bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic and Metabolic Determinants of Plasma Levels of ANGPTL8
Authors: Oldoni Federico , Bass Kevin , Kozlitina Julia , Hudson Hannah , Shihanian Lisa M , Gusarova Viktoria , Cohen Jonathan C , Hobbs Helen H
Published: February 2021

Context

ANGPTL8 (A8) plays a key role in determining the tissue fate of circulating triglycerides (TGs). Plasma A8 levels are associated with several parameters of glucose and TG metabolism, but the causality of these relationships and the contribution of genetic variants to differences in A8 levels have not been explored.

Objective

To characterize the frequency distribution of plasma A8 levels in a diverse population using a newly-developed enzyme-linked immunosorbent assay (ELISA) and to identify genetic factors contributing to differences in plasma A8 levels.

Methods

We studied a population-based sample of Dallas County, comprising individuals in the Dallas Heart Study (DHS-1, n = 3538; DHS-2, n = 3283), including 2131 individuals with repeated measurements 7 to 9 years apart (age 18-85 years; >55% female; 52% Black; 29% White; 17% Hispanic; and 2% other). The main outcome measures were associations of A8 levels with body mass index (BMI), plasma levels of glucose, insulin, lipids, and hepatic TGs, as well as DNA variants identified by exome-wide sequencing.

Results

A8 levels varied over a 150-fold range (2.1-318 ng/mL; median, 13.3 ng/mL) and differed between racial/ethnic groups (Blacks > Hispanics > Whites). A8 levels correlated with BMI, fasting glucose, insulin, and TG levels. A variant in A8, R59W, accounted for 17% of the interindividual variation in A8 levels but was not associated with the metabolic parameters correlated with plasma A8 concentrations.

Conclusions

A8 levels were strongly associated with indices of glucose and TG metabolism, but the lack of association of genetic variants at the A8 locus that impact A8 levels with these parameters indicates that differences in A8 levels are not causally related to the associated metabolic phenotypes.
A Deep Q-Network for the Beer Game: Deep Reinforcement Learning for Inventory Optimization
Authors: Oroojlooyjadid Afshin , Nazari MohammadReza , Snyder Lawrence V. , Takáč Martin
Published: February 2021

Problem definition: The beer game is widely used in supply chain management classes to demonstrate the bullwhip effect and the importance of supply chain coordination. The game is a decentralized, multiagent, cooperative problem that can be modeled as a serial supply chain network in which agents choose order quantities while cooperatively attempting to minimize the network’s total cost, although each agent only observes local information. Academic/practical relevance: Under some conditions, a base-stock replenishment policy is optimal. However, in a decentralized supply chain in which some agents act irrationally, there is no known optimal policy for an agent wishing to act optimally. Methodology: We propose a deep reinforcement learning (RL) algorithm to play the beer game. Our algorithm makes no assumptions about costs or other settings. As with any deep RL algorithm, training is computationally intensive, but once trained, the algorithm executes in real time. We propose a transfer-learning approach so that training performed for one agent can be adapted quickly for other agents and settings. Results: When playing with teammates who follow a base-stock policy, our algorithm obtains near-optimal order quantities. More important, it performs significantly better than a base-stock policy when other agents use a more realistic model of human ordering behavior. We observe similar results using a real-world data set. Sensitivity analysis shows that a trained model is robust to changes in the cost coefficients. Finally, applying transfer learning reduces the training time by one order of magnitude. Managerial implications: This paper shows how artificial intelligence can be applied to inventory optimization. Our approach can be extended to other supply chain optimization problems, especially those in which supply chain partners act in irrational or unpredictable ways. Our RL agent has been integrated into a new online beer game, which has been played more than 17,000 times by more than 4,000 people.
Procurement with Cost and Noncost Attributes: Cost-Sharing Mechanisms
Authors: Gupta Shivam , Wang Shouqiang , Dawande Milind , Janakiraman Ganesh
Published: February 2021

The Benefits of a Simple Procurement Mechanism
Religious component of Soviet ideology as a factor influencing society
Authors:   State Institution Luhansk Taras Shevchenko National University, Bublik Olga
Published: February 2021

The article comprehensively considers the religious component inherent in the development of the Soviet ideological model, the implementation of which began in the 20s of the twentieth century. The aim of the article is a detailed consideration of the religious component of Soviet ideology as a factor in strengthening the Bolshevik influence on the masses, especially during the formation of the Soviet state – 20's – early 30's. According to the author, establishing their own regime, the Bolsheviks tried to establish it as an alternative to the ruling before their coming to power in the USSR Christian Orthodox Church. This was the reason for the way of presenting to society the canons of Soviet ideology, which was based on the involvement of old methods of spreading the Christian religion. As a result of the study, the author concludes that Bolshevism is not just and not so much with the ideological and political movement as with religion. There is a clear substitution in Soviet ideology: just as the Church of Christ was founded on faith in Jesus Christ, so the Bolshevik Party-Church and the new people created had to be based on Lenin, even on his „immortal” body. The author notes that it is no coincidence that the tribunes of the highest ranks of the party and government were created on the mausoleum, above Lenin's body – a direct parallel to the Throne of the Orthodox Church, near which only the clergy can be chosen and which necessarily contains the relics of the saint. The main postulates of Bolshevik atheism were: belief in a bright future „kingdom of God”, belief in the evolutionary origin of man; worship of founders, teachers; the presence of a universal ideology; the idea of ​​world revolution (missionary activity); irreconcilable hostility to other ideologies; the presence of its „clergy” - the party apparatus and the „Inquisition” – the punitive authorities.
The reflection of the formation of the Hellenistic international order in the work of Plutarch „Comparative biographies”
Authors:   State Institution Luhansk Taras Shevchenko National University, Koval Alina
Published: February 2021

