bluuebunny/crossref_metadata_2025 huggingface dataset:
The Affect of The Internet and Social Media: Mathematics Learning Environment Context
Authors: Hidayatullah Achmad , Suprapti Endang
Published: April 2020

Mathematics as one of the lessons in school has quite complex problems, it is often labelled as a difficult subject, poor in innovation and bored. Various methods has been used to make mathematics easier to learn. While on the other hand, the development of the communication industry revolution has changed community's thinking style, learning style, and lifestyle. More specifically, the development of social media, which has an impact on mathematics learning. Students who are classified as millennial, learn more about mathematics using audio visuals such as on YouTube or Instagram. The existence of social media has raised a new form of teacher relations with students. This article discussed and described about how social media has an impact on mathematics learning. The existence of internet social media made the task of the teacher lighter. However, learning mathematics in this era of social media has challenges, advantages, and disadvantages. In this literature study, it will also be explored how social media distorts the role of teachers as educators.
Integrating Islamic Education Based Value: Response to Global Challenges and Socio-Environment
Authors: Subakir Ahmad
Published: April 2020

Difficult problems from time to time are increasingly complex. Today's millennial generation faces various problems, ranging from the issue of moral decline, to the increasing number of liberal and even radical understandings, to the abuse of social media. All of this cannot be denied due to the inability of Islamic education to instill moral values in religious language, as well as the values of national character. At least that is the concentration of Islamic thinkers. That is why this article will discuss about the face of global challenges, it is necessary to seek value-based integrative Islamic education. This short article was written using a qualitative type library research approach. As a godly country, Indonesia places religious education, including Islamic education into the curriculum at every level of education. However, this shows the very strategic role of Islamic education, which should also be accompanied by moderate contextual understanding. The emergence of Amin Abdullah's concept of scientific integration is more or less capable of being an alternative in solving today's millennial problems. Coupled with the existence of value-based Islamic scholarly treasures, it has increasingly spurred efforts to deliver the nation's next generation to be able to compete in this information era. Of course the effort to integrate value-based Islamic education requires support and correction from various parties so that they are truly able to be solutions to global problems and challenges that are always dynamic.
Policy of Environmental Tax In Indonesia: A Review
Authors: Hernimawati Hernimawati , Mirad Abdul , Sudaryanto Sudaryanto
Published: April 2020

The purpose of this study is to analyze the policy of environmental tax in Indonesia. The method used in this study is descriptive qualitative, which aims to analyze the policy of environmental tax in Indonesia. The collected data were analyzed with interactive model of Miles and Huberman. The study results indicated the government of Indonesia’s policy of environmental taxes clearly states the objectives, subjects, objects and tax rates. This policy is included in local taxes and user charges. But the policy needs to be reviewed again so it won’t impress fiscal interests only. The discussion should be done comprehensively, especially concerning the problems surrounding the subject, tariff and budget earmarking it.
Policy of Ecotourism Development in Riau Province: Analysis and Strategies
Authors: Prihati Prihati , Nielwaty Elly , Zuhdi Sulaiman
Published: April 2020

The purpose of this study is to analyze the policy on ecotourism development in Riau Province. The method used in this research is descriptive qualitative, which aims to analyze the policy on ecotourism development in Riau Province. The collected data were analyzed with interactive model of Miles and Huberman. The study results indicated that the policy of ecotourism development in Riau Province is conducted by three parties, and the communities involved in the development of ecotourism are the Department of Tourism and Culture of Riau Province and the private sector. The strategies adopted to develop the ecotourism include technology strategy, strategy of invasion and operational strategy.
A Person-Centered Perspective on the Role of Peer Support and Extreme Peer Orientation in Youth with Type 1 Diabetes: A Longitudinal Study
Authors: Raymaekers Koen , Prikken Sofie , Oris Leen , Vanhalst Janne , Moons Philip , Goossens Eva , Weets Ilse , Luyckx Koen
Published: April 2020

Background

Despite clear evidence that peers are crucial for youth development, research on the role of peers for youth with Type 1 diabetes (T1D) is scarce.

Purpose

The present study identified trajectory classes of perceived peer functioning in youth with T1D, based on peer support and extreme peer orientation (EPO). Further, classes were compared with respect to their trajectories of depressive symptoms, diabetes-specific distress, treatment adherence, and HbA1c values.

Methods

Five hundred and fifty-nine youth (14–25 years) with T1D completed questionnaires at baseline, 1, 2, and 3 years later. Latent class growth analysis identified classes of perceived peer functioning. Multigroup latent growth curve modelling assessed whether these classes were characterized by different trajectories of general and diabetes-specific functioning.

Results

A socially normative class (48%) was characterized by trajectories of high support and low EPO over time. A socially reserved class (29%) was characterized by low support and EPO, and a socially oriented class (17%) by high support and EPO. Finally, a socially vulnerable class (6%) was characterized by low support and high EPO. The normative class functioned significantly better over time than the other classes. The vulnerable class functioned significantly worse compared to the reserved class, despite experiencing equally low levels of support.

