A significance score for protein-protein interaction models through random docking.

Comparing accuracies of structural protein-protein interaction (PPI) models for different complexes on an absolute scale is a challenge, requiring normalization of scores across structures of different sizes and shapes. To help address this challenge, we have developed a statistical significance metric for docking models, called random-docking (RD) p-value. This score evaluates a PPI model based on how likely a random docking process is to produce a model of better or equal accuracy. The binding partners are randomly docked against each other a large number of times, and the probability of sampling a model of equal or greater accuracy from this reference distribution is the RD p-value. Using a subset of top predicted models from CAPRI (Critical Assessment of PRediction of Interactions) rounds over 2017-2020, we find that the ease of achieving a given root mean squared deviation or DOCKQ score varies considerably by target; achieving the same relative metric can be thousands of times easier for one complex compared to another. In contrast, RD p-values inherently normalize scores for models of different complexes, making them globally comparable. Furthermore, one can calculate RD p-values after generating a reference distribution that accounts for prior information about the interface geometry, such as residues involved in binding, by giving the random-docking process access the same information. Thus, one can decouple improvements in prediction accuracy that arise solely from basic modeling constraints from those due to the rest of the method. We provide efficient code for computing RD p-values at https://github.com/Grigoryanlab/RDP.

Long COVID Among Wisconsin Workers in the Workers' Compensation System: Associations With Sociodemographics, Vaccination, and Predominant Variant Period From March 1, 2020 to July 31, 2022.

OBJECTIVE: This analysis aimed to determine the likelihood of developing long COVID among Wisconsin workers while adjusting for sociodemographics, COVID-19 vaccination, industry, and occupation. METHODS: This retrospective analysis determined the odds ratios of developing long COVID among Wisconsin workers who were compensated for COVID-19 lost time during March 1, 2020 to July 31, 2022. RESULTS: A total of 234 workers (11.7%) were determined to have long COVID. Factors associated with long COVID were age ≥40 years, non-White race, infection occurrence during the initial and Omicron variant dominant periods, and the absence of COVID-19 vaccination. Workers in manufacturing and public administration were more likely to develop long COVID compared with those in health care and social assistance. CONCLUSIONS: Long COVID disproportionately affects some worker groups. This calls for more worker protection and preventative care to mitigate its impact.

Measuring Work-related Risk of Coronavirus Disease 2019 (COVID-19): Comparison of COVID-19 Incidence by Occupation and Industry-Wisconsin, September 2020 to May 2021.

BACKGROUND: Work-related exposures play an important role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, yet few studies have compared SARS-CoV-2 expsoure risk across occupations and industries. METHODS: During September 2020 to May 2021, the Wisconsin Department of Health Services collected occupation and industry data as part of routine coronavirus disease 2019 (COVID-19) case investigations. Adults aged 18-64 years with confirmed or probable COVID-19 in Wisconsin were assigned standardized occupation and industry codes. Cumulative incidence rates were weighted for non-response and calculated using full-time equivalent (FTE) workforce denominators from the 2020 American Community Survey. RESULTS: An estimated 11.6% of workers (347 013 of 2.98 million) in Wisconsin, ages 18-64 years, had COVID-19 from September 2020 to May 2021. The highest incidence by occupation (per 100 FTE) occurred among personal care and services workers (22.1), healthcare practitioners and support staff (20.7), and protective services workers (20.7). High-risk sub-groups included nursing assistants and personal care aides (28.8), childcare workers (25.8), food and beverage service workers (25.3), personal appearance workers (24.4), and law enforcement workers (24.1). By industry, incidence was highest in healthcare (18.6); the highest risk sub-sectors were nursing care facilities (30.5) and warehousing (28.5). CONCLUSIONS: This analysis represents one of the most complete examinations to date of COVID-19 incidence by occupation and industry. Our approach demonstrates the value of standardized occupational data collection by public health and may be a model for improved occupational surveillance elsewhere. Workers at higher risk of SARS-CoV-2 exposure may benefit from targeted workplace COVID-19 vaccination and mitigation efforts.

Work and Life in the Balance: COVID-19 Mortality by Usual Occupation and Industry in Wisconsin.

