bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel mechanism of tandem activation of ryanodine receptors by cytosolic and SR luminal Ca2+ during excitation–contraction coupling in atrial myocytes
Authors: Maxwell Joshua T. , Blatter Lothar A. 
Published: December 2016

Key points
In atrial myocytes excitation–contraction coupling is strikingly different from ventricle because atrial myocytes lack a transverse tubule membrane system: Ca2+ release starts in the cell periphery and propagates towards the cell centre by Ca2+‐induced Ca2+ release from the sarcoplasmic reticulum (SR) Ca2+ store.
The cytosolic Ca2+ sensitivity of the ryanodine receptor (RyRs) Ca2+ release channel is low and it is unclear how Ca2+ release can be activated in the interior of atrial cells.
Simultaneous confocal imaging of cytosolic and intra‐SR calcium revealed a transient elevation of store Ca2+ that we termed ‘Ca2+ sensitization signal’.
We propose a novel paradigm of atrial ECC that is based on tandem activation of the RyRs by cytosolic and luminal Ca2+ through a ‘fire–diffuse–uptake–fire’ (or FDUF) mechanism: Ca2+ uptake by SR Ca2+ pumps at the propagation front elevates Ca2+ inside the SR locally, leading to luminal RyR sensitization and lowering of the cytosolic Ca2+ activation threshold.
AbstractIn atrial myocytes Ca2+ release during excitation–contraction coupling (ECC) is strikingly different from ventricular myocytes. In many species atrial myocytes lack a transverse tubule system, dividing the sarcoplasmic reticulum (SR) Ca2+ store into the peripheral subsarcolemmnal junctional (j‐SR) and the much more abundant central non‐junctional (nj‐SR) SR. Action potential (AP)‐induced Ca2+ entry activates Ca2+‐induced Ca2+ release (CICR) from j‐SR ryanodine receptor (RyR) Ca2+ release channels. Peripheral elevation of [Ca2+]i initiates CICR from nj‐SR and sustains propagation of CICR to the cell centre. Simultaneous confocal measurements of cytosolic ([Ca2+]i; with the fluorescent Ca2+ indicator rhod‐2) and intra‐SR ([Ca2+]SR; fluo‐5N) Ca2+ in rabbit atrial myocytes revealed that Ca2+ release from j‐SR resulted in a cytosolic Ca2+ transient of higher amplitude compared to release from nj‐SR; however, the degree of depletion of j‐SR [Ca2+]SR was smaller than nj‐SR [Ca2+]SR. Similarly, Ca2+ signals from individual release sites of the j‐SR showed a larger cytosolic amplitude (Ca2+ sparks) but smaller depletion (Ca2+ blinks) than release from nj‐SR. During AP‐induced Ca2+ release the rise of [Ca2+]i detected at individual release sites of the nj‐SR preceded the depletion of [Ca2+]SR, and during this latency period a transient elevation of [Ca2+]SR occurred. We propose that Ca2+ release from nj‐SR is activated by cytosolic and luminal Ca2+ (tandem RyR activation) via a novel ‘fire—diffuse–uptake–fire’ (FDUF) mechanism. This novel paradigm of atrial ECC predicts that Ca2+ uptake by sarco‐endoplasmic reticulum Ca2+‐ATPase (SERCA) at the propagation front elevates local [Ca2+]SR, leading to luminal RyR sensitization and lowering of the activation threshold for cytosolic CICR.
Effectiveness of Interventions for Children With Developmental Coordination Disorder in Physical Therapy Contexts: A Systematic Literature Review and Meta-Analysis
Authors: Offor Nkechi , Ossom Williamson Peace , Caçola Priscila 
Published: December 2016

