bluuebunny/crossref_metadata_2025 huggingface dataset:
Ongoing mitigation strategies and further needs of the United States food industry to control COVID-19 in the work environment
Authors: Llanos-Soto Sebastian , Bulut Ece , Murphy Sarah I. , Henry Christopher J. , Zoellner Claire , Wiedmann Martin , Wetherington Diane , Adalja Aaron , Alcaine Samuel D. , Ivanek Renata
Published: August 2021

The COVID-19 pandemic has had dire effects on the United States (US) food industry through impacts on workers’ health and wellbeing and supply chain disruptions. The objectives of this study were to determine what the food industry needs to be able to control COVID-19 impacts in the work environment and what mitigation strategies are being implemented. A web-based needs assessment survey was distributed from January to April 2021, via 13 food professional/trade organizations and 2 social networks, targeting management professionals at food (produce, dairy, poultry, and beef/pork) processing facilities and produce farm operations in the US. Statistical analyses evaluated patterns in self-reported adoption of mitigation strategies against COVID-19 in the participants’ facilities/operations and perceived needs of the industry regarding COVID-Responses to open-ended questions were analyzed using thematic analysis. In total 145 responses were received, of which 79 were usable, including 38 (48%) from the dairy, 17 (22%) from the fresh produce, and 24 (30%) from a mixture of other food industry sectors. Only two usable responses were from the beef/pork sector and none from the poultry sector. Findings revealed that several social distancing, biosecurity, and surveillance mitigation strategies against COVID-19 are commonly implemented in the participants’ facilities/operations, but their implementation frequency differs by the facility/operation size and industry sector. Also, findings indicated that collaboration between the food industry and government agencies, contingency plans and appropriate training, and new technologies are needed to control COVID- 19 in the food industry. Subject to limitations associated with the relatively low response rate (possible selection bias), the findings suggest that the US food industry is prepared to safeguard workers’ health and businesses in the event of a new COVID-19 variant or similar future disaster, provided that appropriate structures are put in place to ensure coordination and compliance, both before and during such an outbreak.
Morphological determinants of bite force capacity in insects: a biomechanical analysis of polymorphous leaf-cutter ants
Authors: Püffel Frederik , Pouget Anaya , Liu Xinyue , Zuber Marcus , van de Kamp Thomas , Roces Flavio , Labonte David
Published: August 2021

The extraordinary success of social insects is partially based on ‘division of labour’, i. e. individuals exclusively or preferentially perform specific tasks. Task-preference may correlate with morphological adaptations so implying task-specialisation, but the extent of such specialisation can be difficult to determine. Here, we demonstrate how the physical foundation of some tasks can be leveraged to quantitatively link morphology and performance. We study the allometry of bite force capacity inAtta vollenweiderileaf-cutter ants, polymorphic insects in which the mechanical processing of plant material is a key aspect of the behavioural portfolio. Through a morphometric analysis of tomographic scans, we show that the bite force capacity of the heaviest colony workers is twice as large as predicted by isometry. This disproportionate ‘boost’ is predominantly achieved through increased investment in muscle volume; geometrical parameters such as mechanical advantage, fibre length or pennation angle are likely constrained by the need to maintain a constant mandibular opening range. We analyse this preference for an increase in size-specific muscle volume and the adaptations in internal and external head anatomy required to accommodate it with simple geometric and physical models, so providing a quantitative understanding of the functional anatomy of the musculoskeletal bite apparatus in insects.
Revealing how variations in antibody repertoires correlate with vaccine responses
Authors: Safonova Yana , Shin Sung Bong , Kramer Luke , Reecy James , Watson Corey T. , Smith Timothy P.L. , Pevzner Pavel A.
Published: August 2021

An important challenge in vaccine development is to figure out why a vaccine succeeds in some individuals and fails in others. Although antibody repertoires hold a key to answering this question, there have been very few personalized immunogenomics studies so far aimed at revealing how variations in immunoglobulin genes affect a vaccine response. We conducted an immunosequencing study of 204 calves vaccinated against bovine respiratory disease (BRD) with the goal to reveal variations in immunoglobulin genes and somatic hypermutations that impact the efficacy of vaccine response. Our study represents the largest longitudinal personalized immunogenomics study reported to date across all species, including humans. To analyze the generated dataset, we developed an algorithm for identifying variations of the immunoglobulin genes (as well as frequent somatic hypermutations) that affect various features of the antibody repertoire and titers of neutralizing antibodies. In contrast to relatively short human antibodies, cattle have a large fraction of ultralong antibodies that have opened new therapeutic opportunities. Our study revealed that ultralong antibodies are a key component of the immune response against the costliest disease of beef cattle in North America. The detected variants of the cattle immunoglobulin genes, which are implicated in the success/failure of the BRD vaccine, have the potential to direct the selection of individual cattle for ongoing breeding programs.
Preferential interactions of a crowder protein with the specific binding site of a native protein complex
Authors: Dong Xu , Qin Ling-Yun , Gong Zhou , Qin Sanbo , Zhou Huan-Xiang , Tang Chun
Published: August 2021

