bluuebunny/crossref_metadata_2025 huggingface dataset:
Seroprevalence of anti-SARS-CoV-2 antibodies in Iquitos, Loreto, Peru
Authors: Álvarez-Antonio Carlos , Meza-Sánchez Graciela , Calampa Carlos , Casanova Wilma , Carey Cristiam , Alava Freddy , Rodríguez-Ferrucci Hugo , Quispe Antonio M.
Published: January 2021

Background

Detection of SARS-CoV-2 antibodies among people at risk is critical for understanding both the prior transmission of COVID-19 and vulnerability of the population to the continuing transmission and, when done serially, the intensity of ongoing transmission over an interval in a community. In this study, we estimated the seroprevalence of COVID-19 in a representative population-based cohort of Iquitos, one of the regions with the highest mortality rates from COVID-19 in Peru, where a devastating number of cases occurred in March 2020.

Methods

We conducted a population-based study of transmission tested each participant using the COVID-19 IgG/IgM Rapid Test from Orient Gene Biotech and used survey analysis methods to estimate seroprevalence accounting for the sampling design effect and test performance characteristics. Here we report results from the baseline (13 to 18 July 2020) and the first month of follow-up (13 to 18 August 2020) study.

Findings

We enrolled a total of 716 participants and estimated seroprevalence of 70.0% (95% CI: 67.0%–73.4%), a test-re-test positivity of 65% (95% CI: 61.0%–68.3%), and an incidence of new exposures of 1.8% (95% CI: 0.9%–3.2%) data that suggest that transmission is ongoing but is occurring at low levels. We observed significant differences in the seroprevalence between age groups, with participants 18 to 29 years of age having lower seroprevalence than children <12 years of age (Prevalence ratio =0.85 [PR]; 95% CI: 0.73 – 0.98), suggesting that children were not refractory to infection in this setting.

Interpretation

Iquitos demonstrates one of the highest rates of seroprevalence of COVID-19 worldwide. Current data shows a limited case burden in Iquitos for the past seven months and suggests that these levels are sufficient to provide significant but incomplete herd immunity.

Funding

Dirección Regional de Salud de Loreto, DIRESA, Loreto, Peru
Sleeping under the waves: a longitudinal study across the contagion peaks of COVID-19 pandemic in Italy
Authors: Salfi Federico , D’Atri Aurora , Tempesta Daniela , Ferrara Michele
Published: January 2021

After the March–April 2020 COVID-19 outbreak, a second contagion wave afflicted Europe in autumn. This study aimed to evaluate sleep health/patterns of Italians during this further challenging situation.

A total of 2013 Italians longitudinally participated in a web-based survey during the two contagion peaks of the COVID-19 outbreak. We investigated the risk factors for sleep disturbances during the second wave, and we compared sleep quality and psychological well-being between the two assessments (March–April and November–December 2020). Female gender, low education, evening chronotype, being at high-risk for COVID-19 infection, reporting negative social or economic impact, and evening smartphone overuse predicted a higher risk of poor sleep and insomnia symptoms during the second wave. Advanced age, living with high-risk subjects for COVID-19 infection, and having a relative/friend infected with COVID-19 before the prior two weeks were risk categories for poor sleep quality. Living with children, having contracted COVID-19 before the prior two weeks, being pessimistic on the vaccine, and working in healthcare were risk factors for insomnia symptoms. The follow-up assessment highlighted reduced insomnia symptoms and anxiety. Nevertheless, we showed reduced sleep duration, higher daytime dysfunction and sleep medication use, and advanced sleep phase, confirming the alarming prevalence of poor sleepers (∼60%) and severe depression (∼20%) in a context of increased perceived stress.

This study demonstrated a persistent impact of the COVID-19 pandemic on sleep and mental health. Large-scale interventions to counteract the chronicity and exacerbation of sleep and psychological disturbances are necessary, especially for the risk categories.
Optimizing SARS-CoV-2 vaccination strategies in France: Results from a stochastic agent-based model
Authors: Hoertel Nicolas , Blachier Martin , Limosin Frédéric , Sánchez-Rico Marina , Blanco Carlos , Olfson Mark , Luchini Stéphane , Schwarzinger Michaël , Leleu Henri
Published: January 2021

The COVID-19 pandemic is a major global societal, economic and health threat. The availability of COVID-19 vaccines has raised hopes for a decline in the pandemic. We built upon a stochastic agent-based microsimulation model of the COVID-19 epidemic in France. We examined the potential impact of different vaccination strategies, defined according to the age, medical conditions, and expected vaccination acceptance of the target non-immunized adult population, on disease cumulative incidence, mortality, and number of hospital admissions. Specifically, we examined whether these vaccination strategies would allow to lift all non-pharmacological interventions (NPIs), based on a sufficiently low cumulative mortality and number of hospital admissions. While vaccinating the full adult non-immunized population, if performed immediately, would be highly effective in reducing incidence, mortality and hospital-bed occupancy, and would allow discontinuing all NPIs, this strategy would require a large number of vaccine doses. Vaccinating only adults at higher risk for severe SARS-CoV-2 infection, i.e. those aged over 65 years or with medical conditions, would be insufficient to lift NPIs. Immediately vaccinating only adults aged over 45 years, or only adults aged over 55 years with mandatory vaccination of those aged over 65 years, would enable lifting all NPIs with a substantially lower number of vaccine doses, particularly with the latter vaccination strategy. Benefits of these strategies would be markedly reduced if the vaccination was delayed, was less effective than expected on virus transmission or in preventing COVID-19 among older adults, or was not widely accepted.
Population-scale patient safety data reveal inequalities in adverse events before and during COVID-19 pandemic
Authors: Zhang Xiang , Sumathipala Marissa , Zitnik Marinka
Published: January 2021

