bluuebunny/crossref_metadata_2025 huggingface dataset:
PathCNN: interpretable convolutional neural networks for survival prediction and pathway analysis applied to glioblastoma
Authors: Oh Jung Hun , Choi Wookjin , Ko Euiseong , Kang Mingon , Tannenbaum Allen , Deasy Joseph O
Published: April 2021

Motivation

Convolutional neural networks (CNNs) have achieved great success in the areas of image processing and computer vision, handling grid-structured inputs and efficiently capturing local dependencies through multiple levels of abstraction. However, a lack of interpretability remains a key barrier to the adoption of deep neural networks, particularly in predictive modeling of disease outcomes. Moreover, because biological array data are generally represented in a non-grid structured format, CNNs cannot be applied directly.

Results

To address these issues, we propose a novel method, called PathCNN, that constructs an interpretable CNN model on integrated multi-omics data using a newly defined pathway image. PathCNN showed promising predictive performance in differentiating between long-term survival (LTS) and non-LTS when applied to glioblastoma multiforme (GBM). The adoption of a visualization tool coupled with statistical analysis enabled the identification of plausible pathways associated with survival in GBM. In summary, PathCNN demonstrates that CNNs can be effectively applied to multi-omics data in an interpretable manner, resulting in promising predictive power while identifying key biological correlates of disease.

Availability and implementation

The source code is freely available at: https://github.com/mskspi/PathCNN.
Bacteriophage classification for assembled contigs using graph convolutional network
Authors: Shang Jiayu , Jiang Jingzhe , Sun Yanni
Published: April 2021

Motivation

Bacteriophages (aka phages), which mainly infect bacteria, play key roles in the biology of microbes. As the most abundant biological entities on the planet, the number of discovered phages is only the tip of the iceberg. Recently, many new phages have been revealed using high-throughput sequencing, particularly metagenomic sequencing. Compared to the fast accumulation of phage-like sequences, there is a serious lag in taxonomic classification of phages. High diversity, abundance and limited known phages pose great challenges for taxonomic analysis. In particular, alignment-based tools have difficulty in classifying fast accumulating contigs assembled from metagenomic data.

Results

In this work, we present a novel semi-supervised learning model, named PhaGCN, to conduct taxonomic classification for phage contigs. In this learning model, we construct a knowledge graph by combining the DNA sequence features learned by convolutional neural network and protein sequence similarity gained from gene-sharing network. Then we apply graph convolutional network to utilize both the labeled and unlabeled samples in training to enhance the learning ability. We tested PhaGCN on both simulated and real sequencing data. The results clearly show that our method competes favorably against available phage classification tools.

Availability and implementation

The source code of PhaGCN is available via: https://github.com/KennthShang/PhaGCN.
Classification below the species level: when are infraspecific groups biologically meaningful?
Authors: Reydon Thomas A C , Kunz Werner
Published: April 2021

Infraspecific taxa (subspecies, races and varieties) are often seen as real entities in nature and recognized as biologically meaningful groups. But because infraspecific taxa by definition are subdivisions of species, their status depends entirely on the status of ‘their’ species. This makes the status of infraspecific taxa crucially dependent on the way species are considered and thus on the various species concepts that have been advanced as answers to the ‘species problem’. Accordingly, there is a profound lack of clarity regarding the following questions. What are infraspecific taxa? What is their biological meaning? Are they real entities or merely instrumental units? When should an infraspecific group be ranked and named as an infraspecific taxon? In this paper, we aim to contribute to greater clarity about these issues by examining which types of infraspecific groups are biologically meaningful in light of the main results from the species debate.
Defining indocyanine green fluorescence to assess anastomotic perfusion during gastrointestinal surgery: systematic review
Authors: Slooter M D , Mansvelders M S E , Bloemen P R , Gisbertz S S , Bemelman W A , Tanis P J , Hompes R , van Berge Henegouwen M I , de Bruin D M
Published: April 2021

Background

The aim of this systematic review was to identify all methods to quantify intraoperative fluorescence angiography (FA) of the gastrointestinal anastomosis, and to find potential thresholds to predict patient outcomes, including anastomotic leakage and necrosis.

Methods

This systematic review adhered to the PRISMA guidelines. A PubMed and Embase literature search was performed. Articles were included when FA with indocyanine green was performed to assess gastrointestinal perfusion in human or animals, and the fluorescence signal was analysed using quantitative parameters. A parameter was defined as quantitative when a diagnostic numeral threshold for patient outcomes could potentially be produced.

Results

Some 1317 articles were identified, of which 23 were included. Fourteen studies were done in patients and nine in animals. Eight studies applied FA during upper and 15 during lower gastrointestinal surgery. The quantitative parameters were divided into four categories: time to fluorescence (20 studies); contrast-to-background ratio (3); pixel intensity (2); and numeric classification score (2). The first category was subdivided into manually assessed time (7 studies) and software-derived fluorescence–time curves (13). Cut-off values were derived for manually assessed time (speed in gastric conduit wall) and derivatives of the fluorescence–time curves (Fmax, T1/2, TR and slope) to predict patient outcomes.

