Discovery of a CCR2-targeting pepducin therapy for chronic pain.

Targeting the CCL2/CCR2 chemokine axis has been shown to be effective at relieving pain in rodent models of inflammatory and neuropathic pain, therefore representing a promising avenue for the development of non-opioid analgesics. However, clinical trials targeting this receptor for inflammatory conditions and painful neuropathies have failed to meet expectations and have all been discontinued due to lack of efficacy. To overcome the poor selectivity of CCR2 chemokine receptor antagonists, we generated and characterized the function of intracellular cell-penetrating allosteric modulators targeting CCR2, namely pepducins.

Regulatory T cell-derived enkephalin gates nociception.

T cells have emerged as sex-dependent orchestrators of pain chronification but the sexually dimorphic mechanisms by which T cells control pain sensitivity is not resolved. Here, we demonstrate an influence of regulatory T cells (Tregs) on pain processing that is distinct from their canonical functions of immune regulation and tissue repair. Specifically, meningeal Tregs (mTregs) express the endogenous opioid, enkephalin, and mTreg-derived enkephalin exerts an antinociceptive action through a presynaptic opioid receptor signaling mechanism that is dispensable for immunosuppression.

Neuropeptide substance P alters stem cell fate to aid wound healing and promote epidermal stratification through asymmetric stem cell divisions.

Loss of sensory innervation delays wound healing and administration of the neuropeptide substance P improves re-epithelialization. Keratinocyte hyperproliferation post-wounding may result from symmetric stem cell (SC) self-renewal, asymmetric SC self-renewal, committed progenitor divisions, or a combination of these. However, the effects of sensory denervation and of neuropeptides on SC proliferation are not known.

BIO-CXRNET: a robust multimodal stacking machine learning technique for mortality risk prediction of COVID-19 patients using chest X-ray images and clinical data.

Unlabelled: Nowadays, quick, and accurate diagnosis of COVID-19 is a pressing need. This study presents a multimodal system to meet this need. The presented system employs a machine learning module that learns the required knowledge from the datasets collected from 930 COVID-19 patients hospitalized in Italy during the first wave of COVID-19 (March-June 2020).

An application of the participatory approach to develop an integrated water resources management (IWRM) system for the drought-affected region of Bangladesh.

In many cases, poor management of water supplies is to blame for a crisis. Scholars and practitioners have proposed developing enhanced modalities of water governance that promote the implementation of Integrated Water Resources Management (IWRM) to meet the interconnected problems of assuring access to sustainable water supplies for the world's populations. Therefore, this research aims to do two things: 1) evaluate the current status of water and related resources, and 2) create an operational decision-support system for the sustainable use of water resources based on integrated water resources management (IWRM).

Local IL-23 is required for proliferation and retention of skin-resident memory T17 cells.

The cytokine interleukin-23 (IL-23) is critical for development and maintenance of autoimmune inflammation in nonlymphoid tissues; however, the mechanism through which IL-23 supports tissue-specific immunity remains unclear. In mice, we found that circulating memory T cells were dispensable for anamnestic protection from skin infection, and tissue-resident memory (T) cell-mediated protection from reinfection required IL-23. Administration of anti-IL-23 receptor antibody to mice after resolution of primary infection resulted in loss of CD69 CD103 tissue-resident memory T helper 17 (T) cells from skin, and clinical anti-IL-23 therapy depleted T cells from skin of patients with psoriasis.

Microwave brain imaging system to detect brain tumor using metamaterial loaded stacked antenna array.

In this paper, proposes a microwave brain imaging system to detect brain tumors using a metamaterial (MTM) loaded three-dimensional (3D) stacked wideband antenna array. The antenna is comprised of metamaterial-loaded with three substrate layers, including two air gaps. One 1 × 4 MTM array element is used in the top layer and middle layer, and one 3 × 2 MTM array element is used in the bottom layer.

QCovSML: A reliable COVID-19 detection system using CBC biomarkers by a stacking machine learning model.

The reverse transcription-polymerase chain reaction (RT-PCR) test is considered the current gold standard for the detection of coronavirus disease (COVID-19), although it suffers from some shortcomings, namely comparatively longer turnaround time, higher false-negative rates around 20-25%, and higher cost equipment. Therefore, finding an efficient, robust, accurate, and widely available, and accessible alternative to RT-PCR for COVID-19 diagnosis is a matter of utmost importance. This study proposes a complete blood count (CBC) biomarkers-based COVID-19 detection system using a stacking machine learning (SML) model, which could be a fast and less expensive alternative.

Development and Validation of an Early Scoring System for Prediction of Disease Severity in COVID-19 Using Complete Blood Count Parameters.

