bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional and structural biomarkers of cognitive outcomes after brain tumor resection
Authors: García Meritxell , Aguasvivas José , Gil-Robles Santiago , Pomposo Iñigo , Amorouso Lucia , Carreiras Manuel , Quiñones Ileana
Published: September 2020

Cognitive explorations have demonstrated the activation of plastic mechanisms in slow-growing brain lesions, generating structural and functional changes. Due to its incidence, it is essential to investigate the reorganization of functional areas in brain tumor patients as well as formulating new approaches for predicting patient’s quality of life after tumor resection.

Following this perspective, we formulated an efficient methodology for postsurgical prognosis prediction, not only in terms of the structural damage but also to measure the neuroplastic changes associated with tumor appearence. Of note, most of previous studies employed a limited number of neuropsychological and clinical features for predicting patient prognosis. Our objective is to optimize the traditional model and to develop a method that can predict outcomes with high accuracy and identify the most significant features for cognitive impairment, working memory, executive control and language outcomes. Our approach is based on the inclusion of a large battery of neuropsychological tests as well as the introduction of grey and white matter morphological measures for model optimization. We employed Support Vector Machine (SVM), Decision Tree, and Naïve Bayes algorithms for testing the models and outcomes. Overall, SVM performance showed to be more accurate as compared to Decision Tree and Naïve Bayes. Specifically, we found that, by introducing connectivity variables (e.g., grey and white matter measures) Cognitive Status and Working Memory exhibited a predictive improvement. However, Language and Executive Control outcomes were not significantly predicted in none of the models. The importance of the present study resides in the employment of structural and functional variables for postsurgical outcome prediction. We found that connectivity variables are sensitive for predicting the postsurgical quality of life.
Equivalent SARS-CoV-2 viral loads between nasopharyngeal swab and saliva in symptomatic patients
Authors: Yokota Isao , Hattori Takeshi , Shane Peter Y , Konno Satoshi , Nagasaka Atsushi , Takeyabu Kimihiro , Fujisawa Shinichi , Nishida Mutsumi , Teshima Takanori
Published: September 2020

COVID-19 is diagnosed by detecting SARS-CoV-2 by nasopharyngeal swab (NPS) using real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Emerging evidences have shown the utility of saliva, although conflicting results have been reported regarding viral loads between NPS and saliva. We conducted a study to compare the viral loads in 42 patients with COVID-19. Both NPS and saliva specimens were simultaneously obtained at a median of 6 days (range, 1-12) after symptom onset. SARS-CoV-2 was detected in 34 (81%) using NPS (median Ct value [IQR]=27.4 [21.3, 35.6]) and 38 (90%) using saliva (median Ct value [IQR]= 28.9 [23.1, 33.6]). There was no significance difference between them (Wilcoxon signed rank test: P=0.79) and Kendall’s W was 0.82, showing a high degree of agreement, indicating equivalent viral loads in NPS and saliva. After symptom onset, the Ct values of both NPS and saliva continued to increase over time, with no substantial difference. Self-collected saliva has a detection sensitivity comparable to that of NPS and is a useful diagnostic tool with mitigating uncomfortable process and the risk of aerosol transmission to healthcare workers.
Email vs. Instagram recruitment strategies for online survey research
Authors: Moraes Rafael R. , Correa Marcos B. , Daneris Ândrea , Queiroz Ana B. , Lopes João P. , Lima Giana S. , Cenci Maximiliano S. , D’Avila Otávio P. , Pannuti Claudio M. , Pereira-Cenci Tatiana , Demarco Flávio F.
Published: September 2020

In this study, we describe and evaluate a method for reaching a target population (i.e., dentists practicing in Brazil) to engage in survey research using traditional e-mail invites compared with recruitment campaigns created on Instagram. A pre-tested questionnaire was used and participants were recruited for 10 days via a source list of email addresses and two discrete Instagram organic open campaigns. A total of 3,122 responses were collected: 509 participants were recruited by email (2.1% response rate) and 2,613 by the two Instagram campaigns (20.7% and 11.7% conversion rates), respectively. Response/min collection rates in the first 24 h ranged between 0.23 (email) and 1.09 (first campaign). In total, 98.8% of all responses were received in the first 48 h for the different recruitment strategies. There were significant differences for all demographic variables (p<0.001) between email and Instagram respondents, except for sex (p=0.373). Instagram respondents were slightly older, had more professional experience (years in practice), and a higher graduate education level than email respondents. Moreover, most email and Instagram respondents worked in the public sector and private practice, respectively. Although both strategies could collect responses from all Brazilian regions, email responses were slightly better distributed across the five territorial areas compared to Instagram. In conclusion, this study provides evidence that survey recruitment of a large sample using Instagram is feasible. However, using Instagram to engage participants is challenging and has limitations that warrant further investigation. Combination of email and Instagram recruitment led to a more diverse population and improved response rates.
The Impact of Psychology Interventions on Changing Mental Health Status and Sleep Quality in University Students during the COVID-19 Pandemic
Authors: Xiao Jing , Jiang Yu , Zhang Yu , Gu Xinyi , Ma Wenjing , Zhuang Bo , Zhou Ziqi , Sang Lingli , Luo Yitian , Lian Yulong
Published: September 2020

Objective

We evaluated the change in mental health and sleep quality of college students at four time periods.

