bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of vaccination on the spread patterns of the COVID epidemic
Authors: Below D. , Mairanowski F.
Published: May 2021

A modified model of the epidemic under conditions of mass vaccination was developed. A comparison of the model results with statistical observations in Israel shows good agreement.

Model calculations are performed on the efficacy of limiting the development of an epidemic by both lockdown and vaccination. Mass vaccination of the population is the most radical method of limiting the growth of the epidemic. The introduction of a lockdown cannot completely prevent the development of an epidemic. The likelihood of the emergence of new strains of the virus is assessed. Without vaccination, the probability of more than two new virus strains per year affecting the epidemic growth process is found to be about 60%. A controlled calculation was made of the effect of the timing of changes in lockdown conditions during the vaccination period on the development of the epidemic. It was particularly shown that the cancellation of the lockdown together with the start of vaccination did not reduce the maximum number of new infections. A controlling calculation was made of the effects of gradually cancelling lockdown. On the basis of these calculations, it is possible to assess the development of the epidemic in different variants of partial lockdown cancellation.

Three dimensionless complexes, made up of the intensities of transmission, vaccination and lockdown restrictions, are found to determine the epidemic’s development.

The intensity of the coronavirus epidemic depends on climatic characteristics, in particular air temperature and the UV index. A relationship is given to estimate the influence of these factors on infection growth.

The way forward for further development of the model is outlined. The immediate goal of modifying the model is to use it for each age group in the population and to find out the links between vaccination rates and the psychological state of the population, i.e. people’s readiness for mass vaccination.
Cost-Effectiveness Analysis of Statins for Treatment of Hospitalized COVID-19 Patients
Authors: Chow Ronald , Prsic Elizabeth Horn , Shin Hyun Joon
Published: May 2021

Introduction

A recent systematic review and meta-analysis by our group reported on thirteen published cohorts investigating 110,078 patients. Patients administered statins after their COVID-19 diagnosis and hospitalization were found to have a lower risk of mortality. Given this reported superiority, a logical next question would be whether statins are cost-effective treatment options for hospitalized COVID-19 patients. In this paper, we report on a cost-effectiveness analysis of statin-containing treatment regimens for hospitalized COVID-19 patients, from a United States healthcare perspective.

Methods

A Markov model was used, to compare statin use and no statin use among hospitalized COVID-19 patients. The cycle length was one week, with a time horizon of 4 weeks. A Monte Carlo microsimulation, with 20,000 samples were used. All analyses were conducted using TreeAge Pro Healthcare Version 2021 R1.1.

Results

Treatment of hospitalized COVID-19 patients with statins was both cheaper and more effective than treatment without statins; statin-containing therapy dominates over non-statin therapy.

Conclusion

Statin for treatment of COVID-19 should be further investigated in RCTs, especially considering its cost-effective nature. Optimistically and pending the results of future RCTs, statins may also be used broadly for treatment of hospitalized COVID-19 patients.
Relationships between freezing of gait severity and cognitive deficits in Parkinson’s disease
Authors: Scholl Jamie L. , Espinoza Arturo I. , Rai Wijdan , Leedom Matt , Baugh Lee A. , Berg-Poppe Patti , Singh Arun
Published: May 2021

Objective

Evidence supports an association between freezing of gait (FOG) severity and cognitive functioning in patients with Parkinson’s disease (PD); however, results are varied. Here we sought to explore the differences in cognitive measurements via multivariable statistical models in patients with PD.

Methods

PD patients with (PDFOG+, n=41) and without FOG (PDFOG–, n=39) and control healthy subjects (n=41) participated in the study. The NIH toolbox cognition battery, Montreal cognitive assessment (MoCA), and interval timing task were used to test cognitive domains. Measurements were compared between groups using multivariable models and adjusting for covariates. Correlation analyses, linear regression, and mediation models were applied to examine relationships among disease duration and severity, FOG severity, and cognitive functioning.

Results

Significant differences were observed between controls and PD patients for all cognitive domains. PDFOG+ and PDFOG– exhibited differences in the dimensional change card sort (DCCS) test, interval timing task, and MoCA scores. After adjusting for covariates in two different models, PDFOG+ and PDFOG– differed in both MoCA and DCCS scores. In addition, significant relationships between FOG severity and cognitive function (MoCA, DCCS, and interval timing) were also found. Regression models suggest that FOG severity may be a predictor of cognitive impairment, and mediation models show the effects of cognitive impairment on the relationship between disease severity and FOG severity.

Conclusions

Overall, this study provides insight into the relationship between cognitive and FOG severity in patients with PD, which could aid in the development of therapeutic interventions to manage both.
Transition in learning approach for undergraduate medical students of Bangladesh in Covid 19 pandemic: A situation analysis
Authors: Jeenia Fatiha Tasmin , Uddin Tanin Md Jamal , Ferdoush Jannatul , Johora Fatema , Hoque Afroza , Abbasy Asma Akter , Sadia Halima , Urmi Rehnuma , Moitra Priyanka , Sarah Quazi Saheli , Ata Maliha , Parveen Kohinoor
Published: May 2021

Background

The outbreak of Covid-19 pandemic has fundamentally transformed the landscape of medical education system upside down worldwide. This unanticipated transition without any pre build infrastructure has made this altered prospect more challenging in Bangladesh. Though many countries across the world utilize Web Based Learning (WBL), but medical students of Bangladesh are mostly unfamiliar and unaccustomed with this newly imposed online learning avenue. Therefore, this study has evaluated the familiarity, usage, attitude of students towards online class and figured out the barriers witnessed by students in Bangladesh prospect.

