bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistence of SARS-CoV-2 virus and viral RNA on hydrophobic and hydrophilic surfaces and investigating contamination concentration
Authors: Paton Susan , Spencer Antony , Garratt Isobel , Thompson Katy-Anne , Dinesh Ikshitaa , Aranega-Bou Paz , Stevenson David , Clark Simon , Dunning Jake , Bennett Allan , Pottage Thomas
Published: March 2021

The transmission of SARS-CoV-2 is likely to occur through a number of routes, including contact with contaminated surfaces. Many studies have used RT-PCR analysis to detect SARS-CoV-2 RNA on surfaces but seldom has viable virus been detected. This paper investigates the viability over time of SARS-CoV-2 dried onto a range of materials and compares viability of the virus to RNA copies recovered, and whether virus viability is concentration dependant.

Viable virus persisted for the longest time on surgical mask material and stainless steel with a 99.9% reduction in viability by 124 and 113 hours respectively. Viability of SARS-CoV-2 reduced the fastest on a polyester shirt, with a 99.9% reduction within 2.5 hours. Viability on cotton was reduced second fastest, with 99.9% reduction in 72 hours. RNA on all the surfaces exhibited a one log reduction in genome copy recovery over 21 days.

The findings show that SARS-CoV-2 is most stable on non-porous hydrophobic surfaces. RNA is highly stable when dried on surfaces with only one log reduction in recovery over three weeks. In comparison, SARS-CoV-2 viability reduced more rapidly, but this loss in viability was found to be independent of starting concentration. Expected levels of SARS-CoV-2 viable environmental surface contamination would lead to undetectable levels within two days. Therefore, when RNA is detected on surfaces it does not directly indicate presence of viable virus even at high CT values.

Importance

This study shows the impact of material type on the viability of SARS-CoV-2 on surfaces. It demonstrates that the decay rate of viable SARS-CoV-2 is independent of starting concentration. However, RNA shows high stability on surfaces over extended periods. This has implications for interpretation of surface sampling results using RT-PCR to determine the possibility of viable virus from a surface. Unless sampled immediately after contamination it is difficult to align RNA copy numbers to quantity of viable virus on a surface.
Diurnal variation in SARS-CoV-2 PCR test results: Test accuracy may vary by time of day
Authors: McNaughton Candace D. , Adams Nicholas M. , Johnson Carl Hirschie , Ward Michael J. , Lasko Thomas A.
Published: March 2021

False negative tests for SARS-CoV-2 are common and have important public health and medical implications. We tested the hypothesis that the proportion of positive SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) tests varied by time of day, suggesting variation in viral shedding by time of day. Among 30,000 clinical tests performed among symptomatic and asymptomatic patients in the Vanderbilt Affiliated Healthcare Network from March-June 2020, we found evidence for diurnal variation in the proportion of positive SARS-CoV-2 tests, with a peak around 2pm in the afternoon and 2-fold variation over the day. Variation was most pronounced in outpatient and inpatient testing locations. These findings have important implications for public health testing and vaccination strategies.
Modeling the use of SARS-CoV-2 vaccination to safely relax non-pharmaceutical interventions
Authors: Kraay Alicia N.M. , Gallagher Molly E. , Ge Yang , Han Peichun , Baker Julia M. , Koelle Katia , Handel Andreas , Lopman Benjamin A
Published: March 2021

In response to the COVID-19 pandemic, widespread non-pharmaceutical interventions (NPIs), including physical distancing, mask wearing, and enhanced hygiene, have been implemented. As of March 2021, three effective vaccines have been approved for emergency use in the United States, with several other vaccines in the pipeline. We use a transmission model to study when and how NPIs could be relaxed in the United States with relative safety as vaccination becomes more widespread. We compare different relaxation scenarios where NPIs begin to relax 0-9 months after vaccination begins for both a one dose and two dose strategy, with historical levels of social interactions being reached within 1 month to 1 year. In our model, vaccination can allow widespread relaxation of NPIs to begin safely within 2 to 9 months, greatly reducing deaths and peak health system burden compared to relaxing NPIs without vaccination. Vaccinated individuals can safely begin to relax NPIs sooner than unvaccinated individuals. The extent of delay needed to safely reopen depends primarily on the rate of vaccine rollout, with the degree of protection against asymptomatic infection playing a secondary role. If a vaccination rate of 3 million doses/day can be achieved, similar to the typical rollout speed of seasonal influenza vaccination, NPIs could begin to be safely relaxed in 2-3 months. With a vaccination rate of 1 million doses/day, a 6–9-month delay is needed. A one dose strategy is preferred if relative efficacy is similar to a two-dose series, but the relative benefit of this strategy is minimal when vaccine rollout is fast. Due to the urgent need to pursue strategies that enable safe relaxation of NPIs, we recommend a two-dose strategy with an initial delay of at least 3 months in relaxing restrictions further, and that the speed of vaccine rollout be given immediate priority.
Limits of lockdown: characterising essential contacts during strict physical distancing
Authors: Thomas Amy , Danon Leon , Christensen Hannah , Northstone Kate , Smith Daniel , Nixon Emily , Trickey Adam , Hemani Gibran , Sauchelli Sarah , Finn Adam , Timpson Nicholas , Brooks-Pollock Ellen
Published: March 2021

