Forecasting Pediatric Trauma Volumes: Insights From a Retrospective Study Using Machine Learning.

Introduction: Rising pediatric firearm-related fatalities in the United States strain Trauma Centers. Predicting trauma volume could improve resource management and preparedness, particularly if daily forecasts are achievable. The aim of the study is to evaluate various machine learning models' accuracy on monthly, weekly, and daily data.

C/EBPδ Mediates Immunity to Renal Autoinflammatory Disorders in a Stage-specific Manner.

Kidney disease represents a major medical and economic burden for which improved treatments are urgently needed. Emerging data have implicated Th17 cells and IL-17 signaling in the underlying pathogenesis of autoantibody-induced glomerulonephritis (AGN). However, the downstream transduction pathways mediated by IL-17 in autoimmunity are not well defined.

The RNA binding protein Arid5a drives IL-17-dependent autoantibody-induced glomerulonephritis.

Autoantibody-mediated glomerulonephritis (AGN) arises from dysregulated renal inflammation, with urgent need for improved treatments. IL-17 is implicated in AGN and drives pathology in a kidney-intrinsic manner via renal tubular epithelial cells (RTECs). Nonetheless, downstream signaling mechanisms provoking kidney pathology are poorly understood.

Combinatorial actions of IL-22 and IL-17 drive optimal immunity to oral candidiasis through SPRRs.

Oropharyngeal candidiasis (OPC) is the most common human fungal infection, arising typically from T cell immune impairments. IL-17 and IL-22 contribute individually to OPC responses, but here we demonstrate that the combined actions of both cytokines are essential for resistance to OPC. Mice lacking IL-17RA and IL-22RA1 exhibited high fungal loads in esophagus- and intestinal tract, severe weight loss, and symptoms of colitis.

Conditions for the spread of CRISPR-Cas immune systems into bacterial populations.

Bacteria contain a wide variety of innate and adaptive immune systems which provide protection to the host against invading genetic material, including bacteriophages (phages). It is becoming increasingly clear that bacterial immune systems are frequently lost and gained through horizontal gene transfer. However, how and when new immune systems can become established in a bacterial population have remained largely unstudied.

Multi-layered genome defences in bacteria.

Bacteria have evolved a variety of defence mechanisms to protect against mobile genetic elements, including restriction-modification systems and CRISPR-Cas. In recent years, dozens of previously unknown defence systems (DSs) have been discovered. Notably, diverse DSs often coexist within the same genome, and some co-occur at frequencies significantly higher than would be expected by chance, implying potential synergistic interactions.

Pseudomonas aeruginosa's adaptive trajectory: diverse origins, convergent paths.

Does genetic background contribute to populations following the same or divergent adaptive trajectories? A recent study by Filipow et al. evolved multiple genetically distinct Pseudomonas aeruginosa strains to an artificial cystic fibrosis lung sputum media. The strains adapted at different rates but converged on similar phenotypes despite their initial diversity.

Mutation bias and adaptation in bacteria.

Genetic mutation, which provides the raw material for evolutionary adaptation, is largely a stochastic force. However, there is ample evidence showing that mutations can also exhibit strong biases, with some mutation types and certain genomic positions mutating more often than others. It is becoming increasingly clear that mutational bias can play a role in determining adaptive outcomes in bacteria in both the laboratory and the clinic.

Evolutionary innovation through transcription factor rewiring in microbes is shaped by levels of transcription factor activity, expression, and existing connectivity.

The survival of a population during environmental shifts depends on whether the rate of phenotypic adaptation keeps up with the rate of changing conditions. A common way to achieve this is via change to gene regulatory network (GRN) connections-known as rewiring-that facilitate novel interactions and innovation of transcription factors. To understand the success of rapidly adapting organisms, we therefore need to determine the rules that create and constrain opportunities for GRN rewiring.

Mutational hotspots lead to robust but suboptimal adaptive outcomes in certain environments.

The observed mutational spectrum of adaptive outcomes can be constrained by many factors. For example, mutational biases can narrow the observed spectrum by increasing the rate of mutation at isolated sites in the genome. In contrast, complex environments can shift the observed spectrum by defining fitness consequences of mutational routes.

IκBζ is an essential mediator of immunity to oropharyngeal candidiasis.

Fungal infections are a global threat; yet, there are no licensed vaccines to any fungal pathogens. Th17 cells mediate immunity to Candida albicans, particularly oropharyngeal candidiasis (OPC), but essential downstream mechanisms remain unclear. In the murine model of OPC, IκBζ (Nfkbiz, a non-canonical NF-κB transcription factor) was upregulated in an interleukin (IL)-17-dependent manner and was essential to prevent candidiasis.

Transcription factor expression levels and environmental signals constrain transcription factor innovation.

Evolutionary innovation of transcription factors frequently drives phenotypic diversification and adaptation to environmental change. Transcription factors can gain or lose connections to target genes, resulting in novel regulatory responses and phenotypes. However the frequency of functional adaptation varies between different regulators, even when they are closely related.