Methods

This cross sectional, questionnaire based study was conducted in medical colleges across Bangladesh. A questionnaire linked to google form were distributed to undergraduate medical students all over Bangladesh through different social platforms. The answered questionnaires were automatically stored in Google drive in a specific email ID.

Results

A total of 1708 students participated. Among the respondents 45.1% were satisfied with online class. Though most students (45.8%) think online class is not effective like traditional lectures but 47.4% agrees to the point that online class should have complementary role in medical education. One of the strong attitude of medical students revealed that, most of them undoubtedly in unison (49.5% disagree, 30.3% strongly disagree) with that online class can never replace traditional class. 77.2% students responded that web based learning is interactive. 54.9% students pointed out interrupted internet connections with low speed during class which is a barrier to WBL. 83.2% of the respondents complained about facing audio visual problem in class which is attributed to poor network connectivity. Most students (74.8%) found online classes costly and 53.8% needed technical supports for online class.

Conclusion

This study finding can suggest a potential reform for online class in Bangladesh. Addressing the obstacles and expectations can execute a fruitful web based learning in Bangladesh.
SARS-CoV-2 bearing a mutation at the S1/S2 cleavage site exhibits attenuated virulence and confers protective immunity
Authors: Sasaki Michihito , Toba Shinsuke , Itakura Yukari , Chambaro Herman M. , Kishimoto Mai , Tabata Koshiro , Intaruck Kittiya , Uemura Kentaro , Sanaki Takao , Sato Akihiko , Hall William W. , Orba Yasuko , Sawa Hirofumi
Published: May 2021

Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) possesses a discriminative polybasic cleavage motif in its spike protein that is recognized by host furin protease. Proteolytic cleavage activates the spike protein and influences both the cellular entry pathway and cell tropism of SARS-CoV-2. Here, we investigated the impact of the furin cleavage site on viral growth and pathogensis using a hamster animal model infected with SARS-CoV-2 variants bearing mutations at the furin cleavage site (S gene mutants). In the airway tissues of hamsters, the S gene mutants exhibited a low growth property. In contrast to parental pathogenic SARS-CoV-2, hamsters infected with the S gene mutants showed no body weight loss and only a mild inflammatory response, indicating the attenuated variant nature of S gene mutants. We reproduced the attenuated growth of S gene mutants in primary differenciated human airway epithelial cells. This transient infection was enough to induce protective neutralizing antibodies crossreacting with different SARS-CoV-2 lineages. Consequently, hamsters inoculated with S gene mutants showed resistance to subsequent infection with both the parental strain and the currently emerging SARS-CoV-2 variants belonging to lineages B.1.1.7 and P.1. Together, our findings revealed that the loss of the furin cleavage site causes attenuation in the airway tissues of SARS-CoV-2 and highlights the potential benefits of S gene mutants as potential immunogens.
BNT162b2 mRNA Covid-19 vaccine does not impair sperm parameters
Authors: Safrai Myriam , Reubinoff Benjamin , Ben-Meir Assaf
Published: May 2021

Mass vaccination using newly approved vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has begun globally. However, their effect on fertility have not yet been investigated. Previous studies demonstrate that SARS-CoV-2 infection may impair sperm parameters. In this study, we are the first to assess the effect of the BNT162b2 mRNA Covid-19 vaccine on sperm parameters. Our results demonstrate that the vaccine does not impair sperm parameters. Thus, we recommend that couples desiring to conceive should vaccinate, as vaccination does not affect sperm whereas SARS-CoV-2 infection does impair sperm.
Rehabilitation needs and mortality associated with the Covid-19 pandemic: a population-based study of all hospitalised and home-healthcare individuals in a Swedish healthcare region
Authors: Divanoglou Anestis , Samuelsson Kersti , Sjödahl Emer. Rune , Andersson Christer , Levi Richard
Published: May 2021

Background

This first report of the Linköping Covid-19 Study (LinCoS) aimed at determination of Covid-19-associated mortality, impairments, activity and participation limitations denoting rehabilitation needs four months after discharge from hospital.

Methods

An ambidirectional population-based cohort study including all confirmed Covid-19 cases admitted to hospital during 1/03-31/05 and those living in home healthcare settings identified through a regional registry and evaluated through medical records, including WHO Clinical Progression Scale (CPS). All patients discharged from hospital were followed-up by structured telephone interview at 4 months post-discharge. Respondents indicated any new or aggravated persisting problems in any of 25 body functions and 12 activity/participation items and rated them for impact on daily life.

Findings

Out of 734 hospitalised patients, 149 were excluded, 125 died, and 460 were alive at 4-month follow-up of whom 433 (94.1%) were interviewed. In total, 40% reported impairments and activity/participation limitations affecting daily life and warranted further multi-professional rehabilitation assessment, predominantly those with severe disease and a considerable proportion of those with moderate disease. Cognitive and affective impairments were equally common in all groups and were reported by 20-40% of cases. Limb weakness was reported by 31%, with CPS 7-9 being four times more likely to report this problem as compared to CPS 4-5. 26% of those working or studying reported difficulties returning to these activities, this being 3.5 times more likely in CPS 7-9 as compared to CPS 4-5. 25% reported problems walking >1 km, with CPS 7-9 over three times more likely to report this as compared to the other two sub-groups. 90-day mortality rate of Covid-19 associated deaths was 15.1%.