Conclusions

The results underscore the need to take youths’ orientation toward the peer context into account alongside support when tapping into the role of peers, because individuals with low levels of support and EPO functioned substantially better than individuals with similar low levels of support but high levels of EPO.
There is no impending crisis: a look beyond the Sixth Circuit’s decision to permit Section 1782 discovery for use in international commercial arbitration
Authors: Tompkins Jonathan J
Published: April 2020

There are few topics in international arbitration that engender more intense sentiments amongst practitioners than discovery. While debate endures over the applicability, suitability and extent of discovery within this autonomous system of justice, it is impossible to escape the reality that national laws and courts will and do have a role—often a significant one—to play in international arbitration proceedings, most notably to assist in the arbitral process. One US federal law in particular, 28 USC § 1782, has become increasingly relevant in recent years, as more parties attempt to harness its potency in facilitating discovery of evidence in aid of foreign arbitration. The application of the statute to foreign or international arbitral tribunals, however, is a murky question, and not one on which all US federal courts agree.

Most recently, the US Court of Appeals for the Sixth Circuit broke with some of its sister circuits in finding that discovery under section 1782 is permissible for use in foreign or international commercial arbitrations. While many have denounced the decision as contrary to, or arguably likely to render less effective, principles or aspects of international arbitration deemed sacrosanct by arbitration enthusiasts, the effect of the Sixth Circuit’s decision on the broader practice of arbitration must not be overstated. Practitioners, tribunals, and the US federal district courts in particular already have ample means at their disposal to thwart section 1782’s potentially broad reach and effectiveness in creating inequities or turmoil in arbitration proceedings. Channeled effectively, these tools and proper considerations of discretion can ensure an appropriate balance between the need for critical evidence and the prevention of drawn-out, inequitable, and inefficient arbitral proceedings.
Sensorimotor Peak Alpha Frequency Is a Reliable Biomarker of Prolonged Pain Sensitivity
Authors: Furman Andrew J , Prokhorenko Mariya , Keaser Michael L , Zhang Jing , Chen Shuo , Mazaheri Ali , Seminowicz David A
Published: April 2020

Previous research has observed that the speed of alpha band oscillations (8–12 Hz range) recorded during resting electroencephalography is slowed in chronic pain patients. While this slowing may reflect pathological changes that occur during the chronification of pain, an alternative explanation is that healthy individuals with slower alpha oscillations are more sensitive to prolonged pain, and by extension, more susceptible to developing chronic pain. To test this hypothesis, we examined the relationship between the pain-free, resting alpha oscillation speed of healthy individuals and their sensitivity to two models of prolonged pain, Phasic Heat Pain and Capsaicin Heat Pain, at two visits separated by 8 weeks on average (n = 61 Visit 1, n = 46 Visit 2). We observed that the speed of an individual’s pain-free alpha oscillations was negatively correlated with sensitivity to both models and that this relationship was reliable across short (minutes) and long (weeks) timescales. Furthermore, the speed of pain-free alpha oscillations can successfully identify the most pain sensitive individuals, which we validated on data from a separate, independent study. These results suggest that alpha oscillation speed is a reliable biomarker of prolonged pain sensitivity with potential for prospectively identifying pain sensitivity in the clinic.
Towards standardization of echocardiography for the evaluation of left ventricular function in adult rodents: a position paper of the ESC Working Group on Myocardial Function
Authors: Zacchigna Serena , Paldino Alessia , Falcão-Pires Inês , Daskalopoulos Evangelos P , Dal Ferro Matteo , Vodret Simone , Lesizza Pierluigi , Cannatà Antonio , Miranda-Silva Daniela , Lourenço André P , Pinamonti Bruno , Sinagra Gianfranco , Weinberger Florian , Eschenhagen Thomas , Carrier Lucie , Kehat Izhak , Tocchetti Carlo G , Russo Michele , Ghigo Alessandra , Cimino James , Hirsch Emilio , Dawson Dana , Ciccarelli Michele , Oliveti Marco , Linke Wolfgang A , Cuijpers Ilona , Heymans Stephane , Hamdani Nazha , de Boer Martine , Duncker Dirk J , Kuster Diederik , van der Velden Jolanda , Beauloye Christophe , Bertrand Luc , Mayr Manuel , Giacca Mauro , Leuschner Florian , Backs Johannes , Thum Thomas
Published: April 2020

Echocardiography is a reliable and reproducible method to assess non-invasively cardiac function in clinical and experimental research. Significant progress in the development of echocardiographic equipment and transducers has led to the successful translation of this methodology from humans to rodents, allowing for the scoring of disease severity and progression, testing of new drugs, and monitoring cardiac function in genetically modified or pharmacologically treated animals. However, as yet, there is no standardization in the procedure to acquire echocardiographic measurements in small animals. This position paper focuses on the appropriate acquisition and analysis of echocardiographic parameters in adult mice and rats, and provides reference values, representative images, and videos for the accurate and reproducible quantification of left ventricular function in healthy and pathological conditions.
Abnormalities in sodium current and calcium homoeostasis as drivers of arrhythmogenesis in hypertrophic cardiomyopathy
Authors: Coppini Raffaele , Santini Lorenzo , Olivotto Iacopo , Ackerman Michael J , Cerbai Elisabetta
Published: April 2020

