bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acid Sphingomyelinase Regulates Platelet Cell Membrane Scrambling, Secretion, and Thrombus Formation
Authors: Münzer Patrick , Borst Oliver , Walker Britta , Schmid Evi , Feijge Marion A. H. , Cosemans Judith M. E. M. , Chatterjee Madhumita , Schmidt Eva-Maria , Schmidt Sebastian , Towhid Syeda T. , Leibrock Christina , Elvers Margitta , Schaller Martin , Seizer Peter , Ferlinz Klaus , May Andreas E. , Gulbins Erich , Heemskerk Johan W. M. , Gawaz Meinrad , Lang Florian 
Published: November 2013

Objective—
Platelet activation is essential for primary hemostasis and acute thrombotic vascular occlusions. On activation, platelets release their prothrombotic granules and expose phosphatidylserine, thus fostering thrombin generation and thrombus formation. In other cell types, both degranulation and phosphatidylserine exposure are modified by sphingomyelinase-dependent formation of ceramide. The present study thus explored whether acid sphingomyelinase participates in the regulation of platelet secretion, phosphatidylserine exposure, and thrombus formation.

Approach and Results—

Collagen-related peptide–induced or thrombin-induced ATP release and P-selectin exposure were significantly blunted in platelets from Asm-deficient mice (
Smpd1
−/−
) when compared with platelets from wild-type mice (
Smpd1

+/+

). Moreover, phosphatidylserine exposure and thrombin generation were significantly less pronounced in
Smpd1
−/−
platelets than in
Smpd1

+/+

platelets. In contrast, platelet integrin α
IIb
β
3
activation and aggregation, as well as activation-dependent Ca
2+
flux, were not significantly different between
Smpd1
−/−
and
Smpd1

+/+

platelets. In vitro thrombus formation at shear rates of 1700 s
−1
and in vivo thrombus formation after FeCl
3
injury were significantly blunted in
Smpd1
−/−
mice while bleeding time was unaffected. Asm-deficient platelets showed significantly reduced activation-dependent ceramide formation, whereas exogenous ceramide rescued diminished platelet secretion and thrombus formation caused by Asm deficiency. Treatment of
Smpd1

+/+

platelets with bacterial sphingomyelinase (0.01 U/mL) increased, whereas treatment with functional acid sphingomyelinase-inhibitors, amitriptyline or fluoxetine (5 μmol/L), blunted activation-dependent platelet degranulation, phosphatidylserine exposure, and thrombus formation. Impaired degranulation and thrombus formation of
Smpd1
−/−
platelets were again overcome by exogenous bacterial sphingomyelinase.

Conclusions—
Acid sphingomyelinase is a completely novel element in the regulation of platelet plasma membrane properties, secretion, and thrombus formation.
Impact of Nonischemic Scar Features on Local Ventricular Electrograms and Scar-Related Ventricular Tachycardia Circuits in Patients With Nonischemic Cardiomyopathy
Authors: Sasaki Takeshi , Miller Christopher F. , Hansford Rozann , Zipunnikov Vadim , Zviman Menekhem M. , Marine Joseph E. , Spragg David , Cheng Alan , Tandri Harikrishna , Sinha Sunil , Kolandaivelu Aravindan , Zimmerman Stefan L. , Bluemke David A. , Tomaselli Gordon F. , Berger Ronald D. , Halperin Henry R. , Calkins Hugh , Nazarian Saman 
Published: November 2013

Background—
The association of local electrogram features with scar morphology and distribution in nonischemic cardiomyopathy has not been investigated. We aimed to quantify the association of scar on late gadolinium-enhanced cardiac magnetic resonance with local electrograms and ventricular tachycardia circuit sites in patients with nonischemic cardiomyopathy.

Methods and Results—

Fifteen patients with nonischemic cardiomyopathy underwent late gadolinium-enhanced cardiac magnetic resonance before ventricular tachycardia ablation. The transmural extent and intramural types (endocardial, midwall, epicardial, patchy, transmural) of scar were measured in late gadolinium-enhanced cardiac magnetic resonance short-axis planes. Electroanatomic map points were registered to late gadolinium-enhanced cardiac magnetic resonance images. Myocardial wall thickness, scar transmurality, and intramural scar types were independently associated with electrogram amplitude, duration, and deflections in linear mixed-effects multivariable models, clustered by patient. Fractionated and isolated potentials were more likely to be observed in regions with higher scar transmurality (
P
<0.0001 by ANOVA) and in regions with patchy scar (versus endocardial, midwall, epicardial scar;
P
<0.05 by ANOVA). Most ventricular tachycardia circuit sites were located in scar with >25% scar transmurality.