Interpretation

Most rehabilitation needs after Covid-19 involved higher cerebral dysfunction both in patients with moderate and severe disease. This should be considered when designing services aiming at minimizing long-term disability.

Funding

ALF grant and Region Östergötland.
Characterization of the skin microbiota in bullous pemphigoid patients and controls reveals novel microbial indicators of disease
Authors: Belheouane Meriem , Hermes Britt M. , Van Beek Nina , Benoit Sandrine , Bernard Philippe , Drenovska Kossara , Gerdes Sascha , Gläser Regine , Goebeler Matthias , Günther Claudia , von Georg Anabelle , Hammers Christoph M. , Holtsche Maike M. , Homey Bernhard , Horváth Orsolya N. , Hübner Franziska , Linnemann Beke , Joly Pascal , Márton Dalma , Patsatsi Aikaterini , Pföhler Claudia , Sárdy Miklós , Huilaja Laura , Vassileva Snejina , Zillikens Detlef , Ibrahim Saleh , Sadik Christian D. , Schmidt Enno , Baines John F.
Published: May 2021

Introduction

Bullous pemphigoid (BP) is the most common autoimmune blistering disease. It predominately afflicts the elderly and is significantly associated with increased mortality. The observation of age-dependent changes in the skin microbiota as well as its involvement in other inflammatory skin disorders suggests that skin microbiota may play a role in the emergence of BP blistering. We hypothesize that changes in microbial diversity associated with BP might occur before the emergence of disease lesions, and thus could represent an early indicator of blistering risk.

Objectives

The present study aims to investigate potential relationships between skin microbiota and BP and elaborate on important changes in microbial diversity associated with blistering in BP.

Methods

The study consisted of an extensive sampling effort of the skin microbiota in patients with BP and age- and sex-matched controls to analyze whether intra-individual, body site, and/or geographical variation correlate with changes in skin microbial composition in BP and/or blistering status.

Results

We find significant differences in the skin microbiota of patients with BP compared to that of controls, and moreover that disease status rather than skin biogeography (body site) governs skin microbiota composition in patients with BP. Our data reveal a discernible transition between normal skin and the skin surrounding BP lesions, which is characterized by a loss of protective microbiota and an increase in sequences matching Staphylococcus aureus, a known inflammation-promoting species. Notably, S. aureus is ubiquitously associated with BP disease status, regardless of the presence of blisters.

Conclusion

The present study suggests S. aureus may be a key taxon associated with BP disease status. Importantly, differences in a few key indicator taxa reliably discriminate between patients with BP and matched controls. This may serve as valuable information for assessing blistering risk and treatment outcomes in a clinical setting.
Haplotype Associated RNA Expression (HARE) Improves Prediction of Complex Traits in Maize
Authors: Giri Anju , Khaipho-Burch Merritt , Buckler Edward S. , Ramstein Guillaume P.
Published: May 2021

Genomic prediction typically relies on associations between single-site polymorphisms and traits of interest. This representation of genomic variability has been successful for prediction within populations. However, it usually cannot capture the complex effects due to combination of alleles in haplotypes. Therefore, accuracy across populations has usually been low. Here we present a novel and cost-effective method for imputingcishaplotype associated RNA expression (HARE, RNA expression of genes by haplotype), studied their transferability across tissues, and evaluated genomic prediction models within and across populations. HARE focuses on tightly linkedcisacting causal variants in the immediate vicinity of the gene, while excludingtranseffects from diffusion and metabolism, so it would be more transferrable across different tissues and populations. We showed that HARE estimates captured one-third of the variation in gene expression and were more transferable across diverse tissues than the measured transcript expression. HARE estimates were used in genomic prediction models evaluated within and across two diverse maize panels – a diverse association panel (Goodman Association panel) and a large half-sib panel (Nested Association Mapping panel) – for predicting 26 complex traits. HARE resulted in up to 15% higher prediction accuracy than control approaches that preserved haplotype structure, suggesting that HARE carried functional information in addition to information about haplotype structure. The largest increase was observed when the model was trained in the Nested Association Mapping panel and tested in the Goodman Association panel. Additionally, HARE yielded higher within-population prediction accuracy as compared to measured expression values. The accuracy achieved by measured expression was variable across tissues whereas accuracy using HARE was more stable across tissues. Therefore, imputing RNA expression of genes by haplotype is stable, cost-effective, and transferable across populations.

