Subungual melanoma with cartilaginous differentiation: Molecular insights.

Melanoma's rare capacity to undergo heterologous differentiation can create significant diagnostic challenges. The molecular mechanisms underlying this phenomenon are not well understood. We present an unusual case of subungual melanoma exhibiting extensive cartilaginous differentiation and provide insights into its molecular and cytogenomic features. Histopathologically, the tumor was predominantly composed of nodules of malignant cartilage in association with a smaller population of nested epithelioid to rhabdoid cells. Immunohistochemically, the tumor cells in both components were positive for S100, SOX10, and PRAME, and were negative for Melan-A and HMB-45. Molecular analysis by whole exome DNA sequence did not detect any pathogenic variants in genes commonly implicated in melanoma. Additional analysis by SNP chromosomal microarray revealed a complex genome characterized by numerous chromosomal losses and gains, including a homozygous deletion of the CDKN2A locus and a heterozygous deletion of the locus containing EXT2, a tumor suppressor implicated in hereditary multiple osteochondromas and secondary chondrosarcomas. This case underscores the importance of recognizing cartilaginous differentiation as a rare manifestation of melanoma, particularly at subungual sites, and suggests that at least some of these melanomas may be driven by non-canonical molecular pathways.

A novel method to assess copy number variations in melanocytic neoplasms: Droplet digital PCR for precise quantitation of MYC and MYB genes.

INTRODUCTION: While most melanocytic neoplasms can be classified as either benign or malignant by histopathology alone, ancillary molecular diagnostic tests can be necessary to establish the correct diagnosis in challenging cases. Currently, the detection of copy number variations (CNVs) by fluorescence in situ hybridization and chromosomal microarray (CMA) are the most popular methods, but remain expensive and inaccessible. We aim to develop a relatively inexpensive, fast, and accessible molecular assay to detect CNVs relevant to melanoma using droplet digital polymerase chain reaction (ddPCR) technology. METHODS: In this proof-of-concept study, we evaluated CNVs in MYC and MYB genes from 73 cases of benign nevi, borderline melanocytic lesions, and primary and metastatic melanoma at our institution from 2015 to 2022. A multiplexed ddPCR assay and CMA were performed on each sample, and the results were compared. RESULTS: Concordance analysis of ddPCR with CMA for quantification of MYC and MYB CNVs revealed a sensitivity and specificity of 89% and 86% for MYC and 83% and 74% for MYB, respectively. CONCLUSION: We demonstrate the first use of a multiplexed ddPCR assay to identify CNVs in melanocytic neoplasms. With further improvement and validation, ddPCR may represent a low-cost and rapid tool to aid in the diagnosis of histopathologically ambiguous melanocytic tumors.

Anti-PL-7, anti-Ro/SSA, anti-Mi-2, and anti-TIF1-γ correlate with specific patterns of histopathologic features in dermatomyositis: An analysis of 39 skin biopsy specimens from 25 patients.

BACKGROUND: In dermatomyositis (DM), myositis-specific and myositis-associated antibodies have been correlated with clinical features. It is unknown if histopathologic findings in lesional skin biopsies correlate with serologic subtypes of DM. METHODS: A retrospective chart review of patients with DM was performed. Patients with myositis antibodies and DM lesional skin biopsies were included in the study. Skin biopsies were reviewed by blinded dermatopathologists for 20 histopathologic features. RESULTS: There was a statistically significant (p < 0.05) association between anti-PL-7 serology and decreased degree of vacuolar degeneration, necrotic keratinocytes, and thickening of the epidermal basement membrane. Anti-aminoacyl tRNA synthetase (anti-ARS) antibodies had the same significant negative association with degree of vacuolar degeneration, necrotic keratinocytes, and thickening of the epidermal basement membrane. A similar pattern was seen with an anti-cytoplasmic serology; where there was a significant association with an increased degree of vacuolar degeneration and necrotic keratinocytes, and a nonsignificant trend of minimally thickened epidermal basement membrane. There was a statistically significant association between anti-Ro/SSA serology and increased degree of vacuolar degeneration. Anti-TIF1-γ serology was significantly associated with the increased presence of necrotic keratinocytes and pigment incontinence, and displayed a pattern of increased neutrophils. There was a significant association between anti-Mi-2 antibodies and pigment incontinence, as well as between myositis-specific antibodies and pigment incontinence. A statistically significant positive association was found between nuclear antibodies and degree of vacuolar degeneration, thickened epidermal basement membrane, pigment incontinence, and epidermal atrophy. CONCLUSION: In patients with DM, some specific serotypes, including anti-PL-7, anti-Ro/SSA, anti-Mi-2, and anti-TIF1-γ, may have characteristic histopathologic features.

