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In Rhode Island, malignant melanoma of skin causes about 30 deaths a year. Early detection has been shown to reduce mortality risk.Dermatology volunteers and public health professionals convened 27 free skin cancer screenings at public beaches in 2015-2019 to raise skin cancer awareness and screen patients for malignancy. Participants with suspicious lesions were referred for follow-up and later telephoned to ascertain outcomes.Of 2354 people screened, 597 (25%) were referred. 319 of 597 (53%) were later reached by telephone. 196 of 319 (61%) who had kept appointments by the time of the telephone call reported the following diagnoses: 7 malignant melanomas, 32 keratinocyte carcinomas, and 34 actinic keratoses, yielding 3.0 as number needed to biopsy (NNB), and 18.3 as number needed to screen (NNS).Our results demonstrate the value of convenient skin cancer screening events, suggesting the desirability of additional interventions of this type.

AI virtual assistants have significant potential to alleviate the pressure on overly burdened healthcare systems by enabling patients to self-assess their symptoms and to seek further care when appropriate. For these systems to make a meaningful contribution to healthcare globally, they must be trusted by patients and healthcare professionals alike, and service the needs of patients in diverse regions and segments of the population. We developed an AI virtual assistant which provides patients with triage and diagnostic information. Crucially, the system is based on a generative model, which allows for relatively straightforward re-parameterization to reflect local disease and risk factor burden in diverse regions and population segments. This is an appealing property, particularly when considering the potential of AI systems to improve the provision of healthcare on a global scale in many regions and for both developing and developed countries. We performed a prospective validation study of the accuracy and safety of the AI system and human doctors. Importantly, we assessed the accuracy and safety of both the AI and human doctors independently against identical clinical cases and, unlike previous studies, also accounted for the information gathering process of both agents. Overall, we found that the AI system is able to provide patients with triage and diagnostic information with a level of clinical accuracy and safety comparable to that of human doctors. Through this approach and study, we hope to start building trust in AI-powered systems by directly comparing their performance to human doctors, who do not always agree with each other on the cause of patients’ symptoms or the most appropriate triage recommendation.