Author summary

The increasing availability of genomic data has been widely used in the prediction of many traits. However, genome wide prediction has been mostly carried out within populations and without explicit modeling of RNA or protein expression. In this study, we explored the prediction of field traits within and across populations using estimated RNA expression attributable to only the DNA sequence around a gene. We showed that the estimated RNA expression was more transferable than overall measured RNA expression. We improved prediction of field traits up to 15% using estimated gene expression as compared to observed expression or gene sequence alone. Overall, these findings indicate that structural and functional information in the gene sequence are highly transferable.
Treatment with sodium butyrate induces autophagy resulting in therapeutic benefits for spinocerebellar ataxia type 3
Authors: Watchon Maxinne , Robinson Katherine J. , Luu Luan , An Yousun , Yuan Kristy C. , Plenderleith Stuart K. , Cheng Flora , Don Emily K. , Nicholson Garth A. , Lee Albert , Laird Angela S.
Published: May 2021

Spinocerebellar ataxia type 3 (SCA3, also known as Machado Joseph disease) is a fatal neurodegenerative disease caused by expansion of the trinucleotide repeat region within theATXN3/MJDgene. Mutation ofATXN3causes formation of ataxin-3 protein aggregates, neurodegeneration and motor deficits. Here we investigated the therapeutic potential and mechanistic activity of sodium butyrate (SB), the sodium salt of butyric acid, a metabolite naturally produced by gut microbiota, on cultured SH-SY5Y cells and transgenic zebrafish expressing human ataxin-3 containing 84 glutamine (Q) residues to model SCA3. SCA3 SH-SY5Y cells were found to contain high molecular weight ataxin-3 species and detergent insoluble protein aggregates. Treatment with SB increased activity of the autophagy protein quality control pathway in the SCA3 cells, decreased presence of ataxin-3 aggregates and presence of high molecular weight ataxin-3 in an autophagy-dependent manner. Treatment with SB was also beneficialin vivo,improving swimming performance, increasing activity of the autophagy pathway and decreasing presence of insoluble ataxin-3 protein species in the transgenic SCA3 zebrafish. Co-treating the SCA3 zebrafish with SB and chloroquine, an autophagy inhibitor, prevented the beneficial effects of SB on zebrafish swimming, indicating that the improved swimming performance was autophagy-dependent. To understand the mechanism by which SB induces autophagy we performed proteomic analysis of protein lysates from the SB treated and untreated SCA3 SH-SY5Y cells. We found that SB treatment had increased activity of Protein Kinase A and AMPK signalling, with immunoblot analysis confirming that SB treatment had increased levels of AMPK protein and its substrates. Together our findings indicate that treatment with SB can increase activity of the autophagy pathway through a PKA/AMPK-dependent process and that this has beneficial effectsin vitroandin vivo. We propose that treatment with sodium butyrate warrants further investigation as a potential treatment for neurodegenerative diseases underpinned by mechanisms relating to protein aggregation including SCA3.
Pathway centered analysis to guide clinical decision-making in precision medicine
Authors: Carvalho Luís B. , Capelo J. L. , Lodeiro Carlos , Dhir Rajiv , Pinheiro Luis Campos , Medeiros Mariana , Santos Hugo M.
Published: May 2021

Changes in the human proteome caused by disease before, during and after medical care is phenotype-dependent, so the proteome of each individual at any time point is a snapshot of the body’s response to disease and to disease treatment. Here, we introduce a new concept named differential Personal Pathway index (dPPi). This tool extracts and summates comprehensive disease-specific information contained within an individual’s proteome as a holistic way to follow the response to disease and medical care over time. We demonstrate the principle of the dPPi algorithm on proteins found in urine from patients suffering from neoplasia of the bladder. The relevance of the dPPi results to the individual clinical cases is described. The dPPi concept can be extended to other malignant and non-malignant diseases, and to other types of biopsies, such as plasma, serum or saliva. We envision the dPPi as a tool for clinical decision-making in precision medicine.
Structure of the hexameric fungal plasma membrane proton pump in its auto-inhibited state
Authors: Heit Sabine , Geurts Maxwell M.G. , Murphy Bonnie J. , Corey Robin A. , Mills Deryck J. , Kühlbrandt Werner , Bublitz Maike
Published: May 2021

The fungal plasma membrane H+-ATPase Pma1 is a vital enzyme, generating a proton-motive force that drives the import of essential nutrients. Auto-inhibited Pma1 hexamers in starving fungi are activated by glucose signalling resulting in phosphorylation of the auto-inhibitory domain. As related P-type ATPases are not known to oligomerise, the physiological relevance of Pma1 hexamers remains unknown. We have determined the structure of hexameric Pma1 from Neurospora crassa by cryo-EM at 3.3 Å resolution, elucidating the molecular basis for hexamer formation and auto-inhibition, and providing a basis for structure-based drug development. Coarse-grained molecular dynamics simulations in a lipid bilayer suggest lipid-mediated contacts between monomers and a substantial protein-induced membrane deformation that could act as a proton-attracting funnel.
Unfolding and Translocation of Knotted Proteins by Clp Biological Nanomachines: Synergistic Contribution of Primary Sequence and Topology Revealed by Molecular Dynamics Simulations
Authors: Fonseka Hewafonsekage Yasan Y. , Javidi Alex , Oliveira Luiz F. L. , Micheletti Cristian , Stan George
Published: May 2021