Purpose:The purpose of this systematic literature review and meta-analysis is to identify the types of interventions in physical therapy contexts that have been explored in children with developmental coordination disorder, the most common variables being addressed, and whether these interventions are effective.
Method:This systematic search of MEDLINE, PEDro, CINAHL, SPORTDiscus, PsycINFO, and Cochrane Library identified interventions in physical therapy contexts for children and adolescents with DCD, and studies were screened using these criteria and assessed using the PEDro and NIH quality assessment scales. AMSTAR was used to evaluate systematic reviews and a meta-analysis was conducted.
Results:From the articles reviewed, 29 articles of moderate to good quality were included in the qualitative analysis. Task-oriented approaches as well as motor skill training–based interventions have shown beneficial effects in improving motor function in children with DCD. Data from 14 articles was extracted for inclusion in the meta-analysis, providing support for the effectiveness of physical therapy interventions against inaction.
Conclusion:Researchers recommend the use of task-oriented and traditional physical therapy interventions for children with DCD. In addition, interventions in physical therapy contexts need clear goals and outcome measures for individual children.
Content analysis of UK newspaper and online news representations of women's and men's ‘binge’ drinking: a challenge for communicating evidence-based messages about single-episodic drinking?
Authors: Patterson C , Emslie C , Mason O , Fergie G , Hilton S 
Published: December 2016

ObjectivesIn the UK, men's alcohol-related morbidity and mortality still greatly exceeds women's, despite an increase in women's alcohol consumption in recent decades. New UK alcohol guidelines introduce gender-neutral low-risk alcohol consumption guidance. This study explores how UK newspaper and online news represent women's and men's ‘binge’ drinking to identify opportunities to better align reporting of harmful drinking with evidence.DesignQuantitative and qualitative content analysis of 308 articles published in 7 UK national newspapers and the BBC News website between 1 January 2012 and 31 December 2013.ResultsArticles associated women with ‘binge’ drinking more frequently than men, and presented women's drinking as more problematic. Men were more frequently characterised as violent or disorderly, while women were characterised as out of control, putting themselves in danger, harming their physical appearance and burdening men. Descriptions of female ‘binge’ drinkers' clothing and appearance were typically moralistic.ConclusionsThe UK news media's disproportionate focus on women's ‘binge’ drinking is at odds with epidemiological evidence, may reproduce harmful gender stereotypes and may obstruct public understandings of the gender-neutral weekly consumption limits in newly proposed alcohol guidelines. In order to better align reporting of harmful drinking with current evidence, public health advocates may engage with the media with a view to shifting media framing of ‘binge’ drinking away from specific groups (young people; women) and contexts (public drinking) and towards the health risks of specific drinking behaviours, which affect all groups regardless of context.
Sex and Stroke in Thrombolyzed Patients and Controls
Authors: Hametner Christian , MacIsaac Rachael L. , Kellert Lars , Abdul-Rahim Azmil H. , Ringleb Peter A. , Lees Kennedy R. , Alexandrov A. , Bath P.M. , Bluhmki E. , Bornstein N. , Chen C. , Claesson L. , Davis S.M. , Donnan G. , Diener H.C. , Fisher M. , Ginsberg M. , Gregson B. , Grotta J. , Hacke W. , Hennerici M.G. , Hommel M. , Kaste M. , Lyden P. , Marler J. , Muir K. , Venketasubramanian N. , Sacco R. , Shuaib A. , Teal P. , Wahlgren N.G. , Warach S. , Weimar C. 
Published: December 2016

Background and Purpose—
We hypothesized that any sex-related difference in outcome poststroke is explained by other prognostic factors and that the response to intravenous recombinant tissue-type plasminogen activator (r-tPA) is equal in males and females after adjustment for such factors.

Methods—
We accessed an independent collection of randomized clinical trials—the VISTA (Virtual International Stroke Trials Archive). Data were preprocessed by selecting complete cases (n=8028) and matching females to males (coarsened exact matching, n=4575, 24.3% r-tPA). Outcome was assessed by the 7-point modified Rankin Scale (mRS) measured at 90 days after ischemic stroke. Relationship among variables was estimated by adjusted regression analysis.