Conclusion

Time to fluorescence seems the most promising category for quantitation of FA. Future research might focus on fluorescence–time curves, as many different parameters can be derived and the fluorescence intensity can be bypassed. However, consensus on study set-up, calibration of fluorescence imaging systems, and validation of software programs is mandatory to allow future data comparison.
GC–MS and Surface Characteristics of Polyvinyl Siloxane–An In Vitro Analysis
Authors: Kasim Mohamed K , Fathima Banu R , Anand Kumar V , Sundaram Lakshmi , Thyagarajan S P
Published: April 2021

Objective

To assess the surface characteristics, composition and release of components of Polyvinyl siloxane (PVS) impression material and explore the use of the material other than for impressions.

Methods

Forty samples of 0.5-mm thickness and 8-mm diameter PVS discs, with few perforations, were prepared and divided into four groups. Group 1 in methanol was analyzed by GC–MS immediately and on 1st, 7th and 14th day. Group 2 and 3 placed in 10 mL of human saliva and in artificial nasal fluid, respectively, were analyzed by GC–MS at 24 hours. Group 4 was subjected to surface characteristics analysis by placing five PVS discs each in 1 mL of human saliva and 1 mL of artificial nasal fluid, respectively.

Results

On Day 1, Dodecanoic acid, methyl ester, Cyclononasiloxane, octadecamethyl, Cyclodecasiloxane and eicosamethyl (four peaks) were observed in Group 1. At 24 hours, Group 2 had additional compounds of 2-Decene,7-methyl-(Z)-, 2-Undecene,8-methyl-(Z)- and Lauryl acetate. Group 3 showed release of 32 compounds, but their retention time was less. Surface characteristics on Day 14 revealed no noticeable changes.

Conclusions

The study revealed that there was a lack of any adverse component release from PVS for a period of 2 weeks based on GC–MS analysis.
Breaking botnets: A quantitative analysis of individual, technical, isolationist, and multilateral approaches to cybersecurity
Authors: Haner Justin K , Knake Robert K
Published: April 2021

Malicious networks of botnets continue to grow in strength as millions of new users and devices connect to the internet each day, many becoming unsuspectingly complicit in cyber-attacks or unwitting accomplices to cybercrimes. Both states and nonstate actors use botnets to surreptitiously control the combined computing power of infected devices to engage in espionage, hacking, and to carry out distributed denial of service attacks to disable internet-connected targets from businesses and banks to power grids and electronic voting systems. Although cybersecurity professionals have established a variety of best practices to fight botnets, many important questions remain concerning why levels of botnet infections differ sharply from country to country, as relatively little empirical testing has been done to establish which policies and approaches to cybersecurity are actually the most effective. Using newly available time-series data on botnets, this article outlines and tests the conventionally held beliefs and cybersecurity strategies at every level—individual, technical, isolationist, and multilateral. This study finds that wealthier countries are more vulnerable than less wealthy countries; that technical solutions, including patching software, preventing spoofing, and securing servers, consistently outperform attempts to educate citizens about cybersecurity; and that countries which favor digital isolation and restrictions on internet freedom are not actually better protected than those who embrace digital freedom and multilateral approaches to cybersecurity. This latter finding is of particular importance as China’s attempts to fundamentally reshape the internet via the “Digital Silk Road” component of the Belt and Road Initiative will actually end up making both China and the world less secure. Due to the interconnected nature of threats in cyberspace, states should instead embrace multilateral, technical solutions to better govern this global common and increase cybersecurity around the world.
Safety assessment of condensed phosphate intake from fishery and processed marine food products in Korea with respect to gender, age, and region
Authors: Kim Hyung Soo , Jang Dae Yong , Koo Ye Ji , Pack Eun Chul , Lee Seung Ha , Choi Dal Woong
Published: April 2021

Condensed phosphates are used as food additives, especially in marine products and meat, to improve food quality. The import and consumption of fishery and processed marine food products in Republic of Korea have reportedly increased by ~5 per cent annually. However, processed marine food products are often intentionally adulterated with excessive amounts of condensed phosphates to increase their weight. Excessive intake of condensed phosphates via consuming processed marine food products can lead to various adverse effects on human health due to anionic imbalance. Herein, we conducted a safety assessment of condensed phosphates in 14 types of fishery and processed marine food products in Korea for the first time. Subgroup analysis of various factors including gender, age, and region was also performed, and the risk level of exposure for each group was estimated. Safety assessments by age and gender indicated that infants were at the highest risk. In the regional safety assessment, Chungnam, the most inland region, showed the lowest risk. For both the general and the high-intake groups (95th percentile) in all classifications, the risk was lower (<20 per cent) than the international standard, and the phosphorus content of the 14 types of processed marine products in Korea was confirmed to be safe for human consumption.
Exposure to Brands Makes Preferential Decisions Easier
Authors: Rahinel Ryan , Otto Ashley S , Grossman Daniel M , Clarkson Joshua J
Published: April 2021

The most consequential consideration of brands arises during preferential decision-making. This article proposes that as a consequence of the repeated pairing of brands and preferential decisions, exposure to brands initiates a cognitive state of readiness for preferential decisions (which we term decision readiness) that subsequently makes preferential decisions easier. Using both real and fictitious brands across a variety of choice contexts, seven experiments demonstrate that consumers find preferential decision-making easier when it occurs in the presence (vs. absence) of brands. Consistent with the details of our framework, this effect: (i) is explained by the activation of decision readiness, (ii) leads to outcomes such as increased outcome satisfaction and decreased decision delegation, and (iii) is attenuated when exposure is to only one brand. Collectively, these findings demonstrate the importance of exposure to brands for decision-making which, in turn, offers novel insight into existing literatures on brand exposure, decision difficulty, and brand roles.
Splenic abscess after laparoscopic sleeve gastrectomy. A rare complication—case report and literature review
Authors: Batayyah Esam , Yaseen Waed , Alshareef Faris
Published: April 2021