The crowded cellular environments provide ample opportunities for proteins to interact with bystander macromolecules, yet direct evidence, let alone residue-specific information, for such nonspecific binding is rare. Here, by combining NMR spectroscopy and atomistic modeling, we investigated how crowders influence the association equilibrium and kinetics of two protein partners, EIN and HPr. Ficoll-70 increases the EIN-HPr binding affinity whereas bovine serum albumin (BSA) decreases the affinity. The opposite effects of the two crowders are quantitatively explained by atomistic modeling, which shows that the stabilizing effect of Ficoll-70 arises from volume exclusion favoring the bound state. In contrast, the destabilizing effect of BSA arises from preferential soft interactions with the free state; notably, BSA has favorable electrostatic interactions with positively charged HPr residues within the EIN-binding site. Some of the residues from this site indeed experience significant chemical shift perturbation when titrated with BSA, while the relaxation rates of HPr backbone amides exhibit overall elevation. Furthermore, relaxation dispersion data indicate that Ficoll-70 and BSA both slow down the EIN-HPr association rate, but change the dissociate rate in opposite directions. The observations on kinetics are accounted for by two effects of the crowders: increasing the solution microviscosity and reshaping the EIN-HPr interaction energy surface. The kind of preferential interactions between BSA and HPr that leads to competition with EIN should be prevalent in cellular environments. Our NMR results and atomistic modeling provide benchmarks, at both qualitative and quantitative levels, for the effects of crowded cellular environments on protein-protein specific interactions.

Significance Statement

Although nonspecific binding of crowder macromolecules with functional proteins is likely prevalentin vivo, direct evidence is rare. Here we present NMR characterizations showing that bovine serum albumin preferentially interacts with a specific binding site on HPr, leading to competition with the latter’s partner EIN. The preferential interactions result in destabilization of the EIN-HPr native complex and speedup of its dissociation, contrary to expectations from excluded-volume and viscosity effects. Atomistic modeling of macromolecular crowding rationalizes the experimental observations, and provides qualitative and quantitative insight into the influences of the crowded cellular environment on protein-protein specific interactions. Our work also has implications for evolution, regarding how nonspecific binding can be either minimized or exploited for gaining new functions.
Ciliary IFT88 safeguards coordinated epiphyseal vascularisation, resorption and ossification from disruptive physiological mechanical forces
Authors: Coveney C. R. , Samvelyan H. J. , Miotla-Zarebska J. , Carnegie J. , Chang E. , Corrin C. J. , Coveney T. , Stott B. , Parisi I. , Duarte C. , Vincent T. L. , Staines K. A. , Wann A.K.T.
Published: August 2021

In the musculoskeletal system, appropriate cell and tissue responses to mechanical force delineate morphogenesis and ensure lifelong health. Despite this, how mechanical cues are integrated into biological programmes remains unclear. Primary cilia are microtubule-based organelles that tune a range of cell activities, including signalling cascades activated or modulated, by extracellular biophysical cues. Here, we demonstrate that the inducible, cartilage-specific deletion of Intraflagellar transport protein 88 (IFT88), which reduces ciliation in the adolescent mouse growth plate (GP), uncouples chondrocyte differentiation from cartilage resorption and mineralisation in a mechano-dependent manner. Targeting IFT88, inhibits hypertrophic chondrocyte VEGF expression, vascular recruitment, osteoclastic activity and the replacement of cartilage with bone. These effects are largely restricted to peripheral tibial regions beneath the load-bearing compartments of the knee. Increases in physiological loading, in control mice, also impairs ossification in the peripheral GP, mimicking the effects of IFT88 deletion. Strikingly, limb immobilisation rescues disrupted VEGF and restores epiphyseal dynamics inIft88cKO mice. These data indicate, that during this pivotal phase in adolescent skeletal maturation that defines the cessation of growth, ciliary IFT88 protects the coordinated ossification of the growth plate from an otherwise disruptive heterogeneity of physiological mechanical forces.
Comparative cytogenomics reveals genome reshuffling and centromere repositioning in the legume tribe Phaseoleae
Authors: Montenegro Claudio , do Vale Martins Lívia , de Oliveira Bustamante Fernanda , Brasileiro-Vidal Ana Christina , Pedrosa-Harand Andrea
Published: August 2021

The tribe Phaseoleae (Leguminosae; Papilionoideae) includes several legume crops with assembled genomes. Comparative genomic studies indicate the preservation of large genomic blocks among legumes, however, the chromosome dynamics during Phaseoleae evolution has not been investigated yet. We conducted a comparative genomic analysis to define an informative genomic block (GB) system and to reconstruct the ancestral Phaseoleae karyotype (APK). We defined the GBs based on the orthologous genes betweenPhaseolus vulgarisandVigna unguiculatagenomes. We searched for these GBs in different genome species belonging to the Phaseolinae (P. lunatus) and Glycininae subtribes (Amphicarpaea edgeworthiiandSpatholobus suberectus), and in theMedicago truncalutaoutgroup. To support ourin silicoanalysis, we used oligo-FISH probes ofP. vulgarischromosomes 2 and 3 to paint the orthologous chromosomes of two non-sequenced Phaseolinae species (Macroptilium atropurpureumandLablab purpureus). We inferred the APK withn= 11 and 19 GBs (A to S). We hypothesized five chromosome fusions that reduced the ancestral legume karyotype withn= 16 ton= 11 in APK. Furthermore, we identified the main rearrangements within Phaseolinae and observed an extensive centromere repositioning resulting from evolutionary new centromeres (ENC) in thePhaseoluslineage. Additionally, we demonstrated that theA. edgeworthiigenome is more reshuffled than the dysploidS. suberectusgenome, in which we could reconstruct the main events that lead the chromosome number reduction. The development of the GB system and the proposed APK provide useful approaches for future comparative genomic analyses of legume species.
Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography
Authors: Atherton Joseph , Stouffer Melissa , Francis Fiona , Moores Carolyn A.
Published: August 2021