Conclusions—
Electrogram features are associated with scar morphology and distribution in patients with nonischemic cardiomyopathy. Previous knowledge of electrogram image associations may optimize procedural strategies including the decision to obtain epicardial access.
Spatial Profiles of Electrical Mismatch Determine Vulnerability to Conduction Failure Across a Host–Donor Cell Interface
Authors: Kirkton Robert D. , Badie Nima , Bursac Nenad 
Published: November 2013

Background—
Electrophysiological mismatch between host cardiomyocytes and donor cells can directly affect the electrical safety of cardiac cell therapies; however, the ability to study host–donor interactions at the microscopic scale in situ is severely limited. We systematically explored how action potential (AP) differences between cardiomyocytes and other excitable cells modulate vulnerability to conduction failure in vitro.

Methods and Results—

AP propagation was optically mapped at 75 μm resolution in micropatterned strands (n=152) in which host neonatal rat ventricular myocytes (AP duration=153.2±2.3 ms, conduction velocity=22.3±0.3 cm/s) seamlessly interfaced with genetically engineered excitable donor cells expressing inward rectifier potassium (Kir2.1) and cardiac sodium (Na
v
1.5) channels with either weak (conduction velocity=3.1±0.1 cm/s) or strong (conduction velocity=22.1±0.4 cm/s) electrical coupling. Selective prolongation of engineered donor cell AP duration (31.9–139.1 ms) by low-dose BaCl
2
generated a wide range of host–donor repolarization time (RT) profiles with maximum gradients (∇RT
max
) of 5.5 to 257 ms/mm. During programmed stimulation of donor cells, the vulnerable time window for conduction block across the host–donor interface most strongly correlated with ∇RT
max
. Compared with well-coupled donor cells, the interface composed of poorly coupled cells significantly shortened the RT profile width by 19.7% and increased ∇RT
max
and vulnerable time window by 22.2% and 19%, respectively. Flattening the RT profile by perfusion of 50 μmol/L BaCl
2
eliminated coupling-induced differences in vulnerability to block.

Conclusions—
Our results quantify how the degree of electrical mismatch across a cardiomyocyte–donor cell interface affects vulnerability to conduction block, with important implications for the design of safe cardiac cell and gene therapies.
Modeling Obliquity and CO2 Effects on Southern Hemisphere Climate during the Past 408 ka*
Authors: Timmermann Axel , Friedrich Tobias , Timm Oliver Elison , Chikamoto Megumi O. , Abe-Ouchi Ayako , Ganopolski Andrey 
Published: November 2013

AbstractThe effect of obliquity and CO2 changes on Southern Hemispheric climate is studied with a series of numerical modeling experiments. Using the Earth system model of intermediate complexity Loch–VECODE–ECBilt–CLIO–Agism Model (LOVECLIM) and a coupled general circulation model [Model for Interdisciplinary Research on Climate (MIROC)], it is shown in time-slice simulations that phases of low obliquity enhance the meridional extratropical temperature gradient, increase the atmospheric baroclinicity, and intensify the lower and middle troposphere Southern Hemisphere westerlies and storm tracks. Furthermore, a transient model simulation is conducted with LOVECLIM that covers the greenhouse gas, ice sheet, and orbital forcing history of the past 408 ka. This simulation reproduces reconstructed glacial–interglacial variations in temperature and sea ice qualitatively well and shows that the meridional heat transport associated with the orbitally paced modulation of middle troposphere westerlies and storm tracks partly offsets the effects of the direct shortwave obliquity forcing over Antarctica, thereby reinforcing the high correlation between CO2 radiative forcing and Antarctic temperature. The overall timing of temperature changes in Antarctica is hence determined by a balance of shortwave obliquity forcing, atmospheric heat transport changes, and greenhouse gas forcing. A shorter 130-ka transient model experiment with constant CO2 concentrations further demonstrates that surface Southern Hemisphere westerlies are primarily modulated by the obliquity cycle rather than by the CO2 radiative forcing.
Lower anterior cingulate volume in seriously violent men with antisocial personality disorder or schizophrenia and a history of childhood abuse
Authors: Kumari Veena , Uddin Shahir , Premkumar Preethi , Young Susan , Gudjonsson Gisli H , Raghuvanshi Satya , Barkataki Ian , Sumich Alexander , Taylor Pamela , Das Mrigendra 
Published: November 2013