We use Langevin dynamics simulations to model, at atomistic resolution, how various natively–knotted proteins are unfolded in repeated allosteric translocating cycles of the ClpY ATPase. We consider proteins representative of different topologies, from the simplest knot (trefoil 31), to the three–twist 52knot, to the most complex stevedore, 61, knot. We harness the atomistic detail of the simulations to address aspects that have so far remained largely unexplored, such as sequence–dependent effects on the ruggedness of the landscape traversed during knot sliding. Our simulations reveal the combined effect on translocation of the knotted protein structure, i.e. backbone topology and geometry, and primary sequence, i.e. side chain size and interactions, and show that the latter can even dominate translocation hindrance. In addition, we observe that, due to the interplay between the knotted topology and intramolecular contacts, the transmission of tension along the peptide chain occurs very differently from homopolymers. Finally, by considering native and non–native interactions, we examine how the disruption or formation of such contacts can affect the translocation processivity and concomitantly create multiple unfolding pathways with very different activation barriers.
Modular development enables rapid design of media for alternative hosts
Authors: Biedermann Andrew M. , Gengaro Isabella R. , Rodriguez-Aponte Sergio A. , Love Kerry R. , Love J. Christopher
Published: May 2021

Developing media to sustain cell growth and production is an essential and ongoing activity in bioprocess development. Modifications to media can often address host or product-specific challenges, such as low productivity or poor product quality. For other applications, systematic design of new media can facilitate the adoption of new industrially relevant alternative hosts. Despite manifold existing methods, common approaches for optimization often remain time and labor intensive. We present here a novel approach to conventional media blending that leverages stable, simple, concentrated stock solutions to enable rapid improvement of measurable phenotypes of interest. We applied this modular methodology to generate high-performing media for two phenotypes of interest: biomass accumulation and heterologous protein production, using high-throughput, milliliter-scale batch fermentations ofPichia pastorisas a model system. In addition to these examples, we also created a flexible open-source package for modular blending automation on a low-cost liquid handling system to facilitate wide use of this method. Our modular blending method enables rapid, flexible media development, requiring minimal labor investment and prior knowledge of the host organism, and should enable developing improved media for other hosts and phenotypes of interest.
ImprovedApis melliferareference genome based on the alternative long-read-based assemblies
Authors: Kaskinova Milyausha , Yunusbayev Bayazit , Altinbaev Radick , Raffiudin Rika , Carpenter Madeline H. , Nikolenko Alexey , Harpur Brock A. , Yunusbaev Ural
Published: May 2021

Apis melliferaL., the western honey bee is a major crop pollinator that plays a key role in beekeeping and serves as an important model organism in social behavior studies. Recent efforts have improved on the quality of the honey bee reference genome and developed a chromosome-level assembly of sixteen chromosomes, two of which are gapless. However, the rest suffer from 51 gaps, 160 unplaced/unlocalized scaffolds, and the lack of 2 distal telomeres. The gaps are located at the hard-to-assemble extended highly repetitive chromosomal regions that may contain functional genomic elements. Here, we usede-novore-assemblies from the most recent reference genome Amel_HAv_3.1 raw reads and other long-read-based assemblies (INRA_AMelMel_1.0, ASM1384120v1, and ASM1384124v1) of the honey bee genome to resolve 13 gaps, five unplaced/unlocalized scaffolds and, the lacking telomeres of the Amel_HAv_3.1. The total length of the resolved gaps is 848,747 bp. The accuracy of the corrected assembly was validated by mapping PacBio reads and performing gene annotation assessment. Comparative analysis suggests that the PacBio-reads-based assemblies of the honey bee genomes failed in the same highly repetitive extended regions of the chromosomes, especially on chromosome 10. To fully resolve these extended repetitive regions, further work using ultra-long Nanopore sequencing would be needed. Our updated assembly facilitates more accurate reference-guided scaffolding and marker/sequence mapping in honey bee genomics studies.
Use of U.S. Blood Donors for National Serosurveillance of SARS-CoV-2 Antibodies: Basis for an Expanded National Donor Serosurveillance Program
Authors: Stone Mars , Germanio Clara Di , Wright David J. , Sulaeman Hasan , Dave Honey , Fink Rebecca V. , Notari Edward P. , Green Valerie , Strauss Donna , Kessler Debra , Destree Mark , Saa Paula , Williamson Phillip C. , Simmons Graham , Stramer Susan L. , Opsomer Jean , Jones Jefferson M. , Kleinman Steven , Busch Michael P. ,   for the NHLBI Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P)
Published: May 2021

Introduction

The REDS-IV-P Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE) seroprevalence study conducted monthly cross-sectional testing for SARS-CoV-2 antibodies on blood donors in six U.S. metropolitan regions to estimate the extent of SARS-COV-2 infections over time.

Study Design/Methods

During March-August 2020, approximately ≥1,000 serum specimens were collected monthly from each region and tested for SARS-CoV-2 antibodies using a well-validated algorithm. Regional seroprevalence estimates were weighted based on demographic differences with the general population. Seroprevalence was compared with reported COVID-19 case rates over time.

Results/Findings

For all regions, seroprevalence was <1.0% in March 2020. New York experienced the biggest increase (peak seroprevalence, 15.8 % in May). All other regions experienced modest increases in seroprevalence(1-2% in May-June to 2-4% in July-August). Seroprevalence was higher in younger, non-Hispanic Black, and Hispanic donors. Temporal increases in donor seroprevalence correlated with reported case rates in each region. In August, 1.3-5.6 estimated cumulative infections (based on seroprevalence data) per COVID-19 case reported to CDC.

Conclusion

Increases in seroprevalence were found in all regions, with the largest increase in New York. Seroprevalence was higher in non-Hispanic Black and Hispanic blood donors than in non-Hispanic White blood donors. SARS-CoV-2 antibody testing of blood donor samples can be used to estimate the seroprevalence in the general population by region and demographic group. The methods derived from the RESPONSE seroprevalence study served as the basis for expanding SARS-CoV-2 seroprevalence surveillance to all 50 states and Puerto Rico.