Methods

Mental health status and sleep quality were using the Pittsburgh Sleep Quality Index (PSQI) and Symptom Checklist-90-Revised (SCL-90-R) questionnaire across four time periods. Psychology interventions were carried out from the third period.

Results

Students in the third period had higher PSQI total scores [mean (SD), 6.01 (3.27)] than those in the first period [5.60 (3.11)], second period [4.17 (2.10)] and fourth period [4.09 (2.80)]. After adjustment for covariates there was a decline of 1.89 points in the PSQI in the fourth period compared with the highest period. The SCL-90-R scores were highest in the second period [121.19 (47.83)], and were higher than the scores in the first [107.60 (52.21)] and second period [107.79 (27.20)] and lowest in the fourth period [97.82 (17.12)]. The decline in scores was 23.38 points after adjustment for covariates. The prevalence of psychological distress and sleep disturbances respectively decreased from 28.6% to 11.7% and from 10.4% to 2.6% comparing to the highest period. Sleep quality showed a significant positive correlation with mental health status.

Conclusions

The pattern of change in mental health status was different to that of sleep quality. The implementation of comprehensive psychology intervention may improve mental health and sleep quality. These findings may inform public health policy during the reopening of schools in other regions.
A simple model for detailed visual cortex maps predicts fixed hypercolumn sizes
Authors: Weigand Marvin , Cuntz Hermann
Published: September 2020

Orientation hypercolumns in the visual cortex are delimited by the repeating pinwheel patterns of orientation selective neurons. We design a generative model for visual cortex maps that reproduces such orientation hypercolumns as well as ocular dominance maps while preserving retinotopy. The model uses a neural placement method based on t–distributed stochastic neighbour embedding (t–SNE) to create maps that order common features in the connectivity matrix of the circuit. We find that, in our model, hypercolumns generally appear with fixed cell numbers independently of the overall network size. These results would suggest that existing differences in absolute pinwheel densities are a consequence of variations in neuronal density. Indeed, available measurements in the visual cortex indicate that pinwheels consist of a constant number of ∼30, 000 neurons. Our model is able to reproduce a large number of characteristic properties known for visual cortex maps. We provide the corresponding software in ourMAPStoolboxforMatlab.

In brief

We present a generative model that predicts visual map structures in the brain and a large number of their characteristic properties; a neural placement method for any given connectivity matrix.

Highlights

Generative model with retinotopy, orientation preference and ocular dominance.

Prediction of constant neuronal numbers per orientation hypercolumn.

Curated data shows constant ∼30, 000 neurons per pinwheel across species.

Simple explanation for constant pinwheel and orientation hypercolumn ratios.

Precise prediction of ∼80% nearest neighbour singularities with opposing polarity.

Model asymptotically approaches realistic normalised pinwheel densities.

Small brains with < ∼300 potential pinwheels exhibit salt-and-pepper maps.

Different map phenotypes can exist even for similar connectivity.
Granick Revisited: Synthesizing Evolutionary and Ecological Evidence for the Late Origin of Bacteriochlorophyll via Ghost Lineages and Horizontal Gene Transfer
Authors: Ward Lewis M. , Shih Patrick M.
Published: September 2020

Photosynthesis—both oxygenic and more ancient anoxygenic forms—has fueled the bulk of primary productivity on Earth since it first evolved more than 3.4 billion years ago. However, the early evolutionary history of photosynthesis has been challenging to interpret due to the sparse, scattered distribution of metabolic pathways associated with photosynthesis, long timescales of evolution, and poor sampling of the true environmental diversity of photosynthetic bacteria. Here, we reconsider longstanding hypotheses for the evolutionary history of phototrophy by leveraging recent advances in metagenomic sequencing and phylogenetics to analyze relationships among phototrophic organisms and components of their photosynthesis pathways, including reaction centers and individual proteins and complexes involved in the multi-step synthesis of (bacterio)-chlorophyll pigments. We demonstrate that components of the photosynthetic apparatus have undergone extensive, independent histories of horizontal gene transfer. This suggests an evolutionary mode by which modular components of phototrophy are exchanged between diverse taxa in a piecemeal process that has led to biochemical innovation. We hypothesize that the evolution of extant anoxygenic photosynthetic bacteria has been spurred by ecological competition and restricted niches following the evolution of oxygenic Cyanobacteria and the accumulation of O2in the atmosphere, leading to the relatively late evolution of bacteriochlorophyll pigments and the radiation of diverse crown group anoxygenic phototrophs. This hypothesis expands on the classic “Granick hypothesis” for the stepwise evolution of biochemical pathways, synthesizing recent expansion in our understanding of the diversity of phototrophic organisms as well as their evolving ecological context through Earth history.
Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex
Authors: Bartolomé Alberto , Liang Jiani , Wang Pengfei , Ho David D. , Pajvani Utpal B.
Published: September 2020

Angiotensin converting enzyme 2 (ACE2) is a key regulator of the renin-angiotensin system, but also the functional receptor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on structural similarity with other γ-secretase (γS) targets, we hypothesized that ACE2 may be affected by γS proteolytic activity. We found that after ectodomain shedding, ACE2 is targeted for intramembrane proteolysis by γS, releasing a soluble ACE2 C-terminal fragment. Consistently, chemical or genetic inhibition of γS results in the accumulation of a membrane-bound fragment of ectodomain-deficient ACE2. Although chemical inhibition of γS does not alter SARS-CoV-2 cell entry, these data point to a novel pathway for cellular ACE2 trafficking.
Gains and Losses affect Learning Differentially at Low and High Attentional Load
Authors: Boroujeni Kianoush Banaie , Watson Marcus , Womelsdorf Thilo
Published: September 2020