A fava danta (Dimorphandra mollis Benth) é uma espécie do Cerrado e, por suas inúmeras potencialidades fitoquímicas, possui alto potencial econômico. O fruto tem importância econômica, pois é de onde a indústria extrai princípios ativos como rutina, quercetina e ramnose, usados na fabricação de medicamentos e cosméticos. O ponto de colheita de plantas medicinais varia de acordo com o órgão da planta, estágio de desenvolvimento, época do ano e hora do dia. A determinação do melhor período de colheita permite o máximo aproveitamento pós-colheita do produto vegetal, por apresentar melhor qualidade dos compostos de interesse, sem o mínimo de perdas. Assim, objetivou-se avaliar a influência da época de coleta dos frutos e folhas de fava-danta sobre o teor de flavonoides totais e de rutina nos frutos. As coletas foram realizadas na zona rural do município de Montes Claros-MG. Realizaram-se cinco coletas, no período final de maturação dos frutos (0, 7, 14, 21, 28 dias), com intervalos de 7 dias e as épocas de 0, 7 e 14 dias apresentaram frutos ainda com coloração verde. Ao 21 dias, foram observados frutos marrons e outros verdes. No 28º dia, todos os frutos tinham coloração marrom. O estudo foi conduzido em delineamento em blocos casualizados. Foram selecionadas 10 árvores em produção, sendo coletados frutos e folhas em cada época de coleta. Para análises morfológicas, o comprimento, a largura e a espessura dos frutos foram mensurados. Foram determinados a matéria seca e o teor de umidade dos frutos. Folhas e frutos foram submetidos à análise de flavonoides totais, e o teor de rutina foi analisado em frutos por CLAE. Os dados obtidos foram submetidos à análise de variância e, quando significativo o teste F, foram ajustadas equações de regressão para as variáveis, em função das épocas de coleta. O comprimento, a espessura e a largura do fruto não foram influenciados pela época de coleta dos frutos, assim como o teor de flavonoides, por espectrofotometria, no fruto e na folha. Para as características peso seco e umidade, o comportamento foi quadrático. O teor de rutina analisado por CLAE no fruto diferiu estatisticamente, sendo a primeira época com o maior teor médio de 14,3%. Conclui-se que as épocas de coleta avaliadas não influenciam o teor de flavonoides totais de fava-danta, entretanto há maior teor de rutina quando os frutos estão verdes. The fava danta (Dimorphandra mollis Benth) is a Cerrado species and, due to its innumerable phytochemical potentialities, has a high economic potential. The fruit has economic importance because it is from where the industry extracts active principles such as rutine, quercetin, and rhamnose, used in the manufacture of medicines and cosmetics. The collection point of medicinal plants varies according to the organ of the plant, stage of development, time of year and time of day. The determination of the best harvesting period allows the maximum post-harvest use of the vegetal product because it presents better quality of the compounds of interest without the minimum losses. Thus, the objective of this study was to evaluate the influence of the harvesting period of the fruits and leaves of fava-d'anta on the total flavonoids and of rutine in the fruits. The collections were carried out in the rural area of the city of Montes Claros-MG. Five collections were made in the final maturation period of the fruits (0, 7, 14, 21, 28 days), with intervals of 7 days, being that the season 0, 7 and 14 days, presented fruits still with green coloration. At 21 days brown and other green fruits were observed. On the 28th day all the fruits had brown coloration. The study was conducted in a randomized complete block design. Ten trees in production were selected, and fruits and leaves were collected in each collection season. For morphological analyzes, the length, width and the thickness of the fruits were measured. The dry matter and the moisture content of the fruits were determined. Leaves and fruits were submitted to the analysis of total flavonoids and the rutine content was analyzed in fruits by HPLC. The data obtained were submitted to analysis of variance and, when significant the F test were adjusted, regression equations for the variables, as a function of collection times. The length, thickness and width of the fruit were not influenced by the time of fruit collection, as well as the flavonoid content, by spectrophotometry, in the fruit and leaf. For the characteristics dry weight and humidity, the behavior was quadratic. The rutine content analyzed by HPLC in the fruit differed statistically, being the first season with the highest average OF 14,3It is concluded that the collection times evaluated do not influence the total flavonoid content of fava-d'anta, however, there is a higher rutine content when the fruits are green.

A human polyomavirus was recently discovered in Merkel cell carcinoma (MCC) specimens. The Merkel cell polyomavirus (MCPyV) genome undergoes clonal integration into the host cell chromosomes of MCC tumors and expresses small T antigen and truncated large T antigen. Previous studies have consistently reported that MCPyV can be detected in approximately 80% of all MCC tumors. We sought to increase the sensitivity of detection of MCPyV in MCC by developing antibodies capable of detecting large T antigen by immunohistochemistry. In addition, we expanded the repertoire of quantitative PCR primers specific for MCPyV to improve the detection of viral DNA in MCC. Here we report that a novel monoclonal antibody detected MCPyV large T antigen expression in 56 of 58 (97%) unique MCC tumors. PCR analysis specifically detected viral DNA in all 60 unique MCC tumors tested. We also detected inactivating point substitution mutations of TP53 in the two MCC specimens that lacked large T antigen expression and in only 1 of 56 tumors positive for large T antigen. These results indicate that MCPyV is present in MCC tumors more frequently than previously reported and that mutations in TP53 tend to occur in MCC tumors that fail to express MCPyV large T antigen.

