bluuebunny/crossref_metadata_2025 huggingface dataset:
The Warburg Effect Promotes Mitochondrial Injury Regulated by Uncoupling Protein-2 in Septic Acute Kidney Injury
Authors: Ji Ran , Chen Weiwei , Wang Yuming , Gong Fangchen , Huang Shunwei , Zhong Ming , Liu Zhaojun , Chen Ying , Ma Li , Yang Zhitao , Qu Hongping , Mao Enqiang , Chen Erzhen
Published: June 2020

Background:

Evidence implying that metabolism reprogramming plays an important role in the regulation of sepsis is increasing; however, whether it has a similar role in septic organ dysfunction remains unclear. Here, we provide evidence to support a new role of uncoupling protein-2 (UCP2)-regulated Warburg effect, i.e., aerobic glycolysis, in promoting mitochondrial injury in the kidney.

Methods:

To imitate sepsis condition, male C57BL/6 mice were operated by the cecal ligation puncture in vivo, whereas a normal human kidney cell line (HK-2) was treated with lipopolysaccharide in vitro. UCP2 small interfering RNA pretreatment was performed to knock down UCP2 expression in vitro. The glycolysis metabolite was detected by liquid chromatography/tandem mass spectrometry in vivo and detected by commercial kits in vitro. Oxidative phosphorylation level and glycolysis level were monitored by measuring the oxygen consumption rate (indicative of respiration) and extracellular acidification rate (indicative of glycolysis) in vitro. Exogenous lactate was supplied to stimulate HK-2 cells and indicators of mitochondrial dysfunction were also assessed.

Results:

Aerobic glycolysis is enhanced in septic tubular epithelial cells, and the glycolysis inhibitor 2-deoxyglucose can partially restore mitochondrial membrane potential and decrease the reactive oxygen species production. With the knockdown of UCP2, the aerobic glycolysis level upregulates, and mitochondrial injury increases.

Conclusions:

These results provide insights on a new mechanism of metabolic regulation of mitochondrial injury and the importance of targeting aerobic glycolysis for the treatment of septic acute kidney injury.
Hypnagogic Frontal EEG Bursts in Children: Epileptic or Not?
Authors: Datta Anita N.
Published: June 2020

Purpose:

Various EEG patterns emerge in drowsiness. Intermittent bilateral midfrontal slowing (BFS) and hypnogogic frontal predominant sharply contoured waveforms (HFSC), maximal at (Fz, F3-4, and Fp1-2), are often encountered. These do not meet the criteria for epileptiform discharges. The study objective was to determine the clinical significance of BFS and HFSC.

Methods:

Clinical information of children with BFS (n = 49) and HFSC (n = 99) was compared with control subjects with generalized spike-wave (GSW) discharges (n = 102) and normal EEGs (n = 100).

Results:

HFSC was present in younger children (mean age was 3.5 ± 3.6 years), whereas BFS was present in older children (mean 12.9 ± 4.8 years). Seizures occurred in the normal EEG, BFS, HFSC, and GSW groups, respectively, as follows: 22 (22%), 15 (31%), 42 (43%), and 100 (98%) patients, whereas epilepsy occurred in 17 (17%), 10 (20%), 35 (35%), and 95 (93%) patients. The GSW group had more seizures and epilepsy than the other groups (P < 0.001), but the HFSC group also had more seizures (P < 0.001) and epilepsy (P < 0.003) than the normal EEG group. Seizures and neurodevelopmental and psychiatric comorbidities were similar between the BFS and normal EEG groups. Notably, the HFSC group had more developmental delay than the normal EEG group [33 (33%) versus 18 (18%), P < 0.009] but were similar to the GSW group 22 (22%).

Conclusions:

Bilateral midfrontal slowing and HFSC have had unclear significance. Our results suggest that HFSC may be a marker of increased risk of seizure, epilepsy, and developmental delay as compared to children with normal EEGs and has similar risk of developmental delay to those with GSW.
Internet ‘shellebrity' reflects on origin of rare mirror-image snails
Authors: Davison Angus , Thomas Philippe ,   ‘Jeremy the snail’ citizen scientists
Published: June 2020

While animal bodies are typically bilaterally symmetric on the outside, the internal organs nearly always show an invariant left–right (LR) asymmetry. In comparison, snails are both internally and externally LR asymmetric, outwardly obvious in the shell coiling direction, or chirality. Although some species of snail are naturally variable for chirality, sinistral individuals occur very rarely in most species. The developmental and genetic basis of these rare mirror-imaged individuals remains mysterious. To resolve this issue, the finding of a ‘one in a million' sinistral garden snail called ‘Jeremy' was used to recruit citizen scientists to find further sinistral snails. These snails were then bred together to understand whether their occurrence is due an inherited condition. The combined evidence shows that rare sinistral garden snails are not usually produced due to a major effect maternal Mendelian locus. Instead, they are likely mainly produced by a developmental accident. This finding has relevance to understanding the common factors that define cellular and organismal LR asymmetry, and the origin of rare reversed individuals in other animal groups that exhibit nearly invariant LR asymmetry.
Examining the mechanisms underlying the acquisition of animal tool behaviour
Authors: Bandini Elisa , Motes-Rodrigo Alba , Steele Matthew P. , Rutz Christian , Tennie Claudio
Published: June 2020