Adverse patient safety events were associated with 110 thousand deaths in the U.S. alone in 2019. The COVID-19 pandemic has further challenged the ability of healthcare systems to ensure safe medication use, and its effects on patient safety remain unknown. Here, we investigate negative outcomes associated with medication use before and during the pandemic. Using a dataset of 10,443,476 reports involving 3,624 drugs and 19,193 adverse events, we develop an algorithmic approach to analyze the pandemic’s impact on the incidence of drug safety events by evaluating disproportional reporting relative to the pre-pandemic time, quantifying unexpected trends in clinical outcomes, and adjusting for drug interference. Among 64 adverse events identified by our analyses, we find 54 have increased incidence rates during the pandemic, even though adverse event reporting decreased by 4.4% overall. We find clinically relevant differences in drug safety outcomes between demographic groups. Compared to male patients, women report 47.0% more distinct adverse events whose occurrence significantly increased during the pandemic relative to pre-pandemic levels. Out of 53 adverse events with a pre-pandemic gender gap, 33 have an increased gender gap during the pandemic. While musculoskeletal and metabolic side effects are disproportionately enriched in women during the pandemic, immune-related adverse events are enriched only in men. We also find the number of adverse events with an increased reporting ratio is higher in adults (by 16.8%) than in older patients (adjusted for population size). Our findings have implications for safe medication use and tie the variation in adverse events to patients that may be disproportionately affected by preventable inequities during a public health emergency.
Population-based seroprevalence of SARS-CoV-2 antibodies in a high-altitude setting in Peru
Authors: Huamaní Charles , Velásquez Lucio , Montes Sonia , Mayanga-Herrera Ana , Bernabé-Ortiz Antonio
Published: January 2021

Background

Little evidence exists about the prevalence of COVID-19 infection at high altitude. We aimed to estimate the population-based seroprevalence of COVID-19 in Cusco at the end of the first wave.

Methods

A population-based survey was conducted in September 2020 in three settings in Cusco: (1) Cusco city at 3300 meters above the sea level (m.a.s.l.), (2) the periphery of Cusco (Santiago, San Jerónimo, San Sebastián, and Wanchaq) at 3300 m.a.s.l., and (3) Quillabamba city, located at 1050 m.a.s.l. People aged ≥18 years within a family unit were included. The diagnosis of COVID-19 infection was based on identifying total antibodies (IgM and IgG) anti-SARS-CoV-2 in serum using the Elecsys Anti-SARS-CoV-2 chemiluminescence test.

Findings

We enrolled 1924 participants from 712 families. Of the total, 637 participants were COVID-19 seropositive. Seroprevalence was 38·8% (95%CI: 33·4%-44·9%) in Cusco city, 34·9% (95%CI: 30·4%-40·1%) in the periphery of Cusco, and 20·3% (95%CI: 16·2%-25·6%) in Quillabamba. In 141 families (19·8%; 95%CI: 17·0%-22·8%) the whole members were positive to the test. Living with more than three persons in the same house, a positive COVID-19 case at home, and a member who died in the last five months were factors associated with COVID-19 positivity. The smell/taste alteration was the symptom most associated with seropositivity (aOR= 14·27, 95% CI: 8·24-24·70); whereas always wearing a face shield (aOR= 0·62; 95% CI: 0·46-0·84) or a facial mask (aOR= 0·65, 95% CI: 0·47-0·88) reduced that probability.

Interpretation

Seroprevalence of COVID-19 in Cusco was high, with significant differences between settings. Wearing masks and face shields were associated with lower rate of infection; however, efforts must be made to sustain them over time since there is still a high proportion of susceptible people.

Funding

Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica (FONDECYT – Perú) and Universidad Andina del Cusco.
Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions
Authors: Yang Siwy Ling , DeFalco Louis , Anderson Danielle E. , Zhang Yu , Aw Ashley J , Lim Su Ying , Ni Lim Xin , Tan Kiat Yee , Zhang Tong , Chawla Tanu , Su Yan , Lezhava Alexander , de Sessions Paola , Merits Andres , Wang Lin-Fa , Huber Roland G. , Wan Yue
Published: January 2021

SARS-CoV-2 has emerged as a major threat to global public health, resulting in global societal and economic disruptions. Here, we investigate the intramolecular and intermolecular RNA interactions of wildtype (WT) and a mutant (Δ382) SARS-CoV-2 virus in cells using high throughput structure probing on Illumina and Nanopore platforms. We identified twelve potentially functional structural elements within the SARS-CoV-2 genome, observed that identical sequences can fold into divergent structures on different subgenomic RNAs, and that WT and Δ382 virus genomes can fold differently. Proximity ligation sequencing experiments identified hundreds of intramolecular and intermolecular pair-wise interactions within the virus genome and between virus and host RNAs. SARS-CoV-2 binds strongly to mitochondrial and small nucleolar RNAs and is extensively 2’-O-methylated. 2’-O-methylation sites in the virus genome are enriched in the untranslated regions and are associated with increased pair-wise interactions. SARS-CoV-2 infection results in a global decrease of 2’-O-methylation sites on host mRNAs, suggesting that binding to snoRNAs could be a pro-viral mechanism to sequester methylation machinery from host RNAs towards the virus genome. Collectively, these studies deepen our understanding of the molecular basis of SARS-CoV-2 pathogenicity, cellular factors important during infection and provide a platform for targeted therapy.
Measurements of acoustic radiation force of ultrahigh frequency ultrasonic transducers using model-based approach
Authors: Kim Sangnam , Moon Sunho , Rho Sunghoon , Yoon Sangpil
Published: January 2021

