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COVID‐19 patients with rheumatic disease have a higher risk of mechanical ventilation than the general population. The present study was undertaken to assess lung involvement using a validated deep learning algorithm that extracts a quantitative measure of radiographic lung disease severity. We performed a comparative cohort study of rheumatic disease patients with COVID‐19 and ≥1 chest radiograph within ±2 weeks of COVID‐19 diagnosis and matched comparators. We used unadjusted and adjusted (for age, Charlson comorbidity index, and interstitial lung disease) quantile regression to compare the maximum pulmonary x‐ray severity (PXS) score at the 10th to 90th percentiles between groups. We evaluated the association of severe PXS score (>9) with mechanical ventilation and death using Cox regression. We identified 70 patients with rheumatic disease and 463 general population comparators. Maximum PXS scores were similar in the rheumatic disease patients and comparators at the 10th to 60th percentiles but significantly higher among rheumatic disease patients at the 70th to 90th percentiles (90th percentile score of 10.2 versus 9.2; adjusted P= 0.03). Rheumatic disease patients were more likely to have a PXS score of >9 (20% versus 11%; P= 0.02), indicating severe pulmonary disease. Rheumatic disease patients with PXS scores >9 versus ≤9 had higher risk of mechanical ventilation (hazard ratio [HR] 24.1 [95% confidence interval (95% CI) 6.7, 86.9]) and death (HR 8.2 [95% CI 0.7, 90.4]). Rheumatic disease patients with COVID‐19 had more severe radiographic lung involvement than comparators. Higher PXS scores were associated with mechanical ventilation and will be important for future studies leveraging big data to assess COVID‐19 outcomes in rheumatic disease patients.

To determine the association between race/ethnicity and COVID‐19 outcomes in individuals with systemic lupus erythematosus (SLE). Individuals with SLE from the US with data entered into the COVID‐19 Global Rheumatology Alliance registry between March 24, 2020 and August 27, 2021 were included. Variables included age, sex, race, and ethnicity (White, Black, Hispanic, other), comorbidities, disease activity, pandemic time period, glucocorticoid dose, antimalarials, and immunosuppressive drug use. The ordinal outcome categories were: not hospitalized, hospitalized with no oxygenation, hospitalized with any ventilation or oxygenation, and death. We constructed ordinal logistic regression models evaluating the relationship between race/ethnicity and COVID‐19 severity, adjusting for possible confounders. We included 523 patients; 473 (90.4%) were female and the mean ± SD age was 46.6 ± 14.0 years. A total of 358 patients (74.6%) were not hospitalized; 40 patients (8.3%) were hospitalized without oxygen, 64 patients (13.3%) were hospitalized with any oxygenation, and 18 (3.8%) died. In a multivariable model, Black (odds ratio [OR] 2.73 [95% confidence interval (95% CI) 1.36–5.53]) and Hispanic (OR 2.76 [95% CI 1.34–5.69]) individuals had higher odds of more severe outcomes than White individuals. Black and Hispanic individuals with SLE experienced more severe COVID‐19 outcomes, which is consistent with findings in the US general population. These results likely reflect socioeconomic and health disparities and suggest that more aggressive efforts are needed to prevent and treat infection in this population.

As the midterm elections approach, false information is running rampant on the social media platform Can You Trust What You See on TikTok? In addition, the service announced this August that it would be launching an election information portal, which will pop up when a user searches for an election-related hashtag and connect them with authoritative election information, such as how to register to vote. [Extracted from the article]

The article offers information on issues concerning gun control laws in the U.S. It provides an overview on gun control in the country from several kinds of restrictions to responsibilities of gun owners and buyer's background. Information about gunfire at an outdoor music festival in Las Vegas and the view from the National Rifle Association of America on the issue is presented.

A 78-year-old man presented with weeks of progressive fatigue and dysarthria. Brain MRI showed symmetrical middle cerebellar peduncle (MCP) infarctions (Figure, A, B, E). CT angiography showed multifocal bilateral cervical vertebral artery stenoses (Figure, H). Symptoms worsened over 2 weeks, despite antiplatelet therapy. Repeat MRI showed enlargement and mild enhancement of the MCP lesions (Figure, C, D, F, G). CRP was 185 mg/L, and ESR was 97 mm/h. Temporal artery biopsy revealed non-necrotizing arteritis (Figure, I). Isolated lesions of bilateral MCPs are extremely rare and arise from vascular, degenerative, inflammatory, and neoplastic disorders.1,2Giant cell arteritis is a rare cause of stroke and tends to preferentially affect the vertebrobasilar system.

