bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of molecularly-cloned hematopoietic growth factors after acute high-dose radiation exposures
Authors: Lazarus Hillard M , Armitage James O , Gale Robert Peter 
Published: June 2021

Abstract
Therapy of acute, high-dose whole-body exposures of humans to ionizing radiations is a complex medical challenge. Since 1944 more than 400 radiologic accidents have been registered with more than 3000 substantial radiation exposures and 127 fatalities. There are several potential interventions including supportive care, transfusions, preventative or therapeutic anti-infection drugs, molecularly-cloned myeloid growth factors and hematopoietic cell transplants. We discuss the use of the granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) to treat acute high-dose ionizing radiation exposures. Considerable data in experimental models including monkeys indicate use of these drugs accelerates bone marrow recovery and in some but not all instances increases survival. In ten accidents since 1996, 30 victims received G-CSF alone or with other growth factors. Twenty-six victims survived. In seven accidents since 1986, 28 victims received GM-CSF alone or with other growth factors; 18 victims survived. However, absent control or data from randomized trials, it is not possible to know with certainty what role, if any, receiving G-CSF or GM-CSF was of benefit. Given the favorable benefit-to-risk ratio of molecularly-cloned myeloid growth factors, their use soon after exposure to acute, high-dose whole-body ionizing radiations is reasonable.
Redistribution of centrosomal proteins by centromeres and Polo kinase controls partial nuclear envelope breakdown in fission yeast
Authors: Bestul Andrew J. , Yu Zulin , Unruh Jay R. , Jaspersen Sue L. 
Published: June 2021

Partial nuclear envelope breakdown is necessary for fission yeast cells to go through mitosis. Bestul et al., show that the SUN protein, Sad1, is vital in carrying out this localized breakdown that is regulated by the centromere and Polo kinase.
Inflammation: A Mediator Between Hypertension and Neurodegenerative Diseases
Authors: Youwakim Jessica , Girouard Hélène 
Published: June 2021

AbstractHypertension is the most prevalent and modifiable risk factor for stroke, vascular cognitive impairment, and Alzheimer’s disease. However, the mechanistic link between hypertension and neurodegenerative diseases remains to be understood. Recent evidence indicates that inflammation is a common pathophysiological trait for both hypertension and neurodegenerative diseases. Low-grade chronic inflammation at the systemic and central nervous system levels is now recognized to contribute to the physiopathology of hypertension. This review speculates that inflammation represents a mediator between hypertension and neurodegenerative diseases, either by a decrease in cerebral blood flow or a disruption of the blood–brain barrier which will, in turn, let inflammatory cells and neurotoxic molecules enter the brain parenchyma. This may impact brain functions including cognition and contribute to neurodegenerative diseases. This review will thus discuss the relationship between hypertension, systemic inflammation, cerebrovascular functions, neuroinflammation, and brain dysfunctions. The potential clinical future of immunotherapies against hypertension and associated cerebrovascular risks will also be presented.
Inter-Hospital Escalation-of-Care Referrals for Severe Alcohol-Related Liver Disease with Recent Drinking During the COVID-19 Pandemic
Authors: Chen Po-Hung , Ting Peng-Sheng , Almazan Erik , Chander Geetanjali , Cameron Andrew M , Gurakar Ahmet 
Published: June 2021

Abstract
Alcohol sales and consumption have increased during the coronavirus disease 2019 pandemic, but their downstream effects on alcohol-related liver disease (ALD) are unclear. We analyzed inter-hospital escalation-of-care referrals to our tertiary care inpatient liver unit across 18 months through December 2020. There was a significant rise in severe ALD with recent unhealthy drinking in our regional community during the pandemic.
Functional brain imaging using 18F-fluorodeoxyglucose positron emission tomography/computerized tomography in 138 patients with Kleine–Levin syndrome: an early marker?
Authors: Dudoignon Benjamin , Tainturier Laure-Eugénie , Dodet Pauline , Bera Géraldine , Groos Elisabeth , Chaumereuil Charlotte , Maranci Jean-Baptiste , Kas Aurélie , Arnulf Isabelle 
Published: June 2021