SARS-CoV-2 ORF8 Mediates Signals in Macrophages and Monocytes through MyD88 Independently of the IL-17 Receptor.

SARS-CoV-2 has caused an estimated 7 million deaths worldwide to date. A secreted SARS-CoV-2 accessory protein, known as open reading frame 8 (ORF8), elicits inflammatory pulmonary cytokine responses and is associated with disease severity in COVID-19 patients. Recent reports proposed that ORF8 mediates downstream signals in macrophages and monocytes through the IL-17 receptor complex (IL-17RA, IL-17RC).

Transient mutation bias increases the predictability of evolution on an empirical genotype-phenotype landscape.

Predicting how a population will likely navigate a genotype-phenotype landscape requires consideration of selection in combination with mutation bias, which can skew the likelihood of following a particular trajectory. Strong and persistent directional selection can drive populations to ascend toward a peak. However, with a greater number of peaks and more routes to reach them, adaptation inevitably becomes less predictable.

A gut-oral microbiome-driven axis controls oropharyngeal candidiasis through retinoic acid.

A side effect of antibiotics is outgrowth of the opportunistic fungus Candida albicans in the oropharynx (oropharyngeal candidiasis, OPC). IL-17 signaling is vital for immunity to OPC, but how the microbiome impacts antifungal immunity is not well understood. Mice in standard specific pathogen-free (SPF) conditions are resistant to OPC, whereas we show that germ-free (GF) or antibiotic-treated mice are susceptible.

Arid5a Mediates an IL-17-Dependent Pathway That Drives Autoimmunity but Not Antifungal Host Defense.

IL-17 contributes to the pathogenesis of certain autoimmune diseases, but conversely is essential for host defense against fungi. Ab-based biologic drugs that neutralize IL-17 are effective in autoimmunity but can be accompanied by adverse side effects. is a commensal fungus that is the primary causative agent of oropharyngeal and disseminated candidiasis.

Environmental and societal factors associated with COVID-19-related death in people with rheumatic disease: an observational study.

Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally.

Methods: In this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021.

Causes of Death Among Individuals With Systemic Lupus Erythematosus by Race and Ethnicity: A Population-Based Study.

Objective: Non-White populations are at higher risk of developing systemic lupus erythematosus (SLE) and have more severe outcomes, including mortality. The present study was undertaken to examine how specific causes of death vary by race and ethnicity, including Asian and Hispanic individuals.

Methods: The California Lupus Surveillance Project included SLE cases identified among residents of San Francisco County, CA during January 1, 2007 to December 31, 2009.

Natural selection on crosstalk between gene regulatory networks facilitates bacterial adaptation to novel environments.

At the level of the gene, mutation is the raw material for natural selection. However, at the level of the gene regulatory network (GRN), variation is revealed to selection via promiscuous regulator activity ('crosstalk'), which creates opportunities for genetic innovation that can facilitate adaptation. Many genetic and environmental features can contribute to increasing potential for crosstalk by facilitating non-cognate interactions between regulatory elements.

A mutational hotspot that determines highly repeatable evolution can be built and broken by silent genetic changes.

Mutational hotspots can determine evolutionary outcomes and make evolution repeatable. Hotspots are products of multiple evolutionary forces including mutation rate heterogeneity, but this variable is often hard to identify. In this work, we reveal that a near-deterministic genetic hotspot can be built and broken by a handful of silent mutations.

The mA reader IMP2 directs autoimmune inflammation through an IL-17- and TNFα-dependent C/EBP transcription factor axis.

Excessive cytokine activity underlies many autoimmune conditions, particularly through the interleukin-17 (IL-17) and tumor necrosis factor-α (TNFα) signaling axis. Both cytokines activate nuclear factor κB, but appropriate induction of downstream effector genes requires coordinated activation of other transcription factors, notably, CCAAT/enhancer binding proteins (C/EBPs). Here, we demonstrate the unexpected involvement of a posttranscriptional "epitranscriptomic" mRNA modification [N6-methyladenosine (mA)] in regulating C/EBPβ and C/EBPδ in response to IL-17A, as well as IL-17F and TNFα.

The racial/ethnic and sociocultural aspects of the pandemic in rheumatology.

The disproportionate impact of coronavirus-2019 (COVID-19) on communities of color is gaining global attention. Current research demonstrates that historically marginalized populations are experiencing disproportionate levels of SARS-Cov-2 infection and adverse clinical outcomes. However, research examining whether COVID-19 outcomes vary by race and ethnicity within the rheumatic disease population is limited.

Association of Race and Ethnicity With COVID-19 Outcomes in Rheumatic Disease: Data From the COVID-19 Global Rheumatology Alliance Physician Registry.

Objective: Racial/ethnic minorities experience more severe outcomes of coronavirus disease 2019 (COVID-19) in the general US population. This study was undertaken to examine the association between race/ethnicity and COVID-19 hospitalization, ventilation status, and mortality in people with rheumatic disease.

Methods: US patients with rheumatic disease and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance physician registry between March 24, 2020 and August 26, 2020 were included.