Results—

In nonthrombolyzed patients, ordinal analysis of mRS adjusting for stroke- and sex-related prognostic factors suggested comparable outcomes for females and males (odds ratio, 0.96; 95% confidence interval, 0.85–1.06). Females responded comparably to r-tPA as did males, irrespective of the outcome definition of mRS (ordinal:
P
Interaction
=0.46, relative excess risk because of interaction=0). The number needed to treat was 6.8 and 11.2 for 1 female to achieve mRS score of 0 to 2 and 0 to 1, which was highly congruent with males. Analysis for a nonlinear variation of age-by-sex revealed a good outcome for females <45 years with significant disadvantage thereafter (mRS score of 0–2:
P
Interaction
=0.004). No relationship between sex, r-tPA, and bleeding complications was evident.

Conclusions—
Functional outcome (mRS) without r-tPA was overall similar between the sexes, as was the response to r-tPA. Nonlinear sex-by-age interaction improved estimates of functional independence; this should be considered in sex-related studies in stroke.
Strokes Associated With Pregnancy and Puerperium
Authors: Yoshida Kazumichi , Takahashi Jun C. , Takenobu Yohei , Suzuki Norihiro , Ogawa Akira , Miyamoto Susumu 
Published: December 2016

Background and Purpose—
The incidence and cause of strokes associated with pregnancy and the puerperium are still not fully understood. The aim of this study was to characterize pregnancy-related strokes in Japan using a large-scale survey with current imaging techniques.

Methods—
A retrospective analysis was conducted based on clinical chart reviews in 736 stroke teaching hospitals certified by the Japan Stroke Society between 2012 and 2013, using a web-based questionnaire requesting the detailed clinical course without any personally identifying information. The collection rate of this questionnaire was 70.5%, with 151 pregnancy-associated strokes extracted.

Results—
Hemorrhagic strokes were observed in 111 cases (73.5%), ischemic strokes in 37 (24.5%), and mixed type in 3 cases (2.0%). The estimated incidence of pregnancy-associated stroke was 10.2 per 100 000 deliveries. Major causes of hemorrhage were aneurysm (19.8%), arteriovenous malformation (17.1%), pregnancy-induced hypertension (11.7%), and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) (8.1%). Preexisting cerebrovascular diseases responsible for hemorrhage were detected in 59 cases (53.1%). Among the ischemic strokes, 28 (75.7%) were arterial and 9 (24.3%) were venous infarctions. The most frequent cause of arterial infarctions was reversible cerebral vasoconstriction syndrome. Hemorrhagic stroke showed much poorer prognosis than ischemic stroke.

Conclusions—
The incidence of pregnancy-associated stroke in Japan did not seem higher than that in other Asian and Western countries. The proportion of hemorrhagic stroke among Japanese women was much higher than that in white women. Preexisting cerebrovascular diseases and reversible cerebral vasoconstriction syndrome play a key role in hemorrhagic and ischemic stroke, respectively.
Cost-Effectiveness of Solitaire Stent Retriever Thrombectomy for Acute Ischemic Stroke
Authors: Shireman Theresa I. , Wang Kaijun , Saver Jeffrey L. , Goyal Mayank , Bonafé Alain , Diener Hans-Christoph , Levy Elad I. , Pereira Vitor M. , Albers Gregory W. , Cognard Christophe , Hacke Werner , Jansen Olav , Jovin Tudor G. , Mattle Heinrich P. , Nogueira Raul G. , Siddiqui Adnan H. , Yavagal Dileep R. , Devlin Thomas G. , Lopes Demetrius K. , Reddy Vivek K. , du Mesnil de Rochemont Richard , Jahan Reza , Vilain Katherine A. , House John , Lee Jin-Moo , Cohen David J. 
Published: December 2016

Background and Purpose—
Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions.

Methods—
In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors.

Results—

Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578;
P
<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174;
P
=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752;
P
<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105;
P
=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates.

Conclusions—
Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01657461.
Cannabis, Tobacco, Alcohol Use, and the Risk of Early Stroke
Authors: Falkstedt Daniel , Wolff Valerie , Allebeck Peter , Hemmingsson Tomas , Danielsson Anna-Karin 
Published: December 2016

Background and Purpose—
Current knowledge on cannabis use in relation to stroke is based almost exclusively on clinical reports. By using a population-based cohort, we aimed to find out whether there was an association between cannabis use and early-onset stroke, when accounting for the use of tobacco and alcohol.