Hypertrophic cardiomyopathy (HCM) is a common inherited monogenic disease with a prevalence of 1/500 in the general population, representing an important cause of arrhythmic sudden cardiac death (SCD), heart failure, and atrial fibrillation in the young. HCM is a global condition, diagnosed in >50 countries and in all continents. HCM affects people of both sexes and various ethnic and racial origins, with similar clinical course and phenotypic expression. The most unpredictable and devastating consequence of HCM is represented by arrhythmic SCD, most commonly caused by sustained ventricular tachycardia or ventricular fibrillation. Indeed, HCM represents one of the main causes of arrhythmic SCD in the young, with a marked preference for children and adults <30 years. SCD is most prevalent in patients with paediatric onset of HCM but may occur at any age. However, risk is substantially lower after 60 years, suggesting that the potential for ventricular tachyarrhythmias is mitigated by ageing. SCD had been linked originally to sports and vigorous activity in HCM patients. However, it is increasingly clear that the majority of events occurs at rest or during routine daily occupations, suggesting that triggers are far from consistent. In general, the pathophysiology of SCD in HCM remains unresolved. While the pathologic and physiologic substrates abound and have been described in detail, specific factors precipitating ventricular tachyarrhythmias are still unknown. SCD is a rare phenomenon in HCM cohorts (<1%/year) and attempts to identify patients at risk, while generating clinically useful algorithms for primary prevention, remain very inaccurate on an individual basis. One of the reasons for our limited understanding of these phenomena is that limited translational research exists in the field, while most efforts have focused on clinical markers of risk derived from pathology, instrumental patient evaluation, and imaging. Specifically, few studies conducted in animal models and human samples have focused on targeting the cellular mechanisms of arrhythmogenesis in HCM, despite potential implications for therapeutic innovation and SCD prevention. These studies found that altered intracellular Ca2+ homoeostasis and increased late Na+ current, leading to an increased likelihood of early and delayed after-depolarizations, contribute to generate arrhythmic events in diseased cardiomyocytes. As an array of novel experimental opportunities have emerged to investigate these mechanisms, including novel ‘disease-in-the-dish’ cellular models with patient-specific induced pluripotent stem cell-derived cardiomyocytes, important gaps in knowledge remain. Accordingly, the aim of the present review is to provide a contemporary reappraisal of the cellular basis of SCD-predisposing arrhythmias in patients with HCM and discuss the implications for risk stratification and management.
Day-to-Day Contact and Help Among Neighbors Measured in the Natural Environment
Authors: Seifert Alexander
Published: April 2020

Background and Objectives

Empirical evidence suggests that the concept of “neighboring” (i.e., social contact and social support within a neighborhood) is related to between-person differences in well-being among older adults. However, little is known about the within-person differences in older adults’ everyday lives, which limits the ecological validity of prior findings. This study examined within-person associations between neighboring and the existence of positive valence, loneliness, and attachment to one’s neighborhood.

Research Design and Methods

The sample consisted of 4,620 observations of 20 days, drawn from 77 adults aged between 61 and 90 years. A mobile application on a smartphone was used for data collection.

Results

The results of the multilevel analysis suggest that daily contact with one’s neighbors was not significantly associated with daily positive valence, but it was positively related to daily feelings of not being alone and daily attachment to one’s neighborhood.

Discussion and Implications

The study makes noteworthy contributions to the field of gerontology by applying a micro-longitudinal research design to assess real-life within-person information.
The burden of household out-of-pocket health expenditures in Ethiopia: estimates from a nationally representative survey (2015–16)
Authors: Kiros Mizan , Dessie Ermias , Jbaily Abdulrahman , Tolla Mieraf Taddesse , Johansson Kjell Arne , Norheim Ole F , Memirie Solomon Tessema , Verguet Stéphane
Published: April 2020

In Ethiopia, little is known about the extent of out-of-pocket health expenditures and the associated financial hardships at national and regional levels. We estimated the incidence of both catastrophic and impoverishing health expenditures using data from the 2015/16 Ethiopian household consumption and expenditure and welfare monitoring surveys. We computed incidence of catastrophic health expenditures (CHE) at 10% and 25% thresholds of total household consumption and 40% threshold of household capacity to pay, and impoverishing health expenditures (IHE) using Ethiopia's national poverty line (ETB 7184 per adult per year). Around 2.1% (SE: 0.2, P < 0.001) of households would face CHE with a 10% threshold of total consumption, and 0.9% (SE: 0.1, P < 0.001) of households would encounter IHE, annually in Ethiopia. CHE rates were high in the regions of Afar (5.8%, SE: 1.0, P < 0.001) and Benshangul-Gumuz (4.0%, SE: 0.8, P < 0.001). Oromia (n = 902 000), Amhara (n = 275 000) and Southern Nations Nationalities and Peoples (SNNP) (n = 268 000) regions would have the largest numbers of affected households, due to large population size. The IHE rates would also show similar patterns: high rates in Afar (5.0%, SE: 0.96, P < 0.001), Oromia (1.1%, SE: 0.22, P < 0.001) and Benshangul-Gumuz (0.9%, SE: 0.4, P = 0.02); a large number of households would be impoverished in Oromia (n = 356 000) and Amhara (n = 202 000) regions. In summary, a large number of households is facing financial hardship in Ethiopia, particularly in Afar, Benshangul-Gumuz, Oromia, Amhara and SNNP regions and this number would likely increase with greater health services utilization. We recommend regional-level analyses on services coverage to be conducted as some of the estimated low CHE/IHE regional values might be due to low services coverage. Periodic analyses on the financial hardship status of households could also be monitored to infer progress towards universal health coverage.
Variants in CAPZA2, a member of an F-actin capping complex, cause intellectual disability and developmental delay
Authors: Huang Yan , Mao Xiao , van Jaarsveld Richard H , Shu Li , Terhal Paulien A , Jia Zhengjun , Xi Hui , Peng Ying , Yan Huiming , Yuan Shan , Li Qibin , Wang Hua , Bellen Hugo J
Published: April 2020