The coronavirus disease 2019 (COVID-19) after outbreaking in Wuhan increasingly spread throughout the world. Fast, reliable, and easily accessible clinical assessment of the severity of the disease can help in allocating and prioritizing resources to reduce mortality. The objective of the study was to develop and validate an early scoring tool to stratify the risk of death using readily available complete blood count (CBC) biomarkers.

Skilful precipitation nowcasting using deep generative models of radar.

Precipitation nowcasting, the high-resolution forecasting of precipitation up to two hours ahead, supports the real-world socioeconomic needs of many sectors reliant on weather-dependent decision-making. State-of-the-art operational nowcasting methods typically advect precipitation fields with radar-based wind estimates, and struggle to capture important non-linear events such as convective initiations. Recently introduced deep learning methods use radar to directly predict future rain rates, free of physical constraints.

Exploring the nexus between social vulnerability, built environment, and the prevalence of COVID-19: A case study of Chicago.

COVID-19 has significantly and unevenly impacted the United States, disproportionately affecting socially vulnerable communities. While epidemiologists and public health officials have suggested social distancing and shelter-in-place orders to halt the spread of this virus, the ability to comply with these guidelines is dependent on neighborhood, household, and individual characteristics related to social vulnerability. We use structural equation modeling and multiple data sources, including anonymized mobile phone location data from SafeGraph, to examine the effects of different social vulnerability and built environment factors on COVID-19 prevalence over two overlapping time periods (March to May and March to November of 2020).

Single-Cell Profiling Reveals Divergent, Globally Patterned Immune Responses in Murine Skin Inflammation.

Inflammatory response heterogeneity has impeded high-resolution dissection of diverse immune cell populations during activation. We characterize mouse cutaneous immune cells by single-cell RNA sequencing, after inducing inflammation using imiquimod and oxazolone dermatitis models. We identify 13 CD45 subpopulations, which broadly represent most functionally characterized immune cell types.

Isolation of Murine Skin Resident and Migratory Dendritic Cells via Enzymatic Digestion.

Dendritic cells (DCs) are a highly specialized subset of professional antigen-presenting cells (APCs) that reside in peripheral and lymphoid tissues. DCs capture antigen in the periphery and migrate to the lymph node where they prime naïve T cells. In addition, DCs have been recently appreciated to have function in innate immunity within tissues.

Inflammatory arthritis in pediatric patients with morphea.

Background: Morphea or localized scleroderma is an inflammatory disorder resulting in fibrosis of the skin and subcutaneous tissues. Joint contractures, arthralgias, and functional compromise are recognized associations of pediatric morphea. The co-existence of inflammatory arthritis and morphea is not well-described in the literature.

Antigen-Presenting Cells in the Skin.

Professional antigen-presenting cells (APCs) in the skin include dendritic cells, monocytes, and macrophages. They are highly dynamic, with the capacity to enter skin from the peripheral circulation, patrol within tissue, and migrate through lymphatics to draining lymph nodes. Skin APCs are endowed with antigen-sensing, -processing, and -presenting machinery and play key roles in initiating, modulating, and resolving cutaneous inflammation.

Pathogenic and Protective Autoantibodies in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED).

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare disorder caused by mutations in the autoimmune regulator () gene, leading to defects in T cell selection. The disease manifestations include both autoimmune tissue destruction and immunodeficiency, with specific susceptibility to chronic mucocutaneous candidiasis. Studies have demonstrated a wide repertoire of high affinity tissue- and cytokine-specific antibodies in patients with APECED.

Different Lymphocyte Populations Direct Dichotomous Eosinophil or Neutrophil Responses to Pulmonary Cryptococcus Infection.

Many pulmonary infections elicit lymphocyte responses that lead to an accumulation of granulocytes in the lungs. A variety of lymphocytes are capable of directing eosinophils or neutrophils to the lungs, but the contribution of each subset remains enigmatic. In this study, we used a murine model to examine lymphocyte subsets that ultimately drive the eosinophil or neutrophil response to infection with the fungal pathogen Cryptococcus neoformans.

Skin Immunity to Candida albicans.

Candida albicans is a dimorphic commensal fungus that colonizes healthy human skin, mucosa, and the reproductive tract. C. albicans is also a predominantly opportunistic fungal pathogen, leading to disease manifestations such as disseminated candidiasis and chronic mucocutaneous candidiasis (CMC).

Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β.

Cells of the immune system that reside in barrier epithelia provide a first line of defense against pathogens. Langerhans cells (LCs) and CD8(+) tissue-resident memory T cells (TRM cells) require active transforming growth factor-β1 (TGF-β) for epidermal residence. Here we found that integrins αvβ6 and αvβ8 were expressed in non-overlapping patterns by keratinocytes (KCs) and maintained the epidermal residence of LCs and TRM cells by activating latent TGF-β.