COVID-19 has exposed health inequalities within countries and globally. The fundamental determining factor behind an individual’s risk of infection is the number of social contacts they make. In many countries, physical distancing measures have been implemented to control transmission of SARS-CoV-2, reducing social contacts to a minimum. Characterising unavoidable social contacts is key for understanding the inequalities behind differential risks and planning vaccination programmes. We utilised an existing English longitudinal birth cohort, which is broadly representative of the wider population (n=6807), to explore social contact patterns and behaviours when strict physical distancing measures were in place during the UK’s first lockdown in March-May 2020. Essential workers, specifically those in healthcare, had 4.5 times as many contacts as non-essential workers [incident rate ratio = 4.42 (CI95%: 3.88–5.04)], whilst essential workers in other sectors, mainly teaching and the police force had three times as many contacts [IRR = 2.84 (2.58–3.13)]. The number of individuals in a household, which is conflated by number of children, increases essential social contacts by 40%. Self-isolation effectively reduces numbers of contacts outside of the home, but not entirely. Together, these findings will aid the interpretation of epidemiological data and impact the design of effective SARS-CoV-2 control strategies, such as vaccination, testing and contact tracing.
Serum Vitamin D levels are associated with increased COVID-19 severity and mortality independent of whole-body and visceral adiposity
Authors: Vanegas-Cedillo Pablo Esteban , Bello-Chavolla Omar Yaxmehen , Ramírez-Pedraza Natalia , Encinas Bethsabel Rodríguez , Pérez Carrión Carolina Isabel , Jasso-Ávila María Isabel , Valladares-García Jorge Carlos , Hernández-Juárez Diana , Vargas-Vázquez Arsenio , Antonio-Villa Neftali Eduardo , Chapa-Ibarguengoitia Monica , de Leon Alfredo Ponce , Sifuentes-Osornio José , Aguilar-Salinas Carlos A. , Mehta Roopa
Published: March 2021

INTRODUCTION

Coronavirus disease (COVID-19) is a global pandemic. Vitamin D deficiency has been associated with susceptibility to infectious disease. In this study, the association between COVID-19 outcomes and vitamin D levels in patients attending a COVID-19 reference center in Mexico City are examined.

METHODS

Consecutive patients with confirmed COVID-19 were evaluated. All patients underwent clinical evaluation and follow-up, laboratory measurements and a thoracic computerized tomography, including the measurement of epicardial fat thickness. Low vitamin D was defined as levels <20ng/mL (<50nmol/L) and deficient Vitamin D as a level ≤12ng/mL (<30nmol/L)

RESULTS

Of the 551 patients included, low vitamin D levels were present in 45.6% and deficient levels in 10.9%. Deficient Vitamin D levels were associated with mortality (HR 2.11, 95%CI 1.24-3.58, p=0.006) but not with critical COVID-19, adjusted for age, sex, body-mass index and epicardial fat. Using model-based causal mediation analyses the increased risk of COVID-19 mortality conferred by low vitamin D levels was partly mediated by its effect on D-dimer and cardiac ultrasensitive troponins. Notably, increased risk of COVID-19 mortality conferred by low vitamin D levels was independent of BMI and epicardial fat.

CONCLUSION

Vitamin D deficiency (≤12ng/mL or <30nmol/L), is independently associated with COVID-19 mortality after adjustment for visceral fat (epicardial fat thickness). Low vitamin D may contribute to a pro-inflammatory and pro-thrombotic state, increasing the risk for adverse COVID-19 outcomes.
Seroprevalence of Antibodies to SARS-CoV-2 among Health Care Workers in Kenya
Authors: Etyang Anthony O. , Lucinde Ruth , Karanja Henry , Kalu Catherine , Mugo Daisy , Nyagwange James , Gitonga John , Tuju James , Wanjiku Perpetual , Karani Angela , Mutua Shadrack , Maroko Hosea , Nzomo Eddy , Maitha Eric , Kamuri Evanson , Kaugiria Thuranira , Weru Justus , Ochola Lucy B. , Kilimo Nelson , Charo Sande , Emukule Namdala , Moracha Wycliffe , Mukabi David , Okuku Rosemary , Ogutu Monicah , Angujo Barrack , Otiende Mark , Bottomley Christian , Otieno Edward , Ndwiga Leonard , Nyaguara Amek , Voller Shirine , Agoti Charles , Nokes David James , Ochola-Oyier Lynette Isabella , Aman Rashid , Amoth Patrick , Mwangangi Mercy , Kasera Kadondi , Ng’ang’a Wangari , Adetifa Ifedayo , Kagucia E. Wangeci , Gallagher Katherine , Uyoga Sophie , Tsofa Benjamin , Barasa Edwine , Bejon Philip , Scott J. Anthony G. , Agweyu Ambrose , Warimwe George
Published: March 2021

Background

Few studies have assessed the seroprevalence of antibodies against SARS-CoV-2 among Health Care Workers (HCWs) in Africa. We report findings from a survey among HCWs in three counties in Kenya.

Methods

We recruited 684 HCWs from Kilifi (rural), Busia (rural) and Nairobi (urban) counties. The serosurvey was conducted between 30thJuly 2020 and 4thDecember 2020. We tested for IgG antibodies to SARS-CoV-2 spike protein using ELISA. Assay sensitivity and specificity were 93% (95% CI 88-96%) and 99% (95% CI 98-99.5%), respectively. We adjusted prevalence estimates using Bayesian modeling to account for assay performance.