Eruptive syringomas associated with milia-like idiopathic calcinosis cutis.

An 11-year-old boy presented generalized eruptive syringomas (ESs) associated with multiple milia-like whitish palmar papules corresponding to dermal calcium deposits. A relationship between calcium deposits distribution to an underlying eccrine duct was noted on pathology. The observation of dermal calcium deposits and its association with generalized ESs may support a possible sweat duct origin of this uncommon and peculiar form of superficial calcinosis cutis.

Evaluation of Different Types of Stimuli in an Event-Related Potential-Based Brain-Computer Interface Speller under Rapid Serial Visual Presentation.

Rapid serial visual presentation (RSVP) is currently a suitable gaze-independent paradigm for controlling visual brain-computer interfaces (BCIs) based on event-related potentials (ERPs), especially for users with limited eye movement control. However, unlike gaze-dependent paradigms, gaze-independent ones have received less attention concerning the specific choice of visual stimuli that are used. In gaze-dependent BCIs, images of faces-particularly those tinted red-have been shown to be effective stimuli. This study aims to evaluate whether the colour of faces used as visual stimuli influences ERP-BCI performance under RSVP. Fifteen participants tested four conditions that varied only in the visual stimulus used: grey letters (GL), red famous faces with letters (RFF), green famous faces with letters (GFF), and blue famous faces with letters (BFF). The results indicated significant accuracy differences only between the GL and GFF conditions, unlike prior gaze-dependent studies. Additionally, GL achieved higher comfort ratings compared with other face-related conditions. This study highlights that the choice of stimulus type impacts both performance and user comfort, suggesting implications for future ERP-BCI designs for users requiring gaze-independent systems.

Continuing Bonds in grieving men: A comparative description of Costa Rica and Spain.

Continuing Bonds among grieving men from Costa Rica and Spain were compared, with the primary hypothesis that there would be significant differences between the two groups. A descriptive, comparative, and cross-sectional research study was conducted. Non-probability and convenience sampling was employed, involving 227 grieving men who completed an online questionnaire comprising sociodemographic data, mediators of mourning, and the Continuing Bonds Scale. The results did not reveal significant differences in Continuing Bonds expressions. However, upon controlling for the interaction between degree of kinship with the deceased person, notable differences emerged in Continuing Bonds and internalized and externalized Continuing Bonds (p < 0.05). The influence of sociocultural factors in each country on Continuing Bonds expressions is considered. The findings could support the development of strategies centered on grieving men, Continuing Bonds, and their specific needs.

Isotope Engineered Fluorinated Single and Bilayer Graphene: Insights into Fluorination Selectivity, Stability, and Defect Passivation.

Tailoring the physicochemical properties of graphene through functionalization remains a major interest for next-generation technological applications. However, defect formation due to functionalization greatly endangers the intrinsic properties of graphene, which remains a serious concern. Despite numerous attempts to address this issue, a comprehensive analysis has not been conducted. This work reports a two-step fluorination process to stabilize the fluorinated graphene and obtain control over the fluorination-induced defects in graphene layers. The structural, electronic and isotope-mass-sensitive spectroscopic characterization unveils several not-yet-resolved facts, such as fluorination sites and CF bond stability in partially-fluorinated graphene (F-SLG). The stability of fluorine has been correlated to fluorine co-shared between two graphene layers in fluorinated-bilayer-graphene (F-BLG). The desorption energy of co-shared fluorine is an order of magnitude higher than the CF bond energy in F-SLG due to the electrostatic interaction and the inhibition of defluorination in the F-BLG. Additionally, F-BLG exhibits enhanced light-matter interaction, which has been utilized to design a proof-of-concept field-effect phototransistor that produces high photocurrent response at a time <200 µs. Thus, the study paves a new avenue for the in-depth understanding and practical utilization of fluorinated graphenic carbon.

