Effects of dimension reduction of hyperspectral images in skin gross pathology.

BACKGROUND: Hyperspectral imaging (HSI) is an emerging modality for the gross pathology of the skin. Spectral signatures of HSI could discriminate malignant from benign tissue. Because of inherent redundancies in HSI and in order to facilitate the use of deep-learning models, dimension reduction is a common preprocessing step. The effects of dimension reduction choice, training scope, and number of retained dimensions have not been evaluated on skin HSI for segmentation tasks. MATERIALS AND METHODS: An in-house dataset of HSI signatures from pigmented skin lesions was prepared and labeled with histology. Eleven different dimension reduction methods were used as preprocessing for tumor margin detection with support vector machines. Cluster-wise principal component analysis (ClusterPCA), a new variant of PCA, was proposed. The scope of application for dimension reduction was also investigated. RESULTS: The components produced by ClusterPCA show good agreement with the expected optical properties of skin chromophores. Random forest importance performed best during classification. However, all methods suffered from low sensitivity and generalization. CONCLUSION: Investigation of more complex reduction and segmentation schemes with emphasis on the nature of HSI and optical properties of the skin is necessary. Insights on dimension reduction for skin tissue could facilitate the development of HSI-based systems for cancer margin detection at gross level.

Application of fluorescence in situ hybridization in distinguishing acral melanoma in situ from acral junctional melanocytic nevus on the volar skin in Japanese patients.

Four-colored fluorescence in situ hybridization (FISH) is an ancillary diagnostic tool for melanoma. However, most studies that have investigated the usefulness of FISH primarily focused on advanced melanomas. The aim of the current study was to evaluate the effectiveness of FISH in distinguishing acral melanoma (AM) in situ from benign acral junctional nevus (AJN), two types of lesions that are difficult to differentiate via traditional clinical means. The authors investigated the usefulness of FISH in 91 acral melanocytic lesions, including 50 lesions with diagnostic discrepancies between dermoscopic and pathologic approaches or difficulty diagnosing between AM in situ and AJN, on the volar skin of Japanese patients. The authors classified the lesions based on the diagnosis of dermatologists and pathologists into four groups: (I) lesions with a unanimous diagnosis by dermatologists and pathologists as AM in situ or AJN (n = 41); (II) lesions with a unanimous diagnosis by dermatologists only as AM in situ or AJN (n = 21); (III) lesions with a unanimous diagnosis by pathologists only as AM in situ or AJN (n = 15); and (IV) all other lesions (n = 14). The dermatologists diagnosed the lesions by clinical and dermoscopic photographs alone, while the pathologists diagnosed the lesions by microscopy of hematoxylin and eosin-stained slides alone. In group I (AM in situ [n = 20] and AJN [n = 21]), four-colored FISH demonstrated 90% sensitivity and 81% specificity in distinguishing AM in situ from AJN. There was a significant correlation between the FISH results and the unanimous diagnoses by pathologists alone (p = 0.03) in group III. However, FISH results were not significantly correlated with the unanimous diagnoses by dermatologists alone (p = 0.33) in group II. In conclusion, the four-colored FISH probe kit was useful in distinguishing between AM in situ and AJN and may be an ancillary method when pathologists who are not experts of dermatopathology diagnose melanocytic lesions.

Mucocutaneous manifestations of Behçet's disease: Pathogenesis and management from perspectives of vasculitis.

Behçet's disease (BD) is a systemic inflammatory disorder characterized by vasculitis affecting blood vessels of any caliber or type. It can present with a wide spectrum of vasculitic lesions, including erythema nodosum-like lesions and retinal vasculitis, and may also lead to larger vessel diseases, such as aortic aneurysm and deep vein thrombosis. The full etiology of BD remains unclear, but it is considered a polygenetic disease with multiple genetic risk factors that promote immune dysregulation and thrombophilia. Inflammation can be triggered by environmental factors, such as bacteria or viruses, and the dysregulation of innate and adaptive immune cell subsets. Neutrophils and lymphocytes are the primary players involved in BD pathogenesis, with specific innate (i.e., neutrophil-derived reactive oxygen species and neutrophil extracellular traps) and adaptive (i.e., anti-endothelial cell antibodies) processes inducing endothelial cell activation and chemotaxis of inflammatory cells, leading to coagulation and vasculitis. These inflammation-induced vasculitic or vasculopathic features are observed in most mucocutaneous BD lesions, although vasculitis per se is often pathologically evident only during a brief period of the disease process. Due to the multifactorial nature of BD-associated inflammation, broad-spectrum anti-inflammatory medications, including glucocorticoids and immunosuppressive drugs, have been the mainstay for managing BD. In addition, inhibitors of interleukin (IL)-1, tumor necrosis factor (TNF)-α, and IL-17, which target innate and adaptive immune functions dysregulated in BD, have emerged as promising new therapeutics. In this review, we discuss the muco-cutaneous manifestations of BD by focusing on the underlying vasculitic components in their pathologies, as well as the current array of treatment options.