Results

Crude overall seroprevalence was 19.7% (135/684). After adjustment for assay performance seroprevalence was 20.8% (95% CI 17.5-24.4%). Seroprevalence varied significantly (p<0.001) by site: 43.8% (CI 35.8-52.2%) in Nairobi, 12.6% (CI 8.8-17.1%) in Busia and 11.5% (CI 7.2-17.6%) in Kilifi. In a multivariable model controlling for age, sex and site, professional cadre was not associated with differences in seroprevalence.

Conclusion

These initial data demonstrate a high seroprevalence of antibodies to SARS-CoV-2 among HCWs in Kenya. There was significant variation in seroprevalence by region, but not by cadre.
All Models Are Useful: Bayesian Ensembling for Robust High Resolution COVID-19 Forecasting
Authors: Adiga Aniruddha , Wang Lijing , Hurt Benjamin , Peddireddy Akhil , Porebski Przemyslaw , Venkatramanan Srinivasan , Lewis Bryan , Marathe Madhav
Published: March 2021

Timely, high-resolution forecasts of infectious disease incidence are useful for policy makers in deciding intervention measures and estimating healthcare resource burden. In this paper, we consider the task of forecasting COVID-19 confirmed cases at the county level for the United States. Although multiple methods have been explored for this task, their performance has varied across space and time due to noisy data and the inherent dynamic nature of the pandemic. We present a forecasting pipeline which incorporates probabilistic forecasts from multiple statistical, machine learning and mechanistic methods through a Bayesian ensembling scheme, and has been operational for nearly 6 months serving local, state and federal policymakers in the United States. While showing that the Bayesian ensemble is at least as good as the individual methods, we also show that each individual method contributes significantly for different spatial regions and time points. We compare our model’s performance with other similar models being integrated into CDC-initiated COVID-19 Forecast Hub, and show better performance at longer forecast horizons. Finally, we also describe how such forecasts are used to increase lead time for training mechanistic scenario projections. Our work demonstrates that such a real-time high resolution forecasting pipeline can be developed by integrating multiple methods within a performance-based ensemble to support pandemic response.

ACM Reference Format

Aniruddha Adiga, Lijing Wang, Benjamin Hurt, Akhil Peddireddy, Przemys-law Porebski,, Srinivasan Venkatramanan, Bryan Lewis, Madhav Marathe. 2021. All Models Are Useful: Bayesian Ensembling for Robust High Resolution COVID-19 Forecasting. InProceedings of ACM Conference (Conference’17). ACM, New York, NY, USA, 9 pages.https://doi.org/10.1145/nnnnnnn.nnnnnnn
Multi-resolution characterization of the COVID-19 pandemic: A unified framework and open-source tool
Authors: Shi Andy , Gaynor Sheila M. , Quick Corbin , Lin Xihong
Published: March 2021

Amidst the continuing spread of COVID-19, real-time data analysis and visualization remain critical to track the pandemic’s impact and inform policy making. Multiple metrics have been considered to evaluate the spread, infection, and mortality of infectious diseases. For example, numbers of new cases and deaths provide measures of absolute impact within a given population and time frame, while the effective reproduction rate provides a measure of the rate of spread. It is critical to evaluate multiple metrics concurrently, as they provide complementary insights into the impact and current state of the pandemic. We describe a unified framework for estimating and quantifying the uncertainty in the smoothed daily effective reproduction number, case rate, and death rate in a region using log-linear models. We apply this framework to characterize COVID-19 impact at multiple geographic resolutions, including by US county and state as well as by country, demonstrating the variation across resolutions and the need for harmonized efforts to control the pandemic. We provide an open-source online dashboard for real-time analysis and visualization of multiple key metrics, which are critical to evaluate the impact of COVID-19 and make informed policy decisions.
A potential SARS-CoV-2 variant of interest (VOI) harboring mutation E484K in the Spike protein was identified within lineage B.1.1.33 circulating in Brazil
Authors: Resende Paola Cristina , Gräf Tiago , Paixão Anna Carolina Dias , Appolinario Luciana , Lopes Renata Serrano , da Fonseca Mendonça Ana Carolina , da Rocha Alice Sampaio Barreto , Motta Fernando Couto , Neto Lidio Gonçalves Lima , Khouri Ricardo , de Oliveira Camila Indiani , Santos-Muccillo Pedro , Bezerra Joao Felipe , Teixeira Dalane Loudal Florentino , Riediger Irina , do Carmo Debur Maria , Ribeiro-Rodrigues Rodrigo , Leite Anderson Brandao , do Santos Cliomar Alves , Gregianini Tatiana Schäffer , Fernandes Sandra Bianchini , Bernardes André Felipe Leal , Cavalcanti Andrea Cony , Miyajima Fábio , Sachhi Claudio , Mattos Tirza , da Costa Cristiano Fernandes , Delatorre Edson , Wallau Gabriel L , Naveca Felipe G , Bello Gonzalo , Siqueira Marilda Mendonça
Published: March 2021

