Testing a candidate composite serum protein marker of skin severity in systemic sclerosis.

Objectives: Using an integrated multi-omic analysis, we previously derived a candidate marker that estimates the modified Rodnan Skin Score (mRSS) and thus the severity of skin involvement in SSc. In the present study we explore technical and biological validation of this composite marker in a well-characterized cohort of SSc patients.

Methods: Cartilage oligomeric matrix protein (COMP), collagen type IV (COL4A1), tenascin-C (TNC) and spondin-1 (SPON1) were examined in serum samples from two independent cohorts of patients with dcSSc.

Single-cell analysis reveals key differences between early-stage and late-stage systemic sclerosis skin across autoantibody subgroups.

Objectives: The severity of skin involvement in diffuse cutaneous systemic sclerosis (dcSSc) depends on stage of disease and differs between anti-RNA-polymerase III (ARA) and anti-topoisomerase antibody (ATA) subsets. We have investigated cellular differences in well-characterised dcSSc patients compared with healthy controls (HCs).

Methods: We performed single-cell RNA sequencing on 4 mm skin biopsy samples from 12 patients with dcSSc and HCs (n=3) using droplet-based sequencing (10× genomics).

Clinical and pathogenic significance of S100A4 overexpression in systemic sclerosis.

Objectives: We have studied the damage-associated molecular pattern protein S100A4 as a driver of fibroblast activation in systemic sclerosis (SSc).

Methods: S100A4 protein concentration was measured by ELISA in serum of SSc (n=94) and healthy controls (n=15). Protein expression in skin fibroblast cultures from diffuse cutaneous SSc (SScF, n=6) and healthy controls (normal fibroblasts (NF), n=6) was assessed.

Skin biopsy analysis of concurrent keloidal morphoea and systemic sclerosis confirms overlapping pathogenic pathways.

Objectives: Although localised forms of scleroderma (morphoea) have very different clinical features and outcomes from systemic sclerosis the two conditions can occur together in some patients. In this study we have explored skin gene expression in a series of patients with keloidal morphoea, a distinct clinical variant, concurrently with systemic sclerosis.

Methods: We compared skin gene expression from the keloidal lesions with that from skin elsewhere.

Integrated analysis of dermal blister fluid proteomics and genome-wide skin gene expression in systemic sclerosis: an observational study.

Background: Skin fibrosis is a hallmark feature of systemic sclerosis. Skin biopsy transcriptomics and blister fluid proteomics give insight into the local environment of the skin. We have integrated these modalities with the aim of developing a surrogate for the modified Rodnan skin score (mRSS), using candidate genes and proteins from the skin and blister fluid as anchors to identify key analytes in the plasma.

Combinations of scleroderma hallmark autoantibodies associate with distinct clinical phenotypes.

Systemic sclerosis (SSc) is characterized by the presence of SSc-specific or SSc-associated antibodies (SSc-Abs): anti-topoisomerase I (ATA), anti-centromere (ACA), anti-RNA polymerase III (ARA), anti-U3RNP (U3RNP), anti-U1RNP (U1RNP), anti-PmScl (PmScl), anti-Ku (Ku) and anti-Th/To (Th/To), each being associated with specific clinical features and prognosis. The detection of more than one SSc-Abs in SSc patients is rare and only few data about these patients' clinical phenotype is available. The aim of our study was to evaluate the frequency and the disease's features associated with the presence of > 1 SSc-Abs positivity in a large cohort of SSc patients.

COVID-19 Cases and Hospitalizations Among Medicare Beneficiaries With and Without Disabilities - United States, January 1, 2020-November 20, 2021.

Approximately 27% of adults in the United States live with a disability,* some of whom qualify for Medicare benefits. Persons with disabilities are at increased risk for severe COVID-19-associated outcomes compared with the general population (1); however, existing studies have limited generalizability or only pertain to a specific disability (e.g.

The pan-PPAR agonist lanifibranor reduces development of lung fibrosis and attenuates cardiorespiratory manifestations in a transgenic mouse model of systemic sclerosis.

Background: The TβRII∆k-fib transgenic (TG) mouse model of scleroderma replicates key fibrotic and vasculopathic complications of systemic sclerosis through fibroblast-directed upregulation of TGFβ signalling. We have examined peroxisome proliferator-activated receptor (PPAR) pathway perturbation in this model and explored the impact of the pan-PPAR agonist lanifibranor on the cardiorespiratory phenotype.

Methods: PPAR pathway gene and protein expression differences from TG and WT sex-matched littermate mice were determined at baseline and following administration of one of two doses of lanifibranor (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks.

Outcomes linked to eligibility for stem cell transplantation trials in diffuse cutaneous systemic sclerosis.

