bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular disease and COVID-19: a consensus paper from the ESC Working Group on Coronary Pathophysiology & Microcirculation, ESC Working Group on Thrombosis and the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Heart Rhythm Association (EHRA)
Authors: Cenko Edina , Badimon Lina , Bugiardini Raffaele , Claeys Marc J , De Luca Giuseppe , de Wit Cor , Derumeaux Geneviève , Dorobantu Maria , Duncker Dirk J , Eringa Etto C , Gorog Diana A , Hassager Christian , Heinzel Frank R , Huber Kurt , Manfrini Olivia , Milicic Davor , Oikonomou Evangelos , Padro Teresa , Trifunovic-Zamaklar Danijela , Vasiljevic-Pokrajcic Zorana , Vavlukis Marija , Vilahur Gemma , Tousoulis Dimitris 
Published: September 2021

Abstract
The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as ‘post-acute COVID-19’ may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance.
Third-party induced cyber incidents—much ado about nothing?
Authors: Benaroch Michel 
Published: September 2021

AbstractGrowing reliance on third-party services, such as cloud computing, is believed to increase client firms’ exposure to third-party induced cyber incidents. However, we lack empirical research on the prevalence and scale of third-party induced cyber incidents. Moreover, we do not know who pays more of the price for experiencing these incidents—the client firm and/or the third-party provider firm. We study these questions using a sample of 1397 cyber incidents in public firms between 2000 and 2020 of which 246 are third-party induced incidents. Our findings offer several novel insights. Third-party induced cyber incidents are not growing in prevalence any faster than other incidents, but they do compromise greater volumes of confidential data per incident. As to the price paid for third-party induced incidents, the picture is more nuanced. Client (first-party) firms suffer drops in equity returns that are comparable to those for homegrown incidents, while small third-party provider firms suffer significantly larger drops in equity returns and large third-party provider firms do not suffer a discernible drop in equity returns. We discuss implications of these findings for client firms and service providers.
COVIDium: a COVID-19 resource compendium
Authors: Satyam Rohit , Yousef Malik , Qazi Sahar , Bhat Adil Manzoor , Raza Khalid 
Published: September 2021

Abstract
The severe acute respiratory syndrome coronavirus 2 that causes coronavirus disease 2019 (COVID-19) disrupted the normal functioning throughout the world since early 2020 and it continues to do so. Nonetheless, the global pandemic was taken up as a challenge by researchers across the globe to discover an effective cure, either in the form of a drug or vaccine. This resulted in an unprecedented surge of experimental and computational data and publications, which often translated their findings in the form of databases (DBs) and tools. Over 160 such DBs and more than 80 software tools were developed, which are uncharacterized, unannotated, deployed at different universal resource locators and are challenging to reach out through a normal web search. Besides, most of the DBs/tools are present on preprints and are either underutilized or unrecognized because of their inability to make it to top Google search hits. Henceforth, there was a need to crawl and characterize these DBs and create a compendium for easy referencing. The current article is one such concerted effort in this direction to create a COVID-19 resource compendium (COVIDium) that would facilitate the researchers to find suitable DBs and tools for their research studies. COVIDium tries to classify the DBs and tools into 11 broad categories for quick navigation. It also provides end-users some generic hit terms to filter the DB entries for quick access to the resources. Additionally, the DB provides Tracker Dashboard, Neuro Resources, references to COVID-19 datasets and protein–protein interactions. This compendium will be periodically updated to accommodate new resources.
Database URL: The COVIDium is accessible through http://kraza.in/covidium/
Safety and efficacy of different prophylactic anticoagulation dosing regimens in critically and non-critically ill patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials
Authors: Ortega-Paz Luis , Galli Mattia , Capodanno Davide , Franchi Francesco , Rollini Fabiana , Bikdeli Behnood , Mehran Roxana , Montalescot Gilles , Gibson C Michael , Lopes Renato D , Andreotti Felicita , Angiolillo Dominick J 
Published: September 2021

Abstract

Background
The clinical impact of different prophylactic anticoagulation regimens among hospitalized patients with coronavirus disease 2019 (COVID-19) remains unclear. We pooled evidence from available randomized controlled trials (RCTs) to provide insights on this topic.