The actin cytoskeleton is regulated by many proteins including capping proteins that stabilize actin filaments (F-actin) by inhibiting actin polymerization and depolymerization. Here, we report two pediatric probands who carry damaging heterozygous de novo mutations in CAPZA2 (HGNC: 1490) and exhibit neurological symptoms with shared phenotypes including global motor development delay, speech delay, intellectual disability, hypotonia and a history of seizures. CAPZA2 encodes a subunit of an F-actin-capping protein complex (CapZ). CapZ is an obligate heterodimer consisting of α and β heterodimer conserved from yeast to human. Vertebrate genomes contain three α subunits encoded by three different genes and CAPZA2 encodes the α2 subunit. The single orthologue of CAPZA genes in Drosophila is cpa. Loss of cpa leads to lethality in early development and expression of the human reference; CAPZA2 rescues this lethality. However, the two CAPZA2 variants identified in the probands rescue this lethality at lower efficiency than the reference. Moreover, expression of the CAPZA2 variants affects bristle morphogenesis, a process that requires extensive actin polymerization and bundling during development. Taken together, our findings suggest that variants in CAPZA2 lead to a non-syndromic neurodevelopmental disorder in children.
Maternal body mass index in early pregnancy and severe asphyxia-related complications in preterm infants
Authors: Mitha Ayoub , Chen Ruoqing , Johansson Stefan , Razaz Neda , Cnattingius Sven
Published: April 2020

Background

Little is known about the associations between maternal body mass index (BMI) and asphyxia-related morbidity in preterm infants (<37 weeks). We aimed to investigate associations between maternal BMI in early pregnancy and severe asphyxia-related neonatal complications in preterm infants (<37 weeks) and to examine whether possible associations were mediated by overweight- or obesity-related complications.

Methods

In this Swedish population-based cohort of 62 499 singleton non-malformed preterm infants born from 1997 to 2011, risks of low Apgar scores (0–3) at 5 and 10 minutes, neonatal seizures and intraventricular haemorrhage (IVH) were estimated through two analytical approaches. In the conventional approach, the denominator for risk was all live births at a given gestational age. In the fetuses-at-risk (FAR) approach, the denominator for risk was ongoing pregnancies at a given gestational age.

Results

Using the conventional approach, adjusted risk ratios per 10-unit BMI increase were 1.32 [95% confidence interval (CI) 1.13–1.54] and 1.37 (95% CI 1.12–1.67) for low Apgar scores at 5 and 10 minutes, respectively; 1.28 (95% CI 1.00–1.65) for neonatal seizures; and 1.18 (95% CI 1.01–1.37) for IVH. Using the FAR approach, corresponding risks were higher. These associations varied by gestational age (<32 and 32–36 weeks). Associations between maternal BMI and asphyxia-related outcomes were partly mediated through lower gestational age.

Conclusions

Increasing maternal BMI in early pregnancy is associated with increased risks of severe asphyxia-related complications in preterm infants. Our findings add to the evidence to support interventions to reduce obesity in woman of reproductive age.
Simple Current Extensions of Tensor Products of Vertex Operator Algebras
Authors: Yamada Hiromichi , Yamauchi Hiroshi
Published: April 2020

We study simple current extensions of tensor products of two vertex operator algebras satisfying certain conditions. We establish the relationship between the fusion rule for the simple current extension and the fusion rule for a tensor factor. In a special case, we construct a chain of simple current extensions. We discuss certain irreducible twisted modules for the simple current extension as well.
Odour in the court: CJEU finds that General Court applied the wrong method for comparing trade marks
Authors: Strath Janet
Published: April 2020

Case C-328/18 P EUIPO v Equivalenza Manufactory SL, EU:C:2020:156, 4 March 2020
Che-1/AATF binds to RNA polymerase I machinery and sustains ribosomal RNA gene transcription
Authors: Sorino Cristina , Catena Valeria , Bruno Tiziana , De Nicola Francesca , Scalera Stefano , Bossi Gianluca , Fabretti Francesca , Mano Miguel , De Smaele Enrico , Fanciulli Maurizio , Iezzi Simona
Published: April 2020

Originally identified as an RNA polymerase II interactor, Che-1/AATF (Che-1) has now been recognized as a multifunctional protein involved in cell-cycle regulation and cancer progression, as well as apoptosis inhibition and response to stress. This protein displays a peculiar nucleolar localization and it has recently been implicated in pre-rRNA processing and ribosome biogenesis. Here, we report the identification of a novel function of Che-1 in the regulation of ribosomal RNA (rRNA) synthesis, in both cancer and normal cells. We demonstrate that Che-1 interacts with RNA polymerase I and nucleolar upstream binding factor (UBF) and promotes RNA polymerase I-dependent transcription. Furthermore, this protein binds to the rRNA gene (rDNA) promoter and modulates its epigenetic state by contrasting the recruitment of HDAC1. Che-1 downregulation affects RNA polymerase I and UBF recruitment on rDNA and leads to reducing rDNA promoter activity and 47S pre-rRNA production. Interestingly, Che-1 depletion induces abnormal nucleolar morphology associated with re-distribution of nucleolar proteins. Finally, we show that upon DNA damage Che-1 re-localizes from rDNA to TP53 gene promoter to induce cell-cycle arrest. This previously uncharacterized function of Che-1 confirms the important role of this protein in the regulation of ribosome biogenesis, cellular proliferation and response to stress.
Dynamic landscape and evolution of m6A methylation in human
Authors: Zhang Hui , Shi Xinrui , Huang Tao , Zhao Xueni , Chen Wanying , Gu Nannan , Zhang Rui
Published: April 2020