Despite major advances in the study of animal tool behaviour, researchers continue to debate how exactly certain behaviours are acquired. While specific mechanisms, such as genetic predispositions or action copying, are sometimes suspected to play a major role in behavioural acquisition, controlled experiments are required to provide conclusive evidence. In this opinion piece, we refer to classic ethological methodologies to emphasize the need for studying the relative contributions of different factors to the emergence of specific tool behaviours. We describe a methodology, consisting of a carefully staged series of baseline and social-learning conditions, that enables us to tease apart the roles of different mechanisms in the development of behavioural repertoires. Experiments employing our proposed methodology will not only advance our understanding of animal learning and culture, but as a result, will also help inform hypotheses about human cognitive, cultural and technological evolution. More generally, our conceptual framework is suitable for guiding the detailed investigation of other seemingly complex animal behaviours.
Predictability of food supply modulates nocturnal hypothermia in a small passerine
Authors: Nilsson Johan F. , Nilsson Jan-Åke , Broggi Juli , Watson Hannah
Published: June 2020

The combination of short days and long cold winter nights, in temperate regions, presents a major challenge for small diurnal birds. Small birds regularly employ heterothermy and enter rest-phase hypothermia during winter nights to conserve energy. However, we know little about how environmental conditions, such as food availability, shape these strategies. We experimentally manipulated food availability in winter to free-living great titsParus major. A ‘predictable' and constant food supply was provided to birds in one area of a forest, while birds in another area did not have access to a reliable supplementary food source. We found that predictability of food affected the extent of nocturnal hypothermia, but the response differed between the sexes. Whereas male nocturnal body temperature was similar regardless of food availability, females exposed to a naturally ‘unpredictable' food supply entered deeper hypothermia at night, compared with females that had access to predictable food and compared with males in both treatment groups. We suggest that this response is likely a consequence of dominance, and subdominant females subject to unpredictable food resources cannot maintain sufficient energy intake, resulting in a higher demand for energy conservation at night.
Patterns of mtDNA introgression suggest population replacement in Palaearctic whiskered bat species
Authors: Çoraman Emrah , Dundarova Heliana , Dietz Christian , Mayer Frieder
Published: June 2020

Secondary contacts can play a major role in the evolutionary histories of species. Various taxa diverge in allopatry and later on come into secondary contact during range expansions. When they meet, their interactions and the extent of gene flow depend on the level of their ecological differentiation and the strength of their reproductive isolation. In this study, we present the multilocus phylogeography of two cryptic whiskered bat species,Myotis mystacinusandM. davidii, with a particular focus on their putative sympatric zone. Our findings suggest thatM. mystacinusandM. davidiievolved in allopatry and came into secondary contact during range expansions. Individuals in the area of secondary contact, in Anatolia and the Balkans, have discordant population assignments based on the mitochondrial and the nuclear datasets. These observed patterns suggest that the localM. mystacinuspopulations hybridized with expandingM. davidiipopulations, which resulted in mitochondrial introgression from the former. In the introgression area,M. mystacinusindividuals with concordant nuclear and mitochondrial genotypes were identified in relatively few locations, suggesting that the indigenous populations might have been largely replaced by invadingM. davidii. Changing environmental conditions coupled with ecological competition is the likely reason for this replacement. Our study presents one possible example of a historical population replacement that was captured in phylogeographic patterns.
A miniature Ordovician hurdiid from Wales demonstrates the adaptability of Radiodonta
Authors: Pates Stephen , Botting Joseph P. , McCobb Lucy M. E. , Muir Lucy A.
Published: June 2020

Originally considered as large, solely Cambrian apex predators, Radiodonta—a clade of stem-group euarthropods includingAnomalocaris—now comprises a diverse group of predators, sediment sifters and filter feeders. These animals are only known from deposits preserving non-biomineralized material, with radiodonts often the first and/or only taxa known from such deposits. Despite the widespread and diverse nature of the group, only a handful of radiodonts are known from post-Cambrian deposits, and all originate from deposits or localities rich in other total-group euarthropods. In this contribution, we describe the first radiodont from the UK, an isolated hurdiid frontal appendage from the Tremadocian (Lower Ordovician) Dol-cyn-Afon Formation, Wales, UK. This finding is unusual in two major aspects: firstly, the appendage (1.8 mm in size) is less than half the size of the next smallest radiodont frontal appendage known, and probably belonged to an animal between 6 and 15 mm in length; secondly, it was discovered in the sponge-dominated Afon Gam Biota, one of only a handful of non-biomineralized total-group euarthropods known from this deposit. This Welsh hurdiid breaks new ground for Radiodonta in terms of both its small size and sponge-dominated habitat. This occurrence demonstrates the adaptability of the group in response to the partitioning of ecosystems and environments in the late Cambrian and Early Ordovician world.
On effective criterion of stability of partial indices for matrix polynomials
Authors: Adukova N. V. , Adukov V. M.
Published: June 2020

In the work, we obtain an effective criterion of the stability of the partial indices for matrix polynomials under an arbitrary sufficiently small perturbation. Verification of the stability is reduced to calculation of the ranks for two explicitly defined Toeplitz matrices. Furthermore, we define a notion of the stability of the partial indices in the given class of matrix functions. This means that we will consider an allowable small perturbation such that a perturbed matrix function belong to the same class as the original one. We prove that in the class of matrix polynomials the Gohberg–Krein–Bojarsky criterion is preserved, i.e. new stability cases do not arise. Our proof of the stability criterion in this class does not use the Gohberg–Krein–Bojarsky theorem.
Annular and circular rigid inclusions planted into a penny-shaped crack and factorization of triangular matrices
Authors: Antipov Y. A. , Mkhitaryan S. M.
Published: June 2020