SARS-CoV-2 serosurveillance data from blood donors in 6 US regions were used to estimate population weighted seroprevalence. Seroprevelance rates were higher in case rates. The study was expanded to a national donor serosurveillance program.

Disclaimer

The content is solely the responsibility of the authors and does not represent the policy of the National Institutes of Health or the Department of Health and Human Services. Any specific brandnames included in this manuscript are for identification purposes only and are not intended to represent an endorsement by CDC. The findings and conclusions in this report are those of the authorsand do not necessarily represent the official position of the Centers of Disease Control and Prevention.
THE EFFECT OF A BOARDING RESTRICTION PROTOCOL ON EMERGENCY DEPARTMENT CROWDING
Authors: Lee Ji Hwan , Kim Ji Hoon , Park Incheol , Lee Hyun Sim , Park Joon Min , Chung Sung Phil , Kim Hyeon Chang , Kim Min Joung
Published: May 2021

Background

Access block due to a lack of hospital beds causes emergency department (ED) crowding. We initiated the “boarding restriction protocol” that limits ED length of stay (LOS) for patients awaiting hospitalization to 24 hours from arrival. This study aimed to determine the effect of the protocol on ED crowding.

Method

This was a pre-post comparative study to compare ED crowding before and after protocol implementation. The primary outcome was the red stage fraction with more than 71 occupying patients in the ED (severe crowding level). LOS in the ED, treatment time and boarding time were compared. Additionally, the pattern of boarding patients staying in the ED according to the day of the week was confirmed.

Results

Analysis of the number of occupying patients in the ED, measured at 10-minute intervals, indicated a decrease from 65.0 (51.0–79.0) to 55.0 (43.0–65.0) in the pre- and post-periods, respectively (p<0.0001). The red stage fraction decreased from 38.9% to 15.1% of the pre- and post-periods, respectively (p<0.0001). The proportion beyond the goal of this protocol of 24 hours decreased from 7.6% to 4.0% (p<0.0001). The ED LOS of all patients was similar: 238.2 (134.0–465.2) and 238.3 (136.9–451.2) minutes in the pre- and post-periods, respectively. In admitted patients, ED LOS decreased from 770.7 (421.4–1587.1) to 630.2 (398.0–1156.8) minutes (p<0.0001); treatment time increased from 319.6 (198.5–482.8) to 344.7 (213.4–519.5) minutes (p<0.0001); and boarding time decreased from 298.9 (109.5–1149.0) to 204.1 (98.7–545.7) minutes (p<0.0001). In the pre-period, boarding patients accumulated in the ED on weekdays, with the accumulation resolved on Fridays; this pattern was alleviated in the post-period.

Conclusions

The protocol effectively resolved excessive ED crowding by alleviating the accumulation of boarding patients in the ED on weekdays. Additional studies should be conducted on changes this protocol brings to patient flow hospital-wide.
Linear causal filtering: definition and theory
Authors: Pascual-Marqui Roberto D. , Biscay Rolando J. , Bosch-Bayard Jorge , Achermann Peter , Faber Pascal , Kinoshita Toshihiko , Kochi Kieko
Published: May 2021

1.

This work provides a framework based on multivariate autoregressive modeling for linear causal filtering in the sense of Granger. In its bivariate form, the linear causal filter defined here takes as input signals A and B, and it filters out the causal effect of B on A, thus yielding two new signals only containing the Granger-causal effect of A on B. In its general multivariate form for more than two signals, the effect of all indirect causal connections between A and B, mediated by all other signals, are accounted for, partialled out, and filtered out also. The importance of this filter is that it enables the estimation of directional measures of causal information flow from any non-causal, non-directional measure of association. For instance, based on the classic coherence, a directional measure of strength of information flow from A to B is obtained when applied to the linear causal filtered pair containing only A to B connectivity information. This particular case is equivalent to the isolated effective coherence (doi.org/10.3389/fnhum.2014.00448). Of more recent interest are the large family of phase-phase, phase-amplitude, and amplitude-amplitude cross-frequency coupling measures which are non-directional. The linear causal filter makes it now possible to estimate the directional causal versions these measures of association. One important field of application is in brain connectivity analysis based on cortical signals of electric neuronal activity (e.g. estimated sources of EEG and MEG, and invasive intracranial ECoG recordings). The linear causal filter introduced here provides a novel solution to the problem of estimating the direction of information flow from any non-directional measure of association. This work provides definitions, non-ambiguous equations, and clear prescriptions for implementing the linear causal filter in diverse settings.
Embryonic hyperglycemia perturbs the development of specific retinal cell types, including photoreceptors
Authors: Titialii-Torres Kayla F. , Morris Ann C.
Published: May 2021

