiore , Mazzeo Anna , Pareyson Davide , Schenone Angelo , Taroni Franco , Vita Giuseppe , Bellone Emilia , Ferrarini Moreno , Garibaldi Matteo , Magri Stefania , Padua Luca , Pennisi Elena , Pisciotta Chiara , Riva Nilo , Scaioli Vidmer , Scarlato Marina , Tozza Stefano , Geroldi Alessandro , Jordanova Albena , Ferrari Maurizio , Molineris Ivan , Reilly Mary M. , Comi Giancarlo , Carrera Paola , Devoto Marcella , Bolino Alessandra 
Published: June 2019

BackgroundInherited peripheral neuropathies (IPNs) represent a broad group of genetically and clinically heterogeneous disorders, including axonal Charcot-Marie-Tooth type 2 (CMT2) and hereditary motor neuropathy (HMN). Approximately 60%–70% of cases with HMN/CMT2 still remain without a genetic diagnosis. Interestingly, mutations in HMN/CMT2 genes may also be responsible for motor neuron disorders or other neuromuscular diseases, suggesting a broad phenotypic spectrum of clinically and genetically related conditions. Thus, it is of paramount importance to identify novel causative variants in HMN/CMT2 patients to better predict clinical outcome and progression.MethodsWe designed a collaborative study for the identification of variants responsible for HMN/CMT2. We collected 15 HMN/CMT2 families with evidence for autosomal recessive inheritance, who had tested negative for mutations in 94 known IPN genes, who underwent whole-exome sequencing (WES) analyses. Candidate genes identified by WES were sequenced in an additional cohort of 167 familial or sporadic HMN/CMT2 patients using next-generation sequencing (NGS) panel analysis.ResultsBioinformatic analyses led to the identification of novel or very rare variants in genes, which have not been previously associated with HMN/CMT2 (ARHGEF28,KBTBD13,AGRNandGNE); in genes previously associated with HMN/CMT2 but in combination with different clinical phenotypes (VRK1andPNKP), and in theSIGMAR1gene, which has been linked to HMN/CMT2 in only a few cases. These findings were further validated by Sanger sequencing, segregation analyses and functional studies.ConclusionsThese results demonstrate the broad spectrum of clinical phenotypes that can be associated with a specific disease gene, as well as the complexity of the pathogenesis of neuromuscular disorders.
CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics
Authors: Jeppsson Anna , Wikkelsö Carsten , Blennow Kaj , Zetterberg Henrik , Constantinescu Radu , Remes Anne M , Herukka Sanna-Kaisa , Rauramaa Tuomas , Nagga Katarina , Leinonen Ville , Tullberg Mats 
Published: June 2019

ObjectiveTo examine the differential diagnostic significance of cerebrospinal fluid (CSF) biomarkers reflecting Alzheimer’s disease-related amyloid β (Aβ) production and aggregation, cortical neuronal damage, tau pathology, damage to long myelinated axons and astrocyte activation, which hypothetically separates patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders.MethodsThe study included lumbar CSF samples from 82 patients with iNPH, 75 with vascular dementia, 70 with Parkinson’s disease, 34 with multiple system atrophy, 34 with progressive supranuclear palsy, 15 with corticobasal degeneration, 50 with Alzheimer’s disease, 19 with frontotemporal lobar degeneration and 54 healthy individuals (HIs). We analysed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ), Aβ species (Aβ38, Aβ40 and Aβ42), total tau (T-tau), phosphorylated tau, neurofilament light and monocyte chemoattractant protein 1 (MCP-1).ResultsPatients with iNPH had lower concentrations of tau and APP-derived proteins in combination with elevated MCP-1 compared with HI and the non-iNPH disorders. T-tau, Aβ40 and MCP-1 together yielded an area under the curve of 0.86, differentiating iNPH from the other disorders. A prediction algorithm consisting of T-tau, Aβ40 and MCP-1 was designed as a diagnostic tool using CSF biomarkers.ConclusionsThe combination of the CSF biomarkers T-tau, Aβ40 and MCP-1 separates iNPH from cognitive and movement disorders with good diagnostic sensitivity and specificity. This may have important implications for diagnosis and clinical research on disease mechanisms for iNPH.
Impact of e-cigarette and cigarette prices on youth and young adult e-cigarette and cigarette behaviour: evidence from a national longitudinal cohort
Authors: Cantrell Jennifer , Huang Jidong , Greenberg Marisa S , Xiao Haijuan , Hair Elizabeth C , Vallone Donna 
Published: June 2019

