bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocytic glycogen accumulation drives the pathophysiology of neurodegeneration in Lafora disease
Authors: Duran Jordi , Hervera Arnau , Markussen Kia H , Varea Olga , López-Soldado Iliana , Sun Ramon C , del Río Jose Antonio , Gentry Matthew S , Guinovart Joan J 
Published: March 2021

AbstractThe hallmark of Lafora disease, a fatal neurodegenerative disorder, is the accumulation of intracellular glycogen aggregates called Lafora bodies. Until recently, it was widely believed that brain Lafora bodies were present exclusively in neurons and thus that Lafora disease pathology derived from their accumulation in this cell population. However, recent evidence indicates that Lafora bodies are also present in astrocytes. To define the role of astrocytic Lafora bodies in Lafora disease pathology, we deleted glycogen synthase specifically from astrocytes in a mouse model of the disease (malinKO). Strikingly, blocking glycogen synthesis in astrocytes—thus impeding Lafora bodies accumulation in this cell type—prevented the increase in neurodegeneration markers, autophagy impairment, and metabolic changes characteristic of the malinKO model. Conversely, mice that over-accumulate glycogen in astrocytes showed an increase in these markers. These results unveil the deleterious consequences of the deregulation of glycogen metabolism in astrocytes and change the perspective that Lafora disease is caused solely by alterations in neurons.
Emergence of blockchain-technology application in peer-to-peer electrical-energy trading: a review
Authors: Thukral Manish Kumar 
Published: March 2021

Abstract
Renewable-energy resources require overwhelming adoption by the common masses for safeguarding the environment from pollution. In this context, the prosumer is an important emerging concept. A prosumer in simple terms is the one who consumes as well as produces electricity and sells it either to the grid or to a neighbour. In the present scenario, peer-to-peer (P2P) energy trading is gaining momentum as a new vista of research that is viewed as a possible way for prosumers to sell energy to neighbours. Enabling P2P energy trading is the only method of making renewable-energy sources popular among the common masses. For making P2P energy trading successful, blockchain technology is sparking considerable interest among researchers. Combined with smart contracts, a blockchain provides secure tamper-proof records of transactions that are recorded in distributed ledgers that are immutable. This paper explores, using a thorough review of recently published research work, how the existing power sector is reshaping in the direction of P2P energy trading with the application of blockchain technology. Various challenges that are being faced by researchers in the implementation of blockchain technology in the energy sector are discussed. Further, this paper presents different start-ups that have emerged in the energy-sector domain that are using blockchain technology. To give insight into the application of blockchain technology in the energy sector, a case of the application of blockchain technology in P2P trading in electrical-vehicle charging is discussed. At the end, some possible areas of research in the application of blockchain technology in the energy sector are discussed.
PREVAIL IV: A Randomized, Double-Blind, 2-Phase, Phase 2 Trial of Remdesivir vs Placebo for Reduction of Ebola Virus RNA in the Semen of Male Survivors
Authors: Higgs Elizabeth S , Gayedyu-Dennis Dehkontee , Fischer II William A , Nason Martha , Reilly Cavan , Beavogui Abdoul Habib , Aboulhab Jamila , Nordwall Jacqueline , Lobbo Princess , Wachekwa Ian , Cao Huyen , Cihlar Tomas , Hensley Lisa , Lane H Clifford 
Published: March 2021

Abstract

Background
Ebola virus RNA persists in the semen of male Ebola survivors for months to years after the acute infection, and male-to-female sexual transmission of the virus is well documented. We investigated whether remdesivir can safely reduce persistence of seminal Ebola virus RNA.

Methods
We recruited men with persistent seminal Ebola RNA in Liberia and Guinea. Participants were randomized 1:1 to receive intravenous remdesivir (GS-5734; Gilead Sciences) or matching placebo administered once daily by intravenous infusion over 1 hour on 5 consecutive days. Stratification was by country and number of positive (1 or 2) preenrollment semen tests. We evaluated the difference in mean assay negativity rate (ANR), that is, the proportion of negative tests for each participant in each group in the treatment (days 1–28) and follow-up (months 2–6) phases on an intention-to-treat basis.