INTRODUCTION: Work is central to the discourse surrounding the pandemic. Going to work during the COVID-19 pandemic put individuals at risk for both disease and death. This study assesses COVID-19 mortality by industry and occupation for working-age adults in Wisconsin and applies a health equity lens to understand COVID-19, demographics, work, and mortality in the state. METHODS: We used vital records data to evaluate COVID-19 mortality in Wisconsin. We assessed the demographics of working-age decedents using chi-square tests and logistic regression. We also classified decedents by usual occupation with Standard Occupational Classification (2018) and North American Industry Classification System (2017) codes to calculate mortality rates. We then calculated proportional mortality ratios to evaluate if mortality rates from COVID-19 in industry or occupation groups were significantly higher than the overall (ie, average) mortality rate from COVID-19 among all working-age Wisconsin adults. RESULTS: Both Asian/Pacific Islander and Hispanic individuals in Wisconsin had elevated likelihoods of dying from COVID-19. Lower levels of education also were associated with a higher likelihood of COVID-19-attributable death. Additionally, we found several occupations and industries that had elevated mortality rates from COVID-19. Proportional mortality ratios showed higher than expected mortality for several occupations including Protective Service; Office and Administrative Support; Farming, Fishing, and Forestry; and Installation, Maintenance, and Repair. Moreover, several industries had elevated proportional mortality ratios, including Agriculture, Forestry, Fishing, and Hunting; Finance and Insurance; Transportation and Warehousing; and Public Administration. DISCUSSION: The lessons of the pandemic are important for public health and worker safety. Understanding who bears disparate risks allows us to prepare, communicate, and mitigate risk.

Incidence of COVID-19 and Worker's Compensation Utilization Among Food Manufacturing in Wisconsin, October 1, 2020 - December 31, 2021.

BACKGROUND: The food manufacturing industry is a critical economic sector and has been a high-risk industry for COVID-19. This analysis aimed to describe COVID-19 cumulative case incidence rates among Wisconsin food manufacturing workers and their worker's compensation utilization. METHODS: This was a descriptive analysis of COVID-19 cases among food manufacturing industry workers in Wisconsin from October 1, 2020, through December 31, 2021. RESULTS: Occupations with the highest cumulative case incidence rate (per 1000 workers) were Packers and Packagers, Hand (275; 95% CI, 252-300), Packaging and Filling Machine Operators and Tenders (266; 95% CI, 254-277), and Laborers and Freight, Stock and Material Movers, Hand (261; 95% CI, 247-276). Two worker's compensation claims were paid to food manufacturing workers. DISCUSSION: Wisconsin food manufacturing workers were disproportionately affected by COVID-19, with a high cumulative case incidence rate exceeding that of the manufacturing industry overall, statewide non-institutionalized working-age adults, and the ambulatory health care industry. There was also a disproportionately low use of worker's compensation benefits in Wisconsin compared to the high COVID-19 disease incidence. Improved worker protections for occupational infectious diseases with high risk of transmission are needed as well as improvements to the worker's compensation system.

School District Prevention Policies and Risk of COVID-19 Among In-Person K-12 Educators, Wisconsin, 2021.

Objectives. To assess the rate of COVID-19 among in-person K-12 educators and the rate's association with various COVID-19 prevention policies in school districts. Methods. We linked actively working, in-person K-12 educators in Wisconsin to COVID-19 cases with onset from September 2 to November 24, 2021. A mixed-effects Cox proportional hazards model, adjusted for pertinent person- and community-level confounders, compared the hazard rate of COVID-19 among educators working in districts with and without specific COVID-19 prevention policies. Results. In-person educators working in school districts that required masking for students and staff experienced 19% lower hazards of COVID-19 than did those in districts without any masking policy (hazard ratio = 0.81; 95% confidence interval = 0.72, 0.92). Reduced COVID-19 hazards were consistent and remained statistically significant when educators were stratified by elementary, middle, and high school environments. Conclusions. In Wisconsin's K-12 school districts, during the fall 2021 academic semester, a policy that required both students and staff to mask was associated with significantly reduced risk of COVID-19 among in-person educators across all grade levels. (Am J Public Health. 2022;112(12):1791-1799. https://doi.org/10.2105/AJPH.2022.307095).

Lost time: COVID-19 indemnity claim reporting and results in the Wisconsin workers' compensation system from March 12 to December 31, 2020.

BACKGROUND: The COVID-19 pandemic introduced a new compensable infectious disease to workplaces. METHODS: This was a descriptive analysis of Wisconsin COVID workers' compensation (WC) claims between March 12 and December 31, 2020. The impact of the presumption law (March 12 to June 10, 2020) was also evaluated. RESULTS: Less than 1% of working-age residents with COVID-19 filed a claim. COVID-19 WC claim rates (per 100,000 FTE) were notably low for frontline industry sectors such as Retail Trade (n = 115), Manufacturing (n = 88), and Wholesale Trade (n = 31). Healthcare workers (764 claims per 100,000 FTE) comprised 73.2% of COVID-19 claims. Most claims (52.8%) were denied and the proportion of denied claims increased significantly after the presumption period for both first responders and other occupations. CONCLUSION: The presumption law made benefits accessible primarily to first responders. Further changes to WC systems are needed to offset the individual and collective costs of infectious diseases.

Intersectionality in pandemic youth suicide attempt trends.