Neurons navigate long distances and extend axons to form the complex circuitry of the mature brain. This depends on the coordinated response and continuous remodelling of the microtubule and F-actin networks in the axonal growth cone. Growth cone architecture remains poorly understood at nanoscales. We therefore investigated mouse hippocampal neuron growth cones using cryo-electron tomography to directly visualise their three-dimensional subcellular architecture with molecular detail. Our data show the hexagonal arrays of actin bundles that form filopodia penetrate the growth cone interior and terminate in the transition zone. We directly observe the modulation of these and other growth cone actin bundles by alteration of individual F-actin helical structures. Blunt-ended microtubules predominate in the growth cone, frequently contain lumenal particles and carry lattice defects. Investigation of the effect of absence of doublecortin, a neurodevelopmental cytoskeleton regulator, on growth cone cytoskeleton shows no major anomalies in overall growth cone organisation or in F-actin subpopulations. However, our data suggest that microtubules sustain more structural defects, highlighting the importance of microtubule integrity during growth cone migration.

Summary statement

Cryo-electron tomographic reconstruction of neuronal growth cone subdomains reveals distinctive F-actin and microtubule cytoskeleton architectures and modulation at molecular detail.
Good and bad lettuce leaf microbes? Unravelling the genetic architecture of the microbiome to inform plant breeding for enhanced food safety and reduced food waste
Authors: Damerum A , Arnold EC , Bernard V , Smith HK , Taylor G
Published: August 2021

Lettuce is a high value food crop, consumed raw around the world. Engineering of the leaf microbiome could provide significant benefits for enhanced crop yield and stress resistance and help to reduce food waste caused by microbial spoilage. Lettuce leaves also act as a vector for human pathogens, implicated in several high-profile food-borne disease outbreaks. Since host genotype helps determine microbiome composition, we hypothesize that leaf surface traits can be defined that associate with ‘good’ bacterial microbiomes providing benefits to the crop and that ‘bad’ microbiomes, where spoilage organisms and human pathogens are abundant, can also be associated to underlying leaf genetics, providing key targets for future crop breeding. Using a Recombinant Inbred Line (RIL) population, we show that cultivated and wild parental genotypes differ with reduced bacterial diversity, larger leaves and fewer, larger stomata, smaller epidermal cells and more hydrophilic leaf surfaces found in the cultivated compared to wild lettuce. Functional analysis of the associated microbiome revealed increased abundance of genes associated with disease virulence for the cultivated lettuce genotype, suggesting domestication has had broad impacts on leaf and associated bacterial microbiome traits. We defined the core lettuce bacterial microbiome from 171 RILs, comprised of 45 taxa in the phyla Proteobacteria, Actinobacteria, Firmicutes, Chloroflexi and Deinococcus-Thermus. Leaf surface characteristics important in influencing bacterial diversity and abundance were identified as stomatal size (length and width), epidermal cell area and number and leaf surface hydrophobicity of the abaxial leaf surface. Quantitative trait loci (QTL) for leaf surface traits, frequently mapped alongside those for the extended phenotype of bacterial taxa abundance, including for human pathogensCampylobacterspp.,Escherichia-Shigellaspp.,Clostridiumspp. (LG 4, 5 and 6) and spoilage bacteria,Pseudomonasspp. (LG 1, 3, 4, 6 and 9). Candidate genes underlying these QTL were enriched in GO terms for cell wall assembly and modification, defence response, hormone-mediated signalling and biosynthesis and anatomical structure development. This work provides the first insight into the genetic architecture of host surface traits in a leafy crop alongside the mapped genetic architecture of bacterial communities and has identified areas of the lettuce genome as important targets for future microbiome engineering.
Shotgun proteomic profiling of dormant, ‘non-culturable’Mycobacterium tuberculosis
Authors: Nikitushkin V. , Shleeva M. , Loginov D. , Dycka F. , Sterba J. , Kaprelyants A.
Published: August 2021