Abstract
Kleine–Levin syndrome is a rare disorder characterized by relapsing-remitting episodes of severe hypersomnia, cognitive impairment, apathy, derealization and behavioural disturbances. Between episodes, most patients experience normal sleep, mood and behaviour, but they may have some residual abnormalities in brain functional imaging; however, the frequency, localization and significance of abnormal imaging are unknown, as brain functional imaging have been scarce and heterogenous [including scintigraphy 18F-fluorodeoxyglucose positron emission tomography/computerized tomography (FDG-PET/CT) and functional MRI during resting state and cognitive effort] and based on case reports or on group analysis in small groups. Using visual individual analysis of 18F-fluorodeoxyglucose positron emission tomography/computerized tomography at the time of Kleine–Levin syndrome diagnosis, we examined the frequency, localization and clinical determinants of hypo- and hypermetabolism in a cross-sectional study. Among 179 patients with Kleine–Levin syndrome who underwent 18F-fluorodeoxyglucose positron emission tomography/computerized tomography, the visual analysis was restricted to the 138 untreated patients studied during asymptomatic periods. As many as 70% of patients had hypometabolism, mostly affecting the posterior associative cortex and the hippocampus. Hypometabolism was associated with younger age, recent (&lt;3 years) disease course and a higher number of episodes during the preceding year. The hypometabolism was more extensive (from the left temporo-occipital junction to the entire homolateral and then the bilateral posterior associative cortex) at the beginning of the disorder. In contrast, there was hypermetabolism in the prefrontal dorsolateral cortex in half of the patients (almost all having concomitant hypometabolism in the posterior areas), which was also associated with younger age and shorter disease course. The cognitive performances (including episodic memory) were similar in patients with versus without hippocampus hypometabolism. In conclusion, hypometabolism is frequently observed upon individual visual analysis of 18F-fluorodeoxyglucose positron emission tomography/computerized tomography during asymptomatic Kleine–Levin syndrome periods; it is mostly affecting the posterior associative cortex and the hippocampus and is mostly in young patients with recent-onset disease. Hypometabolism provides a trait marker during the first years of Kleine–Levin syndrome, which could help clinicians during the diagnosis process.
Chronically elevated branched chain amino acid levels are pro-arrhythmic
Authors: Portero Vincent , Nicol Thomas , Podliesna Svitlana , Marchal Gerard A , Baartscheer Antonius , Casini Simona , Tadros Rafik , Treur Jorien L , Tanck Michael W T , Cox I Jane , Probert Fay , Hough Tertius A , Falcone Sara , Beekman Leander , Müller-Nurasyid Martina , Kastenmüller Gabi , Gieger Christian , Peters Annette , Kääb Stefan , Sinner Moritz F , Blease Andrew , Verkerk Arie O , Bezzina Connie R , Potter Paul K , Remme Carol Ann 
Published: June 2021

Abstract

Aims
Cardiac arrhythmias comprise a major health and economic burden and are associated with significant morbidity and mortality, including cardiac failure, stroke, and sudden cardiac death (SCD). Development of efficient preventive and therapeutic strategies is hampered by incomplete knowledge of disease mechanisms and pathways. Our aim is to identify novel mechanisms underlying cardiac arrhythmia and SCD using an unbiased approach.

Methods and results
We employed a phenotype-driven N-ethyl-N-nitrosourea mutagenesis screen and identified a mouse line with a high incidence of sudden death at young age (6–9 weeks) in the absence of prior symptoms. Affected mice were found to be homozygous for the nonsense mutation Bcat2p.Q300*/p.Q300* in the Bcat2 gene encoding branched chain amino acid transaminase 2. At the age of 4–5 weeks, Bcat2p.Q300*/p.Q300* mice displayed drastic increase of plasma levels of branch chain amino acids (BCAAs—leucine, isoleucine, valine) due to the incomplete catabolism of BCAAs, in addition to inducible arrhythmias ex vivo as well as cardiac conduction and repolarization disturbances. In line with these findings, plasma BCAA levels were positively correlated to electrocardiogram indices of conduction and repolarization in the German community-based KORA F4 Study. Isolated cardiomyocytes from Bcat2p.Q300*/p.Q300* mice revealed action potential (AP) prolongation, pro-arrhythmic events (early and late afterdepolarizations, triggered APs), and dysregulated calcium homeostasis. Incubation of human pluripotent stem cell-derived cardiomyocytes with elevated concentration of BCAAs induced similar calcium dysregulation and pro-arrhythmic events which were prevented by rapamycin, demonstrating the crucial involvement of mTOR pathway activation.