Chronic hyperglycemia has been linked to various long-term metabolic disruptions in adults, such as neuropathy, nephropathy, and diabetic retinopathy. According to the 2020 National Diabetes Statistics Report, 10.5% of the US population has diabetes and may be susceptible to long-term complications if blood glucose is not tightly regulated. Further, in 2018, 7.6% of US pregnancies were affected by gestational diabetes, with an average of 1-14% annually [1]. During pregnancy, glucose can pass through the placental barrier, and plays an important role in fetal development and survival. However, excess maternal glucose can also result in diabetic embryopathy. While many studies have examined the teratogenic effects of maternal diabetes on fetal heart development, little is known about the consequences of maternal hyperglycemia on the development of the embryonic retina. To address this question, we investigated retinal cell type differentiation and survival in both a genetic and nutritional model of embryonic hyperglycemia in zebrafish. Strikingly, we found that hyperglycemic larvae displayed a significant reduction in rod and cone photoreceptors and horizontal cells, whereas other retinal neurons were not affected. We also observed signs of reactive gliosis in the retinal Müller cells, as well as increased reactive oxygen species (ROS) production in hyperglycemic retinas. Hyperglycemic larvae displayed altered expression of metabolism related genes and had a slower optokinetic response than normoglycemic larvae, indicating altered visual function. Further analysis of early events in retinogenesis revealed a delay in retinal cell differentiation at 48 hpf in hyperglycemic embryos, that coincided with an increase in reactive oxygen species. Taken together, our results suggest that embryonic hyperglycemia results in abnormal retinal cell development via altered timing of retinal cell differentiation and ROS production, which is accompanied by visual defects. As the population with diabetes continues to grow, it is imperative to pinpoint the effects of embryonic hyperglycemia on retinal development. Further studies using zebrafish models of hyperglycemia will allow us to understand the molecular mechanisms underlying these effects, which could aid in the development of therapeutic strategies.
Evaluation of efficacy of carfentrazone + metsulfuron, sulfosulfuron + metsulfuron and halauxifen againstRumexspp. in wheat (Triticum aestivum) in Western Haryana
Authors: Soni Sunil , Singh Samunder , Garg Rajbir
Published: May 2021

Rumexspp. is most dominating broad-leaf weed of wheat crop. Complaints of poor efficacy of different herbicides againstRumexspp. have reported recently from different locations of Haryana state. Therefore, the present study was carried out under completely randomised design, replicated thrice, using three different herbicides namely carfentrazone + metsulfuron, sulfosulfuron + metsulfuron and halauxifen as treatments applied with three doses against four populations ofRumexspp. Plant height, chlorophyll fluorescence, electrical conductivity, mortality percentage and dry weight were recorded as observations. Results indicated that most of theRumexbiotypes were found resistant against sulfosulfuron + metsulfuron application. Majority of biotypes were moderately controlled by the application of halauxifen. Carfentrazone + metsulfuron effectively controlled theRumexspp. and provided 70-90 % control to all biotypes at double of the recommended dose. As per results of this study, carfentrazone + metsulfuron can be recommended for control ofRumexspp. in wheat.
Principled decision-making workflow with hierarchical Bayesian models of high throughput dose-response measurements
Authors: Ma Eric J. , Kummer Arkadij
Published: May 2021

We present a case study applying hierarchical Bayesian estimation on high throughput protein melting point data measured across the tree of life. We show that the model is able to impute reasonable melting temperatures even in the face of unreasonably noisy data. Additionally, we demonstrate how to use the variance in melting temperature posterior distribution estimates to enable principled decision-making in common high throughput measurement tasks, and contrast the decision-making workflow against simple maximum-likelihood curve fitting. We conclude with a discussion of the relative merits of each workflow.
Acidophilic Micrarchaeon Seems to Maintain a Slightly Alkaline Cytosolic pH
Authors: Winkler Dennis , Gfrerer Sabrina , Gescher Johannes
Published: May 2021

Despite several discoveries in recent years, the physiology of acidophilic Micrarchaeota remains largely enigmatic. “CandidatusMicrarchaeum harzensis A_DKE”, for example, highly expresses numerous genes encoding hypothetical proteins and their function is difficult to elucidate due to a lacking genetic system. Still, not even the intracellular pH value of A_DKE is known, and heterologous production attempts are generally missing so far. Hence, A_DKE’s isocitrate dehydrogenase (MhIDH) was recombinantly produced inEscherichia coliand purified for bio-chemical characterisation. MhIDH appeared to be specific for NADP+, yet promiscuous regarding divalent cations as cofactors. Kinetic studies showedKM-values of 53.03±5.63 µM and 1.94±0.12 mM andkcat-values of 38.48±1.62 s-1and 43.99±1.46 s-1for DL-isocitrate and NADP+, respectively.MhIDH’s exceptionally low affinity for NADP+, potentially limiting its reaction rate, can be likely attributed to the presence of a proline residue in the NADP+binding-pocket, which might cause a decrease in hydrogen bonding of the cofactor and a distortion of local secondary structure. Furthermore, a pH optimum of 7.89 implies, that A_DKE applies potent mechanisms of proton homoeostasis, to maintain a slightly alkaline cytosolic milieu in a highly acidic environment.
3D printed pacifier-shaped mouthpiece for fMRI-compatible gustometers
Authors: Munoz Tord David , Coppin Géraldine , Pool Eva R. , Mermoud Christophe , Pataky Zoltan , Sander David , Delplanque Sylvain
Published: May 2021