The article comprehensively deals with the evidence of the peculiarities of the formation of the Hellenistic international order in the IV century BC. The author notes that the development of the Ukrainian historiography, among other things, is characterized by a deep interest of historians in studying the problems of international interaction between Eastern and Western civilizations. The study of this question allows to find answers to key questions – whether it is possible to create a universal global order based on common political and humanitarian values, or is it just an utopia, because no unifying model can take into account all the specifics of unique cultures, initially doomed to failure. In this context, it is important for the author to consider the history of such interaction between civilizations, in particular during the creation of the Hellenistic regional order in the IV century BC. This aspect is covered in detail in the treatise „Comparative Biographies”, compiled by the ancient Greek writer Plutarch (approximately 46 - 120/127 AD), the analysis of which is the main purpose of the article. As a result of the study, the author concluded that the biography of Alexander the Great presented by Plutarch allows us to consider the process of creating a Hellenistic empire, which united the key territories of West and East, to identify the logic of certain actions of the commander. Plutarch's description also allowed the author to conclude that in creating a new international order in the East, Alexander faced the traditional challenges of the time – increasing conflict with the tribal aristocracy, which for a long time stood behind him and used for personal gain closeness to the king. As a way out of this crisis, Alexander was forced to resort to strengthening his power, in fact reproducing the foundations of Eastern despotism.
Cities of modern Luhansk region in the XIX – early XX centuries (on statistical materials)
Authors:   State Institution Luhansk Taras Shevchenko National University, Zabudkova Olha
Published: February 2021

The article analyzes the situation of cities in the modern Luhansk region during the XIX – early XX centuries on the basis of statistical materials collected and published by the official bodies of the Russian Empire. The main attention is paid to the cities that had the official status – Starobilsk, Slavyanoserbsk, Belovodsk, Luhansk. At the same time, the statistics included the largest rural settlements of the region, information about which is also taken into account in the work. The population dynamics of cities and the largest settlements of the region is studied. The issue of population density in urban settlements is considered separately are given. Another indicator under consideration is social composition and employment. Much of the article is devoted to the analysis of the economic condition of cities according to statistical collections. Quantitative indicators of industrial development, handicrafts, fair, market and stationary trade are analyzed. It was found that by the beginning of the twentieth century. each city had its own economic specialization – industrial (Luhansk), trade (Starobilsk), craft (Belovodsk). In addition, some rural settlements were no less important as economic centers than cities (Belovodsk, Svatova Luchka). It turned out that all this affected the amount of income that cities received, which was studied. It is concluded that the development of the cities of Luhansk region was embedded in the general trends in the Russian Empire, but from the second half of the nineteenth century. Under the influence of industrial development Luhansk gradually occupied a central place in the region, which, having a significant peasant component, combined the features of old rural and new industrial settlements.
The Revolutionary Ukrainian Party – in terms of the document
Authors:   State Institution Luhansk Taras Shevchenko National University, Mikhalskiy Igor
Published: February 2021

The article describes the beginning of the activities of the Ukrainian Revolutionary Party and the charging document of the prosecutor of the court of justice, which is stored in the Central State Historical Archive of Ukraine in Lviv, is introduced into scientific use. It allows to concretize information about active party leaders, in particular P. Andrijewskyj, P. Steshenko, M. Popov, G. Kollard, I. Manzheley. It is stated that the first Ukrainian party, which was created in 1900, began its active work in 1902–1903, which attracted the attention of the Department for Protecting the Public Security and Order in Kharkiv. The document that is being published belongs to this period. It is noted that researchers have been studying the history and analysis of the activities of the first Ukrainian party since the 20s of the XX century, in particular, the most fundamental work belongs to the famous political and public figure, historian A. Germeise, who not only brought the history of the party to the reader, but also published 53 leaflets and proclamations of the Revolutionary Ukrainian Party. The sources of private origin also contain a lot of valuable material on the activities of the Ukrainian Revolutionary Party. At the end of the 20th century, various collections of documents devoted to the Ukrainian independence movement were published. However, even today there are a large number of documents that are unfamiliar to a wide range of researchers. Therefore, the purpose of this article is to introduce a document that additionally reflects the activities of the Revolutionary Ukrainian Party at the beginning of the 20th century, into scientific use.
Historical circumstances of the establishment and development of the newspaper „Zhovtnevyi hudok” – periodic eidition of Luhansk diesel locomotve plant (1928–2017)
Authors:   Department of Sustainable Development and Internal Communications of JSC ", Ruban Mykola ,   Ukrzaliznytsia", Mashkov Valentyn
Published: February 2021