Validation of the International Consultation on Incontinence Questionnaire-Pediatric Lower Urinary Tract Symptoms (ICIQ-CLUTS) for Spanish-speaking children.

The International Consultation on Incontinence Questionnaire-Pediatric Lower Urinary Tract Symptoms (ICIQ-CLUTS) is a 12-item self-administered tool to screen lower urinary tract symptoms (LUTS) in children. The aim of this study is to translate and validate the ICIQ-CLUTS into Spanish (ICIQ-CLUTS-Sp) and to study its psychometric properties. The cross-cultural adaptation of the ICIQ-CLUTS was performed following international recommendations. The psychometric analysis of the ICIQ-CLUTS-Sp was carried out to determine the reliability, validity, and diagnostic accuracy in a sample of 155 children and parents who completed the Spanish version ICIQ-CLUTS. The reliability indicators for the ICIQ-CLUTS-Sp were excellent (Cronbach's alpha was > 0.8 and ICC > 0.9 both for children's and parents' versions). There was a high Pearson r > 0.6 and a high agreement level between children's and parents' answers (ICC > 0.6), except in 4 items. For parents, the standard error of measurement (SEm) was 0.41, and the minimal detectable change (MDC) was 1.14 points. In children, these results were 0.42 and 1.16 points, respectively. Cut-off points greater than 15 points in the parent version or 16 points in the children version have the highest sensitivity and specificity for detecting LUTS.  Conclusion: The Spanish version of the ICIQ-CLUTS questionnaire is a valid, reliable, and diagnostically accurate instrument to identify cases of children with LUTS. Therefore, it can be used to screen for lower urinary tract symptoms in Spanish speaking children and/or parents, as well as to monitor the effects of interventions. What is Known: • Lower urinary tract symptoms in children should be assessed multimodally using minimally invasive diagnostic procedures. One way to do this is to use the questionnaire to differentiate these cases in paediatric patients. • A cross-cultural adaptation of the ICIQ-CLUTS questionnaire to Spanish has not yet been done. What is New: • Based on a comprehensive validation methodology, this study highlights that the ICIQ-CLUTSSp questionnaire has good psychometric properties.

Hemosiderotic Xanthelasmas. A New Clinicopathological Variant of Xanthelasma Palpebrarum or a Localized Variant of Xanthosiderohistiocytosis of the Eyelids?

ABSTRACT: Xanthelasma palpebrarum represent the most common subtype of cutaneous plane xanthomas. Xanthosiderohistiocytosis is considered a rare variant of xanthoma disseminatum, with only 4 cases reported to date. We report the case of a man with progressive pigmented lesions on the 4 eyelids that could correspond to hemosiderotic xanthelasmas or a localized variant of xanthosiderohistiocytosis.

Slope until reaching the plateau: a new predictor of valve response obtained by lumbar infusion test for idiopathic normal pressure hydrocephalus.