Analytical solutions to two axisymmetric problems of a penny-shaped crack when an annulus-shaped (model 1) or a disc-shaped (model 2) rigid inclusion of arbitrary profile are embedded into the crack are derived. The problems are governed by integral equations with the Weber–Sonine kernel on two segments. By the Mellin convolution theorem, the integral equations associated with models 1 and 2 reduce to vector Riemann–Hilbert problems with 3 × 3 and 2 × 2 triangular matrix coefficients whose entries consist of meromorphic and plus or minus infinite indices exponential functions. Canonical matrices of factorization are derived and the partial indices are computed. Exact representation formulae for the normal stress, the stress intensity factors (SIFs) at the crack and inclusion edges, and the normal displacement are obtained and the results of numerical tests are reported. In addition, simple asymptotic formulae for the SIFs are derived.
DCDC2READ1 regulatory element: how temporal processing differences may shape language
Authors: Tang Kevin , DeMille Mellissa M. C. , Frijters Jan C. , Gruen Jeffrey R.
Published: June 2020

Classic linguistic theory ascribes language change and diversity to population migrations, conquests, and geographical isolation, with the assumption that human populations have equivalent language processing abilities. We hypothesize that spectral and temporal characteristics make some consonant manners vulnerable to differences in temporal precision associated with specific population allele frequencies. To test this hypothesis, we modelled association between RU1-1 alleles ofDCDC2and manner of articulation in 51 populations spanning five continents, and adjusting for geographical proximity, and genetic and linguistic relatedness. RU1-1 alleles, acting through increased expression ofDCDC2, appear to increase auditory processing precision that enhances stop-consonant discrimination, favouring retention in some populations and loss by others. These findings enhance classical linguistic theories by adding a genetic dimension, which until recently, has not been considered to be a significant catalyst for language change.
Below the canopy: global trends in forest vertebrate populations and their drivers
Authors: Green Elizabeth J. , McRae Louise , Freeman Robin , Harfoot Mike B. J. , Hill Samantha L. L. , Baldwin-Cantello William , Simonson William D.
Published: June 2020

Global forest assessments use forest area as an indicator of biodiversity status, which may mask below-canopy pressures driving forest biodiversity loss and ‘empty forest’ syndrome. The status of forest biodiversity is important not only for species conservation but also because species loss can have consequences for forest health and carbon storage. We aimed to develop a global indicator of forest specialist vertebrate populations to improve assessments of forest biodiversity status. Using the Living Planet Index methodology, we developed a weighted composite Forest Specialist Index for the period 1970–2014. We then investigated potential correlates of forest vertebrate population change. We analysed the relationship between the average rate of change of forest vertebrate populations and satellite-derived tree cover trends, as well as other pressures. On average, forest vertebrate populations declined by 53% between 1970 and 2014. We found little evidence of a consistent global effect of tree cover change on forest vertebrate populations, but a significant negative effect of exploitation threat on forest specialists. In conclusion, we found that the forest area is a poor indicator of forest biodiversity status. For forest biodiversity to recover, conservation management needs to be informed by monitoring all threats to vertebrates, including those below the canopy.
Biotic stability mechanisms in Inner Mongolian grassland
Authors: Wang Yonghui , Niu Xiaxia , Zhao Liqing , Liang Cunzhu , Miao Bailing , Zhang Qing , Zhang Jinghui , Schmid Bernhard , Ma Wenhong
Published: June 2020

Biotic mechanisms associated with species diversity are expected to stabilize communities in theoretical and experimental studies but may be difficult to detect in natural communities exposed to large environmental variation. We investigated biotic stability mechanisms in a multi-site study across Inner Mongolian grassland characterized by large spatial variations in species richness and composition and temporal fluctuations in precipitation. We used a new additive-partitioning method to separate species synchrony and population dynamics within communities into different species-abundance groups. Community stability was independent of species richness but was regulated by species synchrony and population dynamics, especially of abundant species. Precipitation fluctuations synchronized population dynamics within communities, reducing their stability. Our results indicate generality of biotic stability mechanisms in natural ecosystems and suggest that for accurate predictions of community stability in changing environments uneven species composition should be considered by partitioning stabilizing mechanisms into different species-abundance groups.
Rapid generation of rotavirus single-gene reassortants by means of eleven plasmid-only based reverse genetics
Authors: Fukuda Saori , Hatazawa Riona , Kawamura Yoshiki , Yoshikawa Tetsushi , Murata Takayuki , Taniguchi Koki , Komoto Satoshi
Published: June 2020

