bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of an interactive, agent-based local stochastic model of COVID-19 transmission and evaluation of mitigation strategies illustrated for the state of Massachusetts, USA
Authors: Kirpich Alexander , Koniukhovskii Vladimir , Shvartc Vladimir , Skums Pavel , Weppelmann Thomas A. , Imyanitov Evgeny , Semyonov Semyon , Barsukov Konstantin , Gankin Yuriy
Published: May 2020

Since its discovery in the Hubei province of China, the global spread of the novel coronavirus SARS-CoV-2 has resulted in millions of COVID-19 cases and hundreds of thousands of deaths. The spread throughout Asia, Europe, and the Americas has presented one of the greatest infectious disease threats in recent history and has tested the capacity of global health infrastructures. Since no effective vaccine is available, isolation techniques to prevent infection such as home quarantine and social distancing while in public have remained the cornerstone of public health interventions. While government and health officials were charged with implementing stay-at-home strategies, many of which had little guidance as to the consequences of how quickly to begin them. Moreover, as the local epidemic curves have been flattened, the same officials must wrestle with when to ease or cease such restrictions as to not impose economic turmoil. To evaluate the effects of quarantine strategies during the initial epidemic, an agent based modeling framework was created to take into account local spread based on geographic and population data with a corresponding interactive desktop and web-based application. Using the state of Massachusetts in the United States of America, we have illustrated the consequences of implementing quarantines at different time points after the initial seeding of the state with COVID-19 cases. Furthermore, we suggest that this application can be adapted to other states, small countries, or regions within a country to provide decision makers with critical information necessary to best protect human health.
Pathophysiological regulation of lung function by the free fatty acid receptor FFA4
Authors: Prihandoko Rudi , Kaur Davinder , Wiegman Coen H. , Alvarez-Curto Elisa , Donovan Chantal , Chachi Latifa , Ulven Trond , Tyas Martha R. , Euston Eloise , Dong Zhaoyang , Alharbi Abdulrahman Ghali M , Kim Richard , Lowe Jack G. , Hansbro Philip M. , Chung Kian Fan , Brightling Christopher E. , Milligan Graeme , Tobin Andrew B.
Published: May 2020

Increased prevalence of inflammatory airway diseases including asthma and chronic obstructive pulmonary disease (COPD) together with a significant number of patients being inadequately controlled by current frontline treatments means that there is a need to define novel therapeutic targets for these conditions1. Here we investigate a member of the G protein-coupled receptor (GPCR) family, FFA4, which responds to free circulating fatty acids, including dietary omega-3 fatty acids found in fish oils2–4. Although usually associated with metabolic responses linked with food intake, we show that FFA4 is expressed in the lung where it is coupled to Gq/11-signalling. Activation of FFA4 by drug-like agonists produced relaxation of murine airway smooth muscle mediated, at least in part, by the release of the prostaglandin PGE2that subsequently acts on EP2prostanoid receptors. In normal mice, activation of FFA4 resulted in a decrease in lung resistance. Importantly, in acute and chronic ozone models of pollution-mediated inflammation, and in house-dust mite and cigarette smoke-induced inflammatory disease, FFA4 agonists acted to reduce airway resistance, whilst this response was absent in mice lacking expression of FFA4. The expression profile of FFA4 in human lung was very similar to that observed in mice and the response to FFA4/FFA1 agonists similarly mediated human airway smooth muscle relaxation. Hence, our study provides evidence that pharmacological targeting of lung FFA4, and possibly combined activation of FFA4 and FFA1, hasin vivoefficacy that might have therapeutic value in the treatment of bronchoconstriction associated with inflammatory airway diseases such as asthma and COPD.
Cardiac MRI in common marmosets revealing age-dependency of cardiac function
Authors: Moussavi Amir , Mietsch Matthias , Drummer Charis , Behr Rüdiger , Mylius Judith , Boretius Susann
Published: May 2020

The aim of this study was to establish a feasible and robust magnetic resonance imaging protocol for the quantitative assessment of cardiac function in marmosets and to present normal values of cardiac function across different ages from young adult, middle-aged, to very old clinically healthy animals.

Cardiac MRI of 33 anesthetized marmosets at the age of 2-15 years was performed at 9.4 T using IntraGate-FLASH that operates without any ECG-triggering and breath holding. Normalized to post-mortem heart weight, the left ventricular end-diastolic volume (LV-EDV) was significantly reduced in older marmosets. The LV end-systolic volume (LV-ESV) and the LV stroke volume (LV-SV) showed a similar trend while the LV ejection fraction (LV-EF) and wall thickening remained unchanged. Similar observations were made for the right ventricle. Moreover, the total ventricular myocardial volume was lower in older monkeys while no significant difference in heart weight was found.