Defining the molecular networks that drive breast cancer has led to therapeutic interventions and improved patient survival. However, the aggressive triple-negative breast cancer subtype (TNBC) remains recalcitrant to targeted therapies because its molecular etiology is poorly defined. In this study, we used a forward genetic screen to discover an oncogenic network driving human TNBC. SCYL1, TEX14, and PLK1 (“STP axis”) cooperatively trigger degradation of the REST tumor suppressor protein, a frequent event in human TNBC. The STP axis induces REST degradation by phosphorylating a conserved REST phospho-degron and bridging REST interaction with the ubiquitin-ligase βTRCP. Inhibition of the STP axis leads to increased REST protein levels and impairs TNBC transformation, tumor progression, and metastasis. Expression of the STP axis correlates with low REST protein levels in human TNBCs and poor clinical outcome for TNBC patients. Our findings demonstrate that the STP-REST axis is a molecular driver of human TNBC.

In the central nervous system (CNS), neural stem cells (NSCs) differentiate into neurons, astrocytes, and oligodendrocytes—these cell lineages are considered unidirectional and irreversible under normal conditions. The introduction of a defined set of transcription factors has been shown to directly convert terminally differentiated cells into pluripotent stem cells, reinforcing the notion that preserving cellular identity is an active process. Indeed, recent studies highlight that tumor suppressor genes (TSGs) such as Ink4a/Arfand p53, control the barrier to efficient reprogramming, leaving open the question whether the same TSGs function to maintain the differentiated state. During malignancy or following brain injury, mature astrocytes have been reported to re-express neuronal genes and re-gain neurogenic potential to a certain degree, yet few studies have addressed the underlying mechanisms due to a limited number of cellular models or tools to probe this process. Here, we use a synthetic small-molecule (isoxazole) to demonstrate that highly malignant EGFRvIII-expressing Ink4a/Arf−/−; Pten−/−astrocytes downregulated their astrocyte character, re-entered the cell cycle, and upregulated neuronal gene expression. As a collateral discovery, isoxazole small-molecules blocked tumor cell proliferation in vitro, a phenotype likely coupled to activation of neuronal gene expression. Similarly, histone deacetylase inhibitors induced neuronal gene expression and morphologic changes associated with the neuronal phenotype, suggesting the involvement of epigenetic-mediated gene activation. Our study assesses the contribution of specific genetic pathways underlying the de-differentiation potential of astrocytes and uncovers a novel pharmacological tool to explore astrocyte plasticity, which may bring insight to reprogramming and anti-tumor strategies.

Background: Staphylococcus aureusis a leading cause of healthcare- and community-associated infections and can be difficult to treat due to antimicrobial resistance. About 30% of individuals carry S. aureusasymptomatically in their nares, a risk factor for later infection, and interactions with other species in the nasal microbiome likely modulate its carriage. It is thus important to identify ecological or functional genetic elements within the maternal or infant nasal microbiomes that influence S. aureusacquisition and retention in early life. Results: We recruited 36 mother-infant pairs and profiled a subset of monthly longitudinal nasal samples from the first year after birth using shotgun metagenomic sequencing. The infant nasal microbiome is highly variable, particularly within the first 2 months. It is weakly influenced by maternal nasal microbiome composition, but primarily shaped by developmental and external factors, such as daycare. Infants display distinctive patterns of S. aureuscarriage, positively associated with Acinetobacterspecies, Streptococcus parasanguinis, Streptococcus salivarius, and Veillonellaspecies and inversely associated with maternal Dolosigranulum pigrum. Furthermore, we identify a gene family, likely acting as a taxonomic marker for an unclassified species, that is significantly anti-correlated with S. aureusin infants and mothers. In gene content-based strain profiling, infant S. aureusstrains are more similar to maternal strains. Conclusions: This improved understanding of S. aureuscolonization is an important first step toward the development of novel, ecological therapies for controlling S. aureuscarriage.