Even though ultrahigh frequency ultrasonic transducers over 60 MHz have been used for single cell level manipulation such as intracellular delivery, acoustic tweezers, and stimulation to investigate cell phenotype and cell mechanics, no techniques have been available to measure actual acoustic radiation force (ARF) applied to target cells. Therefore, we have developed an approach to measure ARF of ultrahigh frequency ultrasonic transducers using theoretical model of the dynamics of a solid sphere in a gelatin phantom. To estimate ARF at the focus of 130 MHz transducer, we matched measured maximum displacements of a solid sphere with theoretical calculations. We selected appropriate ranges of input voltages and pulse durations for single cell applications and estimated ARF were in the range of tens of pN to nN. FRET live cell imaging was demonstrated to visualize calcium transport between cells after a target single cell was stimulated by the developed ultrasonic transducer.
The unapparent effect of climate forcing on urban amoebiasis in Mexico City
Authors: Baeza Andres , Santos-Vega Mauricio , Escalante Ana E. , Eakin Hallie
Published: January 2021

Abstract

Despite advances in the provision of sanitation infrastructure in cities, diarrheal-related illnesses continue to be a global burden. In cities of the developing world, explanations for the persistence of diarrheal-related diseases revolve around the role of sanitation, poverty, and individual behavior. Less is known about the role of climate in forcing the inter-annual variability of transmission. We quantified the contribution of rainfall to the transmission of a diarrhoeal disease caused by the protozoan Entamoeba histolytica. We formulated a process-based model of the population dynamics of Entamoeba histolytica in 6 municipalities of Mexico City, and we reconstructed the interannual variability of the observed cases of amebiasis between 2005 and 2012. Using inference methods for non-linear systems, we estimated that 10% of the susceptible individuals were infected in early 2005 and 90% of those infections were causally related to the exposure to the environmental stage of the pathogen after rainfall events. The magnitude of these results underscores the importance of considering the interaction between climate forcing and water management as ecological determinants of health in megacities.
Comparative and Stability Study of Glucose Concentrations Measured in both Sodium Fluoride and Serum Separator tubes
Authors: Dibbasey Mustapha , Price Cathy , Lawal Bolarinde , Umukoro Solomon
Published: January 2021

Introduction

Sodium fluoride/potassium oxalate (NaF/KOx) tubes were once regarded as the gold-standard tubes for glucose analysis. Even though their ineffectiveness in immediately inhibiting glycolysis has been reported in several studies especially in the first 1–4hours, they are still used in our clinical Biochemistry laboratory for glucose measurement. However in its absence, only SSTs are employed for glucose measurement.

Aim

To determine whether SSTs can replace NaF/KOx tubes for laboratory-based measurement of blood glucose and to assess the stability of glucose concentrations for 3 days period

Methods

During the study period (1 March to 11 April, 2015), a total of 50 paired samples collected separately in NaF/KOx tubes and SSTs from healthy adult participants in the Gambia Adults Reference Intervals Study (GARIS) project were used as the project sample size. The samples were analysed within 2hours, and at 24hours, 42hours and 72hours time-points following blood collection and separation using Vitros 350 dry chemistry analyser. The GARIS samples were treated as clinical samples.

Results

There was no significant difference in the mean glucose concentrations between the two tubes (Mean difference= 0.06mmol/L; P=0.38) recorded in the different time-points. Using growth trajectory and mixed effects model, the study data showed no significant change in the glucose concentrations (p=0.25) for three days period.

Conclusions

The study confirms that SSTs can produce similar glucose results when employed in the absence of NaF/KOx tubes. Besides, the glucose concentrations were stable in both tubes for three days when the samples were separated within two hours and refrigerated in 2-8°C.
Predicting spatial and seasonal patterns of wildlife-vehicle collisions in high-risk areas
Authors: Nguyen Hanh K.D. , Buettel Jessie C. , Fielding Matthew W. , Brook Barry W.
Published: January 2021

Context

Vehicle collisions with wildlife can injure or kill animals, threaten human safety, and threaten the viability of rare species. This has led to a focus in road-ecology research on identifying the key predictors of ‘road-kill’ risk, with the goal of guiding management to mitigate its impact. However, because of the complex and context-dependent nature of the causes of risk exposure, modelling road-kill data in ways that yield consistent recommendations has proven challenging.

Aim

Here we used a novel multi-model machine-learning approach to identify the spatio-temporal predictors, such as traffic volume, road shape, surrounding vegetation and distance to human settlements, associated with road-kill risk.

Methods

We collected data on the location, identity and size of each road mortality across four seasons along eight roads in southern Tasmania – a ‘road-kill hotspot’ of management concern. We focused on three large-bodied and frequently impacted crepuscular Australian marsupial herbivore species, the rufous-bellied pademelon (Thylogale billardierii), Bennett’s wallaby (Macropus rufogriseus) and the bare-nosed wombat (Vombatus ursinus). We fit the point-location data using ‘lasso-regularization’ of a logistic generalized linear model (LL-GLM) and out-of-bag optimization of a decision-tree-based ‘random forests’ (RF) algorithm.