Prospective gains and losses modulate cognitive processing, but it is unresolved whether gains and losses can facilitate flexible learning in changing environments. The prospect of gains might enhance flexible learning through prioritized processing of reward-predicting stimuli but is unclear how far this learning benefit extends when task demands increase. Similarly, experiencing losses might facilitate learning when they trigger attentional re-orienting away from loss-inducing stimuli, but losses may also impair learning by reducing the precise encoding of loss-inducing stimuli. To clarify these divergent views, we tested how varying magnitudes of gains and losses affect the flexible learning of object values in environments that varied attentional load by increasing the number of interfering object features during learning. With this task design we found that larger prospective gains improved learning efficacy and learning speed, but only when attentional load was low. In contrast, expecting losses generally impaired learning efficacy and this impairment was larger at higher attentional load. These findings functionally dissociate the contributions of prospective gains and losses on flexible learning, suggesting they operate via separate control mechanisms. One process is triggered by experiencing loss and seems to disrupt the encoding of specific loss-inducing features which leads to less efficient exploration during learning. The second process is triggered by experiencing gains which enhances learning through a more efficient prioritizing of reward-predicting stimulus features as long as the interference of distracting information is limited. These results demonstrate strengths and limitations of motivational regulation of learning efficacy in multidimensional environments having variable attentional loads.

Significance statement

Increasing the prospective gains is assumed to enhance flexible learning, but there is no consensus on whether imposing losses enhances or impairs flexible learning. We show that anticipating loss of already attained assets generally reduced learning changes in the relevance of visual objects and that this learning impediment is more pronounced when learning demands higher attentional control of interference from distracting object features. Moreover, we show that increasing the prospective gains indeed facilitates learning, but only when the learning problem has intermediate or low attentional demands. These findings document that the beneficial effects of gains hit a limit when task demands increase, and that prospective losses reduce cognitive flexibility already at low task demands which is exacerbated when task demands increase. These findings provide novel insight into the strengths and limitations of gains and of losses to support flexible learning in multidimensional environments imposing variable attentional loads.
An intestinal cell type in zebrafish is the nexus for the SARS-CoV-2 receptor and the Renin-Angiotensin-Aldosterone System that contributes to COVID-19 comorbidities
Authors: Postlethwait John H. , Farnsworth Dylan R. , Miller Adam C.
Published: September 2020

People with underlying conditions, including hypertension, obesity, and diabetes, are especially susceptible to negative outcomes after infection with the coronavirus SARS-CoV-2. These COVID-19 comorbidities are exacerbated by the Renin-Angiotensin-Aldosterone System (RAAS), which normally protects from rapidly dropping blood pressure or dehydration via the peptide Angiotensin II (Ang II) produced by the enzyme Ace. The Ace paralog Ace2 degrades Ang II, thus counteracting its chronic effects. Ace2 is also the SARS-CoV-2 receptor.Ace, the coronavirus, and COVID-19 comorbidities all regulateAce2, but we don’t yet understand how. To exploit zebrafish (Danio rerio) as a disease model to understand mechanisms regulating the RAAS and its relationship to COVID-19 comorbidities, we must first identify zebrafish orthologs and co-orthologs of human RAAS genes, and second, understand where and when these genes are expressed in specific cells in zebrafish development. To achieve these goals, we conducted genomic analyses and investigated single cell transcriptomes. Results showed that most human RAAS genes have an ortholog in zebrafish and some have two or more co-orthologs. Results further identified a specific intestinal cell type in zebrafish larvae as the site of expression for key RAAS components, including Ace, Ace2, the coronavirus co-receptor Slc6a19, and the Angiotensin-related peptide cleaving enzymes Anpep and Enpep. Results also identified specific vascular cell subtypes as expressing Ang II receptors,apelin, andapelin receptorgenes. These results identify specific genes and cell types to exploit zebrafish as a disease model for understanding the mechanisms leading to COVID-19 comorbidities.

SUMMARY STATEMENT

Genomic analyses identify zebrafish orthologs of the Renin-Angiotensin-Aldosterone System that contribute to COVID-19 comorbidities and single-cell transcriptomics show that they act in a specialized intestinal cell type.
C1 compounds shape the microbial community of an abandoned century-old oil exploration well
Authors: Rojas-Gätjens Diego , Fuentes-Schweizer Paola , Rojas-Jimenez Keilor , Pérez-Pantoja Danilo , Avendaño Roberto , Alpízar Randall , Coronado-Ruíz Carolina , Chavarría Max
Published: September 2020