m6A is a prevalent internal modification in mRNAs and has been linked to the diverse effects on mRNA fate. To explore the landscape and evolution of human m6A, we generated 27 m6A methylomes across major adult tissues. These data reveal dynamic m6A methylation across tissue types, uncover both broadly or tissue-specifically methylated sites, and identify an unexpected enrichment of m6A methylation at non-canonical cleavage sites. A comparison of fetal and adult m6A methylomes reveals that m6A preferentially occupies CDS regions in fetal tissues. Moreover, the m6A sub-motifs vary between fetal and adult tissues or across tissue types. From the evolutionary perspective, we uncover that the selection pressure on m6A sites varies and depends on their genic locations. Unexpectedly, we found that ∼40% of the 3′UTR m6A sites are under negative selection, which is higher than the evolutionary constraint on miRNA binding sites, and much higher than that on A-to-I RNA modification. Moreover, the recently gained m6A sites in human populations are clearly under positive selection and associated with traits or diseases. Our work provides a resource of human m6A profile for future studies of m6A functions, and suggests a role of m6A modification in human evolutionary adaptation and disease susceptibility.
Post Hoc Assessment of Time to Clinical Response Among Adults Hospitalized with Community-Acquired Bacterial Pneumonia Who Received Either Lefamulin or Moxifloxacin in 2 Phase III Randomized, Double-Blind, Double-Dummy Clinical Trials
Authors: Lodise Thomas , Colman Sam , Stein Daniel S , Fitts David , Goldberg Lisa , Alexander Elizabeth , Scoble Patrick J , Schranz Jennifer
Published: April 2020

Time to clinical response, a proxy for hospital “discharge readiness,” was compared between CABP inpatients who received lefamulin or moxifloxacin in the Lefamulin Evaluation Against Pneumonia (LEAP) trials. The analysis included 926 inpatients. A short and comparable median time to clinical response (4 days) was observed in both treatment groups.
Near Total Versus Gross Total Resection of Large Vestibular Schwannomas: Facial Nerve Outcome
Authors: Schneider Julia R , Chiluwal Amrit K , Arapi Orseola , Kwan Kevin , Dehdashti Amir R
Published: April 2020

BACKGROUND

Large vestibular schwannomas (VSs) with brainstem compression are generally reserved for surgical resection. Surgical aggressiveness must be balanced with morbidity from cranial nerve injury. The purpose of the present investigation is to evaluate the clinical presentation, management modality, and patient outcomes following near total resection (NTR) vs gross total resection (GTR) of large VSs.

OBJECTIVE

To assess facial nerve outcome differences between GTR and NTR patient cohorts.

METHODS

Between January 2010 and March 2018, a retrospective chart review was completed to capture patients continuously who had VSs with Hannover grades T4a and T4b. NTR was decided upon intraoperatively. Primary data points were collected, including preoperative symptoms, tumor size, extent of resection, and postoperative neurological outcome.

RESULTS

A total of 37 patients underwent surgery for treatment of large and giant (grade 4a and 4b) VSs. Facial nerve integrity was preserved in 36 patients (97%) at the completion of surgery. A total of 27 patients underwent complete resection, and 10 had near total (>95%) resection. Among patients with GTR, 78% (21/27) had House-Brackmann (HB) grade I-II facial nerve function at follow-up, whereas 100% (10/10) of the group with NTR had HB grade I-II facial nerve function. Risk of meningitis, cerebrospinal fluid leak, and sinus thromboses were not statistically different between the 2 groups. There was no stroke, brainstem injury, or death. The mean follow-up was 36 mo.

CONCLUSION

NTR seems to offer a benefit in terms of facial nerve functional outcome compared to GTR in surgical management of large VSs without significant risk of recurrence.
The risk and trend of pulmonary embolism and deep vein thrombosis in rheumatoid arthritis: a general population-based study
Authors: Li Lingyi , Lu Na , Avina-Galindo Ana Michelle , Zheng Yufei , Lacaille Diane , Esdaile John M , Choi Hyon K , Aviña-Zubieta J Antonio
Published: April 2020

Objectives

To estimate the overall risk of venous thromboembolism (VTE), pulmonary embolism (PE) and deep vein thrombosis (DVT) among patients newly diagnosed with RA compared with the general population without RA; and to estimate the risk trends of VTE, PE and DVT after RA diagnosis up to 5 years compared with the general population.

Methods

Using previously validated RA case definition, we conducted a matched cohort study using the population-based administrative health database from the province of British Columbia, Canada. We calculated incidence rates (IRs) and fully adjusted hazard ratios (HRs) for the risk of VTE, DVT and PE after RA index date.

Results

Among 39 142 incident RA patients (66% female, mean age 60), 1432, 543 and 1068 developed VTE, PE and DVT, respectively. IRs for the RA cohort were 3.79, 1.43 and 2.82 per 1000 person-years vs 2.70, 1.03 and 1.94 per 1000 person-years for the non-RA cohort. After adjusting for VTE risk factors, the HRs (95% CI) were 1.28 (1.20, 1.36), 1.25 (1.13, 1.39) and 1.30 (1.21, 1.40) for VTE, PE and DVT, respectively. The fully adjusted HRs for VTE during the first five years after RA diagnosis were 1.60, 1.47, 1.40, 1.30 and 1.28, respectively. A similar trend was shown in PE.

