bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of the Hypoxia-Inducible Factor 1α–Induced Cardiospecific HERNA1 Enhance-Templated RNA Protects From Heart Disease
Authors: Mirtschink Peter , Bischof Corinne , Pham Minh-Duc , Sharma Rahul , Khadayate Sanjay , Rossi Geetha , Fankhauser Niklaus , Traub Shuyang , Sossalla Samuel , Hagag Eman , Berthonneche Corinne , Sarre Alexandre , Stehr Sebastian. N. , Grote Phillip , Pedrazzini Thierry , Dimmeler Stefanie , Krek Wilhelm , Krishnan Jaya 
Published: March 2019

Background:
Enhancers are genomic regulatory elements conferring spatiotemporal and signal-dependent control of gene expression. Recent evidence suggests that enhancers can generate noncoding enhancer RNAs, but their (patho)biological functions remain largely elusive.

Methods:

We performed chromatin immunoprecipitation–coupled sequencing of histone marks combined with RNA sequencing of left ventricular biopsies from experimental and genetic mouse models of human cardiac hypertrophy to identify transcripts revealing enhancer localization, conservation with the human genome, and hypoxia-inducible factor 1α dependence. The most promising candidate, hypoxia-inducible enhancer RNA (
HERNA
)1, was further examined by investigating its capacity to modulate neighboring coding gene expression by binding to their gene promoters by using chromatin isolation by RNA purification and λN–BoxB tethering–based reporter assays. The role of HERNA1 and its neighboring genes for pathological stress–induced growth and contractile dysfunction, and the therapeutic potential of HERNA1 inhibition was studied in gapmer-mediated loss-of-function studies in vitro using human induced pluripotent stem cell–derived cardiomyocytes and various in vivo models of human pathological cardiac hypertrophy.

Results:

HERNA1
is robustly induced on pathological stress. Production of
HERNA1
is initiated by direct hypoxia-inducible factor 1α binding to a hypoxia-response element in the histoneH3-lysine27acetylation marks–enriched promoter of the enhancer and confers hypoxia responsiveness to nearby genes including synaptotagmin XVII, a member of the family of membrane-trafficking and Ca
2+
-sensing proteins and
SMG1
, encoding a phosphatidylinositol 3-kinase–related kinase. Consequently, a substrate of SMG1, ATP-dependent RNA helicase upframeshift 1, is hyperphoshorylated in a HERNA1- and SMG1-dependent manner. In vitro and in vivo inactivation of
SMG1
and
SYT17
revealed overlapping and distinct roles in modulating cardiac hypertrophy. Finally, in vivo administration of antisense oligonucleotides targeting
HERNA1
protected mice from stress-induced pathological hypertrophy. The inhibition of
HERNA1
postdisease development reversed left ventricular growth and dysfunction, resulting in increased overall survival.

Conclusions:

HERNA1
is a novel heart-specific noncoding RNA with key regulatory functions in modulating the growth, metabolic, and contractile gene program in disease, and reveals a molecular target amenable to therapeutic exploitation.
Physical Activity After Percutaneous Coronary Intervention for Chronic Total Occlusion and Its Association With Health Status
Authors: Peri‐Okonny Poghni A. , Spertus John A. , Grantham J. Aaron , Gosch Kensey , Kirtane Ajay , Sapontis James , Lombardi William , Karmpaliotis Dimitri , Moses Jeffrey , Nicholson William , Salisbury Adam C. 
Published: March 2019

Background

Patients with chronic total occlusion (
CTO
) may not participate in regular exercise because of refractory angina. Exercise participation after percutaneous coronary intervention (PCI) for
CTO
(
CTO PCI
) and the association of exercise with health status after
CTO PCI
is unknown.

