bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydralazine protects the heart against acute ischaemia/reperfusion injury by inhibiting Drp1-mediated mitochondrial fission
Authors: Kalkhoran Siavash Beikoghli , Kriston-Vizi Janos , Hernandez-Resendiz Sauri , Crespo-Avilan Gustavo E , Rosdah Ayeshah A , Lees Jarmon G , Costa Joana Rodrigues Simoes Da , Ling Naomi X Y , Holien Jessica K , Samangouei Parisa , Chinda Kroekkiat , Yap En Ping , Riquelme Jaime A , Ketteler Robin , Yellon Derek M , Lim Shiang Y , Hausenloy Derek J 
Published: December 2020

Abstract

Aims
Genetic and pharmacological inhibition of mitochondrial fission induced by acute myocardial ischaemia/reperfusion injury (IRI) has been shown to reduce myocardial infarct size. The clinically used anti-hypertensive and heart failure medication, hydralazine, is known to have anti-oxidant and anti-apoptotic effects. Here, we investigated whether hydralazine confers acute cardioprotection by inhibiting Drp1-mediated mitochondrial fission.

Methods and results
Pre-treatment with hydralazine was shown to inhibit both mitochondrial fission and mitochondrial membrane depolarisation induced by oxidative stress in HeLa cells. In mouse embryonic fibroblasts (MEFs), pre-treatment with hydralazine attenuated mitochondrial fission and cell death induced by oxidative stress, but this effect was absent in MEFs deficient in the mitochondrial fission protein, Drp1. Molecular docking and surface plasmon resonance studies demonstrated binding of hydralazine to the GTPase domain of the mitochondrial fission protein, Drp1 (KD 8.6±1.0 µM), and inhibition of Drp1 GTPase activity in a dose-dependent manner. In isolated adult murine cardiomyocytes subjected to simulated IRI, hydralazine inhibited mitochondrial fission, preserved mitochondrial fusion events, and reduced cardiomyocyte death (hydralazine 24.7±2.5% vs. control 34.1±1.5%, P=0.0012). In ex vivo perfused murine hearts subjected to acute IRI, pre-treatment with hydralazine reduced myocardial infarct size (as % left ventricle: hydralazine 29.6±6.5% vs. vehicle control 54.1±4.9%, P=0.0083), and in the murine heart subjected to in vivo IRI, the administration of hydralazine at reperfusion, decreased myocardial infarct size (as % area-at-risk: hydralazine 28.9±3.0% vs. vehicle control 58.2±3.8%, P&lt;0.001).

Conclusion
We show that, in addition to its antioxidant and anti-apoptotic effects, hydralazine, confers acute cardioprotection by inhibiting IRI-induced mitochondrial fission, raising the possibility of repurposing hydralazine as a novel cardioprotective therapy for improving post-infarction outcomes.
Defining and Assessing the Reproducibility of Crohn’s Disease Endoscopic Lesions: A Delphi-like Method from the GETAID
Authors: Buisson A , Filippi J , Amiot A , Cadiot G , Allez M , Marteau P , Bouhnik Y , Pineton de Chambrun G , Pelletier A L , Nancey S , Moussata D , Attar A , Blain A , Vuitton L , Vernier-Massouille G , Seksik P , Nachury M , Dupas J L , Laharie D , Peyrin-Biroulet L , Louis E , Mary J Y 
Published: December 2020

Abstract

Background and Aims
Defining and assessing the reproducibility of Crohn’s disease [CD] endoscopic lesions is essential in assessing endoscopic healing.

Methods
Twelve endoscopic CD experts from the GETAID defined aphthoid erosions [AE], superficial ulcerations [SU], deep ulcerations [DU], stenosis, and fistulas according to a Delphi-like method. Thirty different GETAID physicians declared if they found acceptable each definition. Intra- and inter-observer agreements were investigated using 100 videos with one tagged specific lesion [AE, SU, DU, or sham lesion] read by 15 independent endoscopists at baseline and 1 month later in a randomised order. Video quality was determined by an external reader. According to kappa estimate [κ ±standard error], intra or inter-observer agreement was qualified as ‘moderate’ [0.4–0.6], ‘substantial’ [0.6–0.8], or ‘almost perfect’ [0.8–1.0].

