Clinical, mechanistic, and therapeutic landscape of cutaneous fibrosis.

When dysregulated, skin fibrosis can lead to a multitude of pathologies. We provide a framework for understanding the wide clinical spectrum, mechanisms, and management of cutaneous fibrosis encompassing a variety of matrix disorders, fibrohistiocytic neoplasms, injury-induced scarring, and autoimmune scleroses. Underlying such entities are common mechanistic pathways that leverage morphogenic signaling, immune activation, and mechanotransduction to modulate fibroblast function. In light of the limited array of available treatments for cutaneous fibrosis, scientific insights have opened new therapeutic and investigative avenues for conditions that still lack effective interventions.

Recruitment of CXCR4+ type 1 innate lymphoid cells distinguishes sarcoidosis from other skin granulomatous diseases.

Sarcoidosis is a multiorgan granulomatous disease that lacks diagnostic biomarkers and targeted treatments. Using blood and skin from patients with sarcoid and non-sarcoid skin granulomas, we discovered that skin granulomas from different diseases exhibit unique immune cell recruitment and molecular signatures. Sarcoid skin granulomas were specifically enriched for type 1 innate lymphoid cells (ILC1s) and B cells and exhibited molecular programs associated with formation of mature tertiary lymphoid structures (TLSs), including increased CXCL12/CXCR4 signaling. Lung sarcoidosis granulomas also displayed similar immune cell recruitment. Thus, granuloma formation was not a generic molecular response. In addition to tissue-specific effects, patients with sarcoidosis exhibited an 8-fold increase in circulating ILC1s, which correlated with treatment status. Multiple immune cell types induced CXCL12/CXCR4 signaling in sarcoidosis, including Th1 T cells, macrophages, and ILCs. Mechanistically, CXCR4 inhibition reduced sarcoidosis-activated immune cell migration, and targeting CXCR4 or total ILCs attenuated granuloma formation in a noninfectious mouse model. Taken together, our results show that ILC1s are a tissue and circulating biomarker that distinguishes sarcoidosis from other skin granulomatous diseases. Repurposing existing CXCR4 inhibitors may offer a new targeted treatment for this devastating disease.

Prompt Cytopathological Diagnosis of Multiple Xanthomatous Skin Nodules in an Adolescent Girl Opening the Doors to Detection of Familial Hypercholesterolemia.

BACKGROUND: Xanthomas are papulo-nodular, yellow, soft, painless, dermal-based non-neoplastic cutaneous lesions that comprise of localized aggregates of lipid-laden histiocytes. CASE REPORT: A thirteen-year-old adolescent girl presented with multiple, large, bilateral, nodules present over elbows, posterior aspect of heel, and knees for five years. Fine needle aspiration cytology was performed, and the smears showed numerous foamy histiocytes, a few benign spindle cells, and foreign-body giant cells against a lipidaceous background. Her maternal aunt and grandmother also had xanthelasma palpebrarum. Serum lipid levels were advised and were markedly deranged in all three of them. Based on the corroborative clinical, biochemical, and cytopathological findings, a final diagnosis of familial hypercholesterolemia (FH) was rendered. CONCLUSION: The present case sheds light on the importance of prompt cytopathological diagnosis of xanthomatous lesions, especially in children and adolescents, as it can help prevent morbidity and mortality due to associated premature adverse cardiovascular and cerebrovascular events if left undiagnosed.

Revised version with tracked changes oral Magnesium reduces levels of pathogenic autoantibodies and skin disease in murine lupus.

BACKGROUND: Systemic Lupus Erythematosus (SLE) has a strong genetic susceptibility, but little is known about the impact of diet on disease severity. The Western diet is typically deficient in magnesium (Mg), and given the immunomodulatory effects of Mg, we hypothesized that the low Mg intake increases disease risk and that increasing Mg intake would reduce severity of murine lupus. Here, we placed 12-week old MRL/lpr female lupus mice on a normal (Mg500) or a high (Mg2800) Mg diet for 9 weeks. Urine and blood were collected during the study for quantification of urinary albumin, BUN, anti-dsDNA antibodies, and immune phenotyping. RESULTS: MRL/lpr lupus mice on high Mg2800 diet had significantly fewer skin lesions and less severe skin histology score, and reduced levels of pathogenic anti-dsDNA antibodies, compared with the Mg500 group (143.8±75.0 vs. 47.4±36.2 × 106U/ml; P < 0.05). The high Mg2800 group had a nearly two-fold increase in the percentage of CD4+FOXP3+ Treg cells compared to controls (19.9±5.4 vs. 11.4±5.5%; P < 0.05). Treg percentages inversely correlated with the concentration of anti-dsDNA. None of the mice developed arthritis during the observation period and there were no significant differences in weight, proteinuria, BUN or kidney histology. CONCLUSION: In conclusion, oral supplementation of Mg has a protective effect in a murine lupus model and may represent an inexpensive and safe adjuvant in the treatment of SLsE.