BACKGROUND: Diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is based on clinical, radiological, and hydrodynamic data of cerebrospinal fluid (CSF) obtained by invasive methods such as lumbar infusion test, which is used to determine the resistance to CSF outflow (Rout). However, Rout has limitations, and its value as predictor of valve response is questioned. Other variables can be obtained by lumbar infusion test, such as the time to reach the plateau (TRP) and the slope until reaching the plateau (SRP). The objectives were to determine if SRP could be a predictor of response to ventriculoperitoneal shunt (VPS) and what variable (Rout versus SRP) would have greater predictive value. METHOD: Patients with probable iNPH who underwent a lumbar infusion test and were indicated for a VPS were retrospectively studied. Two groups were established, responders and non-responders. Rout, TRP (period between the start of infusion until reaching the plateau measured in seconds) and SRP ((plateau pressure-opening pressure)/TRP) were obtained. For Rout and SRP, the receiver operating curves (ROC) with its areas under the curve (AUC) were calculated. RESULTS: One hundred ten patients were included, being 86 responders (78.20%). Shunt responders had a significantly greater Rout (17.02 (14.45-20.23) versus 13.34 (12.10-16.28) mmHg/ml/min, p = 0.002) and SRP (0.049 (0.043-0.054) versus 0.031 (0.026-0.036) mmHg/sec, p < 0.001) and smaller TRP (641.28 (584.83-697.73) versus 777.65 (654.03-901.27) sec, p = 0.028) than non-responders. The AUC for SRP was greater than the AUC for Rout (0.763 (95 % CI 0.655-0.871, p < 0.001) versus 0.673 (95 % CI 0.595-0.801, p = 0.008), respectively), but the differences were not significant (p = 0.180). CONCLUSIONS: SRP could be considered predictor of response to VPS, and its accuracy tends to be better than Rout. So, this variable may be a useful tool to select shunt candidates among patients with probable iNPH.

Comparison of Two Paradigms Based on Stimulation with Images in a Spelling Brain-Computer Interface.

A P300-based speller can be used to control a home automation system via brain activity. Evaluation of the visual stimuli used in a P300-based speller is a common topic in the field of brain-computer interfaces (BCIs). The aim of the present work is to compare, using the usability approach, two types of stimuli that have provided high performance in previous studies. Twelve participants controlled a BCI under two conditions, which varied in terms of the type of stimulus employed: a red famous face surrounded by a white rectangle (RFW) and a range of neutral pictures (NPs). The usability approach included variables related to effectiveness (accuracy and information transfer rate), efficiency (stress and fatigue), and satisfaction (pleasantness and System Usability Scale and Affect Grid questionnaires). The results indicated that there were no significant differences in effectiveness, but the system that used NPs was reported as significantly more pleasant. Hence, since satisfaction variables should also be considered in systems that potential users are likely to employ regularly, the use of different NPs may be a more suitable option than the use of a single RFW for the development of a home automation system based on a visual P300-based speller.

Large cell neuroendocrine carcinoma at the esophagogastric junction. An extremely rare entity.

We present the third case described to date of large cell neuroendocrine carcinoma located at the esophagogastric junction (LCNEC). Esophageal neuroendocrine tumours account for 0.03-0.05% of all malignant esophageal tumours. Within oesophageal NETs, LCNEC accounts for 1% of esophageal NETs. This tumour type is characterised by elevated levels of certain markers: synaptophysin, chromogranin A and CD56. In fact, 100% of patients will have chromogranin or synaptophysin, or at least one of these three markers. In turn, 78% will have lymphovascular invasion and 26% will have perineural invasion. Only 11% of patients will have stage I-II, which implies an aggressive course and worse prognosis.

Mini pulse corticosteroid therapy with oral dexamethasone for moderate to severe alopecia areata: A multicentric study.

Extensive subtypes of alopecia areata (AA) (totalis, universalis, or multifocal) still have no approved and effective treatments in Europe, although Janus kinase inhibitors, such as baricitinib, are promising treatments that have been recently approved by the FDA. Nowadays, the higher costs and the lower experience with Janus kinase inhibitors, provide more difficulties in its accessibility. On the other hand, different corticosteroids regimens have been evaluated with conflicting results from decades. In 2016, a new regimen of mini pulse corticosteroid therapy with oral dexamethasone (MPCT-OD) 0.1mg/kg/day twice per week for adult patients with alopecia areata totalis or universalis, was reported to be effective with a lower rate of adverse effects. We performed a retrospective and multicentric study to collect data from patients with extensive forms of alopecia areata who had received MPCTOD (0.1 mg/kg/day twice weekly of dexamethasone) for at least 24 weeks. We included adult patients (≥18 years) with extensive forms of AA (SALT index ≥ 10) that did not respond to previous treatments. Variables including epidemiological and clinical data were recorded. Therapeutic response was assessed through the % change in SALT score (from 0 to 100%) and the changes in eyebrow and eyelash alopecia index (EBA, ELA) from baseline to 24 weeks after the beginning of the treatment. Dexamethasone dosage, duration of the treatment, time until response, time to relapse, adverse effects, and discontinuation were also recorded.