The search for microorganisms that degrade hydrocarbons is highly relevant because it enables the bioremediation of these substances cheaply and without dangerous by-products. In this work, we studied the microbial communities of an exploratory oil well, abandoned a century ago, located in the Cahuita National Park of Costa Rica. Cahuita well is characterized by a continuous efflux of methane and the presence of a mixture of hydrocarbons including C2-dibenzothiophene, phenanthrene or anthracene, fluoranthene pyrene, dibenzothiophene, tricyclic terpanes, pyrene, sesquiterpenes, sterane and n-alkanes. Based on the analysis of 16S rRNA gene amplicons, we detected a significant abundance of methylotrophic bacteria (Methylobacillus(6.3-26.0 % of total reads) andMethylococcus(4.1-30.6 %)) and the presence of common genera associated with hydrocarbon degradation, such asComamonas(0.8-4.6 %),Hydrogenophaga(1.5-3.3 %)Rhodobacter(1.0-4.9 %) andFlavobacterium(1.1-6.5 %). We evidenced the presence of methane monooxygenase (MMO) activities, responsible for the first step in methane metabolism, by amplifying thepmogene from environmental DNA. We also isolated a strain ofMethylorubrum rhodesianum, which was capable of using methanol as its sole carbon source. This work represents a contribution to the understanding of the ecology of communities of microorganisms in environments with permanently high concentrations of methane and hydrocarbons, which also has biotechnological implications for the bioremediation of highly polluting petroleum components.
Response of endolithic Chroococcidiopsis strains from the polyextreme Atacama Desert to light radiation
Authors: Casero María Cristina , Ascaso Carmen , Quesada Antonio , Mazur-Marzec Hanna , Wierzchos Jacek
Published: September 2020

The Atacama Desert is known to be the place on Earth with one of the highest solar radiation limiting the presence of life to endolithic microhabitats and soil microbial ecosystems. Endolithic microbial communities are supported by photosynthetic primary producers, mainly cyanobacteria, which can be injured by UVR. Nevertheless, cyanobacteria exposed to high solar radiation and its harmful effects have developed a series of defense mechanisms: avoidance, antioxidant systems or production of photoprotective compounds such as scytonemin among others. Scytonemin is a liposoluble pigment whose absorption maxima are located in UVA and UVC range and highly absorbing in the UVB range. In order to elucidate the protection capacity of endolithic cyanobacteria against harmful radiation, two cyanobacterial strains from Chroococcidiopsis genus were isolated from different endolithic microhabitats in the Atacama Desert: UAM813 strain, originally from the cryptoendolithic microhabitat of halite (NaCl), and UAM816 strain from chasmoendolithic microhabitat of calcite (CaCO3). Both were exposed to PAR and UVR+PAR conditions studying their short-term response, as oxidative stress and long-term response, as scytonemin production, metabolic activity and ultrastructural damage. The observed response of both strains reveals a high sensitivity to direct light exposure, even to PAR. The differences in their acclimation suggest specific adaptation strategies related to their original microhabitat, revealing their protective potential and the strain specific environmental pressure selection to inhabit different microhabitats and exposed to different light conditions.

Importance

Cyanobacteria are photosynthetic prokaryotes that inhabit most types of illuminated environments, even the endolithic microhabitats in cold and hot deserts. The environmental pressure caused by the extreme solar irradiation in the Atacama Desert involve that only those cyanobacterial strains able to cope with it can be found in these endolithic communities, usually dominated by members belonging to the extremotolerant Chroococcidiopsis genus. Here, a comprehensive analysis of multiple lines of defense against harmful sun radiation was conducted to diagnose the response of two Chroococcidiopsis strains isolated from different endolithic microhabitats and lithic substrates, and identify its relation with the original microenvironmental conditions of each strain. Our results contribute to a better understanding of the acclimation strategies developed by these cyanobacterial strains and its potential protective role for the whole endolithic microbial community.
Pharmacokinetics and predicted neutralization coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials
Authors: Huang Yunda , Naidoo Logashvari , Zhang Lily , Carpp Lindsay N. , Rudnicki Erika , Randhawa April , Gonzales Pedro , McDermott Adrian , Ledgerwood Julie , Lorenzo Margarita M. Gomez , Burns David , DeCamp Allan , Juraska Michal , Mascola John , Edupuganti Srilatha , Mgodi Nyaradzo , Cohen Myron , Corey Larry , Andrew Philip , Karuna Shelly , Gilbert Peter B. , Mngadi Kathryn , Lazarus Erica
Published: September 2020

The phase 2b AMP trials are testing whether the broadly neutralizing antibody VRC01 prevents HIV-1 infection in two cohorts: women in sub-Saharan Africa, and men and transgender persons who have sex with men (MSM/TG) in the Americas and Switzerland. We used nonlinear mixed effects modeling of longitudinal serum VRC01 concentrations to characterize pharmacokinetics and predict HIV-1 neutralization coverage. We found that body weight significantly influenced clearance, and that the mean peripheral volume of distribution, steady state volume of distribution, elimination half-life, and accumulation ratio were significantly higher in MSM/TG than in women. Neutralization coverage was predicted to be higher in the first (versus second) half of a given 8-week infusion interval, and appeared to be higher in MSM/TG than in women overall. Study cohort differences in pharmacokinetics and neutralization coverage provide insights for interpreting the AMP results and for investigating how VRC01 concentration and neutralization correlate with HIV incidence.
Pooling saliva to increase SARS-CoV-2 testing capacity
Authors: Watkins Anne E. , Fenichel Eli P. , Weinberger Daniel M. , Vogels Chantal B.F. , Brackney Doug E. , Casanovas-Massana Arnau , Campbell Melissa , Fournier John , Bermejo Santos , Datta Rupak ,   the Yale IMPACT Research Team, Dela Cruz Charles S. , Farhadian Shelli F. , Iwasaki Akiko , Ko Albert I. , Grubaugh Nathan D. , Wyllie Anne L.
Published: September 2020

Expanding testing capabilities is integral to managing the further spread of SARS-CoV-2 and developing reopening strategies, particularly in regards to identifying and isolating asymptomatic and pre-symptomatic individuals. Central to meeting testing demands are specimens that can be easily and reliably collected and laboratory capacity to rapidly ramp up to scale. We and others have demonstrated that high and consistent levels of SARS-CoV-2 RNA can be detected in saliva from COVID-19 inpatients, outpatients, and asymptomatic individuals. As saliva collection is non-invasive, extending this strategy to test pooled saliva samples from multiple individuals could thus provide a simple method to expand testing capacity.