Hyperspectral imaging for tumor segmentation on pigmented skin lesions.

Significance: Malignant skin tumors, which include melanoma and nonmelanoma skin cancers, are the most prevalent type of malignant tumor. Gross pathology of pigmented skin lesions (PSL) remains manual, time-consuming, and heavily dependent on the expertise of the medical personnel. Hyperspectral imaging (HSI) can assist in the detection of tumors and evaluate the status of tumor margins by their spectral signatures. Aim: Tumor segmentation of medical HSI data is a research field. The goal of this study is to propose a framework for HSI-based tumor segmentation of PSL. Approach: An HSI dataset of 28 PSL was prepared. Two frameworks for data preprocessing and tumor segmentation were proposed. Models based on machine learning and deep learning were used at the core of each framework. Results: Cross-validation performance showed that pixel-wise processing achieves higher segmentation performance, in terms of the Jaccard coefficient. Simultaneous use of spatio-spectral features produced more comprehensive tumor masks. A three-dimensional Xception-based network achieved performance similar to state-of-the-art networks while allowing for more detailed detection of the tumor border. Conclusions: Good performance was achieved for melanocytic lesions, but margins were difficult to detect in some cases of basal cell carcinoma. The frameworks proposed in this study could be further improved for robustness against different pathologies and detailed delineation of tissue margins to facilitate computer-assisted diagnosis during gross pathology.

A combination of polyglycolic acid fabric and fibrin glue prevents air leakage from a lung defect.

OBJECTIVES: Air leakage after lung resection is a common morbidity that may lengthen hospital stay. Applying sealant to a lesion is an effective prophylaxis in clinical practice. This study aimed to examine the effect of a combination of a bioabsorbable polyglycolic acid (PGA) fabric and fibrin glue (FG) on air sealing by measuring the in vitro mechanical strength and degradation of the fabric, and in vivo histological changes after implantation. METHODS: A defect was created in the canine left upper lung lobe, and then filled with a fibrinogen solution and covered with a PGA sheet spray-coated with fibrinogen and thrombin. After 1 and 4 weeks, air leakage from the lesion was examined in vivo under airway pressure. Tissue samples were harvested for histological assessment. RESULTS: The mechanical strength of the PGA fabric remained at 80-90% of the baseline level for 1 week in phosphate-buffered saline, and then rapidly decreased to zero thereafter. Air leakage from the lung defect was prevented by the combination of PGA fabric and FG at 1 and 4 weeks. Histological examinations showed that PGA bundles persisted with a non-specific inflammatory response for 2 weeks and then gradually broke into sparse yarns surrounded by collagen fibres and capillaries by 8 weeks. The lung defect was filled with FG at 1 week and by granulation tissue thereafter. CONCLUSIONS: These results provide evidence for the efficacy of a combination of PGA fabric and FG for the prevention of air leakage in the critical period after lung surgery.

Gelatin hydrogel nonwoven fabrics of a cell culture scaffold to formulate 3-dimensional cell constructs.