Conclusions
Our findings identify for the first time a causative link between elevated BCAAs and arrhythmia, which has implications for arrhythmogenesis in conditions associated with BCAA metabolism dysregulation such as diabetes, metabolic syndrome, and heart failure.
L’histoire immobile?A reappraisal of French economic growth using the demand-side approach, 1280–1850
Authors: Ridolfi Leonardo , Nuvolari Alessandro 
Published: June 2021

ABSTRACTWe construct a new series of GDP per capita for France for the period 1280–1850 using the demand-side approach. Our estimates point to a long-run stability of the French economy with a very gradual acceleration toward modern economic growth. In comparative perspective, our new estimates suggest that England and France were characterized by similar levels of economic performance until the second half of the seventeenth century. It is only after that period that the English economy “forges ahead” in a consistent way.
A thematic analysis to examine the feasibility of EHR-based clinical decision support for implementing Choosing Wisely® guidelines
Authors: Douthit Brian J , Staes Catherine J , Del Fiol Guilherme , Richesson Rachel L 
Published: June 2021

Abstract

Objective
To identify important barriers and facilitators relating to the feasibility of implementing clinical practice guidelines (CPGs) as clinical decision support (CDS).

Materials and Methods
We conducted a qualitative, thematic analysis of interviews from seven interviews with dyads (one clinical expert and one systems analyst) who discussed the feasibility of implementing 10 Choosing Wisely® guidelines at their institutions. We conducted a content analysis to extract salient themes describing facilitators, challenges, and other feasibility considerations regarding implementing CPGs as CDS.

Results
We identified five themes: concern about data quality impacts implementation planning; the availability of data in a computable format is a primary factor for implementation feasibility; customized strategies are needed to mitigate uncertainty and ambiguity when translating CPGs to an electronic health record-based tool; misalignment of expected CDS with pre-existing clinical workflows impact implementation; and individual level factors of end-users must be considered when selecting and implementing CDS tools.

Discussion
The themes reveal several considerations for CPG as CDS implementations regarding data quality, knowledge representation, and sociotechnical issues. Guideline authors should be aware that using CDS to implement CPGs is becoming increasingly popular and should consider providing clear guidelines to aid implementation. The complex nature of CPG as CDS implementation necessitates a unified effort to overcome these challenges.

Conclusion
Our analysis highlights the importance of cooperation and co-development of standards, strategies, and infrastructure to address the difficulties of implementing CPGs as CDS. The complex interactions between the concepts revealed in the interviews necessitates the need that such work should not be conducted in silos. We also implore that implementers disseminate their experiences.
Practical Knowledge without Luminosity
Authors: Beddor Bob , Pavese Carlotta 
Published: June 2021

Abstract
According to a rich tradition in philosophy of action, intentional action requires practical knowledge: someone who acts intentionally knows what they are doing while they are doing it. Piñeros Glasscock (2020) argues that an anti-luminosity argument, of the sort developed in Williamson (2000), can be readily adapted to provide a reductio of an epistemic condition on intentional action. This paper undertakes a rescue mission on behalf of an epistemic condition on intentional action. We formulate and defend a version of an epistemic condition that is free from any luminosity commitments. While this version of an epistemic condition escapes reductio, it comes with substantive commitments of its own. In particular, we will see that it forces us to deny the existence of any essentially intentional actions. We go on to argue that this consequence should be embraced. On the resulting picture, intentional action is not luminous. But it still entails practical knowledge.
Reboot: a straightforward approach to identify genes and splicing isoforms associated with cancer patient prognosis
Authors: dos Santos Felipe R C , Guardia Gabriela D A , dos Santos Filipe F , Ohara Daniel T , Galante Pedro A F 
Published: June 2021

