bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential epigenetic factors in the prediction of cardiovascular risk in diabetic patients
Authors: Napoli Claudio , Benincasa Giuditta , Schiano Concetta , Salvatore Marco 
Published: October 2019

Abstract
Hyperglycaemia can strongly alter the epigenetic signatures in many types of human vascular cells providing persistent perturbations of protein–protein interactions both in micro- and macro-domains. The establishment of these epigenetic changes may precede cardiovascular (CV) complications and help us to predict vascular lesions in diabetic patients. Importantly, these epigenetic marks may be transmitted across several generations (transgenerational effect) and increase the individual risk of disease. Aberrant DNA methylation and imbalance of histone modifications, mainly acetylation and methylation of H3, represent key determinants of vascular lesions and, thus, putative useful biomarkers for prevention and diagnosis of CV risk in diabetics. Moreover, a differential expression of some micro-RNAs (miRNAs), mainly miR-126, may be a useful prognostic biomarker for atherosclerosis development in asymptomatic subjects. Recently, also environmental-induced chemical perturbations in mRNA (epitranscriptome), mainly the N6-methyladenosine, have been associated with obesity and diabetes. Importantly, reversal of epigenetic changes by modulation of lifestyle and use of metformin, statins, fenofibrate, and apabetalone may offer useful therapeutic options to prevent or delay CV events in diabetics increasing the opportunity for personalized therapy. Network medicine is a promising molecular-bioinformatic approach to identify the signalling pathways underlying the pathogenesis of CV lesions in diabetic patients. Moreover, machine learning tools combined with tomography are advancing the individualized assessment of CV risk in these patients. We remark the need for combining epigenetics and advanced bioinformatic platforms to improve the prediction of vascular lesions in diabetics increasing the opportunity for CV precision medicine.
Association of preceding antithrombotic therapy in atrial fibrillation patients with ischaemic stroke, intracranial haemorrhage, or gastrointestinal bleed and mortality
Authors: Komen Joris J , Forslund Tomas , Mantel-Teeuwisse Aukje K , Klungel Olaf H , von Euler Mia , Braunschweig Frieder , Wallén Håkan , Hjemdahl Paul 
Published: October 2019

AbstractAimsTo analyse 90-day mortality in atrial fibrillation (AF) patients after a stroke or a severe bleed and assess associations with the type of antithrombotic treatment at the event.Methods and resultsFrom the Stockholm Healthcare database, we selected 6017 patients with a known history of AF who were diagnosed with ischaemic stroke, 3006 with intracranial haemorrhage, and 4291 with a severe gastrointestinal bleed (GIB). The 90-day mortality rates were 25.1% after ischaemic stroke, 31.6% after intracranial haemorrhage, and 16.2% after severe GIB. We used Cox regression and propensity score-matched analyses to test the association between antithrombotic treatment at the event and 90-day mortality. After intracranial haemorrhage, there was a significantly higher mortality rate in warfarin compared to non-vitamin K oral anticoagulant (NOAC)-treated patients [adjusted hazard ratio (aHR) 1.36, 95% confidence interval (CI) 1.04–1.78]. After an ischaemic stroke and a severe GIB, patients receiving antiplatelets or no antithrombotic treatment had significantly higher mortality rates compared to patients on NOACs, but there was no difference comparing warfarin to NOACs (aHR 0.84, CI 0.63–1.12 after ischaemic stroke, aHR 0.91, CI 0.66–1.25 after severe GIB). Propensity score-matched analysis yielded similar results.ConclusionMortality rates were high in AF patients suffering from an ischaemic stroke, an intracranial haemorrhage, or a severe GIB. NOAC treatment was associated with a lower 90-day mortality after intracranial haemorrhage than warfarin.
Postexposure Effects of Vaccines on Infectious Diseases
Authors: Gallagher Tara , Lipsitch Marc 
Published: October 2019