Conclusion

This population-based study demonstrates that RA patients have an increased risk of VTE, PE and DVT after diagnosis compared with the general population. This risk is independent of traditional VTE risk factors and is highest during the first year after RA diagnosis, then progressively declined.
Effector membrane translocation biosensors reveal G protein and βarrestin coupling profiles of 100 therapeutically relevant GPCRs
Authors: Avet Charlotte , Mancini Arturo , Breton Billy , Gouill Christian Le , Hauser Alexander S. , Normand Claire , Kobayashi Hiroyuki , Gross Florence , Hogue Mireille , Lukasheva Viktoriya , St-Onge Stéphane , Carrier Marilyn , Héroux Madeleine , Morissette Sandra , Fauman Eric , Fortin Jean-Philippe , Schann Stephan , Leroy Xavier , Gloriam David E. , Bouvier Michel
Published: April 2020

The recognition that individual GPCRs can activate multiple signaling pathways has raised the possibility of developing drugs selectively targeting therapeutically relevant ones. This requires tools to determine which G proteins and βarrestins are activated by a given receptor. Here, we present a set of BRET sensors monitoring the activation of the 12 G protein subtypes based on the translocation of their effectors to the plasma membrane (EMTA). Unlike most of the existing detection systems, EMTA does not require modification of receptors or G proteins (except for Gs). EMTA was found to be suitable for the detection of constitutive activity, inverse agonism, biased signaling and polypharmacology. Profiling of 100 therapeutically relevant human GPCRs resulted in 1,500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity. Overall, this work describes unique resources for studying the complexities underlying GPCR signaling and pharmacology.
Colchicine inhibits neutrophil extracellular trap formation in acute coronary syndrome patients after percutaneous coronary intervention
Authors: Vaidya Kaivan , Tucker Bradley , Kurup Rahul , Khandkar Chinmay , Pandzic Elvis , Barraclough Jennifer , Machet Joshua , Misra Ashish , Kavurma Mary , Martinez Gonzalo , Rye Kerry-Anne , Cochran Blake J , Patel Sanjay
Published: April 2020

Objective

Release of neutrophil extracellular traps (NETs) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is associated with peri-procedural myocardial infarction, as a result of microvascular obstruction via pro-inflammatory and pro-thrombotic pathways. Colchicine is a potent, well-established anti-inflammatory agent with growing evidence to support use in patients with coronary disease. However, its effects on post-PCI NET formation in ACS has not been explored.

Approach and Results

60 patients (40 ACS; 20 stable angina pectoris [SAP]) were prospectively recruited and allocated to colchicine or no treatment. Within 24 h of treatment, serial coronary sinus blood samples were collected during PCI. Isolated neutrophils from 10 ACS patients post-PCI and 4 healthy controls were treated in vitro with colchicine (25 nM) and stimulated with either ionomycin (5 μM) or phorbol 12-myristate 13-acetate (PMA, 50 nM). Extracellular DNA was quantified using Sytox Green and fixed cells were stained with Hoechst and anti-alpha tubulin. Baseline characteristics were similar across both treatment and control arms. ACS patients had higher NET release versus SAP patients (p<0.001), which was reduced with colchicine treatment (AUC: 0.58 vs. 4.29; p<0.001). In vitro, colchicine suppressed spontaneous (p=0.004), PMA-induced (p=0.03) and ionomycin-induced (p=0.02) NET formation in neutrophils isolated from ACS patients post-PCI, but not healthy controls. Tubulin organisation was impaired in neutrophils from patients with ACS but was restored by colchicine treatment.

Conclusions

Colchicine suppresses NET formation in ACS patients post-PCI by restoring cytoskeletal dynamics. These findings warrant further investigation in randomised trials powered for clinical endpoints.

Graphical Abstract
Epidemiological characteristics of COVID-19 in medical staff members of neurosurgery departments in Hubei province: A multicentre descriptive study
Authors: Wang Qiangping , Huang Xing , Bai Yansen , Wang Xuan , Wang Haijun , Hu Xuebin , Wang Feng , Wang Xianke , Chen Jincao , Chen Qianxue , Jiang Xiaobing , Zhao Hongyang
Published: April 2020

Background

The novel coronavirus (SARS-CoV-2) has infected a large number of healthcare workers in Hubei province, China. In addition to infectious and respiratory disease physicians, many doctors in other medical fields have been infected.

Methods

We prospectively collected epidemiological data on medical staff members who are working in neurosurgery departments in 107 hospitals in Hubei province through self-reported questionnaires or telephone interviews. Data of medical staff members with laboratory-confirmed coronavirus disease 2019 (COVID-19) were analysed. The final follow-up date was 1 March 2020.

Findings

A total of 5,442 neurosurgery department medical staff members were surveyed. One hundred and twenty cases, involving 54 doctors and 66 nurses, were found to have been infected with SARS-CoV-2. The overall incidence was 2.2%. These cases were concentrated in 26 centres, 16 of which had admitted a total of 59 patients with COVID-19 complicated by craniocerebral disease. Medical staff members in centres receiving COVID-19 patients had a higher risk of contracting infection than those in centres not receiving COVID-19 patients (relative risk: 19.6; 95% confidence interval: 12.6–30.6). Contact with either COVID-19 patients (62.5%, 75/120) or infected colleagues (30.8%, 37/120) was the most common mode of transmission. About 78.3% (94/120) of the infected cases wore surgical masks, whereas 20.8% (25/120) failed to use protection when exposed to the source of infection. Severe infections were observed in 11.7% (14/120) of the cases, with one death (0.8%, 1/120). All the infected medical staff members had been discharged from the hospital. A total of 1,287 medical staff members were dispatched to participate in the frontline response to COVID-19 under level 2 protection of whom one was infected. Medical staff members who took inadequate protection had a higher risk of contracting infection than those using level 2 protection (relative risk: 36.9; 95% confidence interval: 5.2–263.6).