PURPOSE The objective of this study was to evaluate the palliative treatment benefit of surface-mold computer-optimized high-dose-rate brachytherapy (SMBT) for in-transit cutaneous metastases of Merkel cell carcinoma (MCC). METHODS Ten patients with in-transit cutaneous MCC metastases were treated with SMBT at the Dana-Farber/Brigham & Women's Cancer Center between 2006 and 2012. RESULTS The median age at diagnosis was 76 years (range, 63-87 years). Seven patients had in-transit metastases on the lower extremities (70%), 2 patients on the head and neck (20%), and 1 patient on an upper extremity (10%). A total of 152 metastatic MCC lesions were treated with SMBT. All SMBT-treated lesions resolved clinically within a few weeks of therapy. The median follow-up was 34 months (range, 22-85 months). Two of 152 treated lesions recurred during the study period for a local control rate of 99%. Eight patients (80%) developed additional in-transit metastases outside the original SMBT fields. Five of these 8 patients underwent additional SMBT. At study conclusion, 3 patients (30%) are alive without disease, 3 patients (30%) are alive with disease, and 4 patients (40%) died of MCC. DISCUSSION Surface-mold computer-optimized high-dose-rate brachytherapy offers effective and durable palliation for cutaneous metastases of MCC, although it does not appear to alter disease course.

Background The use of many of the standard skin-directed mycosis fungoides (MF) therapies on facial skin may be limited by site-specific increased risks of side effects, excessive inflammation, and ocular toxicity. Objective Our study aimed to describe the levels of erythema, scale, and induration of facial lesions in MF before and after low-dose high-dose-rate surface applicator brachytherapy and to examine the overall clinical response to brachytherapy. Methods A total of 23 facial MF lesions in 10 patients were treated with high-dose-rate brachytherapy doses of 4 Gy per session for a total of 2 fractions at our multidisciplinary cutaneous oncology clinic between August 17, 2009, and March 12, 2012. Results In all 23 lesions, dramatic clinical improvement was observed. Patients were followed up for a median of 6.3 months. No recurrences were reported in the follow-up period. Limitations Long-term follow-up is lacking. Reassessment of all included patients at annual intervals for a period of at least 5 years is the authors' goal. Conclusion Low-dose high-dose-rate brachytherapy using custom-made surface molds is a highly efficacious therapy in the treatment of facial lesions in MF.

Studies on the formation and migration of colloidal iron sulfide in porous media were carried out using consolidated artificial alumina–kaolin cores sintered at 1500°C. The artificial alumina–kaolin cores were imbibed with a solution containing thioacetamide and ferrous ions and heated at 80°C to obtain the formation of FeS particles. Scanning electron micrographs showed particles less than 1 μm in diameter and aggregates of different sizes covering the surface of the porous media. Core flooding experiments showed that the migration of the fine FeS particles reduced the permeability of core and the injection of surfactant solutions at constant salinity restored the original permeability after the production of the redispersed iron sulfide particles, in some cases.

Background Merkel cell carcinoma (MCC) is a rare and lethal cutaneous neuroendocrine carcinoma. Imaging is crucial for accurate staging, which remains a strong predictor of survival, as well as earlier detection of recurrence and progression, which are common despite aggressive management. There is no consensus on the role of initial and subsequent imaging for MCC. Objective We sought to evaluate the use of 2-fluoro-[ 18 F]-deoxy-2-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the management of MCC. Methods In all, 270 FDG-PET/CT studies were performed in 97 patients with pathology-proven MCC at the Dana-Farber/Brigham and Women's Cancer Center, Boston, Mass, from August 2003 to December 2010. Results FDG-PET/CT scans were obtained as part of the initial (61 scans in 61 patients) and subsequent (209 scans in 79 patients) treatment strategies. MCCs were FDG-avid with a mean maximum standardized uptake value of primary lesions of 6.5 (range 1.3-12.9) and a mean maximum standardized uptake value of regional and distant metastases of 7.2 (range 1.5-9.9). FDG-PET/CT upstaged 16% of patients who underwent baseline scans. FDG-PET/CT studies showed that bone and bone-marrow metastases were more common than previously reported, and were often undetected by CT. Limitations Our study is limited by its retrospective design, and potential referral bias associated with a tertiary care center. Conclusions FDG-PET/CT performed as part of the initial management strategy tended to upstage patients with more advanced disease. FDG-PET/CT performed as part of the subsequent treatment strategy identified metastatic disease, particularly in bone/bone marrow, which was not seen on CT. FDG-PET/CT imaging is a valuable staging and restaging tool in MCC management.