However, hesitation towards pooled sample testing arises due to the dilution of positive samples, potentially shifting weakly positive samples below the detection limit for SARS-CoV-2 and thereby decreasing the sensitivity. Here, we investigated the potential of pooling saliva samples by 5, 10, and 20 samples prior to RNA extraction and RT-qPCR detection of SARS-CoV-2. Based on samples tested, we conservatively estimated a reduction of 7.41%, 11.11%, and 14.81% sensitivity, for each of the pool sizes, respectively. Using these estimates we modeled anticipated changes in RT-qPCR cycle threshold to show the practical impact of pooling on results of SARS-CoV-2 testing. In tested populations with greater than 3% prevalence, testing samples in pools of 5 requires the least overall number of tests. Below 1% however, pools of 10 or 20 are more beneficial and likely more supportive of ongoing surveillance strategies.
Development and validation of a multiplex bead based assay for the detection of antibodies directed against SARS-CoV-2 proteins
Authors: Bray Robert A. , Lee Jar-How , Brescia Peter , Kumar Deepali , Nong Thoa , Shih Remi , Woodle E. Steve , Maltzman Jonathan S. , Gebel Howard M.
Published: September 2020

Transplant recipients who develop COVID-19 may be at increased risk for morbidity and mortality. Determining antibody status against SARS-CoV-2 in candidates and recipients will be important to understand the epidemiology and clinical course of COVID-19 infection in this population. There are multiple antibody tests to detect antibodies to SARS-CoV-2, but their performance varies according to their platforms and the antigenic targets, making interpretation of the results challenging. Additionally, currently available serological tests do not exclude the possibility that positive responses are due to cross reactive antibodies to community coronaviruses. This study describes the development and validation of a high throughput multiplex bead based antibody detection assay with the capacity to identify, simultaneously, patient responses to five distinct SARS-CoV-2 proteins. The antibody response to these proteins are SARS-CoV-2 specific as antibodies against four community coronaviruses do not cross-react. Assay configuration is essentially identical to the single antigen bead assays used in the majority of histocompatibility laboratories around the world and could easily be implemented into routine screening of transplant candidates and recipients. This new assay provides a novel tool to interrogate the spectrum of immune responses to SAR-CoV-2 and is uniquely suitable for use in the transplant setting.
Onset of effects of non-pharmaceutical interventions on COVID-19 worldwide
Authors: Zeilinger Elisabeth L. , Nader Ingo W. , Jomar Dana , Zauchner Clemens
Published: September 2020

During the initial phase of the global COVID-19 outbreak, most countries responded with non-pharmaceutical interventions (NPIs). The effectiveness of these NPIs has been investigated with simulation studies, that rely on assumptions and by empirical studies with few countries and controversial results. However, it has not been investigated in detail how long different NPIs need to be in place to take effect, or how long they should be in place for their maximum effect to unfold. We used global data and a non-parametric machine learning model to estimate the effects of NPIs in relation to how long they have been in place. Here we show that closure and regulation of schools was the most important NPI, associated with a pronounced effect about 10 days after implementation. Restrictions of mass gatherings and restrictions and regulations of businesses were found to have a more gradual effect, and social distancing was associated with a delayed effect starting about 18 days after implementation. Generally, effects increased until about 40 to 50 days after implementation. Our results can inform political decisions regarding the choice of NPIs and how long they need to be in place to take effect.
The role of masks in reducing the risk of new waves of COVID-19 in low transmission settings: a modeling study
Authors: Stuart RM , Abeysuriya Romesh G , Kerr Cliff C , Mistry Dina , Klein Daniel J , Gray Richard , Hellard Margaret , Scott Nick
Published: September 2020

Objectives

To evaluate the risk of a new wave of coronavirus disease 2019 (COVID-19) in a setting with ongoing low transmission, high mobility, and an effective test-and-trace system, under different assumptions about mask uptake.

Design

We used a stochastic agent-based microsimulation model to create multiple simulations of possible epidemic trajectories that could eventuate over a five-week period following prolonged low levels of community transmission.

Setting

We calibrated the model to the epidemiological and policy environment in New South Wales, Australia, at the end of August 2020.

Participants

None

Intervention

From September 1, 2020, we ran the stochastic model with the same initial conditions(i.e., those prevailing at August 31, 2020), and analyzed the outputs of the model to determine the probability of exceeding a given number of new diagnoses and active cases within five weeks, under three assumptions about future mask usage: a baseline scenario of 30% uptake, a scenario assuming no mask usage, and a scenario assuming mandatory mask usage with near-universal uptake (95%).

Main outcome measure

Probability of exceeding a given number of new diagnoses and active cases within five weeks.