Objectives: The aim of this study was to explore outcomes in a cohort of dcSSc patients fulfilling eligibility criteria for stem cell transplantation (SCT) studies but receiving standard immunosuppression.

Methods: From a large single-centre dcSSc cohort (n = 636), patients were identified using the published SCT trials' inclusion criteria. Patients meeting the trials' exclusion criteria were excluded.

Molecular basis for clinical diversity between autoantibody subsets in diffuse cutaneous systemic sclerosis.

Objectives: Clinical heterogeneity is a cardinal feature of systemic sclerosis (SSc). Hallmark SSc autoantibodies are central to diagnosis and associate with distinct patterns of skin-based and organ-based complications. Understanding molecular differences between patients will benefit clinical practice and research and give insight into pathogenesis of the disease.

Assessment of the Hemophagocytic Lymphohistiocytosis HScore in Patients With Coronavirus Disease 2019.

The clinical manifestation of moderate to severe coronavirus disease 2019 (COVID-19) has parallels to secondary hemophagocytic lymphohistiocytosis (HLH) both clinically and based on molecular inflammatory response. We found no evidence to support the utility of risk-stratifying COVID-19 patients using risk scoring methodology designed for HLH.

Safety of intravenous anakinra in COVID-19 with evidence of hyperinflammation, a case series.

Objectives: Anakinra is a selective IL-1 inhibitor, which has been used in the context of secondary haemophagocytic lymphohistiocytosis. Although usually given in the s.c.

In-Orbit Performance of the GRACE Follow-on Laser Ranging Interferometer.

The Laser Ranging Interferometer (LRI) instrument on the Gravity Recovery and Climate Experiment (GRACE) Follow-On mission has provided the first laser interferometric range measurements between remote spacecraft, separated by approximately 220 km. Autonomous controls that lock the laser frequency to a cavity reference and establish the 5 degrees of freedom two-way laser link between remote spacecraft succeeded on the first attempt. Active beam pointing based on differential wave front sensing compensates spacecraft attitude fluctuations.

Autoimmunity and immunodeficiency at the crossroad: autoimmune disorders as the presenting feature of selective IgM deficiency.

Selective immunoglobulin M deficiency (sIgMD) is an immunodeficiency with undefined pathogenesis and commonly presenting with recurrent infections. The European Society for Immunodeficiencies Registry defines sIgMD as a serum IgM level repeatedly below 2 SD of normal with normal levels of serum IgA, IgG and IgG subclasses, normal vaccination responses, absence of T-cell defects and absence of causative external factors. Rarely it can also be associated with autoimmune diseases.

The public cancer radiology imaging collections of The Cancer Imaging Archive.

The Cancer Imaging Archive (TCIA) is the U.S. National Cancer Institute's repository for cancer imaging and related information.

A review of inflammatory idiopathic myopathy focusing on polymyositis.

Inflammatory idiopathic myopathies are a group of autoimmune diseases affecting predominantly the proximal skeletal muscles, with raised muscle enzymes, with or without skin involvement and extramuscular organ involvement. Autoantibodies help to characterize patients into different clinical phenotypes. Successful treatment necessitates controlling inflammation early with corticosteroids and invariably requires additional immunosuppressive therapy.

A critical analysis of the tools to evaluate neuropsychiatric lupus.

Neuropsychiatric symptoms occur commonly in patients with systemic lupus erythematosus, but they are not always due to active disease. It is crucial to identify cases that are due to active systemic lupus erythematosus so that appropriate treatment can be instituted. There is no single serological or imaging test that distinguishes active neuropsychiatric systemic lupus erythematosus from neuropsychiatric manifestations caused by other factors such as infection.

Multiplex serum protein analysis reveals potential mechanisms and markers of response to hyperimmune caprine serum in systemic sclerosis.

Background: Hyperimmune caprine serum (HICS) is a novel biological therapy with potential benefit for skin in established diffuse cutaneous systemic sclerosis. Here we report multiplex protein analysis of blood samples from a placebo-controlled phase II clinical trial and explore mechanisms of action and markers of response.

Methods: Patients were treated with HICS (n = 10) or placebo (n = 10) over 26 weeks, with follow-up open-label treatment to 52 weeks in 14 patients.

Beach safety education for primary school children.

Childhood drowning remains a serious public health problem worldwide. The Australian Water Safety Council has set as one of its highest priorities the reduction of drowning deaths in children aged 0-14 years. However, concerns have recently been raised that many students completing primary school still lack the ability to recognize potential aquatic risks, cope with emergencies or assist someone else in danger.

Emergency response readiness for primary school children.

Objective The aim of the present study was to determine whether a 1-day basic life support (BLS) training program can significantly increase emergency response readiness for primary school children. Methods One hundred and seven children aged 11-12 years completed a program led by surf lifesaving instructors. A 50-item quiz was administered 1 week before and 1 and 8 weeks after training.