Methods—
The cohort comprises 49 321 Swedish men, born between 1949 and 1951, who were conscripted into compulsory military service between the ages of 18 and 20. All men answered 2 detailed questionnaires at conscription and were subject to examinations of physical aptitude, psychological functioning, and medical status. Information on stroke events up to ≈60 years of age was obtained from national databases; this includes strokes experienced before 45 years of age.

Results—
No associations between cannabis use in young adulthood and strokes experienced ≤45 years of age or beyond were found in multivariable models: cannabis use >50 times, hazard ratios=0.93 (95% confidence interval [CI], 0.34–2.57) and 0.95 (95% CI, 0.59–1.53). Although an almost doubled risk of ischemic stroke was observed in those with cannabis use >50 times, this risk was attenuated when adjusted for tobacco usage: hazards ratio=1.47 (95% CI, 0.83–2.56). Smoking ≥20 cigarettes per day was clearly associated both with strokes before 45 years of age, hazards ratio=5.04 (95% CI, 2.80–9.06), and with strokes throughout the follow-up, hazards ratio=2.15 (95% CI, 1.61–2.88).

Conclusions—
We found no evident association between cannabis use in young adulthood and stroke, including strokes before 45 years of age. Tobacco smoking, however, showed a clear, dose–response shaped association with stroke.
Multiple myeloma cells’ capacity to decompose H2O2 determines lenalidomide sensitivity
Authors: Sebastian Sinto , Zhu Yuan X. , Braggio Esteban , Shi Chang-Xin , Panchabhai Sonali C. , Van Wier Scott A. , Ahmann Greg J. , Chesi Marta , Bergsagel P. Leif , Stewart A. Keith , Fonseca Rafael 
Published: December 2016

Key Points
IMiDs inhibit TrxR-mediated intracellular decomposition of H2O2 and caused oxidative stress in MM cells. MM cells with lower antioxidative capacity were more vulnerable to lenalidomide-induced H2O2 accumulation and its associated cytotoxicity.
Gene regulatory network inference using PLS-based methods
Authors: Guo Shun , Jiang Qingshan , Chen Lifei , Guo Donghui 
Published: December 2016

Abstract
Background
Inferring the topology of gene regulatory networks (GRNs) from microarray gene expression data has many potential applications, such as identifying candidate drug targets and providing valuable insights into the biological processes. It remains a challenge due to the fact that the data is noisy and high dimensional, and there exists a large number of potential interactions.

Results
We introduce an ensemble gene regulatory network inference method PLSNET, which decomposes the GRN inference problem with p genes into p subproblems and solves each of the subproblems by using Partial least squares (PLS) based feature selection algorithm. Then, a statistical technique is used to refine the predictions in our method. The proposed method was evaluated on the DREAM4 and DREAM5 benchmark datasets and achieved higher accuracy than the winners of those competitions and other state-of-the-art GRN inference methods.

Conclusions
Superior accuracy achieved on different benchmark datasets, including both in silico and in vivo networks, shows that PLSNET reaches state-of-the-art performance.
TCGA Workflow: Analyze cancer genomics and epigenomics data using Bioconductor packages
Authors: Silva Tiago C. , Colaprico Antonio , Olsen Catharina , D'Angelo Fulvio , Bontempi Gianluca , Ceccarelli Michele , Noushmehr Houtan 
Published: December 2016