Results

The policy environment at the end of August is sufficient to slow the rate of epidemic growth, but may not stop the epidemic from growing: we estimate a 20% chance that NSW will be diagnosing at least 50 new cases per day within five weeks from the date of this analysis. Mandatory mask usage would reduce this to 6–9%.

Conclusions

Mandating the use of masks in community settings would significantly reduce the risk of epidemic resurgence.
Systematic review and meta-analysis of veterinary-related occupational exposures to hazards
Authors: Adebowale OO , Fasanmi OG , Awosile B.B , Afolabi MO , Fasina FO
Published: September 2020

Objective

Understanding hazards within the veterinary profession is critical for developing strategies to ensure health and safety in the work environment. This study was conducted to systematically review and synthesize data on reported risks within veterinary workplaces.

Methods

A systematic review of published data reporting occupational hazards and associated risk factors were searched within three database platforms namely PubMed, Ebscohost, and Google scholar. To determine the proportion estimates of hazards and pooled odds ratio, two random-effects meta-analysis were performed.

Results

Data showed veterinarians and students were at high risk of exposure to diverse physical, chemical, and biological hazards. For the biological, chemical and physical hazards, the pooled proportion estimates were 17% (95% CI: 15.0–19.0, p < 0.001), 7.0% (95% CI: 6.0–9.0%, p < 0.001) and 65.0% (95% CI: 39.0–91.0%, p < 0.001) respectively. A pooled odds ratio indicated the odds of physical (OR = 1.012, 95% CI: 1.008–1.017, p < 0.001) and biological exposures (OR = 2.07, 95% CI: 1.70–2.52, p < 0.001) increased more when working with or in contact with animals than non-contact.

Conclusions

This review has provided a better understanding of occupational health and safety status of veterinarians and gaps within the developing countries. Veterinarians including students are at considerable risk of occupational-related hazards. The need to improve government and organisation policies and measures on occupational health and safety is therefore crucial, most importantly in Africa.
Revealing the extent of the COVID-19 pandemic in Kenya based on serological and PCR-test data
Authors: Ojal John , Brand Samuel P. C. , Were Vincent , Okiro Emelda A , Kombe Ivy K , Mburu Caroline , Aziza Rabia , Ogero Morris , Agweyu Ambrose , Warimwe George M , Uyoga Sophie , Adetifa Ifedayo M O , Scott J Anthony G , Otieno Edward , Ochola-Oyier Lynette I , Agoti Charles N , Kasera Kadondi , Amoth Patrick , Mwangangi Mercy , Aman Rashid , Ng’ang’a Wangari , Tsofa Benjamin , Bejon Philip , Barasa Edwine , Keeling Matt. J. , Nokes D. James.
Published: September 2020

Policy makers in Africa need robust estimates of the current and future spread of SARS-CoV-2. Data suitable for this purpose are scant. We used national surveillance PCR test, serological survey and mobility data to develop and fit a county-specific transmission model for Kenya. We estimate that the SARS-CoV-2 pandemic peaked before the end of July 2020 in the major urban counties, with 34 - 41% of residents infected, and will peak elsewhere in the country within 2-3 months. Despite this penetration, reported severe cases and deaths are low. Our analysis suggests the COVID-19 disease burden in Kenya may be far less than initially feared. A similar scenario across sub-Saharan Africa would have implications for balancing the consequences of restrictions with those of COVID-19.
Home and work-related injuries in Makwanpur district, Nepal: a household survey
Authors: Pant Puspa Raj , Deave Toity , Banstola Amrit , Bhatta Sumiksha , Joshi Elisha , Adhikari Dhruba , Manandhar Sunil , Joshi Sunil Kumar , Mytton Julie
Published: September 2020

Objective

This paper describes the epidemiology of home- and work-related injuries, their mechanisms, inequalities and costs associated with these injuries.

Methods

A household survey was undertaken in three palikas (administrative areas) of Makwanpur district between April-June, 2019. Data were collected electronically on non-fatal injuries that occurred in the previous three months and fatal injuries that occurred in the previous five years.

Findings

17,593 individuals were surveyed from 3,327 households. The injury rate was 8.0/1000 population for home injuries and 6.4/1000 for work-related injuries; 61.0% of home injuries were among females and 69.9% of work-related injuries among males. Forty-eight percent of all home injuries were due to falls (28 males (50.9%) and 40 females (46.5%)); burn/scalds were higher among females 15 (10.5%). Cuts and piercings accounted for 40% of all work-related injuries and 36.3% were falls. Injury incidence varied by ethnic group: home injuries were highest in Brahmin (12/1000) and work-related injuries highest in Rai groups (21.0 per 1000). The total mean cost of work-related injury was US$143.3 (SD 276.7), higher than for home injuries (US$130.4, SD 347.6). The number of home (n = 74, 64.9%) and work-related (n = 67, 77.9%) injuries were higher in families below the poverty line (<US$1.9) than families in the next income bracket (US$1.9–3.2)(home: n = 22, 19.3%; work: n = 11, 12.8%).

Conclusions

Home and occupational fall injuries are common. The inequalities in injury identified in our study by rurality, age, sex, income level and ethnic group can help target injury prevention interventions for vulnerable groups.

What is already known on the subject

Limited epidemiological data are available in Nepal about the location of injury, activity taking place when injury occurred and the costs of injury

There is limited information about the distribution of injuries by ethnicity and income groups.