IntroductionUnderstanding the impact of prices for tobacco and nicotine products is critical for creating policies to prevent use among young people. This study examines the impact of electronic cigarette (e-cigarette) and cigarette prices on current e-cigarette and cigarette use among youth and young adults.MethodsData were from a national probability-based sample aged 15–21 collected in 2014 and followed every 6 months for 2.5 years through 2016. We conducted separate conditional likelihood logistic regression models with past 30-day e-cigarette use and past 30-day cigarette use outcomes on the sample of individuals who participated in at least two survey waves (n=11 578) with linked Nielsen market-level price data for rechargeable e-cigarettes and cigarettes. Models controlled for time-varying variables at the individual and state policy levels, and fixed effects at the individual, wave and market levels.ResultsHigher cigarette prices were associated with increased past 30-day e-cigarette use, indicating e-cigarettes may serve as a substitute for cigarettes. We did not find a statistically significant relationship between rechargeable e-cigarette prices and past 30-day e-cigarette use; neither did we find a significant relationship between rechargeable e-cigarette prices and past 30-day cigarette smoking.ConclusionThis is the first study to examine e-cigarette and cigarette prices on e-cigarette and cigarette behaviour longitudinally among young people. Findings suggest the need for better measuring the costs associated with e-cigarette use among this population, as well as a careful assessment of price and tax policies that takes into account cross-product impact to sufficiently discourage e-cigarette and cigarette use among young people.
Effects of cerebellar transcranial direct current stimulation on the cognitive stage of sequence learning
Authors: Ballard Hannah K. , Goen James R. M. , Maldonado Ted , Bernard Jessica A. 
Published: June 2019

Though the cerebellum has been previously implicated in explicit sequence learning, the exact role of this structure in the acquisition of motor skills is not completely clear. The cerebellum contributes to both motor and nonmotor behavior. Thus, this structure not only may contribute to the motoric aspects of sequence learning but may also play a role in the cognitive components of these learning paradigms. Therefore, we investigated the consequence of both disrupting and facilitating cerebellar function using high-definition transcranial direct current stimulation (tDCS) before the completion of an explicit motor sequence learning paradigm. Using a mixed within- and between-subjects design, we employed cathodal ( n = 21) and anodal ( n = 23) tDCS (relative to sham), targeting the lateral posterior cerebellum, to temporarily modulate function and investigate the resulting effects on the acquisition of a sequential pattern of finger movements. Results indicate that cathodal stimulation has a positive influence on learning while anodal stimulation has the opposite effect, relative to sham. Though the cerebellum is presumed to be primarily involved in motor function and movement coordination, our results support a cognitive contribution that may come into play during the initial stages of learning. Using tDCS targeting the right posterior cerebellum, which communicates with the prefrontal cortex via closed-loop circuits, we found polarity-specific effects of cathodal and anodal stimulation on sequence learning. Thus, our results substantiate the role of the cerebellum in the cognitive aspect of motor learning and provide important new insights into the polarity-specific effects of tDCS in this area. NEW & NOTEWORTHY The cerebellum contributes to motor and cognitive processes. Investigating the cognitive contributions of the cerebellum in explicit sequence learning stands to provide new insights into this learning domain, and cerebellar function more generally. Using high-definition transcranial direct current stimulation, we demonstrated polarity-specific effects of stimulation on explicit sequence learning. We speculate that this is due to facilitation of working memory processes. This provides new evidence supporting a role for the cerebellum in the cognitive aspects of sequence learning.
Allergies and Asthma in Relation to Cancer Risk
Authors: Kantor Elizabeth D. , Hsu Meier , Du Mengmeng , Signorello Lisa B. 
Published: June 2019