Dormant cells ofMycobacterium tuberculosis, in addition to low metabolic activity and a high level of drug resistance, are characterized by ‘non-culturability’ – a specific reversible state of the inability of the cells to grow on solid media. The biochemical characterization of this physiological state of the pathogen is only superficial, pending clarification of the metabolic processes that may exist in such cells. In this study, applying LC-MS proteomic profiling, we report the analysis of proteins accumulated in dormant, ‘non-culturable’M. tuberculosiscells in anin vitromodel of self-acidification of mycobacteria in the post-stationary phase, simulating thein vivopersistence conditions. This approach revealed the accumulation of a significant number of proteins (1379) in cells after 4 months of storage in dormancy; among them, 468 proteins were significantly different from those in the actively growing cells and bore a positive fold change (FC). Differential analysis revealed the proteins of the pH-dependent regulatory system phoP and allowed the reconstruction of the reactions of central carbon/glycerol metabolism, as well as revealing the salvaged pathways of mycothiol and UMP biosynthesis, establishing the cohort of survival enzymes of dormancy. The annotated pathways mirror the adaptation of the mycobacterial metabolic machinery to life within lipid-rich macrophages, especially the involvement of the methyl citrate and glyoxylate pathways. Thus, the currentin vitromodel ofM. tuberculosisself-acidification reflects the biochemical adaptation of these bacteria to persistencein vivo. Comparative analysis with published proteins with antigenic properties makes it possible to distinguish immunoreactive proteins (40) among the proteins bearing a positive FC in dormancy, which may include specific antigens of latent tuberculosis. Additionally, the biotransformatory enzymes (oxidoreductases and hydrolases) capable of prodrug activation and stored up in the dormant state were annotated. These findings may potentially lead to the discovery of immunodiagnostic tests for early latent tuberculosis and trigger the discovery of efficient drugs/prodrugs with potency against non-replicating, dormant populations of mycobacteria.
In vitro activity of bedaquiline and imipenem against actively growing, nutrient-starved, and intracellular Mycobacterium abscessus
Authors: Martins Olumide , Lee Jin , Kaushik Amit , Ammerman Nicole C. , Dooley Kelly E. , Nuermberger Eric L.
Published: August 2021

Mycobacterium abscessus lung disease is difficult to treat due to intrinsic drug resistance and the persistence of drug-tolerant bacteria. Currently, the standard of care is a multi-drug regimen with at least 3 active drugs, preferably including a β-lactam (imipenem or cefoxitin). These regimens are lengthy, toxic, and have limited efficacy. The search for more efficacious regimens led us to evaluate bedaquiline, a diarylquinoline licensed for treatment of multidrug-resistant tuberculosis. We performed in vitro time-kill experiments to evaluate the activity of bedaquiline alone and in combination with the first-line drug imipenem against M. abscessus under various conditions. Against actively growing bacteria, bedaquiline was largely bacteriostatic and antagonized the bactericidal activity of imipenem. Contrarily, against nutrient-starved persisters, bedaquiline was bactericidal, while imipenem was not, and bedaquiline drove the activity of the combination. In an intracellular infection model, bedaquiline and imipenem had additive bactericidal effects. Correlations between ATP levels and the bactericidal activity of imipenem and its antagonism by bedaquiline were observed. Interestingly, the presence of Tween 80 in the media affected the activity of both drugs, enhancing the activity of imipenem and reducing that of bedaquiline. Overall, these results show that bedaquiline and imipenem interact differently depending on culture conditions. Previously reported antagonistic effects of bedaquiline on imipenem were limited to conditions with actively multiplying bacteria and/or the presence of Tween 80, whereas the combination was additive or indifferent against nutrient-starved and intracellular M. abscessus, where promising bactericidal activity of the combination suggests it may have a role in future treatment regimens.
Machine learning detects SARS-CoV-2 and variants rapidly on DNA aptamer metasurfaces
Authors: Torun Hulya , Bilgin Buse , Ilgu Muslum , Yanik Cenk , Batur Numan , Celik Suleyman , Ozturk Meric , Dogan Ozlem , Ergonul Onder , Solaroglu Ihsan , Can Fusun , Onbasli Mehmet Cengiz
Published: August 2021

COVID-19 is detected using reverse transcription polymerase chain reaction (RT-PCR) of nasal swabs. A very sensitive and rapid detection technique using easily-collected fluids like saliva must be developed for safe and precise mass testing. Here, we introduce a metasurface platform for direct sensing of COVID-19 from unprocessed saliva. We computationally screen gold metasurfaces out of a pattern space of 2100 combinations for strongly-enhanced light-virus interaction with machine learning and use it to investigate the presence and concentration of the SARS-CoV-2. We use machine learning to identify the virus from Raman spectra with 95.2% sensitivity and specificity on 36 PCR positive and 33 negative clinical samples and to distinguish wild-type, alpha, and beta variants. Our results could pave the way for effective, safe and quantitative preventive screening and identification of variants.
COVID-19 in Brazilian children and adolescents: findings from 21 hospitals
Authors: Liu Priscila Menezes Ferri , de Melo Maria do Carmo Barros , Diniz Lilian Martins Oliveira , Dias Cristiane dos Santos , de Moura Costa André Soares , Farace Bárbara Lopes , da Silva Carla Thais Candida Alves , Anschau Fernando , Aranha Fernando Graça , Nascimento Guilherme Fagundes , Duani Helena , Costa Jamille Hemétrio Salles Martins , Ruschel Karen Brasil , Nogueira Matheus Carvalho Alves , de Oliveira Neimy Ramos , Pozza Roberta , Francisco Saionara Cristina , Lage Thalita Martins , Ramires Yuri Carlotto , Pereira Daniella Nunes , Reis Zilma Silveira Nogueira , Chatkin José Miguel , Marcolino Milena Soriano
Published: August 2021

Introduction

Children and adolescents with Covid-19 have been shown lower mortality less intense symptoms when compared to adults, but studies in Brazil have been based on the compulsory notifying system only.