Laparoscopic sleeve gastrectomy is currently a stand-alone bariatric procedure with a low complication profile. A rare complication of leak following sleeve gastrectomy was reported in this study. Its rareness and nonspecific clinical presentation could make the diagnosis difficult and could be easily confused with leak and subdiaphragmatic abscess. A 22-year-old Saudi female with body mass index 41 underwent laparoscopic sleeve gastrectomy in 2017, presented 18 months later to emergency department complaining of fever and abdominal pain for 3 months prior to presentation. Computed tomography of abdomen revealed a large splenic abscess, upper gastrointestinal studies were unremarkable. Patient was taken for laparoscopic exploration with finding of splenic abscess and gastric fistula, splenectomy and clipping of fistula was performed. The management of splenic abscess remains controversial. Splenectomy and antibiotics have generally been the definitive treatment particularly with large multilobulated collection. Familiarity with the rare complications as splenic abscess will allow for a prompt diagnosis and treatment.
A rare case of a migrating fishbone lodged in the larynx for 6 months in a patient with delayed presentation due to COVID-19 pandemic
Authors: Alreefi Mohamed , Althawadi Noora , Patel Ankit , Dwivedi Raghav
Published: April 2021

A foreign body sensation following fishbone ingestion is a common presentation to the Accident and Emergency Department. Simple removal is achieved with acute presentations and accessible locations. The risk of complications increases with delay in seeking medical attention. We report a case of a migratory fishbone lodged in the larynx for 6 months in a patient with delayed presentation due to COVID-19 pandemic
Stab injury to the spine without neurological involvement: a report of a rare case
Authors: Castillo Amaya Carlos , Prieto Meré Jose Antonio , Cobar Bustamante Andres , Herrera Ovalle Rudolf Mauricio , Alonzo Francisco
Published: April 2021

The annual incidence of traumatic spinal cord injury worldwide is 35 patients per million; this incidence is likely to be much higher in Latin America, where stab injuries are a common incidence. Stab injuries to the spine represent a small percentage of these cases; these are rare injuries; its management may differ compared with other penetrating injuries; these injuries are frequently complicated with neurological damage; the most common clinical manifestation is Brown–Sequard syndrome, and the most common segment involved is the thoracic region; stab injuries to the lumbar spine are rarely found in the literature. The management of patients without neurological involvement is controversial due to the risk of neurologic deterioration intraoperatively. However, failure to adequately intervene increases the risk of permanent neurological deficit, worsening functional outcomes, cerebral fluid leakage and infections. A short review of the literature and a case report are presented.
Integrating transcriptome, co-expression and QTL-seq analysis reveals that primary root growth in maize is regulated via flavonoid biosynthesis and auxin signal transduction
Authors: Wang Yunyun , Sun Hui , Wang Houmiao , Yang Xiaoyi , Xu Yang , Yang Zefeng , Xu Chenwu , Li Pengcheng
Published: April 2021

The primary root is critical for early seedling growth and survival. To understand the molecular mechanisms governing primary root development, we performed a dynamic transcriptome analysis of two maize (Zea mays) inbred lines with contrasting primary root length at nine time points over a 12-day period. A total of 18 702 genes were differentially expressed between two lines or different time points. Gene enrichment, phytohormone content determination, and metabolomics analysis showed that auxin biosynthesis and signal transduction, as well as the phenylpropanoid and flavonoid biosynthesis pathways, were associated with root development. Co-expression network analysis revealed that eight modules were associated with lines/stages, as well as primary or lateral root length. In root-related modules, flavonoid metabolism accompanied by auxin biosynthesis and signal transduction constituted a complex gene regulatory network during primary root development. Two candidate genes (rootless concerning crown and seminal roots, rtcs and Zm00001d012781) involved in auxin signaling and flavonoid biosynthesis were identified by co-expression network analysis, QTL-seq and functional annotation. These results increase our understanding of the regulatory network controlling the development of primary and lateral root length, and provide a valuable genetic resource for improvement of root performance in maize.
Homoploid F1 hybrids and segmental allotetraploids of japonica and indica rice subspecies show similar and enhanced tolerance to nitrogen deficiency than parental lines
Authors: Sun Yue , Wu Ying , Wang Yangzhi , Wang Shengnan , Wang Xiaofei , Li Guo , Zhang Xue , Liang Zidong , Li Jiahao , Gong Lei , Wendel Jonathan F , Wang Deli , Liu Bao
Published: April 2021