Methods and results
We searched for RCTs comparing treatment with an escalated-dose (intermediate-dose or therapeutic-dose) vs. a standard-dose prophylactic anticoagulation regimen in critically and non-critically ill COVID-19 patients requiring hospitalization and without a formal indication for anticoagulation. The primary efficacy endpoint was all-cause death, and the primary safety endpoint was major bleeding. Seven RCTs were identified, including 5154 patients followed on an average of 33 days. Compared to standard-dose prophylactic anticoagulation, escalated-dose prophylactic anticoagulation was not associated with a reduction of all-cause death [17.8% vs. 18.6%; risk ratio (RR) 0.96, 95% confidence interval (CI) 0.78–1.18] but was associated with an increase in major bleeding (2.4% vs. 1.4%; RR 1.73, 95%CI 1.15–2.60). Compared to prophylactic anticoagulation used at a standard dose, an escalated dose was associated with lower rates of venous thromboembolism (2.5% vs. 4.7%; RR 0.55, 95%CI 0.41–0.74) without a significant effect on myocardial infarction (RR 0.80, 95%CI 0.47–1.36), stroke (RR 0.94, 95%CI 0.43–2.09), or systemic arterial embolism (RR 1.20, 95%CI 0.29–4.95). There were no significant interactions in the subgroup analysis for critically and non-critically ill patients.

Conclusions
Our findings provide comprehensive and high-quality evidence for the use of standard-dose prophylactic anticoagulation over an escalated-dose regimen as routine standard of care for hospitalized patients with COVID-19 who do not have an indication for therapeutic anticoagulation, irrespective of disease severity.

Study registration
This study is registered in PROSPERO (CRD42021257203).
Is the Way Forward to Step Back? Documenting the Frequency With Which Study Goals Are Misaligned With Study Methods and Interpretations in the Epidemiologic Literature
Authors: Kezios Katrina L 
Published: September 2021

Abstract
In any research study, there is an underlying process that should begin with a clear articulation of the study’s goal. The study’s goal drives this process; it determines many study features, including the estimand of interest, the analytic approaches that can be used to estimate it, and which coefficients, if any, should be interpreted. Misalignment can occur in this process when analytic approaches and/or interpretations do not match the study’s goal; misalignment is potentially more likely to arise when study goals are ambiguously framed. In this study, misalignment in the observational epidemiologic literature was documented and how the framing of study goals contributes to misalignment was explored. The following 2 misalignments were examined: use of an inappropriate variable selection approach for the goal (a “goal–methods” misalignment) and interpretation of coefficients of variables for which causal considerations were not made (e.g., Table 2 Fallacy, a “goal–interpretation” misalignment). A random sample of 100 articles published 2014–2018 in the top 5 general epidemiology journals were reviewed. Most reviewed studies were causal, with either explicitly stated (n = 13; 13%) or associational-framed (n = 71; 69%) aims. Full alignment of goal–methods–interpretations was infrequent (n = 9; 9%), although clearly causal studies (n = 5 of 13; 38%) were more often fully aligned than were seemingly causal ones (n = 3 of 71; 4%). Goal–methods misalignments were common (n = 34 of 103; 33%), but most frequently, methods were insufficiently reported to draw conclusions (n = 47; 46%). Goal–interpretations misalignments occurred in 31% (n = 32) of the studies and occurred less often when the methods were aligned (n = 2; 2%) compared with when the methods were misaligned (n = 13; 13%).
Pacing therapy for atrioventricular dromotropathy: a combined computational–experimental–clinical study
Authors: Salden Floor C W M , Huntjens Peter R , Schreurs Rick , Willemen Erik , Kuiper Marion , Wouters Philippe , Maessen Jos G , Bordachar Pierre , Delhaas Tammo , Luermans Justin , Meine Mathias , Allaart Cornelis P , van Stipdonk Antonius M W , Prinzen Frits W , Lumens Joost , Vernooy Kevin 
Published: September 2021

Abstract

Aims
Investigate haemodynamic effects, and their mechanisms, of restoring atrioventricular (AV)-coupling using pacemaker therapy in normal and failing hearts in a combined computational–experimental–clinical study.

Methods and results
Computer simulations were performed in the CircAdapt model of the normal and failing human heart and circulation. Experiments were performed in a porcine model of AV dromotropathy. In a proof-of-principle clinical study, left ventricular (LV) pressure and volume were measured in 22 heart failure (HF) patients (LV ejection fraction &lt;35%) with prolonged PR interval (&gt;230 ms) and narrow or non-left bundle branch block QRS complex. Computer simulations and animal studies in normal hearts showed that restoring of AV-coupling with unchanged ventricular activation sequence significantly increased LV filling, mean arterial pressure, and cardiac output by 10–15%. In computer simulations of failing hearts and in HF patients, reducing PR interval by biventricular (BiV) pacing (patients: from 300 ± 61 to 137 ± 30 ms) resulted in significant increases in LV stroke volume and stroke work (patients: 34 ± 40% and 26 ± 31%, respectively). However, worsening of ventricular dyssynchrony by using right ventricular (RV) pacing abrogated the benefit of restoring AV-coupling. In model simulations, animals and patients, the increase of LV filling and associated improvement of LV pump function coincided with both larger mitral inflow (E- and A-wave area) and reduction of diastolic mitral regurgitation.