The objective of this study is to evaluate the possibility of gelatin hydrogel nonwoven fabrics (GHNF) of a cell culture scaffold to formulate 3-dimensional (3D) cell construct. The thickness of cell construct is about 1 mm and the cells inside are live and bio-active, irrespective of their internal distribution. The GHNF were prepared by the solution blow method of gelatin, following by dehydrothermal crosslinking. The GHNF showed a mechanical strength strong enough not to allow the shape to deform even in a wet state. The wet GHNF also showed resistance against repeated compression. After human mesenchymal stromal cells (hMSC) were seeded and cultured, the inner distribution in GHNF, the apoptosis, hypoxia inducible factor (HIF)-1α, Ki67, collagen or sulfated glycosaminoglycan (sGAG) secretion of cells were evaluated. The hMSC proliferated inside the GHNF with time while a homogeneous distribution in the number of cells proliferated from the surface to the 1000 µm depth of GHNF was observed. The number of apoptosis and HIF-1α positive cells was significantly low compared with that of polypropylene nonwoven fabrics with the similar fiber diameters and intra-structure. The GHNF were degraded during cell culture, and completely replaced by collagen and sGAG secreted. It is concluded that the GHNF is a promising cell culture scaffold for 3D cell constructs.

Texture analysis of muscle MRI: machine learning-based classifications in idiopathic inflammatory myopathies.

To develop a machine learning (ML) model that predicts disease groups or autoantibodies in patients with idiopathic inflammatory myopathies (IIMs) using muscle MRI radiomics features. Twenty-two patients with dermatomyositis (DM), 14 with amyopathic dermatomyositis (ADM), 19 with polymyositis (PM) and 19 with non-IIM were enrolled. Using 2D manual segmentation, 93 original features as well as 93 local binary pattern (LBP) features were extracted from MRI (short-tau inversion recovery [STIR] imaging) of proximal limb muscles. To construct and compare ML models that predict disease groups using each set of features, dimensional reductions were performed using a reproducibility analysis by inter-reader and intra-reader correlation coefficients, collinearity analysis, and the sequential feature selection (SFS) algorithm. Models were created using the linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), support vector machine (SVM), k-nearest neighbors (k-NN), random forest (RF) and multi-layer perceptron (MLP) classifiers, and validated using tenfold cross-validation repeated 100 times. We also investigated whether it was possible to construct models predicting autoantibody status. Our ML-based MRI radiomics models showed the potential to distinguish between PM, DM, and ADM. Models using LBP features provided better results, with macro-average AUC values of 0.767 and 0.714, accuracy of 61.2 and 61.4%, and macro-average recall of 61.9 and 59.8%, in the LDA and k-NN classifiers, respectively. In contrast, the accuracies of radiomics models distinguishing between non-IIM and IIM disease groups were low. A subgroup analysis showed that classification models for anti-Jo-1 and anti-ARS antibodies provided AUC values of 0.646-0.853 and 0.692-0.792, with accuracy of 71.5-81.0 and 65.8-78.3%, respectively. ML-based TA of muscle MRI may be used to predict disease groups or the autoantibody status in patients with IIM and is useful in non-invasive assessments of disease mechanisms.

Normolipemic xanthomatized Sweet's syndrome: A variant of Sweet's syndrome with myelodysplastic syndrome.

We report a rare case of xanthomatized Sweet's syndrome with myelodysplastic syndrome (MDS) in a patient who presented with erythematous plaques on his chest that were elevated and became yellowish. A diagnosis of MDS with single lineage dysplasia was made during the development of the eruption. Bone marrow biopsy showed an increased number of megakaryoblasts. Histopathologically, there was neutrophil infiltration with leukocytoclasia and the infiltration of xanthomatous cells. Immunohistochemical analysis revealed that the xanthomatized cells were predominantly CD163 positive. We propose that our case of xanthomatized neutrophilic dermatosis is a rare clinicopathological variant of Sweet's syndrome associated with a hematologic disorder.

Gelatin Hydrogel-Fragmented Fibers Suppress Shrinkage of Cell Sheet.

The objective of this study is to investigate the utility of gelatin hydrogel-fragmented fibers (GHFF) as a material to suppress the shrinkage of cell sheets, which often happens upon detaching from a culture plate. The GHFF were fabricated by cutting gelatin hydrogel nonwoven fabrics. MC3T3-E1 cells were simply mixed with different amounts of GHFF, followed by culturing to formulate the cell sheet homogeneously incorporating GHFF. When detached from the culture plate, the cell sheet formulated without GHFF shrunk while the area became about 23% of the original one before detachment. On the contrary, the cell sheet formulated with GHFF hardly shrunk. The lactate/glucose ratio of a metabolic activity was significantly lower and the adenosine triphosphate (ATP) production was higher for the cell sheet formulated with the GHFF than that obtained without the GHFF. An osteogenic activity was high for the cell sheet formulated with the GHFF compared with that obtained without the GHFF. The GHFF addition was a simple and promising method to fabricate active cell sheets without size change. Impact Statement This study introduces the utility of gelatin hydrogel-fragmented fibers (GHFF) for cell sheet engineering. Upon detaching from the culture plate, the cell sheet formulated without GHFF shrunk, while the area became about 23% of the original one before detachment. On the contrary, the cell sheet formulated with GHFF hardly shrunk. The GHFF allowed cell sheets to enhance the metabolic and osteogenic activities. The GHFF addition was a simple and promising method to fabricate active cell sheets without size change.