The SARS-CoV-2 epidemic in Brazil was dominated by two lineages designated as B.1.1.28 and B.1.1.33. Two SARS-CoV-2 variants harboring mutations at the receptor-binding domain of the Spike (S) protein, designated as lineages P.1 and P.2, evolved within lineage B.1.1.28 and are rapidly spreading in Brazil. Lineage P.1 is considered a Variant of Concern (VOC) because of the presence of multiple mutations in the S protein (including K417T, E484K, N501Y), while lineage P.2 only harbors mutation S:E484K and is considered a Variant of Interest (VOI). Here we report the identification of a new SARS-CoV-2 VOI within lineage B.1.1.33 that also harbors mutation S:E484K and was detected in Brazil between November 2020 and February 2021. This VOI displayed four non-synonymous lineage-defining mutations (NSP3:A1711V, NSP6:F36L, S:E484K, and NS7b:E33A) and was designated as lineage N.9. The VOI N.9 probably emerged in August 2020 and has spread across different Brazilian states from the Southeast, South, North and Northeast regions.
16S rRNA Gene Amplicon Profiling of the New Zealand parasitic blowflyCalliphora vicina
Authors: Palevich Nikola , Maclean Paul H. , Carvalho Luis , Jauregui Ruy
Published: March 2021

Here, we present a 16S rRNA gene amplicon sequence data set and profiles demonstrating the bacterial diversity of larval and adultCalliphora vicina, collected from Ashhurst, New Zealand (May 2020). The three dominant genera among adult male and femaleC. vicinawereSerratiaandMorganella(phylumProteobacteria) andCarnobacterium(phylumFirmicutes), while the larvae were also dominated by the generaLactobacillus(phylumFirmicutes).
Rare transmission of commensal and pathogenic bacteria in the gut microbiome of hospitalized adults
Authors: Siranosian Benjamin A. , Brooks Erin F. , Andermann Tessa , Rezvani Andrew R. , Banaei Niaz , Tang Hua , Bhatt Ami S.
Published: March 2021

Bacterial bloodstream infections are a major cause of morbidity and mortality among patients undergoing hematopoietic cell transplantation (HCT). Although previous research has demonstrated that pathogenic organisms may translocate from the gut microbiome into the bloodstream to cause infections, the mechanisms by which HCT patients acquire pathogens in their microbiome have not yet been described. We hypothesized that patient-patient transmission may be responsible for pathogens colonizing the microbiome of HCT patients, and that patients who share time and space in the hospital are more likely to share bacterial strains.

Here, we used linked-read and short-read metagenomic sequencing to analyze 401 stool samples collected from 149 adults undergoing HCT and hospitalized in the same unit over five years. We used metagenomic assembly and strain-specific comparison methods to investigate transmission of gut microbiota between individuals. While patients who shared time and space in the hospital did not converge in overall microbiome composition, we did observe four pairs of patients who harbor identical or nearly identicalE. faeciumstrains in their microbiome. These strains may be the result of transmission between patients who shared a room and bathroom, acquisition from a common source in the hospital or transmission from an unsampled source.

We also observed identicalAkkermansia muciniphilaandHungatella hathewayistrains in two pairs of patients. In both cases, the patients were roommates for at least one day, the strain was absent in the putative recipient’s microbiome prior to the period of roommate overlap and the putative recipient had a microbiome perturbed by antibiotic treatment for a bloodstream infection. Finally, we identified multiple patients who harbored identical strains of several species commonly found in commercial probiotics and dairy products, includingLactobacillus rhamnosus,Lactobacillus gasseriandStreptococcus thermophilus. Overall, our findings indicate that pathogenic organisms from a single source are not frequently colonizing the gut microbiome of multiple patients. However, the potential transmission of commensal microbes with immunomodulatory properties raises questions about the recovery of microbiome diversity after HCT, and indicates that patients in this setting may acquire new microbes by sharing space with others.
Yersinia pestislipopolysaccharide remodeling confers resistance to aXenopsylla cheopiscecropin
Authors: Mathew Basil , Aoyagi Kari L. , Fisher Mark A.
Published: March 2021

Fleas are major vectors ofYersinia pestis,the causative agent of plague. It has been proposed thatY. pestishas developed the ability to overcome the innate immune responses of fleas. Despite the fact that they transmit a number of bacterial infections, very little is known about the immune responses in fleas. In this study, we describe the antimicrobial activities of cecropin fromXenopsylla cheopis(cheopin), a major vector forY. pestisin the wild. This is the first cecropin-class antimicrobial peptide described from Siphonaptera insects. Cheopin showed potent activity against Gram-negative bacteria, but little activity against wild-typeY. pestisKIM6+. Deletion of the aminoarabinose operon, which is responsible for the 4-amino-4-deoxy-L-arabinose (Ara4N) modification of LPS, renderedY. pestishighly susceptible to cheopin. Confocal microscopy and whole cell binding assays indicated that Ara4N modification reduces the affinity of cheopin forY. pestis.Further, cheopin only permeabilized bacterial membranes in the absence of Ara4N-modified LPS, which was correlated with bacterial killing. This study provides insights into innate immunity of the flea and evidence for the crucial role of Ara4N modification ofY. pestisLPS in conferring resistance against flea antimicrobial peptides.
Clinical Knowledge Extraction via Sparse Embedding Regression (KESER) with Multi-Center Large Scale Electronic Health Record Data
Authors: Hong Chuan , Rush Everett , Liu Molei , Zhou Doudou , Sun Jiehuan , Sonabend Aaron , Castro Victor M. , Schubert Petra , Panickan Vidul A. , Cai Tianrun , Costa Lauren , He Zeling , Link Nicholas , Hauser Ronald , Gaziano J. Michael , Murphy Shawn N. , Ostrouchov George , Ho Yuk-Lam , Begoli Edmon , Lu Junwei , Cho Kelly , Liao Katherine P. , Cai Tianxi ,   with the VA Million Veteran Program
Published: March 2021

Objective

The increasing availability of Electronic Health Record (EHR) systems has created enormous potential for translational research. Even with a working knowledge of EHR, it is difficult to know all the relevant codes related to a phenotype due to the large number of codes available. Traditional data mining approaches often require the use of patient-level data, which hinders the ability to share data across institutions to establish a cooperative and integrated knowledge network. In this project, we demonstrate that multi-center large-scale code embeddings can be used to efficiently identify relevant features related to a disease or condition of interest.

