bluuebunny/crossref_metadata_2025 huggingface dataset:
The prevalence and characteristics of rapid response systems in hospitals with pediatric intensive care units in Japan and barriers to their use
Authors: Haga Taiki , Kurosawa Hiroshi , Maruyama Junji , Sakamoto Katsuko , Ikebe Ryo , Tokuhira Natsuko , Takeuchi Muneyuki
Published: April 2020

Objective

The use of pediatric rapid response systems (RRSs) to improve the safety of hospitalized children has spread in various western countries including the United States and the United Kingdom. We aimed to determine the prevalence and characteristics of pediatric RRSs and barriers to use in Japan, where epidemiological information is limited.

Design

A cross-sectional online survey.

Setting

All 34 hospitals in Japan with pediatric intensive care units (PICUs) in 2019.

Participants

One PICU physician per hospital responded to the questionnaire as a delegate.

Main outcome measures

Prevalence of pediatric RRSs in Japan and barriers to their use.

Results

The survey response rate was 100%. Pediatric RRSs had been introduced in 14 (41.2%) institutions, and response teams comprised a median of 6 core members. Most response teams employed no full-time members and largely comprised members from multiple disciplines and departments who served in addition to their main duties. Of 20 institutions without pediatric RRSs, 11 (55%) hoped to introduce them, 14 (70%) had insufficient knowledge concerning them and 11 (55%) considered that their introduction might be difficult. The main barrier to adopting RRSs was a perceived personnel and/or funding shortage. There was no significant difference in hospital beds (mean, 472 vs. 524, P = 0.86) and PICU beds (mean, 10 vs. 8, P = 0.34) between institutions with/without pediatric RRSs.

Conclusions

Fewer than half of Japanese institutions with PICUs had pediatric RRSs. Operating methods for and obstructions to RRSs were diverse. Our findings may help to popularize pediatric RRSs.
Dissipation, Processing, Leaching, and Safety Evaluation of Flonicamid and Its Metabolites in Tea
Authors: Yang Ya , Liu Xiangwu , Zhang Qingtao , Chen Ya , Zhang Sumei , Lu Ping , Hu Deyu
Published: April 2020

Background

Tea is a popular traditional non-alcoholic beverage worldwide. Flonicamid is a selective systemic pyridine carboxamide insecticide that is widely used for controlling tea leafhopper in tea.

Objective

The leaching rates, dissipation dynamics, and residue levels of flonicamid and its metabolites in tea leaves during processing and transferring were investigated to validate the safe risk in tea and transfer behavior using high performance liquid chromatography–tandem mass spectrometry with a convenient pretreatment method.

Method

The extracting method and immersion rate experiments were optimized by single factor analysis and orthogonal tests. The acetonitrile extracting solvent with 0.5% formic acid was used and optimal leaching conditions were obtained with a regime of 15 min immersion time, 100°C temperature, three immersions and a tea-to-water ratio of 1:50.

Results

Average recoveries in processed green tea and infusions were 80.85–98.75% with relative standard deviations <5.87%. LODs and LOQs of flonicamid, 4-trifluoromethylnicotinic acid (TFNA), N-(4-trifluoromethylnicotinoyl) glycine (TFNG), and 4-trifluoromethylnicotinamide (TFNA-AM) were 0.0013–0.350 and 0.004–1 μg/g, respectively. The processing factor of flonicamid was 0.36–5.52 during green tea manufacture. The leaching rates were 22.9-97.4% from processed tea to infusion.

Conclusions

The risk of long-term and short-term dietary intake of flonicamid was safe in tea infusions with the risk quotient (RQ) values <1 for the Chinese consumer. This work may provide guidance for safe and reasonable consumption of flonicamid in tea in China.

Highlights

The suitable leaching factors of flonicamid and its metabolites in tea infusions were optimized by orthogonal experimentation for the first time.
From ‘Sherlockian Venture’ to a ‘Matter of Trial’: Delhi High Court adds to the plight of the Indian direct selling market
Authors: Gupta Aditya
Published: April 2020

Amazon Seller Services Pvt Ltd & Ors v Amway India Enterprises Pvt Ltd & Ors, Delhi High Court, 31 January 2020
The Benefits of PSM: An Oasis or a Mirage?
Authors: Awan Sahar , Bel Germà , Esteve Marc
Published: April 2020

Scholarly interest in public service motivation (PSM) has yielded a vast amount of research, exploring its potential for benefitting public-sector organizations through increased employee job satisfaction, enhanced individual performance, employee retention, and enhanced organizational commitment and citizenship behavior. However, a closer inspection of the literature reveals mixed empirical evidence for each impact of PSM. The present study carries out a meta-analysis of five key impacts of PSM to explain the divergence of results in the existing literature. We find evidence of the existence of a true effect for PSM over all the dependent variables, except for turnover intentions. In addition, we find a possible explanation for the mixed empirical evidence found in previous studies. We demonstrate that individual and organizational benefits of PSM are not accrued equally in all public sector workplaces and that the contextual variables legal origin and endemic countrywide corruption influence the extent to which PSM can produce positive outcomes in the workplace.
Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease After Introduction Into Routine Pediatric Use
Authors: Baxter Roger , Aukes Laurie , Pelton Stephen I , Yee Arnold , Klein Nicola P , Gruber William C , Scott Daniel A , Center Kimberly J
Published: April 2020

Background

In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced 7-valent PCV (PCV7) for protection against invasive pneumococcal disease (IPD). This study used laboratory surveillance data to examine the effect of PCV13 on IPD before and after PCV13 introduction among children aged 6 weeks to <6 years and those aged ≥6 weeks.