AbstractBackground:Allergies and asthma, conditions commonly characterized by immunoglobulin E–mediated atopic reactions, may decrease cancer risk via increases in immunosurveillance, but may increase risk due to persistent immune stimulation. Associations between allergies and asthma and cancer risk remain unclear, and it is unknown whether associations vary by race/ethnicity.Methods:We evaluated these associations in the Southern Community Cohort Study. At baseline (2002–2009), 64,170 participants were queried on history of allergies and asthma; participants were followed through 2011, during which time 3,628 incident, invasive cancers were identified, including 667 lung cancers, 539 breast cancers, and 529 prostate cancers. Cox proportional hazards regression was used to estimate multivariable-adjusted HRs and 95% confidence intervals (CI).Results:Neither allergies nor asthma was associated with risk of developing invasive cancer overall. Asthma was associated with increased lung cancer risk (HR, 1.25; 95% CI, 1.00–1.57), with no variation by race/ethnicity (Pinteraction = 0.84). Conversely, history of allergies was associated with decreased lung cancer risk (HR, 0.80; 95% CI, 0.65–1.00), with an inverse association observed among non-Hispanic whites (HR, 0.65; 95% CI, 0.45–0.94) but not non-Hispanic blacks (HR, 0.95; 95% CI, 0.73–1.25; Pinteraction = 0.10). No statistically significant associations were observed for risk of breast or prostate cancers, overall or by race/ethnicity.Conclusions:No associations were observed for risk of overall cancer, breast cancer, or prostate cancer. While asthma was associated with increased lung cancer risk, history of allergies was associated with decreased risk, an association driven by an inverse association among non-Hispanic whites.Impact:Associations pertaining to lung cancer merit follow up in a large, diverse study.
Ocorrência de intercalação de rocha fosfática na Formação Ponta Grossa em Rio Verde de Mato Grosso, Mato Grosso do Sul: implicações paleoambientais
Authors: Montibeller Cibele Carolina , Zanardo Antenor , Navarro Guillermo Rafael Beltran 
Published: June 2019

Entre as rochas da Formação Ponta Grossa, aflorantes no município de Rio Verde de Mato Grosso, é registrada a presença de camadas constituídas predominantemente por apatita, não fossilíferas, que ocorrem como estratos destacados intercalados em folhelhos cinzas-escuros a pretos. Petrograficamente, essa rocha fosfática apresenta estrutura sutilmente laminada e não são observadas feições indicativas de algas, restos fósseis ou de estruturas orgânicas. Possui teores de P2O5 variando entre 12,96 e 23,35%, teores de CaO variando entre 19,85 e 33,04%, e possui alta concentração de elementos terras raras (ETR) em relação à média da crosta continental superior. Essa ocorrência não possui evidências de ação biogênica — o que é confirmado pela microscopia eletrônica — e possui relictos de oxi-hidróxidos, preferencialmente de ferro, com pequena quantidade de manganês, sugerindo origem pela dessorção de fosfato por comportamento redox a partir desses relictos. As condições de formação dessas fosforitas — se não condicionadas a aporte externo de oxi-hidróxidos de ferro pela proximidade da costa, por ambientes deltaicos ou por contribuições hidrotermais e/ou vulcânicas — colocam as camadas fosfáticas de Rio Verde de Mato Grosso, Mato Grosso do Sul, em condições de ambiente marinho plataformal raso, com profundidade entre 200 e 300 m, de águas frias e com baixa salinidade, preferencialmente anóxico, e suscetível a estabelecimento de zona de ressurgência.
High-Power (40–50 W) Radiofrequency Ablation Guided by Unipolar Signal Modification for Pulmonary Vein Isolation
Authors: Pambrun Thomas , Durand Cyril , Constantin Marion , Masse Alexandre , Marra Céline , Meillet Valentin , Haïssaguerre Michel , Jaïs Pierre , Bortone Agustín 
Published: June 2019

Background:
Although proposed to facilitate pulmonary vein isolation (PVI), high-power ablation may favor extracardiac damage. Negative component abolition of the unipolar signal reflects lesion transmurality. The present study sought to evaluate the safety and efficacy of high-power ablation using unipolar signal modification as a local end point.