Method

We constructed large-scale code embeddings for a wide range of codified concepts, including diagnosis codes, medications, procedures, and laboratory tests from EHRs from two large medical centers. We developed knowledge extraction via sparse embedding regression (KESER) for feature selection and integrative network analysis based on the trained code embeddings. We evaluated the quality of the code embeddings and assessed the performance of KESER in feature selection for eight diseases. Besides, we developed an integrated clinical knowledge map combining embedding data from both institutions.

Results

The features selected by KESER were comprehensive compared to lists of codified data generated by domain experts. Additionally, features identified automatically via KESER used in the development of phenotype algorithms resulted in comparable performance to those built upon features selected manually or identified via existing feature selection methods with patient-level data. The knowledge map created using an integrative analysis identified disease-disease and disease-drug pairs more accurately compared to those identified using single institution data.

Conclusion

Analysis of code embeddings via KESER can effectively reveal clinical knowledge and infer relatedness among diseases, treatment, procedures, and laboratory measurement. This approach automates the grouping of clinical features facilitating studies of the condition. KESER bypasses the need for patient-level data in individual analyses providing a significant advance in enabling multi-center studies using EHR data.
How a sticky fluid facilitates prey retention in a carnivorous pitcher plant (Nepenthes rafflesiana)
Authors: Kang Victor , Isermann Hannah , Sharma Saksham , Wilson D Ian , Federle Walter
Published: March 2021

Nepenthespitcher plants live in nutrient-poor soils and produce large pitfall traps to obtain additional nutrients from animal prey. Previous research has shown that the digestive secretion inN. rafflesianais a sticky viscoelastic fluid that is much more effective at retaining insects than water, even after significant dilution. Although the physical properties of the fluid are important for its retentive function, it is unclear how the fluid interacts with insect cuticle and how its sticky nature affects struggling insects. In this study, we investigated the mechanisms behind the efficient prey retention inN. rafflesianapitcher fluid. By measuring the attractive forces exerted on insect body parts moving in and out of test fluids, we show that it costs insects significantly more energy to separate from pitcher fluid than from water. Moreover, both the maximum force and the energy required for retraction increase after the first contact with the pitcher fluid. We found that insects sink more easily into pitcher fluid than water and, accordingly, the surface tension ofN. rafflesianapitcher fluid was significantly lower than that of water (60.2 vs. 72.3 mN/m). By analysing the pitcher fluid dewetting behaviour, we demonstrate that it strongly resists dewetting from all surfaces tested, leaving behind residual films and filaments that can facilitate re-wetting. This inhibition of dewetting may be a further consequence of the fluid’s viscoelastic nature and likely represents a key mechanism underlying prey retention inNepenthespitcher plants.
A robust voice-selective response in the human brain as revealed by electrophysiological recordings and fast periodic auditory stimulation
Authors: Barbero Francesca M. , Calce Roberta P. , Talwar Siddharth , Rossion Bruno , Collignon Olivier
Published: March 2021

Voices are arguably among the most relevant sounds in humans’ everyday life, and several studies have suggested the existence of voice-selective regions in the human brain. Despite two decades of research, defining the human brain regions supporting voice recognition remains challenging. Moreover, whether neural selectivity to voices is merely driven by acoustic properties specific to human voices (e.g. spectrogram, harmonicity), or whether it also reflects a higher-level categorization response is still under debate. Here, we objectively measured rapid automatic categorization responses to human voices with Fast Periodic Auditory Stimulation (FPAS) combined with electroencephalography (EEG). Participants were tested with stimulation sequences containing heterogeneous non-vocal sounds from different categories presented at 4 Hz (i.e., 4 stimuli/second), with vocal sounds appearing every 3 stimuli (1.333 Hz). A few minutes of stimulation are sufficient to elicit robust 1.333 Hz voice-selective focal brain responses over superior temporal regions of individual participants. This response is virtually absent for sequences using frequency-scrambled sounds, but is clearly observed when voices are presented among sounds from musical instruments matched for pitch and harmonicity-to-noise ratio. Overall, our FPAS paradigm demonstrates that the human brain seamlessly categorizes human voices when compared to other sounds including matched musical instruments and that voice-selective responses are at least partially independent from low-level acoustic features, making it a powerful and versatile tool to understand human auditory categorization in general.