Methods

Observational laboratory-based IPD surveillance data were compared for the periods May 2010–April 2018 and May 2008–April 2010 (the PCV7 period) using a database of Kaiser Permanente Northern California (KPNC) members with laboratory-confirmed IPD.

Results

Among children aged 6 weeks to 6 years, overall IPD incidence decreased from 11.57 per 100 000 during the PCV7 period to 4.09 per 100 000 after PCV13 introduction; PCV13-type IPD incidence decreased from 5.12 to 0.84 per 100 000. Non-PCV13−serotype IPD did not change significantly in this age group (PCV7 period, 1.71 per 100 000 and after PCV13, 2.52 per 100 000). Of cases occurring in this group, bacteremia was the most common clinical diagnosis. Across all ages, IPD decreased from 9.49 to 6.23 per 100 000 and PCV13-type IPD decreased from 4.67 to 1.89 per 100 000, changes being mostly due to decreases in serotypes 19A and 7F. IPD caused by non-PCV13 serotypes did not change (3.34 and 3.35 per 100 000). Overall, pneumococci isolated after PCV13 introduction had increased susceptibility to penicillin, cefotaxime, and ceftriaxone.

This prospective, laboratory-based surveillance study in Kaiser Permanente Northern California members examined annual IPD incidence before and after PCV13 introduction. In children aged 6 weeks to <6 years, IPD caused by PCV13 serotypes decreased significantly (84%) during the surveillance period.

Conclusions

IPD incidence decreased further in every age group after PCV13 introduction, suggesting both direct vaccination effects in the infant population and indirect effects in adults.

Clinical Trials Registration

NCT01128439.
Deep Brain Stimulation in Epilepsy: A Role for Modulation of the Mammillothalamic Tract in Seizure Control?
Authors: Schaper Frédéric L W V J , Plantinga Birgit R , Colon Albert J , Wagner G Louis , Boon Paul , Blom Nadia , Gommer Erik D , Hoogland Govert , Ackermans Linda , Rouhl Rob P W , Temel Yasin
Published: April 2020

BACKGROUND

Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) can improve seizure control for patients with drug-resistant epilepsy (DRE). Yet, one cannot overlook the high discrepancy in efficacy among patients, possibly resulting from differences in stimulation site.

OBJECTIVE

To test the hypothesis that stimulation at the junction of the ANT and mammillothalamic tract (ANT-MTT junction) increases seizure control.

METHODS

The relationship between seizure control and the location of the active contacts to the ANT-MTT junction was investigated in 20 patients treated with ANT-DBS for DRE. Coordinates and Euclidean distance of the active contacts relative to the ANT-MTT junction were calculated and related to seizure control. Stimulation sites were mapped by modelling the volume of tissue activation (VTA) and generating stimulation heat maps.

RESULTS

After 1 yr of stimulation, patients had a median 46% reduction in total seizure frequency, 50% were responders, and 20% of patients were seizure-free. The Euclidean distance of the active contacts to the ANT-MTT junction correlates to change in seizure frequency (r2
 = 0.24, P = .01) and is ∼30% smaller (P = .015) in responders than in non-responders. VTA models and stimulation heat maps indicate a hot-spot at the ANT-MTT junction for responders, whereas non-responders had no evident hot-spot.

CONCLUSION

Stimulation at the ANT-MTT junction correlates to increased seizure control. Our findings suggest a relationship between the stimulation site and therapy response in ANT-DBS for epilepsy with a potential role for the MTT. DBS directed at white matter merits further exploration for the treatment of epilepsy.
Development of mouse preimplantation embryos in space
Authors: Lei Xiaohua , Cao Yujing , Ma Baohua , Zhang Yunfang , Ning Lina , Qian Jingjing , Zhang Liwen , Qu Yongcun , Zhang Tao , Li Dehong , Chen Qi , Shi Junchao , Zhang Xudong , Ma Chiyuan , Zhang Ying , Duan Enkui
Published: April 2020

The development of life beyond planet Earth is a long-standing quest of the human race, but whether normal mammalian embryonic development can occur in space is still unclear. Here, we show unequivocally that preimplantation mouse embryos can develop in space, but the rate of blastocyst formation and blastocyst quality are compromised. Additionally, the cells in the embryo contain severe DNA damage, while the genome of the blastocysts developed in space is globally hypomethylated with a unique set of differentially methylated regions. The developmental defects, DNA damage and epigenetic abnormalities can be largely mimicked by the treatment with ground-based low-dose radiation. However, the exposure to simulated microgravity alone does not cause major disruptions of embryonic development, indicating that radiation is the main cause for the developmental defects. This work advances the understanding of embryonic development in space and reveals long-term extreme low-dose radiation as a hazardous factor for mammalian reproduction.
The Weaknesses of Weak Preemptionism
Authors: Hauswald Rico
Published: April 2020

