Major depressive disorder is a common disease with high mortality and morbidity worldwide. Though peak onset is during late adolescence, the prevalence of major depressive disorder remains high ...throughout adulthood. Leveraging an association study design, this study screened a large number of variables in the 2017 National Survey on Drug Use and Health to characterize differences between adult and youth depression across a wide array of phenotypic measurements.
All dichotomous variables were manually identified from the survey for association screening. Association between each dichotomous variable and past-year major depressive episode (MDE) occurrence was calculated as an odds ratio for adults (≥18 years) and youth (12-17 years), and tested for significance with Fischer's exact test. Logarithm of the calculated odds ratios were plotted and fitted to a linear model to assess correlation between adult and youth risk factors.
Many of the screened variables showed similar association between past-year depressive episode occurrence in youth and adults; Lin's concordance correlation coefficient between adult and youth associations was 0.91 (95% CI 0.89-0.92). Differentially associated variables were identified, tracking: female sex, alcohol use, cigarette use, marijuana use, Medicaid/CHIP coverage, cognitive changes due to a mental, physical or emotional condition, and respondents' identification of a single depressive event as the worst experienced.
While some youth-specific correlates of major depressive episodes were identified through screening, including some novel associations, most examined variables showed similar association with youth and adult depression. Further study of results is warranted, especially concerning the finding of increased association between marijuana use and depressive episodes in youth.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Age-related macular degeneration (AMD) is a neurodegenerative disorder characterized by photoreceptor and retinal pigment epithelium loss often complicated by neovascularization and is one of the ...leading causes of irreversible vision loss worldwide. However, the precise pathophysiology of AMD remains to date unclear, and there is a dearth of effective therapies for the early stages of the disease. A growing body of evidence has identified microglia-mediated neuroinflammation as a key driver of neuronal damage in AMD, presenting a novel avenue for the development of pharmacological agents targeting this cell population. The local microglial response interacts with other glia as well as engages in crosstalk with peripheral immunological niches. This article presents a review of the current evidence regarding the involvement of glia in the pathophysiology of AMD, an overview of the key immune circuits and effector mechanisms shown to be active in AMD, and potential therapeutic avenues targeting glial involvement.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Optical coherence tomography angiography (OCTA) is an emerging non-invasive technique for imaging the retinal vasculature. While there are many promising clinical applications for OCTA, determination ...of image quality remains a challenge. We developed a deep learning-based system using a ResNet152 neural network classifier, pretrained using ImageNet, to classify images of the superficial capillary plexus in 347 scans from 134 patients. Images were also manually graded by two independent graders as a ground truth for the supervised learning models. Because requirements for image quality may vary depending on the clinical or research setting, two models were trained-one to identify high-quality images and one to identify low-quality images. Our neural network models demonstrated outstanding area under the curve (AUC) metrics for both low quality image identification (AUC = 0.99, 95%CI 0.98-1.00, Formula: see text = 0.90) and high quality image identification (AUC = 0.97, 95%CI 0.96-0.99, Formula: see text = 0.81), significantly outperforming machine-reported signal strength (AUC = 0.82, 95%CI 0.77-0.86, Formula: see text= 0.52 and AUC = 0.78, 95%CI 0.73-0.83, Formula: see text = 0.27 respectively). Our study demonstrates that techniques from machine learning may be used to develop flexible and robust methods for quality control of OCTA images.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Post-acute infection syndromes may develop after acute viral disease
. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with ...long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions
. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Due to commonalities in pathophysiology, age-related macular degeneration (AMD) represents a uniquely accessible model to investigate therapies for neurodegenerative diseases, leading us to examine ...whether pathways of disease progression are shared across neurodegenerative conditions. Here we use single-nucleus RNA sequencing to profile lesions from 11 postmortem human retinas with age-related macular degeneration and 6 control retinas with no history of retinal disease. We create a machine-learning pipeline based on recent advances in data geometry and topology and identify activated glial populations enriched in the early phase of disease. Examining single-cell data from Alzheimer's disease and progressive multiple sclerosis with our pipeline, we find a similar glial activation profile enriched in the early phase of these neurodegenerative diseases. In late-stage age-related macular degeneration, we identify a microglia-to-astrocyte signaling axis mediated by interleukin-1β which drives angiogenesis characteristic of disease pathogenesis. We validated this mechanism using in vitro and in vivo assays in mouse, identifying a possible new therapeutic target for AMD and possibly other neurodegenerative conditions. Thus, due to shared glial states, the retina provides a potential system for investigating therapeutic approaches in neurodegenerative diseases.
