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Cytology is a low-cost and non-invasive diagnostic procedure employed to support the diagnosis of a broad range of pathologies. Cells are harvested from tissues by aspiration or scraping, and it is still predominantly performed manually by medical or laboratory professionals extensively trained for this purpose. It is a time-consuming and repetitive process where many diagnostic criteria are subjective and vulnerable to human interpretation. Computer Vision technologies, by automatically generating quantitative and objective descriptions of examinations' contents, can help minimize the chances of misdiagnoses and shorten the time required for analysis. To identify the state-of-art of computer vision techniques currently applied to cytology, we conducted a Systematic Literature Review, searching for approaches for the segmentation, detection, quantification, and classification of cells and organelles using computer vision on cytology slides. We analyzed papers published in the last 4 years. The initial search was executed in September 2020 and resulted in 431 articles. After applying the inclusion/exclusion criteria, 157 papers remained, which we analyzed to build a picture of the tendencies and problems present in this research area, highlighting the computer vision methods, staining techniques, evaluation metrics, and the availability of the used datasets and computer code. As a result, we identified that the most used methods in the analyzed works are deep learning-based (70 papers), while fewer works employ classic computer vision only (101 papers). The most recurrent metric used for classification and object detection was the accuracy (33 papers and 5 papers), while for segmentation it was the Dice Similarity Coefficient (38 papers). Regarding staining techniques, Papanicolaou was the most employed one (130 papers), followed by HE (20 papers) and Feulgen (5 papers). Twelve of the datasets used in the papers are publicly available, with the DTU/Herlev dataset being the most used one. We conclude that there still is a lack of high-quality datasets for many types of stains and most of the works are not mature enough to be applied in a daily clinical diagnostic routine. We also identified a growing tendency towards adopting deep learning-based approaches as the methods of choice.

Cervical cancer is the second most common cancer type in women around the world. In some countries, due to non-existent or inadequate screening, it is often detected at late stages, making standard treatment options often absent or unaffordable. It is a deadly disease that could benefit from early detection approaches. It is usually done by cytological exams which consist of visually inspecting the nuclei searching for morphological alteration. Since it is done by humans, naturally, some subjectivity is introduced. Computational methods could be used to reduce this, where the first stage of the process would be the nuclei segmentation. In this context, we present a complete pipeline for the segmentation of nuclei in Feulgen-stained images using Convolutional Neural Networks. Here we show the entire process of segmentation, since the collection of the samples, passing through pre-processing, training the network, post-processing and results evaluation. We achieved an overall IoU of 0.78, showing the affordability of the approach of nuclei segmentation on Feulgen-stained images. The code is available in: https://github.com/luizbuschetto/feulgen_nuclei_segmentation., 7 pages, 8 figures (Figure 2 with "a" and "b"), conference paper accepted for presentation in XI Computer on the Beach (https://www.computeronthebeach.com.br/)

Persistent human papillomavirus (HPV) infection is an essential factor of cervical cancer. This study evaluated the analytical performance of restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) assay compared to PapilloCheck® microarray to identify human papilloma virus (HPV) in cervical cells. Three hundred and twenty-five women were analyzed. One sample was used for conventional cytology and another sample was collected using BD SurePath™ kit for HPV tests. Eighty samples (24.6%) were positive for HPV gene by PCR-Multiplex and were then submitted to PCR-RFLP and PapilloCheck® microarray. There was a genotyping agreement in 71.25% (57/80) on at least one HPV type between PCR-RFLP and PapilloCheck® microarray. In 22 samples (27.5%), the results were discordant and those samples were additionally analyzed by DNA sequencing. HPV 16 was the most prevalent HPV type found in both methods, followed by HPVs 53, 68, 18, 39, and 66 using PCR-RFLP analysis, and HPVs 39, 53, 68, 56, 31, and 66 using PapilloCheck® microarray. In the present study, a perfect agreement using Cohen's kappa (κ) was found in HPV 33 and 58 (κ=1), very good for HPV 51, and good for types 16, 18, 53, 59, 66, 68, 70, and 73. PCR-RFLP analysis identified only 25% (20/80) HPV coinfection, and PapilloCheck® microarray found 62.5% (50/80). Our Cohen's kappa results indicate that our in-house HPV genotyping testing (PCR-RFLP analysis) could be applied as a primary HPV test screening, especially in low income countries. If multiple HPV types are found in this primary test, a more descriptive test, such as PapilloCheck® microarray, could be performed.