The article attempts to investigate the historical circumstances of the founding and development of the legendary periodical of the Luhansk Locomotive Plant (1928–2017) – the newspaper „Zhovtnevyi hudok”. It is proved that the magazine emerged as a relevant and necessary means of mass information, internal communication and political propaganda among the staff of the enterprise during its fundamental technological reconstruction in 1928 – 1933. The organizational measures of the newspapers „Zhovtnevyi hudok” and „Luhanska pravda” to increase efficiency work of the staff of the locomotive enterprise by carrying out joint raids on production and coverage of the progress of increasing the production capacity of the locomotive plant, the struggle for the implementation of planned indicators, the implementation of shock obligations, postwar reconstruction, etc. It was found out that the editorial board of the factory magazine, which became resource of professionals for regional journalism in Luhansk region, was awarded the Diploma of the Presidium of the Verkhovna Rada of the USSR, and the newspaper itself was repeatedly recognized as the best production publication in Ukraine and equated to the city district. Despite the fact that during the 1990s and 2000s the volume and circulation of the newspaper were significantly limited and the editorial staff was redundant, the newspaper „Zhovtnevyi hudok”, having withstood numerous economic crises, continued to cover the production activities of the Luhansk diesel locomotive plant, remaining in high demand. layers of workers of the enterprise and professional specialists. Unfortunately, due to the infamous events and the related crisis of the legendary machine-building enterprise, in the 90th year of its existence, the newspaper „Zhovtnevyi hudok” was abolished in 2017.
Pharmacology of opioids and application to practice
Authors: Kemp Neil
Published: February 2021

This article analyses the pharmacological considerations when administering opioids in practice. Beginning with a basic review of pain pathways, followed by a more in-depth analysis of opioid pharmacology. The focus will be on the three most commonly used full mu agonist opioids (methadone, morphine, fentanyl). The aim of this article is to show the importance of applying pharmacology to a clinical situation, promoting individual pain management assessment. This involves the application of the most appropriate opioid, as part of a more extensive pain management plan to improve analgesic efficacy and patient outcomes.
Highly polarization-sensitive, broadband, low dark current, high responsivity graphene-based photodetector utilizing a metal nano-grating at telecommunication wavelengths
Authors: Khosravian Elham , Mashayekhi Hamid Reza , Farmani Ali
Published: February 2021

Recent advances in graphene-based photodetectors have demonstrated the feasibility of utilizing graphene as a fantastic material for the development of future high-performance photodetectors. In this paper, a high-performance graphene-based photodetector is proposed with plasmonic structure by employing a single graphene layer, periodic metal nano-grating, and

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substrate. The plasmonic coupling phenomena between graphene and the metal nano-grating can cause absorption enhancement in this structure. The proposed structure has almost perfect absorption at the telecommunication wavelength (1.55 µm), and its optical response shows a polarization-sensitive characteristic in the spectral range from 1 µm to 2.1 µm. Moreover, the electrical characterization and the dynamic response of this structure are obtained. Based on simulation results, the proposed structure under 0.5 mW incident optical power and at a wavelength of 1.55 µm exhibits a low dark current on the order of about 0.001 mA, maximum photocurrent of 0.81 mA, and responsivity of 1650 mA/W at a bias voltage of 3 V. Also, the rise time of the dynamic response is determined to be about 87 ps, and the 3 dB bandwidth of the frequency response is obtained to be about 4 GHz.
Structural color from a coupled nanowire pair beyond the bonding and antibonding model
Authors: Li Qitong , Wu Tong , van de Groep Jorik , Lalanne Philippe , Brongersma Mark L.
Published: February 2021

Optical resonances in nanostructures can be harnessed to produce a wide
range of structural colors. Conversely, the analysis of structural
colors has been used to clarify the nature of optical resonances.
Here, we show that silicon nanowire (NW) pairs can display a wide
range of structural colors by controlling their radiative coupling.
This is accomplished by exciting a series of Fabry–Pérot-like modes
where light is repeatedly scattered between two NWs. These modes are
beyond the expectation from the conventional chemical bonding model
under a quasi-electrostatic approximation, in which only bonding and
antibonding modes can be formed in a pair system through modal
hybridization. The additional eigenmodes found in a two-resonator
system originate from the nonlinear, frequency-dependent coupling
strength derived from the radiative nature of low-Q
resonators. The Fabry–Pérot modes can be tuned across the entire
visible frequency range by varying the distance between two NWs,
leading to what we believe is a new type of universal building blocks
that can provide structural color within a subwavelength footprint.
The presented results pave the way toward the design and usage of
highly tunable resonances that exploit the radiative coupling of
high-index nanostructures.
Behavioral phenotyping of mice lacking the deubiquitinase USP2
Authors: Srikanta Shashank Bangalore , Stojkovic Katarina , Cermakian Nicolas
Published: February 2021