Biotechnological advances in sequencing have led to an explosion of publicly available data via large international consortia such as The Cancer Genome Atlas (TCGA), The Encyclopedia of DNA Elements (ENCODE), and The NIH Roadmap Epigenomics Mapping Consortium (Roadmap). These projects have provided unprecedented opportunities to interrogate the epigenome of cultured cancer cell lines as well as normal and tumor tissues with high genomic resolution. The Bioconductor project offers more than 1,000 open-source software and statistical packages to analyze high-throughput genomic data. However, most packages are designed for specific data types (e.g. expression, epigenetics, genomics) and there is no one comprehensive tool that provides a complete integrative analysis of the resources and data provided by all three public projects. A need to create an integration of these different analyses was recently proposed. In this workflow, we provide a series of biologically focused integrative analyses of different molecular data. We describe how to download, process and prepare TCGA data and by harnessing several key Bioconductor packages, we describe how to extract biologically meaningful genomic and epigenomic data. Using Roadmap and ENCODE data, we provide a work plan to identify biologically relevant functional epigenomic elements associated with cancer. To illustrate our workflow, we analyzed two types of brain tumors: low-grade glioma (LGG) versus high-grade glioma (glioblastoma multiform or GBM). This workflow introduces the following Bioconductor packages: AnnotationHub, ChIPSeeker, ComplexHeatmap, pathview, ELMER, GAIA, MINET, RTCGAToolbox, TCGAbiolinks.
Level of personality integration in psychopathy
Authors: Cierpiałkowska Lidia , Groth Jarosław , Kleka Paweł 
Published: December 2016

Cel pracyCelem prezentowanych badań było stwierdzenie czy występujące w obrazie klinicznym psychopatii różnice, które pozwalają na wyodrębnienie jej podtypów, mają u podłoża różny poziom patologii organizacji (integracji) osobowości wg O. Kernberga.MetodaBadaniami objęto grupę 417 osób – 88,5% stanowili przestępcy, 11,5% nieprzestępcy. Nasilenie psychopatii zmierzono Kwestionariuszem Osobowości Psychopatycznej (PPI-R) S.O. Lilienfelda, natomiast poziom integracji osobowości Kwestionariuszem Osobowości Borderline (BPI) F. Leichsenringa. Posłużono się analizą skupień k-średnich i metodą AUC.WynikiAnaliza skupień pozwoliła na wyodrębnienie dwóch grup osób: skupienie 1 – psychopaci nieustraszono-dominujący, zaś skupienie 2 – psychopaci ekscentryczno-impulsywni. Psychopaci egocentryczno-impulsywni istotnie częściej niż psychopaci nieustraszono-dominujący charakteryzują się organizacją osobowości borderline. Wykazują oni, obok objawów psychopatii, głębsze zaburzenia tożsamości, częściej stosują prymitywne mechanizmy obronne, wykazują lęk przed fuzją oraz poważniejsze problemy w testowaniu rzeczywistości.WnioskiRóżnice w obrazie klinicznym psychopatii są odzwierciedleniem różnego poziomu integracji osobowości. Potwierdzona została teza o dystynktywnym charakterze bezduszności i jej obecności w obrazie psychopatii niezależnie od konfiguracji cech w wyłonionych podtypach.
Reduction of 30-Day Hospital Readmissions after Patient-centric Telephonic Medication Therapy Management Services
Authors: Miller Daryl E. , Roane Teresa E. , McLin Karen D. 
Published: December 2016

Background Transitional care programs are a growing topic in health care systems across the country, with a focus on achieving a reduction in hospital readmissions and improving patient and medication safety. Numerous strategies have been employed and studied to determine successful approaches to patient transition from the hospital setting to the home setting. Pharmacist-mediated postdischarge telephonic outreach has demonstrated decreased hospital readmission rates in multiple hospital systems. Objective To evaluate the effectiveness of pharmacist-facilitated telephonic medication therapy management (MTM) services on reducing hospital readmissions. Methods A retrospective chart analysis ( n = 314) was performed for patients who received MTM services following hospital discharge between February 23, 2014 and July 4, 2014. The primary outcome was 30-day all-cause readmission. The secondary outcomes were identification of pharmacist interventions for and recommendations about medication-related problems and discrepancies found between the patients' reported medication list and the hospital discharge medication list. Results The data revealed no statistically significant difference in hospital readmission rates between the intervention and control groups (odds ratio, 1.04; 95% CI, 0.68–1.60). Pharmacists intervened on 189 medication-related problems via facsimile to the prescriber (35.7% of charts), contacted prescribers by phone for 23 medication-related or health-related issues, and identified 823 medication list discrepancies (78.34% of charts). Conclusion Although the provision of telephonic MTM services by pharmacists did not result in an improvement in the readmission rate during this study period, pharmacists were able to intervene on numerous medication-related problems and medication list discrepancies.