Significance statement

Voices are arguably among the most relevant sounds we hear in our everyday life, and several studies have corroborated the existence of regions in the human brain that respond preferentially to voices. However, whether this preference is driven by specific acoustic properties of voices or if it rather reflects a higher-level categorization response to voices is still under debate. We propose a new approach to objectively identify rapid automatic voice-selective responses with frequency tagging and electroencephalographic recordings. In four minutes of recording only, we recorded robust voice-selective responses independent from low-level acoustic cues, making this approach highly promising for studying auditory perception in children and clinical populations.
Symmetry processing in the macaque visual cortex
Authors: Audurier Pauline , Héjja-Brichard Yseult , De Castro Vanessa , Kohler Peter J. , Norcia Anthony M. , Durand Jean-Baptiste , Cottereau Benoit R.
Published: March 2021

Symmetry is a highly salient feature of the natural world that is perceived by many species of the animal kingdom and that impacts a large array of behaviours such as partner selection or food choice. In humans, the cerebral areas processing symmetry are now well identified from neuroimaging measurements. However, we currently lack an animal model to explore the underlying neural mechanisms. Macaque is a potentially good candidate, but a previous comparative study (1) found that functional magnetic resonance imaging (fMRI) responses to mirror symmetry in this species were substantially weaker than those observed in humans under similar experimental conditions. Here, we re-examined symmetry processing in macaques from a broader perspective, using both rotation (experiment 1) and reflection (experiment 2) symmetry. Our experimental design was directly derived from that of a previous human fMRI study (2), in order to facilitate the comparison between the two primate species. Highly consistent responses to symmetry were found in a large network of areas (notably V3, V3A, V4, V4A and PITd), in line with what has been observed in humans. Within this network, response properties in areas V3 and V4 (notably their dependency on the rotation symmetry order) were strikingly similar to those observed in their human counterparts. Our results suggest that the cortical networks that process symmetry in humans and macaques are much more similar than previously reported and point toward macaque as a relevant model for understanding symmetry processing.

Significance statement

Symmetry processing is an important aspect of human visual perception. We currently lack an animal model for characterizing the neural mechanisms that underlie it at the microscopic scale. Here, we use fMRI measurements in macaques to demonstrate that the cortical responses to symmetry in this species are comparable to those observed in humans under similar experimental conditions to a much higher extent than previously documented. Our results call for a re-examination of the relevance of the macaque model for symmetry processing in humans and open the door to an exploration of the underlying neural mechanisms at the single-cell level, notably in V3, an area often neglected in most current models of visual processing.
Clomipramine suppresses ACE2-mediated SARS-CoV-2 entry
Authors: Kato Yuri , Yamada Shigeru , Nishiyama Kazuhiro , Satsuka Ayano , Re Suyong , Tomokiyo Daiki , Lee Jae Man , Tanaka Tomohiro , Nishimura Akiyuki , Yonemitsu Kenzo , Asakura Hiroshi , Ibuki Yuko , Imai Yumiko , Kamiya Noriho , Mizuguchi Kenji , Kusakabe Takahiro , Kanda Yasunari , Nishida Motohiro
Published: March 2021

Myocardial damage caused by the newly emerged coronavirus (SARS-CoV-2) infection is one of key determinants of COVID-19 severity and mortality. SARS-CoV-2 entry to host cells are initiated by binding with its receptor, angiotensin converting enzyme (ACE) 2, and the ACE2 abundance is thought to reflect the susceptibility to infection. Here, we found that clomipramine, a tricyclic antidepressant, potently inhibits SARS-CoV-2 infection and metabolic disorder in human iPS-derived cardiomyocytes. Among 13 approved drugs that we have previously identified as potential inhibitor of doxorubicin-induced cardiotoxicity, clomipramine showed the best potency to inhibit SARS-CoV-2 spike glycoprotein pseudovirus-stimulated ACE2 internalization. Indeed, SARS-CoV-2 infection to human iPS-derived cardiomyocytes (iPS-CMs) and TMPRSS2-expressing VeroE6 cells were dramatically suppressed even after treatment with clomipramine. Furthermore, the combined use of clomipramine and remdesivir was revealed to synergistically suppress SARS-CoV-2 infection. Our results will provide the potentiality of clomipramine for the breakthrough treatment of severe COVID-19.
Using recent baselines as benchmarks for megafauna restoration places an unfair burden on the Global South
Authors: Monsarrat Sophie , Svenning Jens-Christian
Published: March 2021

The potential for megafauna restoration is unevenly distributed across the world, along with the socio-political capacity of countries to support these restoration initiatives. We show that choosing a recent baseline to identify species’ indigenous range puts a higher burden for megafauna restoration on countries in the Global South, which also have less capacity to support these restoration initiatives. We introduce the Megafauna Index, which considers large mammal’s potential species richness and range area at country-level, to explore how the responsibility for megafauna restoration distributes across the world according to four scenarios using various temporal benchmarks to define species’ indigenous range – current, historical (1500AD), mid-Holocene and Pleistocene. We test how the distribution of restoration burden across the world correlates to indicators of conservation funding, human development, and governance. Using a recent or historical baseline as a benchmark for restoration puts a higher pressure on African and southeast Asian countries while lifting the responsibility from the Global North, where extinctions happened a long time ago. When using a mid-Holocene or Pleistocene baseline, new opportunities arise for megafauna restoration in Europe and North America respectively, where countries have a higher financial and societal capacity to support megafauna restoration. These results contribute to the debate around benchmarks in rewilding initiatives and the ethical implications of using recent baselines to guide restoration efforts. We suggest that countries from the Global North should reflect on their responsibility in supporting global restoration efforts, by increasing their support for capacity building in the South and taking responsibility for restoring lost biodiversity at home.
DeepLncLoc: a deep learning framework for long non-coding RNA subcellular localization prediction based on subsequence embedding
Authors: Zeng Min , Wu Yifan , Lu Chengqian , Zhang Fuhao , Wu Fang-Xiang , Li Min
Published: March 2021

Motivation

Long non-coding RNAs (IncRNAs) are a class of RNA molecules with more than 200 nucleotides. A growing amount of evidence reveals that subcellular localization of lncRNAs can provide valuable insights into their biological functions. Existing computational methods for predicting lncRNA subcellular localization use k-mer features to encode lncRNA sequences. However, the sequence order information is lost by using only k-mer features.