Ubiquitin specific peptidase 2 (USP2) is a deubiquitinating enzyme expressed almost ubiquitously in the body, including in multiple brain regions. We previously showed that mice lacking USP2 present altered locomotor activity rhythms and response of the clock to light. However, the possible implication of USP2 in regulating other behaviors has yet to be tested. To address this, we ran a battery of behavioral tests on Usp2 KO mice. Firstly, we confirmed our prior findings of increased daily activity and reduced activity fragmentation in Usp2 KO mice. Further, mice lacking USP2 showed impaired motor coordination and equilibrium, a decrease in anxiety-like behavior, a deficit in working memory and in sensorimotor gating. On the other hand, no effects of Usp2 gene deletion were found on spatial memory. Hence, our data uncover the implication of USP2 in different behaviors and expands the range of the known functions of this deubiquitinase.
Accelerating Hepatitis C virus elimination in Egypt by 2030: A national survey of communication for behavioral development as a modelling study
Authors: Metwally Ammal M. , Elmosalami Dalia M. , Elhariri Hazem , El Etreby Lobna A. , Aboulghate Ahmed , El-Sonbaty Marwa M. , Mohsen Amira , Saleh Rehan M. , Abdel-Latif Ghada A. , Samy Sahar , El Deeb Sherif E. , Fathy Asmaa M. , Salah Mohab M. , Abdel Mawla Mohamed A. , Imam Hanaa M. , Ibrahim Nihad A. , Shaaban Fatma A. , Elamir Reham Y. , Abdelrahman Mohamed , El-Sayed Manal H.
Published: February 2021

Aim of the work

This study aimed at assessing the dominance of risk practices associated with HCV endemicity in Egypt and detecting the behavioral development level concerning different aspects of HCV risk behaviors with respect to age and gender. The survey highlights the most cost-effective strategies that could accelerate HCV elimination in Egypt.

Subjects and methods

A national household survey targeted 3780 individuals (age range: 10–85 years). The sample was a systematic probability proportionate to size from 6 governorates representing the six major subdivisions of Egypt. The indicators used for assessing the behavioral development level towards HCV included six domains: awareness (7 indicators), perceived risk (5 indicators), motivation with the intention to change (4 and 5 indicators for males and females respectively), trial, rejection or adoption (6 and 5 indicators for males and females respectively).

Results

The study revealed that along the continuum of behavior development, the percentage of the participants who acquired half of the scores was as follows: 73.1% aware, 69.8% developed perceived risk, 80.6% motivated with only 28.9% adopting the recommended behaviors, 32% rejected them, 2.3% were in the trial stage versus 35.8% who did not try any. Adolescents had significantly lower levels of development for almost all domains when compared to adults. Statistical higher significance was detected in favor of adults, employees, married, Lower Egypt governorates, and university-educated participants (p<0.001) regarding awareness, perceived risk, and motivation scores. More than half of the participants incorrectly believed that contaminated food, sharing food utilities, contaminated water, mosquitoes, and schistosomiasis would lead to HCV transmission.

Conclusion

Egypt would be closer to HCV elimination when cost-effective strategies are directed not towards creating awareness, perceived risk or motivation to change- (at an acceptable level)- but towards motivating adopting risk-reduction behaviors for HCV, tackling misconceptions and reinforcement of social support.
Response of bitter and sweet Chenopodium quinoa varieties to cucumber mosaic virus: Transcriptome and small RNASeq perspective
Authors: Soltani Nourolah , Staton Margaret , Gwinn Kimberly D.
Published: February 2021

Saponins are secondary metabolites with antiviral properties. Low saponin (sweet) varieties of quinoa (Chenopodium quinoa) have been developed because seeds high in saponins taste bitter. The aim of this study was to elucidate the role of saponin in resistance of quinoa to Cucumber mosaic virus (CMV). Differential gene expression was studied in time-series study of CMV infection. High-throughput transcriptome sequence data were obtained from 36 samples (3 varieties × +/- CMV × 1 or 4 days after inoculation × 3 replicates). Translation, lipid, nitrogen, amino acid metabolism, and mono- and sesquiterpenoid biosynthesis genes were upregulated in CMV infections. In ‘Red Head’ (bitter), CMV-induced systemic symptoms were concurrent with downregulation of a key saponin biosynthesis gene, TSARL1, four days after inoculation. In local lesion responses (sweet and semi-sweet), TSARL1 levels remained up-regulated. Known microRNAs (miRNA) (81) from 11 miR families and 876 predicted novel miRNAs were identified. Differentially expressed miRNA and short interfering RNA clusters (24nt) induced by CMV infection are predicted to target genomic and intergenic regions enriched in repetitive elements. This is the first report of integrated RNASeq and sRNASeq data in quinoa-virus interactions and provides comprehensive understanding of involved genes, non-coding regions, and biological pathways in virus resistance.
Nutrient availability is a dominant predictor of soil bacterial and fungal community composition after nitrogen addition in subtropical acidic forests
Authors: Cui Juyan , Yuan Xiaochun , Zhang Qiufang , Zhou Jiacong , Lin Kaimiao , Xu Jianguo , Zeng Yaozhong , Wu Yue , Cheng Lei , Zeng Quanxin , Mei Kongcan , Chen Yuehmin
Published: February 2021

