Deep learning for diagnosis and survival prediction in soft tissue sarcoma.

BACKGROUND: Clinical management of soft tissue sarcoma (STS) is particularly challenging. Here, we used digital pathology and deep learning (DL) for diagnosis and prognosis prediction of STS. PATIENTS AND METHODS: Our retrospective, multicenter study included a total of 506 histopathological slides from 291 patients with STS. The Cancer Genome Atlas cohort (240 patients) served as training and validation set. A second, multicenter cohort (51 patients) served as an additional test set. The use of the DL model (DLM) as a clinical decision support system was evaluated by nine pathologists with different levels of expertise. For prognosis prediction, 139 slides from 85 patients with leiomyosarcoma (LMS) were used. Area under the receiver operating characteristic (AUROC) and accuracy served as main outcome measures. RESULTS: The DLM achieved a mean AUROC of 0.97 (±0.01) and an accuracy of 79.9% (±6.1%) in diagnosing the five most common STS subtypes. The DLM significantly improved the accuracy of the pathologists from 46.3% (±15.5%) to 87.1% (±11.1%). Furthermore, they were significantly faster and more certain in their diagnosis. In LMS, the mean AUROC in predicting the disease-specific survival status was 0.91 (±0.1) and the accuracy was 88.9% (±9.9%). Cox regression showed the DLM's prediction to be a significant independent prognostic factor (P = 0.008, hazard ratio 5.5, 95% confidence interval 1.56-19.7) in these patients, outperforming other risk factors. CONCLUSIONS: DL can be used to accurately diagnose frequent subtypes of STS from conventional histopathological slides. It might be used for prognosis prediction in LMS, the most prevalent STS subtype in our cohort. It can also help pathologists to make faster and more accurate diagnoses. This could substantially improve the clinical management of STS patients.

Pelvimetry of multiparous Nellore cows in the cycling and early puerperal stages / Pelvimetria de vacas pluríparas da raça Nellore em estágio cíclico e início do puerpério

Pelvis is an osteoligamentous complex, which is classified as dolichopellic in ruminants. Impairments linked to incompatibility of pelvic canal and fetal size is directly related to pelvic anatomy and disposition. Heritability of pelvic area characteristics varies from moderate to high, demonstrating its importance for animal selection. Pelvimetry can be performed through direct and indirect methods that were accessed in this study aiming to establish a correlation between internal and external pelvic dimensions in multiparous Nellore cows (26 animals) at cycling and early puerperal (up to 30 days postpartum) reproductive stages. Pelvic dimensions measured by descriptive analysis were higher at early puerperal stage. Strong Pearson's correlation was determined between internal and external pelvic dimensions, between reproductive stages, and between pelvic girdle area and internal pelvic area. Significant Tukey's test differences between animals in internal and external dimensions were also found. According to the results, the pelvic anatomy of Nellore cows varies according to their reproductive stage. We detach that and provide data regarding the use of internal pelvic area for animal selection studies on this breed is determined and should be measured using the proposed formula, since it can confirm statistical differences in the areas of pelvic components between animals in the cycling and early puerperal stages.(AU)

A pelve é considerada um complexo osteoligamentoso, classificada como dolicopélvica em ruminantes. Prejuízos ligados à incompatibilidade canal pélvico/tamanho fetal relacionam-se diretamente à anatomia e disposição pélvica. A característica de área pélvica apresenta herdabilidade variando de moderada a alta, indicando sua importância na seleção animal. A pelvimetria inclui formas direta e indireta. Neste estudo utilizaram-se vinte e seis vacas multíparas, da raça Nelore, agrupadas de acordo com o estágio reprodutivo, cíclico e em início de estágio puerperal (até 30 dias pós-parto). Através deste, objetivou-se evidenciar a relação das medidas pélvicas internas e externas nos diferentes períodos reprodutivos e coletar obter dados referentes a utilização da área interna do hexágono no estudo pelvimétrico dessa espécie em estágio cíclico ou puerperal. Para tanto, realizou-se, a pelvimetria direta e indireta. Os resultados obtidos, pela análise descritiva, foram maiores para animais em início de estágio puerperal. Por meio da correlação de Pearson podem-se observar fortes correlações entre mensurações pélvicas internas e externas, também entre os grupos propostos, e forte correlação entre elipse pélvica e área interna do hexágono. Pelo teste Tukey diferenças significativas tanto em medidas internas e externas puderam ser demonstradas. Conclui-se que as condições anatômicas da pelve variam de acordo com o estágio reprodutivo do animal, que aferição da área pélvica utilizando a formula proposta para área do hexágono interno é relevante pois foi possível comprovar a diferenças estatísticas de áreas nas fases cíclica e puerperal.(AU)

[Prognostic significance of immune cell infiltrates in tumor pathology]. / Prognostische Bedeutung von Immunzellinfiltraten in der Tumorpathologie.