Results
We enrolled 38 men from July 2016 through June 2018. The mean treatment phase ANRs were 85% (standard deviation [SD] = 24%) and 76% (SD = 30%) in the remdesivir and placebo arms, respectively (P = .270). The mean follow-up phase ANRs were 96% (SD = 10%) and 81% (SD = 29%) in the remdesivir and placebo arms, respectively (P = .041). The 5-day remdesivir regimen was well tolerated with no safety concerns.

Conclusions
In this small trial, remdesivir 100 mg/day for 5 days safely reduced the presence of Ebola virus RNA in the semen of Ebola survivors 2 to 6 months after administration. A larger follow-up study is necessary to confirm results.
Clinical Trials Registration . NCT02818582
Plasma Kynurenine-to-Tryptophan Ratio, a Highly Sensitive Blood-Based Diagnostic Tool for Tuberculosis in Pregnant Women Living With Human Immunodeficiency Virus (HIV)
Authors: Adu-Gyamfi Clement , Savulescu Dana , Mikhathani Lillian , Otwombe Kennedy , Salazar-Austin Nicole , Chaisson Richard , Martinson Neil , George Jaya , Suchard Melinda 
Published: March 2021

Abstract

Background
For pregnant women living with human immunodeficiency virus (HIV), concurrent active tuberculosis (TB) disease increases the risk of maternal mortality and poor pregnancy outcomes. Plasma indoleamine 2,3-dioxygenase (IDO) activity measured by kynurenine-to-tryptophan (K/T) ratio has been proposed as a blood-based TB biomarker. We investigated whether plasma K/T ratio could be used to diagnose active TB among pregnant women with HIV.

Methods
Using an enzyme-linked immunosorbent assay (ELISA), we measured K/T ratio in 72 pregnant women with and active TB and compared them to 117 pregnant women with HIB but without TB, matched by age and gestational age.

Results
Plasma K/T ratio was significantly elevated during pregnancy compared to sampling done after pregnancy (P &lt; .0001). Pregnant women who had received isoniazid preventive therapy (IPT) before enrollment had decreased plasma K/T ratio compared to those who had not received IPT (P = .0174). Plasma K/T ratio was elevated in women with active TB at time of diagnosis compared to those without TB (P &lt; .0001). Using a cutoff of 0.100, plasma K/T ratio gave a diagnostic sensitivity of 94% (95% confidence interval [CI]: 82–95), specificity of 90% (95% CI: 80–91), positive predictive value (PPV) 85% and negative predictive value (NPV) 98%. A receiver operating characteristic curve (ROC) gave an area under the curve of 0.95 (95% CI: .92–.97, P &lt; .0001).
In conclusion, plasma K/T ratio is a sensitive blood-based diagnostic test for active TB disease in pregnant women living with HIV. Plasma K/T ratio should be further evaluated as an initial TB diagnostic test to determine its impact on patient care.
Simultaneous spontaneous arterial dissections in a 38-year-old woman presenting during the covid-19 pandemic: a case report
Authors: Hewitson Lynsey , Wong Chih , Aziz Shahid , Dastidar Amardeep 
Published: March 2021

Abstract

Background
Spontaneous coronary artery dissection (SCAD) is an increasingly recognized and important cause of acute myocardial infarction, particularly in women under 50, often with minimal risk factors. Many patients have underlying arteriopathy, most commonly in the form of fibromuscular dysplasia.

Case summary
A 38-year-old woman presented to the hospital with chest pain and elevated high-sensitivity Troponin. Invasive coronary angiography demonstrated SCAD of the left anterior descending artery. The same day the patient developed a severe progressive headache and subsequent imaging revealed a left vertebral artery dissection. She was managed conservatively with optimal medical therapy and was successfully discharged from hospital on Day 7.