Methods and Results

Overall, 1000 patients enrolled in the Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion OPEN CTO is a registry were asked about participation in regular exercise at baseline and 12 months after
CTO PCI
, and the frequency of exercise (<1, 1–2, ≥3 times/week) was collected among exercisers. Health status was assessed using the Seattle Angina Questionnaire (
SAQ
). Multivariable regression assessed 12‐month health status change across 4 groups defined by exercise frequency at baseline and 12 months after
CTO PCI
(no regular exercise at baseline and 12 months, reduced, increased, and consistent exercise at 12 months). Among 869 patients with complete exercise data, the proportion that exercised regularly increased from 33.5% at baseline to 56.6% 12 months after
CTO PCI
(
P
<0.01). Predictors of regular exercise at 12 months included baseline exercise, smoking, baseline and increase in
SAQ
scores for angina frequency, physical limitation, quality of life, and summary. After multivariable adjustment, consistent or increased exercise frequency was associated with significantly greater improvement in
SAQ
scores for angina frequency, physical limitation, quality of life, and summary (
P
<0.01).

Conclusions

Participation in regular exercise increased significantly 12 months after
CTO PCI
, and patients who had greater health status benefit after
PCI
were more likely to exercise regularly at 12 months.
CTO PCI
may enable coronary artery disease patients with limiting symptoms to engage in regular exercise and to support better long‐term outcomes.
Ruth in the Days of the Judges: Women, Foreignness and Violence
Authors: Shepherd David J. 
Published: March 2019

AbstractThe basic premise that Ruth 2 depicts the threat of violence against Ruth has been increasingly recognised by commentators, even if not all take sufficiently seriously the nature of this violence as potentially lethal and almost certainly sexual. What is less clear, however, is the extent to which the narrative implies that part of Ruth’s vulnerability to (sexual) violence in the fields of Bethlehem relates to the fact that she is not a Bethlehemite but a migrant recently arrived from Moab. Taking seriously Ruth’s own situating of itself ‘in the days of the Judges’, this study begins by exploring the way in which the gendered violence of Judges 19-21 flows from the account of an act of sexual violence against a woman who is treated as ‘foreign’ (Judges 19). Such a context is shown to resonate with Ruth 2 where – as is often case even today – Ruth’s vulnerability to violence turns out to be intimately bound up with her multiple identities as woman, worker and foreigner.
Plebs, Class and Everything in Between
Authors: Bonin Hugo 
Published: March 2019

Abstract
Following a summary of M. Breaugh’s book The Plebeian Experience, the question of the relationship of plebs and class is addressed. Drawing on N. Thoburn’s discussion of the ‘lumpenproletariat’ as well as E.P. Thompson’s conception of class, the case is made for keeping ‘plebeian’ and ‘class’ experiences in conceptual tension.
Capitalism, Colonialism, and the War on Human Life
Authors: Noonan Jeff 
Published: March 2019

Abstract
Dussel’s complex work calls into question the standard history of philosophy, reveals a counter-history at work beneath the official history that gives voice to the victims of capitalism and colonialism, and systematically develops a novel ‘material ethics’ grounded in an unqualified, universal affirmation of life as the foundation of liberatory values. The Ethics of Liberation brings together the major problems explored in Dussel’s prolific body of earlier work: the relationship between Western philosophy and the expansion of European society; the relationship between centre and periphery in global political economy, considered as both a philosophical and an ethical problem; the ethical interpretation of Marxism; the politics of liberation in the colonial context; the defence of universal foundations of ethical norms; and the (all-important) distinction between formal and critical ethics.
‘Hegel Belongs in the Old Testament of the New Philosophy’
Authors: Kryluk Michael 
Published: March 2019

Abstract
This article is an Introduction to a translation of ‘Zur Beurteilung der Schrift Das Wesen des Christentums’ by Ludwig Feuerbach (see DOI 10.1163/1569206X-12341620). To my knowledge, no English translation of this essay currently exists. It was published in February 1842 and functions as both a general reply to critics of his 1841 book The Essence of Christianity, as well as a specific response to the claim of an anonymous reviewer that Feuerbach’s interpretation of religion was the same as that of his fellow Young Hegelian Bruno Bauer. Besides capturing a central moment in Feuerbach’s development between The Essence of Christianity and his well-known works of 1842–4, the essay also sheds light on the rest of the Young Hegelian movement and provides crucial context for some of Marx’s later comments on Feuerbach and his philosophy.
The Bulgarian 19th-Century Book as a Crossroads of Professional Literary Practices
Authors: Zagorov Vasil 
Published: March 2019