According to preemptionism, a layperson should treat the fact that an epistemic authority believes p as a reason to believe p that replaces her other reasons relevant to believing p and is not simply added to them. Many authors have found the unqualified version of preemptionism, as defended by Linda Zagzebski, too strong. At the same time, a number of them have recently advocated weakened or qualified preemptionist accounts. In this paper, I criticise these accounts. I argue that some of them cannot explain the possibility of rational persistent disagreements between laypeople and epistemic authorities, while those that can explain it fail to account either for the extent to which justification is a holistic phenomenon or for the role of what I call ‘control reasons’ in the laypeople's epistemic conduct.
What Do Fund Flows Reveal about Asset Pricing Models and Investor Sophistication?
Authors: Jegadeesh Narasimhan , Mangipudi Chandra Sekhar
Published: April 2020

Recent evidence indicates that market model alphas are stronger predictors of mutual fund flows than alphas with other models. Some recent papers have interpreted this evidence to mean that CAPM is the best asset pricing model, but some others have interpreted it as evidence against investor sophistication. We evaluate the merits of these mutually exclusive interpretations. We show that no tenable inference about the validity of any asset pricing model can be drawn from this evidence. Rejecting the investor sophistication hypothesis is tenable, but the appropriate benchmark to judge sophistication is different from that used in this literature.
New Gambling Task Reveals an Atypical Relation Between Social Anxiety and Social Avoidance in Schizophrenia
Authors: Muthesius Ana , Hölzer Susanne , Grothey Anna Farina , Rubruck Jirko , Vogeley Kai , Schultz Johannes
Published: April 2020

A core symptom of schizophrenia is a deficit in social cognition. Furthermore, many patients suffer from relevant social anxiety. How social anxiety relates to social avoidance in schizophrenia is, however, still unclear. To address this question empirically, 30 participants with schizophrenia were compared to individually matched controls in a recently developed experimental task. In each trial, participants chose between a monetary gamble with a human partner providing social feedback and a defined monetary amount that varied across trials. The tendency to avoid the interaction under acceptance of monetary loss served as a measure of social avoidance. Patients showed higher levels of social anxiety assessed using the Liebowitz Social Anxiety Scale (LSAS) than controls, took longer to decide whether to engage in the social interaction and rated social feedback as less intense. Despite making rational decisions, patients surprisingly showed no social avoidance. We assume that the lack of experimentally induced social avoidance in contrast to the well-known social avoidance behavior in everyday life, also reflected by elevated self-rated LSAS scores, was due to a partial compensation of delayed social information processing in the absence of the time constraints in our task. This additional time may have allowed rational decisions and masked potential social avoidance behavior. We conclude that social anxiety in schizophrenia may have different characteristics than in individuals without schizophrenia, namely avoidance of negative feedback caused by prolonged social processing instead of fear of supposed negative feedback. Treatment strategies for social anxiety in schizophrenia may benefit from considering these differences.
Effects of Horseradish Oil and Eight Isothiocyanates Vapour Treatment on Postharvest Disease Control and Their Efficacy as Preservatives of Mature Green Tomato
Authors: Ren Jing-jing , Zhang Dan , Hou Pu-xing , Wu Hua
Published: April 2020

This study evaluated the potential of horseradish (Armoracia rusticana) oil (ARO) and eight isothiocyanates (propyl ITC [ProITC], isopropyl ITC [IsoproITC], n-butyl ITC [n-BuITC], 3-butenyl ITC [3-BeITC], phenyl ITC [PhITC], benzyl ITC [BzITC], 2-phenylethyl ITC [PhEITC], and allyl ITC [AITC]) as preservatives and antifungal agents for postharvest tomato disease control. Results showed that ARO and eight ITCs demonstrated antifungal activities against Botrytis cinerea, Alternaria alternata, Rhizopus stolonifer, and Geotrichum candidum, which can cause the decay of mature green tomato during storage. Allyl-ITC (AITC) had the lowest EC50values of mycelia growth suppression, with 0.18, 0.44, 0.29, and 0.43 μg/ml air for B. cinerea, A. alternata, R. stolonifer, and G. candidum, respectively. ARO, 2-PhEITC, BzITC, and AITC exhibited better efficacy as preservatives of mature green tomato than other ITCs on the basis of some parameters, such as low decay rate, slow reduction in weight loss, slight change in hardness, slow decrease in acidity, and total soluble solid content of treated tomatoes. GC-MS revealed that 2-PhEITC (77.78%) and AITC (15.87%) were the major components of ARO. These results can be used as a basis to develop preservative products composed of ITCs.
The hidden army: corallivorous crown-of-thorns seastars can spend years as herbivorous juveniles
Authors: Deaker Dione J. , Agüera Antonio , Lin Huang-An , Lawson Corinne , Budden Claire , Dworjanyn Symon A. , Mos Benjamin , Byrne Maria
Published: April 2020

Crown-of-thorns seastar (COTS) outbreaks are a major threat to coral reefs. Although the herbivorous juveniles and their switch to corallivory are key to seeding outbreaks, they remain a black box in our understanding of COTS. We investigated the impact of a delay in diet transition due to coral scarcity in cohorts reared on crustose coralline algae for 10 months and 6.5 years before being offered coral. Both cohorts achieved an asymptotic size (16–18 mm diameter) on algae and had similar exponential growth on coral. After 6.5 years of herbivory, COTS were competent coral predators. This trophic and growth plasticity results in a marked age–size disconnect adding unappreciated complexity to COTS boom–bust dynamics. The potential that herbivorous juveniles accumulate in the reef infrastructure to seed outbreaks when favourable conditions arise has implications for management of COTS populations.
A poor substitute for the real thing: captive-reared monarch butterflies are weaker, paler and have less elongated wings than wild migrants
Authors: Davis Andrew K. , Smith Farran M. , Ballew Ashley M.
Published: April 2020