Methods
High power and standard power were compared in 4 swine and 100 consecutive patients referred for PVI. The first 50 patients were included in the control group (25–30 W) and the last 50 patients in the study group (40–50 W). Atrial radiofrequency applications were stopped 2 s (study group and swine) or 5 s (control group) after unipolar signal modification. Ventricular radiofrequency applications of 500 J (25 W·20 s versus 50 W·10 s) were performed at the swine epicardium.

Results:

Swine gross necropsy did not show any extracardiac damage related to atrial lesions. At equal energy of 500 J, 50 W lesions were deeper (3±0.9 versus 2.6±1.1 mm;
P
=0.03) and wider (6.2±2 versus 5±2.3 mm;
P
=0.006) than 25 W lesions. No complications occurred during the clinical study, whatever the power output used for PVI. For a similar sinus rhythm maintenance at 12 months (90% versus 88%;
P
=0.75), the study group displayed higher first-pass PVI (92% versus 73%;
P
<0.001), lower acute pulmonary vein reconnection (2% versus 17%;
P
<0.001), reduced procedure time (73.1±18.2 versus 107.4±21.2 min;
P
<0.001), and ablation time (13±2.9 versus 30.3±8.8 min;
P
<0.001).

Conclusions:
High-power PVI guided by unipolar signal modification safely decreases procedural burden while ensuring robust 12-month outcomes.
Age at Menarche and Risk of Cardiovascular Disease Outcomes: Findings From the National Heart Lung and Blood Institute‐Sponsored Women's Ischemia Syndrome Evaluation
Authors: Lee Julie J. , Cook‐Wiens Galen , Johnson B. Delia , Braunstein Glenn D. , Berga Sarah L. , Stanczyk Frank Z. , Pepine Carl J. , Bairey Merz C. Noel , Shufelt Chrisandra L. 
Published: June 2019

Background

Previous studies have reported an association between the timing of menarche and cardiovascular disease (
CVD
). However, emerging studies have not examined the timing of menarche in relation to role of estrogen over a lifetime and major adverse cardiac events (
MACE
).

Methods and Results

A total of 648 women without surgical menopause undergoing coronary angiography for suspected ischemia in the
WISE
(Women's Ischemia Syndrome Evaluation) study were evaluated at baseline and followed for 6 years (median) to assess major adverse
CVD
outcomes.
MACE
was defined as the first occurrence of all‐cause death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization. Age at menarche was self‐reported and categorized (≤10, 11, 12, 13, 14, ≥15 years) with age 12 as reference. Total estrogen time and supra–total estrogen time were calculated. Cox regression analysis was performed adjusting for
CVD
risk factors. Baseline age was 57.9 ± 12 years (mean ±
SD
), body mass index was 29.5 ± 6.5 kg/m
2
, total estrogen time was 32.2 ± 8.9 years, and supra–total estrogen time was 41.4 ± 8.8 years.
MACE
occurred in 172 (27%), and its adjusted regression model was J‐shaped. Compared with women with menarche at age 12 years, the adjusted
MACE
hazard ratio for menarche at ≤10 years was 4.53 (95%
CI
2.13‐9.63); and at ≥15 years risk for
MACE
was 2.58 (95%
CI
, 1.28‐5.21).