Conclusions

Neurosurgical staff members in Hubei province were seriously affected by COVID-19. Level 2 protection and strengthening of protective measures are likely to be effective in preventing medical workers from being infected.
Understanding the Collective Responses of Populations to the COVID-19 Pandemic in Mainland China
Authors: Xiong Haoyi , Liu Ji , Huang Jizhou , Huang Siyu , An Haozhe , Kang Qi , Li Ying , Dou Dejing , Wang Haifeng
Published: April 2020

Timely information acquisition and stay-at-home measures have been considered as two effective steps that every person could take to help contain the coronavirus (COVID-19) pandemic. From the perspectives of information and mobility, this work aims at evaluating to what degree the massive population has responded to the emergencies of the COVID-19 pandemic in China. Using the real-time and historical data collected from the Baidu Maps and Baidu search engines, we confirm the strong correlation between the local pandemic situation in every major Chinese city and the population inflows from Wuhan between 1 January and 23 January 2020. We further evidence that, in cities under more critical situations, people are likely to engage COVID-19-related searches more frequently, while they are not likely to escape from the cities. Finally, the correlation analysis using search and mobility data shows that well-informed individuals are likely to travel less, even while the overall travel demands are low compared to the historical records. Partial correlation analysis has been conducted to test the significance of these observations with respect to other controlling factors.
Estimating the burden of SARS-CoV-2 in France
Authors: Salje Henrik , Kiem Cécile Tran , Lefrancq Noémie , Courtejoie Noémie , Bosetti Paolo , Paireau Juliette , Andronico Alessio , Hozé Nathanaël , Richet Jehanne , Dubost Claire-Lise , Strat Yann Le , Lessler Justin , Bruhl Daniel Levy , Fontanet Arnaud , Opatowski Lulla , Boelle Pierre-Yves , Cauchemez Simon
Published: April 2020

France has been heavily affected by the SARS-CoV-2 epidemic and went into lockdown on the 17th March 2020. Using models applied to hospital and death data, we estimate the impact of the lockdown and current population immunity. We find 2.6% of infected individuals are hospitalized and 0.53% die, ranging from 0.001% in those <20y to 8.3% in those >80y. Across all ages, men are more likely to be hospitalized, enter intensive care, and die than women. The lockdown reduced the reproductive number from 3.3 to 0.5 (84% reduction). By 11 May, when interventions are scheduled to be eased, we project 3.7 million (range: 2.3-6.7) people, 5.7% of the population, will have been infected. Population immunity appears insufficient to avoid a second wave if all control measures are released at the end of the lockdown.
Prediction of the Peak, Effect of Intervention and Total Infected by the Coronavirus Disease in India
Authors: Shah Parth Vipul
Published: April 2020

We study the effect of the coronavirus disease 2019 (COVID-19) in India using the SEIR compartmental model. After it’s outbreak in Wuhan, China, it has been imported to India which is a densely populated country. India is fighting against this disease by ensuring nationwide social distancing. We estimate the infection rate to be 0.258 using a least square method with Poisson noise and estimate the reproduction number to be 2.58. We approximate the peak of the epidemic to be August 11, 2020. We estimate that a 25% drop in infection rate will delay the peak by 38 days for a 1 month intervention period. We estimate that the total individuals infected in India will be approximately 9% of the total population.
Monitoring COVID-19 progression: Look at Us Today, See Yourself Tomorrow
Authors: Noh Jungsik
Published: April 2020

The coronavirus disease 2019 (COVID-19) pandemic is causing public health emergency and economic crisis all over the globe. Being widely spread, the virus can make any place in the world a new epicenter of the possible second wave of outbreaks. To control the pandemic progression, monitoring of the virus spreading is imperative. This paper proposes a simple and robust approach to monitor the COVID-19 pandemic progression in many countries or regions. This data science pipeline can provide actionable insights via straightforward COVID-19 data visualization for many regions at a glance, which informs of relative time delay of the pandemic progression, projected numbers of confirmed cases in the near future, and the sizes of infections.
Indexing Cerebrovascular Health Using Transcranial Doppler Ultrasound
Authors: Afkhami R. Ghorbani , Wong R. , Ramadan S. , Walker F. R. , Johnson S. J.
Published: April 2020

Transcranial Doppler (TCD) blood flow velocity has been extensively used in biomedical research as it provides a cost-effective and relatively simple approach to assess changes in cerebral blood flow dynamics and track cerebrovascular health status. In this paper, we introduce a new TCD based timing index, TItcd, as an indicator of vascular stiffening and vascular health. We investigate the correlations of the new index and the existing indices, namely the pulsatility index (PItcd) and the augmentation index (AITCD), with age, cardiorespiratory fitness (CRF) and magnetic resonance imaging (MRI) blood flow pulsatility index (PImri). Notably, the new TItcd index showed stronger correlations with CRF (r = −0.79) and PImri (r = 0.53) compared to AItcd (r = −0.65 with CRF and no significant correlation with PImri) and PITCD (no significant correlations with CRF or PImri) and similar correlations with age as AItcd. The clearer relationship of the proposed timing index with vascular aging factors represented by cerebrovascular resistance (CVR) suggests its utility as an early indicator of vascular stiffening.
Effect of storage conditions on peripheral leukocytes transcriptome
Authors: Xing Yanru , Yang Xi , Chen Haixiao , Zhu Sujun , Xu Jinjin , Chen Yuan , Zeng Juan , Chen Fang , Johnson Mark Richard , Jiang Hui , Wang Wen-Jing
Published: April 2020