Results
Among 30 different experts, 83% to 97% found acceptable the definitions retrieved from the Delphi-like method. Intra-observer κ was 0.717 [±0.019] for SU, 0.681 [±0.027] for AE, 0.856 [±0.014] for DU, showing ‘substantial’ agreement. It was 0.801 [±0.016] for any ulceration [DU or SU]. There was a high variability across readers from ‘moderate’ to ‘almost perfect’ agreement. Inter-observer κ was 0.548 [±0.042] for SU, 0.554 [±0.028] for AE 0.694 [±0.041] for DU, and 0.705 [±0.042] for any ulceration. Inter-observer agreement increased when reading the 53 high-quality videos: 0.787 [±0.064] [p = 0.001], 0.607 [±0.043] [p = 0.001], and 0.782 [±0.064][p = 0.001] for DU, AE, and any ulceration, respectively.

Conclusions
Despite variable intra-agreement level across readers, the GETAID definitions for CD endoscopic lesions provided ‘substantial’ inter-observer agreements, especially in case of high-quality videos.
Digital Transformation and Subjective Job Insecurity in Germany
Authors: Dengler Katharina , Gundert Stefanie 
Published: December 2020

Abstract
The present study examines to what extent employees in Germany are afraid of losing their jobs, depending on the degree of computerization of their occupations. So far, empirical evidence on the relationship between digital transformation and subjective job insecurity is scarce. We distinguish three interrelated insecurity measures: cognitive job insecurity, i.e. the individual assessment of job loss probability, labour market insecurity, i.e. the perceived availability of job alternatives, and affective job insecurity, i.e. the extent to which individuals are worried about a potential job loss. The analysis is based on a large-scale panel study from Germany and refers to the period between 2013 and 2016. Computerization is measured by the occupation-specific substitution potential, i.e. the extent to which occupational tasks are substitutable by computers or computer-controlled machines. The results from multivariate panel analysis suggest that the digital transformation has a negative impact on cognitive job insecurity. We do not find effects on labour market insecurity and affective job insecurity.
Focal Impulse and Rotor Modulation Ablation vs. Pulmonary Vein isolation for the treatment of paroxysmal Atrial Fibrillation: results from the FIRMAP AF study
Authors: Tilz Roland R , Lenz Corinna , Sommer Philipp , Roza Meyer-Saraei , Sarver Anne E , Williams Christopher G , Heeger Christian , Hindricks Gerhard , Vogler Julia , Eitel Charlotte 
Published: December 2020

AbstractAimsPulmonary vein isolation (PVI) is the gold standard for atrial fibrillation (AF) ablation. Recently, catheter ablation targeting rotors or focal sources has been developed for treatment of AF. This study sought to compare the safety and effectiveness of Focal Impulse and Rotor Modulation (FIRM)-guided ablation as the sole ablative strategy with PVI in patients with paroxysmal AF.Methods and resultsWe conducted a multicentre, randomized trial to determine whether FIRM-guided radiofrequency ablation without PVI (FIRM group) was non-inferior to PVI (PVI group) for treatment of paroxysmal AF. The two primary efficacy end points were (i) acute success defined as elimination of AF rotors (FIRM group) or isolation of all pulmonary veins (PVI group) and (ii) long-term success defined as single-procedure freedom from AF/atrial tachycardia (AT) recurrence 12 months after ablation. The study was closed early by the sponsor. At the time of study closure, any pending follow-up visits were waived. A total of 51 patients (mean age 63 ± 10.6 years, 57% male) were enrolled. All PVs were successfully isolated in the PVI group and all rotors were successfully eliminated in the FIRM group. Single-procedure effectiveness was 31.3% (5/16) in the FIRM group and 80% (8/10) in the PVI group at 12 months. Three vascular access complications occurred in the FIRM group.ConclusionThese partial study effectiveness results reinforce the importance of PVI in paroxysmal AF patients and indicate that FIRM-guided ablation alone (without PVI) is not an effective strategy for treatment of paroxysmal AF in most patients.
Efficient identification of scars using heterogeneous model hierarchies
Authors: Chegini Fatemeh , Kopaničáková Alena , Krause Rolf , Weiser Martin 
Published: December 2020

