bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human iPSC modelling of a familial form of atrial fibrillation reveals a gain of function of If and ICaL in patient-derived cardiomyocytes
Authors: Benzoni Patrizia , Campostrini Giulia , Landi Sara , Bertini Valeria , Marchina Eleonora , Iascone Maria , Ahlberg Gustav , Olesen Morten Salling , Crescini Elisabetta , Mora Cristina , Bisleri Gianluigi , Muneretto Claudio , Ronca Roberto , Presta Marco , Poliani Pier Luigi , Piovani Giovanna , Verardi Rosanna , Di Pasquale Elisa , Consiglio Antonella , Raya Angel , Torre Eleonora , Lodrini Alessandra Maria , Milanesi Raffaella , Rocchetti Marcella , Baruscotti Mirko , DiFrancesco Dario , Memo Maurizio , Barbuti Andrea , Dell’Era Patrizia 
Published: August 2019

Abstract

Aims
Atrial fibrillation (AF) is the most common type of cardiac arrhythmias, whose incidence is likely to increase with the aging of the population. It is considered a progressive condition, frequently observed as a complication of other cardiovascular disorders. However, recent genetic studies revealed the presence of several mutations and variants linked to AF, findings that define AF as a multifactorial disease. Due to the complex genetics and paucity of models, molecular mechanisms underlying the initiation of AF are still poorly understood. Here we investigate the pathophysiological mechanisms of a familial form of AF, with particular attention to the identification of putative triggering cellular mechanisms, using patient’s derived cardiomyocytes (CMs) differentiated from induced pluripotent stem cells (iPSCs).

Methods and results
Here we report the clinical case of three siblings with untreatable persistent AF whose whole-exome sequence analysis revealed several mutated genes. To understand the pathophysiology of this multifactorial form of AF we generated three iPSC clones from two of these patients and differentiated these cells towards the cardiac lineage. Electrophysiological characterization of patient-derived CMs (AF-CMs) revealed that they have higher beating rates compared to control (CTRL)-CMs. The analysis showed an increased contribution of the If and ICaL currents. No differences were observed in the repolarizing current IKr and in the sarcoplasmic reticulum calcium handling. Paced AF-CMs presented significantly prolonged action potentials and, under stressful conditions, generated both delayed after-depolarizations of bigger amplitude and more ectopic beats than CTRL cells.

Conclusions
Our results demonstrate that the common genetic background of the patients induces functional alterations of If and ICaL currents leading to a cardiac substrate more prone to develop arrhythmias under demanding conditions. To our knowledge this is the first report that, using patient-derived CMs differentiated from iPSC, suggests a plausible cellular mechanism underlying this complex familial form of AF.
To share or not to share: a behavioral perspective on human participation in security information sharing
Authors: Mermoud Alain , Keupp Marcus Matthias , Huguenin Kévin , Palmié Maximilian , Percia David Dimitri 
Published: August 2019

AbstractSecurity information sharing (SIS) is an activity whereby individuals exchange information that is relevant to analyze or prevent cybersecurity incidents. However, despite technological advances and increased regulatory pressure, individuals still seem reluctant to share security information. Few contributions have addressed this conundrum to date. Adopting an interdisciplinary approach, our study proposes a behavioral framework that theorizes how and why human behavior and SIS may be associated. We use psychometric methods to test these associations, analyzing a unique sample of human Information Sharing and Analysis Center members who share real security information. We also provide a dual empirical operationalization of SIS by introducing the measures of SIS frequency and intensity. We find significant associations between human behavior and SIS. Thus, the study contributes to clarifying why SIS, while beneficial, is underutilized by pointing to the pivotal role of human behavior for economic outcomes. It therefore extends the growing field of the economics of information security. By the same token, it informs managers and regulators about the significance of human behavior as they propagate goal alignment and shape institutions. Finally, the study defines a broad agenda for future research on SIS.
How to diagnose heart failure with preserved ejection fraction: the HFA–PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)
Authors: Pieske Burkert , Tschöpe Carsten , de Boer Rudolf A , Fraser Alan G , Anker Stefan D , Donal Erwan , Edelmann Frank , Fu Michael , Guazzi Marco , Lam Carolyn S P , Lancellotti Patrizio , Melenovsky Vojtech , Morris Daniel A , Nagel Eike , Pieske-Kraigher Elisabeth , Ponikowski Piotr , Solomon Scott D , Vasan Ramachandran S , Rutten Frans H , Voors Adriaan A , Ruschitzka Frank , Paulus Walter J , Seferovic Petar , Filippatos Gerasimos 
Published: August 2019