In conclusion, IntraGate-FLASH allowed for quantification of left ventricular cardiac function but seems to underestimate the volumes of the right ventricle. Although less strong and without significant sex differences, the observed age related changes were similar to previously reported findings in humans supporting marmosets as a model system for age related cardiovascular human diseases.
AlteredN-glycan composition impacts flagella mediated adhesion inChlamydomonas reinhardtii
Authors: Xu Nannan , Oltmanns Anne , Zhao Longsheng , Girot Antoine , Karimi Marzieh , Hoepfner Lara , Kelterborn Simon , Scholz Martin , Beißel Julia , Hegemann Peter , Bäumchen Oliver , Liu Luning N. , Huang Kaiyao , Hippler Michael
Published: May 2020

For the unicellular algaChlamydomonas reinhardtii, the presence ofN-glycosylated proteins on the surface of two flagella is crucial for both cell-cell interaction during mating and flagellar surface adhesion. It is unknown whether the composition ofN-glycans attached to respective proteins is important for these processes. To this end, we examined severalC. reinhardtiiinsertional mutants and a CRIPSR/Cas9 knockout mutant of xylosyltransferase 1A, all possessing alteredN-glycan compositions. Taking advantage of atomic force microscopy and micropipette force measurements, our data revealed that reduction inN-glycan complexity impedes the adhesion force required for binding the flagella to surfaces. In addition, polystyrene bead binding and transport is impaired. Notably, assembly, Intraflagellar Transport and FMG-1B transport into flagella are not affected by alteredN-glycosylation. Thus, we conclude that properN-glycosylation of flagellar proteins is crucial for adheringC. reinhardtiicells onto surfaces, indicating thatN-glycans mediate surface adhesion via direct surface contact.
Widening the bottleneck: Heterologous expression, purification, and characterization of theKtedonobacter racemiferminimal type II polyketide synthase inEscherichia coli
Authors: Klein Joshua G. , Wu Yang , Kokona Bashkim , Charkoudian Louise K.
Published: May 2020

Enzyme assemblies such as type II polyketide synthases (PKSs) produce a wide array of bioactive secondary metabolites. While the molecules produced by type II PKSs have found remarkable success in the clinic, the biosynthetic prowess of these enzymes has been stymied by: 1) the inability to reconstitute the bioactivity of the minimal PKS enzymesin vitroand 2) limited exploration of type II PKSs from diverse phyla. Towards filling this unmet need, we expressed, purified, and characterized the ketosynthase chain length factor (KSCLF) and acyl carrier protein (ACP) fromKtedonobacter racemifer. UsingE. colias a heterologous host, we obtained soluble proteins in titers representing significant improvements over previous KSCLF heterologous expression efforts. Characterization of these enzymes reveals thatKrACP has self-malonylating activity. Sedimentation velocity analytical ultracentrifugation (SV-AUC) analysis ofholo-KrACP andKrKSCLF indicates that these enzymes do not interactin vitro, suggesting that the acylated state of these proteins might play an important role in facilitating biosynthetically relevant interactions. Given the potential impact of obtaining soluble core type II PKS biosynthetic enzymes to enablein vitrocharacterization studies, these results lay important groundwork for optimizing the interaction betweenKrKSCLF andKrACP and exploring the biosynthetic potential of other non-actinomycete type II PKSs.
Changes in RT-PCR-positive SARS-CoV-2 rates in adults and children according to the epidemic stages
Authors: Levy Corinne , Basmaci Romain , Bensaid Philippe , Bru Cécile Bost , Coinde Edeline , Dessioux Emmanuelle , Fournial Cécile , Gashignard Jean , Haas Hervé , Hentgen Véronique , Huet Frédéric , Lalande Muriel , Martinot Alain , Pons Charlotte , Romain Anne Sophie , Ursulescu Nicoleta , Sage François Vie Le , Raymond Josette , Béchet Stéphane , Toubiana Julie , Cohen Robert
Published: May 2020

Aim

To describe the trends of RT-PCR positive SARS-CoV-2 rates in children and adults according to the time of COVID-19 epidemic.

Methods

In this prospective multicenter study involving 45 pediatric units, we collected the results of nasopharyngeal swabs in France from March 2, 2020 to April 26, 2020.

Results

During the study period, 52,588 RT-PCR tests for SARS-CoV-2 were performed, 6,490 in children and 46,098 in adults. The risk ratio of RT-PCR positive SARS-CoV-2 tests for adults compared to children was 3.5 (95% CI [3.2;3.9]) for the whole study period. These rates varied according to the time of the epidemic and were higher at the peak. The lower rates of positive test in children persisted during the surveillance period but varied according to the time in the epidemic.

Conclusion

The rate of positive RT-PCR positive SARS-CoV-2 tests for children was always less than that for adults but vary according to the epidemic stage.
The "Double Eights Mask Brace" Improves the Fit and Protection and Protection of a Basic Surgical Mask Amidst Covid-19 Pandemic
Authors: Runde Daniel P , Harland Karisa , Van Heukelom Paul , Faine Brett , OShaughnessy Patrick , Mohr Nicholas
Published: May 2020

Study Objective:

The COVID-19 pandemic has resulted in widespread shortages in personal protective equipment, including N95 respirators. While basic surgical facemasks are more commonly available, their efficacy is limited due primarily to their poor face seal. This pilot study examined the impact of a rubber band mask brace on a basic surgical mask, as determined by quantitative fit testing.

Methods:

Subjects wearing a basic surgical facemask and the rubber band mask brace underwent quantitative fit testing using machinery designed to certify N95 mask fit. Subjects were tested with the brace anchored behind their eyes, with a paperclip behind the head, and on the side knobs of their face shields. The primary outcome measure was whether the subject passed the quantitative fit test at or above the OSHA verified standard for N95 masks.