Objective: Antisocial personality disorder (ASPD) and schizophrenia, as well as childhood abuse, are associated with violent behaviour and show marked volumetric reduction in the anterior cingulate (AC), a brain region implicated in regulation of violence through its involvement in decision making, empathy, impulse control, and emotion regulation. The present study examined, for the first time to the authors’ knowledge, the grey matter volume of the AC in relation to seriously violent behaviour and childhood psychosocial deprivation (including physical and sexual abuse) in the context of a mental disorder (schizophrenia or ASPD). Methods: Fifty-seven men [14 with ASPD and a history of serious violence; 13 with schizophrenia and a history of serious violence (VSZ); 15 with schizophrenia without a violence history (SZ); 15 nonviolent healthy participants] underwent whole-brain magnetic resonance imaging and were rated on the presence of physical abuse, sexual abuse, neglect, extreme poverty, foster home placement, criminal parent, severe family conflict, and broken home (collectively ‘psychosocial deprivation’). Stereological volumetric ratings of the AC were examined for group differences and their association with childhood psychosocial deprivation. Results: A higher proportion of ASPD and VSZ patients had suffered psychosocial deprivation as children, in particular severe physical abuse, relative to SZ patients and healthy participants. ASPD and VSZ, but not SZ, patients had significantly lower AC volume relative to healthy participants. AC volumes correlated negatively with (total) psychosocial deprivation as well as physical and sexual abuse ratings. Group differences in AC volume became nonsignificant when psychosocial deprivation ratings were covaried for. Conclusions: Violent mentally disordered individuals with ASPD or schizophrenia suffer from a significant AC volume loss and this deficit, at least in part, is explained by their histories of stressful childhood experiences. Current and future therapies aiming to reduce violence in such populations would benefit by attending to biological (and other) correlates of childhood abuse.
Revisiting formulation: Part 1. The tasks of formulation: their rationale and philosophic basis
Authors: Smith Graeme C 
Published: November 2013

Objective: This paper notes the continuing problems that Royal Australian and New Zealand College of Psychiatry (RANZCP) candidates and other professionals have with the task of formulation. It re-establishes this as a problematic to be understood and reviews its intellectual history, its rationale, the tools of reasoning that it requires and the nature of the challenges that it can pose to individuals. Its premise is that an understanding of the theoretical basis of formulation is required prior to application of pedagogical tools in teaching and remediation. Four tasks of formulation implied in the definition provided in the RANZCP Formulation Guidelines for Candidates are identified, and their rationale and theoretical status reviewed. Conclusion: Task 1, classification, must address both diagnoses and problems. Task 2, using theory to infer meaning, ideally requires multiple models and theories in development of a set of hypotheses, using inductive inference (plausibility). Task 3, prioritising hypotheses, requires abduction, defined as inference to the best explanation. Task 4, integrating hypotheses, may aim for reconciling systems (syncretism), but is likely to use the more problematic eclecticism. The task of formulation is thus challenging but well prescribed by philosophers for thousands of years.
LUNOKID: can numerical American Thoracic Society/European Respiratory Society quality criteria replace visual inspection of spirometry?
Authors: Müller-Brandes Christine , Krämer Ursula , Gappa Monika , Seitner-Sorge Gabriele , Hüls Anke , von Berg Andrea , Hoffmann Barbara , Schuster Antje , Illi Sabina , Wisbauer Matthias , Berdel Dietrich 
Published: November 2013