Abstract
Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the ‘HFA–PEFF diagnostic algorithm’. Step 1 (P=Pre-test assessment) is typically performed in the ambulatory setting and includes assessment for HF symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non-cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e′), left ventricular (LV) filling pressure estimated using E/e′, left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2–4 points) implies diagnostic uncertainty, in which case Step 3 (F1: Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F2: Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.
The political economy of health financing reform in Malaysia
Authors: Croke Kevin , Mohd Yusoff Mariana Binti , Abdullah Zalilah , Mohd Hanafiah Ainul Nadziha , Mokhtaruddin Khairiah , Ramli Emira Soleha , Borhan Nor Filzatun , Almodovar-Diaz Yadira , Atun Rifat , Virk Amrit Kaur 
Published: August 2019

AbstractThere is growing evidence that political economy factors are central to whether or not proposed health financing reforms are adopted, but there is little consensus about which political and institutional factors determine the fate of reform proposals. One set of scholars see the relative strength of interest groups in favour of and opposed to reform as the determining factor. An alternative literature identifies aspects of a country’s political institutions–specifically the number and strength of formal ‘veto gates’ in the political decision-making process—as a key predictor of reform’s prospects. A third group of scholars highlight path dependence and ‘policy feedback’ effects, stressing that the sequence in which health policies are implemented determines the set of feasible reform paths, since successive policy regimes bring into existence patterns of public opinion and interest group mobilization which can lock in the status quo. We examine these theories in the context of Malaysia, a successful health system which has experienced several instances of proposed, but ultimately blocked, health financing reforms. We argue that policy feedback effects on public opinion were the most important factor inhibiting changes to Malaysia’s health financing system. Interest group opposition was a closely related factor; this opposition was particularly powerful because political leaders perceived that it had strong public support. Institutional veto gates, by contrast, played a minimal role in preventing health financing reform in Malaysia. Malaysia’s dramatic early success at achieving near-universal access to public sector healthcare at low cost created public opinion resistant to any change which could threaten the status quo. We conclude by analysing the implications of these dynamics for future attempts at health financing reform in Malaysia.
Professional football clubs’ involvement in health promotion in Spain: an audit of current practices
Authors: Lozano-Sufrategui Lorena , Pringle Andy , Zwolinsky Stephen , Drew Kevin J 
Published: August 2019

Abstract
The implementation of effective community-based health interventions within Spanish football clubs has the potential to positively influence the public health agenda and enable the healthcare system in Spain to be more successful and sustainable. This paper aims to explore the involvement of Spanish football clubs in health promotion activities, their potential for future involvement and what that would require. A mixed methods explanatory sequential design, with a purposive sample of La Liga clubs. Data collection included online questionnaires and phone interviews. Quantitative methods enabled us to describe the number and types of programmes the clubs are currently involved in. Qualitative data was useful to further unpick the processes followed by the clubs in planning and developing health promotion programmes, while identifying any determinants to change. Seventeen clubs completed questionnaires and 11 participated in interviews. Clubs generally support inclusive programmes that target disadvantaged groups. Health-related programmes focus on healthy eating, physical activity and blood donation. Thematic analysis of interviews with 11 representatives of La Liga clubs resulted in three-key themes. These related to: (i) Diversity of programmes; (ii) (Lack of) evidence-based approaches to intervention design and evaluation and (iii) Contrasting views about a club’s role in health promotion interventions. Spanish football clubs have potential to reach into communities that are currently underserved. However, there is limited infrastructure and understanding within the clubs to do this. Nevertheless, there is huge opportunity for organizations with public health responsibility in Spain to implement translational approaches within football-based settings.
Neuronal over-expression of Oxr1 is protective against ALS-associated mutant TDP-43 mislocalisation in motor neurons and neuromuscular defects in vivo
Authors: Williamson Matthew G , Finelli Mattéa J , Sleigh James N , Reddington Amy , Gordon David , Talbot Kevin , Davies Kay E , Oliver Peter L 
Published: August 2019

