A educação de jovens e adultos no município de Bagé/RS e as percepções dos atores sociais sobre a educação empreendedora no território

This paper presents an analysis of the perception of social actors regarding the Entrepreneurial Education proposed through the Young and Adult Education (EJA) in the territory of Bagé/RS. A qualitative research was carried out using data collection techniques such as bibliographic research and interviews, involving 59 subjects, among them students, technicians and managers of public schools that offer EJA in the municipality of Bagé/RS. The specialised bibliography reiterates that initiatives related to entrepreneurship, when inserted into the formal teaching and learning process, improve the quality of life, benefit less privileged communities and bring about processes of personal transformation. Although some students have expressed little motivation and/or interest in entrepreneurship, it is observed that, for the most part, those who had the opportunity of contact with Entrepreneurship Education showed satisfaction and recognition as to the importance of this subject. Moreover, the involvement, commitment and motivation of all the social actors analysed were decisive for the implementation of Entrepreneurship Education in the analysed territory.  Keywords: Entrepreneurship Education. Regional actors. Youth and Adult Education.Este artículo presenta un análisis de la percepción de los actores sociales sobre la Educación Emprendedora propuesta a través de la Enseñanza de Jóvenes y Adultos (EJA) en el territorio de Bagé/RS. Se realizó una investigación cualitativa con el uso de técnicas de recolección de datos como investigación bibliográfica y entrevistas, involucrando a 59 sujetos, entre ellos estudiantes, técnicos y gerentes de escuelas públicas que ofrecen EJA en el municipio de Bagé/RS. La bibliografía especializada refuerza que las iniciativas relacionadas con el emprendimiento, cuando se insertan en el proceso de enseñanza y aprendizaje formal amplían la calidad de vida, benefician a las comunidades menos privilegiadas y concretan procesos de transformación personal. Si bien algunos estudiantes han expresado poca motivación y/o interés por el emprendimiento, se observa que, en su mayoría, quienes tuvieron la oportunidad de contactar con Educación Emprendedora evidenciaron satisfacción y reconocimiento con respecto a la importancia de este tema. Además, la implicación, compromiso y motivación de todos los actores sociales analizados fue determinante para la efectividad de la Educación Emprendedora en el territorio analizado. Palabras clave: Educación emprendedora. Actores regionales. Educación de jóvenes y adultos.O presente artigo realiza uma análise sobre a percepção de atores sociais quanto à Educação Empreendedora proposta por meio do Ensino de Jovens e Adultos (EJA) no território de Bagé/RS. Realizou-se uma pesquisa de caráter qualitativo com a utilização de técnicas de coleta de dados como a pesquisa bibliográfica e entrevistas, envolvendo 59 sujeitos, entre eles alunos, técnicos e gestores de escolas públicas que oferecem o EJA no município de Bagé/RS. A bibliografia especializada reitera que iniciativas relacionadas ao empreendedorismo, quando inseridas no processo de ensino e aprendizagem formal, ampliam a qualidade de vida, beneficiam comunidades menos privilegiadas e concretizam processos de transformação pessoal. Embora alguns alunos tenham manifestado pouca motivação e/ou interesse em empreender, observa-se que, em sua maioria, aqueles que tiveram a oportunidade de contato com a Educação Empreendedora evidenciaram possuir satisfação e reconhecimento quanto à importância desta temática. Outrossim, o envolvimento, o comprometimento e a motivação de todos os atores sociais analisados foi determinante para a efetivação da Educação Empreendedora no território analisado.  Palavras-chave: Educação Empreendedora. Atores regionais. Educação de Jovens e Adultos

Intestinal Microbiota Shifts towards Elevated Commensal Escherichia coli Loads Abrogate Colonization Resistance against Campylobacter jejuni in Mice

Background: The zoonotic pathogen Campylobacter jejuni is a leading cause of bacterial foodborne enterocolitis in humans worldwide. The understanding of immunopathology underlying human campylobacteriosis is hampered by the fact that mice display strong colonization resistance against the pathogen due to their host specific gut microbiota composition. Methodology/Principal Findings: Since the microbiota composition changes significantly during intestinal inflammation we dissected factors contributing to colonization resistance against C. jejuni in murine ileitis, colitis and in infant mice. In contrast to healthy animals C. jejuni could stably colonize mice suffering from intestinal inflammation. Strikingly, in mice with Toxoplasma gondii-induced acute ileitis, C. jejuni disseminated to mesenteric lymphnodes, spleen, liver, kidney, and blood. In infant mice C. jejuni infection induced enterocolitis. Mice suffering from intestinal inflammation and C. jejuni susceptible infant mice displayed characteristical microbiota shifts dominated by increased numbers of commensal Escherichia coli. To further dissect the pivotal role of those distinct microbiota shifts in abrogating colonization resistance, we investigated C. jejuni infection in healthy adult mice in which the microbiota was artificially modified by feeding live commensal E. coli. Strikingly, in animals harboring supra-physiological intestinal E. coli loads, colonization resistance was significantly diminished and C. jejuni infection induced enterocolitis mimicking key features of human campylobacteriosis. Conclusion/Significance: Murine colonization resistance against C. jejuni is abrogated by changes in the microbiot

Novel Murine Infection Models Provide Deep Insights into the “Ménage à Trois” of Campylobacter jejuni, Microbiota and Host Innate Immunity