Abstract
The Bulgarian printed book began to develop dynamically only at the beginning of the 19th century. The delay in printing in the Bulgarian language for almost 350 years led to the accumulation of a number of peculiarities related to the material and textual aspects of the Bulgarian book. On the one hand, these peculiarities are related to the strong influence of the contemporary 19th century Bulgarian manuscripts; on the other hand, those peculiarities differ depending on the divergent foreign influence—Austrian, Russian, etc. The article discusses how peculiarities in the Bulgarian books produced during the Revival period (1806-78) are obstructing the creation of the Digital Database and Information Retrieval System.
The Position of the Defence and Adequate Facilities
Authors: Karnavas Michael G. 
Published: March 2019

Suppose that procedural settings of national jurisdictions do not work for international criminal proceedings, that victims’ justice is delayed, and tribunals’ resources are drained on account of the burdensome defence. And suppose that accused may not need the same procedural rights and safeguards in international criminal proceedings as in national proceedings. Might it be time for a new and ‘better’ approach considering the unique demands of trying international crimes? From the defence perspective, these suppositions presume a preference for international criminal proceedings that yield quick, nimble, and cheap desired convictions – risking legitimacy essential to these judicial institutions. Might there be other institutional or systemic reasons – independent of whatever burdens caused by the defence – that warrant resolving? Might it be that the defence is sufficiently handicapped as is, militating against adopting procedural modalities that further erode a suspect’s or accused’s enjoyment of fair trial rights?
On the Intersectionality of Religious and Racial Discrimination: A Case Study on the Applicability of ICERD with Respect to China’s Uyghur Muslim Minority
Authors: Holder Ross 
Published: March 2019

Abstract
As an officially recognised minority nationality in China, the Uyghurs’ unique religious identity is ostensibly protected under Chinese national law. In reality, such protections are limited in practice, with frequent claims by Uyghur activists, human rights NGOs and scholars that government policies result in the religious discrimination of the Uyghur population in Xinjiang. In light of the inefficacy of state legislation in protecting the Uyghurs’ religious freedoms, this article considers the protections offered within the Human Rights Treaty System of the United Nations (UN), of which China is both a charter member and an increasingly active participant. However, any attempt to consider Freedom of Religion or Belief protections within the UN’s core treaties remains frustrated as China has yet to ratify the International Covenant on Civil and Political Rights, which is the sole UN human rights instrument to contain provisions dedicated to religious and minority rights. To overcome this issue, this article argues that acts of religious discrimination against the Uyghur minority may also fall into contention with the protections contained within the International Convention on the Elimination of All Forms of Racial Discrimination, a treaty that has been ratified by China and is therefore legally obligated to comply with.
The ‘Aura’ of Home
Authors: Issa Dima 
Published: March 2019

Abstract
In Arabic restaurants, sitting rooms and cars around the world, her voice filters through the airwaves, transporting listeners to narrow alleyways, cobblestones and the Mediterranean Sea, to a time of innocence and peace, determination and war, stability and acceptance. Her songs, melancholy memory and patriotic love shape Arab heritage and offer a focal point for identity construction. For many Arabs in the diaspora, Fairouz’s music is a tool of expression, a proxy for nostalgia and a call for resistance. Through a theoretical framework that combines affect, the mnemonic imagination and migration, I highlight the preliminary findings of my PhD research. This research involves a series of interviews with members of the Arab diaspora living in Doha, Qatar. I examine the role Fairouz’s music played in the lives of these interview subjects.
From Icons of Evil to Features of Princely Pleasure: Mongols in Fourteenth-Century Italian Illuminated Manuscripts
Authors: Manzari Francesca 
Published: March 2019

AbstractThe representation of Mongols in Late-Medieval Italian illuminated manuscripts undergoes a transformation in the fourteenth century. In literature connected to the Crusades and in historical writings they are usually portrayed as symbols of Evil or of the Deadly Vices. In other instances, nonetheless, they seem to lose this significant iconic value and to turn into an exotic component for the amusement of princely patrons. It is certainly not by chance that illuminations comprising Mongols were produced in the cities most strongly tied to the East by trading routes and commercial interests, like Venice and Genoa. The appearance of Mongols within more widespread iconographies, both sacred and secular, and their metamorphosis as exotic decorations are connected to manuscript illumination at the Angevin court in Naples. This contribution re-evaluates both types of instances, with the purpose of achieving a survey of these types of representation in Italian gothic illuminated manuscripts.
Informed Consent and Advance Care Directives: Cornerstones and Outstanding Issues in the Newly Enacted Italian Legislation
Authors: Montanari Vergallo Gianluca , Spagnolo Antonio G. 
Published: March 2019