Objective

To analyse clinical, laboratory, radiological characteristics and outcomes of hospitalized patients under 20 years with Covid-19.

Methods

Cases series of hospitalized patients with confirmed Covid-19 under 20 years, obtained from a cohort study in 37 hospitals from five states of Brazil.

Results

From 36 patients, 20 (55.5%) were adolescentes, 20 (55.5%) were male, 18 (50.0%) had comorbidities, 2 were pregnant and in 7 (19.4%), initial symptoms occurred during hospitalization for other causes, of whom 3 were possibly infected in the hospital. Fever (61.1%), dyspnea (33.3%) and neurological symptoms (33.0%) were the most common complaints. C-reactive protein was higher than 50mg/L in 16.7% and D-dimer was above the reference limit in 22.2%. Chest X-rays were performed in 20 (55.5%) patients, 9 had abnormalities, and chest tomography in 5. Hospital length of stay ranged from 1-40 days (median 5 [interquartile range 3-10]), 16 (44.4%) needed intensive therapy, 6 (16.7%) required mechanical ventilation and one patient (2.8%) died.

Conclusion

In case series patients under 20 years from hospitals from 5 states of Brazil, comorbidities were frequent, and most common symptoms were fever, dyspnea and neurological symptoms. Forty-four percent required intensive therapy, showing that the disease was not as mild as it was expected, and one patient died.
Immunogenicity of BNT162b2 vaccine Against the Alpha and Delta Variants in Immunocompromised Patients
Authors: Hadjadj Jérome , Planas Delphine , Ouedrani Amani , Buffier Solene , Delage Laure , Nguyen Yann , Bruel Timothée , Stolzenberg Marie-Claude , Staropoli Isabelle , Ermak Natalia , Macraigne Laure , Morbieu Caroline , Henriquez Soledad , Veyer David , Péré Hélène , Casadevall Marion , Mouthon Luc , Rieux-Laucat Frédéric , Chatenoud Lucienne , Schwartz Olivier , Terrier Benjamin
Published: August 2021

Background

The emergence of strains of SARS-CoV-2 exhibiting increase viral fitness and immune escape potential, such as the Delta variant (B.1.617.2), raises concerns in immunocompromised patients. To what extent Delta evades vaccine-induced immunity in immunocompromised individuals with systemic inflammatory diseases remains unclear.

Methods

We conducted a prospective study in patients with systemic inflammatory diseases (cases) and controls receiving two doses of BNT162b2. Primary end points were anti-spike antibodies levels and cross-neutralization of Alpha and Delta variants after BNT162b2 vaccine. Secondary end points were T-cell responses, breakthrough infections and safety.

Results

Sixty-four cases and 21 controls not previously infected with SARS-CoV-2 were analyzed. Kinetics of anti-spike IgG and IgA after BNT162b2 vaccine showed lower and delayed induction in cases, more pronounced with rituximab. Administration of two doses of BNT162b2 generated a neutralizing response against Alpha and Delta in 100% of controls, while sera from only one of rituximab-treated patients neutralized Alpha (5%) and none Delta. Other therapeutic regimens induced a partial neutralizing activity against Alpha, even lower against Delta. All controls and cases except those treated with methotrexate mounted a SARS-CoV-2 specific T-cell response. Methotrexate abrogated T-cell responses after one dose and dramatically impaired T-cell responses after 2 doses of BNT162b2.

Conclusions

Rituximab and methotrexate differentially impact the immunogenicity of BNT162b2, by impairing B-cell and T-cell responses, respectively. Delta fully escapes the humoral response of individuals treated with rituximab. These findings support efforts to improve BNT162b2 immunogenicity in immunocompromised individuals (Funded by the Fonds IMMUNOV;ClinicalTrials.govnumber,NCT04870411).
The effect of eye protection on SARS-CoV-2 transmission: a systematic review
Authors: Byambasuren Oyungerel , Beller Elaine , Clark Justin , Collignon Peter , Glasziou Paul
Published: August 2021

Background

The effect of eye protection to prevent SARS-CoV-2 infection in the real-world remains uncertain. We aimed to synthesize all available research on the potential impact of eye protection on transmission of SARS-CoV-2.

Methods

We searched PROSPERO, PubMed, Embase, The Cochrane Library for clinical trials and comparative observational studies in CENTRAL, and Europe PMC for pre-prints. We included studies that reported sufficient data to estimate the effect of any form of eye protection including face shields and variants, goggles, and glasses, on subsequent confirmed infection with SARS-CoV-2.

Findings

We screened 898 articles and included 6 reports of 5 observational studies from 4 countries (USA, India, Columbia, and United Kingdom) that tested face shields, googles and wraparound eyewear on 7567 healthcare workers. The three before-and-after and one retrospective cohort studies showed statistically significant and substantial reductions in SARS-CoV-2 infections favouring eye protection with odds ratios ranging from 0.04 to 0.6, corresponding to relative risk reductions of 96% to 40%. These reductions were not explained by changes in the community rates. However, the one case-control study reported odds ratio favouring no eye protection (OR 1.7, 95% CI 0.99, 3.0). The high heterogeneity between studies precluded any meaningful meta-analysis. None of the studies adjusted for potential confounders such as other protective behaviours, thus increasing the risk of bias, and decreasing the certainty of evidence to very low.