Nutrient addition to forest ecosystems significantly influences belowground microbial diversity, community structure, and ecosystem functioning. Nitrogen (N) addition in forests is common in China, especially in the southeast region. However, the influence of N addition on belowground soil microbial community diversity in subtropical forests remains unclear. In May 2018, we randomly selected 12 experimental plots in a Pinus taiwanensis forest within the Daiyun Mountain Nature Reserve, Fujian Province, China, and subjected them to N addition treatments for one year. We investigated the responses of the soil microbial communities and identified the major elements that influenced microbial community composition in the experimental plots. The present study included three N treatments, i.e., the control (CT), low N addition (LN, 40 kg N ha-1 yr-1), and high N addition (HN, 80 kg N ha-1 yr-1), and two depths, 0−10 cm (topsoil) and 10−20 cm (subsoil), which were all sampled in the growing season (May) of 2019. Soil microbial diversity and community composition in the topsoil and subsoil were investigated using high-throughput sequencing of bacterial 16S rDNA genes and fungal internal transcribed spacer sequences. According to our results, 1) soil dissolved organic carbon (DOC) significantly decreased after HN addition, and available nitrogen (AN) significantly declined after LN addition, 2) bacterial α-diversity in the subsoil significantly decreased with HN addition, which was affected significantly by the interaction between N addition and soil layer, and 3) soil DOC, rather than pH, was the dominant environmental factor influencing soil bacterial community composition, while AN and MBN were the best predictors of soil fungal community structure dynamics. Moreover, N addition influence both diversity and community composition of soil bacteria more than those of fungi in the subtropical forests. The results of the present study provide further evidence to support shifts in soil microbial community structure in acidic subtropical forests in response to increasing N deposition.
Honest signaling in academic publishing
Authors: Tiokhin Leonid , Panchanathan Karthik , Lakens Daniel , Vazire Simine , Morgan Thomas , Zollman Kevin
Published: February 2021

Academic journals provide a key quality-control mechanism in science. Yet, information asymmetries and conflicts of interests incentivize scientists to deceive journals about the quality of their research. How can honesty be ensured, despite incentives for deception? Here, we address this question by applying the theory of honest signaling to the publication process. Our models demonstrate that several mechanisms can ensure honest journal submission, including differential benefits, differential costs, and costs to resubmitting rejected papers. Without submission costs, scientists benefit from submitting all papers to high-ranking journals, unless papers can only be submitted a limited number of times. Counterintuitively, our analysis implies that inefficiencies in academic publishing (e.g., arbitrary formatting requirements, long review times) can serve a function by disincentivizing scientists from submitting low-quality work to high-ranking journals. Our models provide simple, powerful tools for understanding how to promote honest paper submission in academic publishing.
Clonal diversity and spatial dissemination of multi-antibiotics resistant Staphylococcus aureus pathotypes in Southwest Nigeria
Authors: Akinduti Akinniyi Paul , Osiyemi Joshua Adekunle , Banjo Temitope Temitayo , Ejilude Oluwaseun , El-Ashker Maged , Adeyemi Adewale Gideon , Obafemi Yemisi Dorcas , Isibor Patrick Omoregie
Published: February 2021

Spread of genetically diverseStaphylococcus aureuscharacterized with multi-antibiotic resistance and regulated by high levelagrfunctionalities in several communities in southwest Nigeria was investigated and evaluated for infection control.Staphylococcus aureuspathotypes recovered from 256 cases including purulent pus from skin infections, soft tissue aspirates, wounds, otorrhea, eye, throat and endocervical infections were assayed for biofilm and antibiogram. Further genotyped with micro-array, mapped for geospatial distribution and evaluated for clonal diversity and functional accessory gene regulators (agr). Significant Staphylococci infection among the ages (OR:0.021, CI:0.545–1.914) and female gender with prevalence rate of MSSA (53.0%) and MRSA (1.5%) (OR:1.021, CI:0.374–1.785) were observed. More than 52.5% resistance rates to tetracycline and amoxicillin with significant median resistance were observed in all the infection cases (p = 0.001). Resistance rate of 78.8% at MIC5032μg/ml and MIC90128μg/ml to amoxicillin-clavulanate, and more than 40% resistance to ceftazidime, ciprofloxacin and tetracycline of MIC90and MIC50at 32 μg/ml were observed. Strains with multi-antibiotic resistance index above 0.83, high beta-lactamase and strong biofilm clustered into separate phylo-group. Heterogeneous t442 (wound and pus), t657 (wound), t091 (ear) and t657 (ear and wound) revealed high phylogenetic diversity. Only 4.6%pvl+ MSSA-CC1agrI,pvl+ MSSA-CC5 (13.6%) andpvl+ MRSA-CC7agrII (4.6%), expressed enterotoxin, leukocidins, proteases and resistance gene determinants. Livestock clonal types clustered with identified community-associated strains. Clonal dissemination of resistantpvl+MSSA-CC1 and MRSA-CC5 encodingagrwere predominant in several peri-urban communities where adequate geno-surveillance, population-target antimicrobial stewardship, extensive community structured infection control programs are needed to prevent further focal dissemination.
Development and validation of a prediction model for tocilizumab failure in hospitalized patients with SARS-CoV-2 infection
Authors: Mussini Cristina , Cozzi-Lepri Alessandro , Menozzi Marianna , Meschiari Marianna , Franceschini Erica , Milic Jovana , Brugioni Lucio , Pietrangelo Antonello , Girardis Massimo , Cossarizza Andrea , Tonelli Roberto , Clini Enrico , Massari Marco , Bartoletti Michele , Ferrari Anna , Cattelan Anna Maria , Zuccalà Paola , Lichtner Miriam , Rossotti Roberto , Girardi Enrico , Nicastri Emanuele , Puoti Massimo , Antinori Andrea , Viale Pierluigi , Guaraldi Giovanni
Published: February 2021