AbstractNowadays, the massive amount of data generated by modern sequencing technologies provides an unprecedented opportunity to find genes associated with cancer patient prognosis, connecting basic and translational research. However, treating high dimensionality of gene expression data and integrating it with clinical variables are major challenges to perform these analyses. Here, we present Reboot, an integrative approach to find and validate genes and transcripts (splicing isoforms) associated with cancer patient prognosis from high dimensional expression datasets. Reboot innovates by using a multivariate strategy with penalized Cox regression (LASSO method) combined with a bootstrap approach, in addition to statistical tests and plots to support the findings. Applying Reboot on data from 154 glioblastoma patients, we identified a three-gene signature (IKBIP, OSMR, PODNL1) whose increased derived risk score was significantly associated with worse patients’ prognosis. Similarly, Reboot was able to find a seven-splicing isoforms signature related to worse overall survival in 177 pancreatic adenocarcinoma patients with elevated risk scores after uni- and multivariate analyses. In summary, Reboot is an efficient, intuitive and straightforward way of finding genes or splicing isoforms signatures relevant to patient prognosis, which can democratize this kind of analysis and shed light on still under-investigated cancer-related genes and splicing isoforms.
Decline, Renewal, and the Invention of Christian Progress
Authors: Watts Edward J. 
Published: June 2021

Abstract
The emperor Diocletian stabilized the Roman Empire in the 280s and early 290s by creating the tetrarchy, a system of shared imperial authority in which four emperors each operated in a different region of the empire. Panegyrists celebrated Diocletian, Maximian, and their colleague Constantius I for restoring Roman prosperity and peace. By the early 300s, imperial attention shifted to maintaining the new order. This change prompted a series of strong imperial interventions in Roman life that culminated with the Great Persecution of Christians. It ended just before the emperor Constantine’s conversion to Christianity. Christian authors like Eusebius and Lactantius celebrated this event, but Constantine nevertheless framed his new religious policies not as a break with the past but as a restoration of the worship of the one original God away from which Roman polytheism had drifted.
Old Rome, New Rome, and Future Rome
Authors: Watts Edward J. 
Published: June 2021

Abstract
Eastern Roman control of central Italy became increasingly tenuous as the eighth century progressed. The result was a series of popes gradually exercising greater independence from Constantinople. By the middle of the century, popes had begun using the rhetoric of Roman restoration to provide grounds for papal assumption of territorial control over stretches of central Italy taken from the Lombards by the Franks. Papal temporal authority then rested on a forged document called the Donation of Constantine, a document whose claims underpinned Leo IIl’s crowning of Charlemagne as Roman emperor in 800. Although Charlemagne’s Roman imperial title was manufactured, his new Western Roman Empire was framed as a restoration of traditional Western Roman prerogatives that had fallen away—and his new capital at Aachen embodied this transition with buildings constructed from old Roman materials taken from Italy.
Imperial Women of Rome
Authors: Boatwright Mary T. 
Published: June 2021

Abstract
This book explores the constraints and opportunities of the women in the Roman emperor’s family from 35 BCE, when Octavia and Livia received unprecedented privileges from the state, to 235 CE, when Julia Mamaea was assassinated with her son Severus Alexander. Historical vignettes feature Agrippina the Younger, Domitia Longina, and some others as the book analyzes the history of Rome’s most eminent women in legal, religious, military, and other key settings of the principate. It also examines the women’s exemplarity through imaging as well as their presence in the city of Rome and in the empire. Evidence comes from coins, inscriptions, papyri, sculpture, and law codes as well as ancient authors. Numerous illustrations, maps, genealogical trees, and detailed tables and appendices complement the text. The whole reveals imperial women’s fluctuating but persistent marginalization and lack of agency despite their potential, even as it elucidates Rome’s imperial power, legal system, family ideology, religion and imperial cult, court, capital city, and military customs.
Forgiveness
Authors: Warmke Brandon , Nelkin Dana Kay , McKenna Michael 
Published: June 2021