Results

The RF model, with high-level feature interactions, yielded superior results to the linear additive model, with a RF classification accuracy of 84.8% for the 871 road-kill observations and a true skill statistic of 0.708, compared to 61.2% and 0.205 for the LL-GLM.

Conclusions

Forested areas with no roadside barrier fence along curved sections of road posed the highest risk to animals. Seasonally, the frequency of wildlife-vehicle collisions increased notably for females during oestrus, when they were more dispersive and so had a higher encounter rate with roads.

Implications

These findings illustrate the value of using data-driven approaches to predictive modelling, as well as offering a guide to practical management interventions that can mitigate road-related hazards.
Initial Clinical Outcomes from NOCD Digital Behavioral Health Treatment of Obsessive-Compulsive Disorder Using Exposure and Response Prevention
Authors: Feusner Jamie D. , McGrath Patrick B. , Faneuff Ted , Lonsway Stephanie , Mohideen Reza , Trusky Larry , Smith Stephen M.
Published: January 2021

Effective first-line treatments for obsessive-compulsive disorder (OCD) include exposure and response prevention (ERP) therapy. Despite extensive evidence of its efficacy in clinical studies and real-world samples, ERP is still underutilized as a treatment, likely due to access to care barriers such as the availability of adequately trained ERP therapists, geographical location, time, and cost. NOCD has created a digital behavioral health treatment for OCD using ERP delivered via teletherapy and between-session support. We examined preliminary treatment outcomes in a large naturalistic sample of 2069 adults, children, and adolescents with a primary OCD diagnosis. Treatment consisted of twice-weekly live teletherapy ERP for three weeks, followed by six weeks of once-weekly brief teletherapy check-ins. Assessments were conducted at baseline, after completion of three weeks of twice-weekly sessions, and at the end of the six weeks of brief check-ins. Treatment resulted in significant improvements, with a 45% mean reduction in OCD symptoms and a 71% response rate (≥35% reduction in OCD symptoms).Treatment also resulted in a significant, 43% reduction in depression, a 49% reduction in anxiety, and a 35% reduction in stress symptoms. Quality of life improved by a mean of 35%. The mean duration of treatment was approximately 11 weeks, and the total therapist time was approximately 11 hours, which is less than half the total time compared with standard once-weekly outpatient treatment. In sum, in this preliminary sample, NOCD’s treatment model for OCD, delivered in a readily-accessible format for patients, has demonstrated to be effective and efficient.
Viral dispersion in open air
Authors: Machado Gabriella Trombini , de Carvalho Pinto Claudia Ramos , da Fonseca Luisa Andrea Villanueva , dos Santos Ramos Taissa Cristina , Pereira Paggi Tuanny Fernanda , Spira Beny
Published: January 2021

The SARS-CoV-2 pandemic has revived the debate about the routes of virus transmission and their likelihoods. It is of utmost importance to assess the risks of contamination of susceptible people by infectious individuals and to evaluate the level of viral transmission in the community. Most countries have imposed non-pharmaceutical measures to contain SARS-CoV-2 transmission, including social distancing and mask wearing. Here we evaluated the spreading of viruses in open air using harmless Escherichia coli bacteriophages as a surrogate. Phages were sprayed towards Petri dishes seeded with bacteria at different lengths and angles. Median droplets size was 127 µm, similar to those produced by sneeze. Our results showed that the transmission rate decreased exponentially with distance. The highest recorded transmission rate was 9 × 10−6 PFU/plate when phages were sprayed from a 1 m distance, suggesting that the probability of transmission of a single virus at a 1 m distance is 1:100,000. These results agree with the WHO recommendation that face mask protection in an uncrowded well-ventilated space is not required.
Association between polygenic propensity for a psychiatric disorder and nutrient intake
Authors: Hunjan Avina K. , Hübel Christopher , Lin Yuhao , Eley Thalia C. , Breen Gerome
Published: January 2021

Background

Despite the observed associations between psychiatric disorders and nutrient intake, genetic studies are limited.

Aims

We examined whether polygenic scores for psychiatric disorders, including anorexia nervosa, major depressive disorder and schizophrenia, are associated with self-reported nutrient intake.

Methods

We used data obtained by the UK Biobank ‘Diet by 24-hour recall’ questionnaire (N=163,619). Association was assessed using linear mixed models for the analysis of data with repeated measures.

Results

We find polygenic scores for psychiatric disorders are differentially associated with nutrient intake, with attention-deficit/hyperactivity disorder, bipolar disorder and schizophrenia showing the strongest associations, whilst autism spectrum disorder showed no association. Expressed as the effect of a one standard deviation higher polygenic score, anorexia nervosa polygenic score was associated with higher intake of fibre (0.06 g), folate (0.93 μg), iron (0.03 mg) and vitamin C (0.92 μg). Similarly, a higher major depressive disorder polygenic score was associated with 0.04 mg lower iron and 1.13 μg lower vitamin C intake per day, and a greater obsessive-compulsive disorder polygenic score with 0.06 g higher fibre intake. These associations were predominantly driven by socioeconomic status and educational attainment. However, a higher alcohol dependence polygenic score was associated with higher alcohol intake and individuals with higher persistent thinness polygenic scores reported their food to weigh 8.61 g less, both independent of socioeconomic status.