Unilateral ulcerations on the forehead and scalp.

We describe a patient with unilateral ulcerations on the forehead and scalp, occurring 3 months after herpes zoster infection. Further investigations were unremarkable. Histology showed epidermal and upper dermal ulceration associated with a mild nonspecific dermal inflammatory infiltrate composed of lymphoid cells and histiocytes.

Mohs Micrographic Surgery Versus Wide Local Excision in the Treatment of Merkel Cell Carcinoma: A Systematic Review.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neoplasm with high rates of recurrences. Current guidelines recommend wide local excision (WLE) with 1 to 2 cm margins. However, Mohs micrographic surgery (MMS) offers a potential advantage over WLE because of its ability of sparing healthy tissue and assessing 100% of margins. OBJECTIVE: To systematically evaluate the surgical modalities for the treatment of MCC. MATERIALS AND METHODS: Eligible articles were identified using MEDLINE, Scopus, EMBASE, and Cochrane Library. All available studies investigating surgical treatment of MCC with WLE or MMS were considered. RESULTS: Forty studies met the inclusion criteria. Thirty-one studies described patients treated with WLE, 3 with MMS, and 6 with either WLE or MMS. Subgroup analysis of Stage I MCC showed recurrence rates similar in both surgical modalities with local recurrence rate of 6.8% for WLE versus 8.5% for MMS (p = .64) and a regional recurrence rate of 15.2% for WLE versus 15.3% for MMS (p = .99). CONCLUSION: Overall WLE cases were at a higher stage at presentation. Subgroup analysis showed that MMS is not inferior to WLE excision for the treatment of Stage I MCC and is a reasonable option for anatomic locations where tissue sparing is important.

Acquired palmoplantar keratoderma associated with primary biliary cholangitis: Complete and persistent resolution after ursodeoxycholic acid treatment.

A 57-year-old woman presenting an acquired and persisting palmoplantar keratoderma associated with primary biliary cholangitis is reported. Treatment with oral ursodeoxycholic acid was prescribed, and a complete and persistent resolution of skin lesions was noted. This observation seems to support that acquired palmoplantar keratoderma is an uncommon cutaneous manifestation of primary biliary cholangitis.

Hepatitis E virus genotype 3 microbiological surveillance by the Spanish Reference Laboratory: geographic distribution and phylogenetic analysis of subtypes from 2009 to 2019.

BackgroundHepatitis E virus genotype 3 (HEV-3) is widely distributed throughout Europe, with incidence of infections increasing in many countries. Belgium, Bulgaria, France, Germany, Italy, the Netherlands and the United Kingdom have reported the distribution of HEV-3 subtypes in cohorts of patients with hepatic disease.AimTo describe the distribution of the HEV-3 subtypes in Spain at national and autonomous community (AC) levels between 2009 and 2019. The study was also extended to Andorra.MethodsOf 5,197 samples received by the National Reference Laboratory during the study, 409 were HEV-RNA-positive. Among these, 294 (71.9%) were further typed based on an ORF2 sequence fragment, or, for a subset of 74, based on the full-coding genome sequence.ResultsHEV-3 was detected in 291 samples. The dominant subtype in Spain was HEV-3f (88.3%; 257/291), which occurred in all ACs, with no change in detection level over time. Within this subtype, three subclusters were characterised: HEV-3f-B, HEV-3f-A1 and HEV-3f-A2. The second most common HEV subtype was the recently described HEV-3m (7%; 21/291), with two subclusters identified: HEV-3m-A, which has been known since 2010, and HEV-3m-B, since 2014. The third most encountered subtype was HEV-3c (4.1%; 12/291), with a frequency not increasing over time, unlike observations in some European countries.ConclusionThe importance of the surveillance of HEV-3 subtype and subcluster circulation is yet to be assessed. This surveillance together with the comprehensive epidemiological characterisation of clinical cases, could support the identification of sources of transmission and the establishment of control measures nationally and internationally.