Repeated serological testing tells about the change in the overall infection in a community. This study aimed to evaluate changes in antibody prevalence and kinetics in a closed cohort over six ...months in different sub-populations in India. The study included 10,000 participants from rural and urban areas in five states and measured SARS-CoV-2 antibodies in serum in three follow-up rounds. The overall seroprevalence increased from 73.9% in round one to 90.7% in round two and 92.9% in round three. Among seropositive rural participants in round one, 98.2% remained positive in round two, and this percentage remained stable in urban and tribal areas in round three. The results showed high antibody prevalence that increased over time and was not different based on area, age group, or sex. Vaccinated individuals had higher antibody prevalence, and nearly all participants had antibody positivity for up to six months.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Age-related macular degeneration (AMD) is a neurodegenerative disease and a leading cause of irreversible vision loss in the developed world. While not classically described as an inflammatory ...disease, a growing body of evidence has implicated several components of the innate immune system in the pathophysiology of age-related macular degeneration. In particular, complement activation, microglial involvement, and blood-retinal-barrier disruption have been shown to play key roles in disease progression, and subsequent vision loss. This review discusses the role of the innate immune system in age-related macular degeneration as well as recent developments in single-cell transcriptomics that help advance the understanding and treatment of age-related macular degeneration. We also explore the several potential therapeutic targets for age-related macular degeneration in the context of innate immune activation.
We have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most ...kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6–12.0, p = 2.4 × 10-7). We estimate there are 130–234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1.
► Association of duplications of the Williams syndrome region, 7q11.23 ► Replication of findings of increased de novo CNVs in autism spectrum disorders ► Strong association with ASD at 7q11.23, 15q11.2-13, 16p11.2, and NRXN1 ► Prediction of 130–234 ASD-related de novo CNV regions
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recent advancements in single-cell technologies allow characterization of experimental perturbations at single-cell resolution. While methods have been developed to analyze such experiments, the ...application of a strict causal framework has not yet been explored for the inference of treatment effects at the single-cell level. Here we present a causal-inference-based approach to single-cell perturbation analysis, termed CINEMA-OT (causal independent effect module attribution + optimal transport). CINEMA-OT separates confounding sources of variation from perturbation effects to obtain an optimal transport matching that reflects counterfactual cell pairs. These cell pairs represent causal perturbation responses permitting a number of novel analyses, such as individual treatment-effect analysis, response clustering, attribution analysis, and synergy analysis. We benchmark CINEMA-OT on an array of treatment-effect estimation tasks for several simulated and real datasets and show that it outperforms other single-cell perturbation analysis methods. Finally, we perform CINEMA-OT analysis of two newly generated datasets: (1) rhinovirus and cigarette-smoke-exposed airway organoids, and (2) combinatorial cytokine stimulation of immune cells. In these experiments, CINEMA-OT reveals potential mechanisms by which cigarette-smoke exposure dulls the airway antiviral response, as well as the logic that governs chemokine secretion and peripheral immune cell recruitment.
We conducted 3 population-based cross-sectional surveys, at 1-month intervals, to estimate the prevalence and time-trend of severe acute respiratory syndrome coronavirus 2 infection in Puducherry, ...India. Seropositivity rate increased from 4.9% to 34.5% over 2 months and was 20-fold higher than the number of diagnosed cases of infection.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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