The gold standard for assessing quality of forced expiratory manoeuvres is visual inspection by an expert. American Thoracic Society/European Respiratory Society numerical quality criteria (NQC) include back-extrapolated volume (BEV), repeatability and forced expiratory time (FET). Equipment currently available provides feedback tempting the investigator to use NQC as pass–fail criterion.To investigate whether using NQC instead of visual acceptability is a valid option, we analysed data from a multicentre national reference study in Germany of children aged 4–18 years. Spirometry was performed under field conditions. Receiver operating characteristic analysis was used to assess performance of BEV, repeatability, FET and a combination thereof in relation to visual acceptability.We included data from 3133 healthy Caucasians in the analyses; 72% delivered at least two visually acceptable manoeuvres. Of these, 59% would have been rejected based on combined NQC, mainly because the FET criterion was not feasible. Specificity of the NQC was generally low (BEV 10%, repeatability 30% and FET 50%). Receiver operating characteristic analysis showed that a combination of the three measures could reach at best a sensitivity of 90% and specificity of 56%.We conclude that visual control is mandatory and NQC may help obtain the best possible results, but a fixed cut-off for FET should be abandoned.
Effects of apolipoprotein E genotype on serum lipids in obstructive sleep apnoea
Authors: Tisko Radovan , Sopkova Zuzana , Habalova Viera , Dorkova Zuzana , Slaba Eva , Javorsky Martin , Tkac Ivan , Riha Renata L. , Tkacova Ruzena 
Published: November 2013

There is increasing evidence that intermittent hypoxia resulting from obstructive sleep apnoea (OSA) is independently associated with dyslipidaemia. Currently, no data exist on potential links between OSA-related dyslipidaemia and susceptibility genes for dyslipidaemia in such patients. Our aim was to study the effects of the apolipoprotein E (APOE) genotype and sleep apnoea severity on atherogenic dyslipidaemia in patients with OSA.519 clinically stable subjects prospectively recruited at a tertiary referral teaching hospital underwent full polysomnography.APOEgene polymorphisms were assessed using real-time PCR.In allAPOEgenotype groups, serum triglycerides increased while high-density lipoprotein (HDL) cholesterol was reduced with increasing severity of OSA in eachAPOEgenotype group, whereas the deleterious effects of OSA on serum apolipoprotein (Apo)B levels were observed in ϵ2 carriers and the ϵ3/ϵ3 genotype only. Nevertheless, the ϵ4 allele carriers had ApoB levels within the risk range, irrespective of nocturnal hypoxia. In addition, among patients with the high-risk ϵ4 genotype, those with the most severe nocturnal hypoxia had significantly higher triglyceride and lower HDL cholesterol levels compared with nonhypoxic ϵ4 subjects.APOEgenotype and the oxygen desaturation index were both independent predictors of serum triglyceride levels (p=0.009 and p<0.001, respectively;R2=0.148) and ApoB levels (p=0.001 and p=0.003, respectively;R2=0.104).Our findings suggest that OSA has adverse effects on several lipid parameters over and above the effects carried byAPOEgenotype. Further st1udies are needed to analyse the effects of high-risk genotypes on metabolic and cardiovascular outcomes in patients with OSA.
STaRRRT: a table of short tandem repeats in regulatory regions of the human genome
Authors: Bolton Katherine A , Ross Jason P , Grice Desma M , Bowden Nikola A , Holliday Elizabeth G , Avery-Kiejda Kelly A , Scott Rodney J 
Published: November 2013

Abstract

Background
Tandem repeats (TRs) are unstable regions commonly found within genomes that have consequences for evolution and disease. In humans, polymorphic TRs are known to cause neurodegenerative and neuromuscular disorders as well as being associated with complex diseases such as diabetes and cancer. If present in upstream regulatory regions, TRs can modify chromatin structure and affect transcription; resulting in altered gene expression and protein abundance. The most common TRs are short tandem repeats (STRs), or microsatellites. Promoter located STRs are considerably more polymorphic than coding region STRs. As such, they may be a common driver of phenotypic variation. To study STRs located in regulatory regions, we have performed genome-wide analysis to identify all STRs present in a region that is 2 kilobases upstream and 1 kilobase downstream of the transcription start sites of genes.

Results
The Short Tandem Repeats in Regulatory Regions Table, STaRRRT, contains the results of the genome-wide analysis, outlining the characteristics of 5,264 STRs present in the upstream regulatory region of 4,441 human genes. Gene set enrichment analysis has revealed significant enrichment for STRs in cellular, transcriptional and neurological system gene promoters and genes important in ion and calcium homeostasis. The set of enriched terms has broad similarity to that seen in coding regions, suggesting that regulatory region STRs are subject to similar evolutionary pressures as STRs in coding regions and may, like coding region STRs, have an important role in controlling gene expression.

