Epiphany Biosciences (United States)

Chondroid syringoma (mixed tumor) is a rare benign sweat gland tumor that commonly arises on the head and neck [1]. Recurrence is rare and typically results from incomplete excision [1]. The standard treatment is surgical excision, but literature describing the use of Mohs micrographic surgery (MMS) for chondroid syringomas, particularly on the lip, a site of both functional and aesthetic significance, is limited [2]. We present a recurrent branching alveolar subtype of chondroid syringoma on the upper lip successfully treated with MMS and crescentic advancement flap reconstruction, representing, to our knowledge, the first such report. A 39-year-old female with Fitzpatrick skin type V presented for MMS of a recurrent cutaneous chondroid syringoma on the right upper cutaneous lip. Seven months prior, she had noticed a small bump that was excised 3 months later, confirming chondroid syringoma. The lesion regrew within 2 months at the same site, prompting evaluation with our team. Examination revealed a firm, well-circumscribed, smooth, pink papule measuring 0.6 × 0.5 cm on the right upper cutaneous lip, inferolateral to the nasal ala and medial to the melolabial fold (Figure 1a). Given the recurrence, aesthetic location, and potential for subclinical extension, MMS was performed to ensure complete margin control. The clinically visible tumor was first debulked, and a microscopic-controlled layer with a 0.1-mm peripheral margin was taken. Frozen sections were processed en face with complete margin evaluation and showed a well-circumscribed, multinodular dermal tumor composed of epithelial and myoepithelial cells embedded in a chondromyxoid stroma (Figure 2a). The epithelial cells were arranged in ductal structures, surrounded by a dense eosinophilic matrix. The first Mohs stage (1.3 × 1.2 cm) revealed invasion into subcutaneous fat with persistent nodular growth but no mitotic activity or cytologic atypia (Figure 2b). A second stage was taken in a similar fashion with a 0.1-mm margin and en face frozen section processing, which revealed limited extension into muscle. All margins were cleared at this stage, resulting in a final defect of 1.4 × 1.3 cm. Because of the proximity to the vermillion border and minimal skin laxity, a crescentic advancement flap extending to the vermilion was designed to hide suture lines (Figure 1b). At 1-week follow-up, the wound was well healed with an excellent cosmetic outcome (Figure 1c). Fewer than 50 facial cases of benign chondroid syringoma have been documented, with most treated by wide local excision [2]. In rare instances, MMS has been employed for lesions involving the brow, cheek, and nasal dorsum [2, 3]. One prior case involved the upper lip, although it did not represent a recurrent or branching alveolar subtype [4]. Histologically, our case demonstrated the branching alveolar pattern, characterized by complex ductal structures within a chondromyxoid stroma, which to our knowledge has not previously been treated with MMS. Reconstruction of the upper lip requires meticulous restoration of both form and function. While linear closures may be appropriate in some cases, flap-based techniques are often beneficial in preventing contour and free margin distortion, especially in patients with minimal redundant skin. In this case, the crescentic advancement flap provided a tension-free closure that maintained philtral alignment and preserved vermilion definition without blunting the nasolabial fold or distorting the oral commissure. Although alternatives such as V-Y advancement flap could be considered, this technique carries a higher risk of pincushioning and creates horizontal linear scars, which are less easily concealed than vertical scars that align with natural perioral wrinkles, making it a suboptimal choice in this delicate region [5]. This case highlights the value of MMS for recurrent, histologically benign but locally invasive tumors in cosmetically sensitive areas to achieve optimal aesthetic and functional outcomes through individualized reconstructive planning. The authors have nothing to report. This article did not require IRB approval as it involves no experimental interventions or investigations beyond standard clinical practice. Patient consent was obtained for publication. Dr. Tolkachjov is an investigator and speaker for CASTLE Biosciences, Kerecis, Boehringer Ingelheim, and Regeneron. No relevant conflicts of interest. The other authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Biodiversity continues to decline despite protected area expansion and global conservation commitments. Biodiversity losses occur in existing protected areas, yet common methods used to select protected areas ignore postimplementation threats that reduce effectiveness. We developed a conservation planning framework that considers the ongoing anthropogenic threats within protected areas when selecting sites and the value of planning for costly threat-mitigating activities (i.e., enforcement) at the time of siting decisions. We applied the framework to a set of landscapes that contained the range of possible correlations between species richness and threat. Accounting for threats and implementing enforcement activities increased benefits from protected areas without increasing budgets. Threat information was valuable in conserving more species per spending level even without enforcement, especially on landscapes with randomly distributed threats. Benefits from including threat information and enforcement were greatest when human threats peaked in areas of high species richness and were lowest where human threats were negatively associated with species richness. Because acquiring information on threats and using threat-mitigating activities are costly, our findings can guide decision-makers regarding the settings in which to pursue these planning steps.