Background

The aim of this secondary analysis of the TESEO cohort is to identify, early in the course of treatment with tocilizumab, factors associated with the risk of progressing to mechanical ventilation and death and develop a risk score to estimate the risk of this outcome according to patients’ profile.

Methods

Patients with COVID-19 severe pneumonia receiving standard of care + tocilizumab who were alive and free from mechanical ventilation at day 6 after treatment initiation were included in this retrospective, multicenter cohort study. Multivariable logistic regression models were built to identify predictors of mechanical ventilation or death by day-28 from treatment initiation and β-coefficients were used to develop a risk score. Secondary outcome was mortality. Patients with the same inclusion criteria as the derivation cohort from 3 independent hospitals were used as validation cohort.

Results

266 patients treated with tocilizumab were included. By day 28 of hospital follow-up post treatment initiation, 40 (15%) underwent mechanical ventilation or died [26 (10%)]. At multivariable analysis, sex, day-4 PaO2/FiO2 ratio, platelets and CRP were independently associated with the risk of developing the study outcomes and were used to generate the proposed risk score. The accuracy of the score in AUC was 0.80 and 0.70 in internal validation and test for the composite endpoint and 0.92 and 0.69 for death, respectively.

Conclusions

Our score could assist clinicians in identifying, early after tocilizumab administration, patients who are likely to progress to mechanical ventilation or death, so that they could be selected for eventual rescue therapies.
Prevalence and predictors of secondary traumatic stress symptoms in health care professionals working with trauma victims: A cross-sectional study
Authors: Ogińska-Bulik Nina , Gurowiec Piotr Jerzy , Michalska Paulina , Kędra Edyta
Published: February 2021

Introduction

Medical personnel is an occupational group that is especially prone to secondary traumatic stress. The factors conditioning its occurrence include organizational and work-related factors, as well as personal features and traits. The aim of this study was to determine Secondary Traumatic Stress (STS) indicators in a group of medical personnel, considering occupational load, job satisfaction, social support, and cognitive processing of trauma.

Material and methods

Results obtained from 419 medical professionals, paramedics and nurses, were analyzed. The age of study participants ranged from 19 to 65 (M = 39.60, SD = 11.03). A questionnaire developed for this research including questions about occupational indicators as well as four standard evaluation tools: Secondary Traumatic Stress Inventory, Job Satisfaction Scale, Social Support Scale which measures four support sources (supervisors, coworkers, family, friends) and Cognitive Processing of Trauma Scale which allows to evaluate cognitive coping strategies (positive cognitive restructuring, downward comparison, resolution/acceptance, denial, regret) were used in the study.

Results

The results showed that the main predictor of STS symptoms in the studied group of medical personnel is job satisfaction. Two cognitive strategies also turned out to be predictors of STS, that is regret (positive relation) and resolution/acceptance (negative relation). The contribution of other analyzed variables, i.e., denial, workload and social support to explaining the dependent variable is rather small.

Conclusions

Paramedics and nurses are at the high risk of indirect traumatic exposure and thus may be more prone to secondary traumatic stress symptoms development. It is important to include the medical personnel in the actions aiming at prevention and reduction of STS symptoms.
Berberine ameliorates vascular dysfunction by a global modulation of lncRNA and mRNA expression profiles in hypertensive mouse aortae
Authors: Tan Na , Zhang Yi , Zhang Yan , Li Li , Zong Yi , Han Wenwen , Liu Limei
Published: February 2021

Objective

The current study investigated the mechanism underlying the therapeutic effects of berberine in the vasculature in hypertension.

Methods

Angiotensin II (Ang II)-loaded osmotic pumps were implanted in C57BL/6J mice with or without berberine administration. Mouse aortae were suspended in myograph for force measurement. Microarray technology were performed to analyze expression profiles of lncRNAs and mRNAs in the aortae. These dysregulated expressions were then validated by qRT-PCR. LncRNA-mRNA co-expression network was constructed to reveal the specific relationships.