Discussion
To our knowledge, this is the first case report of simultaneous spontaneous coronary and vertebral artery dissections not related to pregnancy. It highlights not only the importance of recognizing and accurately diagnosing SCAD, but also of appreciating the possibility of underlying arteriopathy: this is paramount to ensuring appropriate investigations, follow-up and assessment of any unexplained symptoms in this patient group.
Percutaneous coronary intervention in a patient with heparin resistance due to essential thrombocythaemia: a case report
Authors: Okabe Toshitaka , Yakushiji Tadayuki , Isomura Naoei , Ochiai Masahiko 
Published: March 2021

Abstract

Background
Coronary artery disease is uncommon in patients with essential thrombocythaemia (ET); therefore, no treatment strategies have been established.

Case summary
A 68-year-old man visited our hospital with worsening effort angina complicated with ET. Coronary angiography (CAG) revealed moderate stenosis of the left main trunk and left anterior descending artery (LAD). We planned to perform percutaneous coronary intervention (PCI) only after the patient’s platelet count had fallen below 600 000/μL. Platelet factor 4 levels were markedly elevated (355.0 ng/mL; the normal range is &lt;20 ng/mL). We observed a de novo lesion in the proximal left circumflex artery and stenosis progression in the LAD at the time of the PCI, neither of which had been detected at the previous CAG. During the PCI procedure, argatroban was infused to maintain the activated clotting time (ACT) above 250 s. The PCI was performed successfully without any complications. Follow-up CAG showed no restenosis, and no bleeding complications were observed during the course.

Discussion
In patients with ET, it may be useful to measure platelet factor 4 before PCI and to monitor ACT during the procedure. When heparin resistance is suspected based on blood coagulation tests, infusion of direct thrombin inhibitor during PCI may be considered, with anticoagulation monitoring by ACT.
Updating and Validating the U.S. Veterans Affairs Frailty Index: Transitioning From ICD-9 to ICD-10
Authors: Cheng David , DuMontier Clark , Yildirim Cenk , Charest Brian , Hawley Chelsea E , Zhuo Min , Paik Julie M , Yaksic Enzo , Gaziano J Michael , Do Nhan , Brophy Mary , Cho Kelly , Kim Dae H , Driver Jane A , Fillmore Nathanael R , Orkaby Ariela R 
Published: March 2021

Abstract

Background
The Veterans Affairs Frailty Index (VA-FI) is an electronic frailty index developed to measure frailty using administrative claims and electronic health records data in Veterans. An update to ICD-10 coding is needed to enable contemporary measurement of frailty.

Method
International Classification of Diseases, ninth revision (ICD-9) codes from the original VA-FI were mapped to ICD-10 first using the Centers for Medicaid and Medicare Services (CMS) General Equivalence Mappings. The resulting ICD-10 codes were reviewed by 2 geriatricians. Using a national cohort of Veterans aged 65 years and older, the prevalence of deficits contributing to the VA-FI and associations between the VA-FI and mortality over years 2012–2018 were examined.

Results
The updated VA-FI-10 includes 6422 codes representing 31 health deficits. Annual cohorts defined on October 1 of each year included 2 266 191 to 2 428 115 Veterans, for which the mean age was 76 years, 97%–98% were male, 78%–79% were White, and the mean VA-FI was 0.20–0.22. The VA-FI-10 deficits showed stability before and after the transition to ICD-10 in 2015, and maintained strong associations with mortality. Patients classified as frail (VA-FI &gt; 0.2) consistently had a hazard of death more than 2 times higher than nonfrail patients (VA-FI ≤ 0.1). Distributions of frailty and associations with mortality varied with and without linkage to CMS data and with different assessment periods for capturing deficits.

Conclusions
The updated VA-FI-10 maintains content validity, stability, and predictive validity for mortality in a contemporary cohort of Veterans aged 65 years and older, and may be applied to ICD-9 and ICD-10 claims data to measure frailty.
Motor Imagery Deficits in High-Functioning Older Adults and Its Impact on Fear of Falling and Falls
Authors: Sakurai Ryota , Montero-Odasso Manuel , Suzuki Hiroyuki , Ogawa Susumu , Fujiwara Yoshinori 
Published: March 2021