For many animals and insects that are experiencing dramatic population declines, the only recourse for conservationists is captive rearing. To ensure success, reared individuals should be biologically indistinct from those in the wild. We tested if this is true with monarch butterflies,
Danaus plexippus
, which are increasingly being reared for release by citizens and commercial breeders. Since late-summer monarchs should be as migration capable as possible for surviving the arduous long-distance migration, we evaluated four migration-relevant traits across two groups of captive-reared monarchs (
n
= 41 and 42) and one group of wild-caught migrants (
n
= 41). Monarchs (descendants of wild individuals) were reared from eggs to adulthood either in a warm indoor room next to a window, or in an incubator that mimicked late-summer conditions. Using an apparatus consisting of a perch mounted to an electronic force gauge, we assessed ‘grip strength' of all groups, then used image analysis to measure forewing size, pigmentation and elongation. In three of the four traits, reared monarchs underperformed compared to wild ones, even those reared under conditions that should have produced migration-ready individuals. The average strength of reared monarchs combined was 56% less than the wild group, even when accounting for size. Their orange wing colour was paler (an indicator of poor condition and flight ability) and their forewings were less elongated (elongation is associated with migration propensity) than wild monarchs. The reason(s) behind these effects is unknown but could stem from the frequent disturbance and/or handling of reared monarchs, or the fact that rearing removes the element of natural selection from all stages. Regardless, these results explain prior tagging studies that showed reared monarchs have lower migratory success compared to wild.
Measuring social networks in primates: wearable sensors versus direct observations
Authors: Gelardi Valeria , Godard Jeanne , Paleressompoulle Dany , Claidiere Nicolas , Barrat Alain
Published: April 2020

Network analysis represents a valuable and flexible framework to understand the structure of individual interactions at the population level in animal societies. The versatility of network representations is moreover suited to different types of datasets describing these interactions. However, depending on the data collection method, different pictures of the social bonds between individuals could
a priori
emerge. Understanding how the data collection method influences the description of the social structure of a group is thus essential to assess the reliability of social studies based on different types of data. This is however rarely feasible, especially for animal groups, where data collection is often challenging. Here, we address this issue by comparing datasets of interactions between primates collected through two different methods: behavioural observations and wearable proximity sensors. We show that, although many directly observed interactions are not detected by the sensors, the global pictures obtained when aggregating the data to build interaction networks turn out to be remarkably similar. Moreover, sensor data yield a reliable social network over short time scales and can be used for long-term studies, showing their important potential for detailed studies of the evolution of animal social groups.
Targeting the catecholamine-cytokine axis to prevent SARS-CoV-2 cytokine storm syndrome
Authors: Konig Maximilian F. , Powell Mike , Staedtke Verena , Bai Ren-Yuan , Thomas David L. , Fischer Nicole , Huq Sakibul , Khalafallah Adham M. , Koenecke Allison , Xiong Ruoxuan , Mensh Brett , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert , Vogelstein Joshua T. , Athey Susan , Zhou Shibin , Bettegowda Chetan
Published: April 2020

In Coronavirus disease 2019 (COVID-19), the initial viral-replication phase is often followed by a hyperinflammatory reaction in the lungs and other organ systems that leads to acute respiratory distress syndrome (ARDS), the need for mechanical ventilation, and death despite maximal supportive care. As no antiviral treatments have yet proven effective, efforts to prevent progression to the severe stages of COVID-19 without inhibiting antiviral immune responses are desperately needed. We have previously demonstrated that a common, inexpensive, and well-tolerated class of drugs called alpha-1 adrenergic receptor (α1-AR) antagonists can prevent hyperinflammation (“cytokine storm”) and death in mice. We here present clinical data that supports the use of α1-AR antagonists in the prevention of severe complications of pneumonia, ARDS, and COVID-19.
Interaction between malarial transmission and BCG vaccination with COVID-19 incidence in the world map: A cross-sectional study
Authors: Goswami Rudra Prosad , Mittal Dheeraj , Goswami Rama Prosad
Published: April 2020

Background

COVID-19 (Corona virus Disease-2019) is a new public health emergency and is a pandemic currently. Incidence and mortality of COVID-19 vary in different geographical areas. In this study we aimed to analyse the relationship between malaria transmission and BCG vaccination with COVID-19 incidence in the world map.

Materials and methods

We collected malaria cases data (World Health Organisation (WHO), 2018), worldwide COVID-19 cases and mortality data (European Centre for Disease Prevention and Control) and data on BCG vaccination. COVID-19 incidence and mortality was compared.