Abstract
We searched the PubMed database for clinical trials and observational human studies about postexposure vaccination effects, targeting infections with approved vaccines and vaccines licensed outside the United States against dengue, hepatitis E, malaria, and tick-borne encephalitis. Studies of animal models, serologic testing, and pipeline vaccines were excluded. Eligible studies were evaluated by definition of exposure; attempts to distinguish pre- and postexposure effects were rated on a scale of 1 to 4. We screened 4,518 articles and ultimately identified for this review 14 clinical trials and 31 observational studies spanning 7 of the 28 vaccine-preventable diseases. For secondary attack rate, the following medians were found for postexposure vaccination effectiveness: hepatitis A, 85% (interquartile range (IQR), 28; n = 5 sources); hepatitis B, 85% (IQR, 22; n = 5 sources); measles, 83% (IQR, 21; n = 8 sources); varicella, 67% (IQR: 48; n = 9 sources); smallpox, 45% (IQR, 39; n = 4 sources); and mumps, 38% (IQR, 7; n = 2 sources). For case fatality proportions resulting from rabies and smallpox, the median vaccine postexposure efficacies were 100% (IQR, 0; n = 6 sources) and 63% (IQR, 50; n = 8 sources), respectively. Many available vaccines can modify or preclude disease if administered after exposure. This postexposure effectiveness could be important to consider during vaccine trials and while developing new vaccines.
Gender in cardiovascular medicine: chest pain and coronary artery disease
Authors: Mehta Puja K , Bess Courtney , Elias-Smale Suzette , Vaccarino Viola , Quyyumi Arshed , Pepine Carl J , Bairey Merz C Noel 
Published: October 2019

Abstract
Ischaemic heart disease (IHD) remains the leading cause of morbidity and mortality among women and men yet women are more often underdiagnosed, have a delay in diagnosis, and/or receive suboptimal treatment. An implicit gender-bias with regard to lack of recognition of sex-related differences in presentation of IHD may, in part, explain these differences in women compared with men. Indeed, existing knowledge demonstrates that angina does not commonly relate to obstructive coronary artery disease (CAD). Emerging knowledge supports an inclusive approach to chest pain symptoms in women, as well as a more thoughtful consideration of percutaneous coronary intervention for angina in stable obstructive CAD, to avoid chasing our tails. Emerging knowledge regarding the cardiac autonomic nervous system and visceral pain pathways in patients with and without obstructive CAD offers explanatory mechanisms for angina. Interdisciplinary investigation approaches that involve cardiologists, biobehavioural specialists, and anaesthesia/pain specialists to improve angina treatment should be pursued.
Warrior Wellness: A Randomized Controlled Pilot Trial of the Effects of Exercise on Physical Function and Clinical Health Risk Factors in Older Military Veterans With PTSD
Authors: Hall Katherine S , Morey Miriam C , Beckham Jean C , Bosworth Hayden B , Sloane Richard , Pieper Carl F , Pebole Michelle M 
Published: October 2019

Abstract

Background
Military veterans living with post-traumatic stress disorder (PTSD) face significant physical and functional health disparities, which are often aggravated over time and in the context aging. Evidence has shown that physical activity can positively impact age-related health conditions, yet exercise trials in older adults with mental disorders are rare. Our study was a tailored and targeted pilot exercise intervention for older veterans with PTSD.

Methods
Fifty-four older veterans with PTSD (mean age = 67.4 years, 90.7% male, 85.2% non-white) were randomized to supervised exercise (n = 38) or wait-list usual care (n = 18) for 12 weeks. Physical activity (MET-min/wk) and aerobic endurance (assessed with the 6-minute walk test) were primary outcomes. Secondary outcomes were physical performance (strength, mobility, balance), cardiometabolic risk factors (eg, waist circumference), and health-related quality of life.

Results
At 12 weeks, a large effect of the intervention on physical activity levels (Cohen’s d = 1.37) was observed compared to wait-list usual care. Aerobic endurance improved by 69 m in the exercise group compared to 10 m in wait-list group, reflecting a moderate between-group effect (Cohen’s d = 0.50). Between-group differences on 12-week changes in physical performance, cardiometabolic risk factors, and health-related quality of life ranged from small to large effects (Cohen’s d = 0.28–1.48), favoring the exercise arm.