AbstractBackgroundOlder adults at risk of falling or who have fear of falling (FoF) present a discrepancy between “imagined” and “performed” actions. Using the gait-related motor imagery paradigm, we investigated whether prediction accuracy in motor execution is associated with the onset of FoF and with prospective falls among older adults with FoF.MethodsA cohort of 184 community-dwelling older adults was tested for imaginary and executed Timed Up and Go (TUG) tests at a fast pace at baseline. They were first asked to imagine performing TUG and estimate the time taken to complete it (iTUG) and then to perform the actual trial (aTUG); the difference between the 2 times was calculated. Prospective falls were monitored between baseline and 2-year follow-up of FoF assessment.ResultsAt follow-up, 27 of 85 participants without FoF at baseline (31.8%) had developed FoF. Twenty-seven of 99 participants (27.2%) with FoF at baseline experienced falls. A significantly shorter iTUG duration, when compared with aTUG, was observed in those who developed FoF or experienced multiple prospective falls, indicating overestimation of their TUG performance. The adjusted logistic regression model showed that a greater ΔTUG (ie, tendency to overestimate) at baseline was associated with an increased risk of new-onset FoF among those without FoF at baseline and multiple prospective falls among those with FoF at baseline.ConclusionsDeficits in motor imagery (ie, overestimation of physical capabilities), reflecting impairment in motor planning, could provide an additional explanation of the high risk of FoF and recurrent falls among people with FoF.
Pan-selectin inhibitors as potential therapeutics for COVID-19 treatment: in silico screening study
Authors: Šmak Pavel , Chandrabose Selvaraj , Tvaroška Igor , Koča Jaroslav 
Published: March 2021

AbstractCoronavirus disease 2019 (COVID-19) has spread rapidly throughout the globe. The spectrum of disease is broad but among hospitalized patients with COVID-19, respiratory failure from acute respiratory distress syndrome is the leading cause of mortality. There is an urgent need for an effective treatment. The current focus has been developing novel therapeutics, including antivirals, protease inhibitors, vaccines and targeting the overactive cytokine response with anti-cytokine therapy. The overproduction of early response proinflammatory cytokines results in what has been described as a “cytokine storm” is leading eventually to death when the cells fail to terminate the inflammatory response. Accumulating evidence shows that inflammatory cytokines induce selectin ligands that play a crucial role in the pathogenesis of inflammatory diseases by mediating leukocyte migration from the blood into the tissue. Thus, the selectins and selectin ligands represent a promising therapeutic target for the treatment of COVID-19. In this paper, potential pan-selectin inhibitors were identified employing a virtual screening using a docking procedure. For this purpose, the Asinex and ZINC databases of ligands, including approved drugs, biogenic compounds and glycomimetics, altogether 923,602 compounds, were screened against the P-, L- and E-selectin. At first, the experimentally confirmed inhibitors were docked into all three selectins’ carbohydrate recognition domains to assess the suitability of the screening procedure. Finally, based on the evaluation of ligands binding, we propose 10 purchasable pan-selectin inhibitors to develop COVID-19 therapeutics.
Advancing foreign policy analysis by studying leaders from the global South
Authors: Brummer Klaus 
Published: March 2021

Abstract
Using the concept of ‘context sensitivity’ as organizing theme, this article explores different avenues of advancing foreign policy analysis (FPA) scholarship based on insights from the global South. Since foreign policy decision-makers in the global South operate in (at times very) different political environments than their western counterparts, the applicability of FPA approaches cannot be taken as a given, which is why their context sensitivity (i.e., the extent to which core concepts and indicators contained in those approaches travel to non-western settings) needs to be explored. This article suggests that our understanding of the motives and behaviours of individual decision-makers can be advanced in three distinct ways based on insights from the global South. First, several of the FPA constructs that focus on individual decision makers have seen hardly any applications to non-western cases, which is why the latter contributes to ascertaining the analytical scope of those constructs. Second, taking more fully into account the differences in decision-making environments within which leaders from the global South operate can advance leader-oriented FPA approaches by helping to specify certain theoretical assumptions proposed by them. Finally, the aspiration to analyse leaders from the global South can advance FPA in terms of method by, for instance, developing non-English language coding schemes for profiling leaders based on speech acts that are cognizant of the specificities of individual languages, while at the same time allowing for measurement equivalence across different languages.
Political leadership and gendered multilevel games in foreign policy
Authors: Aggestam Karin , True Jacqui 
Published: March 2021