Results:

Subjects (n=11) were 54.5% female, with a median height of 70 inches (IQR 68-74), weight of 170 lbs (IQR 145-215) and BMI of 24.6 (IQR 22.2-27.2), and encompassing 5 distinct N95 mask fit types. We found that 45%, 100% and 100% of subjects passed the quantitative fit test when the brace was anchored behind the ears, with a paperclip and on a face shield respectively.

Conclusion:

Of the 11 subjects included in the analysis, across a range of body habitus and N95 mask fit types, all passed the quantitative fit test when the mask brace was anchored on either face shield or with a paperclip. This data suggests the brace would offer an improved margin of safety when worn with a basic surgical mask.
Performance of six SARS-CoV-2 immunoassays in comparison with microneutralisation
Authors: Jääskeläinen Anne J , Kuivanen Suvi , Kekäläinen Eliisa , Ahava Maarit J , Loginov Raisa , Kallio-Kokko Hannimari , Vapalahti Olli , Jarva Hanna , Kurkela Satu , Lappalainen Maija
Published: May 2020

There is an urgent need for reliable high-throughput serological assays for the management of the ongoing COVID-19 pandemic. Preferably, the performance of serological tests for a novel virus should be determined with clinical specimens against a gold standard, i.e. virus neutralisation.
We evaluated specificity and sensitivity of six commercial immunoassays for the detection of SARS-CoV-2 IgG, IgA and IgM antibodies, including four automated assays [Abbott SARS-COV-2 IgG (CE marked), Diasorin Liaison SARS-CoV-2 S1/S2 IgG (research use only), and Euroimmun SARS-CoV-2 IgG and IgA (CE marked)], and two rapid lateral flow (immunocromatographic) tests [Acro Biotech 2019-nCoV IgG/IgM (CE marked) and Xiamen Biotime Biotechnology SARS-CoV-2 IgG/IgM (CE marked)] in comparison with a microneutralisation test (MNT). Two specimen panels from serum samples sent to Helsinki University Hospital Laboratory (HUSLAB) were compiled: the patient panel included sera from PCR confirmed COVID-19 patients, and the negative panel included sera sent for screening of autoimmune diseases and respiratory virus antibodies in 2018 and 2019. The MNT was carried out for all COVID-19 samples (70 serum samples, 62 individuals) and for 53 samples from the negative panel. Forty-one out of 62 COVID-19 patients showed neutralising antibodies with median of 11 days (range 3-51) after onset of symptoms.
The specificity and sensitivity values of the commercial tests against MNT, respectively, were as follows: 95.1%/80.5% (Abbott Architect SARS-CoV-2 IgG), 94.9%/43.8% (Diasorin Liaison SARS-CoV-2 IgG), 68.3%/87.8% (Euroimmun SARS-CoV-2 IgA), 86.6%/70.7% (Euroimmun SARS-CoV-2 IgG), 74.4%/56.1% (Acro 2019-nCoV IgG), 69.5%/46.3% (Acro 2019-nCoV IgM), 97.5%/71.9% (Xiamen Biotime SARS-CoV-2 IgG), and 88.8%/81.3% (Xiamen Biotime SARS-CoV-2 IgM). This study shows variable performance values. Laboratories should carefully consider their testing process, such as a two-tier approach, in order to optimize the overall performance of SARS-CoV-2 serodiagnostics.
COVID-19 in China: Risk Factors and R0 Revisited
Authors: Khan Irtesam Mahmud , Zhang Wenyi , Zafar Sumaira , Wang Yong , He Junyu , Sun Hailon , Haque Ubydul , Rahman M. Sohel
Published: May 2020

The COVID-19 epidemic had spread rapidly through China and subsequently has proliferated globally leading to a pandemic situation around the globe. Human-to-human transmissions, as well as asymptomatic transmissions of the infection, have been confirmed. As of April 3rd, public health crisis in China due to COVID-19 is potentially under control. We compiled a daily dataset of case counts, mortality, recovery, temperature, population density, and demographic information for each prefecture during the period of January 11 to April 07, 2020 (excluding Wuhan from our analysis due to missing data). Understanding the characteristics of spatiotemporal clustering of the COVID-19 epidemic and R0 is critical in effectively preventing and controlling the ongoing global pandemic. The prefectures were grouped based on several relevant features using unsupervised machine learning techniques. We performed a computational analysis utilizing the reported cases in China to estimate the revised R0 among different regions for prevention planning in an ongoing global pandemic. Finally, our results indicate that the impact of temperature and demographic (different age group percentage compared to the total population) factors on virus transmission may be characterized using a stochastic transmission model. Such predictions will help prioritize segments of a given community/ region for action and provide a visual aid in designing prevention strategies for a specific geographic region. Furthermore, revised estimation and our methodology will aid in improving the human health consequences of COVID-19 elsewhere.
Decision-making in acute viral bronchiolitis: a universal guideline and a publication gap
Authors: Meyburg Jochen , Ries Markus
Published: May 2020