Conclusions
STaRRRT is a readily-searchable resource for investigating potentially polymorphic STRs that could influence the expression of any gene of interest. The processes and genes enriched for regulatory region STRs provide potential novel targets for diagnosing and treating disease, and support a role for these STRs in the evolution of the human genome.
Japanese trends in breastfeeding rate in baby-friendly hospitals between 2007 and 2010: a retrospective hospital-based surveillance study
Authors: Yoda Takashi , Takahashi Kenzo , Yamauchi Yoshitada 
Published: November 2013

Abstract

Background
The goal of Japan’s national “Healthy and Happy Family 21” campaign is to increase the nationwide breastfeeding rate for babies in the first month of life, which is currently below 50%, to a level of 60%. In this article, we summarize the breastfeeding rate for all of Japan’s baby-friendly hospitals (BFHs) and extract their strengths in conjunction with the structural and legislative support that they have in place and finally draw up a policy for dispersing BFH activities to non-BFH delivery facilities, which could be useful for increasing the breastfeeding rate.

Methods
This study included all of the 61 BFHs that are registered in Japan. These hospitals account for approximately 2% of nearly 3,000 Japanese delivery facilities. The surveillance data, which were collected anonymously by the Japan Breastfeeding Association in 2007–2010, were summarized. The numbers of babies who were breastfed after delivery, at discharge from BFHs and at one month of age, were collated. The length of hospital/clinic stay was also collected.

Results
The collection rate was 100% in each year (2007, 2008, 2009 and 2010). The breastfeeding rates during hospital stay, at discharge, and one month were >70%, ~90%, and >75%, respectively. The median length of stay was 5 days (minimum/maximum: 5/8) for primipara.

Conclusions
The breastfeeding rate at BFHs at one month of age was more than 75%. This surpassed the current national average (<50%). The median length of hospital/clinic stay was 5 days. In this 5-day period, BFH activities can play an important role in increasing the breastfeeding rate. Since hospitalization for the reported national median length of stay of 6 days, is legally guaranteed, the disbursement of BFH activities to non-BFH delivery facilities, with special support to mothers who delivered by cesarean delivery, would be a useful strategy for achieving a 60% breastfeeding rate at one month of age.
Sex-for-Crack exchanges: associations with risky sexual and drug use niches in an urban Canadian city
Authors: Duff Putu , Tyndall Mark , Buxton Jane , Zhang Ruth , Kerr Thomas , Shannon Kate 
Published: November 2013

AbstractBackgroundWhile crack cocaine has been associated with elevated sexual risks and transmission of HIV/STIs, particularly in the context of street-based sex work, few empirical studies have examined correlates of direct sex-for-crack exchanges. This study longitudinally examined the correlates of sex-for-crack exchanges and associated effects on sexual risk outcomes among street-based female sex workers (SW) who use drugs in Vancouver, Canada.MethodsData were drawn from a prospective cohort of street-based SWs (2006–2008), restricted to those who smoke crack cocaine. Multivariable generalized estimating equations (GEE) were employed to examine the correlates of exchanging sex for crack. A confounding model using GEE quasi-Poisson regression modeled the independent effect of exchanging sex for crack on number of clients/week.ResultsOf 206 SWs, 101 (49%) reported sex-for-crack exchanges over 18 months of follow-up. In multivariable GEE analyses, sharing a crack pipe with a client (aOR = 1.98; 95%CI: 1.27-3.08) and smoking crack in a group of strangers (e.g., in an alley or crackhouse) (aOR = 1.70; 95% CI: 1.13-2.58) were independently correlated with sex-for-crack exchanges. In our confounding model, exchanging sex for crack (aIRR = 1.34; 95% CI: 1.07-1.69) remained significantly associated with servicing a greater number (>10) of clients/week.ConclusionsThese findings reveal elevated sexual- and drug- risk patterns among those who exchange sex for crack. The physical and social environment featured prominently in our results as a driver of sex-for-crack exchanges, highlighting the need for gender-sensitive multilevel approaches to harm reduction, STI and HIV prevention that address SWs’ environment, individual level factors, and the interplay between them.