Gustometers have allowed the delivery of liquids in fMRI settings for decades and mouthpieces are a critical part of those taste delivery systems. Here we propose an innovative 3D printed mouthpiece inspired by children’s pacifiers that allow participants to swallow while lying down in an MRI scanner. Our results validate the effectiveness of our method by showing significant clusters of activation in the insular and piriform cortex which are regions that have been consistently identified to compute taste processing. We used a large sample (n=85) to validate our method. Our mouthpiece fulfills several criteria guarantying a gustatory stimulus of quality, making the delivery more precise and reliable. Moreover, this new pacifier-shaped design is: simple and cheap to manufacture, hygienic, comfortable to keep in mouth, and flexible to diverse use cases.We hope that this new method will promote and facilitate the study of taste and flavor perception in the context of reward processing in affective neuroscience and thus help provide an integrative approach to the study of the emotional nature of rewards.
Dichaete, a Sox2 homologue, prevents activation of cell death in multiple developmental contexts
Authors: Harding Katherine , Heath Katerina , White Kristin
Published: May 2021

Precisely regulated cell death plays a critical role in normal development and is controlled by the balance of pro-apoptotic and anti-apoptotic signals. InDrosophila, transcription of the clustered cell death activatorsgrimandreaperis turned on in the developing nervous system to eliminate neural stem cells at the end of embryonic development. This transcription is activated by a pulse of the Hox geneabdominal-A. We show here that the Sox2 homologueDichaeteinhibits neural stem cell death when overexpressed, and loss ofDichaetepromotes premature neural stem cell death. The anti-apoptotic activity of Dichaete opposes the pro-apoptotic factorsabdominal-A, as well as the transcription factorgrainyhead. The function of all three genes impinge on an enhancer that regulates the transcription ofgrimandreaper. Furthermore, we find that the balance betweenabdominal-AandDichaeteis likely to regulate the death of other cells during development, including cells in the developing midline, the developing hindgut, and in the early abdominal epidermis. Loss ofDichaeteresults in premature death in these tissues. This death can be rescued by the deletion of the enhancer region betweengrimandreaper. These data suggest thatDichaetefunctions to inhibit cell death activated byabdominal-Ain multiple developmental contexts.
Equilibrium morphologies of a macromolecule under soft confinement
Authors: Biswas Subhadip , Chakrabarti Buddhapriya
Published: May 2021

We study equilibrium shapes and shape transformations of a confined semiflexible chain inside a soft lipid tubule using simulations and continuum theories. The deformed tubular shapes and chain conformations depend on the relative magnitude of their bending moduli. We characterise the collapsed macromolecular shapes by computing statistical quantities that probe the polymer properties at small length scales and report a prolate to toroidal coil transition for stiff chains. Deformed tubular shapes, calculated using elastic theories, agree with simulations. In conjunction with scattering studies, our work may provide a mechanistic understanding of gene encapsulation in soft structures.
Emu: Species-Level Microbial Community Profiling for Full-Length Nanopore 16S Reads
Authors: Curry Kristen D. , Wang Qi , Nute Michael G. , Tyshaieva Alona , Reeves Elizabeth , Soriano Sirena , Graeber Enid , Finzer Patrick , Mendling Werner , Wu Qinglong , Savidge Tor , Villapol Sonia , Dilthey Alexander , Treangen Todd J.
Published: May 2021

16S rRNA based analysis is the established standard for elucidating microbial community composition. While short read 16S analyses are largely confined to genus-level resolution at best since only a portion of the gene is sequenced, full-length 16S sequences have the potential to provide species-level accuracy. However, existing taxonomic identification algorithms are not optimized for the increased read length and error rate of long-read data. Here we present Emu, a novel approach that employs an expectation-maximization (EM) algorithm to generate taxonomic abundance profiles from full-length 16S rRNA reads. Results produced from one simulated data set and two mock communities prove Emu capable of accurate microbial community profiling while obtaining fewer false positives and false negatives than alternative methods. Additionally, we illustrate a real-world application of our new software by comparing clinical sample composition estimates generated by an established whole-genome shotgun sequencing workflow to those returned by full-length 16S sequences processed with Emu.
Homotopic contralesional excitation suppresses spontaneous circuit repair and global network reconnections following ischemic stroke
Authors: Bice Annie R. , Xiao Qingli , Kong Justin , Yan Ping , Rosenthal Zachary P. , Kraft Andrew W. , Smith Karen , Wieloch Tadeusz , Lee Jin-Moo , Culver Joseph P. , Bauer Adam Q.
Published: May 2021

Understanding circuit-level changes that affect the brain’s capacity for plasticity will inform the design of targeted interventions for treating stroke recovery. We combine optogenetic photostimulation with optical neuroimaging to examine how contralesional excitatory activity affects cortical remodeling after stroke in mice. Following photothrombosis of left primary somatosensory forepaw (S1FP) cortex, mice received chronic excitation of right S1FP, a maneuver mimicking the use of the unaffected limb during recovery. Contralesional excitation suppressed perilesional S1FP remapping and was associated with abnormal patterns of evoked activity in the unaffected limb. Contralesional stimulation prevented the restoration of resting-state functional connectivity (RSFC) within the S1FP network, RSFC in several networks functionally-distinct from somatomotor regions, and resulted in persistent limb-use asymmetry. In stimulated mice, perilesional tissue exhibited suppressed transcriptional changes in several genes important for recovery. These results suggest that contralesional excitation impedes local and global circuit reconnection through suppression of several neuroplasticity-related genes after stroke.