Reassortment is an important mechanism in the evolution of group A rotaviruses (RVAs), yielding viruses with novel genetic and phenotypic traits. The classical methods for generating RVA reassortants with the desired genetic combinations are laborious and time-consuming because of the screening and selection processes required to isolate a desired reassortant. Taking advantage of a recently developed RVA reverse genetics system based on just 11 cloned cDNAs encoding the RVA genome (11 plasmid-only system), we prepared a panel of simian SA11-L2 virus-based single-gene reassortants, each containing 1 segment derived from human KU virus of the G1P[8] genotype. It was shown that there was no gene-specific restriction of the reassortment potential. In addition to these 11 single-gene reassortants, a triple-gene reassortant with KU-derived core-encoding VP1–3 gene segments with the SA11-L2 genetic background, which make up a virion composed of the KU-based core, and SA11-L2-based intermediate and outer layers, could also be prepared with the 11 plasmid-only system. Finally, for possible clinical application of this system, we generated a series of VP7 reassortants representing all the major human RVA G genotypes (G1–4, G9 and G12) efficiently. The preparation of each of these single-gene reassortants was achieved within just 2 weeks. Our results demonstrate that the 11 plasmid-only system allows the rapid and reliable generation of RVA single-gene reassortants, which will be useful for basic research and clinical applications.
Role of the unique, non-essential phosphatidylglycerol::prolipoprotein diacylglyceryl transferase (Lgt) in Corynebacterium glutamicum
Authors: Dautin Nathalie , Argentini Manuela , Mohiman Niloofar , Labarre Cécile , Cornu David , Sago Laila , Chami Mohamed , Dietrich Christiane , de Sousa d’Auria Célia , Houssin Christine , Masi Muriel , Salmeron Christophe , Bayan Nicolas
Published: June 2020

Bacterial lipoproteins are secreted proteins that are post-translationally lipidated. Following synthesis, preprolipoproteins are transported through the cytoplasmic membrane via the Sec or Tat translocon. As they exit the transport machinery, they are recognized by a phosphatidylglycerol::prolipoprotein diacylglyceryl transferase (Lgt), which converts them to prolipoproteins by adding a diacylglyceryl group to the sulfhydryl side chain of the invariant Cys+1residue. Lipoprotein signal peptidase (LspA or signal peptidase II) subsequently cleaves the signal peptide, liberating the α-amino group of Cys+1, which can eventually be further modified. Here, we identified thelgtandlspAgenes fromCorynebacterium glutamicumand found that they are unique but not essential. We found that Lgt is necessary for the acylation and membrane anchoring of two model lipoproteins expressed in this species: MusE, aC. glutamicummaltose-binding lipoprotein, and LppX, aMycobacterium tuberculosislipoprotein. However, Lgt is not required for these proteins’ signal peptide cleavage, or for LppX glycosylation. Taken together, these data show that inC. glutamicumthe association of some lipoproteins with membranes through the covalent attachment of a lipid moiety is not essential for further post-translational modification.
Calibrating an Epidemic Compartment Model to Seroprevalence Survey Data
Authors: Halem Michael
Published: June 2020

To date, the Covid-19 epidemic has produced tremendous cost and harm. However, to date, many epidemic models are not calibrated to seroprevalence survey(s). This paper calibrates a relatively simple, SIR plus confirmed cases (“SIRX”) model against seroprevalence survey data released by the State of New York. The intention of this paper is to demonstrate a potentially new technique of calibration for epidemic models used by scientists, public health officials and governments. The technique can then be incorporated in other more complex models. Open source code is included to assist model developers.
Smoking behaviour in Swiss schoolchildren: the LuftiBus in the school survey
Authors: Mozun Rebeca , Ardura-Garcia Cristina , de Jong Carmen C. M. , Goutaki Myrofora , Usemann Jakob , Singer Florian , Latzin Philipp , Kuehni Claudia E. , Moeller Alexander
Published: June 2020

Background

Smoking is a major preventable cause of morbidity and mortality. We assessed smoking behaviour in 6-17-year-olds. In 13-17-year-olds, we studied risk factors for smoking and compared the frequency of respiratory problems between those who smoked and those who did not.

Methods

We used data from LuftiBus in the school, a school-based survey of the respiratory health of children carried out 2013-2016 in the canton of Zurich, Switzerland. Participants were asked about cigarette, shisha, and electronic smoking device (ESD) smoking, and respiratory symptoms and diseases. We studied the association between smoking and risk factors using logistic regression.

Results

We included 3488 schoolchildren with data on active smoking. Five percent of the 6-12-year-olds (90 of 1905) had smoked occasionally (<once/week). Among 13-17-year-olds (N=1583), 563 (36%) had smoked occasionally of whom 414 smoked ESDs, 409 shishas, and 276 cigarettes. Among 54 (3%) 13-17-year-olds who smoked frequently (≥once/week), 41 (76%) smoked cigarettes, and 22% of 15-17-year-olds (104/477) had smoked all three products. Smoking was more common in adolescents who were male, lived in rural areas, and whose mother (adjusted OR 1.7, 95% CI 1.3 - 2.3) or father (aOR 1.5, 95% CI 1.2 – 1.9) smoked. Respiratory symptoms in the past year such as rhinitis, dyspnoea, and wheeze were more common in adolescents who smoked frequently or occasionally than in never smokers.