Conclusion
Participation in supervised exercise improved aerobic endurance, physical performance, and health-related clinical factors in older veterans with PTSD; a medically complex population with multiple morbidity. Group exercise is a low-cost, low-stigma intervention, and implementation efforts among older veterans with PTSD warrants further consideration.
A history of collaboration in US invention: changing patterns of co-invention, complexity and geography
Authors: van der Wouden Frank 
Published: October 2019

AbstractResearch suggests that increasing collaboration in knowledge production is explained by rising complexity of knowledge. Yet, there is little long-run, systematic, empirical evidence on the relationship between complexity and collaboration. A new database is introduced that identifies all (co-)inventors on more than 3 million US patents between 1836 and 1975. Empirical analysis reveals (i) collaboration on US patents began to increase in the 1940s; (ii) there is a robust positive relationship between complexity and collaboration; and (iii) increasing complexity is associated with local rather than nonlocal collaboration.
Policing Canada’s Refugee System: A Critical Analysis of the Canada Border Services Agency
Authors: Atak Idil , Hudson Graham , Nakache Delphine 
Published: October 2019

Abstract
The officers of the Canada Border Services Agency (CBSA) play pivotal roles at various stages in Canada’s refugee system, making decisions that are life-changing for asylum seekers. This article examines the evolving institutional setting and processes that define the CBSA’s enforcement policy and its consequences for asylum seekers in Canada. Drawing on the findings of field-research, conducted between October 2015 and May 2018 in three Canadian provinces (Ontario, British Columbia, and Quebec), it argues that the Agency operates in a specific social universe heavily shaped by the post-9/11 geopolitical context of the criminalization of migration. This situation has been exacerbated by the major overhaul of Canada’s refugee system, undertaken by the previous Conservative government in 2012. The article further contends that the way the CBSA has been involved in refugee status determination turns Canada’s refugee system into an adversarial and unfair process for some groups of asylum seekers. To that end, it highlights the CBSA’s policies in three areas: eligibility determination, front-end security screening of refugee claimants, and ministerial interventions at the Immigration and Refugee Board of Canada.
PAMP-INDUCED SECRETED PEPTIDE 3 (PIP3) modulates immunity in Arabidopsis thaliana
Authors: Najafi Javad , Brembu Tore , Vie Ane Kjersti , Viste Rannveig , Winge Per , Somssich Imre E , Bones Atle M 
Published: October 2019

Abstract
Small post-translationally modified peptides are important signalling components of plant defence responses against phytopathogens, acting both as positive and negative modulators. PAMP-INDUCED SECRETED PEPTIDE (PIP) 1 and 2 has been shown to amplify plant immunity. Here we investigate the role of the related peptide PIP3 in the regulation of immune response in Arabidopsis. Treatment with synthetic PIP peptides led to similar transcriptome reprogramming, indicating an effect on innate immunity-related processes and phytohormones, including jasmonic acid (JA) biosynthesis and signalling. PIP3 overexpressing (OX) plants showed enhanced growth inhibition in response to flg22 exposure. In addition, flg22-induced production of reactive oxygen species and callose deposition were significantly reduced in PIP3-OX plants. Interestingly, PIP3-OX plants showed increased susceptibility both toward Botrytis cinerea and the biotrophic pathogen Pseudomonas syringae. Expression of both JA and salicylic acid biosynthesis and signalling genes was more induced during B. cinerea infection in PIP3-OX plants compared with wild-type plants. Promoter and ChIP-seq analyses indicated that the transcription factors WRKY18, WRKY33 and WRKY40 cooperatively act as repressors for PIP3. The results point to a fine-tuning role for PIP3 in modulation of immunity through the regulation of SA and JA biosynthesis and signalling pathways in Arabidopsis.
Photoperiod-sensitivity genes (Ppd-1): Quantifying their effect on the photoperiod response model in wheat
Authors: Pérez-Gianmarco Thomas I , Severini Alan D , González Fernanda G 
Published: October 2019