This article’s authors delve into, and comment on, some of the key provisions within law no. 219, passed in 2017, which came into full effect in 2018. The legislation presents several innovative aspects: (a) communication time is equated to care; (b) patients may turn down lifesaving treatments, yet doctors must put in place all suitable support processes, from a psychological standpoint as well, in order to make sure that patients make informed decisions in full awareness; (c) refusal to treatment may be expressed prior to the onset of the disease making the patient incapable, as long as the advance directive is laid out by a mentally capable adult who has been provided with all relevant medical information available as to the consequence of a refusal to undergo a given treatment; (d) artificial nutrition and hydration are tantamount to treatment; thus, they may not be carried out and kept in place in absence of valid consent; (e) patients may appoint a healthcare proxy holder, tasked with interacting with doctors and caregivers and expressing consent or refusal; (f) patient will, whether current or advance, must be complied with even under emergency or urgency conditions, provided that clinical conditions and circumstances make it possible to acquire it; (g) doctors may disregard advance directives only when specifically provided for by the law; (h) patients may not demand treatment deemed to be illegal or running counter to ethical codes or scientific evidence. The new legislation, therefore, is meant to uphold the right to exercise self-determination as well as the patient’s quality of life, yet ensuring that doctors remain fully capable of making the decisions that they are best positioned to. Summary: The Italian Parliament has for the first time regulated the issue of consent and refusal of healthcare treatments, whether currently expressed or advance. This article elaborates on recent Italian legislation that details a patient's right to consent to or refuse treatment in advance, including refusal of artificial nutrition and hydration, the duty of doctors in the event of an emergency, the shared planning treatment, the role of durable power of attorney, and advance healthcare directives.
Manganese-enhanced magnetic resonance imaging in the whole visual pathway: chemical identification and neurotoxic changes
Authors: Xiao Zebin , Tang Zuohua , Wu Lingjie , Feng Xiaoyuan , Sun Xinghuai , Tang Weijun , Wang Jie , Jin Lixin , Wang Rong 
Published: March 2019

Background Little is known about the specificity of manganese-enhanced magnetic resonance imaging (MEMRI) and its neurotoxic effect of the whole visual pathway. Purpose To explore the specificity of MEMRI and the neurotoxic effect in the whole visual pathway. Material and Methods Twenty-four rats were divided into four groups, in which 50, 100, 200, and 400 nmol MnCl2 were injected into the left eye of each rat through intravitreal injection, respectively. MEMRI was performed one day after injection of MnCl2. Moreover, another 10 rats were divided into two groups, in which 200 and 400 nmol MnCl2 were injected into the left eye of each rat. One day after injecting, chemical identification and transmission electron microscopy were performed to verify the presence and pathological effects. Results The whole three-dimensional (3D) visual pathway of the left eye was observable on MEMRI with thin slab maximum intensity projection (TSMIP) in all rats except the 50 nmol group, which was confirmed by chemical identification. Higher dose of MnCl2 resulted in greater contrast-to-noise ratio, increasing the effectiveness of the technique. Transmission electron microscopy showed most structures of the visual pathway except the superior colliculus and visual cortex were poisoned in the 200 and 400 nmol groups, especially in the latter group. Conclusion Our study indicated that MEMRI with TSMIP after injection of 200 nmol MnCl2 can best show the entire and 3D visual pathway in the rat with less neurotoxic changes. Additionally, chemical identification is useful for the confirmation of the specificity of MEMRI.
An investigation of the pretend play abilities of children with an acquired brain injury
Authors: Dooley Bridget , Stagnitti Karen , Galvin Jane 
Published: March 2019