The present study investigated the antinociceptive effects of Ocimum basilicum L. (Lamiaceae) leaf essential oil (LEO) and (-)-linalool (LIN) in formalin (2%)-, glutamate (25 µM)- and capsaicin (2.5 µg)- induced orofacial nociception models in mice. The involvement of these substances was further evaluated on the neuronal excitability of the hippocampal dentate gyrus. Male mice (n=8/group) were pretreated separately with LEO and by LIN (50, 100, and 200 mg/kg, i.p.), morphine (5 mg/kg, i.p.) and vehicle (saline + Tween 80 0.2%), before injection of nociceptive agent into the right upper lip (perinasal area). The LEO and LIN reduced the nociceptive face-rubbing behaviour in both phases on formalin test. LEO and LIN, at high doses, produced significantly antinociceptive effect in the capsaicin and glutamate tests. In hippocampal slices, LEO inhibited the population spike generated by stimulation of the hylus (antidromic stimulation), with an IC50 of 0.1±0.05 mg/mL. This response was reversibly blocked by lidocaine (0.5 mg/mL), a known voltage-dependent sodium channel antagonist and by LIN (0.5 mg/mL). Our results suggest that LEO and LIN modulate neurogenic and inflammatory pain in the tests of orofacial nociception induced by formalin, capsaicin and glutamate. Part of these effects may be associated with decreased peripheral and central neuronal excitability.

The central nervous system (CNS) depressant and anticonvulsant activities of citronellal (CT) were investigated in animal models. The CT in doses of 100, 200 and 400 mg/kg injected by i.p. route in mice caused a significant decrease in the motor activity of animals when compared with the control group. The highest dose of CT significantly reduced the remaining time of the animals on the Rota-rod apparatus up to 2 h. Additionally, CT at doses 100, 200 and 400 mg/ kg (i.p.) was also capable to promote an increase of latency for development of convulsions induced by pentylenetetrazole (PTZ). It was efficient in prevents the tonic convulsions induced by maximal electroshock (MES) in doses of 200 and 400 mg/kg, resulting in 30 and 40% of protection, respectively. This compound was also capable to promote an increase of latency for development of convulsions induced by picrotoxin (PIC) at 400 mg/kg. In the same way, the anticonvulsant effect of CT was affected by pretreatment with flumazenil, a selective antagonist of benzodiazepine site of GABA A receptor. These results suggest a possible CNS depressant and anticonvulsant activities.

BACKGROUND. Difficulties with cytologic diagnoses on fine-needle aspiration cytology (FNAC) of the liver can be overcome by the application of immunocytochemical panels applied on smears. The aim of the current study was to analyze the performance of a panel of monoclonal antibodies to differentiate hepatocellular carcinoma (HCC) from metastatic carcinoma (MC) or regenerative nodules, and to identify the to date unknown primary sites of carcinomas that had metastasized to the liver. METHODS. In a validating cohort study, 108 FNACs coin lesions in the liver were routinely evaluated applying immunocytochemistry as an ancillary method. All patients had confirmatory histologic and/or clinical follow-up. A total of 23 HCCs were analyzed for the distinction from MC or regenerative nodules applying a panel of HepPar1, a-fetoprotein, BerEP4, CD31, CD68, and Ki-67. A total of 85 cases of unknown primary tumor metastatic to the liver were used to identify the tumor sites applying a panel of CK5/6, CK7, CK20, CA 125, thyroid transcription factor-1 (TTF-1), and Cdx2. RESULTS. Typing accuracy to differentiate HCC from MC or regenerative nodules was 100% and 90.3%, respectively, to identify the primary tumor site of MC. In 23 cases, the site of the primary tumor remained clinically unknown. CONCLUSIONS. The application of immunocytochemical panels on the same slide used for microscopic diagnosis is a useful tool in the routine assessment of FNACs of the liver to discriminate HCCs from MC or regenerative nodules and for the identification of primary sites of MC. Their performance should be confirmed in a larger series of cases. Cancer (Cancer Cytopathol) 2007;111:259–68. � 2007 American Cancer Society.