A Gelatin Hydrogel Nonwoven Fabric Facilitates Metabolic Activity of Multilayered Cell Sheets.

IMPACT STATEMENT: This study introduces the utility of gelatin hydrogel nonwoven fabrics (GHNFs) for cell sheet engineering. The GHNF had the mechanical property strong enough to hold by forceps even in the swollen condition. The cell sheet harvest and transfer processes were performed simpler and faster than those without using the GHNF. The GHNF facilitates the metabolic activity of three-layered cell sheets, and the cell migration from cell sheets into the GHNF was observed. The GHNF is a promising material used to support cell sheets during the process of assemble formulation and contributes to the improved biological functions of tissue-like cell constructs.

A Case of Paraneoplastic Limbic Encephalitis in a Patient with Invasive Thymoma with Anti-Glutamate Receptor Antibody-Positive Cerebrospinal Fluid: A Case Report.

BACKGROUND: Thymoma is known to cause autoimmune neuromuscular disease. However, anti-glutamate receptor antibody limbic encephalitis (LE) with thymoma is relatively rare. CASE PRESENTATION: A 68-year-old woman was admitted with progressive memory impairment and personality change. Brain magnetic resonance imaging (MRI) revealed high intensity in the bilateral limbic areas on T2-weighted fluid-attenuation inversion recovery (FLAIR) images. Chest computed tomography revealed a mass in the anterior mediastinum. Surgical resection of the tumor, which was consistent with a type B3 thymoma, resulted in clinical improvement. After surgery, the cerebrospinal fluid (CSF) was found to be positive for anti-N-methyl-D-aspartate (NMDA) type glutamate receptor antibodies. These findings led to the diagnosis of paraneoplastic LE (PLE) associated with thymoma. CONCLUSION: When a patient presents with neurologic symptoms of unknown origin, the possibility of LE accompanied by thymoma should be considered. Rapid treatment is desirable before the symptoms become irreversible.

A case of lymphomatosis cerebri mimicking inflammatory diseases.

BACKGROUND: Lymphomatosis cerebri (LC) is a rare subtype of primary central nervous system malignant lymphoma. The typical features of this disease exhibited on magnetic resonance imaging (MRI) without contrast enhancement are similar to those observed with diffuse leukoencephalopathy, mimicking white matter disorders such as encephalitis. Clinical features and examination findings that are suggestive of inflammatory diseases may indeed confound the diagnosis of LC. CASE PRESENTATION: A 66-year-old woman with continuous fever over a two-month period developed left hemiparesis despite presenting in an alert state with normal cognitive function. Sampling tests showed autoantibodies in the serum and inflammatory changes in the cerebrospinal fluid. The results from an MRI demonstrated multiple non-enhanced brain lesions in the splenium of the corpus callosum and deep white matter. Single photon emission computed tomography revealed increases in blood flow in the basal ganglia, thalamus and brainstem. No systemic malignancies were found. The patient was suspected of having a diagnosis of nonvasculitic autoimmune inflammatory meningoencephalitis and treated with intravenous methylprednisolone pulse therapy. Her fever transiently dropped to within the normal range. However, she had a sudden seizure and a second MRI exhibited infiltrative lesions gradually extending throughout the whole brain. We performed a brain biopsy, and LC was histologically diagnosed. The patient received whole-brain radiation therapy, which diminished the fever and seizures. The patient died one year after the initial onset of fever. CONCLUSIONS: The present case yields an important consideration that brain neoplasms, especially LC, cannot be ruled out, even in cases with clinical characteristics and examinations consistent with inflammatory diseases. Careful follow-up and histological study are vital for the correct diagnosis of LC.