Abstract

Aims
Detection and quantification of myocardial scars are helpful for diagnosis of heart diseases and for personalized simulation models. Scar tissue is generally characterized by a different conduction of excitation. We aim at estimating conductivity-related parameters from endocardial mapping data. Solving this inverse problem requires computationally expensive monodomain simulations on fine discretizations. We aim at accelerating the estimation by combining electrophysiology models of different complexity.

Methods and results
Distributed parameter estimation is performed by minimizing the misfit between simulated and measured electrical activity on the endocardial surface, subject to the monodomain model and regularization. We formulate this optimization problem, including the modelling of scar tissue and different regularizations, and design an efficient solver. We consider grid hierarchies and monodomain–eikonal model hierarchies in a recursive multilevel trust-region method. With numerical examples, efficiency and estimation quality, depending on the data, are investigated. The multilevel solver is significantly faster than a comparable single level solver. Endocardial mapping data of realistic density appears to be sufficient to provide quantitatively reasonable estimates of location, size, and shape of scars close to the endocardial surface.

Conclusion
In several situations, scar reconstruction based on eikonal and monodomain models differ significantly, suggesting the use of the more involved monodomain model for this purpose. Eikonal models can accelerate the computations considerably, enabling the use of complex electrophysiology models for estimating myocardial scars from endocardial mapping data.
Imagery and How it Works in Lorca’s Poeta en Nueva York: The Case of ‘1910 (Intermedio)’
Authors: Anderson Andrew A 
Published: December 2020

Abstract
The terms ‘image’ and ‘imagery’ have changed their meanings over time and are employed very inconsistently by commentators. In the early decades of the twentieth century, Marinetti, Pound, Eliot, Reverdy and Breton, among others, weighed in with innovative proposals of their own with respect to what an image was and how it worked. Lorca’s thinking on the subject of metaphor, image and what he called the ‘hecho poético’ evolved too, with analogies to be made between the latter concept and theories of Jean Epstein and Eliot. The variety of critical opinions concerning Poeta en Nueva York mandates careful scrutiny of individual texts, and a stylistic analysis of ‘1910 (Intermedio)’ reveals a mixture of more conventional and more modern imagistic techniques, the most prominent of which align quite closely with Eliot’s notion of the ‘objective correlative’ – in his words ‘a set of objects, a situation, a chain of events which shall be the formula’ of a particular emotion. This finding adds weight to the argument against Surrealism as a dominant factor in the stylistic orientation of many of the poems in the collection.
Should I Do This? Factors Influencing the Decision to Raise Grandchildren Among Custodial Grandparents
Authors: Hayslip Bert , Fruhauf Christine A , Fish Joshua 
Published: December 2020

AbstractBackground and ObjectivesGrandparents often step in to raise grandchildren when the middle generation is unavailable or unwilling. Although the consequences of raising grandchildren are well researched, little is known about the factors influencing grandparents’ decisions to raise grandchildren. The objectives of this study were to (a) explore the factors that influence decision-making processes among grandparent caregivers, and (b) investigate the extent to which these factors reflect a multifaceted, dualistic framework.Research Design and MethodsData were collected from 108 custodial grandparents who answered an open-ended question about their decision to raise grandchildren.ResultsContent analyses of participants’ answers yielded 15 factorial dimensions defined in terms of their negative/push or positive/pull poles, as it related to their decision to raise grandchildren. Chi-squared tests were used to examine each dimension to the extent to which elicited frequencies were differentially represented for positive versus negative poles. For 12 dimensions, the negative decisional parameters outweighed those that were positive.Discussion and ImplicationsGrandparents report both positive and negative parameters when reflecting on their decision to raise grandchildren. These results call for further research to advance the understanding of the decision-making processes that caregiving grandparents make and the role that they may have on their experiences.
Interannual variations of degree 2 from geodetic observations and surface processes
Authors: Rosat S , Gillet N , Boy J-P , Couhert A , Dumberry M 
Published: December 2020