What this study adds

People from rural areas experience more injuries than people living in urban or city areas

Manual workers sustain more work-related injuries than those in other occupations

Certain ethnic groups have higher rates of injuries than other ethnic groups

People with lower income experience more injuries than people with higher incomes

Injury costs are high in relation to average per capita income.
Maximizing and evaluating the impact of test-trace-isolate programs
Authors: Grantz Kyra H. , Lee Elizabeth C. , McGowan Lucy D’Agostino , Lee Kyu Han , Metcalf C. Jessica E. , Gurley Emily S. , Lessler Justin
Published: September 2020

September 2, 2020

Background

Test-trace-isolate programs are an essential part of COVID-19 control that offer a more targeted approach than many other non-pharmaceutical interventions. Effective use of such programs requires methods to estimate their current and anticipated impact.

Methods and Findings

We present a mathematical modeling framework to evaluate the expected reductions in the reproductive number, R, from test-trace-isolate programs. This framework is implemented in a publicly available R package and an online application. We evaluated the effects of case detection, speed of isolation, contact tracing completeness and speed of quarantine using parameters consistent with COVID-19 transmission (R0 = 2.5, generation time 6.5 days). We show that R is most sensitive to changes to the proportion of infections detected in almost all scenarios, and other metrics have a reduced impact when case detection levels are low (< 30%). Although test-trace-isolate programs can contribute substantially to reducing R, exceptional performance across all metrics is needed to bring R below one through test-trace-isolate alone, highlighting the need for comprehensive control strategies. Formally framing the dynamical process also indicates that metrics used to evaluate performance of test-trace-isolate, such as the proportion of identified infections among traced contacts, may be misleading. While estimates of program performance are sensitive to assumptions about COVID-19 natural history, our qualitative findings are robust across numerous sensitivity analyses.

Conclusions

Effective test-trace-isolate programs first need to be strong in the “test” component, as case detection underlies all other program activities. Even moderately effective test-trace-isolate programs are an important tool for controlling the COVID-19 pandemic, and can alleviate the need for more restrictive social distancing measures.
Exostosin-1 Glycosyltransferase Regulates Endoplasmic Reticulum Architecture and Dynamics
Authors: Kerselidou Despoina , Dohai Bushra Saeed , Nelson David R. , Daakour Sarah , De Cock Nicolas , Kim Dae-Kyum , Olivet Julien , El Assal Diana C. , Jaiswal Ashish , Saha Deeya , Pain Charlotte , Matthijssens Filip , Lemaitre Pierre , Herfs Michael , Chapuis Julien , Ghesquiere Bart , Vertommen Didier , Kriechbaumer Verena , Knoops Kèvin , Lopez-Iglesias Carmen , van Zandvoort Marc , Lambert Jean-Charles , Hanson Julien , Desmet Christophe , Thiry Marc , Lauersen Kyle J. , Vidal Marc , Van Vlierberghe Pieter , Dequiedt Franck , Salehi-Ashtiani Kourosh , Twizere Jean-Claude
Published: September 2020

The endoplasmic reticulum (ER) is a central eukaryotic organelle with a tubular network made of hairpin proteins linked by hydrolysis of GTP nucleotides. Among post-translational modifications initiated at the ER level, glycosylation is the most common reaction. However, our understanding of the impact of glycosylation on ER structure remains unclear. Here, we show that Exostosin-1 (EXT1) glycosyltransferase, an enzyme involved inN-glycosylation, is a key regulator of ER morphology and dynamics. We have integrated multi-omics data and super-resolution imaging to characterize the broad effect of EXT1 inactivation, including ER shape-dynamics-function relationships in mammalian cells. We have observed that, inactivating EXT1 induces cell enlargement and enhances metabolic switches such as protein secretion. In particular, suppressing EXT1 in mouse thymocytes causes developmental dysfunctions associated to ER network extension. Our findings suggest that EXT1 drives glycosylation reactions involving ER structural proteins and high-energy nucleotide sugars, which might also apply to other organelles.
BrainPhys neuronal medium optimized for imaging and optogenetics in vitro
Authors: Zabolocki Michael , McCormack Kasandra , van den Hurk Mark , Milky Bridget , Shoubridge Andrew , Adams Robert , Tran Jenne , Mahadevan-Jansen Anita , Reineck Philipp , Thomas Jacob , Hutchinson Mark R , Mak Carmen , Añonuevo Adam , Harold Chew Leon , Hirst Adam J. , Lee Vivian M. , Knock Erin , Bardy Cedric
Published: September 2020