Introduction This study describes the self-initiated pretend play abilities of children who had sustained an acquired brain injury. Method A non-experimental study was conducted with 26 children with acquired brain injury (15 females, mean age 5.08 years, SD 1.58 years), who were out of post-traumatic amnesia, able to sit independently and engage in a play session. The children were assessed individually on one occasion using the Child-Initiated Pretend Play Assessment. Findings All children in the study presented with pretend play deficits, particularly in symbolic play. Inattention, distractibility and limited concentration were common behaviours of the children. Three quarters of the sample (76.48%) were unable to complete the time of the assessment. For many of the children the cessation of their play was sudden and abrupt, even for those who showed complex play ability. Conclusion Cognitive fatigue is argued to have impacted on the children’s play ability due to the considerable amount of cognitive effort required to engage in pretend play. Implications for intervention are to offer short sessions for children with acquired brain injury and pay particular attention to a child’s symbolic play within pretend play ability.
Differential effect of FHM2 mutation on synaptic plasticity in distinct hippocampal regions
Authors: Iure Antonio de , Mazzocchetti Petra , Bastioli Guendalina , Picconi Barbara , Costa Cinzia , Marchionni Ivan , Casari Giorgio , Tozzi Alessandro , Pietrobon Daniela , Calabresi Paolo 
Published: March 2019

Introduction Familial hemiplegic migraine 2 is a pathology linked to mutation of the ATP1A2 gene producing loss of function of the α2 Na+/K+-ATPase (NKA). W887R/+ knock-in (KI) mice are used to model the familial hemiplegic migraine 2 condition and are characterized by 50% reduced NKA expression in the brain and reduced rate of K+ and glutamate clearance by astrocytes. These alterations might, in turn, produce synaptic changes in synaptic transmission and plasticity. Memory and learning deficits observed in familial hemiplegic migraine patients could be ascribed to a possible alteration of hippocampal neuronal plasticity and measuring possible changes of long-term potentiation in familial hemiplegic migraine 2 KI mice might provide insights to strengthen this link. Results Here we have investigated synaptic plasticity in distinct hippocampal regions in familial hemiplegic migraine 2 KI mice. We show that the dentate gyrus long-term potentiation of familial hemiplegic migraine 2 mice is abnormally increased in comparison with control animals. Conversely, in the CA1 area, KI and WT mice express long-term potentiation of similar amplitude. Conclusions The familial hemiplegic migraine 2 KI mice show region-dependent hippocampal plasticity abnormality, which might underlie some of the memory deficits observed in familial migraine.
Lanreotide vs octreotide LAR for patients with advanced gastroenteropancreatic neuroendocrine tumors: An observational time and motion analysis
Authors: Ryan P , McBride A , Ray D , Pulgar S , Ramirez RA , Elquza E , Favaro JP , Dranitsaris G 
Published: March 2019

Background Lanreotide and octreotide acetate suspension for injectable (LAR) are both recommended for clinical use in patients with locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors. However, each agent possesses unique attributes in terms of their drug-delivery characteristics. The study objective was to compare overall drug-delivery efficiency between lanreotide and octreotide LAR in gastroenteropancreatic neuroendocrine tumor patients. Methods This study employed an observational time and motion design among patients treated with lanreotide or octreotide LAR across five US cancer centers. Baseline patient data collection included age, disease grade and duration, prior therapies and performance status. Drug-delivery time (drug preparation and administration), total patient time and resource use data were collected for gastroenteropancreatic neuroendocrine tumors receiving lanreotide (n = 22) or octreotide LAR (n = 22). Following each administration, qualitative data on the drug-delivery experience was collected from patients and nurses. Results Lanreotide was associated with a significant reduction in mean delivery time (2.5 min; 95% CI:2.0 to 3.1) compared to octreotide LAR (6.2 min; 95%CI: 4.4 to 7.9; p = 0.004). The mean total patient time for lanreotide and octreotide LAR was comparable between groups (32.1 vs. 36.6 minutes; p = 0.97). Nurses reported increased concerns with octreotide LAR related to needle clogging ( p = 0.034) and device failures ( p = 0.057). Overall, lanreotide had a median satisfaction score of 5.0 compared to a score of 4.0 with octreotide LAR ( p = 0.03). Conclusions Lanreotide was associated with significant reductions in drug-delivery time compared to octreotide LAR, which contributed to an improvement in overall healthcare efficiency. Trial registration clinicaltrials.gov Identifier: NCT03017690.