Background: Acute viral bronchiolitis is very common in infants and children up to 2 years. Some patients develop serious respiratory symptoms and need to be hospitalized. In 2014, the American Academy of Pediatrics (AAP) published a guideline on acute bronchiolitis which has gained global acceptance. We hypothesized that a publication gap, which is increasingly perceived in clinical medicine, might have also affected these universal recommendations.
Methods: We determined the proportion of published and unpublished studies registered at ClinicalTrials.gov that were marked as completed by October 1st 2018. The major trial and literature databases were used to search for publications. In addition, the study investigators were contacted directly.
Results: Of the 69 registered studies on the treatment of acute viral bronchiolitis, only 50 (72%) have been published by November 2019. Published trials contained data from n=9403 patients, whereas n=4687 patients were enrolled in unpublished trials. Median time to publication was 20 months, and only 8 of 50 trials were published within 12 months after completion. Only 40% of the clinical trials that were completed after the release of the AAP guideline were subsequently published as compared to 80% before 2014.
Conclusion: There is a significant publication gap regarding therapy of acute viral bronchiolitis that may have influenced certain recommendations of the AAP guideline. In turn, recommendations of the guideline might have discouraged investigators to publish their results after its release.
Dynamical model for social distancing in the U.S. during the COVID-19 epidemic
Authors: Chitanvis Shirish M
Published: May 2020

Background Social distancing has led to a flattening of the curve in many states across the U.S. This is part of a novel, massive, global social experiment which has served to mitigate the pandemic in the absence of a vaccine or effective anti-viral drugs. Hence it is important to be able to forecast hospitalizations reasonably accurately.
Methods We propose on phenomenological grounds a generalized diffusion equation which in- corporates the effect of social distancing to forecast the temporal evolution of the probability of having a given number of hospitalizations. The probability density function is log-normal in the number of hospitalizations, which is useful in describing pandemics where the number of hospital- izations is very high.
Findings We used this insight and data to make forecasts for states using Monte Carlo methods. Back testing validates our approach, which yields good results about a week into the future. States are beginning to reopen at the time of publication and our forecasts indicate possible precursors of increased hospitalizations.
Additionally we studied the reproducibility Ro in New York (Italian strain) and California (Wuhan strain). We find that even if there is a difference in the transmission of the two strains, social distancing has been able to control the progression of COVID 19.
Funding None.
Clinical characteristics, outcomes and predictors of patients with leptospirosis admitted to medical intensive care unit: A retrospective review
Authors: Ajjimarungsi Atta , Bhurayanontachai Rungsun , Chusri Sarunyou
Published: May 2020

Background: This study aimed to report the characteristics and outcomes of severe leptospirosis patients admitted to the ICU and to find the predictors of ICU admission.
Methods: This is a retrospective study of patients diagnosed as leptospirosis either from a serology diagnosis or Thai Lepto score (TLS) > 4. Patients were divided into ICU and general ward cases. All data were compared.
Results: Sixty-eight patients with severe leptospirosis were included. Thirty-two patients were ICU admission. ICU patients had higher SOFA score (9.8 +/- 2.7 vs 4.6+/-2.7; p = 0.001), higher TLS (7.6 +/- 2.7 vs 5.7 +/- 2.4; p < 0.001), lower hematocrit ( 32.7 +/- 7.5% vs 36.6 +/- 7.9%; p = 0.04), lower platelet count (88.7 +/- 92.2 vs 173.3 +/- 84.6 x 1000 cell/mm3; p = 0.008), higher total bilirubin (6.2 +/- 6.3 vs 3.0 +/- 3.6 mg/dL; p = 0.01), lower serum albumin (3.0 +/- 0.5 vs 3.4 +/- 0.7 g/dL; p = 0.03), higher creatinine (4.2 +/- 2.4 vs 2.8 +/-2.1 mg/dL; p = 0.02), higher requirements for vasopressor or inotrope (90.6% vs 11.1%; p < 0.001), more mechanical ventilator support (84.4% vs 5.5%; p < 0.001), more renal replacement therapy (37.5% vs 0%; p < 0.001), higher hospital mortality (12.5% vs 0%; p = 0.03), and greater length of hospital stay (10.2 +/- 5.1 vs 6.5 +/- 5.1 days; p = 0.004). The TLS, mechanical ventilator support, and inotrope or vasopressor support were among the independent factors for ICU admission. A TLS > 6 indicated ICU admission.
Conclusion: The TLS, inotrope or vasopressor requirement, and mechanical ventilator support were the independent factors for ICU admission. TLS > 6 indicated ICU admission.
COVID19-Global: A shiny application to perform a global comparative data visualization for the SARS-CoV-2 epidemic
Authors: Tobias Aurelio , satorra pau , Valls Joan , Tebe Cristian
Published: May 2020

Data visualization is an essential tool for exploring and communicating findings in medical research, especially in epidemiological surveillance. The COVID19-Global online web application systematically produces daily updated data visualization and analysis of the SARS-CoV-2 epidemic on a global scale. It collects automatically daily data on COVID-19 diagnosed cases and mortality worldwide from January 1st, 2020 onwards. We have implemented comparative data visualization between countries for the most common indicators in epidemiological surveillance to follow an epidemic: attack rate, population fatality rate, case fatality rate, and basic reproduction number. The application may help for a better understanding of the SARS-CoV-2 epidemic worldwide.
Lung ultrasound findings in patients with novel SARS-CoV2
Authors: Haaksma Mark Evert , Heldeweg Micah L.A. , Lopez Matta Jorge E. , Smit Jasper Martijn , van Trigt Jessica D. , Nooitgedacht Jip Suzanne , Elzo Kraemer Carlos V. , Girbes Armand R.J. , Heunks Leo M.A. , van Westerloo David J. , Tuinman Pieter R.
Published: May 2020

Background:
Over 2 million people worldwide have been infected with Severe Acute Respiratory Distress Syndrome Corona Virus 2 (SARS CoV2). Lung ultrasound has been proposed to diagnose and it. However, little is known about ultrasound findings in these patients. Our aim is to present an overview of lung ultrasound characteristics in critically ill patients with SARS CoV2 pneumonia overall and in relation to the duration of symptoms and clinical parameters.