Findings

Data on 5316978938 persons from 166 countries were analysed. Malaria incidence rate was negatively correlated with COVID-19 incidence rate (correlation coefficient = -0.513, p<0.001). Malaria free countries had significantly higher number of COVID-19 cases compared to malaria endemic countries. In Europe and Americas, countries, which have higher BCG vaccination coverage, had significantly less mortality per thousand population compared to those with low BCG coverage (median 0.0002 (0-0.0005) vs 0.0029 (0.0002-0.0177), p=0.017). The case fatality ratio of COVID-19 was related nonlinearly to the malaria incidence.

Conclusions

The results suggest the changing human immune system as we progress to eliminate parasitic diseases with time. Chloroquine exposure in malaria endemic zones might have a protective effect.

Summary box

“What is already known on this subject?”

To the best of the authors no similar evidence, of the effect of malarial transmission on the COVID-19 global distribution is known. The effect of the Bacille Calmette Guérin (BCG) vaccine on modifying the human immune system has been reported before and is postulated to protective against certain viral infections like Influenza A (H1N1) and herpes virus.

“What this study adds?”

This study finds that COVID-19 incidence, worldwide is less in countries, which are malaria-endemic. In the European and American countries, increased BCG coverage may have some mortality advantage against COVID-19. The case fatality rate was related to malaria incidence, however, in a complex way. This could be a window into the changing landscape of human immune system as we progress to eliminate parasitic disease with time or this could be due to long-term protective body level of anti-malarials like chloroquine or hydroxychloroquine in countries with higher malaria incidence rate.
Anti-apoptotic clone 11 derived peptides induce in vitro death of CD4+ T cells susceptible to HIV-1 infection
Authors: Mikhailova Anastassia , Valle-Casuso José Carlos , David Annie , Monceaux Valérie , Volant Stevenn , Passaes Caroline , Elfidha Amal , Müller-Trutwin Michaela , Poyet Jean-Luc , Sáez-Cirión Asier
Published: April 2020

HIV-1 successfully establishes long-term infection in its target cells despite viral cytotoxic effects. We have recently shown that cell metabolism is an important factor driving CD4+ T-cell susceptibility to HIV-1 and the survival of infected cells. We show here that expression of anti-apoptotic clone 11 (AAC-11), an anti-apoptotic factor upregulated in many cancers, increased with progressive CD4+ T cell memory differentiation in association with the expression of cell cycle, activation and metabolism genes and correlated with susceptibility to HIV-1 infection. Synthetic peptides based on the LZ domain sequence of AAC-11, responsible for its interaction with molecular partners, were previously shown to be cytotoxic to cancer cells. Here we observed that these peptides also blocked HIV-1 infection by inducing cell death of HIV-1 susceptible primary CD4+ T-cells across all T-cell subsets. The peptides targeted metabolically active cells and had the greatest effect on effector and transitional CD4+ T cell memory subsets. Our results suggest that AAC-11 survival pathway is potentially involved in the survival of HIV-1 infectable cells and provide a proof of principle that some cellular characteristics can be targeted to eliminate the cells offering the best conditions to sustain HIV-1 replication.

IMPORTANCE

Although antiretroviral treatment efficiently blocks HIV multiplication, it cannot eliminate the cells already carrying integrated proviruses. In the search for a HIV cure the identification of new potential targets to selectively eliminate infected cells is of the outmost importance. We show here that peptides derived from the anti-apoptotic clone 11 (AAC-11), which expression levels correlated with susceptibility to HIV-1 infection of CD4+ T-cells, induced cytotoxicity in CD4+ T-cells showing the highest levels of activation and metabolic activity, conditions known to favor HIV-1 infection. Accordingly, CD4+ T-cells that survived the cytotoxic action of the AAC-11 peptides were resistant to HIV-1 replication. Our results identify a new potential molecular pathway to target HIV-1 infection.
Understanding the CoVID-19 pandemic Curve through statistical approach
Authors: Akhtar Ibrar ul Hassan
Published: April 2020

Current research is an attempt to understand the CoVID-19 pandemic curve through statistical approach of probability density function with associated skewness and kurtosis measures, change point detection and polynomial fitting to estimate infected population along with 30 days projection. The pandemic curve has been explored for above average affected countries, six regions and global scale during 64 days of 22nd January to 24th March, 2020. The global cases infection as well as recovery rate curves remained in the ranged of 0 – 9.89 and 0 – 8.89%, respectively. The confirmed cases probability density curve is high positive skewed and leptokurtic with mean global infected daily population of 6620. The recovered cases showed bimodal positive skewed curve of leptokurtic type with daily recovery of 1708. The change point detection helped to understand the CoVID-19 curve in term of sudden change in term of mean or mean with variance. This pointed out disease curve is consist of three phases and last segment that varies in term of day lengths. The mean with variance based change detection is better in differentiating phases and associated segment length as compared to mean. Global infected population might rise in the range of 0.750 to 4.680 million by 24thApril 2020, depending upon the pandemic curve progress beyond 24th March, 2020. Expected most affected countries will be USA, Italy, China, Spain, Germany, France, Switzerland, Iran and UK with at least infected population of over 0.100 million. Infected population polynomial projection errors remained in the range of −78.8 to 49.0%.
A systematic framework for assessing the clinical impact of polygenic risk scores
Authors: Kulm Scott , Marderstein Andrew , Mezey Jason , Elemento Olivier
Published: April 2020