Abstract
Gender intersects as a major fault-line in increasingly polarized, contemporary global politics. Many democratic states in the global North and South have adopted pro-gender norms in their foreign policies, while other states and populist regimes have resisted the promotion of gender equality and women's rights. This article analyses how political leaders harness gender dynamics to further their power, status and authority to act in foreign policy. While scholarship on foreign policy analysis has emphasized the role of individuals, political leaders and their followers, and of two-level games balancing domestic and international pressures, we advance a novel theoretical concept: ‘gendered multilevel games’. This new concept highlights the gendered dynamics of the problem of agency and structure in foreign policy, which are generated from the interactions between the domestic, international and transnational levels, and reach within and across states. To illustrate the utility of this concept, we analyse foreign policy leadership and the variation in gendered multilevel games in four vignettes: (1) hyper-masculinity and revisionist leadership; (2) normative leadership and gendered nation-branding; (3) compassionate leadership and gendered transnational symbolism; and (4) contested leadership on pro- and anti-gender norms in foreign policy. Importantly, these empirical illustrations show how adept political leaders navigate pro- and anti-gender norms to achieve core and often divergent foreign policy goals.
Automation, digitalization, and changes in occupational structures in the automobile industry in Germany, Japan, and the United States: a brief history from the early 1990s until 2018
Authors: Krzywdzinski Martin 
Published: March 2021

Abstract
A major concern in the current public discussion is rapidly accelerating automation and in particular the use of robots. Many experts and researchers see it as a driver of employment losses hitting in particular so called routine jobs. The present study challenges this perspective. It examines two central questions: First, what approaches to automation and digitalization have been pursued in the automotive industry in Germany, Japan, and the United States? Second, how have employment and its occupational composition in the automotive industry developed in the three countries? The first part of the study focuses on the evolution of automation and digitalization approaches in the automotive industry from the early 1990s until today. It combines a qualitative analysis of press articles and a quantitative evaluation of the development of the stock of industrial robots from 1993 to 2018 based on the statistics of the International Federation of Robotics. The second part of the study focuses on the change in employment structures using occupational statistics from the Bureau of Labor Statistics (US), the Federal Employment Agency (Germany), and the Statistics Bureau of Japan. The results of the study question the perception of an automation-related threat to employment and especially to production employment. At the same time, they highlight differences between automation and digitalization approaches in Germany, Japan, and the United States as well as different paths of change in employment structures.
Interactivity of biochemical and physical stimuli during epigenetic conditioning and cardiomyocytic differentiation of stem and progenitor cells derived from adult hearts
Authors: Zeng Wendy R , Doran Pauline M 
Published: March 2021

Abstract
Mixed populations of cardiosphere-derived stem and progenitor cells containing proliferative and cardiomyogenically committed cells were obtained from adult rat hearts. The cells were cultured in either static 2D monolayers or dynamic 3D scaffold systems with fluid flow. Cardiomyocyte lineage commitment in terms of GATA4 and Nkx2.5 expression was significantly enhanced in the dynamic 3D cultures compared with static 2D conditions. Treatment of the cells with 5-azacytidine (5-aza) produced different responses in the two culture systems, as activity of this chemical epigenetic conditioning agent depended on the cell attachment and hydrodynamic conditions provided during culture. Cell growth was unaffected by 5-aza in the static 2D cultures but was significantly reduced under dynamic 3D conditions relative to untreated controls. Myogenic differentiation measured as Mef2c expression was markedly upregulated by 5-aza in the dynamic 3D cultures but downregulated in the static 2D cultures. The ability of the physical environment to modulate the cellular cardiomyogenic response to 5-aza underscores the interactivity of biochemical and physical stimuli applied for cell differentiation. Accordingly, observations about the efficacy of 5-aza as a cardiomyocyte induction agent may not be applicable across different culture systems. Overall, use of dynamic 3D rather than static 2D culture was more beneficial for cardio-specific myogenesis than 5-aza treatment, which generated a more ambiguous differentiation response.