It remains unclear whether the merger of two divergent genomes by hybridization at the homoploid level or coupled with whole-genome duplication (WGD; allopolyploidy) can result in plants having better tolerance to stress conditions. In this study, we compared phenotypic performance and gene expression in the two diploid subspecies of rice (Oryza sativa subsp. japonica and indica), their reciprocal F1 hybrids, and in segmental allotetraploids under normal and nitrogen (N)-deficient conditions. We found that F1 hybrids and tetraploids showed higher and similar levels of tolerance to N deficiency than either parent. In parallel, total expression levels of 18 relevant functional genes were less perturbed by N deficiency in the F1 hybrids and tetraploids than in the parents. This was consistent with stable intrinsic partitioning of allelic/homoeologous expression defined by parental legacy in the homoploid F1 hybrids/tetraploids between the two conditions. The results suggest that genetic additivity at both the homoploid and allopolyploidy level might lead to similar beneficial phenotypic responses to nitrogen stress compared with the parents. The lack of synergistic responses to N limitation concomitant with WGD, relative to that exhibited by F1 hybrids, adds new empirical evidence in support of the emerging hypothesis that hybridization by itself can play a significant role in plant adaptive evolution in times of stress.
Interplay Between Geography and HIV Transmission Clusters in Los Angeles County
Authors: Skaathun Britt , Ragonnet-Cronin Manon , Poortinga Kathleen , Sheng Zhijuan , Hu Yunyin W , Wertheim Joel O
Published: April 2021

Background

Clusters of HIV diagnoses in time and space and clusters of genetically linked cases can both serve as alerts for directing prevention and treatment activities. We assessed the interplay between geography and transmission across the Los Angeles County (LAC) HIV genetic transmission network.

Methods

Deidentified surveillance data reported for 8186 people with HIV residing in LAC from 2010 through 2016 were used to construct a transmission network using HIV-TRACE. We explored geographic assortativity, the tendency for people to link within the same geographic region; concordant time–space pairs, the proportion of genetically linked pairs from the same geographic region and diagnosis year; and Jaccard coefficient, the overlap between geographical and genetic clusters.

Results

Geography was assortative in the genetic transmission network but less so than either race/ethnicity or transmission risk. Only 18% of individuals were diagnosed in the same year and location as a genetically linked partner. Jaccard analysis revealed that cis-men and younger age at diagnosis had more overlap between genetic clusters and geography; the inverse association was observed for trans-women and Blacks/African Americans.

Conclusions

Within an urban setting with endemic HIV, genetic clustering may serve as a better indicator than time–space clustering to understand HIV transmission patterns and guide public health action.
A Scoping Review of Physical Activity in People With Lower-Limb Loss: 10,000 Steps Per Day?
Authors: Wong Christopher K , Rissland Maia S , Madagan Deanna M , Jones Kameron N
Published: April 2021

Objective

After amputation, people with lower-limb loss (PLL) face challenges to regain their previous physical activity level. Assessing the scope of evidence regarding physical activity in PLL can identify sources of evidence and gaps within the literature that can influence amputation-related research, outcome assessment choices, and wellness activities. The purpose of this scoping review was to map the evidence regarding steps per day as a physical activity measure for PLL. Specific aims were to (1) identify research designs, (2) catalog population subgroups, (3) document steps per day measurement methods, and (4) provide descriptive data for steps per day in PLL.

Methods

The MEDLINE, CINAHL, Embase, Web of Science, and AMED databases; and the Journal of Prosthetics and Orthotics archive were searched without language or time limits. Exclusion criteria included no PLL subjects, not peer-reviewed, and no direct step count measure. Inclusion criteria allowed any sample size, nonprosthetic use, and self-reported step count. As a scoping review, only descriptive statistics were compiled, and no methodologic quality assessment was performed.

Results

Twenty-one articles using crossover (8), cohort (4), cross-section (8), and case-study (1) designs were included that reported accelerometer (19) or pedometer (2) data. Studies often mixed amputation etiologies (15/21) and most (13/21) excluded transfemoral amputations. Studies primarily examined people with transtibial amputations (81.2%) and people at independent community walking levels (Medicare functional classifications: K3 = 49.2%, K4 = 36.3%). All 21 studies had fewer than 100 participants, and overall included 515 subjects (343, 66.6% male), mean (SD) age 53.2 (22.1) years. Mean (SD) number of pooled steps per day for PLL was 5087 (2998): 5929 (3047) for transtibial amputations and 3553 (2030) for transfemoral amputations.

Conclusions

Most PLL have low activity levels compared with the 10,000 steps per day generally recommended or 6000 common in people with diabetes. Research with larger samples, defined subgroups, and data along the recovery continuum would enhance knowledge of physical activity level in PLL.

Impact

This scoping review has identified gaps in the research related to steps per day as a measure of physical activity in people with lower-limb loss to guide future research.

Lay Summary

People with lower-limb loss take fewer steps per day than suggested for general health. Increasing steps per day may be a useful goal for this population, and this study is a first step in improving knowledge of physical activity levels in people with lower-limb loss.
Homeostatic response to sleep restriction in adolescents
Authors: Skorucak Jelena , Weber Nathan , Carskadon Mary A , Reynolds Chelsea , Coussens Scott , Achermann Peter , Short Michelle A
Published: April 2021