Abstract
A common pathological hallmark of amyotrophic lateral sclerosis (ALS) and the related neurodegenerative disorder frontotemporal dementia, is the cellular mislocalization of transactive response DNA-binding protein 43 kDa (TDP-43). Additionally, multiple mutations in the TARDBP gene (encoding TDP-43) are associated with familial forms of ALS. While the exact role for TDP-43 in the onset and progression of ALS remains unclear, the identification of factors that can prevent aberrant TDP-43 localization and function could be clinically beneficial. Previously, we discovered that the oxidation resistance 1 (Oxr1) protein could alleviate cellular mislocalization phenotypes associated with TDP-43 mutations, and that over-expression of Oxr1 was able to delay neuromuscular abnormalities in the hSOD1G93A ALS mouse model. Here, to determine whether Oxr1 can protect against TDP-43-associated phenotypes in vitro and in vivo, we used the same genetic approach in a newly described transgenic mouse expressing the human TDP-43 locus harbouring an ALS disease mutation (TDP-43M337V). We show in primary motor neurons from TDP-43M337V mice that genetically-driven Oxr1 over-expression significantly alleviates cytoplasmic mislocalization of mutant TDP-43. We also further quantified newly-identified, late-onset neuromuscular phenotypes of this mutant line, and demonstrate that neuronal Oxr1 over-expression causes a significant reduction in muscle denervation and neuromuscular junction degeneration in homozygous mutants in parallel with improved motor function and a reduction in neuroinflammation. Together these data support the application of Oxr1 as a viable and safe modifier of TDP-43-associated ALS phenotypes.
The Association of Medications and Vaccination with Risk of Pneumonia in Inflammatory Bowel Disease
Authors: Gregory Martin H , Ciorba Matthew A , Wiitala Wyndy L , Stidham Ryan W , Higgins Peter , Morley S Celeste , Hou Jason K , Feagins Linda A , Govani Shail M , Cohen-Mekelburg Shirley A , Waljee Akbar K 
Published: August 2019

Abstract

Background
Patients with inflammatory bowel disease (IBD) are at increased risk for pneumonia, and corticosteroids are reported to amplify this risk. Less is known about the impact of corticosteroid-sparing IBD therapies on pneumonia risk or the efficacy of pneumococcal vaccination in reducing all-cause pneumonia in real-world IBD cohorts.

Methods
We performed a population-based study using an established Veterans Health Administration cohort of 29,957 IBD patients. We identified all patients who developed bacterial pneumonia. Cox survival analysis was used to determine the association of corticosteroids at study entry and as a time-varying covariate, corticosteroid-sparing agents (immunomodulators and antitumor necrosis-alpha [TNF] inhibitors), and pneumococcal vaccination with the development of all-cause pneumonia.

Results
Patients with IBD who received corticosteroids had a greater risk of pneumonia when controlling for age, gender, and comorbidities (hazard ratio [HR] 2.21; 95% confidence interval [CI], 1.90–2.57 for prior use; HR = 3.42; 95% CI, 2.92–4.01 for use during follow-up). Anti-TNF inhibitors (HR 1.52; 95% CI, 1.02–2.26), but not immunomodulators (HR 0.91; 95% CI, 0.77–1.07), were associated with a small increase in pneumonia. A history of pneumonia was strongly associated with subsequent pneumonia (HR = 4.41; 95% CI, 3.70–5.27). Less than 15% of patients were vaccinated against pneumococcus, and this was not associated with a reduced risk of pneumonia (HR = 1.02; 95% CI, 0.80–1.30) in this cohort.

