Performance of a deep neural network in teledermatology: a single-centre prospective diagnostic study.

BACKGROUND: The use of artificial intelligence (AI) algorithms for the diagnosis of skin diseases has shown promise in experimental settings but has not been yet tested in real-life conditions. OBJECTIVE: To assess the diagnostic performance and potential clinical utility of a 174-multiclass AI algorithm in a real-life telemedicine setting. METHODS: Prospective, diagnostic accuracy study including consecutive patients who submitted images for teledermatology evaluation. The treating dermatologist chose a single image to upload to a web application during teleconsultation. A follow-up reader study including nine healthcare providers (3 dermatologists, 3 dermatology residents and 3 general practitioners) was performed. RESULTS: A total of 340 cases from 281 patients met study inclusion criteria. The mean (SD) age of patients was 33.7 (17.5) years; 63% (n = 177) were female. Exposure to the AI algorithm results was considered useful in 11.8% of visits (n = 40) and the teledermatologist correctly modified the real-time diagnosis in 0.6% (n = 2) of cases. The overall top-1 accuracy of the algorithm (41.2%) was lower than that of the dermatologists (60.1%), residents (57.8%) and general practitioners (49.3%) (all comparisons P < 0.05, in the reader study). When the analysis was limited to the diagnoses on which the algorithm had been explicitly trained, the balanced top-1 accuracy of the algorithm (47.6%) was comparable to the dermatologists (49.7%) and residents (47.7%) but superior to the general practitioners (39.7%; P = 0.049). Algorithm performance was associated with patient skin type and image quality. CONCLUSIONS: A 174-disease class AI algorithm appears to be a promising tool in the triage and evaluation of lesions with patient-taken photographs via telemedicine.

Tar Spot: An Understudied Disease Threatening Corn Production in the Americas.

Tar spot of corn has been a major foliar disease in several Latin American countries since 1904. In 2015, tar spot was first documented in the United States and has led to significant yield losses of approximately 4.5 million t. Tar spot is caused by an obligate pathogen, Phyllachora maydis, and thus requires a living host to grow and reproduce. Due to its obligate nature, biological and epidemiological studies are limited and impact of disease in corn production has been understudied. Here we present the current literature and gaps in knowledge of tar spot of corn in the Americas, its etiology, distribution, impact and known management strategies as a resource for understanding the pathosystem. This will in tern guide current and future research and aid in the development of effective management strategies for this disease.

Immunohistochemical expression of vitamin D receptor in melanocytic naevi and cutaneous melanoma: a case-control study.

BACKGROUND: Vitamin D deficiency is associated with higher risk of cancer, possibly due to its antiproliferative, antiangiogenic, proapoptotic, cell-differentiating and anti-invasive effects. The anticarcinogenic role of vitamin D in melanoma is still a matter of debate. Loss of nuclear and cytoplasmic vitamin D receptor (VDR) expression in melanoma cells has been reported. OBJECTIVES: To analyse VDR immunohistochemical expression in benign dermal naevi (DN) and malignant melanoma (MM). METHODS: A case-control study evaluated nuclear and cytoplasmic VDR immunohistochemical staining in 54 DN and 55 MM tissue samples. RESULTS: There was significantly higher cytoplasmic VDR positivity in DN compared with MM (59% vs. 16%, P < 0·001). The mean VDR cytoplasmic expression was also higher in DN vs. MM (P < 0·001). No differences in nuclear VDR positivity were observed between groups, but mean nuclear VDR expression was significantly lower in DN vs. MM (P = 0·02). The loss of cytoplasmic VDR in MM was associated with Clark level, tumour staging and American Joint Committee on Cancer pTNM staging (P=0·004, 0·009 and 0·02, respectively). CONCLUSIONS: Alterations in VDR expression and localization are found in MM compared with DN. Loss of cytoplasmic VDR was associated with melanoma tumour size, suggesting that loss of cytoplasmic VDR may be a prognostic factor.

Taxanes-induced cutaneous eruption: another histopathologic mimicker of malignancy.

BACKGROUND: Paclitaxel and docetaxel are antineoplastic drugs that bind the microtubules, producing the arrest of mitoses, which may be seen histopathologically. These histopathologic changes may simulate an intraepidermal keratinocytic malignant neoplasm, and an accurate diagnosis may be only established by clinicopathological correlation. OBJECTIVES: We report six cases of cutaneous eruptions by taxanes in which a striking cytotoxic effect was evident histopathologically. METHODS: Cutaneous biopsies were obtained in each patient. RESULTS: Atypical starburst-like or ring-like mitoses and dyskeratosis on basal and suprabasal layers of the epidermis. Areas of squamous syringometaplasia were also seen in one case. DISCUSSION: These findings were interpreted as expression of mitotic arrest due to taxanes. Similar changes have been described in association with other chemotherapeutic drugs such as vincristine, podophyllin and its derivative etoposide; colchicine, busulfan and maytansine, but cases like ours due to taxanes are exceptional or under-reported. CONCLUSION: Dermatopathologists should be aware of these effects in order to interpret carefully cutaneous biopsy specimens of patients receiving taxanes.

First evidence of late-acting self-incompatibility in the Aristolochiaceae.