The high prevalence of chronic sleep restriction in adolescents underscores the importance of understanding how adolescent sleep is regulated under such conditions. One component of sleep regulation is a homeostatic process: if sleep is restricted, then sleep intensity increases. Our knowledge of this process is primarily informed by total sleep deprivation studies and has been incorporated in mathematical models of human sleep regulation. Several animal studies, however, suggest that adaptation occurs in chronic sleep restriction conditions, showing an attenuated or even decreased homeostatic response. We investigated the homeostatic response of adolescents to different sleep opportunities. Thirty-four participants were allocated to one of three groups with 5, 7.5, or 10 h of sleep opportunity per night for five nights. Each group underwent a protocol of nine nights designed to mimic a school week between two weekends: two baseline nights (10 h sleep opportunity), five condition nights (5, 7.5, or 10 h), and two recovery nights (10 h). Measures of sleep homeostasis (slow-wave activity and slow-wave energy) were calculated from frontal and central EEG derivations and compared to predictions derived from simulations of the homeostatic process of the two-process model of sleep regulation. Only minor differences were found between empirical data and model predictions, indicating that sleep homeostasis is preserved under chronic sleep restriction in adolescents. These findings improve our understanding of effects of repetitive short sleep in adolescents.
Retrospective Assessment of Treatments of Hospitalized Covid-19 Patients
Authors: Ravindra Ghooi , Chitra Lele , Madhur Motwani , Santosh Dixit , Venugopalan Premnath , Sundeep Salvi , Shreepad Bhat , Piyush Chaudhari , Pradeep D’Costa , Ashwini Jahagirdar , Abhay Mane , Vikram Padbidri , Chetan Pande , Urvi Shukla
Published: April 2021

Infection with SARS-Cov-2 virus, is associated with significant morbidity and mortality, in addition to the economic burden it has put on the country. While waiting for a vaccine that gives adequate protection, it is necessary to understand the course of the infection and identify drugs that could reduce its impact. The results of this multicenter study involving 1035 hospitalized patients in Pune, identified diabetes, hypertension and low lymphocyte counts as predictors of mortality. There is also an indication that multiple comorbidities add to risk of severe disease and mortality. Data from metformin treated diabetics raises the possibility of considering repurposing of this drug in a larger study. It is also noted that Hydroxychloroquine, dexamethasone, azithromycin and remdesivir were associated with lower overall mortality. Diabetes and hypertension put Covid infected patients at greater risk of death, coexistence of both diseases further augment the risk, and must be aggressively treated.
COVID-19 vaccination acceptance among healthcare workers in Germany
Authors: Holzmann-Littig Christopher , Braunisch Matthias Christoph , Kranke Peter , Popp Maria , Seeber Christian , Fichtner Falk , Littig Bianca , Carbajo-Lozoya Javier , Allwang Christine , Frank Tamara , Meerpohl Joerg Johannes , Haller Bernhard , Schmaderer Christoph
Published: April 2021

Background

Vaccination hesitancy is a serious threat to achieve herd immunity in a global and rapidly changing pandemic situation. Health care workers play a key role in the treatment of patients with Coronavirus disease 2019 (COVID-19) and in promoting vaccination in the general population. The aim of the study was to provide data on COVID-19 vaccination acceptance and barriers among healthcare workers in Germany to support health policymakers choosing specific vaccination campaign strategies.

Methods

An online survey was conducted among health care workers in Germany in February 2021. The survey included 55 items on demographics, previous vaccination behavior, trust in vaccines, physicians, pharma industry, and health politics as well as fear of adverse effects, assumptions on disease consequences, knowledge about vaccines, information seeking behavior and a short COVID-19 vaccine knowledge test.

Results

A total of 4500 surveys could be analyzed. The overall vaccination acceptance was 91.7%. The age group ≤20 years showed the lowest vaccination acceptance of all age groups. Regarding professional groups, residents showed the highest vaccination acceptance. Main factors for vaccination hesitancy were lack of trust in authorities and pharmaceutical companies. Personal and professional environment influenced the attitude towards a vaccination too. Participants with vaccination hesitancy were more likely to obtain information about COVID-19 vaccines via messenger services or online video platforms and underperformed in the knowledge test.

Conclusions

In conclusion, we found a high acceptance rate amongst German health care workers. Furthermore, several factors associated with vaccination hesitancy were identified which could be targeted in vaccination campaigns.
Comparing mental health trajectories of four different types of key workers with non-key workers: A 12-month follow-up observational study of 21,874 adults in England during the COVID-19 pandemic
Authors: Paul Elise , Mak Hei Wan , Fancourt Daisy , Bu Feifei
Published: April 2021

Background

There are concerns that key workers may be at a greater risk for psychological distress than non-key workers during the COVID-19 pandemic. However, little research has included key workers outside of the healthcare sector or has disaggregated key workers into different subgroups.

Aims

To examine longitudinal changes in mental health over 12 months during the COVID-19 pandemic comparing four different groups of key workers with non-key workers.

Method

Longitudinal data were from 21,874 adults living in England (21 March 2020 to 22 February 2021). Latent growth modelling (LGM) was utilised to compare growth trajectories of depressive and anxiety symptoms in non-key workers and four types of key workers: i) health and social care workers, ii) teachers and childcare workers, iii) public service workers, and iv) essential services key workers (e.g., food chain or utility workers).

Results

When accounting for both time-invariant and time-varying covariates, key workers in the essential services category had consistently higher levels of depressive and anxiety symptoms than non-key workers across the whole of the study period. There was little difference in mental health trajectories between health/social care, teachers/childcare and public service worker categories and non-key workers.