Conclusions

Our findings suggest that polygenic propensity for a psychiatric disorder is associated with dietary behaviour. The nutrient intake is based on self-reported data and findings must therefore be interpreted mindfully.

Declaration of interest

None.
Emergence of a novel SARS-CoV-2 strain in Southern California, USA
Authors: Zhang Wenjuan , Davis Brian D , Chen Stephanie S , Martinez Jorge M Sincuir , Plummer Jasmine T , Vail Eric
Published: January 2021

Since October 2020, novel strains of SARS-CoV-2 including B.1.1.7, have been identified to be of global significance from an infection and surveillance perspective. While this strain (B.1.1.7) may play an important role in increased COVID rates in the UK, there are still no reported strains to account for the spike of cases in Los Angeles (LA) and California as a whole, which currently has some of the highest absolute and per-capita COVID transmission rates in the country. From the early days of the pandemic when LA only had a single viral genome uploaded onto GISAID we have been at the forefront of generating and analyzing the SARS-CoV-2 sequencing data from the LA region. We report a novel strain emerging in Southern California. Most current cases in the catchment population in LA fall into two distinct subclades: 1) 20G (24% of total) is the predominant subclade currently in the United States 2) a relatively novel strain in clade 20C, CAL.20C strain (∼36% of total) is defined by five concurrent mutations. After an analysis of all of the publicly available data and a comparison to our recent sequences, we see a dramatic growth in the relative percentage of the CAL.20C strain beginning in November of 2020. The predominance of this strain coincides with the increased positivity rate seen in this region. Unlike 20G, this novel strain CAL.20C is defined by multiple mutations in the S protein, a characteristic it shares with both the UK and South African strains, both of which are of significant clinical and scientific interest
Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection
Authors: Gupta Rishi K. , Rosenheim Joshua , Bell Lucy C. , Chandran Aneesh , Guerra-Assuncao Jose A. , Pollara Gabriele , Whelan Matthew , Artico Jessica , Joy George , Kurdi Hibba , Altmann Daniel M. , Boyton Rosemary , Maini Mala , McKnight Aine , Lambourne Jonathan , Cutino-moguel Teresa , Manisty Charlotte , Treibel Thomas A. , Moon James C , Chain Benjamin , Noursadeghi Mahdad
Published: January 2021

We hypothesised that host-response biomarkers of viral infections may contribute to early identification of SARS-CoV-2 infected individuals, critical to breaking chains of transmission. We identified 20 candidate blood transcriptomic signatures of viral infection by systematic review and evaluated their ability to detect SARS-CoV-2 infection, compared to the gold-standard of virus PCR tests, among a prospective cohort of 400 hospital staff subjected to weekly testing when fit to attend work. The transcriptional signatures had limited overlap, but were mostly co-correlated as components of type 1 interferon responses. We reconstructed each signature score in blood RNA sequencing data from 41 individuals over sequential weeks spanning a first positive SARS-CoV-2 PCR, and after 6-month convalescence. A single blood transcript for IFI27 provided the highest accuracy for discriminating individuals at the time of their first positive viral PCR result from uninfected controls, with area under the receiver operating characteristic curve (AUROC) of 0.95 (95% confidence interval 0.91–0.99), sensitivity 0.84 (0.7–0.93) and specificity 0.95 (0.85–0.98) at a predefined test threshold. The test performed equally well in individuals with and without symptoms, correlated with viral load, and identified incident infections one week before the first positive viral PCR with sensitivity 0.4 (0.17–0.69) and specificity 0.95 (0.85–0.98). Our findings strongly support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection, for screening individuals such as contacts of index cases, in order to facilitate early case isolation and early antiviral treatments as they emerge.
Forecasting the Spread of the COVID-19 Epidemic in Lombardy: A Dynamic Model Averaging Approach
Authors: Gianmoena Lisa , Rios Vicente
Published: January 2021

Forecasting with accuracy the evolution of COVID-19 daily incidence curves is one of the most important exercises in the field of epidemic modeling. We examine the forecastability of daily COVID-19 cases in the Italian region of Lombardy using Dynamic Model Averaging and Dynamic Model Selection methods. To investigate the predictive accuracy of this approach, we compute forecast performance metrics of sequential out-of-sample real-time forecasts in a back-testing exercise ranging from March 1 to December 10 of 2020. We find that (i) Dynamic Model Averaging leads to a consistent and substantial predictive improvements over alternative epidemiological models and machine learning approaches when producing short-run forecasts. Using estimated posterior inclusion probabilities we also provide evidence on which set of predictors are relevant for forecasting in each period. Our findings also suggest that (ii) future incidences can be forecasted by exploiting information on the epidemic dynamics of neighboring regions, human mobility patterns, pollution and temperatures levels.
Learning from pandemics: using extraordinary events can improve disease now-casting models
Authors: Mesquita Sara , Vieira Cláudio Haupt , Perfeito Lília , Gonçalves-Sá Joana
Published: January 2021