Abstract Detection of large vessel occlusion (LVO) using machine learning on computed tomography angiography (CTA) may help stroke triage, yet applicability across varied patient and image characteristics has not been examined. The study will examine which characteristics are important when using a convolutional neural network to identify LVO on CTA. A retrospective cohort study (November 2017–May 2019) at a comprehensive stroke center evaluated 677 stroke-alerted patients with an LVO of the internal carotid artery, M1, or M2 (n=150) and a matching number without LVO were included. An Inception module-based network was trained for binary classification of LVO presence. Results were examined by LVO location, window settings, non-LVO findings, demographics, risk factors, presentation status and times, interventions, and outcomes. Three hundred patients were included (48% women; median age 65). Mean±95% CI for cross-validation test and external validation, respectively, are area under precision-recall curve 0.871±0.094 and 0.742±0.018 and area under receiver operating characteristic curve 0.920±0.051 and 0.852±0.004. 145 true positive (TP), 5 false negative (FN), 39 false positive (FP), and 111 true negative (TN) patients were identified. Significant comparisons (P<0.05) identified: lower window settings for misclassifications, smoking history for all FN versus 33% TP (P=0.005), and tissue plasminogen activator treatment for 41% FP versus 20% TN (P=0.017). Our LVO detection tool had high performance across patient characteristics with few exceptions. FP had pathology warranting detection, including distal occlusions. Lower window settings among misclassifications highlight the need for image quality when using machine learning for decision support.

Keywords Mohs micrographic surgery, keystone flap, dermatologic surgery, reconstruction, leg, fasciocutaneous

Lichen planopilaris (LPP) is a scarring alopecia rarely described in men. To investigate the clinical and histopathologic features of LPP in men. We performed a retrospective cohort study of male patients with LPP seen at Mayo Clinic between 1992 and 2016. Nineteen men with biopsy-confirmed LPP were included. The disease most commonly presented with diffuse (42.1%) or vertex scalp (42.1%) involvement. None of the patients had eyebrow or body hair involvement. Perifollicular erythema (94.7%) and pruritus (57.9%) were the most frequent clinical findings. Androgenetic alopecia (AGA) co-occurred in 26.3% of patients. Mucosal lichen planus was found in four patients (21.1%). Thyroid disease occurred in three patients (15.8%). Disease improvement (47.3%) occurred with combination topical and systemic therapy, topical clobetasol monotherapy, and minocycline monotherapy. LPP in men has similar clinical and histologic presentations as reported in women. Nonscalp hair loss appears less likely in men with classic LPP than reported in men with frontal fibrosing alopecia, while mucosal lichen planus and thyroid disease appear to be more common in classic LPP. Men with AGA can present with new-onset concomitant LPP. Limitations included small study size, variable follow-up, and lack of standardized clinical assessment due the study's retrospective nature.

The hepatitis C virus (HCV) is a positive-stranded RNA virus classified within the Flaviviridae family. It infects 3-4 MM individuals in the USA alone and an estimated 170 MM worldwide. Around 75% of acute infections develop into life-long infections which are associated with varying levels and types of liver and other diseases. While the majority of infected individuals only have mild forms of hepatitis, some can develop chronic lobular hepatitis that then proceeds sequentially through chronic active hepatitis, liver fibrosis, liver cirrhosis and primary hepatocellular carcinoma. The latter is always preceded by cirrhosis suggesting that the continually-inflamed liver may itself be a direct cause of tumorigenesis. However, certain HCV gene products may also play a role since the nucleocapsid and nonstructural proteins 3 & 4 have been shown to induce tumorigenesis when overexpressed in various cellular and animal models. HCV-associated extrahepatic diseases include mixed cryoglobulinemia, membranoproliferative glomerulonephritis, porphyria cutanea tarda and there is some association with non-Hodgkin's B cell lymphoma. The latter may be mediated by the engagement of the HCV receptor, CD81 by envelope glycoprotein 2 within circulating HCV virions. Many co-factors of HCV-associated disease are known including gender (with the incidence of hepatocellular carcinoma being lower in females), alcohol use, duration of infection and co-infection with other hepatotropic viruses as well as co-infection with HIV. Individuals co-infected with HIV & HCV often develop severe liver disease. Vaccine strategies to prevent the development of persistent infection are now looking promising. Vaccines eliciting cross-neutralising antibodies or cross-reacting cellular immune responses in non-human primates are able to prevent chronic infection following experimental challenge with heterologous viral strains thus mirroring the correlates of protection in humans that are able to spontaneously eradicate acute HCV infection. Standard-of-care therapy comprises pegylated alpha-interferon along with ribavirin, a mixture that is thought to have direct antiviral and immunomodulatory activity. Patients with chronic hepatitis and even liver cirrhosis can be normalized by this therapy with virus eradication, although 12 months of treatment are required for the common genotype 1 infections and even then, less than 50% of patients are permanently cured. However, progress is occurring through the use of more specific antivirals that inhibit the viral serine protease, the viral replicase and other targets like nonstructural protein 5a that plays an essential role in virion production. Therefore, we can anticipate a combination therapy to emerge within the next decade that will cure the large majority of HCV patients and a vaccine that could prevent the chronic sequelae of the estimated 25,000 new infections still occurring annually in the USA alone.

The contents of many valuable web-accessible databases are only accessible through search interfaces and are hence invisible to traditional web “crawlers.” Recent studies have estimated the size of this “hidden web” to be 500 billion pages, while the size of the “crawlable” web is only an estimated two billion pages. Recently, commercial web sites have started to manually organize web-accessible databases into Yahoo!-like hierarchical classification schemes. In this paper, we introduce a method for automating this classification process by using a small number of query probes. To classify a database, our algorithm does not retrieve or inspect any documents or pages from the database, but rather just exploits the number of matches that each query probe generates at the database in question. We have conducted an extensive experimental evaluation of our technique over collections of real documents, including over one hundred web-accessible databases. Our experiments show that our system has low overhead and achieves high classification accuracy across a variety of databases.