The capabilities of imaging technologies, fluorescent sensors, and optogenetics tools for cell biology have improved exponentially in the last ten years. At the same time, advances in cellular reprogramming and organoid engineering have quickly expanded the use of human neuronal modelsin vitro. Altogether this creates an increasing need for tissue culture conditions better adapted to live-cell imaging. Here, we identified multiple caveats of traditional media when used for live imaging and functional assays on neuronal cultures (e.g., phototoxicity, suboptimal fluorescence signals, and unphysiological neuronal activity). To overcome these issues, we developed a new neuromedium, “BrainPhys™ Imaging”, in which we adjusted fluorescent and phototoxic compounds. The new medium is based on the formulation of the original BrainPhys medium, which we designed to better support the neuronal activity of human neuronsin vitro1. We tested the new imaging-optimized formulation on human neurons cultured in monolayers or organoids, and rat primary neurons. BrainPhys Imaging enhanced fluorescence signals and reduced phototoxicity throughout the entire light spectrum. Importantly, consistent with standard BrainPhys, we showed that the new imaging medium optimally supports the electrical and synaptic activity of midbrain and human cortical neurons in culture. We also benchmarked the capacity of the new medium for functional calcium imaging and optogenetic control of human neurons. Altogether, our study shows that the new BrainPhys Imaging improves the quality of a wide range of fluorescence imaging applications with live neuronsin vitrowhile supporting cell viability and neuronal functions.
Local neuronal secretory trafficking dynamics revealed with zapERtrap: a light-inducible ER release system
Authors: Bourke Ashley M. , Schwartz Samantha L. , Bowen Aaron B. , Gutnick Amos , Schwarz Thomas L. , Kennedy Matthew J.
Published: September 2020

For normal synapse and circuit function, neurons must regulate the abundance and localization of transmembrane receptor, channel and adhesion proteins over vast cellular expanses, including remote sites in dendrites and axons. Whether the secretory network can support long-range trafficking of synaptic proteins synthesized in the cell body or precise trafficking of locally generated proteins at remote sites remains poorly characterized. We developed an approach for locally triggering secretory trafficking from specific subcellular domains to explore the rate, activity dependence and cargo-specificity of central and remote trafficking networks. Surprisingly, different postsynaptic proteins processed in the cell body were transported deep into dendrites, but with strikingly different kinetics, spatial distributions and activity dependencies. Proteins locally processed in dendrites were broadly dispersed prior to surface insertion, but could be directed locally to synapses. These results provide a novel interrogation of compartmentalized trafficking and reveal basic principles for protein targeting in complex cellular environments.
SNP-to-gene linking strategies reveal contributions of enhancer-related and candidate master-regulator genes to autoimmune disease
Authors: Dey Kushal K. , Gazal Steven , van de Geijn Bryce , Kim Samuel Sungil , Nasser Joseph , Engreitz Jesse M. , Price Alkes L.
Published: September 2020

Gene regulation is known to play a fundamental role in human disease, but mechanisms of regulation vary greatly across genes. Here, we explore the contributions to disease of two types of genes: genes whose regulation is driven by enhancer regions as opposed to promoter regions (enhancer-related) and genes that regulate other genes in trans (candidate master-regulator). We link these genes to SNPs using a comprehensive set of SNP-to-gene (S2G) strategies and apply stratified LD score regression to the resulting SNP annotations to draw three main conclusions about 11 autoimmune diseases and blood cell traits (average Ncase=13K across 6 autoimmune diseases, average N =443K across 5 blood cell traits). First, several characterizations of enhancer-related genes defined in blood using functional genomics data (e.g. ATAC-seq, RNA-seq, PC-HiC) are conditionally informative for autoimmune disease heritability, after conditioning on a broad set of regulatory annotations from the baseline-LD model. Second, candidate master-regulator genes defined using trans-eQTL in blood are also conditionally informative for autoimmune disease heritability. Third, integrating enhancer-related and candidate master-regulator gene sets with protein-protein interaction (PPI) network information magnified their disease signal. The resulting PPI-enhancer gene score produced >2x stronger conditional signal (maximum standardized SNP annotation effect size (τ*) = 2.0 (s.e. 0.3) vs. 0.91 (s.e. 0.21)), and >2x stronger gene-level enrichment for approved autoimmune disease drug targets (5.3x vs. 2.1x), as compared to the recently proposed Enhancer Domain Score (EDS). In each case, using functionally informed S2G strategies to link genes to SNPs that may regulate them produced much stronger disease signals (4.1x-13x larger τ* values) than conventional window-based S2G strategies. We conclude that our characterizations of enhancer-related and candidate master-regulator genes identify gene sets that are important for autoimmune disease, and that combining those gene sets with functionally informed S2G strategies enables us to identify SNP annotations in which disease heritability is concentrated.
Zinc dysregulation inslc30a8(znt8) mutant zebrafish leads to blindness and disrupts bone mineralisation
Authors: Mackay Eirinn W , Molero Sofía Ibañez , Tirathdas Lavitasha Harjani , Peterson-Maduro Josi , Zang Jingjing , Neuhauss Stephan C.F. , Schulte-Merker Stefan , Wilson Stephen W.
Published: September 2020

Zinc is an essential cofactor for many cellular processes including gene transcription, insulin secretion and retinal function. Excessive free Zn2+is highly toxic and consequently intracellular zinc is tightly controlled by a system of transporters, metallothioneins (MTs) and storage vesicles. Here we describe the developmental consequences of a missense allele of zinc efflux transporterslc30a8(znt8)in zebrafish. Homozygousslc30a8hu1798larvae are virtually blind and develop very little or no bone mineral. We show that zinc is stored in pigmented cells (melanophores) of healthy larvae but inslc30a8hu1798mutants it instead accumulates in the bone and brain. Supporting a role for pigment cells in zinc homeostasis,nacrezebrafish, which lack melanophores, also show disrupted zinc homeostasis. The photoreceptors ofslc30a8hu1798fish are severely depleted while those ofnacrefish are enriched with zinc. We propose that developing zebrafish utilise pigmented cells as a zinc storage organ, and that Slc30a8 is required for transport of zinc into these cells and into photoreceptors.