Conclusion

Smoking of shishas and ESDs is popular among Swiss adolescents and often combined with smoking cigarettes. Structural smoking prevention strategies should include all forms of smoking including shishas and ESDs.
Modelling oral adrenal cortisol support
Authors: Smith David J. , Prete Alessandro , Taylor Angela E. , Karavitaki Niki , Arlt Wiebke
Published: June 2020

A simplified mathematical model of oral hydrocortisone delivery in adrenal insufficiency is described; the model is based on three components (gastric hydrocortisone, free serum cortisol and bound serum cortisol) and is formulated in terms of linear kinetics, taking into account the dynamics of glucocorticoid–protein binding. Motivated by the need to optimise cortisol replacement in the situations of COVID-19 infection, the model is fitted to recently-published data on 50 mg dosing and earlier data on 10 mg dosing. The fitted model is used to predict typical responses to standard dosing regimes, which involve a larger dose in the morning and 1 or 2 smaller doses later in the day, and the same regimes with doses doubled. In all cases there is a circadian-like response, with early morning nadir. The model is also used to consider an alternative dosing strategy based on four equal and equally-spaced doses of 10, 20 or 30 mg per 24 h, resulting in a more even response resembling a response to sustained inflammatory stress.
SIR-PID: A Proportional-Integral-Derivative Controller for COVID-19 Outbreak Containment
Authors: Ianni Aldo , Rossi Nicola
Published: June 2020

Ongoing social restrictions, as distancing and lockdown, adopted by many countries for contrasting the COVID-19 epidemic spread, try to find a trade-off between induced economic crisis, healthcare system collapse and costs in terms of human lives. Applying and removing restrictions on a system with uncontrollable inertia, as represented by an epidemic outbreak, may create critical instabilities, overshoots and strong oscillations of infected people around the desirable set-point, defined as the maximum number of hospitalizations acceptable by a given healthcare system. A good understanding of the system reaction to a change of the input control variable can be reasonably achieved using a proportional-integral-derivative controller, widely used in technological applications. In this paper we make use of this basic control theory for understanding the reaction of COVID-19 propagation to social restrictions and for exploiting a very known technology to reduce the epidemic damages through the correct tuning of the containment policy.
Application of a novel analytical pipeline for high-dimensional multivariate mediation analysis of environmental data
Authors: Aung Max T. , Song Yanyi , Ferguson Kelly K. , Cantonwine David E. , Zeng Lixia , McElrath Thomas F. , Pennathur Subramaniam , Meeker John D. , Mukherjee Bhramar
Published: June 2020

Diverse toxicological mechanisms may mediate the impact of environmental toxicants (phthalates, phenols, polycyclic aromatic hydrocarbons, and metals) on pregnancy outcomes. In this study we introduce an analytical pipeline for high-dimensional mediation analysis to identify mediation pathways (q = 63 mediators) in the relationship between environmental toxicants (p = 38 analytes) and gestational age at delivery. Our analytical pipeline included: (1) conducting pairwise mediation for unique exposure-mediator combinations, (2) subjecting mediators to Bayesian shrinkage mediation analysis and population value decomposition, and (3) exposure dimension reduction by estimating environmental risk scores. Dimension reduction demonstrated that a one unit increase in phthalate risk score was associated with a total effect of 1.09 lower gestational age (in weeks) at delivery (95% confidence interval: 1.78 – 0.36) and eicosanoids from the cytochrome p450 pathway mediated 24.5% of this effect (95% confidence interval: 4%-66%). Eicosanoid products derived from the cytochrome p450 pathway may be important mediators of phthalate toxicity.
The Role of Host Genetic Factors in Coronavirus Susceptibility: Review of Animal and Systematic Review of Human Literature
Authors: LoPresti Marissa , Beck David B. , Duggal Priya , Cummings Derek A. T. , Solomon Benjamin D.
Published: June 2020

Background

The recent SARS-CoV-2 pandemic raises many scientific and clinical questions. One set of questions involves host genetic factors that may affect disease susceptibility and pathogenesis. New work is emerging related to SARS-CoV-2; previous work on other coronaviruses in humans or other host species may be relevant.

Objectives

To review existing literature on host genetic factors and their association with infection and disease with coronaviruses in humans and in other host species.

Methods

We conducted a systematic review of literature on host genetic factors in humans associated with coronavirus outcomes. We also reviewed studies of host genetic factors associated with coronavirus outcomes in non-human species. We categorized articles, summarized themes related to animal studies, and extracted data from human studies for analyses.

Results

We identified 1,187 articles of potential relevance. Forty-five studies examined human host genetic factors related to coronavirus, of which 35 involved analysis of specific genes or loci; aside from one meta-analysis on respiratory infections, all were candidate-driven studies, typically investigating small numbers of research subjects and loci. Multiple significant loci were identified, including 16 related to susceptibility to coronavirus (of which 7 identified protective alleles), and 16 related to outcomes or clinical variables (of which 3 identified protective alleles). The types of cases and controls used varied considerably; four studies used traditional replication/validation cohorts. Of the other studies, 28 involved both human and non-human host genetic factors related to coronavirus, and 174 involved study of non-human (animal) host genetic factors related to coronavirus.

Key findings

We have outlined key genes and loci from animal and human host genetic studies that may bear investigation in the nascent host genetic factor studies of COVID-19. Previous human studies have been limited by relatively low numbers of eligible participants and limited availability of advanced genomic methods. These limitations may be less important to studies of SARS-CoV-2.
Repurposed prophylaxis strategies for COVID-19: a review
Authors: Sallard Erwan , Lescure François-Xavier , Burdet Charles , Guedj Jérémie , Yazdanpanah Yazdan , Peiffer-Smadja Nathan
Published: June 2020

Introduction

Efficient therapeutic strategies are needed to counter the COVID-19 pandemic, caused by the SARSCoV-2 virus. In a context where specific vaccines are not yet available, the containment of the pandemic would be facilitated with efficient prophylaxis.