Conclusions

History of early or late menarche was associated with a higher risk for adverse
CVD
outcomes. These findings highlight age at menarche as a potential screening tool for women at risk of adverse
CVD
events.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00000554.
Revascularization of High-Grade Carotid Stenosis Restores Global Cerebral Energy Metabolism
Authors: Seiler Alexander , Kammerer Sara , Gühl Alexander , Schüre Jan Rüdiger , Deichmann Ralf , Nöth Ulrike , Pfeilschifter Waltraud , Hattingen Elke , Keese Michael , Pilatus Ulrich , Wagner Marlies 
Published: June 2019

Background and Purpose—

Chronic cerebral hemodynamic impairment due to high-grade occlusive carotid disease may lead to compromised energy metabolism. This might result in chronic subtle tissue damage, even in patients without overt brain infarction. The aim of this study was to investigate hypoperfusion-related changes of cerebral energy metabolism and their potential restitution after revascularization. For this purpose, 3-dimensional
31
P magnetic resonance spectroscopy and oxygenation-sensitive T2′ magnetic resonance imaging were used (with 1/T2′=1/T2*−1/T2), which were expected to cross-validate each other.

Methods—
Ten patients with unilateral high-grade carotid artery stenosis resulting in a transient ischemic attack or a nondisabling cerebral ischemia were included. Then, high-energy metabolites, intracellular pH, and oxygenation-sensitive quantitative (q)T2′ values were determined in noninfarcted hypoperfused areas delineated on time-to-peak maps from perfusion-weighted imaging and in unaffected contralateral areas before and shortly after carotid stenting/endarterectomy. Repeated measures ANOVA was used to test for intervention effects.

Results—

Within dependent hypoperfused areas ipsilateral to the stenosis, qT2′ was significantly decreased (
P
<0.05) as compared to corresponding contralateral areas before carotid intervention. There was a significant effect of carotid intervention on qT2′ values in both hemispheres (
P
<0.001). No differences between hemispheres were found for qT2′ after revascularization. Intracellular pH and qT2′ values showed a significant negative relationship (
P
=0.005) irrespective of time point and hemisphere.

Conclusions—
After revascularization of unilateral high-grade carotid stenosis, previously decreased qT2′ in the dependent hypoperfused territory as marker of hypoxia reincreases not only in the dependent territory but also in corresponding contralateral brain tissue. This might indicate a restriction of the whole-brain oxygen metabolism in case of unilateral high-grade carotid stenosis and an improvement of whole-brain oxygenation after revascularization that goes beyond acute clinically apparent affection of the dependent territory. Furthermore, tissue oxygen supply seems to be closely linked to intracellular pH.
Computing Methodologies Supporting the Preservation of Electroacoustic Music from Analog Magnetic Tape
Authors: Pretto Niccoló , Fantozzi Carlo , Micheloni Edoardo , Burini Valentina , Canazza Sergio 
Published: June 2019

Abstract
Electroacoustic music on analog magnetic tape is characterized by several carrier-related specificities that must be considered when creating a copy for digital preservation. The tape recorder needs to be set to the correct speed and equalization, and the magnetic tape could have some intentional or unintentional alterations. During both the creation and the musicological analysis of a digital preservation copy, the quality of the work may be affected by human inattention. This article presents a methodology based on neural networks to recognize and classify the alterations of a magnetic tape from the video of the tape as it passes in front of the tape recorder's playback head. Furthermore, some machine-learning techniques have been tested to recognize a tape's equalization from its background noise. The encouraging results open the way to innovative tools able to unburden audio technicians and musicologists from repetitive tasks and to improve the quality of their work.
Royal Imagery on Kushan Coins: Local Tradition and Arsacid Influences
Authors: Sinisi Fabrizio 
Published: June 2019

Abstract
This article deals with the development of Kushan royal imagery as known from coins in the period between the 1st and the 3rd centuries ad, i.e. from the so-called Heraios series to the coins of Vasudeva. The aim is to challenge the traditional interpretative models which ascribed a crucial role to a Roman contribution, and to highlight instead first the role of the local numismatic tradition, which stretched back to the Graeco-Bactrians, and then the influx of patterns of royal imagery of western Iranian—namely Arsacid Parthian—origin, around the time when Vima Kadphises inaugurated a new imperial coinage.