BACKGROUND: The quantity, distribution, activation status, cytokine profile, and spatial distribution of tumor-infiltrating immune cells have prognostic value and may be predictive of response to immunotherapies. OBJECTIVES: A survey of relevant immune cell populations including their prognostic significance in the most common types of tumors. METHODS: Nonsystematic assessment and a discussion of studies that were conducted to estimate the prognostic significance of certain immune cell subsets and the methodical approaches used. RESULTS: For many tumor entities, prognostically favorable and unfavorable immune cell populations can be differentiated. However, nonspecific cell markers that may partly summarize antithetic immune cell subsets can be employed. Differences in sampling procedures and the determination of cut-off levels further limit the comparability of the studies carried out so far. CONCLUSION: The phenotypic and functional heterogeneity of tumor-infiltrating immune cells requires the use of cell subset-specific antibodies and antibody combinations. Furthermore, harmonized assessment routines, validation studies, and meta-analyses are important prerequisites for potential diagnostic implementation.

An observational study of the relationship between Capacity for Care as an animal shelter management model and cat health, adoption and death in three animal shelters.

Animal shelters struggle to function at their 'right size' in terms of physical, staffing and outcome capacity, especially with seasonal fluctuations in cat intake. To address this, a Capacity for Care (C4C) management model was devised to balance health and welfare requirements of all animals while maintaining or improving goals for positive outcomes, such as adoption or transfer. In this observational study of three shelters, applying the C4C management system gave each organization an optimal average daily shelter cat population target (to be achieved through proactive length of stay management) and helped each shelter to increase the size of their feline housing units. Pre- and post-C4C implementation data were evaluated to determine impact on average monthly isolation ward populations and cat outcomes such as adoptions and shelter deaths (euthanasia/died). Improved outcomes including increased adoption probability, decreased shelter death probability and fewer cats requiring infectious disease isolation were seen after C4C institution. Results suggest that implementation of this management model could help other shelters achieve similar results.

Comparative hematological analysis of Morada Nova and Santa Inês ewes in all reproductive stages / Análise hematológica comparativa de ovelhas Morada Nova e Santa Inês em todos os estágios reprodutivos

Hematologic analysis provides reliable information on the health status of animals. It is an important variable in the assessment of adaptive and productive capacity of breeds under unfavorable environmental conditions. It is an assessment that combined with other genetic and environmental factors and management can become useful for the future sustainability of mainstream agriculture in a hot environment. Adaptive capacity is affected by some factors such as breed, pregnancy and lactation. Therefore, hematological profile is an important indicator of animal health and production. The objective of this study was to perform the comparative hematological analysis of Santa Inês and Morada Nova breeds (native ewes from Brazil) in all different reproductive stages. Twenty Santa Ines and 20 Morada Nova sheep distributed in a completely randomized design in a split-plot arrangement over time were used. To obtain blood counts, blood samples were collected by jugular venipuncture every 14 days, always in the morning, before the animals were released into the pasture. The Morada Nova breed had higher hemoglobin and total leukocyte count than Santa Inês breed. Regarding the influence of pregnancy and puerperium on the eritrogram, there was an increment in red blood cell, hemoglobin and packed cell volume of both breeds in middle pregnancy. However, had a reduction in late pregnancy. There were a reestablishment of the blood cell counts during the puerperium period. It was verified an increase on neutrophil: lymphocyte ratio indicated that ewes in the late pregnancy, postpartum and puerperium were under stress conditions compared to others reproductive stages. The total plasma proteins also increased during this period to compensate for the high nutritional requirements of the fetus, and these levels remained high until the end of the puerperal phase, when the lambs were weaned. The pregnancy and puerperium influenced all erythrocyte indices and changed the total leukocyte count.(AU)

A análise hematológica fornece informação confiável sobre a saúde dos animais. É uma variável importante na avaliação da capacidade adaptativa e produtiva das raças sob condições ambientais desfavoráveis. É uma avaliação que aliada a outros fatores genéticos, ambientais e de manejo pode se tornar cada vez mais útil para a sustentabilidade futura da agricultura convencional em um ambiente quente. A capacidade adaptativa é afetada por alguns fatores como raça, gestação e lactação. Portanto, o perfil hematológico é um indicador importante da saúde e produção animal. O objetivo deste estudo foi realizar a análise hematológica comparativa de ovelhas Morada Nova e Santa Inês (ovelhas nativas do Brasil) em todos os estágios reprodutivos. Foram utilizadas 20 ovelhas Santa Inês e 20 Morada Nova distribuídas em um delineamento inteiramente casualizado, em parcelas subdivididas e medidas repetidas no tempo. Para a análise do sangue, foram coletadas amostras por venopunção jugular a cada 14 dias, sempre colhidas pela manhã, antes que os animais fossem soltos no pasto. A raça Morada Nova apresentou maior teor de hemoglobina e contagem total de leucócitos que a raça Santa Inês. Em relação à influência da gestação e do puerpério sobre o eritrograma, observou-se que houve um incremento dos valores da contagem dos eritrócitos, hematócrito e hemoglobina até o terço médio da gestação, reduzindo no final da gestação e restabelecendo novamente no período puerperal. Foi verificado um aumento na relação neutrófilo/linfócito indicando que ovelhas no final da gestação, no pós-parto e puerpério estavam sob condição de estresse comparado com os outros estágios reprodutivos. As proteínas plasmáticas totais também aumentaram durante o período gestacional para compensar os altos requisitos nutricionais do feto, e estes níveis permaneceram elevados até ao final da fase de puerpério quando os cordeiros foram desmamados. A gestação e o puerpério influenciaram todos os índices eritrocitários com alteração da contagem total de leucócitos.(AU)