Introduction

Peripheral blood leukocytes are essential components of the innate and adaptive immune responses. Their transcriptome reflects an individual’s physiological and pathological state, consequently bulk and single-cell RNA sequencing have been used to assess health and disease. As RNA is dynamic and could be affected byex vivoconditions before RNA stabilization, we have assessed the influence of temporary storage on the transcriptome.

Methods

We collected peripheral blood from six healthy donors and processed it immediately or stored it either at 4□ or room temperature (RT, 18–22□) for 2h, 6h and 24h. Total cellular RNA was extracted from leukocytes after red blood cells lysis and the transcriptome analyzed using RNA sequencing.

Results

We identified 152 up-regulated and 12 down-regulated coding genes in samples stored at 4□ for 24h with most of the up-regulated genes related to nucleosome assembly. More coding genes changed expression at RT, with 1218 increased and 1480 decreased. The increased genes were particularly related to mRNA processing and apoptosis, while the decreased genes were associated with neutrophil activation and cytokine production, implying a reduced proportion of neutrophils, which was confirmed by leukocyte subsets analysis. Most house-keeping genes changed expression during storage, but genes such as TUBB and C1orf43 were relatively stable and could serve as reference genes.

Conclusion

Temporary storage conditions profoundly affect leukocyte gene expression profiles and change leukocyte subset proportions. Blood samples stored at 4□ for 6h largely maintain their original transcriptome.
Mythical and Observable Trends in Human Sex Ratio at Birth
Authors: Long Yanan , Chen Qi , Larsson Henrik , Rzhetsky Andrey
Published: April 2020

The human sex ratio at birth (SRB) is defined as the ratio between the number of newborn boys to the total number of newborns per time unit. It is, typically, slightly greater than(more boys than girls) and fluctuates over time. In this study, we sought to “myth-check” previously reported associations (and test new hypotheses) using variants of mixed-effect regression analyses and time-series models on two very large electronic health record datasets, representing the populations in the United States and Sweden, respectively. Our results revealed that neither dataset supported models in which the SRB changed seasonally or in response to variations in ambient temperature, and that an increased level of a diverse array of pollutants were associated with lower SRBs. Moreover, we found that increased levels of industrial and agricultural activity, which served as proxies for water pollution, were also associated with lower SRBs.
SARS-CoV-2 serological analysis of COVID-19 hospitalized patients, pauci-symptomatic individuals and blood donors
Authors: Grzelak Ludivine , Temmam Sarah , Planchais Cyril , Demeret Caroline , Huon Christèle , Guivel-Benhassine Florence , Staropoli Isabelle , Chazal Maxime , Dufloo Jeremy , Planas Delphine , Buchrieser Julian , Rajah Maaran Michael , Robinot Remy , Porrot Françoise , Albert Mélanie , Chen Kuang-Yu , Crescenzo Bernadette , Donati Flora , Anna François , Souque Philippe , Gransagne Marion , Bellalou Jacques , Nowakowski Mireille , Backovic Marija , Bouadma Lila , Fevre Lucie Le , Hingrat Quentin Le , Descamps Diane , Pourbaix Annabelle , Yazdanpanah Yazdan , Tondeur Laura , Besombes Camille , Ungeheuer Marie-Noëlle , Mellon Guillaume , Morel Pascal , Rolland Simon , Rey Felix , Behillil Sylvie , Enouf Vincent , Lemaitre Audrey , Créach Marie-Aude , Petres Stephane , Escriou Nicolas , Charneau Pierre , Fontanet Arnaud , Hoen Bruno , Bruel Timothée , Eloit Marc , Mouquet Hugo , Schwartz Olivier , van der Werf Sylvie
Published: April 2020

It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their antibody response profile. Here, we performed a pilot study to assess the levels of anti-SARS-CoV-2 antibodies in samples taken from 491 pre-epidemic individuals, 51 patients from Hôpital Bichat (Paris), 209 pauci-symptomatic individuals in the French Oise region and 200 contemporary Oise blood donors. Two in-house ELISA assays, that recognize the full-length nucleoprotein (N) or trimeric Spike (S) ectodomain were implemented. We also developed two novel assays: the S-Flow assay, which is based on the recognition of S at the cell surface by flow-cytometry, and the LIPS assay that recognizes diverse antigens (including S1 or N C-terminal domain) by immunoprecipitation. Overall, the results obtained with the four assays were similar, with differences in sensitivity that can be attributed to the technique and the antigen in use. High antibody titers were associated with neutralisation activity, assessed using infectious SARS-CoV-2 or lentiviral-S pseudotypes. In hospitalized patients, seroconversion and neutralisation occurred on 5-14 days post symptom onset, confirming previous studies. Seropositivity was detected in 29% of pauci-symptomatic individuals within 15 days post-symptoms and 3 % of blood of healthy donors collected in the area of a cluster of COVID cases. Altogether, our assays allow for a broad evaluation of SARS-CoV2 seroprevalence and antibody profiling in different population subsets.