Methods:
On the Intensive Care Unit of two academic hospitals, adult patients who tested positive for SARS-CoV2 were included. Images were analyzed for pleural line characteristics, number and appearance of B-lines, BLUE-profiles (Bedside Lung Ultrasound in Emergency), pathology in the PLAPS (Postero Lateral Alveolar and Pleural Syndrome) point and a LUS-score (lung ultrasound). The primary outcomes were frequencies, percentages and differences in lung ultrasound findings overall and between short (≤14 days) and long (>14 days) duration of symptoms and their correlation with clinical parameters.

Results:
In this pilot observational study, 61 patients were included with 75 examinations for analysis. The most prevalent ultrasound findings were decreased lung sliding (36%), thickening of the pleural line (42%) and a C-profile per view (37%). Patients with ″long″ duration of symptoms presented more frequently with a thickened and irregular pleural line (21% (32) vs 9% (11), p=.01), C-profile per patient (47% (18) vs. 25% (8),p=.01) and pleural effusion (19% (14) vs 5% (3),p=.02) compared to patients with short duration of symptoms. Lung ultrasound findings did not correlate with P/F ratio, fluid balance or dynamic compliance, with the exception of the LUS-score and dynamic compliance (R2=0.27, p=.02).

Conclusion:
SARS CoV2 results in significant ultrasound changes, with decreased lung sliding, thickening of the pleural line and a C-profile being the most observed. With time, a thickened and irregular pleural line, C-profile and pleural effusion become more common findings.
Early experiences with antibody testing in a Flemish nursing home during an acute COVID-19 outbreak: a retrospective cohort study.
Authors: Buntinx Frank , Claes Peter , Gulikers Marjo , Verbakel Jan Y , De Lepeleire Jan , Van der Elst Michael , Van Ranst Marc , Vermeersch Pieter
Published: May 2020

objectives: to assess the prevalence of COVID-19 (PCR-test) in residents and staff of a nursing home. To examine the presence of IgM and IgG antibodies in the sample and the relation between PCR and antibody test results.
design: cross-sectional and (retrospective) cohort study
setting: a nursing home for the elderly Bessemerberg in Lanaken (Belgium) with up to 130 beds. Lanaken is situated in the Belgian province with the highest COVID-19 prevalence.
participants: residents (N=108) and staff members (N=93) of the nursing home
outcomes: PCR, IgM and IgG
results: the prevalence of COVID-19, based on PCR test was 34% (N=40) for residents and 13% (N=11) for staff members, respectively. Of the residents, 13% showed positive IgM results and 15% positive IgG results. In 17% of the residents, at least one of the antibodies was positive. In total 13% of the staff members had positive IgM and 16% had a positive IgG. In 20% of the staff members at least one of these antibody tests was positive. In PCR positive residents, the percentage of IgM positive, IgG positive, and at least one of both was 28%, 34%, and 41%. In PCR positive staff, we found 30%, 60%, and 60%. Additional antibody tests were performed in nine residents between day 11 and 14 after the positive PCR test. Of those, 7 (78%) tested positive on at least one antibody. When retesting three weeks later, all remaining residents also tested positive.
conclusions: Recently it was reported that in Belgium antibodies are present in 3-4% of the general population. Although, the prevalence in our residents is higher, the number is largely insufficient for herd immunity. In staff members of the regional hospital the prevalence of antibodies was 6%. The higher prevalence in nursing home staff (21%) may be related to the complete absence of good quality protection in the first weeks of the outbreak.
The impact of adaptive mosquito behavior and insecticide-treated nets on malaria prevalence
Authors: Ngonghala Calistus N. , Wairimu Josephine , Adamski Jesse , Desai Hardik
Published: May 2020