Results

We proposed a deep learning framework, DeepLncLoc, to predict lncRNA subcellular localization. In DeepLncLoc, we introduced a new subsequence embedding method that keeps the order information of lncRNA sequences. The subsequence embedding method first divides a sequence into some consecutive subsequences, and then extracts the patterns of each subsequence, last combines these patterns to obtain a complete representation of the lncRNA sequence. After that, a text convolutional neural network is employed to learn high-level features and perform the prediction task. Compared to traditional machine learning models with k-mer features and existing predictors, DeepLncLoc achieved better performance, which shows that DeepLncLoc could effectively predict lncRNA subcellular localization. Our study not only presented a novel computational model for predicting lncRNA subcellular localization but also provided a new subsequence embedding method which is expected to be applied in other sequence-based prediction tasks.

Availability

The DeepLncLoc web server, source code and datasets are freely available athttp://bioinformatics.csu.edu.cn/DeepLncLoc/, andhttps://github.com/CSUBioGroup/DeepLncLoc.

Contact

limin@mail.csu.edu.cn
Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex
Authors: Malone Brandon , Chen James , Wang Qi , Llewellyn Eliza , Choi Young Joo , Olinares Paul Dominic B. , Cao Xinyun , Hernandez Carolina , Eng Edward T. , Chait Brian T. , Shaw David E. , Landick Robert , Darst Seth A. , Campbell Elizabeth A.
Published: March 2021

Backtracking, the reverse motion of the transcriptase enzyme on the nucleic acid template, is a universal regulatory feature of transcription in cellular organisms but its role in viruses is not established. Here we present evidence that backtracking extends into the viral realm, where backtracking by the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) may aid viral transcription and replication. Structures of SARS-CoV-2 RdRp bound to the essential nsp13 helicase and RNA suggested the helicase facilitates backtracking. We use cryo-electron microscopy, RNA-protein crosslinking, and unbiased molecular dynamics simulations to characterize SARS-CoV-2 RdRp backtracking. The results establish that the single-stranded 3’-segment of the product-RNA generated by backtracking extrudes through the RdRp NTP-entry tunnel, that a mismatched nucleotide at the product-RNA 3’-end frays and enters the NTP-entry tunnel to initiate backtracking, and that nsp13 stimulates RdRp backtracking. Backtracking may aid proofreading, a crucial process for SARS-CoV-2 resistance against antivirals.

Significance Statement

The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 genome is replicated and transcribed by its RNA-dependent RNA polymerase (RdRp), which is the target for antivirals such as remdesivir. We use a combination of approaches to show that backtracking (backwards motion of the RdRp on the template RNA) is a feature of SARS-CoV-2 replication/transcription. Backtracking may play a critical role in proofreading, a crucial process for SARS-CoV-2 resistance against many antivirals.
Host phenology can drive the evolution of intermediate virulence strategies in some obligate-killer parasites
Authors: MacDonald Hannelore , Akçay Erol , Brisson Dustin
Published: March 2021

Abstract

The traditional mechanistic trade-offs resulting in a negative correlation between transmission and virulence are the foundation of nearly all current theory on the evolution of parasite virulence. Several ecological factors have been shown to modulate the optimal virulence strategies predicted from mechanistic trade-off models, but these ecological factors have not yet been shown to be sufficient to explain the intermediate virulence strategies observed in any natural system. The timing of seasonal activity, or phenology, is a common factor that influences the types and impact of many ecological interactions but is difficult to incorporate into virulence evolution studies. We develop a mathematical model of a disease system with seasonal host activity to study the evolutionary consequences of host phenology on the virulence of obligate-killer parasite. Results from this model demonstrated that seasonal host activity is sufficient to drive the evolution of intermediate parasite virulence in some types of natural disease systems, even when a traditional mechanistic trade-off between transmission and virulence is not assumed in the modeling framework. The optimal virulence strategy in these systems can be determined by both the duration of the host activity period as well as the variation in the host emergence timing. Parasites with low virulence strategies are favored in environments with long host activity periods and in environments in which hosts emerge synchronously. The results demonstrate that host phenology can be sufficient to select for intermediate optimal virulence strategies, providing an alternative mechanism to account for virulence evolution in some natural systems.
Career decision-making difficulties among university students: does employment status matter?
Authors: Yaghi Abdulfattah , Alabed Nizar
Published: March 2021

Purpose

The study adapted the Career Decision Making Difficulties Questionnaire for the Arab world. The purpose of the study was to test a popular but scientifically unverified belief that people who were employed could experience less CDD.

Design/methodology/approach

Career Decision-Making Difficulties Questionnaire was administered to a sample of 500 university students to analyze CDD among full-time and part-time students and examine whether employment status determines to what extent they experience these difficulties. Univariate and bivariate analyses were used.