Interpretation

Current studies suggest that eye protection may play a role in prevention of SARS-CoV-2 infection in healthcare workers. However, robust comparative trials are needed to clearly determine effectiveness of eye protections and wearability issues in both healthcare and general populations.

Funding

There was no funding source for this study. All authors had full access to all data and agreed to final manuscript to be submitted for publication.
A novel method for robust estimation of ants’ walking speed and curvature on convoluted trajectories derived from their gait pattern
Authors: Choi Jibeom , Kim Woojoo , Song Woncheol , Lee Sang-im , Jablonski Piotr Grzegorz
Published: August 2021

Accurate measurements of travel distance and speed are crucial for the analysis of animal movements. Measuring the movements of ants entails measuring the change in locations registered at time intervals. This process involves dilemma of setting the proper time window: a short time window is vulnerable to spatial errors in observation, while a long time window leads to underestimation of the travel distance. To overcome these difficulties, we propose a novel algorithm that successively interpolates two consecutive points of ant’s trajectory for a given time window by embracing the alternating tripod gait of ants. We demonstrate that this algorithm is more reliable compared to the conventional method of travel distance estimation based on the sum of the consecutive straight-line displacements (SLD). After obtaining speed estimates for a range of sampling time windows, we applied a fitting method that can estimate the actual speed without prior knowledge of spatial error distribution. We compared results from several methods of speed and curvature extracted from the empirical data of ant trajectories. We encourage empirical scientists to utilize the proposed methods rather than the conventional SLD method of speed estimation as this process is a more reliable and subjective selection of the sampling time window can be avoided.
Modeling the C. elegans Germline Stem Cell Genetic Network using Automated Reasoning
Authors: Amar Ani , Hubbard E. Jane Albert , Kugler Hillel
Published: August 2021

Computational methods and tools are a powerful complementary approach to experimental work for studying regulatory interactions in living cells and systems. We demonstrate the use of formal reasoning methods as applied to the Caenorhabditis elegans germ line, which is an accessible model system for stem cell research. The dynamics of the underlying genetic networks and their potential regulatory interactions are key for understanding mechanisms that control cellular decision-making between stem cells and differentiation. We model the “stem cell fate” versus entry into the “meiotic development” pathway decision circuit in the young adult germ line based on an extensive study of published experimental data and known/hypothesized genetic interactions. We apply a formal reasoning framework to derive predictive networks for control of differentiation. Using this approach we simultaneously specify many possible scenarios and experiments together with potential genetic interactions, and synthesize genetic networks consistent with all encoded experimental observations. In silico analysis of knock-down and overexpression experiments within our model recapitulate published phenotypes of mutant animals and can be applied to make predictions on cellular decision-making. This work lays a foundation for developing realistic whole tissue models of the C. elegans germ line where each cell in the model will execute a synthesized genetic network.
Cell type determination for cardiac differentiation occurs soon after seeding of human induced pluripotent stem cells
Authors: Jiang Connie L. , Goyal Yogesh , Jain Naveen , Wang Qiaohong , Truitt Rachel E. , Coté Allison J. , Emert Benjamin , Mellis Ian A. , Kiani Karun , Yang Wenli , Jain Rajan , Raj Arjun
Published: August 2021

Cardiac directed differentiation of human induced pluripotent stem cells consistently produces a mixed population of cardiomyocytes and non-cardiac cell types even when using very well-characterized protocols. We wondered whether differentiated cell types might result from intrinsic differences in hiPS cells prior to the onset of differentiation. By associating individual differentiated cells that share a common hiPS cell precursor, we were able to test whether expression variability in differentiated cells was pre-determined from the hiPS cell state. Although within a single experiment, differentiated cells that share an hiPS cell progenitor were more transcriptionally similar to each other than to other cells in the differentiated population, when the same hiPS cells were differentiated in parallel, we did not observe high transcriptional similarity across differentiations. Additionally, we found that substantial cell death occurred during differentiation in a manner that suggested that all cells were equally likely to survive or die, suggesting that there was no intrinsic selection bias for cells descended from particular hiPS cell progenitors. These results led us to wonder about how cells grow out spatially during the directed differentiation process. Labeling cells by their expression of a few canonical cell type marker genes, we showed that cells expressing the same marker tended to occur in patches observable by visual inspection, suggesting that cell type determination across multiple cell types, once initiated, is maintained in a cell-autonomous manner for multiple divisions. Altogether, our results show that while there is substantial heterogeneity in the initial hiPS cell population, that heterogeneity is not responsible for heterogeneous outcomes, and that the window during which cell type specification occurs is likely to begin shortly after the seeding of hiPS cells for differentiation.
Spatial representability of neuronal activity
Authors: Akhtiamov D. , Cohn A. G. , Dabaghian Y.
Published: August 2021