INTRODUCTION: The COVID-19 pandemic has resulted in increased distress at a societal level, with youth and young people bearing a disproportionate burden. A series of recent Morbidity and Mortality Weekly Reports has highlighted emergency department (ED) visit rates for suicide attempts among youth ages 12-25 during the COVID-19 pandemic. This study expands those analyses by adding race and ethnicity to the examination of suspected suicide attempts among youth. METHODS: This study uses National Syndromic Surveillance Program (NSSP) data for Wisconsin from hospitals that consistently reported ED visits between the study period of January 1, 2019 and September 30, 2021. Suspected suicide attempt visits were identified using the CDC-developed suicide attempt query. RESULTS: During the study period, there were 8915 ED visits for suicide attempts by children and youth ages 12-25 in Wisconsin's NSSP system. We confirm gendered patterns of ED visit rates for suspected suicide attempts among youth that were first noted in studies using a non-representative national dataset. Large and significant 2019 vs. 2021 increases were noted for Black females ages 12-17 (79% increase) and White non-Hispanic females ages 12-17 (58%), but no significant change for Hispanic females ages 12-17. Black females ages 18-25 had high and relatively stable rates throughout this period.

Human iPSC Glial Mouse Chimeras Reveal Glial Contributions to Schizophrenia.

In this study, we investigated whether intrinsic glial dysfunction contributes to the pathogenesis of schizophrenia (SCZ). Our approach was to establish humanized glial chimeric mice using glial progenitor cells (GPCs) produced from induced pluripotent stem cells derived from patients with childhood-onset SCZ. After neonatal implantation into myelin-deficient shiverer mice, SCZ GPCs showed premature migration into the cortex, leading to reduced white matter expansion and hypomyelination relative to controls. The SCZ glial chimeras also showed delayed astrocytic differentiation and abnormal astrocytic morphologies. When established in myelin wild-type hosts, SCZ glial mice showed reduced prepulse inhibition and abnormal behavior, including excessive anxiety, antisocial traits, and disturbed sleep. RNA-seq of cultured SCZ human glial progenitor cells (hGPCs) revealed disrupted glial differentiation-associated and synaptic gene expression, indicating that glial pathology was cell autonomous. Our data therefore suggest a causal role for impaired glial maturation in the development of schizophrenia and provide a humanized model for its in vivo assessment.

MAGenTA: a Galaxy implemented tool for complete Tn-Seq analysis and data visualization.

MOTIVATION: Transposon insertion sequencing (Tn-Seq) is a microbial systems-level tool, that can determine on a genome-wide scale and in high-throughput, whether a gene, or a specific genomic region, is important for fitness under a specific experimental condition. RESULTS: Here, we present MAGenTA, a suite of analysis tools which accurately calculate the growth rate for each disrupted gene in the genome to enable the discovery of: (i) new leads for gene function, (ii) non-coding RNAs; (iii) genes, pathways and ncRNAs that are involved in tolerating drugs or induce disease; (iv) higher order genome organization; and (v) host-factors that affect bacterial host susceptibility. MAGenTA is a complete Tn-Seq analysis pipeline making sensitive genome-wide fitness (i.e. growth rate) analysis available for most transposons and Tn-Seq associated approaches (e.g. TraDis, HiTS, IN-Seq) and includes fitness (growth rate) calculations, sliding window analysis, bottleneck calculations and corrections, statistics to compare experiments and strains and genome-wide fitness visualization. AVAILABILITY AND IMPLEMENTATION: MAGenTA is available at the Galaxy public ToolShed repository and all source code can be found and are freely available at https://vanopijnenlab.github.io/MAGenTA/ . CONTACT: vanopijn@bc.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Muscle-specificity of age-related changes in markers of autophagy and sphingolipid metabolism.

Our previous findings indicate that the gastrocnemius muscle of aging rats exhibits impairments of muscle quality (force/unit muscle tissue) and autophagy and increased sarcoplasmic reticulum stress. The purpose of this study was to examine age-related changes in soleus muscle contractility and in markers of autophagy in the soleus and gastrocnemius muscles. We assessed in situ muscle force and size in the soleus muscle of adult (7-8 months) and aged (24-26 months) male, F344/BN rats. We used immunoblotting to compare abundance of markers of autophagy, sarcoplasmic reticulum (SR) stress and sphingolipid metabolism in the soleus and medial gastrocnemius (MG) muscles of these animals. Relative to adults, aged rats maintained soleus muscle quality and increased muscle size, resulting in increased tetanic force production. Immunoblotting revealed a general pattern of an age-related reduction of basal autophagy, despite increases in indicators of SR stress and upstream autophagic pathway activation in the MG. The MG also exhibited changes in markers of sphingolipid metabolism suggestive of increased muscle ceramide. Minimal age-related changes were observed in the soleus. The soleus maintains muscle mass and quality with age, and exhibits fewer age-related changes in markers of stress and autophagy than the MG. Based on these data, we suggest that maintenance of autophagy may preserve muscle quality by preventing excessive SR stress.