Methods

We screened several clinical trials repositories and platforms in search of the prophylactic strategies that are investigated against COVID-19 in late April 2020.

Results

Up to April 27, 2020, we found 68 clinical trials targeting medical workers (n = 43, 63%), patients relatives (n = 16, 24%) or individuals at risk of severe COVID-19 (n = 5, 7%). (Hydroxy)chloroquine was the most frequently evaluated treatment (n = 46, 68%), before BCG vaccine (n = 5, 7%). Sixty-one (90%) clinical trials were randomized with a median of planned inclusions of 600 (IQR 255–1515).

Conclusion

The investigated prophylaxis strategies cover both pre- and post-exposure prophylaxis and study numerous immune enhancers and antivirals, although most research efforts are focused on (hydroxy)chloroquine.
Development and Prospective Validation of a Transparent Deep Learning Algorithm for Predicting Need for Mechanical Ventilation
Authors: Shashikumar Supreeth P. , Wardi Gabriel , Paul Paulina , Paul Paulina , Carlile Morgan , Brenner Laura N , Hibbert Kathryn A , North Crystal M. , Mukerji Shibani S. , Robbins Gregory K. , Shao Yu-Ping , Malhotra Atul , Brandon Westover M. , Nemati Shamim
Published: June 2020

IMPORTANCE

Objective and early identification of hospitalized patients, and particularly those with novel coronavirus disease 2019 (COVID-19), who may require mechanical ventilation is of great importance and may aid in delivering timely treatment.

OBJECTIVE

To develop, externally validate and prospectively test a transparent deep learning algorithm for predicting 24 hours in advance the need for mechanical ventilation in hospitalized patients and those with COVID-19.

DESIGN

Observational cohort study

SETTING

Two academic medical centers from January 01, 2016 to December 31, 2019 (Retrospective cohorts) and February 10, 2020 to May 4, 2020 (Prospective cohorts).

PARTICIPANTS

Over 31,000 admissions to the intensive care units (ICUs) at two hospitals. Additionally, 777 patients with COVID-19 patients were used for prospective validation. Patients who were placed on mechanical ventilation within four hours of their admission were excluded.

MAIN OUTCOME(S) and MEASURE(S)

Electronic health record (EHR) data were extracted on an hourly basis, and a set of 40 features were calculated and passed to an interpretable deep-learning algorithm to predict the future need for mechanical ventilation 24 hours in advance. Additionally, commonly used clinical criteria (based on heart rate, oxygen saturation, respiratory rate, FiO2and pH) was used to assess future need for mechanical ventilation. Performance of the algorithms were evaluated using the area under receiver-operating characteristic curve (AUC), sensitivity, specificity and positive predictive value.

RESULTS

After applying exclusion criteria, the external validation cohort included 3,888 general ICU and 402 COVID-19 patients. The performance of the model (AUC) with a 24-hour prediction horizon at the validation site was 0.882 for the general ICU population and 0.918 for patients with COVID-19. In comparison, commonly used clinical criteria and the ROX score achieved AUCs in the range of 0.773 – 0.782 and 0.768 – 0.810 for the general ICU population and patients with COVID-19, respectively.

CONCLUSIONS and RELEVANCE

A generalizable and transparent deep-learning algorithm improves on traditional clinical criteria to predict the need for mechanical ventilation in hospitalized patients, including those with COVID-19. Such an algorithm may help clinicians with optimizing timing of tracheal intubation, better allocation of mechanical ventilation resources and staff, and improve patient care.
Reduction in stroke patients’ referral to the ED in the COVID-19 era: A four-year comparative study
Authors: Mor Saban , Anna Reznik , Tal Shachar , Roten Sivan-Hoffmann
Published: June 2020

Introduction

Current reports indicate that the increased use of social distancing for preventive COID-19 distribution may have a negative effect on patients who suffering from acute medical conditions.

Aim

We examined the effect of social distancing on acute ischemic stroke (AIS) patients’ referral to the emergency department (ED)

Method

A retrospective archive study was conducted between January 2017 and April 2020 in a comprehensive stroke center. We compare the number of neurologic consultations, time from symptoms onset to ED arrival, patients diagnosis with AIS, number of patients receiving treatment (tPA, endovascular thrombectomy (EVT) or combine) and in-hospital death.

Results

The analysis included a total of 14,626 neurological consultations from the years 2017 to 2020. A significant decrease of 58.6% was noted during the months of January-April of the year 2020 compared to the parallel period of 2017. Percent of final AIS diagnosis for the year of 2020 represent 24.8% of suspected cases, with the highest diagnosis rate demarcated for the year of 2019 with 25.6% of confirmed patients. The most remarkable increase was noted in EVT performance through the examined years (2017, n=21; 2018, n=32; 2019, n=42; 2020, n=47).

Conclusion

COVID-19 pandemic resulted in routing constraints on health care system resources that were dedicated for treating COVID-19 patients.