Malaria prevalence in sub-Saharan Africa remains high. Kenya for example, records about 3.5 million new cases and 11 thousand deaths each year [1]. Most of these cases and deaths are among children under five. The main control method in malaria endemic regions has been through the use of pyrethroid-treated bed nets. Although this approach has been fairly successful, the gains are threatened by mosquito-resistance to pyrethroids, physical and chemical degradation of ITNs that reduce their efficacy, inconsistent and improper use by humans, etc. We present a model to investigate the effects of insecticide-treated bed-net use and mosquito-resistance and adaptation to pyrethroids used to treat bed nets on malaria prevalence and control in malaria endemic regions. The model captures the development and loss of resistance to insecticides, the effects of bed-net use on malaria control in a setting where proper and consistent use is not guaranteed, as well as differentiated biting of human hosts by resistant and sensitive mosquitoes. Important thresholds, including the basic reproduction number R0, and two parameter groupings that are important for disease control and for establishing the existence of endemic equilibria to the model are calculated. Furthermore, a global sensitivity analysis is carried out to identify important parameters such as insecticide treated bed-net coverage, insecticide treated bed-net efficacy, the maximum biting rate of resistant mosquitoes, etc., that drive the system and that can be targeted for disease control. Threshold levels of bed-net coverage and bed-net efficacy required for containing the disease are identified and shown to depend on the type of insecticide-resistance. For example, when mosquito-resistance to insecticides is not permanent and is acquired only through recruitment and the efficacy of insecticide-treated nets is 90%, about 70% net coverage is required to contain malaria. However, for the same insecticide-treated net efficacy, i.e., 90%, approximately 93% net coverage is required to contain the disease when resistance to insecticides is permanent and is acquired through recruitment and mutation in mosquitoes. The model exhibits a backward bifurcation, which implies that simply reducing R0 slightly below unity might not be enough to contain the disease. We conclude that appropriate measures to reduce or eliminate mosquito-resistance to insecticides, ensure that more people in endemic areas own and use insecticide-treated nets properly, and that the efficacy of these nets remain high most of the times, as well as educating populations in malaria endemic areas on how to keep mosquito densities low and minimize mosquito bites are important for containing malaria.
Molecular models of multiple sclerosis severity identify heterogeneity of pathogenic mechanisms
Authors: Barbour Christopher , Kosa Peter , Varosanec Mihael , Greenwood Mark , Bielekova Bibiana
Published: May 2020

The inability to measure putative pathogenic processes in the central nervous system (CNS) of living subjects precludes the determination of their temporal distribution, intra-individual heterogeneity, and their ability to predict disease course. Using multiple sclerosis (MS) as an example of a complex neurological disorder, we sought to determine if cerebrospinal fluid (CSF) biomarkers can be aggregated to predict future rates of MS progression and provide molecular insight into mechanisms of CNS destruction. 1,305 CSF biomarkers were analyzed blindly in the longitudinal training dataset (N=129) of untreated MS patients, using DNA-aptamer assay. Random forest models, validated in an independent longitudinal cohort (N=64), uncovered signatures of MS severity, measured by clinical scales and volumetric brain imaging. Cluster analysis revealed intra-individual molecular heterogeneity of disease mechanisms that include both CNS- and immune-related pathways and may represent novel targets for inhibiting MS progression.
Going by the Numbers : Learning and Modeling COVID-19 Disease Dynamics
Authors: Basu Sayantani , Campbell Roy H.
Published: May 2020

The COrona VIrus Disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has resulted in a challenging number of infections and deaths worldwide. In order to combat the pandemic, several countries worldwide enforced mitigation measures in the forms of lockdowns, social distancing and disinfection measures. In an effort to understand the dynamics of this disease, we propose a Long Short Term Memory (LSTM) based model. We train our model on nearly four months of cumulative COVID-19 cases and deaths. Our model can be adjusted based on the parameters in order to provide predictions as needed. We provide results at both the country and county levels. We also perform a quantitative comparison of mitigation measures in various counties in the United States based on the rate of difference of a short and long window parameter of the proposed LSTM model. The analyses provided by our model can provide valuable insights based on the trends in the rate of infections and deaths. This can also be of help for countries and counties deciding on mitigation and reopening strategies. We believe that the results obtained from the proposed method will contribute to societal benefits for a current global concern.
The iron-responsive genome of the chitonAcanthopleura granulata
Authors: Varney Rebecca M. , Speiser Daniel I. , McDougall Carmel , Degnan Bernard M. , Kocot Kevin M.
Published: May 2020

Molluscs biomineralize structures that vary in composition, form, and function, prompting questions about the genetic mechanisms responsible for their production and the evolution of these mechanisms. Chitons (Mollusca, Polyplacophora) are a promising system for studies of biomineralization because they build a range of calcified structures including shell plates and spine- or scale-like sclerites. Chitons also harden the calcified teeth of their rasp-like radula with a coat of iron (as magnetite). Here we present the genome of the West Indian fuzzy chitonAcanthopleura granulata, the first from any aculiferan mollusc. TheA. granulatagenome contains homologs of many biomineralization genes identified previously in conchiferan molluscs. We expected chitons to lack genes previously identified from pathways conchiferans use to make biominerals like calcite and nacre because chitons do not use these materials in their shells. Surprisingly, theA. granulatagenome has homologs of many of these genes, suggesting that the ancestral mollusc had a more diverse biomineralization toolkit than expected. TheA. granulatagenome has features that may be specialized for iron biomineralization, including a higher proportion of genes regulated directly by iron than other molluscs.A. granulataalso produces two isoforms of soma-like ferritin: one is regulated by iron and similar in sequence to the soma-like ferritins of other molluscs, and the other is constitutively translated and is not found in other molluscs. TheA. granulatagenome is a resource for future studies of molluscan evolution and biomineralization.