Discovery and generalization of tissue structures from spatial omics data.

Tissues are organized into anatomical and functional units at different scales. New technologies for high-dimensional molecular profiling in situ have enabled the characterization of structure-function relationships in increasing molecular detail. However, it remains a challenge to consistently identify key functional units across experiments, tissues, and disease contexts, a task that demands extensive manual annotation. Here, we present spatial cellular graph partitioning (SCGP), a flexible method for the unsupervised annotation of tissue structures. We further present a reference-query extension pipeline, SCGP-Extension, that generalizes reference tissue structure labels to previously unseen samples, performing data integration and tissue structure discovery. Our experiments demonstrate reliable, robust partitioning of spatial data in a wide variety of contexts and best-in-class accuracy in identifying expertly annotated structures. Downstream analysis on SCGP-identified tissue structures reveals disease-relevant insights regarding diabetic kidney disease, skin disorder, and neoplastic diseases, underscoring its potential to drive biological insight and discovery from spatial datasets.

Updated solution for diagnosis and management of calcinosis cutis: A retrospective review.

Calcinosis cutis is classified into 5 main types: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. However, it is occasionally misdiagnosed as a malignancy and its management remains challenging. Therefore, in this study, we report our diagnostic and treatment experiences with patients with calcinosis cutis and suggest strategies for improving patient care. This retrospective study included 7 patients (4 men, 3 women; 44.4 ±â€…32.0 years old) who visited our hospital between March 2013 and December 2022 and were diagnosed with calcinosis cutis through histopathological procedures. The patients underwent complete excision of the mass without a safety margin. Frozen biopsy was not performed during surgery. No significant intraoperative or postoperative complications were noted after the application of various imaging techniques for diagnosis and follow-up. All patients showed complete recovery. Follow-up showed no recurrence or complications in the 6 patients who completed 1 year of follow-up. Radiological tests such as plain radiography, ultrasonography, computed tomography, and magnetic resonance imaging are important for accurate diagnosis and treatment of calcinosis cutis. This approach can ensure precise assessment of preoperative lesions, leading to safe and less invasive patient treatment, recurrence prevention, and complications of calcinosis cutis.

Relationship between skin and body condition in three species of baleen whales.

The assessment of free-ranging cetacean health through the study of skin conditions using photographs has gained prominence in recent years. However, little attention has been given to the relationships between cetacean skin conditions, species, and body condition. To explore this relationship among baleen whale species along the northwestern coast of Spain, we employed a non-invasive method involving photograph analysis. In this study, we examined skin conditions (including injuries, epizoites and ectoparasites, pigmentation disorders, skin lesions, and anatomical malformations) and body condition (overall physical contours and form, as an indicator of nutritional status and health) in 3 species of whales (blue, fin, and minke whales). This methodology facilitated the identification of 29 subcategories of distinct skin conditions and an assessment of body condition over a 5 yr period (2017 to 2021). In our study, we present evidence linking hypopigmentation, protruding pieces of tissue, and tattoo-like lesions to 'Poor' body condition in the 3 baleen whale species. Fin whales exhibited a higher susceptibility to mottling (prevalence = 17.7%), while blue whales were more prone to starbursts (prevalence = 90.5%). Additionally, we found a significant relationship between skin condition diversity and individual body condition. Our findings contribute valuable information to the broader understanding of the health status of baleen whales. Further investigations are necessary to delve into the etiology of the documented skin conditions and their potential implications for individual survival. This study serves as a foundation for ongoing research aimed at advancing our comprehension of these findings.

High-powered 675-nm laser: Safety and efficacy in clinical evaluation and in vitro evidence for different skin disorders.

BACKGROUND: Laser technology is a viable therapeutic option for treating a number of skin pathologic conditions, including pigmented lesions, vascular lesions and acne scars. AIM: In this work, through in vitro and clinical investigations we test the efficacy, the safety and the speed of treatment of high-powered laser system emitting a 675-nm in the management of various skin condition. MATERIALS AND METHODS: In vitro experiments were performed irradiating adult human dermal fibroblasts cells (HDFa) with 675-nm laser for 24, 48 and 72 h with different fluences and Ki-67+ cells were counted. The confocal microscopy images of control and treated samples were acquired. Clinical skin rejuvenation/diseases treatments with 675 nm laser device were performed with different laser parameters in 11 patients with pigmented lesions, 5 patients with acne scars and 23 patients for skin rejuvenation. Data were evaluated with the validated global score using 5-point scales (GAIS) and patient's satisfaction scale. RESULTS: The application of the high-power 675 nm laser has proven effective in stimulating cell proliferation in in vitro experiments and it led to good results for all skin pathologies. GAIS showed values between 3 and 4 points for all treated pathologies, all scores between '75%-good improvements' and '100%-excellent improvements'. The treatment time was reduced by 50% compared to the old parameters setting, resulting in a faster and good patient's satisfying technique. No serious adverse effects were recorded. CONCLUSION: the preclinical and clinical data confirm the efficacy and safety of this high-powered 675 nm laser for several skin condition.