Abstract
Coupling anthesis date to the best environment is critical for wheat (Triticum aestivum L.) adaptation and yield potential. Development to anthesis is controlled by temperature and photoperiod. Response to photoperiod is chiefly modulated by Ppd-1 genes, but their effect on the quantitative response of i) time to anthesis, and ii) pre-anthesis phases to photoperiod remains largely unknown. A photoperiod-sensitive spring cultivar, Paragon, and near-isogenic lines of it carrying different combinations of Ppd-1a insensitivity alleles were tested under a wide range of photoperiods, including switches in photoperiod at the onset of stem elongation. Using multimodel inference we found that Ppd-1a alleles reduced photoperiod sensitivity from a) emergence to anthesis and b) emergence to onset of stem elongation, both in a less than additive manner, while threshold photoperiod and intrinsic earliness were unaffected. Sensitivity to current photoperiod from onset of stem elongation to flag leaf and from then to anthesis was milder than for previous phases and was not related to variability in Ppd-1. But ‘memory’ effects of previously experienced photoperiod on the duration from onset of stem elongation to flag leaf, was. The characterisation and quantification provided here of Ppd-1 allelic combinations’ effects on development should help increase genotype-to-phenotype models’ accuracy for predicting wheat phenology.
The soft X-ray excess: NLS1s versus BLS1s
Authors: Gliozzi Mario , Williams James K 
Published: October 2019

ABSTRACT
The soft X-ray excess – the excess of X-rays below 2 keV with respect to the extrapolation of the hard X-ray spectral continuum model – is a very common feature among type 1 active galactic nuclei (AGNs); yet the nature of the soft X-ray excess is still poorly understood and hotly debated. To shed some light on this issue, we have measured in a model-independent way the soft excess strength in a flux-limited sample of broad- and narrow-line Seyfert 1 galaxies (BLS1s and NLS1s) that are matched in X-ray luminosity but different in terms of the black hole mass and the accretion rate values, with NLS1s being characterized by smaller MBH and larger $\dot{m}$ values. Our analysis, in agreement with previous studies carried out with different AGN samples, indicates that: (1) a soft excess is ubiquitously detected in both BLS1s and NLS1s; (2) the strength of the soft excess is significantly larger in the NLS1 sample, compared to the BLS1 sample; and (3) combining the two samples, the strength of the soft excess appears to positively correlate with the photon index as well as with the accretion rate, whereas there is no correlation with the black hole mass. Importantly, our work also reveals the lack of an anticorrelation between the soft excess strength and the luminosity of the primary X-ray component, predicted by the absorption and reflection scenarios. Our findings suggest that the soft excess is consistent with being produced by a warm Comptonization component. Larger, more complete samples of NLS1s and BLS1s are needed to confirm these conclusions.
Phenomenology, Ontology, Nihilism: Løgstrup, Levinas, and the Limits of Philosophical Anthropology
Authors: Crowell Steven 
Published: October 2019

AbstractDespite recent interest in his work, little has been written about Løgstrup’s relation to phenomenology—what he thinks phenomenology is, how it informs his approach to ethics, and what he believes it can accomplish. Here I hope to stimulate further discussion of these matters. In this, consideration of Levinas’s understanding of phenomenology will be useful. While sharing many of Løgstrup’s concerns, Levinas insists on a distinction between phenomenological ontology and “metaphysics,” one that Løgstrup tends to blur in support of his argument that “absolute nihilism is an impossibility.” After showing why this distinction matters, I will argue that Løgstrup’s goal is better achieved if we embrace Heidegger’s transcendental version of phenomenology rather than follow Løgstrup or Levinas, despite much that remains phenomenologically valuable in both.
Losses of human disease-associated genes in placental mammals
Authors: Sharma Virag , Hiller Michael 
Published: October 2019

AbstractWe systematically investigate whether losses of human disease-associated genes occurred in other mammals during evolution. We first show that genes lost in any of 62 non-human mammals generally have a lower degree of pleiotropy, and are highly depleted in essential and disease-associated genes. Despite this under-representation, we discovered multiple genes implicated in human disease that are truly lost in non-human mammals. In most cases, traits resembling human disease symptoms are present but not deleterious in gene-loss species, exemplified by losses of genes causing human eye or teeth disorders in poor-vision or enamel-less mammals. We also found widespread losses of PCSK9 and CETP genes, where loss-of-function mutations in humans protect from atherosclerosis. Unexpectedly, we discovered losses of disease genes (TYMP, TBX22, ABCG5, ABCG8, MEFV, CTSE) where deleterious phenotypes do not manifest in the respective species. A remarkable example is the uric acid-degrading enzyme UOX, which we found to be inactivated in elephants and manatees. While UOX loss in hominoids led to high serum uric acid levels and a predisposition for gout, elephants and manatees exhibit low uric acid levels, suggesting alternative ways of metabolizing uric acid. Together, our results highlight numerous mammals that are ‘natural knockouts’ of human disease genes.
Introduction
Authors: Pittard John 
Published: October 2019