Findings

Employment status had no statistically significant effect on students' perceptions of CDD; 6 demographic variables were significantly correlated with CDD (gender, age, income, university grade-point average, satisfaction with the current major and social status); and students had dysfunctional beliefs about the career decision-making process, lack self-awareness, and had inconsistent information about internal and external difficulties.

Research limitations/implications

Universities should design adequate career interventions before and after graduation and employers should implement human resource policies that reduce CDD and their negative impact on the workplace. Other methods of data collection and analysis could also be useful in the future, such as interviews. While scope of the study was acceptable, comparing countries and public versus private institutions could produce valuable findings.

Practical implications

The study tested and validated ACDDQ which could be used as diagnostic instrument to design career interventions and training programs. Employers need to allocate resources in the recruitment process to help potential recruits to understand the nature of work, processes, and requirements. Educators need to provide better coaching and career education for students, especially those in senior years.

Social implications

Understanding career decision-making difficulties and factors that influence them will influence long-term human resource management, especially productivity, turn over and job satisfaction.

Originality/value

The study examined the important issue of difficulties in making career decisions among two groups of university students. With more employees go back to college for more education, it was not clear in the literature how career decisions might differ between the two groups. The issue was under-researched, especially within Arab countries.
Comparing the reproductive biological characteristics of the alien invasive Coreopsis lanceolata to those of the non‐invasive alien congener Coreopsis tinctoria
Authors: Zeng Jian‐Jun , Zhou Bing , Wang Ning
Published: March 2021

It is important to determine the characteristics associated with the success of alien species. However, there is no universal syndrome of invasion reproductive characteristics to explain the success of invasiveness has not been identified. Comparative studies on congeneric successful or non‐successful alien species are beneficial for revealing the drivers of invasion success and predicting future distributions. Reproductive biological characteristics, including the mating system, phenology of flowering, floral syndrome, pollination biology and seed germination have been investigated in the invasive Coreopsis lanceolata and non‐successful congener alien species Coreopsis tinctoria. The results revealed that C. lanceolata significantly attracted insect visitors by 11.67 times more than its congener, and the corolla density of C. lanceolata was positively correlated with the number of visiting insects. The high attraction of local insect bees Apis cerana guarantees the reproductive success and high seed production of C. lanceolata. Nevertheless, there was no versatile mating system, because its congener non‐successful alien species C. lanceolata still successfully invaded due to the combination strategies of self‐compatibility and presence of rhizomes. Furthermore, the ability of seed germination of C. lanceolata was lower than that of C. tinctoria, especially under drought and Al3+ stress, suggesting that germination performance can serve as a reference indicator. However, this was not an absolute trait for invasiveness. Hence, these germination traits might slow down the invasiveness of C. lanceolata in south China. These present findings highlight that the combination of self‐incompatibility and rhizomes should be given attention in the risk assessment protocols for plant invasiveness.
Development and implementation of a Pacific Island‐centred COVID‐19 Health Worker Safety Guide
Authors: Gittus Angela , Griffiths Bronwen , de Salis Dominic , Phillips Georgina
Published: March 2021

Objective

Healthcare workers in Pacific Island Countries face unique workload and infection control hazards because of limited resources, cultural practices and local disease burden. In the context of COVID‐19, concern around healthcare worker safety escalated in the region, triggering the need for a relevant resource.

Methods

We describe a collaborative, participatory action‐research approach with a diverse range of local clinicians in Pacific Island Countries to design, develop and implement a practical guideline assisting clinicians to work safely during the pandemic.

Results

The resulting Health Worker Safety Guide for COVID‐19 is a relevant and usable protocol developed using local knowledge and now available in several Pacific languages.

Conclusion

We recommend a creative approach to facilitate meaningful communication with this group of clinicians, including low resolution technology and use of social media platforms.
Retrospective analysis of a single institute's experience of transverse colectomy vs extended colectomy for the management of mid‐transverse colon cancer
Authors: Chow Tom Chi‐man , Wong Chi‐keung , Si Alvin Lok‐ping , Ng Andrew Sheung‐hey , Kong Chi‐kwan
Published: March 2021

Objective

Mid‐transverse colon cancers are uncommon. The optimum operative strategy, whether extended colectomy or limited transverse colectomy, is not well established. Herein we share our local experience.

Methodology

Consecutive patients with mid‐transverse colon cancer resection from January 2000 to January 2020 were identified from electronic records. Short‐ and long‐term outcomes were analyzed. Additional propensity‐score matching adjusted for potential treatment selection bias.

Results

A total of 107 patients were analyzed. 23 patients (21.5%) underwent transverse colectomy (TC) and 84 (78.5%) underwent extended colectomy (EC) of which 68 were extended right hemicolectomy. 53% of all operations were laparoscopic. Similar postoperative complication rate, postoperative length of stay and 30 day mortality rate were found. Although fewer lymph node (median 11 vs 19, P < .01) and shorter closest axial margin (3.8 vs 5.5 cm, P < .01) were achieved in the TC group, similar 5‐years overall survival, and 1‐year disease‐free survival were found. Subgroup analysis revealed a trend of poorer survival amongst stage III/IV patients with transverse colectomy.

Conclusions

Our study verifies the feasibility and safety of transverse colectomy for mid‐transverse colon cancers. Attention should focus on achieving adequate margin length and nodal yield.