Cutaneous T cell lymphoma (CTCL) is a cancer of skin-homing T cells with variants that include leukemic CTCL (L-CTCL), a malignancy of central memory T cells (T(CM)), and mycosis fungoides (MF), a malignancy of skin resident effector memory T cells (T(EM)). We report that low-dose alemtuzumab (αCD52) effectively treated patients with refractory L-CTCL but not MF. Alemtuzumab depleted all T cells in blood and depleted both benign and malignant T(CM) from skin, but a diverse population of skin resident T(EM) remained in skin after therapy. T cell depletion with alemtuzumab required the presence of neutrophils, a cell type frequent in blood but rare in normal skin. These data suggest that T(CM) were depleted because they recirculate between the blood and the skin, whereas skin resident T(EM) were spared because they are sessile and non-recirculating. After alemtuzumab treatment, skin T cells produced lower amounts of interleukin-4 and higher amounts of interferon-γ. Moreover, there was a marked lack of infections in alemtuzumab-treated L-CTCL patients despite the complete absence of T cells in the blood, suggesting that skin resident T(EM) can protect the skin from pathogens even in the absence of T cell recruitment from the circulation. Together, these data suggest that alemtuzumab may treat refractory L-CTCL without severely compromising the immune response to infection by depleting circulating T(CM) but sparing the skin resident T(EM) that provide local immune protection of the skin.

The sporogonic development of the malaria parasite takes place in the mosquito and a wide range of factors modulates it. Among those, the contents of the blood meal can influence the parasite development directly or indirectly through the mosquito response to the infection. We have studied the effect of a second blood meal in previously infected mosquitoes and the effect of anti-sporozoite immune serum on parasite development and mosquito response to the infection. The prevalence and intensity of infection and gene expression of both Plasmodium yoelii and Anopheles stephensi was analyzed. We verified that a second blood meal and its immune status interfere with parasite development and with Plasmodium and mosquito gene expression.

Mefloquine is an antimalarial drug with schizonticidal activity on blood-stage parasites. Studies of the role of mefloquine on the development of Plasmodium berghei ANKA in Anopheles stephensi have been carried out that showed a dose-dependent effect on the sporogonic cycle of these parasites, with changes in the numbers of oocysts and the extent of sporozoite invasion of salivary glands. In this study, we show that mefloquine-resistant P. berghei ANKA blood stage parasites could be selected through drug pressure during continuous cyclical transmission of Anopheles gambiae s.1.

8552 Background: Merkel cell carcinoma (MCC) is a rare (~1,500 cases per year) and highly aggressive (33% mortality) cutaneous neuroendocrine carcinoma that occurs in older white patients on the UV-exposed skin of the head, neck, and extremities. As a patient’s stage at presentation is a strong predictor of survival, and there is a high propensity for locoregional recurrence and distant progression, imaging remains crucial for initial and subsequent management. There is, however, no consensus on the timing or method of imaging for MCC. Methods: We retrospectively reviewed 270 2-fluoro-[18F]-deoxy-2-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) scans performed in 97 patients at the Dana-Farber/Brigham and Women’s Cancer Center from August 2003 to December 2010. Results: The mean SUVmax was 6.5 for primary tumors, 6.4 for regional lymph nodes, 7.2 for distant metastases (all sites), 8.0 for bone/bone marrow metastases, and 9.4 for non-regional metastases in those patients with no identified primary. PET/CT imaging performed for initial management tended to upstage patients with more advanced disease (50% of stage IIIB patients). Metastases to bone/bone marrow (12 patients, 38%) was the 2nd most common site of distant spread after non-regional lymph nodes (19 patients, 59%), followed by skin (8 patients, 25%), liver (6 patients, 19%), lung/pleura (5 patients, 16%), adrenal (3 patients, 9%), muscle (3 patients, 9%), pancreas (2 patients, 6%), and peritoneum (1 patient, 3%). In 10 of 12 patients, PET identified bone/bone marrow metastases that were not seen on CT imaging, which resulted in either upstaging or initiation of more targeted palliative therapy. Conclusions: Added value of PET over CT, such as in the detection of bone/bone marrow metastases, may lead to more accurate staging, and thus prognostication, as well as earlier detection of relapse and initiation of salvage treatment. Its use should be considered in the staging and restaging of MCC.