Conclusion
In a large US cohort, corticosteroids were confirmed to increase pneumonia risk. Tumor necrosis-alpha inhibitors were associated with a smaller increase in the risk of pneumonia. Surprisingly, pneumococcal vaccination did not reduce all-cause pneumonia in this population, though few patients were vaccinated.
On the Pronunciation Dictionaries of Contemporary German: Lexicographic Construction and Multimedia Components
Authors: Nycz Krzysztof , Tęcza Zygmunt 
Published: August 2019

AbstractThe aim of the following paper is to discuss some significant differences between four modern pronunciation dictionaries of the German language, namely: the Großes Wörterbuch der deutschen Aussprache of 1982, DUDEN Aussprachewörterbuch of 2000, Deutsches Aussprachewörterbuch of 2009, and DUDEN Aussprachewörterbuch of 2015. To start with, a brief review of the history of the dictionaries in question is presented. After that, their formal or editorial characteristics and the structures of their lemma lists are discussed. Finally, due attention is paid to the proportion and properties of the multimedia components included in the two most recent works.
Nocturnal Gamma-Hydroxybutyrate Reduces Cortisol-Awakening Response and Morning Kynurenine Pathway Metabolites in Healthy Volunteers
Authors: Dornbierer D A , Boxler M , Voegel C D , Stucky B , Steuer A E , Binz T M , Baumgartner M R , Baur D M , Quednow B B , Kraemer T , Seifritz E , Landolt H P , Bosch O G 
Published: August 2019

AbstractBackgroundGamma-hydroxybutyrate (GHB; or sodium oxybate) is an endogenous GHB-/gamma-aminobutyric acid B receptor agonist. It is approved for application in narcolepsy and has been proposed for the potential treatment of Alzheimer’s disease, Parkinson’s disease, fibromyalgia, and depression, all of which involve neuro-immunological processes. Tryptophan catabolites (TRYCATs), the cortisol-awakening response (CAR), and brain-derived neurotrophic factor (BDNF) have been suggested as peripheral biomarkers of neuropsychiatric disorders. GHB has been shown to induce a delayed reduction of T helper and natural killer cell counts and alter basal cortisol levels, but GHB’s effects on TRYCATs, CAR, and BDNF are unknown.MethodsTherefore, TRYCAT and BDNF serum levels, as well as CAR and the affective state (Positive and Negative Affect Schedule [PANAS]) were measured in the morning after a single nocturnal dose of GHB (50 mg/kg body weight) in 20 healthy male volunteers in a placebo-controlled, balanced, randomized, double-blind, cross-over design.ResultsIn the morning after nocturnal GHB administration, the TRYCATs indolelactic acid, kynurenine, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid; the 3-hydroxykynurenine to kynurenic acid ratio; and the CAR were significantly reduced (P < 0.05–0.001, Benjamini-Hochberg corrected). The quinolinic acid to kynurenic acid ratio was reduced by trend. Serotonin, tryptophan, and BDNF levels, as well as PANAS scores in the morning, remained unchanged after a nocturnal GHB challenge.ConclusionsGHB has post-acute effects on peripheral biomarkers of neuropsychiatric disorders, which might be a model to explain some of its therapeutic effects in disorders involving neuro-immunological pathologies. This study was registered at ClinicalTrials.gov as NCT02342366.
A Recombinant Chlamydia trachomatis MOMP Vaccine Elicits Cross-serogroup Protection in Mice Against Vaginal Shedding and Infertility
Authors: Tifrea Delia F , Pal Sukumar , de la Maza Luis M 
Published: August 2019