Conclusions

Our findings suggest risk for poorer mental health during the COVID-19 pandemic varies within the broad category of key workers generally, and that those working in utility, food chain, and transport roles are especially at risk. Future research should focus on identifying which aspects of working conditions may be contributing to occupational stress in these groups.
Manufacturer Signal-to-Cutoff Threshold Underestimates Cumulative Incidence of SARS-CoV-2 Infection: Evidence from the Los Angeles Firefighters Study
Authors: Toubat Omar , Berg Anders H. , Sobhani Kimia , Mulligan Karen , Hori Acacia M. , Bhattacharya Jay , Sood Neeraj
Published: April 2021

While SARS-CoV-2 serologic testing is used to measure cumulative incidence of COVID-19, appropriate signal-to-cut off (S/Co) thresholds remain unclear. We demonstrate S/Co thresholds based on known negative samples significantly increases seropositivity and more accurately estimates cumulative incidence of disease compared to manufacturer-based thresholds.
Gut microbiota diversity and C-Reactive Protein are predictors of disease severity in COVID-19 patients
Authors: Moreira-Rosário André , Marques Cláudia , Pinheiro Hélder , Araújo João Ricardo , Ribeiro Pedro , Rocha Rita , Mota Inês , Pestana Diogo , Ribeiro Rita , Pereira Ana , de Sousa Maria José , Pereira-Leal José , de Sousa José , Morais Juliana , Teixeira Diana , Rocha Júlio César , Silvestre Marta , Príncipe Nuno , Gatta Nuno , Amado José , Santos Lurdes , Maltez Fernando , Boquinhas Ana , de Sousa Germano , Germano Nuno , Sarmento Gonçalo , Granja Cristina , Póvoa Pedro , Faria Ana , Calhau Conceição
Published: April 2021

Risk factors for COVID-19 disease severity are still poorly understood. Considering the pivotal role of gut microbiota on host immune and inflammatory functions, we investigated the association between changes in gut microbiota composition and the clinical severity of COVID-19. We conducted a multicentre cross-sectional study prospectively enrolling 115 COVID-19 patients categorized according to: 1) WHO Clinical Progression Scale - mild 19 (16.5%), moderate 37 (32.2%) or severe 59 (51.3%); and 2) location of recovery from COVID-19 - ambulatory 14 (household isolation; 12.2%), hospitalized in ward 40 (34.8%) or intensive care unit 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing and data obtained was further related with clinical parameters of COVID-19 patients. Risk factors for COVID-19 severity were identified by univariate and multivariable logistic regression models.

In comparison with mild COVID-19 patients, the gut microbiota of moderate and severe patients has: a) lower Firmicutes/Bacteroidetes ratio, b) higher abundance of Proteobacteria; and c) lower abundance of beneficial butyrate-producing bacteria such asRoseburiaandLachnospiragenera. Multivariable regression analysis showed that Shannon index diversity (odds ratio [OR] 2.85 [95% CI 1.09-7.41]; p=0.032) and C-Reactive Protein (OR 3.45 [95% CI 1.33-8.91]; p=0.011) were risk factors for COVID-19 severe disease (a score of 6 or higher in WHO clinical progression scale).

In conclusion, our results demonstrated that hospitalised moderate and severe COVID-19 patients have microbial signatures of gut dysbiosis and for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker for COVID-19 disease severity.
WRKY33-mediated indole glucosinolate metabolic pathway confers host resistance againstAlternaria brassicicola
Authors: Tao Han , Miao Huiying , Chen Lili , Wang Mengyu , Xia Chuchu , Zeng Wei , Li Yubo , Zhang Shuqun , Li Chuanyou , Wang Qiaomei
Published: April 2021

The tryptophan (Trp)-derived plant secondary metabolites, including camalexin, 4-hydroxy-indole-3-carbonylnitrile (4OH-ICN), and indole glucosinolate (IGS), show broad-spectrum antifungal activity. However, the upstream regulators of these metabolic pathways among different plant species in response to fungus infection are rarely studied. In this study, our results revealed a positive role of WRKY33 in host resistance toAlternaria brassicicolaby directly regulating the transcription of genes involved in the biosynthesis and atypical hydrolysis of IGS both inArabidopsisand Chinese kale. Indole-3-yl-methylglucosinolate (I3G) and 4-methoxyindole-3-yl-methylglucosinolate (4MI3G) are the main components of IGS. WRKY33 induces the expression ofMYB51andCYP83B1which promotes the biosynthesis of I3G, the precursor of 4MI3G. Moreover, it also directly activates the expression ofCYP81F2,IGMT1, andIGMT2to drive side chain modification of I3G to produce 4MI3G, which is in turn hydrolyzed byPEN2.However, Chinese kale showed a more severe symptom thanArabidopsiswhen infected byAlternaria brassicicola. Comparative analyses of the origin and evolution of Trp-metabolism indicate that the loss of camalexin biosynthesis in Brassica crops during evolution might attenuate the resistance of crops toAlternaria brassicicola. As a result, IGS metabolic pathway mediated by WRKY33 becomes essential for Chinese kale to deterAlternaria brassicicola. Our results highlight the differential regulation of Trp-derived camalexin and IGS biosynthetic pathways in plant immunity betweenArabidopsisand Brassica crops.