Irradiated sporozoites are generally thought to elicit protective immune responses that are parasite stage and species specific. But immunization with Plasmodium falciparum sporozoites delivered by the bite of infected mosquitoes protects an average of 60% mice from Plasmodium berghei sporozoite infection. Protection appears to be specific as P. falciparum sporozoite-immunized mice protected against P. berghei remain susceptible to Plasmodium yoelii sporozoite infection. Passively transferred immunoglobulin from P. falciparum sporozoite-immunized mouse serum protected naive mice against challenge with P. berghei sporozoites, indicating that cross-protection is mediated, at least in part, by anti-sporozoite antibody. Antibody-mediated protection may not be due to cross-reaction between P. falciparum and P. berghei CS proteins because mice immunized with the recombinant P. falciparum CS protein repeat vaccine candidate, R32tet32, remain susceptible to P. berghei sporozoite infection.

This is a case report of small cell lung cancer (SCLC) that underwent spontaneous regression. This was associated with severe neuropathy, which was unresponsive to therapy, including corticosteroids and plasmapheresis. We present here the case report and a brief review of the literature.

Merkel cell carcinomas (MCCs) are rare but highly malignant skin cancers associated with a recently described polyomavirus. MCC tumors were infiltrated by T cells, including effector, central memory, and regulatory T cells. Infiltrating T cells showed markedly reduced activation as evidenced by reduced expression of CD69 and CD25. Treatment of MCC tumors in vitro with IL-2 and IL-15 led to T-cell activation, proliferation, enhanced cytokine production, and loss of viable tumor cells from cultures. Expanded tumor-infiltrating lymphocytes showed TCR repertoire skewing and upregulation of CD137. MCC tumors implanted into immunodeficient mice failed to grow unless human T cells in the tumor grafts were depleted with denileukin diftitox, suggesting that tumor-specific T cells capable of controlling tumor growth were present in MCC. Both CD4(+) and CD8(+) FOXP3(+) regulatory T cells were frequent in MCC. Fifty percent of nonactivated T cells in MCC-expressed PD-1, a marker of T-cell exhaustion, and PD-L1 and PD-L2 were expressed by a subset of tumor dendritic cells and macrophages. In summary, we observed tumor-specific T cells with suppressed activity in MCC tumors. Agents that stimulate T-cell activity, block regulatory T cell function, or inhibit PD-1 signaling may be effective in the treatment of this highly malignant skin cancer.

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer with profound but poorly understood resistance to chemotherapy, which poses a significant barrier to clinical MCC treatment. Here we show that ATP-binding cassette member B5 (ABCB5) confers resistance to standard-of-care MCC chemotherapeutic agents and provide proof-of-principle that ABCB5 blockade can inhibit human MCC tumor growth through sensitization to drug-induced cell cytotoxicity. ABCB5 expression was detected in both established MCC lines and clinical MCC specimens at levels significantly higher than those in normal skin. Carboplatin- and etoposide-resistant MCC cell lines exhibited increased expression of ABCB5, along with enhanced ABCB1 and ABCC3 transcript expression. ABCB5-expressing MCC cells in heterogeneous cancers preferentially survived treatment with carboplatin and etoposide in vitro and in human MCC xenograft-bearing mice in vivo. Moreover, patients with MCC also exhibited enhanced ABCB5 positivity after carboplatin- and etoposide-based chemotherapy, pointing to clinical significance of this chemoresistance mechanism. Importantly, ABCB5 blockade reversed MCC drug resistance and impaired tumor growth in xenotransplantation models in vivo. Our results establish ABCB5 as a chemoresistance mechanism in MCC and suggest utility of this molecular target for improved MCC therapy.