Conclusion
Restoration of AV-coupling by BiV pacing in normal and failing hearts with prolonged AV conduction leads to considerable haemodynamic improvement. These results indicate that BiV or physiological pacing, but not RV pacing, may improve cardiac function in patients with HF and prolonged PR interval.
Screening Health-Promoting Compounds for Their Capacity to Induce the Activity of FOXO3
Authors: Jimenez Lucia , Silva Andreia , Calissi Giampaolo , Grenho Inês , Monteiro Rita , Mayoral-Varo Victor , Blanco-Aparicio Carmen , Pastor Joaquin , Bustos Victor , Bracher Franz , Megías Diego , Ferreira Bibiana I , Link Wolfgang 
Published: September 2021

Abstract
Several chemical compounds including natural products have been suggested as being effective against age-related diseases or as beneficial for a healthy life. On the other hand, forkhead box O (FOXO) proteins are emerging as key cellular components associated with extreme human longevity. FOXO proteins are mainly regulated by posttranslational modifications and as these modifications are reversible, activation and inactivation of FOXO are attainable through pharmacological treatment. Here, we questioned whether a panel of compounds with known health-beneficial properties has the capacity to induce the activity of FOXO factors. We show that resveratrol, a phytoalexin present in grapes and other food products, the amide alkaloid piperlongumine found in the fruit of the long pepper, and the plant-derived β-carboline compound harmine induced nuclear translocation of FOXO3. We also show that piperlongumine and harmine but not resveratrol activate FOXO-dependent transcription. We determined the half maximal effective concentration (EC50) values for resveratrol, piperlongumine, and harmine for FOXO translocation, and analyzed their inhibitory impact on chromosomal maintenance 1 (CRM1)-mediated nuclear export and the production of reactive oxygen species (ROS). We also used chemical biology approach and Western blot analysis to explore the underlying molecular mechanisms. We show that harmine, piperlongumine, and resveratrol activate FOXO3 independently of phosphoinositide 3-kinase (PI3K)/AKT signaling and the CRM1-mediated nuclear export. The effect of harmine on FOXO3 activity is at least partially mediated through the inhibition of dual-specificity tyrosine (Y) phosphorylationregulated kinase 1A (DYRK1A) and can be reverted by the inhibition of sirtuins (SIRTs).
Does Adult Day Service Use Improve Well-Being of Black Caregivers of People Living With Dementia?
Authors: Parker Lauren J , Gitlin Laura N 
Published: September 2021

Abstract

Background and Objectives
Despite adult day services (ADS) being the most racially diverse home- and community-based service (HCBS), there is a paucity of research that has examined the impact of ADS on well-being measures among Black caregivers of people living with dementia. To address this gap, this study examined the association between the use of ADS and depressive symptoms among Black dementia caregivers.

Research Design and Methods
Using baseline data from 2 behavioral intervention trials, Advancing Caregiver Training (n = 72) and Care of Persons with Dementia in their Environments (n = 63), we conducted ordinary least squares regression to examine the association between ADS use in the past 6 months and depressive symptoms (n = 135). The dependent variable, depressive symptoms, was assessed by the 10-item Center for Epidemiologic Studies—Depression (CES-D) scale. The independent variable was assessed by self-report of ADS use in the past 6 months.

Results
Nearly 36% of the sample used ADS in the past 6 months. After controlling for caregiver characteristics associated with depression (burden, social support, self-rated health, caregiving relationship status, years caregiving, religious/spiritual coping, and demographic characteristics), caregivers who utilized ADS had a lowered CES-D score (B = −1.97, p = .03) compared to those who did not use ADS.

Discussion and Implications
Black dementia caregivers who utilized ADS had lower depressive symptoms compared to those who did not utilize ADS. ADS may be a critical HCBS that can provide relief to Black caregivers. Research is needed to examine additional benefits of ADS use among Black caregivers and the policy and programming needed to enhance access to ADS.
Desiderata for the development of next-generation electronic health record phenotype libraries
Authors: Chapman Martin , Mumtaz Shahzad , Rasmussen Luke V , Karwath Andreas , Gkoutos Georgios V , Gao Chuang , Thayer Dan , Pacheco Jennifer A , Parkinson Helen , Richesson Rachel L , Jefferson Emily , Denaxas Spiros , Curcin Vasa 
Published: September 2021