Radiomic and deep learning analysis of dermoscopic images for skin lesion pattern decoding.

This study aims to explore the efficacy of a hybrid deep learning and radiomics approach, supplemented with patient metadata, in the noninvasive dermoscopic imaging-based diagnosis of skin lesions. We analyzed dermoscopic images from the International Skin Imaging Collaboration (ISIC) dataset, spanning 2016-2020, encompassing a variety of skin lesions. Our approach integrates deep learning with a comprehensive radiomics analysis, utilizing a vast array of quantitative image features to precisely quantify skin lesion patterns. The dataset includes cases of three, four, and eight different skin lesion types. Our methodology was benchmarked against seven classification methods from the ISIC 2020 challenge and prior research using a binary decision framework. The proposed hybrid model demonstrated superior performance in distinguishing benign from malignant lesions, achieving area under the receiver operating characteristic curve (AUROC) scores of 99%, 95%, and 96%, and multiclass decoding AUROCs of 98.5%, 94.9%, and 96.4%, with sensitivities of 97.6%, 93.9%, and 96.0% and specificities of 98.4%, 96.7%, and 96.9% in the internal ISIC 2018 challenge, as well as in the external Jinan and Longhua datasets, respectively. Our findings suggest that the integration of radiomics and deep learning, utilizing dermoscopic images, effectively captures the heterogeneity and pattern expression of skin lesions.

Hair loss and endocrine dermatosis on horses raised in a Mimosa pudica var. unijuga-invaded area.

A Mimosa pudica var. unijuga-associated toxicity affecting horses occurred in Araguari, Triângulo Mineiro, Southeast Brazil. Affected horses had gradual hair loss of the mane and tail and endocrine dermatosis after grazing for three months during the dry season on a paddock invaded by the plant. The main histological lesions include compact ortho-keratotic hyperkeratosis and numerous flame follicles. Toxicological analysis by HPLC-UV demonstrated 0.8 mg/g of mimosine in the leaves.

The Skin and Lewy Body Disease.

This manuscript reviews the significant skin manifestations of Lewy body disease, including Parkinson's disease and dementia with Lewy bodies, and the diagnostic utility of skin biopsy. Besides classic motor and cognitive symptoms, non-motor manifestations, particularly dermatologic disorders, can play a crucial role in disease presentation and diagnosis. This review explores the intricate relationship between the skin and Lewy body disease. Seborrheic dermatitis, autoimmune blistering diseases (bullous pemphigoid and pemphigus), rosacea, and melanoma are scrutinized for their unique associations with Parkinson's disease, revealing potential links through shared pathophysiological mechanisms. Advances in diagnostic techniques allow the identification of promising biomarkers such as α-synuclein in samples obtained by skin punch biopsy. Understanding the dermatologic aspects of Lewy body disease not only contributes to its holistic characterization but also holds implications for innovative diagnostic approaches.

Bayesian-Edge system for classification and segmentation of skin lesions in Internet of Medical Things.

BACKGROUND: Skin diseases are severe diseases. Identification of these severe diseases depends upon the abstraction of atypical skin regions. The segmentation of these skin diseases is essential to rheumatologists in risk impost and for valuable and vital decision-making. Skin lesion segmentation from images is a crucial step toward achieving this goal-timely exposure of malignancy in psoriasis expressively intensifies the persistence ratio. Defies occur when people presume skin diseases they have without accurately and precisely incepted. However, analyzing malignancy at runtime is a big challenge due to the truncated distinction of the visual similarity between malignance and non-malignance lesions. However, images' different shapes, contrast, and vibrations make skin lesion segmentation challenging. Recently, various researchers have explored the applicability of deep learning models to skin lesion segmentation. MATERIALS AND METHODS: This paper introduces a skin lesions segmentation model that integrates two intelligent methodologies: Bayesian inference and edge intelligence. In the segmentation model, we deal with edge intelligence to utilize the texture features for the segmentation of skin lesions. In contrast, Bayesian inference enhances skin lesion segmentation's accuracy and efficiency. RESULTS: We analyze our work along several dimensions, including input data (datasets, preprocessing, and synthetic data generation), model design (architecture, modules), and evaluation aspects (data annotation requirements and segmentation performance). We discuss these dimensions from seminal works and a systematic viewpoint and examine how these dimensions have influenced current trends. CONCLUSION: We summarize our work with previously used techniques in a comprehensive table to facilitate comparisons. Our experimental results show that Bayesian-Edge networks can boost the diagnostic performance of skin lesions by up to 87.80% without incurring additional parameters of heavy computation.