Introduction: Cervical cancer is one of the most common diseases among women, and cause considerable morbidity and mortality. Considering that cervical cancer is an important neoplasia in northeastern Brazil, and the prevalence of high-risk human papillomavirus (HPV) is directly associated with it, this work had aimed to correlate the cytological and/or colposcopic findings with HPV infection status, and verify the performance of MY09/MY11 and GP5+/6+ primers for HPV detection. Material and method: Patients in this study were from Penedo-AL, a city with high level of poverty (poverty rate of 60.62%). Out of 70 patients with cytological and/or colposcopic changes, 32 agreed to participate in the study. Results: Regarding cytology, 21 (30%) patients presented atypical squamous cells of undetermined significance (ASC-US); 20 (29%), atypical glandular cells of undetermined significance (AGUS); 12 (17%), low-grade intraepithelial lesion (LSIL); five (7%), high-grade intraepithelial lesion (HSIL); and 12 (17%), positive colposcopy. From these, 27 (84%) presented the band gene encoding for human ß-globin. From the 27 patients, eight (30%) were positive for HPV. The results showed that the deoxyribonucleic acid (DNA) of HPV was detected in 15% and 30% by using MY-PCR and GP +-PCR, respectively. Conclusion: This study suggests that more than one type of oligonucleotide primer should be used in clinical samples to increase sensitivity for the detection of HPV. Introdução: O câncer cervical é uma das doenças mais frequentes entre mulheres, e causa considerável morbidade e mortalidade. Com base nos fatos de que o câncer cervical é uma neoplasia importante no nordeste brasileiro, e que a prevalência do papilomavírus humano (HPV) de alto risco está diretamente associado a ele, este trabalho teve como objetivos correlacionar os achados citológicos e/ou colposcópicos com status de infecção de HPV e verificar o desempenho dos iniciadores MY09/MY11 e GP5+/GP6+ para detecção do HPV. Material e métodos: Os pacientes deste estudo foram de Penedo-AL, uma cidade com elevado nível de pobreza (índice de pobreza de 60,62%). Do total de 70 pacientes com alterações citológicas e/ou colposcópicas, 32 aceitaram participar do estudo. Resultados: Com relação a citologia, 21 (30%) pacientes apresentaram células escamosas atípicas de significado indeterminado (ASC-US); 20 (29%), células glandulares atípicas de significado indeterminado (AGUS); 12 (17%), lesão intraepitelial de baixo grau (LSIL); cinco (7%), lesão intraepitelial de alto grau (HSIL); e 12 (17%), colposcopia positiva. Destas, 27 (84%) apresentaram banda do gene que codifica para ß-globina humana. Das 27 pacientes, oito (30%) apresentaram positividade para o HPV. Os resultados mostraram que o ácido desoxirribonucleico (DNA) do HPV foi detectado em 15% e 30%, usando MY-PCR e GP +-PCR, respectivamente. Conclusão: Este estudo sugere que mais de um tipo de iniciador de oligonucleotídeo deve ser utilizado em amostras clínicas para aumentar a sensibilidade na detecção do HPV.

The Psychosocial Care Center (CAPS) is a community-based mental health service in Brazil, which aims to promote the psychosocial rehabilitation of patients. Accordingly, this study describes the drug use evaluation in a primary mental health service in Northeast of Brazil. Setting: CAPS ‘Valter Correia’, São Cristovão, Sergipe, Brazil. Methods: A cross-sectional study was conducted between August 2009 and May 2010. Initially, Medical records were reviewed and evaluated. Then, we applied interviews with the patients (and/or their informal/family caregivers) attended at the CAPS. Informations were obtained regarding to demographic and clinical features, diagnoses and drugs prescribed. All patients registered in the CAPS were included in the study. The results were statistically analyzed using the EpiInfo and were compared with results from literature. Results: The CAPS ‘Valter Correia’ consists of 101 registered patients, the majority were male (58.4%), illiterate (51.5%), without monthly income (49.5%) and the average age of them 42.2 years (SD = 12.0). Schizophrenia was the most frequent mental disorder (31.5%). The average number of medications by patients was 3.11 (SD = 1.41), and the older group of patients (75-80 years) presented the largest consumption of medications (5.50 drugs/patient). The psychiatric drug class most frequently prescribed was antipsychotics (44.8%). Angiotensin-converting enzyme inhibitors were the most prevalent non-psychiatric therapeutic class (15.8%). It was detected 133 drug-drug interactions (3.0% mild, 54.1% moderate, 29.3% severe and 13.5% contraindicated). Conclusion: The results revealed the need for monitoring the pharmacotherapy of patients with mental disorders to encourage the rational use of medications. O Centro de Atenção Psicossocial (CAPS) é um serviço de saúde mental de base comunitária no Brasil, que visa promover a reabilitação psicossocial dos pacientes. O presente estudo descreve a avaliação do uso de medicamentos em um service de saúde mental primário no Nordeste do Brasil. Ambiente: CAPS «Valter Correia», São Cristovão, Sergipe, Brasil. Métodos: Estudo transversal foi realizado entre agosto de 2009 e maio de 2010. Inicialmente, os registros médicos foram revisados e avaliados. Em seguida, foram realizadas entrevistas com os pacientes (e/ou seus cuidadores) atendidos no CAPS. Informações foram obtidas sobre as características demográficas e clínicas, diagnósticos e medicamentos prescritos. Todos os pacientes cadastrados no CAPS foram incluídos no estudo. Os resultados foram analisados estatisticamente utilizando o programa EpiInfo e foram comparados com os resultados da literatura. Resultados: O CAPS "Valter Correia" é composto por 101 pacientes cadastrados, a maioria do sexo masculino (58,4%), analfabetos (51,5%), sem renda mensal (49,5%) e a média de idade deles era de 42,2 anos (DP = 12,0). A esquizofrenia foi o transtorno mental mais freqüente (31,5%). O número médio de medicamentos por pacientes foi de 3,11 (DP = 1,41), e o grupo de pacientes mais velhos (75-80 anos) apresentou o maior consumo de medicamentos (5,50 medicamentos/paciente). A classe de medicamentos psiquiátricos mais prescrita foi a dos antipsicóticos (44,8%). A classe dos inibidores da enzima conversora da angiotensina foi a mais prevalente classe não-psiquiátrica (15,8%). Foram detectadas 133 interações medicamentosas fármaco-fármaco (3,0% de severidade leve, 54,1% moderada, 29,3% grave e 13,5% contra-indicada). Conclusão: Os resultados demonstram a necessidade de acompanhamento da farmacoterapia de pacientes com transtornos mentais para incentivar o uso racional de medicamentos.