The healthcare system must develop and offer complementary solutions that will enable access to health services even during these difficult times.
Evaluating post-vaccine expansion patterns of pneumococcal serotypes
Authors: Phillips Maile T. , Warren Joshua L. , Givon-Lavi Noga , Tothpal Adrienn , Regev-Yochay Gili , Dagan Ron , Weinberger Daniel M.
Published: June 2020

Streptococcus pneumoniae remains a leading cause of morbidity and mortality. Pneumococcal conjugate vaccines (PCVs) are effective but target only a fraction of the more than 90 pneumococcal serotypes. As a result, the introduction of PCVs has been followed by the emergence of non-vaccine serotypes. With higher-valency PCVs currently under development, there is a need to understand and predict patterns of serotype replacement to anticipate future changes. In this study, we evaluated patterns of change in serotype prevalence post-PCV introduction in Israel. We found that the assumption that non-vaccine serotypes increase by the same proportion overestimates changes in serotype prevalence in Jewish and Bedouin children. Furthermore, pre-vaccine prevalence was positively associated with increases in prevalence over the study period. From our analyses, serotypes 12F, 8, 16F, 33F, 9N, 7B, 10A, 22F, 24F, and 17F were estimated to have gained the most cases of invasive pneumococcal disease through serotype replacement in the Jewish population. However, this model also failed to quantify some additional cases gained, suggesting that changes in carriage in children alone may be insufficient to explain serotype replacement in disease. Understanding of serotype replacement is important as higher-valency vaccines are introduced.
Sensitivity and specificity of prediction models based on gustatory disorders in diagnosing COVID-19 patients: a case-control study
Authors: Adamczyk Kamil , Herman Michał , Frączek Janusz , Piec Robert , Szykuła-Piec Barbara , Zaczyński Artur , Wójtowicz Rafał , Bojanowski Krzysztof , Rusyan Ewa , Król Zbigniew , Wierzba Waldemar , Franek Edward
Published: June 2020

Objective

to quantitatively assess disturbances of sweet, sour and salty and bitter tastes in a group of young, asymptomatic or oligosymptomatic COVID-19 patients; establish a reliable, sensitive and specific test that can diagnose COVID-19 on the basis of taste disorders and publish the results according to STARD 2015 statement (Standards for Reporting Diagnostic Accuracy).

Design

case-control study

Setting

isolated rooms in the Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw (which had been transformed into an infectious hospital) and a dormitory in one of Warsaw universities.

Participants

52 SARS-CoV-2 positive (51 men, mean age 21.7 years) and 36 negative students (34 men, mean age 20.8 years).

Main outcome measures

a gustatory function assessment (sweet, salty, sour and bitter taste), with flavour concentrations established previously in healthy subjects was conducted for all subjects. Each participant received one tasteless reference and nine flavour tablets with sucrose concentrations of 40, 80 and 106.4 mg/ml; NaCl at 13.5, 17 and 27 mg/ml; ascorbic acid at 6.25 and 12.5 mg/ml and grapefruit extract at 40 mg/ml.

Results

the only taste that was impaired significantly more frequently in COVID-19 patients was the sweet taste at the lowest flavour concentration (40 mg/ml, p = 0.002). Different screening and diagnostic models were constructed using the examined variables. The highest accuracy screening test consisted of the positive result of a three-question questionnaire (self-reported loss of taste, self-reported loss of smell, or fever within the last month (positive if at least one present) and/or ageusia of sweet taste at a sucrose concentration of 40 mg/ml. The sensitivity of the model was 94% with a specificity of 55%. The highest accuracy diagnostic test consisted of ageusia of sweet taste at a sucrose concentration of 106.4 mg/ml or/and ageusia of salty taste at an NaCl concentration of 13.5 or 17 mg/ml. The specificity of the test was found to be 100%, and the sensitivity was 34%.

Conclusion

as the most effective way of controlling the present pandemic involves testing the wider population for symptomatic, oligosymptomatic and asymptomatic carriers of SARSCoV-2 and isolating or hospitalising infected subjects, in the present study, an inexpensive, simple, fast and sensitive (94%) screening test that can be used for such a purpose is proposed. In addition, a specific (100%) diagnostic test that could be used to refer patients to quarantine in the case of limited availability of genetic or serological tests is proposed.
Meta-analysis of several epidemic characteristics of COVID-19
Authors: Zhang Panpan , Wang Tiandong , Xie Sharon X.
Published: June 2020

As the COVID-19 pandemic has strongly disrupted people’s daily work and life, a great amount of scientific research has been conducted to understand the key characteristics of this new epidemic. In this manuscript, we focus on four crucial epidemic metrics with regard to the COVID-19, namely the basic reproduction number, the incubation period, the serial interval and the epidemic doubling time. We collect relevant studies based on the COVID-19 data in China and conduct a meta-analysis to obtain pooled estimates on the four metrics. From the summary results, we conclude that the COVID-19 has stronger transmissibility than SARS, implying that stringent public health strategies are necessary.
Hospital readmissions of discharged patients with COVID-19
Authors: Ramírez Lina Marcela Parra , Caballero Mireia Cantero , de la Torre Ignacio Morrás , Plaza Alberto Vallejo , Yagüe Itziar Diego , Tejero Elena Jimenez , Rubio Elena Múñez , Asensio Ángel , Cruz Ana Fernández , Martínez Antonio Ramos
Published: June 2020

Background

COVID-19 infection has led to an overwhelming effort by health institutions to meet the high demand for hospital admissions.

Aim

To analyse the clinical variables associated with readmission of patients who had previously been discharged after admission for COVID-19.