Abstract
This chapter introduces the notion of forgiveness. It discusses the nature of forgiveness, including foundational issues such as moral wrongdoing, moral blameworthiness, and standing to forgive. It articulates several accounts of the nature of forgiveness, including emotion accounts, revenge and punishment-forbearance accounts, and performative accounts, and discusses the difference between monist and pluralist accounts. Turning to the norms of forgiveness, the chapter discusses several moral questions raised in the philosophical literature on forgiveness. The chapter concludes by summarizing and contextualizing the chapters in this volume.
Forgiving as a Performative Utterance
Authors: Swinburne Richard 
Published: June 2021

Abstract
When A wrongs B, A incurs an obligation to make atonement to B by apologizing with repentance, making reparation, and perhaps also doing a bit more for B, which I call “penance.” For B to forgive A (in the morally most important sense of “forgive”) is for B to promise to treat A in the future as someone who has not wronged B. It is normally good for B to forgive A after A has made at least some attempt at making atonement, but B has no obligation to forgive. To wrong someone is analogous to occurring an (unauthorized) debt to the person, and forgiving is deeming the debt to have been paid. Christ taught that, in order to forgive humans, God requires them to apologize with repentance. But God requires no reparation or penance (apart from that provided for us by Christ’s life and death) and imposes a condition on forgiving us—that we should forgive other humans who seek our forgiveness.
The Recent History of Veteran Recruitment and Retention
Authors: Rosser Lisa 
Published: June 2021

Abstract
Setting the historical context for this book, this chapter describes the recent history of civilian veteran employment, relaying how the high military veteran unemployment rate in 2010 generated concern and reactions from the government and the public and the private sectors. It then provides examples of how government and companies worked together to improve the employment situation of military veterans through legislation, corporate hiring programs, and corporate partnerships but faced limited success because too few companies were involved. The current situation of veteran employment and retention is outlined, with examples provided of why military veterans may choose to leave civilian employment and suggestions offered to address the issues veteran employees may have in their jobs so that employers can do a better job of retaining them in their workforces.
Why Hire Veterans?
Authors: Haynie J. Michael 
Published: June 2021

Abstract
In order for employers to get the full benefit of hiring military veterans, they need to understand why it is in their best interest to employ and retain these individuals. This chapter presents and expands on the typical understanding of what it means to hire a veteran. It defines the skills and knowledge veterans bring to the organization along with the value associated with decisive efforts to integrate veterans into the civilian workforce. This chapter explores and outlines the subsequent impact of these decisions on a company’s organizational culture and competitive advantage in the marketplace (e.g., how veteran hiring contributes to the corporate bottom line by examining the return on investment of these decisions), looks at the current trends in the marketplace for veteran talent, provides suggestions on hiring veterans, and presents recommendations on how employers can advance the success of veterans in the workplace, including veterans with disabilities and injuries.
The Soft Skills Veterans Bring to the Workforce
Authors: Hayes Theodore L. , Hogan Robert 
Published: June 2021

Abstract
One of the benefits of hiring military veterans is the skill set they bring to the civilian workforce. Veterans are keenly aware, through leadership examples and training, of the importance of dealing with other people’s productively and of managing one’s own behavior. Working effectively with others and managing one’s own behavior are examples of nontechnical or “soft” social skills that can be measured by personality assessments. Examples of the types of attributes that personality assessments test for include the “big five factors” of personality (conscientiousness, agreeableness, neuroticism, openness, and extraversion) as well as political skill. Taken together, these soft social skills reflect one’s capacity to get along with others and one’s capacity to compete with others; both getting along and getting ahead are empirically related to work success. Veterans have an advantage in civilian organizations in terms of using their soft social skills for personal and team growth by finding meaning in work.