Risk prediction models provide empirical recommendations that ultimately aim to deliver optimal patient outcomes. Genetic information, in the form of a polygenic risk score (PRS), may be included in these models to significantly increase their accuracy. Several analyses of PRS accuracy have been completed, nearly all focus on only a few diseases and report limited statistics. This narrow approach has limited our ability to assess as a whole whether PRSs can provide actionable disease predictions. This investigation aims to address this uncertainty by comprehensively analyzing 23 diseases within the UK Biobank. Our results show that including the PRS to a base model containing age, sex and the top ten genetic principal components significantly improves prediction accuracy, as measured by ROC curves, in a majority 21 of 23 diseases and reclassifies on average 68% of the individuals in the top 5% risk group. For heart failure, breast cancer, prostate cancer and gout, decision curve analyses using the 5% risk threshold determined that including the PRS in the base model would correctly identity at least 60 more individuals who develop the disease for every 1000 individuals screened, without making any incorrect predictions. Analyses that included disease-specific risk factors, such as Body-Mass Index, and consider time of disease onset found similar PRS benefits. The improved prediction accuracy was translated to 10 instances in which medications/supplements and 94 instances in which lifestyle modifications lead to significantly greater reduction in disease risk for individuals in the top PRS quintile compared to the bottom PRS quintile. Finally we provide guidance for tailored, future PRS generation by comprehensively ranking methods that generate PRS weights and identifying genome wide association study characteristics that influence PRS predictions. The unification of significantly enhanced disease predictions, novel risk mitigation opportunities and improved methodological clarity indicate that PRSs carry far greater clinical impact than previously known.
Metagenomic evidence for a polymicrobial signature of sepsis
Authors: Tan Cedric Chih Shen , Acman Mislav , van Dorp Lucy , Balloux Francois
Published: April 2020

Our understanding of the host component of sepsis has made significant progress. However, detailed study of the microorganisms causing sepsis, either as single pathogens or microbial assemblages, has received far less attention. Metagenomic data offer opportunities to characterise the microbial communities found in septic and healthy individuals. In this study we apply gradient-boosted tree classifiers and a novel computational decontamination technique built upon SHapley Additive exPlanations (SHAP) to identify microbial hallmarks which discriminate blood metagenomic samples of septic patients from that of healthy individuals. Classifiers had high performance when using the read assignments to microbial genera (AUROC = 0.995), including after removal of species ‘confirmed’ as the cause of sepsis through clinical testing (AUROC = 0.915). Models trained on single genera were inferior to those employing a polymicrobial model and we identified multiple co-occurring bacterial genera absent from healthy controls.

Importance

While prevailing diagnostic paradigms seek to identify single pathogens, our results point to the involvement of a polymicrobial community in sepsis. We demonstrate the importance of the microbial component in characterising sepsis, which may offer new biological insights into the aetiology of sepsis and allow the development of clinical diagnostic or even prognostic tools.
Crystal structure of full-length cytotoxic necrotizing factor CNFYreveals molecular building blocks for intoxication
Authors: Chaoprasid Paweena , Lukat Peer , Mühlen Sabrina , Heidler Thomas , Gazdag Emerich-Mihai , Dong Shuangshuang , Bi Wenjie , Rüter Christian , Kirchenwitz Marco , Steffen Anika , Jänsch Lothar , Stradal Theresia E. B. , Dersch Petra , Blankenfeldt Wulf
Published: April 2020

Cytotoxic necrotizing factors (CNFs) are bacterial single-chain exotoxins that modulate cytokinetic/oncogenic and inflammatory processes through activation of host cell Rho GTPases. To achieve this, they are secreted, bind surface receptors to induce endocytosis and translocate a catalytic unit into the cytosol to intoxicate host cells. A three-dimensional structure that provides insight into the underlying mechanisms is still lacking. Here, we determined the crystal structure of full-lengthYersinia pseudotuberculosisCNFY. CNFYconsists of five domains (D1-D5), and by integrating structural and functional data we demonstrate that D1-3 act as export and translocation module for the catalytic unit (D4-5) or fused β-lactamase reporter proteins. We further found that domain D4, which possesses structural similarity to ADP-ribosyl transferases, but had no equivalent catalytic activity, changed its position to interact extensively with D5 in the crystal structure of the free D4-5 fragment. This liberates D5 from a semi-blocked conformation in full-length CNFY, leading to higher deamidation activity. Finally, sequence comparisons identified the CNF translocation module in many uncharacterized bacterial proteins, suggesting its usability as a universal drug delivery tool.
Applying machine learning in motor activity time series of depressed bipolar and unipolar patients
Authors: Jakobsen Petter , Garcia-Ceja Enrique , Riegler Michael , Stabell Lena Antonsen , Nordgreen Tine , Torresen Jim , Fasmer Ole Bernt , Oedegaard Ketil Joachim
Published: April 2020