A common approach to interpreting spiking activity is based on identifying the firing fields—regions in physical or configuration spaces that elicit responses of neurons. Common examples include hippocampal place cells that fire at preferred locations in the navigated environment, head direction cells that fire at preferred orientations of the animal’s head, view cells that respond to preferred spots in the visual field, etc. In all these cases, firing fields were discovered empirically, by trial and error. We argue that the existence and a number of properties of the firing fields can be established theoretically, through topological analyses of the neuronal spiking activity.
Empirical Transmit Field Bias Correction of T1w/T2w Myelin Maps
Authors: Glasser Matthew F. , Coalson Timothy S. , Harms Michael P. , Xu Junqian , Baum Graham L. , Autio Joonas A. , Auerbach Edward J. , Greve Douglas N. , Yacoub Essa , Van Essen David C. , Bock Nicholas A. , Hayashi Takuya
Published: August 2021

T1-weighted divided by T2-weighted (T1w/T2w) myelin maps were initially developed for neuroanatomical analyses such as identifying cortical areas, but they are increasingly used in statistical comparisons across individuals and groups with other variables of interest. Existing T1w/T2w myelin maps contain radiofrequency transmit field (B1+) biases, which may be correlated with these variables of interest, leading to potentially spurious results. Here we propose two empirical methods for correcting these transmit field biases using either explicit measures of the transmit field or alternatively a ‘pseudo-transmit’ approach that is highly correlated with the transmit field at 3T. We find that the resulting corrected T1w/T2w myelin maps are both better neuroanatomical measures (e.g., for use in cross-species comparisons), and more appropriate for statistical comparisons of relative T1w/T2w differences across individuals and groups (e.g., sex, age, or body-mass-index) within a consistently acquired study at 3T. We recommend that investigators who use the T1w/T2w approach for mapping cortical myelin use these B1+ transmit field corrected myelin maps going forward.
KnowMore: an automated knowledge discovery tool for the FAIR SPARC datasets
Authors: Quey Ryan , Schiefer Matthew A. , Kiran Anmol , Patel Bhavesh
Published: August 2021

This manuscript provides the methods and outcomes of KnowMore, the Grand Prize winning automated knowledge discovery tool developed by our team during the 2021 NIH SPARC FAIR Data Codeathon. The National Institutes of Health Stimulating Peripheral Activity to Relieve Conditions (NIH SPARC) program generates rich datasets from neuromodulation researches, curated according to the Findable, Accessible, Interoperable, and Reusable (FAIR) SPARC data standards. These datasets are publicly available through the SPARC Data Portal at sparc.science. Currently, the process of simultaneously comparing and analyzing multiple SPARC datasets is tedious because it requires investigating each dataset of interest individually and downloading all of them to conduct cross-analyses. It is crucial to enhance this process to enable rapid discoveries across SPARC datasets. To fill this need, we created KnowMore, a tool integrated into the SPARC Portal that only requires the user to select their datasets of interest to launch an automated discovery process. KnowMore uses several SPARC resources (Pennsieve, o2S2PARC, SciCrunch, protocols.io, Biolucida), data science methods, and machine learning algorithms in the back end to generate various visualizations in the front end intended to help the user identify potential similarities, differences, and relations across the datasets. These visualizations can lead to a new discovery, new hypothesis, or simply guide the user to the next logical step in their discovery process. The outcome of this project is a SPARC portal-ready code architecture that helps researchers to use SPARC datasets more efficiently and fully leverages their FAIR characteristics. The tool has been built and documented such that more data analysis methods and visualization items could be easily added. The potential for automated discoveries from SPARC datasets is huge given the unique SPARC data ecosystem promoting FAIR data practices, and KnowMore has only demonstrated a small highlight of what could be achieved to speed up discoveries from SPARC datasets.
SIRT5 is the desuccinylase of LDHA as novel cancer metastatic stimulator in aggressive prostate cancer
Authors: Kwon Oh Kwang , Bang In Hyuk , Choi So Young , Jeon Ju Mi , Na Ann-Yae , Gao Yan , Cho Sam Seok , Ki Sung Hwan , Choe Youngshik , Lee Jun Nyung , Ha Yun-Sok , Bae Eun Ju , Kwon Tae Gyun , Park Byung-Hyun , Lee Sangkyu
Published: August 2021

Prostate cancer (PCa) is the most commonly diagnosed genital cancer in men worldwide. Among patients who developed advanced PCa, 80% suffered from bone metastasis, with a sharp drop in the survival rate. Despite great efforts, the details of the mechanisms underlying castration-resistant PCa (CRPC) remains unclear. SIRT5, an NAD+-dependent desuccinylase, is hypothesized to be a key regulator of various cancers. However, compared to other SIRTs, the role of SIRT5 in cancer has not been extensively studied. Here, we showed significantly decreased SIRT5 levels in aggressive PCa cells relative to the PCa stages. The correlation between the decrease in the SIRT5 level and the patient’s survival rate was also confirmed. Using quantitative global succinylome analysis, we characterized a significant increase of lysine 118 succinylation (K118su) of lactate dehydrogenase A (LDHA), which plays a role in increasing LDH activity. As a substrate of SIRT5, LDHA-K118su significantly increased the migration and invasion of PCa cells and LDH activity in PCa patients. This study investigated the reduction of SIRT5 and LDHA-K118su as a novel mechanism involved in PCa progression. It can also be proposed as a new target that can prevent castration-resistant PCa progression, which is key to PCa treatment.
αS oligomers generated from polyunsaturated fatty acid and dopamine metabolite differentially interact with Aβ to enhance neurotoxicity
Authors: Dhakal Shailendra , Saha Jhinuk , Wyant Courtney E. , Rangachari Vijayaraghavan
Published: August 2021