Online searches have been used to study different health-related behaviours, including monitoring disease outbreaks. An obvious caveat is that several reasons can motivate individuals to seek online information and models that are blind to people’s motivations are of limited use and can even mislead. This is particularly true during extraordinary public health crisis, such as the ongoing pandemic, when fear, curiosity and many other reasons can lead individuals to search for health-related information, masking the disease-driven searches. However, health crisis can also offer an opportunity to disentangle between different drivers and learn about human behavior. Here, we focus on the two pandemics of the 21st century (2009-H1N1 flu and Covid-19) and propose a methodology to discriminate between search patterns linked to general information seeking (media driven) and search patterns possibly more associated with actual infection (disease driven). We show that by learning from such pandemic periods, with high anxiety and media hype, it is possible to select online searches and improve model performance both in pandemic and seasonal settings. Moreover, and despite the common claim that more data is always better, our results indicate that lower volume of the right data can be better than including large volumes of apparently similar data, especially in the long run. Our work provides a general framework that can be applied beyond specific events and diseases, and argues that algorithms can be improved simply by using less (better) data. This has important consequences, for example, to solve the accuracy-explainability trade-off in machine-learning.
RhoA within myofibers controls satellite cell microenvironment to allow hypertrophic growth
Authors: Noviello Chiara , Kobon Kassandra , Delivry Léa , Guilbert Thomas , Julienne Francis , Maire Pascal , Randrianarison-Huetz Voahangy , Sotiropoulos Athanassia
Published: January 2021

Adult skeletal muscle is a plastic tissue that can adapt its size to workload. Here, we show that RhoA within myofibers is needed for overload-induced hypertrophy by controlling satellite cell fusion to the growing myofibers without affecting protein synthesis. At the molecular level, we demonstrate that, in response to increased workload, RhoA controls in a cell autonomous manner Erk1/2 activation and the expressions of extracellular matrix (ECM) regulators such asMmp9/Mmp13/Adam8and of macrophage chemo-attractants such asCcl3/Cx3cl1.Their decreased expression in RhoA mutant is associated with ECM and fibrillar collagen disorganization and lower macrophage infiltration. Moreover, Mmps inhibition and macrophage depletion in controls phenocopied the lack of growth of RhoA mutants. These findings unravel the implication of RhoA within myofibers, in response to increase load, in the building of a permissive microenvironment for muscle growth and for satellite cell accretion through ECM remodeling and inflammatory cell recruitment.
Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera
Authors: Muik Alexander , Wallisch Ann-Kathrin , Sänger Bianca , Swanson Kena A. , Mühl Julia , Chen Wei , Cai Hui , Sarkar Ritu , Türeci Özlem , Dormitzer Philip R. , Sahin Ugur
Published: January 2021

Recently, a new SARS-CoV-2 lineage called B.1.1.7 has emerged in the United Kingdom that was reported to spread more efficiently than other strains. This variant has an unusually large number of mutations with 10 amino acid changes in the spike protein, raising concerns that its recognition by neutralizing antibodies may be affected. Here, we investigated SARS-CoV-2-S pseudoviruses bearing either the Wuhan reference strain or the B.1.1.7 lineage spike protein with sera of 16 participants in a previously reported trial with the mRNA-based COVID-19 vaccine BNT162b2. The immune sera had equivalent neutralizing titers to both variants. These data, together with the combined immunity involving humoral and cellular effectors induced by this vaccine, make it unlikely that the B.1.1.7 lineage will escape BNT162b2-mediated protection.
Primer biases in the molecular assessment of diet in multiple insectivorous mammals
Authors: Browett Samuel S. , Curran Thomas G. , O’Meara Denise B. , Harrington Andrew P. , Sales Naiara Guimarães , Antwis Rachael E. , O’Neill David , McDevitt Allan D.
Published: January 2021

Our understanding of trophic interactions of small insectivorous mammals has been drastically improved with the advent of DNA metabarcoding. The technique has continued to be optimised over the years, with primer choice repeatedly being a vital factor for dietary inferences. However, the majority of dietary studies examining the effect of primer choice often rely onin silicoanalyses or comparing single-niche species. Here we apply DNA metabarcoding to empirically compare the prey detection capabilities of two widely used primer sets when assessing the diets of a flying (lesser horseshoe bat;Rhinolophus hipposideros) and two ground dwelling insectivores (greater white-toothed shrew;Crocidura russulaand pygmy shrew;Sorex minutus). AlthoughR. hipposiderosprimarily rely on two prey orders (Lepidoptera and Diptera), the unique taxa detected by each primer shows that a combination of primers may be the best approach to fully describe bat trophic ecology. However, random forest classifier analysis suggest that one highly degenerate primer set detected the majority of both shrews’ diet despite higher levels of host amplification. The wide range of prey consumed by ground-dwelling insectivores can therefore be accurately documented from using a single broad-range primer set, which can decrease cost and labour. The results presented here show that dietary inferences will differ depending on the primer or primer combination used for insectivores occupying different niches (i.e. hunting in the air or ground) and demonstrate the importance of performing empirical pilot studies for novel study systems.
Conserved Architecture of Brain Transcriptome Changes between Alzheimer’s Disease and Progressive Supranuclear Palsy in Pathologically Affected and Unaffected Regions
Authors: Wang Xue , Allen Mariet , Reddy Joseph S. , Carrasquillo Minerva M. , Asmann Yan W. , Funk Cory , Nguyen Thuy T. , Malphrus Kimberly G. , Younkin Steven G. , Dickson Dennis W. , Price Nathan D. , Golde Todd E. , Ertekin-Taner Nilüfer
Published: January 2021