Current practice of assessing mood episodes in affective disorders largely depends on subjective observations combined with semi-structured clinical rating scales. Motor activity is an objective observation of the inner physiological state expressed in behavior patterns. Alterations of motor activity are essential features of bipolar and unipolar depression. The aim was to investigate if objective measures of motor activity can aid existing diagnostic practice, by applying machine-learning techniques to analyze activity patterns in depressed patients and healthy controls. Random Forrest, Deep Neural Network and Convolutional Neural Network algorithms were used to analyze 14 days of actigraph recorded motor activity from 23 depressed patients and 32 healthy controls. Statistical features analyzed in the dataset were mean activity, standard deviation of mean activity and proportion of zero activity. Various techniques to handle data imbalance were applied, and to ensure generalizability and avoid overfitting a Leave-One-User-Out validation strategy was utilized. All outcomes reports as measures of accuracy for binary tests. A Deep Neural Network combined with random oversampling class balancing technique performed a cut above the rest with a true positive rate of 0.82 (sensitivity) and a true negative rate of 0.84 (specificity). Accuracy was 0.84 and the Matthews Correlation Coefficient 0.65. Misclassifications appear related to data overlapping among the classes, so an appropriate future approach will be to compare mood states intra-individualistic. In summary, machine-learning techniques present promising abilities in discriminating between depressed patients and healthy controls in motor activity time series.
On the role of transcription in positioning nucleosomes
Authors: Jiang Zhongling , Zhang Bin
Published: April 2020

Nucleosome positioning is crucial for the genome’s function. Though the role of DNA sequence in positioning nucleosomes is well understood, a unified framework for studying the impact of transcription remains lacking. Using numerical simulations, we investigated the dependence of nucleosome density profiles on transcription level across multiple species. We found that the low nucleosome affinity of yeast, but not mouse, promoters contributes to the formation of phased nucleosomes arrays for inactive genes. For the active genes, a tug-of-war between two types of remodeling enzymes is essential for reproducing their density profiles. In particular, while ISW2 related enzymes are known to position the +1 nucleosome and align it toward the transcription start site (TSS), enzymes such as ISW1 that use a pair of nucleosomes as their substrate can shift the nucleosome array away from the TSS. Competition between these enzymes results in two types of nucleosome density profiles with well- and ill-positioned +1 nucleosome. Finally, we showed that Pol II assisted histone exchange, if occurring at a fast speed, can abolish the impact of remodeling enzymes. By elucidating the role of individual factors, our study reconciles the seemingly conflicting results on the overall impact of transcription in positioning nucleosomes across species.
A cryptic tubulin-binding domain links MEKK1 to microtubule remodelling
Authors: Filipčík Pavel , Latham Sharissa L. , Cadell Antonia L. , Day Catherine L. , Croucher David R. , Mace Peter D.
Published: April 2020

The MEKK1 protein is a pivotal kinase activator of responses to cellular stress. Activation of MEKK1 can trigger various responses, including mitogen activated protein (MAP) kinases, NF-κB signalling, or cell migration. Notably, MEKK1 activity is triggered by microtubule-targeting chemotherapies, amongst other stressors. Here we show that MEKK1 contains a previously unidentified tumour overexpressed gene (TOG) domain. The MEKK1 TOG domain binds to tubulin heterodimers—a canonical function of TOG domains—but is unusual in that it appears alone rather than as part of a multi-TOG array, and has structural features distinct from previously characterised TOG domains. MEKK1 TOG demonstrates a clear preference for binding curved tubulin heterodimers, which exist in soluble tubulin and at sites of microtubule polymerisation and depolymerisation. Mutations disrupting tubulin-binding lead to destabilisation of the MEKK1 protein in cells, and ultimately a decrease in microtubule density at the leading edge of polarised cells. We also show that MEKK1 mutations at the tubulin-binding interface of the TOG domain recur in patient derived tumour sequences, suggesting selective enrichment of tumour cells with disrupted MEKK1–microtubule association. Together, these findings provide a direct link between the MEKK1 protein and tubulin, which is likely to be relevant to cancer cell migration and response to microtubule-modulating therapies.

SIGNIFICANCE STATEMENT

The protein kinase MEKK1 activates stress response pathways in response to various cellular stressors, including chemotherapies that disrupt dynamics of the tubulin cytoskeleton. Filipčík et al., show that MEKK1 contains a previously uncharacterised domain that can preferentially bind to the curved tubulin heterodimer—which is found at sites of microtubule assembly and disassembly. Mutations that interfere with MEKK1-tubulin binding disrupt microtubule networks in migrating cells and are enriched in patient-derived tumour sequences. These results suggest that MEKK1-tubulin binding may be relevant to cancer progression, and the efficacy of microtubule-disrupting chemotherapies that require the activity of MEKK1.
A one-dimensional manganese(III)–porphyrin coordination polymer: crystal structure and photophysical properties
Authors: Chen Wen-Tong
Published: April 2020

A novel manganese(III)–porphyrin complex, namely, catena-poly[[chloridomanganese(III)]-μ2-5,10,15,20-tetrakis(pyridin-3-yl)-21H,23H-porphinato(2−)-κ5
N
21,N
22,N
23,N
24:N
5], [MnCl(C40H24N8)]
n
, 1, was prepared by the hydrothermal reaction of manganese chloride with 5,10,15,20-tetrakis(pyridin-3-yl)-21H,23H-porphine. The crystal structure was determined by single-crystal X-ray diffraction. The porphyrin macrocycle exhibits a saddle-like distortion geometry. The MnIII atom has a six-coordination geometry. Each porphyrin unit links to two neighbouring units to yield a one-dimensional coordination polymer. These chains are further interlinked by hydrogen bonds to form a two-dimensional network. The complex shows red photoluminescence emission bands in ethanol solution, which can be attributed to ligand-to-ligand charge transfer (LLCT) accompanied by partial metal-to-ligand charge transfer (MLCT), as revealed by TDDFT calculations.
How social exclusion and temporal distance influence product choices: the role of coping strategies
Authors: Xu Wei , Jin XiaoTong
Published: April 2020

Purpose

We examine how social exclusion and temporal distance (i.e. being socially excluded in the present or the anticipation of exclusion in the future) shape whether people choose hedonic or utilitarian products.