It is increasingly becoming clear that neurodegenerative diseases are not as discrete as originally thought to be but rather display significant overlap in histopathological and clinical presentations. For example, nearly half of the patients with Alzheimer disease (AD) and synucleinopathies such as Parkinson disease (PD) show symptoms and pathological features of one another. Yet, the molecular events and features that underlie such comorbidities in neurodegenerative diseases remain poorly understood. Here, inspired to uncover the molecular underpinnings of the overlap between AD and PD, we investigated the interactions between amyloid-β (Aβ) and α-synuclein (αS), aggregates of which form the major components of amyloid plaques and Lewy bodies, respectively. Specifically, we focused on αS oligomers generated from the dopamine metabolite called dihydroxyphenylacetaldehyde (DOPAL), and a polyunsaturated fatty acid docosahexaenoic acid (DHA). Both αS oligomers showed structural and conformational differences confirmed by their disparity in size, secondary structure, susceptibility to proteinase K digestion and cytotoxicity. More importantly, the two oligomers differentially modulated Aβ aggregation. While both oligomers inhibited Aβ aggregation to varying extents, they induced structurally different Aβ assemblies. Furthermore, Aβ seeded with DHA-derived αS oligomers showed greater toxicity than DOPAL-derived αS oligomers in SH-SY5Y neuroblastoma cells. These results provide insights into the interactions between two amyloid proteins with empirically distinctive biophysical and cellular manifestations, enunciating a basis for potentially ubiquitous cross-amyloid interactions across many neurodegenerative diseases.
Analyzing the Perceptual Attributes of Electro-tactile Stimuli as Function of Various Signal Properties
Authors: Rahimi Mehdi , Jiang Fang , Shen Yantao
Published: August 2021

This study is designed to determine the proper electrical signals that induce various perceptual qualities. These perceptions are chosen from a wide range of feelings, comfort and even surface qualities such as smoothness or flatness. The goal is to derive the relationship between the electrical signal properties (i.e. voltage, frequency and duty cycle) and the perceived qualities which are understood by human observers and reveal any pattens in their reports. A total of 144 measurements are collected from 8 participants. The results are analyzed using numerous statistical methods. In the end, the governing factors are identified and a signal with specific properties is is determined for each of the perception qualities. A great number of plots are included in this study to facilitate the process of choosing the appropriate signal for each factor.
Economic policy uncertainty and stock prices in BRIC countries: evidence from asymmetric frequency domain causality approach
Authors: Aydin Mucahit , Pata Ugur Korkut , Inal Veysel
Published: August 2021

Purpose

The aim of this study is to investigate the relationship between economic policy uncertainty (EPU) and stock prices during the period from March 2003 to March 2021.

Design/methodology/approach

The study uses asymmetric and symmetric frequency domain causality tests and focuses on BRIC countries, namely, Brazil, Russia, India and China.

Findings

The findings of the symmetric causality test confirm unidirectional permanent causality from EPU to stock prices for Brazil and India and bidirectional causality for China. However, according to the asymmetric causality test, the findings for China show that there is no causality between the variables. The results for Brazil and India indicate that there is unidirectional permanent causality from positive components of EPU to positive components of stock prices. Moreover, for Brazil, there is unidirectional temporary causality from the negative components of EPU to the negative components of stock prices. For India, there is temporary causality in the opposite direction.

Originality/value

The reactions of financial markets to positive and negative shocks differ. In this context, to the best of the authors’ knowledge, this study is the first attempt to examine the causal relationships between stock prices and uncertainty using an asymmetric frequency domain approach. Thus, the study enables the analysis of the effects of positive and negative shocks in the stock market separately.
Do generous trade credit terms provide a competitive edge?
Authors: Osiichuk Dmytro , Wnuczak Paweł
Published: August 2021

Purpose

The authors document a persistent negative link between contemporaneous trade credit provision and subsequent firm-level operating performance.

Design/methodology/approach

Textual analysis of firms' profile descriptions is used to study the role of market segmentation and product differentiation in intermediating the nexus between trade credit and corporate performance. The paper relies on dynamic panel regression modeling to investigate the postulated empirical relationships. This approach allows to address endogeneity issues and to test a number of different model specifications.

Findings

Despite fueling short-term sales growth, the more generous trade credit terms are found to be associated with lower post hoc margins and declining overall business profitability. The market share is not affected by firms' proclivity to provide trade credit suggesting that the latter may not be effectively used as a long-term growth enhancement strategy. Firms' similarity to their competitors is found to play a salient role in altering the magnitude of the discovered negative relationship.

Originality/value

The authors find that the intensity of intra-industry competition measured by firms' similarity to their competitors magnifies the discovered negative trade credit-performance nexus. Therefore, generous trade credit may play a more important role in solidifying client–supplier relationships on the more segmented markets with a higher degree of product differentiation.