CXCR4 and CXCR7 form a functional receptor unit for SDF-1/CXCL12 in primary rodent microglia.

AIMS: Microglial cells have been originally identified as a target for the CXC chemokine, SDF-1, by their expression of CXCR4. More recently, it has been recognized that SDF-1 additionally binds to CXCR7, which depending on the cell type acts as either a nonclassical, a classical or a scavenger chemokine receptor. Here, we asked whether primary microglial cells additionally express CXCR7 and if so how this chemokine receptor functions in this cell type. METHODS: CXCR4 and CXCR7 expression was analysed in cultured rat microglia and in the brain of animals with permanent occlusion of the middle cerebral artery (MCAO) by either Western blotting, RT-PCR, flow cytometry and/or immunocytochemistry. The function of CXCR4 and CXCR7 was assessed in the presence of selective antagonists. RESULTS: Cultured primary rat microglia expressed CXCR4 and CXCR7 to similar levels. Treatment with SDF-1 resulted in the activation of Erk1/2 and Akt signalling. Erk1/2 and Akt signalling were required for subsequent SDF-1-dependent promotion of microglial proliferation. In contrast, Erk1/2 signalling was sufficient for SDF-1-induced migration of microglial cells. Both SDF-1-dependent signalling and the resulting effects on microglial proliferation and migration were abrogated following pharmacological inactivation of either CXCR4 or CXCR7. Moreover, treatment of cultured microglia with lipopolysaccharide resulted in the co-ordinated up-regulation of CXCR4 and CXCR7 expression. Likewise, reactive microglia accumulating in the area adjacent to the lesion core in MCAO rats expressed both CXCR4 and CXCR7. CONCLUSIONS: CXCR4 and CXCR7 form a functional receptor unit in microglial cells, which is up-regulated during activation of microglia both in vitro and in vivo.

Reproductive effects of estradiol cypionate in postparturient dairy cows.

OBJECTIVE: To determine the effects of estradiol cypionate (ECP) on measures of reproductive efficiency in postparturient dairy cows. DESIGN: Randomized clinical trial. ANIMALS: 273 cows in a single herd in California. PROCEDURE: Twenty-four hours after parturition, 122 cows were treated with ECP (4 mg, IM); the remaining 151 cows were untreated controls. Percentages of cattle with abnormal findings during uterine palpation 27 to 40 days after parturition were compared between groups, along with days to first artificial insemination (AI), percentages of cows that were not pregnant after the first AI, and days to pregnancy. RESULTS: Treatment with ECP did not have a significant effect on whether results of uterine palpation 27 to 40 days after parturition were abnormal, days to first AI, or odds that a cow would be pregnant after the first AI. Treatment with ECP appeared to have a negative effect on days to pregnancy (hazard ratio, 0.72) CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that prophylactic administration of ECP during the early postparturient period in dairy cows did not have measurable beneficial effects on reproductive efficiency.

Some aspects of dermatophytoses seen at University Hospital in Florianópolis, Santa Catarina, Brazil.

Dematophytoses comprise mycoses which are very frequently diagnosed in the routine of clinical laboratories of Florianópolis, like any other Brazilian cities. However, no clinical or epidemiological studies data have been published for that city so far. To partially clarify these questions, we carried out a study on this subject on patients who sought the mycology services of Hospital of Federal University of Santa Catarina, from January 1995 to November 1996. The most prevalent dermatophyte was Trichophyton rubrum (58.6%), followed by T. mentagrophytes (25.3%), Epidermophyton floccosum (7.2%), Microsporum canis (4.8%), T. tonsurans T. violaceum (1.6%) and M. gypseum (0.8%). The prevalence of T. mentagrophytes was significantly higher for females than for males, with a frequency of 37.3% and 16.0% respectively, which could be explained by higher infection of T. mentagrophytes in feet and nails, which were percentually more affected in females than in males. These results suggest that, in general, the clinical and epidemiological characteristics of dermatophytoses of our study have similar patterns of those occurring in other southern and southeastern Brazilian cities.