One-sentence Summary

Pathogen-responsive WRKY33 directly regulates indole glucosinolates biosynthesis and atypical hydrolysis, conferring to host resistance toAlternaria brassicicolainArabidopsisand Brassica crops.
Inactivation of SARS-CoV-2 by β-propiolactone Causes Aggregation of Viral Particles and Loss of Antigenic Potential
Authors: Gupta Divya , Parthasarathy Haripriya , Sah Vishal , Tandel Dixit , Vedagiri Dhiviya , Reddy Shashikala , Harshan Krishnan H
Published: April 2021

Inactivated viral preparations are important resources in vaccine and antisera industry. Of the many vaccines that are being developed against COVID-19, inactivated whole-virus vaccines are also considered effective. β-propiolactone (BPL) is a widely used chemical inactivator of several viruses. Here, we analyze various concentrations of BPL to effectively inactivate SARS-CoV-2 and their effects on the biochemical properties of the virion particles. BPL at 1:2000 (v/v) concentrations effectively inactivated SARS-CoV-2. However, higher BPL concentrations resulted in the loss of both protein content as well as the antigenic integrity of the structural proteins. Higher concentrations also caused substantial aggregation of the virion particles possibly causing undesirable outcomes including a potential immune escape by infectious virions, and a loss in antigenic potential. We also identify that the viral RNA content in the culture supernatants can be a direct indicator of their antigenic content. Our findings may have important implications in the vaccine and antisera industry during COVID-19 pandemic.
A two-level, dynamic fitness landscape of hepatitis C virus revealed by self-organized haplotype maps
Authors: Delgado Soledad , Perales Celia , García-Crespo Carlos , Soria María Eugenia , Gallego Isabel , de Ávila Ana Isabel , Martínez-González Brenda , Vázquez-Sirvent Lucía , López-Galíndez Cecilio , Morán Federico , Domingo Esteban
Published: April 2021

Fitness landscapes reflect the adaptive potential of viruses. There is no information on how fitness peaks evolve when a virus replicates extensively in a controlled cell culture environment. Here we report the construction of Self-Organized Maps (SOMs), based on deep sequencing reads of three amplicons of the NS5A-NS5B-coding region of hepatitis C virus (HCV). A two-dimensional neural network was constructed and organized according to sequence relatedness. The third dimension of the fitness profile was given by the haplotype frequencies at each neuron. Fitness maps were derived for 44 HCV populations that share a common ancestor that was passaged up to 210 times in human hepatoma Huh-7.5 cells. As the virus increased its adaptation to the cells, the number of fitness peaks expanded, and their distribution shifted in sequence space. The landscape consisted of an extended basal platform, and a lower number of protruding higher fitness peaks. The function that relates fitness level and peak abundance corresponds a power law, a relationship observed with other complex natural phenomena. The dense basal platform may serve as spring-board to attain high fitness peaks. The study documents a highly dynamic, double-layer fitness landscape of HCV when evolving in a monotonous cell culture environment. This information may help interpreting HCV fitness landscapes in complex in vivo environments.

IMPORTANCE

The study provides for the first time the fitness landscape of a virus in the course of its adaptation to a cell culture environment, in absence of external selective constraints. The deep sequencing-based self-organized maps document a two-layer fitness distribution with an ample basal platform, and a lower number of protruding, high fitness peaks. This landscape structure offers potential benefits for virus resilience to mutational inputs.
COV-ID: A LAMP sequencing approach for high-throughput co-detection of SARS-CoV-2 and influenza virus in human saliva
Authors: Warneford-Thomson Robert , Shah Parisha P. , Lundgren Patrick , Lerner Jonathan , Abella Benjamin S. , Zaret Kenneth S. , Schug Jonathan , Jain Rajan , Thaiss Christoph A. , Bonasio Roberto
Published: April 2021

The COVID-19 pandemic has created an urgent need for rapid, effective, and low-cost SARS-CoV-2 diagnostic testing. Here, we describe COV-ID, an approach that combines RT-LAMP with deep sequencing to detect SARS-CoV-2 in unprocessed human saliva with high sensitivity (5–10 virions). Based on a multi-dimensional barcoding strategy, COV-ID can be used to test thousands of samples overnight in a single sequencing run with limited labor and laboratory equipment. The sequencing-based readout allows COV-ID to detect multiple amplicons simultaneously, including key controls such as host transcripts and artificial spike-ins, as well as multiple pathogens. Here we demonstrate this flexibility by simultaneous detection of 4 amplicons in contrived saliva samples: SARS-CoV-2, influenza A, humanSTATHERIN, and an artificial SARS spike-in. The approach was validated on clinical saliva samples, where it showed 100% agreement with RT-qPCR. COV-ID can also be performed directly on saliva adsorbed on filter paper, simplifying collection logistics and sample handling.
A trade-off between stress resistance and tolerance underlies the adaptive response to hydrogen peroxide
Authors: Jacquel Basile , Kavčič Bor , Aspert Théo , Matifas Audrey , Kuehn Antoine , Zhuralev Andrei , Byckov Elena , Morgan Bruce , Julou Thomas , Charvin Gilles
Published: April 2021