AbstractBackgroundHigh-quality phenotype definitions are desirable to enable the extraction of patient cohorts from large electronic health record repositories and are characterized by properties such as portability, reproducibility, and validity. Phenotype libraries, where definitions are stored, have the potential to contribute significantly to the quality of the definitions they host. In this work, we present a set of desiderata for the design of a next-generation phenotype library that is able to ensure the quality of hosted definitions by combining the functionality currently offered by disparate tooling.MethodsA group of researchers examined work to date on phenotype models, implementation, and validation, as well as contemporary phenotype libraries developed as a part of their own phenomics communities. Existing phenotype frameworks were also examined. This work was translated and refined by all the authors into a set of best practices.ResultsWe present 14 library desiderata that promote high-quality phenotype definitions, in the areas of modelling, logging, validation, and sharing and warehousing.ConclusionsThere are a number of choices to be made when constructing phenotype libraries. Our considerations distil the best practices in the field and include pointers towards their further development to support portable, reproducible, and clinically valid phenotype design. The provision of high-quality phenotype definitions enables electronic health record data to be more effectively used in medical domains.
Rethinking the Virtuous Circle Hypothesis on Social Media: Subjective versus Objective Knowledge and Political Participation
Authors: Lee Sangwon , Diehl Trevor , Valenzuela Sebastián 
Published: September 2021

Abstract
Despite early promise, scholarship has shown little empirical evidence of learning from the news on social media. At the same time, scholars have documented the problem of information ‘snacking’ and information quality on these platforms. These parallel trends in the literature challenge long-held assumptions about the pro-social effects of news consumption and political participation. We argue that reliance on social media for news does not contribute to people’s real level of political knowledge (objective knowledge), but instead only influences people’s impression of being informed (subjective knowledge). Subjective knowledge is just as important for driving political participation, a potentially troubling trend given the nature of news consumption on social media. We test this expectation with panel survey data from the 2018 U.S. midterm elections. Two path model specifications (fixed effects and autoregressive) support our theoretical model. Implications for the study of the ‘dark side’ of social media and democracy are discussed.
Compound heterozygous variants in SHQ1 are associated with a spectrum of neurological features, including early-onset dystonia
Authors: Sleiman Sophie , Marshall Aren E , Dong Xiaomin , Mhanni Aziz , Alidou-D’Anjou Ismaël , Frosk Patrick , Marin Samantha E , Stark Zornitza , Del Bigio Marc R , McBride Arran , Sadedin Simon , Gallacher Lyndon ,   Care4Rare Canada Consortium, Christodoulou John , Boycott Kym M , Dragon François , Kernohan Kristin D 
Published: September 2021

Abstract
SHQ1 is essential for biogenesis of H/ACA ribonucleoproteins, a class of molecules important for processing ribosomal RNAs, modifying spliceosomal small nuclear RNAs and stabilizing telomerase. Components of the H/ACA ribonucleoprotein complex have been linked to neurological developmental defects. Here, we report two sibling pairs from unrelated families with compound heterozygous variants in SHQ1. Exome sequencing was used to detect disease causing variants, which were submitted to ‘matching’ platforms linked to MatchMaker Exchange. Phenotype comparisons supported these matches. The affected individuals present with early-onset dystonia, with individuals from one family displaying additional neurological phenotypes, including neurodegeneration. As a result of cerebrospinal fluid studies suggesting possible abnormal dopamine metabolism, a trial of levodopa replacement therapy was started but no clear response was noted. We show that fibroblasts from affected individuals have dramatic loss of SHQ1 protein. Variants from both families were expressed in Saccharomyces cerevisiae, resulting in a strong reduction in H/ACA snoRNA production and remarkable defects in rRNA processing and ribosome formation. Our study identifies SHQ1 as associated with neurological disease, including early-onset dystonia, and begins to delineate the molecular etiology of this novel condition.
Mevalonate Kinase Deficiency: A Cause of Severe Very-Early-Onset Inflammatory Bowel Disease
Authors: Bader-Meunier Brigitte , Martins Andreia Luís , Charbit-Henrion Fabienne , Meinzer Ulrich , Belot Alexandre , Cuisset Laurence , Faye Albert , Georgin-Lavialle Sophie , Quartier Pierre , Remy-Piccolo Vanessa , Ruemmele Frank , Uettwiller Florence , Viala Jérôme , Cerf Bensussan Nadine , Berrebi Dominique , Melki Isabelle 
Published: September 2021

Abstract
Mevalonate kinase deficiency should be considered in patients with severe very-early-onset inflammatory bowel disease (IBD), especially in patients with a history of recurrent or chronic fever, peritoneal adhesions, and atypical IBD pathology. Anti-interleukin-1 therapy may be efficacious in these patients with monogenic very-early-onset IBD.