Effect of Stimulus Size in a Visual ERP-Based BCI under RSVP.

Rapid serial visual presentation (RSVP) is currently one of the most suitable paradigms for use with a visual brain-computer interface based on event-related potentials (ERP-BCI) by patients with a lack of ocular motility. However, gaze-independent paradigms have not been studied as closely as gaze-dependent ones, and variables such as the sizes of the stimuli presented have not yet been explored under RSVP. Hence, the aim of the present work is to assess whether stimulus size has an impact on ERP-BCI performance under the RSVP paradigm. Twelve participants tested the ERP-BCI under RSVP using three different stimulus sizes: small (0.1 × 0.1 cm), medium (1.9 × 1.8 cm), and large (20.05 × 19.9 cm) at 60 cm. The results showed significant differences in accuracy between the conditions; the larger the stimulus, the better the accuracy obtained. It was also shown that these differences were not due to incorrect perception of the stimuli since there was no effect from the size in a perceptual discrimination task. The present work therefore shows that stimulus size has an impact on the performance of an ERP-BCI under RSVP. This finding should be considered by future ERP-BCI proposals aimed at users who need gaze-independent systems.

Production and Characterization of Nanostructured Powders of Nd2Fe14B and Fe90Al10 by Mechanical Alloying.

The objective of this work is to evaluate the applicability of exchange coupling between nanoparticles of Nd2Fe14B (hard magnetic material) and Fe90Al10 (soft magnetic material), as permanent magnets produced by surfactant-assisted mechanical alloying. The obtained powders were then mixed with 85% of the Nd2Fe14B system and 15% of the Fe90Al10 system and subsequently sintered at 300 °C, 400 °C and 500 °C for one hour. The results obtained by Mössbauer spectrometry (MS) show a ferromagnetic behavior with six magnetic sites represented by sextets (16k1, 16k2, 8j1, 8j2, 4c and 4e), characteristic of the Nd2Fe14B system. X-ray diffraction (XRD) results show a tetragonal and BCC structure for the Nd2Fe14B and FeAl systems, respectively. The results obtained by vibrating sample magnetometry (VSM), for mixtures of the Nd2Fe14B and Fe90Al10 sy stems sintered at 300 °C, 400 °C and 500 °C, allow for the conclusion that the coercive field (Hc) decreases drastically with temperature and the percentage of soft phase at values of Hc = 132 Oe compared to the coercive field values reported for Nd2Fe14B Hc = 6883 Oe, respectively. Images obtained by transmission electron microscopy (TEM), for the Fe90Al10 system, show a tendency for the nanoparticles to agglomerate.

Bikini textile contact dermatitis: A Sherlockian approach revealing 2,4-dichlorophenol as a potential textile contact allergen.

BACKGROUND: Different textile constituents may act as allergens and/or irritants and provoke textile contact dermatitis (TCD). OBJECTIVES: To report a case of TCD caused by ethylene glycol monododecyl ether and 2,4-dichlorophenol, present in a bikini. METHODS: A woman presented with an eczematous, pruritic rash in the area of the bikini straps and back. Patch testing was performed with the European baseline, textile, sunscreen, and photo-patch series, the bikini "as is", and ethanol and acetone extracts of the bikini. Thin-layer chromatography (TLC) of the extracts and gas chromatography-mass spectrometry (GC-MS) analysis were used to elucidate the culprit agents. RESULTS: Positive reactions were found to the bikini "as is" and to the ethanol and acetone extracts. Patch testing with TLC strips showed a strong reaction to spots-fractions 3 and 4. GC-MS was performed to identify substances in each fraction and those suspected to be skin sensitisers were patch tested. On day (D) 4 positive reactions to ethylene glycol monododecyl ether (irritant reaction) and 2,4-dichlorophenol (++) were observed. CONCLUSION: A myriad of chemical compounds can be found in clothing. Ethylene glycol monododecyl ether and 2,4-dichlorophenol were identified as the potential culprits of this bikini TCD.