AbstractBackgroundChlamydia trachomatis is the most common sexually transmitted bacterial pathogen worldwide. Here, we determined the ability of a C. trachomatis recombinant major outer membrane protein (rMOMP) vaccine to elicit cross-serogroup protection.MethodsFemale C3H/HeN mice were vaccinated by mucosal and systemic routes with C. trachomatis serovar D (UW-3/Cx) rMOMP and challenged in the ovarian bursa with serovars D (UW-3/Cx), D (UCI-96/Cx), E (IOL-43), or F (N.I.1). CpG-1826 and Montanide ISA 720 were used as adjuvants.ResultsImmune responses following vaccination were more robust against the most closely related serovars. Following a genital challenge (as determined by number of mice with positive vaginal cultures, number of positive cultures, number of inclusion forming units recovered, and number of days with positive cultures) mice challenged with C. trachomatis serovars of the same complex were protected but not those challenged with serovar F (N.I.1) from a different subcomplex. Females were caged with male mice. Based on fertility rates, number of embryos, and hydrosalpinx formation, vaccinated mice were protected against challenges with serovars D (UW-3/Cx), D (UCI-96/Cx), and E (IOL-43) but not F (N.I.1).ConclusionsThis is the first subunit vaccine shown to protect mice against infection, pathology, and infertility caused by different C. trachomatis serovars.
Indonesia’s South–South cooperation: when normative and material interests converged
Authors: Winanti Poppy S , Alvian Rizky Alif 
Published: August 2019

Abstract
This article analyzes how and why contemporary Global South countries’ South–South cooperation (SSC) exhibits a convergence between normative and material interests. The normative approach underlines that SSC is driven by a country’s experience with colonialism and underdevelopment. SSC is perceived as a mechanism to alter the Global South’s asymmetrical relations with the dominant Global North. The material approach highlights the strategic values of SSC for Southern powers. Through SSC, Southern countries desire to improve their reputation, garner support from other South countries in international fora, and pursue their own broader economic agendas. By utilizing domestic politics analysis, Indonesia’s experience shows that a more pragmatic approach to SSC reflects a broader transformation of Indonesia’s domestic political configuration. While Indonesia’s early practices of SSC prefer normative over material interests, the country’s current policies display a convergence of its material and normative interests, which signifies the emergence of ‘interest-based Third World solidarity’.
The Relationship between Contributors’ Domestic Abuses and Peacekeeper Misconduct in United Nations Peacekeeping Operations
Authors: Horne Cale , Robinson Kellan , Lloyd Megan 
Published: August 2019

AbstractRecent research has begun to examine patterns of sexual exploitation and abuse (SEA) perpetrated by peacekeepers deployed in United Nations (UN) peacekeeping operations (PKOs). Yet, SEA makes up only a fraction of credible allegations of misconduct by peacekeepers. In this article we explore the contours of misconduct in UN PKOs beyond SEA allegations. We argue that the behavior of military forces in their own countries should easily predict their behavior when deployed as part of UN PKOs, which are typically set in fragile, postconflict countries where civilians have minimal protections or legal recourse. Using an original dataset of misconduct in PKOs from 2009 to 2016, we find the behavior of PKO contributor states toward their own populations strongly and consistently predicts the behavior of these states’ military forces in UN PKOs. These findings have implications for the vetting, supervision, and composition of PKOs.
Electoral Rules, Interest Group Pressures, and the Price of Democratic Default
Authors: Connell Brendan J 
Published: August 2019

AbstractConventional wisdom dictates that democracies are reliable in upholding their international commitments. However, this assertion is at odds with democratic behavior in sovereign borrowing where democracies have sometimes imposed considerable losses on foreign creditors. Why do some democracies choose to renege on extremely large portions of their sovereign debt during economic crisis? This article argues that costs incurred by creditors are dependent on how the borrowing state's electoral system aggregates competing domestic economic interests. Internationally oriented economic interests prefer to minimize creditor losses since sizeable debt reductions are more likely to compromise access to foreign credit. Conversely, workers and domestic-oriented economic interests prefer to maximize losses faced by foreign creditors in order to ease the costs of austerity at home. By shaping the political incentives of policymakers, I argue that democracies with candidate-centric electoral systems should be associated with sovereign defaults that are less costly for foreign creditors. Under these electoral systems, governments hold incentives to cater primarily to internationally oriented economic interests that are best able to overcome the costs of collective action. Statistical evidence from 53 sovereign debt restructurings between 1978 and 2012 supports the main argument.