Design/methodology/approach

We conduct four experiments to test the hypotheses. Study 1a and study 1b provide the initial evidence that consumers strategically engage in differentiation in response to social exclusion in the present and in the future. Study 2 and study 3 replicate the basic interaction effect of social exclusion and temporal distance on product choices and test the underlying mechanism.

Findings

We find that temporal distance affects consumer product choices through people’s coping strategies. When consumers are socially excluded, they are more likely to have a problem-solving tendency and more likely to choose utilitarian products. In contrast, when consumers imagine being socially excluded in the future, they are more likely to have to use emotions to solve problems and choose hedonic products.

Originality/value

Our study contributes to the literature in several ways. First, it deepens our understanding of the psychological drivers of social exclusion in consumer research. Second, it offers insights into understanding prior findings that document both problem-solving and emotion-regulating behavior in response to social exclusion. Third, by showing that social exclusion and temporal distance can influence the type of products selected, our findings contribute to a new stream of work that examines the impact of people’s fundamental desire for control on consumer behavior.
Financing needs of micro-enterprises along their evolution
Authors: Prijadi Ruslan , Wulandari Permata , Desiana Putri Mega , Pinagara Fajar Ayu , Novita Maya
Published: April 2020

Purpose

The purpose of this paper aims to investigate micro enterprises financing in Indonesia and examines how this financing differs, depending on the enterprise’s development stage. This research also identifies some structural problems related to micro-financing and provides workable solutions.

Design/methodology/approach

This research uses the entrepreneurial network model of Schutjens and Stam (2003) to examine how Indonesian micro and small enterprises (MSEs) evolve even before they become regular small businesses. Content analysis is used on 10 micro-enterprises from Jakarta, the capital city of Indonesia and its surroundings. Financing issues at each stage of enterprise development are identified and deeply examined.

Findings

This research not only confirms the significant financing problems micro-enterprises face but also clarifies that these problems are unique to each stage of the MSEs’ development. One insight is that most micro-enterprises do not use funding from formal institutions. That is, business owners rely more on funding from non-formal institutions. This is because these enterprises’ managers generally cannot prepare loans application and/or they are lack of knowledge/training on financing matters. They hesitate to borrow from formal financial institutions, as the rates are high but the processing time is longer than those of the loan sharks.

Originality/value

This research contributes to the field of entrepreneurial finance by identifying the structural problems inherent in micro-finance and providing workable solutions for overcoming these problems.
The multi-generation
Authors: Dorie Amy , Loranger David
Published: April 2020

Purpose

The aim of this research is to advance the understanding of multi-channel behaviour in terms of different generational cohorts' usage and spending patterns.

Design/methodology/approach

Building on previous studies on multi-channel behaviour, differences in shopping channel usage and purchase amounts were investigated between baby boomers, Gen X, xennials and millennials.

Findings

There were significant differences found between the generations in terms of multi-channel behaviour regarding purchasing frequency and average purchase amounts via a) mobile phone, b) tablet, c) computer, d) social media and e) brick-and-mortar. Fewer differences were found amongst the generational cohorts in terms of amount spent per channel.

Research limitations/implications

The research was successful in analysing variances in multi-channel behaviour amongst the baby boomer, Generation X, xennial and millennial cohorts, while updating the body of literature to consider generational channel usage of mobile and social media in multi-channel retailing.

Practical implications

Marketers should consider xennials’ channel behaviour and focus on converting sales through integrated programmes based on their channel usage. Retailers should also consider millennials' heavy engagement with social media in their lives but spend lower amounts via the medium, which may be an opportunity to use this medium as a viable stand-alone channel in targeting millennials' shopping dollars.

Originality/value

This study updates the body of research on multi-channel behaviour by considering generation as a factor in channel usage and spend amount.
Coworkers, supervisors and frontline restaurant employees: social judgments and the mediating effects of exhaustion and cynicism
Authors: Bufquin Diego
Published: April 2020

Purpose

The current study assesses the relationships between the social judgments made by frontline restaurant employees toward their direct supervisors and coworkers and employees' cynicism, exhaustion and turnover intentions. The mediating effects of cynicism and exhaustion are also examined.

Design/methodology/approach

The model was tested on 477 frontline restaurant employees using a questionnaire survey. Data were analyzed using descriptive statistics, confirmatory factor analysis and structural equation modeling, which included bootstrapping.

Findings

Results indicate that the aforementioned social judgments significantly decrease frontline restaurant employees' exhaustion and cynicism, which are then positively related to turnover intentions. Furthermore, exhaustion and cynicism mediate the relationships between employees' evaluations of their supervisors and coworkers and turnover intentions.

Originality/value

This study is the first to analyze the effects of warmth, competence and morality – which represent fundamental social traits that people use to evaluate others – on turnover intentions via cynicism and exhaustion.