Most Aristolochiaceae species studied so far are from temperate regions, bearing self-compatible protogynous trap flowers. Although self-incompatibility has been suggested for tropical species, the causes of self-sterility in this family remain unknown. To fill this gap, we studied the pollination of the tropical Aristolochia esperanzae, including the physical and physiological anti-selfing mechanisms. Floral visitors trapped inside flowers were collected to determine the pollinators. Protogyny was characterized by observing the temporal expression of sexual phases and stigmatic receptivity tests. The breeding system was investigated using hand-pollination treatments. Pollen tube growth was observed using epifluorescence to identify the self-incompatibility mechanism. Flies were the most frequent visitors found inside A. esperanzae trap flowers, with individuals from the family Ulidiidae being potential pollinators since they carried pollen. The characteristic flower odour and presence of larvae indicate that A. esperanzae deceives flies through oviposition-site mimicry. Although this species showed incomplete protogyny, stigmatic receptivity decreased during the male phase, avoiding self-pollination. Fruits developed only after cross- and open pollination, indicating that the population is non-autonomous, non-apomictic, and self-sterile. This occurred through a delay in the growth of geitonogamous pollen tubes to the ovary and lower ovule penetration, indicating a late-acting self-incompatibility mechanism. Our findings expand the number of families in which late-acting self-incompatibility has been reported, demonstrating that it is more widespread than previously thought, especially when considering less-studied tropical species among the basal angiosperms.

FOXP1 acts through a negative feedback loop to suppress FOXO-induced apoptosis.

Transcriptional activity of Forkhead box transcription factor class O (FOXO) proteins can result in a variety of cellular outcomes depending on cell type and activating stimulus. These transcription factors are negatively regulated by the phosphoinositol 3-kinase (PI3K)-protein kinase B (PKB) signaling pathway, which is thought to have a pivotal role in regulating survival of tumor cells in a variety of cancers. Recently, it has become clear that FOXO proteins can promote resistance to anti-cancer therapeutics, designed to inhibit PI3K-PKB activity, by inducing the expression of proteins that provide feedback at different levels of this pathway. We questioned whether such a feedback mechanism may also exist directly at the level of FOXO-induced transcription. To identify critical modulators of FOXO transcriptional output, we performed gene expression analyses after conditional activation of key components of the PI3K-PKB-FOXO signaling pathway and identified FOXP1 as a direct FOXO transcriptional target. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that FOXP1 binds enhancers that are pre-occupied by FOXO3. By sequencing the transcriptomes of cells in which FOXO is specifically activated in the absence of FOXP1, we demonstrate that FOXP1 can modulate the expression of a specific subset of FOXO target genes, including inhibiting expression of the pro-apoptotic gene BIK. FOXO activation in FOXP1-knockdown cells resulted in increased cell death, demonstrating that FOXP1 prevents FOXO-induced apoptosis. We therefore propose that FOXP1 represents an important modulator of FOXO-induced transcription, promoting cellular survival.

Vitamin D axis and its role in skin carcinogenesis: a comprehensive review

Vitamin D (VD) is a secosteroid hormone that is mainly synthesized in the skin upon exposure to UVB radiation. VD is widely known for its role in calcium metabolism; however, multiple endocrine, paracrine and autocrine functions of VD have been described, including a prominent role on carcinogenesis. In recent years, multiple associations between VD deficiency and different types of cancer have been described, supported by evidence of anti-proliferative, anti-angiogenic, pro-apoptotic, cell-differentiating and anti-invasive effects of this hormone. An immunomodulatory role of VD associated to cancer microenvironment has also been suggested. Regarding skin cancer, it has been shown that VD inhibits tumor development in basal cell carcinoma, squamous cell carcinoma, and melanoma in vitro. Some studies have suggested that lower VD levels may be a risk factor for skin cancer, while others have shown the opposite; there is also preliminary evidence on the role of VD supplementation for the prevention of melanoma in vivo. In this review, we explore the mechanisms of VD effects on carcinogenesis and the available scientific evidence of the interplay between VD and the genesis of both non-melanoma and melanoma skin cancer. (AU)

Relationship of estrogen and progesterone receptor protein levels in carcinomatous and adjacent non-neoplastic epithelium of the breast: a histopathologic and image cytometric study.

BACKGROUND: Results of a previous study demonstrating a correlation between steroid hormone receptor concentrations in benign and tumor tissue in patients with breast carcinoma suggest that receptor levels in breast epithelium undergoing malignant transformation may play a role in determining the receptor levels in the resulting carcinoma. Data used in that study were derived from ligand binding assays and may reflect shortcomings inherent in this methodology, particularly the dilution of receptor proteins from benign and malignant epithelial cells by stromal components. METHODS: We performed a correlation study of steroid hormone receptor expression in benign and malignant breast epithelial cells using computerized image cytometry and histologic sections stained for estrogen (ER) and progesterone receptor (PR), avoiding the problems of contribution of stromal cells to the measurements and uncertainty about the histologic composition of the sample. Sections which contained both tumor and non-neoplastic breast elements were obtained from surgical specimens from 50 patients with breast carcinoma. RESULTS: Positive area (PA) scores for ER in benign and malignant epithelium showed direct correlation that was significant (r = 0.46, p < 0.001), whereas those for PR, although trended in the same direction, did not (r = 0.17, p > 0.2). PA levels for both receptor proteins were higher in benign breast epithelium with proliferative features, compared to non-proliferative benign epithelium, and in tumors when the associated benign tissue had proliferative changes, but neither of these differences were statistically significant, suggesting that the correlation of ER levels in benign and malignant epithelium was not simply a function of proliferative change. CONCLUSION: Our results provide support for the concept that ER expression in breast carcinoma depends partially on epithelial cell receptor levels in the breast in which it arises, but not for the analogous hypothesis for PR. When costs and benefits of tamoxifen chemoprevention are weighed for a patient at risk for breast carcinoma, and when cyto- or histopathologic breast tissue specimens are available, it may be reasonable to include breast epithelial ER levels among the factors considered in making the treatment decision.