T-Cell Responses to Tyrosinase-Derived Self-Peptides in Patients with Leukoderma Induced by Rhododendrol: Implications for Immunotherapy Targeting Melanoma.

BACKGROUND: Rhododendrol, a phenolic compound contained in lightening/whitening cosmetics, can bind and inhibit tyrosinase and was reported to induce leukoderma in Japan. Only 2% of the cosmetics users are affected, and tacrolimus is effective in treatment of the condition. OBJECTIVE: To test the hypothesis that the disease is an autoimmune disorder. METHODS: Short-term T-cell lines were established using peripheral blood mononuclear cells from 8 patients with human melanoma-associated and tyrosinase-derived synthetic peptides. The effects of rhododendrol on melanoma immunization were also examined. RESULTS: Seven out of 8 patients were positive for HLA-DR4. Both class I- and class II-restricted and tyrosinase peptide-specific T-cell responses were observed. Immunization of mice with rhododendrol-treated and irradiated B16 melanoma cells successfully delayed the growth of melanoma cells in vivo. CONCLUSION: Rhododendrol-induced leukoderma is an autoimmune disorder, with rhododendrol as an environmental factor and HLA-DR4 as a genetic factor. Rhododendrol might be effective in treating melanomas.

Coenzyme A contained in mothers' milk is associated with the potential to induce atopic dermatitis.

T(h)2 adjuvant activity can be qualitatively and quantitatively evaluated using a mixed lymphocyte reaction and by changes in the intracellular cyclic adenosine 3',5'-monophosphate concentration, using human dendritic cells in vitro. The current study shows that mothers, whose children (n = 55) developed atopic dermatitis (AD) within 6 months after birth, often demonstrate a higher T(h)2 adjuvant activity in their milk, in comparison to those whose children did not develop such symptoms. Such an activity was recovered in a liquid phase of mothers' milk and was eluted as a single fraction by reversed-phase HPLC. Further analysis of this fraction by mass spectrometry showed that signals originating from a factor with a molecular weight of 767.53 are observed, exclusively in milk with a high T(h)2 adjuvant activity. The mass is exactly that of Coenzyme A (CoA), and indeed, a low concentration of CoA exhibited T(h)2 adjuvant activity both in vitro and in vivo. Moreover, mesenteric lymph node non-T cells obtained from mice that were orally treated with CoA led allogeneic naive CD4(+) T cells to differentiate into T(h)2. Furthermore, the oral administration of CoA induced rough skin, hyperplasia of the epidermis, hypergranulosis in the spinous layer and the thickening of the stratum in mice. These data collectively indicate that some of the patients with AD were exposed to mothers' milk carrying high T(h)2 adjuvant activity right after birth, which may be attributable to presence of CoA contained in the milk.

Superficial type of multiple Basal cell carcinomas: detailed comparative study of its dermoscopic and histopathological findings.

We investigated in detail the dermoscopic and histopathological findings in a case of a superficial type of multiple basal cell carcinomas (BCCs). These multiple lesions (occurring in the chest, neck, and back) showed three different findings, respectively. Dermoscopy of the erythematous and brown-colored patch on the anterior chest showed spoke wheel areas, and the histopathological cross-section revealed vertical spoke wheel structures. In the black- and brown-colored patch at the neck, the dermatoscopy showed a maple leaf-like structure, which was in accordance with the strengthening of the histological lateral connection of the lesion. The brown-colored patch of the lateral back histologically showed irregularly enlarged spoke wheel-like areas with peripheral increased melanin pigments, which correlated with the dark black color of dermoscopic maple leaf-like areas. The vertical spoke wheel areas by dermatoscopy revealed a horizontal spoke wheel structure by histopathology.

Detoxification system for inorganic arsenic: transformation of As2O3 into TMAO by vitamin B12 derivatives and conversion of TMAO into arsenobetaine.

A new two-step synthetic pathway developed for the transformation of arsenic trioxide [iAs(III); As(2)O(3)] into arsenobetaine (AB; Me(3)As(+)CH(2)CO(2)(-)) involves treatment of iAs(III) with native B(12) or biomimetic B(12) in the presence of glutathione (GSH) to give TMAO with a high selectivity and a high conversion rate; subsequent treatment of TMAO with iodoacetic acid in the presence of GSH gives arsenobetaine.