Summary
Geodetic observations from space continuously record surface deformation and global mass redistribution with an increasing accuracy. In parallel, surficial processes (oceanic, atmospheric, and hydrological loading) are more and more precisely modeled.We propose a confrontation of the geodetic Global Positioning System (GPS) and gravity-field satellite laser ranging (SLR) observations at decadal and interannual time scales, in terms of resolution, correlation and comparison with surficial loading models. We focus on the largest global scale signals of degree 2. At interannual periods, surface deformations retrieved from GPS time-series do not exceed 0.8 mm. Our analysis does not reveal the presence of a dominant signal at a specific period, except perhaps for a signal of approximately 3 yr likely connected to the loading response to El Nio / Southern Oscillations. Contrary to the results of previous studies, we do not find in GPS time-series a clear 6-yr oscillation associated with a degree-2 order-2 pattern. Interannual variations in the degree-2 Stokes coefficients of the gravity field do not exceed 2 × 10−11. We do not detect a dominant gravity signal at one specific period but instead a broad spectrum of frequencies. The comparison between the degree 2 deformations built from GPS time-series with a prediction from SLR derived gravity variations reveals some correlations, though their differences remain important. This highlights the present day limitations of these techniques in their ability to characterize global scale interannual variations. Hydrological loading models show some correlations with both GPS and SLR signals, but we cannot firmly establish that continental hydrology is dominantly responsible for the observed variations. Given the current limits in the resolution of both gravity and surface deformation and in the modelling of surface processes, we conclude that it will be a challenge to retrieve a geodetic signal of sub-decadal period originating in the Earth’s core.
Essentially Derived Varieties in View of New Breeding Technologies – Plant Breeders’ Rights at a Crossroads
Authors: Kock Michael A 
Published: December 2020

Abstract
Plant breeders’ rights (PBR) within the framework of the International Convention for the Protection of New Varieties of Plants (UPOV) are the sui generis intellectual property (IP) system of choice for plant varieties. It achieves a balance between the protection of new varieties and access to protected breeding material for further improvement. The extension of the protection to essentially derived varieties (EDVs) in the UPOV 1991 Convention1 was controversial from the beginning as it creates a tension with the breeders’ exemption. The 2017 UPOV Explanatory Notes on EDVs further fueled the debate as they were seen to limit the EDV extension, while some argue that the EDV scope should extend to all predominantly derived varieties merely on the basis of genetic conformity. With the rise of new breeding technologies (NBTs), legal certainty on the EDV definition is of fundamental importance to avoid a chilling effect on these promising technologies. Not only would a broad EDV definition block critical innovation and restrict the full potential of NBTs to a few multinational companies,2 it would also substantially limit the scope of protection of NBT-derived varieties, as an EDV itself is not entitled to the EDV extension: Valuable NBT-derived varieties would become easy prey for plagiarism. This article shows that the legislative intent of the EDV provision does not limit innovative breeding to conventional crossing and that there is no basis for extending EDV protection to new, innovative varieties which do not retain the essential characteristics of the initial variety (IV) even if there is a high genetic conformity. By analogy with the doctrine of equivalents under the patent system, a derived variety cannot qualify as an EDV if it (i) does not retain all the essential characteristic of the IV and (ii) is ‘non-obvious’ and causes a ‘significant technical progress of considerable economic interest’. The article finally suggests guidelines and processes to overcome the current EDV dilemma.
‘A natural passion?’ The 1810 reflections of a Yorkshire farmer on homosexuality*
Authors: O’Keeffe Eamonn 
Published: December 2020