SIGNIFICANCE STATEMENT

Chitons are molluscs that make shell plates, spine- or scale-like sclerites, and iron-coated teeth. Currently, all molluscs with sequenced genomes lie within one major clade (Conchifera). Sequencing the genome of a representative from the other major clade (Aculifera) helps us learn about the origins and evolution of molluscan traits. The genome of the West Indian Fuzzy Chiton,Acanthopleura granulata, reveals chitons have homologs of many genes other molluscs use to make shells, suggesting all molluscs share some shell-making pathways. The genome ofA. granulatahas more genes that may be regulated directly by iron than other molluscs, and chitons produce a unique isoform of a major iron-transport protein (ferritin), suggesting that chitons have genomic specializations that contribute to their production of iron-coated teeth.
Transient resting-state network dynamics in cognitive ageing
Authors: Tibon Roni , Tsvetanov Kamen , Price Darren , Nesbitt David ,   Cam-CAN, Henson Richard
Published: May 2020

It is important to maintain cognitive function in old age, yet the neural substrates that support successful cognitive ageing remain unclear. One factor that might be crucial, but has been overlooked due to limitations of previous data and methods, is the ability of brain networks to flexibly reorganise and coordinate over a millisecond time-scale. Magnetoencephalography (MEG) provides such temporal resolution, and can be combined with Hidden Markov Models (HMMs) to characterise transient neural states. We applied HMMs to resting-state MEG data from a large cohort (N=594) of population-based adults (aged 18-88), who also completed a range of cognitive tasks. Using multivariate analysis of neural and cognitive profiles, we found that decreased occurrence of “lower-order” brain networks, coupled with increased occurrence of “higher-order” networks, was associated with both increasing age and impaired fluid intelligence. These results favour theories of age-related reductions in neural efficiency over current theories of age-related functional compensation.
Presence of a resident species aids invader evolution
Authors: Lachapelle Josianne , Bestion Elvire , Jackson Eleanor E , Schaum C-Elisa
Published: May 2020

Phytoplankton populations are intrinsically large and genetically variable, and interactions between species in these populations shape their physiological and evolutionary responses. Yet, evolutionary responses of microbial organisms in novel environments are investigated almost exclusively through the lens of species colonising new environments on their own, and invasion studies are often of short duration. Although exceptions exist, neither type of study usually measures ecologically relevant traits beyond growth rates. Here, we experimentally evolved populations of fresh- and seawater phytoplankton as monocultures (the green algaeChlamydomonas moewusiiandOstreococcus tauri, each colonising a novel, unoccupied salinity) and co-cultures (invading a novel salinity occupied by a resident species) for 200 generations. Colonisers and invaders differed in extinction risks, phenotypes (e.g. size, primary production rates) and strength of local adaptation: invaders had systematically lower extinction rates and broader salinity and temperature preferences than colonisers – regardless of the environment that the invader originated from. We emphasise that the presence of a locally adapted species has the potential to alter the invading species’ eco-evolutionary trajectories in a replicable way across environments of differing quality, and that the evolution of small cell size and high ROS tolerance may explain high invader fitness. To predict phytoplankton responses in a changing world, such interspecific relationships need to be accounted for.
Poultry farmer response to disease outbreaks in smallholder farming systems
Authors: Delabouglise Alexis , Le Thanh Nguyen Thi , Ai Xuyen Huynh Thi , Nguyen-Van-Yen Benjamin , Tuyet Phung Ngoc , Lam Ha Minh , Boni Maciej F.
Published: May 2020

Avian influenza outbreaks have been occurring on smallholder poultry farms in Asia for two decades. Farmer responses to these outbreaks can slow down or accelerate virus transmission. We used a longitudinal survey of 53 small-scale chicken farms in southern Vietnam to investigate the impact of outbreaks with disease-induced mortality on harvest rate, vaccination, and disinfection behaviors. We found that in small broiler flocks (≤16 birds/flock) the estimated probability of harvest was 56% higher when an outbreak occurred, and 214% higher if an outbreak with sudden deaths occurred in the same month. Vaccination and disinfection were strongly positively correlated with flock size and farm size, respectively. Small-scale farmers – the overwhelming majority of poultry producers in low-income countries – tend to rely on rapid sale of birds to mitigate losses from diseases. As depopulated birds are sent to markets or trading networks, this reactive behavior has the potential to enhance onward transmission.

One sentence summary

A cohort study of fifty three small-scale poultry farms in southern Vietnam reveals that when outbreaks occur with symptoms similar to highly pathogenic avian influenza, farmers respond by sending their chickens to market early, potentially exacerbating the effects of the outbreak.
Examining Blunted Initial Response to Reward and Recent Suicidal Ideation in Children and Adolescents Using Event-Related Potentials: Failure to Conceptually Replicate Across Two Independent Samples
Authors: Gallyer Austin J. , Burani Kreshnik , Mulligan Elizabeth M. , Santopetro Nicholas , Dougherty Sean P. , Jeon Min Eun , Nelson Brady D. , Joiner Thomas E. , Hajcak Greg
Published: May 2020