We identify a striking correlation in the directionality and magnitude of gene expression changes in brain transcriptomes between Alzheimer’s disease (AD) and Progressive Supranuclear Palsy (PSP). Further, the transcriptome architecture in AD and PSP is highly conserved between the temporal and cerebellar cortices, indicating highly similar transcriptional changes occur in pathologically affected and “unaffected” areas of the brain. These data have broad implications for interpreting transcriptomic data in neurodegenerative disorders.
Interaction Between Phosphoinositide 3-Kinase and the VDAC2 Channel Tethers Endosomes to Mitochondria and Promotes Endosome Maturation
Authors: Satoh Aya O. , Fujioka Yoichiro , Kashiwagi Sayaka , Yoshida Aiko , Fujioka Mari , Sasajima Hitoshi , Nanbo Asuka , Amano Maho , Ohba Yusuke
Published: January 2021

Intracellular organelles of mammalian cells communicate with each other during various cellular processes. The functions and molecular mechanisms of such interorganelle association remain largely unclear, however. We here identified voltage-dependent anion channel 2 (VDAC2), a mitochondrial outer membrane protein, as a binding partner of phosphoinositide 3-kinase (PI3K), a regulator of clathrin-independent endocytosis downstream of the small GTPase Ras. VDAC2 was found to tether endosomes positive for the Ras-PI3K complex to mitochondria in response to cell stimulation with epidermal growth factor and to promote clathrin-independent endocytosis as well as endosome maturation at membrane contact sites. With a newly developed optogenetics system to induce mitochondrion-endosome association, we found that, in addition to its structural role in such association, the pore function of VDAC2 is also required for the promotion of endosome maturation. Our findings thus uncover a previously unappreciated role of mitochondrion-endosome association in the regulation of endocytosis and endosome maturation.

Highlights

The mitochondrial protein VDAC2 binds PI3K and tethers endosomes to mitochondria

VDAC2 promotes clathrin-independent endocytosis

VDAC2-PI3K interaction induces acidification of endosomes associated with mitochondria

The pore function of VDAC2 also contributes to endosome maturation at contact sites
A nexus of intrinsic dynamics underlies translocase priming
Authors: Krishnamurthy Srinath , Eleftheriadis Nikolaos , Karathanou Konstantina , Smit Jochem H. , Portaliou Athina G. , Chatzi Katerina E. , Karamanou Spyridoula , Bondar Ana-Nicoleta , Gouridis Giorgos , Economou Anastassios
Published: January 2021

The cytoplasmic ATPase SecA and the membrane-embedded SecYEG channel assemble to form the functional Sec translocase. How this interaction primes and catalytically activates the translocase remains unclear. We now show that priming exploits a sophisticated nexus of intrinsic dynamics in SecA. Using atomistic simulations, single molecule FRET and hydrogen/deuterium exchange mass spectrometry we reveal multiple distributed dynamic islands that cross-talk with domain and quaternary motions. These dynamic elements are highly conserved and essential for function. Central to the nexus is a slender Stem through which, motions in the helicase ATPase domain of SecA biases how the preprotein binding domain rotates between open-closed clamping states. Multi-tier dynamics are enabled by an H-bonded framework covering most of the SecA structure and allowing conformational alterations with minimal energy inputs. As a result, dimerization, the channel and nucleotides select pre-existing conformations, and alter local dynamics to restrict or promote catalytic activity and clamp motions. These events prime the translocase for high affinity reception of non-folded preprotein clients. Such dynamics nexuses are likely universal and essential in multi-liganded protein machines.
A Chromosome-scale draft genome sequence of horsegram (Macrotyloma uniflorum)
Authors: Shirasawa Kenta , Chahota Rakesh , Hirakawa Hideki , Nagano Soichiro , Nagasaki Hideki , Sharma Tilak , Isobe Sachiko
Published: January 2021

Horsegram [Macrotyloma uniflorum(Lam.) Verdc.] is an underutilized warm season diploid legume (2n=20, 22), It is consumed as a food legume in India, and animal feed and fodder in Africa and Australia. Because of its ability to grow under water-deficient and marginal soil conditions, horsegram is a preferred choice in the era of the global climatic change. In recognition of its potential as a crop species, we generated and analyzed a draft genome sequence for HPK-4. The genome sequences of HPK-4 were generated by Illumina platform. Ten chromosome-scale pseudomolecules were created by aligning scaffold sequences onto a linkage map. The total length of the ten pseudomolecules were 259.2 Mb, covering 89% of the total length of the assembled sequences. A total of 36,105 genes were predicted on the assembled sequences, and 14,736 were considered to be horsegram specific genes by comparative analysis withPhaseolus. vulgaris,Vigna. angularis,Lotus. japonicusandArabidopsis. thaliana. The results of macrosynteny analysis suggested that the genome structure ofV. angularisis more similar to horsegram than that ofP. vulgaris.Diversity analysis in the 91 accessions of horsegram with dd-RAD-Seq analysis indicated narrow genetic diversity among the horsegram accessions. This is the first attempt to generate a draft genome sequence in horsegram and will provide a reference for sequence-based analysis of the horsegram germplasm to elucidate the genetic basis of important traits.
Human Neural Stem Cells Differentiate and Integrate, Innervating Implanted zQ175 Huntington’s Disease Mouse Striatum
Authors: Holley Sandra M. , Reidling Jack C. , Cepeda Carlos , Lau Alice , Moore Cindy , Orellana Iliana , Fury Brian , Kopan Lexi , Yeung Sylvia , Neel Michael , Coleal-Bergum Dane , Monuki Edwin S. , Meshul Charles K. , Bauer Gerhard , Levine Michael S. , Thompson Leslie M.
Published: January 2021