Design and methods

We studied a retrospective cohort of patients with laboratory-confirmed SARS-CoV-2 infection who were admitted and subsequently discharged alive. We then conducted a nested case-control study paired (1:1 ratio) by age, sex and period of admission.

Results

Out of 1368 patients who were discharged during the study period, 61 patients (4.4%) were readmitted. Immunocompromised patients were at increased risk for readmission. There was also a trend towards a higher probability of readmission in hypertensive patients (p=0.07). Cases had had a shorter hospital stay and a higher prevalence of fever during the 48 hours prior to discharge. There were no significant differences in oxygen levels measured at admission and discharge by pulse oximetry intra-subject or between the groups. Neutrophil/lymphocyte ratio at hospital admission tended to be higher in cases than in controls (p=0.06). The motive for readmission in 10 patients (16.4%), was a thrombotic event in venous or arterial territory (p<0.001). Neither glucocorticoids nor anticoagulants prescribed at hospital discharge were associated with a lower readmission rate.

Conclusions

The rate of readmission after discharge from hospital for COVID-19 was low. Immunocompromised patients and those presenting with fever during the 48 hours prior to discharge are at greater risk of readmission to hospital.
COVID-19 trend in Bangladesh: deviation from epidemiological model and critical analysis of the possible factors
Authors: Ahmed Asif , Rahman Mohammad Mahmudur
Published: June 2020

Background

Since its first report on March 08, COVID-19 positive cases and number of deaths are increasing in Bangladesh. In the first month of COVID-19 infection, incidence of daily positive cases did follow the susceptible, infected and recovered (SIR) based predictions we reported in April, but started to deviate in the following months. COVID-19 transmission and disease progression depends on multifaceted determinants e.g. viral genetics, host immunity, social distancing, co-morbidity, socio-demographic and environmental parameters. Therefore deviation in confirmed cases from predicted model may appear and warrant thorough investigation.

Methods

In this short report, we compared real data with SIR model and analyzed the possible factors associated with the deviation which included preventive intervention strategies, socioeconomic capabilities, climatic and meteorological indexes, acquired immunity of Bangladeshi population, demographic characteristics, health indicators and food habits.

Results

The key factor responsible for the observed deviation was found to be the number of tests performed. Having population with low median age, young age groups are being mostly infected. Low prevalence of non-communicable diseases among them and strong immunity compared to the elderly might have kept most of them asymptomatic with silent recovery. Warm temperature, humidity and UV index of Bangladesh during this summer period might have contributed to the slow progression of infection. Longer daylight mediated immunity, fresh air circulations and ventilation, less population density in rural areas and certain food habits perhaps helped the large number of populations to restrict the infection up to a level.

Conclusion

Despite all these helpful determinants in Bangladesh, person to person contact is still the leading risk factor for COVID-19 transmission. Infection may increase rapidly if safe distance and preventive measures are not strictly followed while resuming the normal social and work life. Expanding test capacity, strong collaborative action plans, strategies and implementation are needed immediately to prevent catastrophe.

Highlights

Limited number of tests compared to large population was the key reason for possible low daily positive cases reported in Bangladesh.

Controlled interventions viz. official leave; transport ban and social distancing had helped initially to slow down the transmission.

Warm weather, high humidity and UV index, sunlight mediated immunity, fresh air circulations, low pollutions, food habit and heterologous immunity might have reduced the transmission capabilities of SARS-CoV-2.

Having large number of young people with strong immunity might have kept most of the infected asymptomatic who recovered silently.

Person to person contact still remain as key risk factor in COVID-19 transmission, so strict health measures should be in place even after reopening social activities to contain further transmission.
High-throughput Screening with Pluripotent Stem Cells Identifies CUDC-907 as an Effective Compound for Restoring the Proinflammatory Phenotype of Nakajo-Nishimura Syndrome
Authors: Kase Naoya , Terashima Madoka , Ohta Akira , Niwa Akira , Honda-Ozaki Fumiko , Kawasaki Yuri , Nakahata Tatsutoshi , Kanazawa Nobuo , Saito Megumu K.
Published: June 2020

Nakajo-Nishimura syndrome (NNS) is an autoinflammatory disorder caused by a homozygous mutations inPSMB8gene. The administration of systemic corticosteroids is partially effective, but continuous treatment causes severe side effects. We previously established a pluripotent stem cell (PSC)-derived NNS disease model that reproduces several inflammatory phenotypes including the overproduction of monocyte chemoattractant protein-1 (MCP-1) and interferon gamma-induced protein-10 (IP-10). Here we performed high-throughput compound screening (HTS) using this PSC-derived NNS model to find potential therapeutic candidates and identified CUDC-907 as an effective inhibitor of the release of MCP-1 and IP-10. CUDC-907 did not induce cell death within therapeutic concentrations and was also effective on primary patient cells. Further analysis indicated that the inhibitory effect was post-transcriptional. These findings suggest that HTS with PSC-derived disease models is useful for finding drug candidates for autoinflammatory diseases.

Significance statement

In this study, we identified a histone deacetylase inhibitor CUDC-907 as a potential effective compound for ameliorating overproduction of inflammatory chemokines in an autoinflammatory disease named Nakajo-Nishimura syndrome. We performed high-throughput screening using pluripotent stem cell-derived monocytic cell lines. Our data prove the validity of screening system as a versatile platform for seeking candidate compounds for the treatment of congenital immunological disorders associated with monocytic lineage cells.