Purpose: Recent studies have detected aberrant promoter methylation of adenomatous polyposis coli promoter 1 A (APC), cyclin-dependent kinase inhibitor-2A (p16INK4a), retinoic acid receptor β2, and RAS association domain family protein 1 (RASSF1A) in bronchial aspirates and suggested their use as biomarkers for lung cancer diagnostics. The purpose of this study was to validate these candidate marker genes in a retrospective cohort study. Experimental Design: Bronchial aspirates collected from a cohort comprising 247 patients with suspected lung cancer were investigated retrospectively regarding aberrant promoter methylation using a quantitative methylation-specific real-time PCR (QMSP). Results: Eighty-nine patients were diagnosed with primary lung cancer, 102 had benign lung disease, and 56 showed miscellaneous other conditions. A panel consisting of APC, p16INK4a, and RASSF1A emerged as useful combination. This panel detected aberrant methylation in bronchial aspirates of 22 of 35 (63%) and 21 of 44 (44%) centrally and peripherally located primary lung cancers, respectively. Bronchial aspirates also showed aberrant methylation in 5 of 7 (71%) patients with a recurrent lung cancer and in 8 of 30 (27%) cases without tumor recurrence. In contrast, only 1 of 102 patients with benign lung disease displayed a (false) positive test result. Rarely, aberrant methylation was found in patients with other malignancies (3 of 16). The QMSP assay correctly confirmed lung cancer in 8 of 12 (67%) cases with an ambiguous cytology. Moreover, it disclosed 9 of 26 (35%) of peripheral tumors lacking simultaneous cytologic or histologic diagnosis of malignancy. Conclusions: Our findings suggest that the QMSP assay could be applied as a reflex test in cases of suspected lung cancer that defy a definite diagnosis by conventional methods. Thus, the assay could be a useful diagnostic adjunct especially regarding peripheral tumors.

The anti-inflammatory and redox protective effects of the citronellal (CT) were evaluated using in vivo and in vitro tests. Intraperitoneal (i.p.) administration of CT (50, 100, and 200 mg/kg) inhibited (p < 0.05) the carrageenan-induced leukocyte migration to the peritoneal cavity. Additionally, the carrageenan- and arachidonic acid-induced rat hind paw edema was significantly inhibited (p < 0.05) by i.p. administration of 100 and 200 mg/kg of the compound. When the redox activity was evaluated, CT (200 mg/kg) significantly reduced hepatic lipoperoxidation (p < 0.001), as well as oxidation of plasmatic (p < 0.05) and hepatic (p < 0.01) proteins. The results of the present study support the hypothesis that CT possesses anti-inflammatory and redox protective activities. It is suggested that its effects are associated with the inhibition of the enzymes in the arachidonic acid pathway, which prevent cell migration by inhibiting leukotriene production, edema formation and the increase of reactive oxygen species in tissues. Therefore, CT is of potential benefit to manage inflammatory disorders and correlated damages caused by oxidant agents.