Results

Ang Ⅱ resulted in a significant increase in the blood pressure of mice, which was suppressed by berberine. The impaired endothelium-dependent aortic relaxation was restored in hypertensive mice. Microarray data revealed that 578 lncRNAs and 554 mRNAs were up-regulated, while 320 lncRNAs and 377 mRNAs were down-regulated in the aortae by Ang Ⅱ; both were reversed by berberine treatment. qRT-PCR validation results of differentially expressed genes (14 lncRNAs and 6 mRNAs) were completely consistent with the microarray data. GO analysis showed that these verified differentially expressed genes were significantly enriched in terms of “cellular process”, “biological regulation” and “regulation of biological process”, whilst KEGG analysis identified vascular function-related pathways including cAMP signaling pathway, cGMP-PKG signaling pathway, and calcium signaling pathway etc. Importantly, we observed that lncRNA ENSMUST00000144849, ENSMUST00000155383, and AK041185 were majorly expressed in endothelial cells.

Conclusion

The present results suggest that the five lncRNAs ENSMUST00000144849, NR_028422, ENSMUST00000155383, AK041185, and uc.335+ might serve critical regulatory roles in hypertensive vasculature by targeting pivotal mRNAs and subsequently affecting vascular function-related pathways. Moreover, these lncRNAs were modulated by berberine, therefore providing the novel potential therapeutic targets of berberine in hypertension. Furthermore, lncRNA ENSMUST00000144849, ENSMUST00000155383, and AK041185 might be involved in the preservation of vascular endothelial cell function.
Antibody affinity versus dengue morphology influences neutralization
Authors: Fibriansah Guntur , Lim Elisa X. Y. , Marzinek Jan K. , Ng Thiam-Seng , Tan Joanne L. , Huber Roland G. , Lim Xin-Ni , Chew Valerie S. Y. , Kostyuchenko Victor A. , Shi Jian , Anand Ganesh S. , Bond Peter J. , Crowe James E. , Lok Shee-Mei
Published: February 2021

Different strains within a dengue serotype (DENV1-4) can have smooth, or “bumpy” surface morphologies with different antigenic characteristics at average body temperature (37°C). We determined the neutralizing properties of a serotype cross-reactive human monoclonal antibody (HMAb) 1C19 for strains with differing morphologies within the DENV1 and DENV2 serotypes. We mapped the 1C19 epitope to E protein domain II by hydrogen deuterium exchange mass spectrometry, cryoEM and molecular dynamics simulations, revealing that this epitope is likely partially hidden on the virus surface. We showed the antibody has high affinity for binding to recombinant DENV1 E proteins compared to those of DENV2, consistent with its strong neutralizing activities for all DENV1 strains tested regardless of their morphologies. This finding suggests that the antibody could out-compete E-to-E interaction for binding to its epitope. In contrast, for DENV2, HMAb 1C19 can only neutralize when the epitope becomes exposed on the bumpy-surfaced particle. Although HMAb 1C19 is not a suitable therapeutic candidate, this study with HMAb 1C19 shows the importance of choosing a high-affinity antibody that could neutralize diverse dengue virus morphologies for therapeutic purposes.
Therapeutic targeting of measles virus polymerase with ERDRP-0519 suppresses all RNA synthesis activity
Authors: Cox Robert M. , Sourimant Julien , Govindarajan Mugunthan , Natchus Michael G. , Plemper Richard K.
Published: February 2021

Morbilliviruses, such as measles virus (MeV) and canine distemper virus (CDV), are highly infectious members of the paramyxovirus family. MeV is responsible for major morbidity and mortality in non-vaccinated populations. ERDRP-0519, a pan-morbillivirus small molecule inhibitor for the treatment of measles, targets the morbillivirus RNA-dependent RNA-polymerase (RdRP) complex and displayed unparalleled oral efficacy against lethal infection of ferrets with CDV, an established surrogate model for human measles. Resistance profiling identified the L subunit of the RdRP, which harbors all enzymatic activity of the polymerase complex, as the molecular target of inhibition. Here, we examined binding characteristics, physical docking site, and the molecular mechanism of action of ERDRP-0519 through label-free biolayer interferometry, photoaffinity cross-linking, and in vitro RdRP assays using purified MeV RdRP complexes and synthetic templates. Results demonstrate that unlike all other mononegavirus small molecule inhibitors identified to date, ERDRP-0519 inhibits all phosphodiester bond formation in both de novo initiation of RNA synthesis at the promoter and RNA elongation by a committed polymerase complex. Photocrosslinking and resistance profiling-informed ligand docking revealed that this unprecedented mechanism of action of ERDRP-0519 is due to simultaneous engagement of the L protein polyribonucleotidyl transferase (PRNTase)-like domain and the flexible intrusion loop by the compound, pharmacologically locking the polymerase in pre-initiation conformation. This study informs selection of ERDRP-0519 as clinical candidate for measles therapy and identifies a previously unrecognized druggable site in mononegavirus L polymerase proteins that can silence all synthesis of viral RNA.
A közvetlen külföldi befektetések és a korrupció közötti kapcsolat (The connection of Foreign Direct Investment and corruption)
Authors: Erdődi-Kovács Viktória , Hegedűs Krisztina
Published: February 2021