Huntington’s disease (HD), a genetic neurodegenerative disorder, primarily impacts the striatum and cortex with progressive loss of medium-sized spiny neurons (MSNs) and pyramidal neurons, disrupting cortico-striatal circuitry. A promising regenerative therapeutic strategy of transplanting human neural stem cells (hNSCs) is challenged by the need for long-term functional integration. We previously described that hNSCs transplanted into the striatum of HD mouse models differentiated into electrophysiologically active immature neurons, improving behavior and biochemical deficits. Here we show that 8-month implantation of hNSCs into the striatum of zQ175 HD mice ameliorates behavioral deficits, increases brain-derived neurotrophic factor (BDNF) and reduces mutant Huntingtin (mHTT) accumulation. Patch clamp recordings, immunohistochemistry and electron microscopy demonstrates that hNSCs differentiate into diverse neuronal populations, including MSN- and interneuron-like cells. Remarkably, hNSCs receive synaptic inputs, innervate host neurons, and improve membrane and synaptic properties. Overall, the findings support hNSC transplantation for further evaluation and clinical development for HD.
ACVR1R206Hincreases osteogenic/ECM gene expression and impairs myofiber formation in human skeletal muscle stem cells
Authors: Barruet Emilie , Garcia Steven M. , Wu Jake , Morales Blanca M. , Tamaki Stanley , Moody Tania , Pomerantz Jason H. , Hsiao Edward C.
Published: January 2021

Abnormalities in skeletal muscle repair lead to poor function and complications such as scarring or heterotopic ossification (HO). Here, we use fibrodysplasia ossificans progressiva (FOP), a disease of progressive HO caused by ACVR1R206H(Activin receptor type-1 receptor) mutation, to elucidate how ACVR1 affects skeletal muscle repair. Rare and unique primary FOP human muscle stem cells (Hu-MuSCs) isolated from cadaveric skeletal muscle demonstrated increased ECM marker expression, and showed skeletal muscle-specific impaired engraftment and regeneration ability. Human induced pluripotent stem cell (iPSC)-derived muscle stem/progenitor cells (iMPCs) Single cell transcriptome analyses from FOP also revealed unusually increased ECM and osteogenic marker expression compared to control iMPCs. These results show that iMPCs can recapitulate many aspects of Hu-MuSCs for detailed in vitro study, that ACVR1 is a key regulator of Hu-MuSC function and skeletal muscle repair; and that ACVR1 activation in iMPCs or Hu-MuSCs contributes to HO by changing the local tissue environment.
Single-cell trajectory inference guided enhancement of thyroid maturationin vitrousing TGF-beta inhibition
Authors: Romitti Mírian , Eski Sema Elif , Fonseca Barbara Faria , Singh Sumeet Pal , Costagliola Sabine
Published: January 2021

The thyroid gland regulates metabolism and growth via secretion of thyroid hormones by thyroid follicular cells (TFCs). Loss of TFCs, by cellular dysfunction, autoimmune destruction or surgical resection, underlies hypothyroidism. Recovery of thyroid hormone levels by transplantation of mature TFCs derived from stem cellsin vitroholds great therapeutic promise. However, the utilization ofin vitroderived tissue for regenerative medicine is restricted by the efficiency of differentiation protocols to generate mature organoids. Here, to improve the differentiation efficiency for thyroid organoids, we utilized single-cell RNA-Seq to chart the molecular steps undertaken by individual cells during thein vitrotransformation of mouse embryonic stem cells to TFCs. Our single-cell atlas of mouse organoid systematically and comprehensively identifies, for the first time, the cell types generated during production of thyroid organoids. Using pseudotime analysis, we identify TGF-beta and planar-cell polarity (PCP) pathways as regulators of thyroid maturationin vitro. Using pharmacological manipulation of TGF-beta pathway, we improve the level of thyroid maturation, in particular the induction ofNisexpression. This in turn, leads to an enhancement of iodide organificationin vitro, suggesting functional improvement of the thyroid organoid. Our study highlights the potential of single-cell molecular characterization in understanding and improving thyroid maturation and paves the way for identification of therapeutic targets against thyroid disorders.
Computational and experimental approaches to controlling bacterial microcompartment assembly
Authors: Li Yaohua , Kennedy Nolan W. , Li Siyu , Mills Carolyn E. , Tullman-Ercek Danielle , de la Cruz Monica Olvera
Published: January 2021

Bacterial microcompartments compartmentalize the enzymes that aid chemical and energy production in many bacterial species. These protein organelles are found in various bacterial phyla and are postulated to help many of these organisms survive in hostile environments such as the gut of their hosts. Metabolic engineers are interested in repurposing these organelles for non-native functions. Here, we use computational, theoretical and experimental approaches to determine mechanisms that effectively control microcompartment self-assembly. As a model system, we find via multiscale modeling and mutagenesis studies, the interactions responsible for the binding of hexamer-forming proteins propanediol utilization bacterial microcompartments from Salmonella and establish conditions that form various morphologies. We determine how the changes in the microcompartment hexamer protein preferred angles and interaction strengths can modify the assembled morphologies including the naturally occurring polyhedral microcompartment shape, as well as other extended shapes or quasi-closed shapes. We demonstrate experimentally that such altered strengths and angles are achieved via amino acid mutations. A thermodynamic model that agrees with the coarse-grained simulations provides guidelines to design microcompartments. These findings yield insight in controlled protein assembly and provide principles for assembling microcompartments for biochemical or energy applications as nanoreactors.