A recent study by Tsypes and colleagues (2019) found that children with recent suicidal ideation had blunted neural reward processing, as measured by the reward positivity (RewP), compared to matched controls, and that this difference was driven by reduced neural responses to monetary loss, rather than to reward. Here, we aimed to conceptually replicate and extend these findings in two samples (n= 264, 27 with suicidal ideation; andn= 314, 49 with suicidal ideation at baseline) of children and adolescents (11 to 15 years and 8 to 15 years, respectively). Results from both samples showed no evidence that children and adolescents with suicidal ideation have abnormal reward or loss processing, nor that reward processing predicts suicidal ideation two years later. The results highlight the need for greater statistical power, as well as continued research examining the neural underpinnings of suicidal thoughts and behaviors.
PLCG2as a Risk Factor for Alzheimer’s Disease
Authors: Tsai Andy P. , Dong Chuanpeng , Preuss Christoph , Moutinho Miguel , Lin Peter Bor-Chian , Hajicek Nicole , Sondek John , Bissel Stephanie J. , Oblak Adrian L. , Carter Gregory W. , Liu Yunlong , Landreth Gary E. , Lamb Bruce T. , Nho Kwangsik
Published: May 2020

Alzheimer’s disease (AD) is characterized by robust microgliosis and phenotypic changes that accompany disease pathogenesis. Indeed, genetic variants in microglial genes are linked to risk for AD. Phospholipase Cγ2 (PLCG2) participates in the transduction of signals emanating from immune cell-surface receptors that regulate the inflammatory response and is selectively expressed by microglia in the brain. A rare variant inPLCG2(P522R) was previously found to be protective against AD, indicating thatPLCG2may play a role in AD pathophysiology. Here, we report that a rare missense variant inPLCG2confers increased AD risk (p=0.047; OR=1.164 [95% CI=1.002-1.351]). Additionally, we observed thatPLCG2expression levels are increased in several brain regions of AD patients, correlating with brain amyloid deposition. This provides further evidence thatPLCG2may play an important role in AD pathophysiology. Together, our findings indicate thatPLCG2is a potential new therapeutic target for AD.
Discordant evolution of organellar genomes in peas (PisumL.)
Authors: Bogdanova Vera S. , Shatskaya Natalia V. , Mglinets Anatoliy V. , Kosterin Oleg E. , Vasiliev Gennadiy V.
Published: May 2020

Plastids and mitochondria have their own small genomes which do not undergo meiotic recombination and may have evolutionary fate different from each other and nuclear genome, thus highlighting interesting phenomena in plant evolution. We for the first time sequenced mitochondrial genomes of pea (PisumL.), in 38 accessions mostly representing diverse wild germplasm from all over pea geographical range. Six structural types of pea mitochondrial genome were revealed. From the same accessions, plastid genomes were sequenced. Bayesian phylogenetic trees based on the plastid and mitochondrial genomes were compared. The topologies of these trees were highly discordant implying not less than six events of hybridisation of diverged wild peas in the past, with plastids and mitochondria differently inherited by the descendants. Such discordant inheritance of organelles is supposed to have been driven by plastid-nuclear incompatibility, known to be widespread in pea wide crosses and apparently shaping the organellar phylogenies. The topology of a phylogenetic tree based on the nucleotide sequence of a nuclear geneHis5coding for a histone H1 subtype corresponds to the current taxonomy and resembles that based on the plastid genome. Wild peas (Pisum sativumsubsp.elatiuss.l.) inhabiting Southern Europe were shown to be of hybrid origin resulting from crosses of peas similar to those presently inhabiting south-east and north-east Mediterranean in broad sense.
Feeding dihydroquercetin and vitamin E to broiler chickens reared at standard and high ambient temperatures
Authors: Pirgozliev V. , Westbrook C. , Woods S. , Mansbridge S.C. , Rose S.P. , Whiting I.M. , Yovchev D. , Atanasov A.G. , Kljak K. , Staykova G.P. , Ivanova S. , Karagecili M.R. , Karadas F. , Stringhini J.H.
Published: May 2020

The use of natural antioxidants, in particular polyphenols such as dihydroquercetin (DHQ), in animal nutrition have recently increased in popularity. This may partly be due to the risk of increased incidences of heat stress associated with raising livestock in warmer ambient temperatures, facilitated by global warming, reducing antioxidant capacity. The current research demonstrates the effect of dietary DHQ, vitamin E and standard or high ambient temperatures on growth performance, energy and nutrient metabolism, gastrointestinal tract development (GIT), jejunal villus morphometry and antioxidant status in broiler chickens. Each of the four experimental diets were fed to 16 pens of five birds, which were allocated to four rooms (four pens in each room). The temperature in two rooms was maintained at a constant 35 °C (high temperature; HT), and the temperature in the other two rooms was gradually reduced from 27 °C at 7d of age to 22 °C at 20d of age (standard temperature; ST). Rearing birds at HT reduced: feed intake, weight gain, weight of small intestine, total GIT, liver, spleen, heart, villus height, villus surface area and lowered blood glutationperoxidase (GSH-Px). Dietary DHQ increased blood GSH-Px and total antioxidant status, increased heart weight and reduced caecal size. When fed separately, DHQ and vitamin E improved hepatic vitamin E concentration. Feeding vitamin E increased spleen and liver weights. When fed together, DHQ and vitamin E reduced villus height, villus height to crypt depth ratio and villus surface area. Temperature and antioxidants did not affect energy and nutrient metabolism. There were no effects of dietary antioxidants on growth performance of broiler chickens and there were no mortalities. At present it is unclear if feeding antioxidants (in particular DHQ) at different levels, using different dietary formulations, and rearing birds under a range of environmental conditions may be effective at enhancing production performance and bird health in hot ambient climates.