Abstract
In a newly discovered passage from an 1810 diary, Yorkshire tenant farmer Matthew Tomlinson considers the notion that homosexual desire is a natural, divinely ordained human tendency, discernible from adolescence and undeserving of capital punishment. Although ultimately inconclusive, his reflections offer tantalizing evidence that historical attitudes towards same-sex love in early nineteenth-century British society could be more diverse and sympathetic than previously assumed. This article contextualizes Tomlinson’s comments by considering his broader views on religion and sexuality alongside other contemporary or near-contemporary iterations of the argument that same-sex attraction is innate and blameless.
Association of Anti-TNF Therapy With Increased Risk of Acute Cholangitis in Patients With Primary Sclerosing Cholangitis
Authors: Kulkarni Chiraag , Murag Soumya , Cholankeril George , Fardeen Touran , Mannalithara Ajitha , Lerrigo Robert , Kamal Ahmad , Ahmed Aijaz , Goel Aparna , Sinha Sidhartha R 
Published: December 2020

Abstract

Background
Patients with primary sclerosing cholangitis (PSC) are at increased risk of developing acute cholangitis. The majority of patients with PSC have comorbid inflammatory bowel disease, and many take immunosuppressive medications. The epidemiological risks for the development of acute cholangitis in patients with PSC, including the impact of immunosuppressive therapy, are unknown.

Methods
We conducted a 2-center, retrospective cohort study using data from 228 patients at Stanford University Medical Center and Santa Clara Valley Medical Center (CA), a county health care system. Patient demographics, medications, PSC disease severity, and inflammatory bowel disease status were extracted. Using stepwise variable selection, we included demographic and covariate predictors in the multiple logistic regression model assessing risk factors for cholangitis. Time-to-event analysis was performed to evaluate specific immunosuppressive medications and development of cholangitis.

Results
Thirty-one percent of patients had at least 1 episode of acute cholangitis (n = 72). Anti-tumor necrosis factor (TNF) therapy was associated with increased odds of acute cholangitis (odds ratio, 7.29; 95% confidence interval, 2.63-12.43), but immunomodulator use was protective against acute cholangitis (odds ratio, 0.23; 95% confidence interval, 0.05-0.76). Anti-TNF therapy was associated with decreased time-to-cholangitis, with a median time of 28.4 months; in contrast, only 11.1% of patients who were prescribed immunomodulators developed cholangitis over the same time period (P &lt; 0.001).

Conclusions
Our observations suggest that classes of immunosuppressive medications differentially modify the odds of acute cholangitis. Biologic therapy, ie, anti-TNF therapy, was shown to have significantly higher odds for patients developing acute cholangitis whereas immunomodulator therapy was shown to have a potential protective effect. These findings may help guide physicians in decision-making for determining appropriate immunosuppressive therapy.
Distinguishing Amnestic Mild Cognitive Impairment From HIV-Associated Neurocognitive Disorders
Authors: Sundermann Erin E , Bondi Mark W , Campbell Laura M , Gouaux Ben , Moore Raeanne C , Soontornniyomkij Virawudh , Moore David J 
Published: December 2020

Abstract

Background
Memory impairment occurs in human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) and amnestic mild cognitive impairment (aMCI), the precursor to Alzheimer disease (AD). Methods are needed to distinguish aMCI-associated from HAND-associated impairment in people with HIV (PWH). We developed a neuropsychological method of identifying aMCI in PWH and tested this by relating AD neuropathology (β-amyloid, phospho-Tau) to aMCI versus HAND classification.

Methods
Seventy-four HIV-positive cases (aged 50−68 years) from the National NeuroAIDS Tissue Consortium had neurocognitive data within 1 year of death and data on β-amyloid and phospho-Tau pathology in frontal brain tissue. High aMCI risk was defined as impairment (&lt;1.0 SD below normative mean) on 2 of 4 delayed recall or recognition outcomes from a verbal and nonverbal memory test (at least 1 recognition impairment required). Differences in β-amyloid and phospho-Tau by aMCI and HAND classification were examined.

Results
High aMCI risk was more common in HAND (69.0%) versus no HAND (37.5%) group. β-amyloid pathology was 4.75 times more likely in high versus low aMCI risk group. Phospho-Tau pathology did not differ between aMCI groups. Neither neuropathological feature differed by HAND status.

Conclusions
Amnestic mild cognitive impairment criteria that include recognition impairment may help to detect AD-like cognitive/biomarker profiles among PWH.