Abstract
This introduction begins by providing an initial sketch of the argument for disagreement-motivated religious skepticism that will be assessed in this book. According to this argument, facts about religious disagreement give you good reason to think that any beliefs you may have on controversial religious questions are the product of processes that do not reliably lead to true belief. And if you have good reason to think that some belief of yours is the product of such unreliable processes, then it is not reasonable for you to confidently persist in that belief. After sketching this skeptical position, a preview is given of the argument that unfolds over the following chapters. The introduction then concludes with reading plans for readers with different interests.
Disagreement-Motivated Religious Skepticism and the Commitment to Impartiality
Authors: Pittard John 
Published: October 2019

Abstract
This chapter begins by clarifying the focus of the book, which is what may be called the “higher-order argument for disagreement-motivated religious skepticism.” A key premise of this argument is that a suitably informed religious believer lacks justification for thinking that his or her process of religious belief formation is significantly more reliable than the collective reliability of the processes that otherwise epistemically qualified people use to form religious beliefs. Arguments for this premise that appeal to the rational symmetry of competing processes of religious belief formation are shown to be inadequate. It is argued that a viable argument for the key premise must posit three constraints on the factors that may justifiably ground epistemic self-trust in the face of religious disagreement: an “internal reason constraint,” an “agent impartiality constraint,” and a “reasons impartiality constraint.”
From Impartiality to Instrumentalism
Authors: Pittard John 
Published: October 2019

Abstract
This chapter defends an approach to disagreement that rejects the strong epistemic impartiality requirement endorsed by “strong conciliationists.” The central tenet of the “weak conciliationism” that is defended here is a requirement called “instrumentalism.” Instrumentalism supplies a basis for demanding conciliatory requirements in disagreements that are rationally superficial but does not support similarly demanding requirements in fundamental disagreements that are the result of divergent epistemic starting points. It is argued that the radical impartiality requirement of strong conciliationism, which does issue demanding conciliatory prescriptions in fundamental disputes, is unmotivated in light of the explanatory power of instrumentalism. The penultimate section addresses two objections to weak conciliationism. The first objection, adapted from Schoenfield, claims that following weak conciliationism has a lower expected “accuracy” than following strong conciliationism. The second objection holds that the instrumentalist framework, when pushed far enough, supports a strong epistemic impartiality requirement.
Partisan Justification and Religious Belief
Authors: Pittard John 
Published: October 2019

Abstract
Weak conciliationism affirms that many of one’s epistemic starting points enjoy “partisan justification,” justified confidence that exceeds the degree of confidence that is supportable on impartial grounds. But weak conciliationism does not itself supply an account that says when such partisan justification is and is not available. This chapter begins by identifying the options for an account of partisan justification. It then argues for an exclusively rationalist account according to which partisan justification is grounded in rational insight and is not available in disagreements with acknowledged internal rational parity. This argument presents a challenge for “reformed epistemologists,” like Alston and Plantinga, who deemphasize the role of rational insight in religious belief and who defend religious belief by emphasizing similarities between religious belief formation and the formation of perceptual beliefs. It is argued that the religious epistemologies of Alston and Plantinga cannot successfully meet the higher-order challenge posed by religious disagreement.
Unpalatable Conclusions and Deliberative Vertigo
Authors: Pittard John 
Published: October 2019

Abstract
Some claim that maintaining robust commitment to one’s favored religious outlook is likely to be compatible with following strong conciliationism even if strong conciliationism rules out having controversial religious beliefs. This is because there are nondoxastic forms of religious commitment that do not require confident belief in the religious outlook to which one is committed. This chapter challenges such optimism about the compatibility of religious skepticism and religious commitment. It is argued, first, that those who adopt impartial credences and follow a cost-benefit approach to religious decision-making are likely to find that their approach to decision-making requires adopting a highly unpalatable form of religious commitment. A second argument concludes that no religious commitment is rational if strong conciliationism is correct. According to this argument, the normative uncertainty required by epistemic impartiality brings about a “deliberative vertigo” that prevents rationally motivated engagement any religious or irreligious way of life.