A szerzők tanulmányának középpontjában a közvetlen külföldi befektetések és a korrupció kapcsolata áll. Feltételezésük az, hogy a közvetlen külföldi befektetők a kevésbé korrupt országokat kedvelik, mivel a korrupció egy további kockázati tényezőt jelent a befektetők számára, amely növelheti a befektetések költségeit. Megítélésük szerint ezt kvantitatív módszerekkel érdemes vizsgálni, így elemzésük során 79 országot vizsgálnak meg tíz évre vonatkozó átlagokkal a Gretl-program és az OLS becslőfüggvény segítségével. Több modell lefuttatása után azt az eredményt kapták, hogy a közvetlen külföldi befektetők döntéseiben a korrupció szignifikáns tényező, a két változó között negatív korrelációt figyeltek meg. / === / The study focuses on the connection of Foreign Direct Investment and corruption. The authors assume that investors prefer countries where corruption level is lower, as corruption an additional risk factor that might increase the cost of investment. They believe that the best way to prove the previous statement if they use quantitative methods, so they set up a model where 79 countries are tested for 10 years averages, with the help of the Gretl and OLS estimator. After running several models their finding was that corruption is a significant factor in the decisions of foreign investors, and there is a negative correlation between corruption and FDI.
The Impact of COVID-19 on Stock Returns of the Indian Healthcare and Pharmaceutical Sector
Authors: Mittal Shivam , Sharma Dipasha
Published: February 2021

Increasing COVID-19 cases has not only impacted health and day-to-day lives of people, but it has also had a material effect on India’s economic growth. Stock returns of various sectors are evidence of a country’s stagnated growth but the healthcare and pharmaceutical sector might be affected in a different manner. The purpose of this paper is to find out how has this pandemic has impacted the healthcare and pharma stocks. Daily closing prices of sector specific indexes for 233 days ranging from 15 May 2019 to 24 April 2020 have been taken to compare different sectors with our test sector, on the basis of different criteria. This study has applied the widely used event study methodology on our test sector; calculated abnormal returns, cumulative abnormal returns and also tested their significance. Event study approach suggests that there have been significant abnormal returns and cumulative abnormal returns in our test sector (healthcare and pharmaceutical sector) over the event window, though while comparing it with other sectors through another econometric model, the returns are not statistically significant and do not explicitly indicate the same.
A Study on the Impact of COVID- 19 on Investor Behaviour of Individuals in a Small Town in the State of Madhya Pradesh, India
Authors: Gurbaxani Arpita , Gupte Rajani
Published: February 2021

Purpose: To understand how the COVID-19 pandemic has impacted investment and financial decisions of individuals in small towns in developing nations such as India. Methodology: A literature review was undertaken on COVID-19 and steps taken by the government to fight the pandemic. A sample survey was conducted to determine the impact of COVID-19 on individuals’ financial transactions in Madhya Pradesh (MP) . The respondents either belonged to the service sector or owned businesses. The relationship between the COVID-19 pandemic and change in investment decisions of individuals with respect to SIPs was studied. Findings: Significant association was found between measures taken to prevent the spread of COVID-19 (such as lockdown and travel restrictions) and individual income; such preventive measures directly impacted savings and investment behaviour. Indeed, respondents reported a 43% drop in SIP investments during the COVID-19 pandemic. While decline in investment was common to genders, the difference between percentage decline was statistically non-significant. Furthermore, investment behaviour did not vary with investor age. Research Implications: Results highlight the socioeconomic effects of the COVID-19 outbreak at the micro-level and may enable financial institutions and individuals to better handle such situations in future. The scope of the present research is limited. Future studies could consider larger samples and different contexts to gain deeper insights into the socioeconomic effects of the COVID-19 pandemic. Studies could also suggest policies and measures to help governments effectively deal with future crises. Originality/ Value: Hitherto, the impact of COVID-19 outbreak on investment decisions of individuals in Tier 3 cities had remained under-examined; this is one of the first studies to carry out such an investigation.
Organizational Inclusion and Leadership in Times of Global Crisis
Authors: Kuknor Sunaina , Bhattacharya Shubhasheesh
Published: February 2021

The globe is facing a never before seen pandemic situation because of Covid-19. Virtual workspaces have become a reality today. With the emergence of newer ways of working, it is necessary to ensure that employees contribute and feel involved in the workspace. This paper attempts to explore the ways in which practitioners and policymakers of inclusion perceive it at the workplace in the current COVID-19 pandemic, outline the role of leaders in fostering inclusion, and empirically test how organizational inclusion (OI) impacts organizational outcomes during the disturbing times. The participants were employees working in the service sector companies in India. A mixed-method approach would be adopted for data collection. The content analysis technique would be used for the qualitative data analysis and Partial Least Square – Structural Equation Modelling (PLS-SEM) to analyze the quantitative data. The paper provides insights on how inclusion is perceived differently by each individual, and though organizations have policies in place, getting them into practice is yet to be accomplished. The findings of the study indicate the benefits of having an inclusive work environment along with leadership commitment during disruption. The study is a novel attempt to empirically examine the way of leveraging a diverse workforce through inclusion to benefit the organization in the times of global crisis. It also adds to the existing body of knowledge on how inclusion and role of a leader are experienced by the employer and employee in Indian companies, which is a niche area of research.