The physiological adaptation to environmental stress involves complex molecular responses leading to separate cellular fates aimed at maximizing fitness: either cells can maintain proliferation by degrading the effects of the stressor (i.e. resistance), or they focus on ensuring cell survival (i.e. tolerance), even at the expense of proliferation. These strategies are complementary, yet whether they are coordinated to ensure an optimal physiological stress response remains unknown. Here, we used microfluidics and live cell imaging to explore the genetic basis of the interplay between resistance and tolerance during the response to hydrogen peroxide (H2O2) in budding yeast. Our analysis unraveled that the deletion ofzwf1Δ, which is responsible for NADPH synthesis via the PPP pathway, led to a decrease in resistance that was counterbalanced by an unexpected exacerbation of tolerance to H2O2. This trade-off between stress resistance and stress tolerance was further characterized using both genetic and environmental interventions, and we confirmed that it was conserved in bacteria. Our results support a model in which redox signaling triggers the switch to a nutrients-dependent non-proliferative tolerant state via inhibition of protein kinase A when the H2O2homeostatic response is overwhelmed. Our framework could help develop synergistic therapies that target mechanisms driving both resistance and tolerance to prevent drug escape mechanisms and disease relapse.
Diffusion and distal linkages govern interchromosomal dynamics during meiotic prophase
Authors: Newman Trent A. C. , Beltran Bruno , McGehee James M. , Elnatan Daniel , Cahoon Cori K. , Paddy Michael R. , Chu Daniel B. , Spakowitz Andrew J. , Burgess Sean M.
Published: April 2021

The pairing of homologous chromosomes (homologs) in meiosis is essential for distributing the correct numbers of chromosomes into haploid gametes. In budding yeast, pairing depends on the formation of 150-200 Spo11-mediated double-strand breaks (DSBs) that are distributed among 16 homolog pairs, but it is not known if all, or only a subset of these DSBs, contribute to the close juxtaposition of homologs. Having established a system to measure the position of fluorescently tagged chromosomal loci in 3D space over time, we analyzed locus trajectories to determine how frequently, and how long, loci spend colocalized or apart. Continuous imaging revealed highly heterogeneous cell-to-cell behavior of foci, with the majority of cells exhibiting a “mixed” phenotype where foci move into and out of proximity, even at late stages of prophase, suggesting that the axial structures of the synaptonemal complex may be more dynamic than anticipated. The observed plateaus of the mean-squared change in distance (MSCD) between foci informed the development of a biophysical model of two diffusing polymers that captures the loss of centromere linkages as cells enter meiosis, nuclear confinement, and the formation of Spo11-dependent linkages. The predicted number of linkages per chromosome in our theoretical model closely approximates the small number (~2-4) of estimated synapsis-initiation sites, suggesting that excess DSBs have negligible effects on the overall juxtaposition of homologs. These insights into the dynamic in-terchromosomal behavior displayed during homolog pairing demonstrate the power of combining time-resolvedin vivoanalysis with modeling at the granular level.

Significance Statement

Essential for sexual reproduction, meiosis is a specialized cell division required for the production of haploid gametes. Critical to this process is the pairing, recombination, and segregation of homologous chromosomes (homologs). While pairing and recombination are linked, it is not known how many linkages are sufficient to hold homologs in proximity. Here, we reveal that random diffusion and the placement of a small number of linkages are sufficient to establish the apparent “pairing” of homologs. We also show that colocalization between any two loci is more dynamic than anticipated. Our study is the first to provide observations of live interchromosomal dynamics during meiosis and illustrates the power of combining single-cell measurements with theoretical polymer modeling.
Dravet variantSCN1AA1783Vimpairs interneuron firing predominantly by altered channel activation
Authors: Layer N. , Sonnenberg L. , Pardo González E. , Benda J. , Lerche H. , Koch H. , Wuttke TV.
Published: April 2021

Dravet syndrome (DS) is a developmental epileptic encephalopathy mainly caused by functional NaV1.1 haploinsufficiency in interneurons (IN). Recently, a new conditional mouse model expressing the recurrent human p.A1783V missense variant has become available. Here we provide an electrophysiological characterization of this variant in tsA201 cells, revealing both altered voltage-dependence of activation and slow inactivation without reduced sodium peak current density. Simulating IN excitability in a Hodgkin-Huxley one-compartment model suggested surprisingly similar firing deficits forScn1aA1783Vand full haploinsufficiency as caused by heterozygous truncation variants. Impaired NaVA1783Vchannel activation was predicted to have a significantly larger impact on channel function than altered slow inactivation and is therefore proposed as the main mechanism underlying IN dysfunction. The computational model was validated in cortical organotypic slice cultures derived from conditionalScn1aA1783Vmice. Pan-neuronal activation of the p.A1783V variantin vitroconfirmed the predicted IN firing deficit while demonstrating normal excitability of pyramidal neurons. Taken together these data demonstrate that despite maintained physiological peak currents density LOF gating properties may match effects of full haploinsufficiency on neuronal level, thereby causing DS.

Highlights

NaV1.1A1783Valters voltage-dependence of activation and slow inactivation while not affecting fast inactivation.

Depolarizing and hyperpolarizing shifts of activation and slow inactivation curves result in combined channel loss of function (LOF).

Simulations of NaV1.1A1783Vinterneuronal properties indicate reduced action potential firing rates comparable to fullSCN1Ahaploinsufficiency, which is often found in Dravet syndrome.

In silicomodelling identifies impaired channel activation as the predominant mechanism of channel LOF.

Panneuronal induction ofScn1a+/A1783Vin a cortical slice culture model confirms restriction of loss of function and its restriction to interneurons.