BACKGROUND: Although Campylobacter jejuni-infections have a high prevalence worldwide and represent a significant socioeconomic burden, it is still not well understood how C. jejuni causes intestinal inflammation. Detailed investigation of C. jejuni-mediated intestinal immunopathology is hampered by the lack of appropriate vertebrate models. In particular, mice display colonization resistance against this pathogen. METHODOLOGY/PRINCIPAL FINDINGS: To overcome these limitations we developed a novel C. jejuni-infection model using gnotobiotic mice in which the intestinal flora was eradicated by antibiotic treatment. These animals could then be permanently associated with a complete human (hfa) or murine (mfa) microbiota. After peroral infection C. jejuni colonized the gastrointestinal tract of gnotobiotic and hfa mice for six weeks, whereas mfa mice cleared the pathogen within two days. Strikingly, stable C. jejuni colonization was accompanied by a pro-inflammatory immune response indicated by increased numbers of T- and B-lymphocytes, regulatory T-cells, neutrophils and apoptotic cells, as well as increased concentrations of TNF-α, IL-6, and MCP-1 in the colon mucosa of hfa mice. Analysis of MyD88(-/-), TRIF(-/-), TLR4(-/-), and TLR9(-/-) mice revealed that TLR4- and TLR9-signaling was essential for immunopathology following C. jejuni-infection. Interestingly, C. jejuni-mutant strains deficient in formic acid metabolism and perception induced less intestinal immunopathology compared to the parental strain infection. In summary, the murine gut flora is essential for colonization resistance against C. jejuni and can be overcome by reconstitution of gnotobiotic mice with human flora. Detection of C. jejuni-LPS and -CpG-DNA by host TLR4 and TLR9, respectively, plays a key role in immunopathology. Finally, the host immune response is tightly coupled to bacterial formic acid metabolism and invasion fitness. CONCLUSION/SIGNIFICANCE: We conclude that gnotobiotic and "humanized" mice represent excellent novel C. jejuni-infection and -inflammation models and provide deep insights into the immunological and molecular interplays between C. jejuni, microbiota and innate immunity in human campylobacteriosis

Cytotoxicity of Catalysed Silicone Resin Coatings for Smart Biomedical Devices

Equipping medical devices with smart technologies holds great potential for the development of modern medical products. The development requires the identification of new integration strategies and the research of new material combinations due to the miniaturization of systems and increasing production figures. The realization of Smart Biomedical Devices requires a sufficient barrier effect (bioprotection) by appropriate encapsulation of the electronic components. Thinnest polymer coatings have proven to be suitable for conformal encapsulation. The aim of the study was to investigate the fundamental suitability of thin-film lacquers added with catalysts as coating materials for electronic systems with regard to their biological use. Due to long curing times of up to 14 days, eight different catalysts based on different chemical structures were added to the coating materials and their influence on a cytotoxic effect was investigated. A non-cytotoxic effect was observed for the organometallic catalysts based on tin, zirconium, titanium, bismuth, and tertiary amine. Most were resistant to steam sterilization. The curing time of the non-cytotoxic coatings could be significantly reduced by the addition of catalysts. The shortening of process times is an important economic aspect in the production of mass-produced Smart Biomedical Devices

Explainable convolutional neural networks for assessing head and neck cancer histopathology

Abstract Purpose Although neural networks have shown remarkable performance in medical image analysis, their translation into clinical practice remains difficult due to their lack of interpretability. An emerging field that addresses this problem is Explainable AI. Methods Here, we aimed to investigate the ability of Convolutional Neural Networks (CNNs) to classify head and neck cancer histopathology. To this end, we manually annotated 101 histopathological slides of locally advanced head and neck squamous cell carcinoma. We trained a CNN to classify tumor and non-tumor tissue, and another CNN to semantically segment four classes - tumor, non-tumor, non-specified tissue, and background. We applied Explainable AI techniques, namely Grad-CAM and HR-CAM, to both networks and explored important features that contributed to their decisions. Results The classification network achieved an accuracy of 89.9% on previously unseen data. Our segmentation network achieved a class-averaged Intersection over Union score of 0.690, and 0.782 for tumor tissue in particular. Explainable AI methods demonstrated that both networks rely on features agreeing with the pathologist’s expert opinion. Conclusion Our work suggests that CNNs can predict head and neck cancer with high accuracy. Especially if accompanied by visual explanations, CNNs seem promising for assisting pathologists in the assessment of cancer sections

The modified Polsby–Popper score, a novel quantitative histomorphological biomarker and its potential to predict lymph node positivity and cancer‐specific survival in oral tongue squamous cell carcinoma

Abstract Background The significance of different histological spreading patterns of tumor tissue in oral tongue squamous cell carcinoma (TSCC) is well known. Our aim was to construct a numeric parameter on a continuous scale, that is, the modified Polsby–Popper (MPP) score, to describe the aggressiveness of tumor growth and infiltration, with the potential to analyze hematoxylin and eosin‐stained whole slide images (WSIs) in an automated manner. We investigated the application of the MPP score in predicting survival and cervical lymph node metastases as well as in determining patients at risk in the context of different surgical margin scenarios. Methods We developed a semiautomated image analysis pipeline to detect areas belonging to the tumor tissue compartment. Perimeter and area measurements of all detected tissue regions were derived, and a specific mathematical formula was applied to reflect the perimeter/area ratio in a comparable, observer‐independent manner across digitized WSIs. We demonstrated the plausibility of the MPP score by correlating it with well‐established clinicopathologic parameters. We then performed survival analysis to assess the relevance of the MPP score, with an emphasis on different surgical margin scenarios. Machine learning models were developed to assess the relevance of the MPP score in predicting survival and occult cervical nodal metastases. Results The MPP score was associated with unfavorable tumor growth and infiltration patterns, the presence of lymph node metastases, the extracapsular spread of tumor cells, and higher tumor thickness. Higher MPP scores were associated with worse overall survival (OS) and tongue carcinoma‐specific survival (TCSS), both when assessing all pT‐categories and pT1‐pT2 categories only; moreover, higher MPP scores were associated with a significantly worse TCSS in cases where a cancer‐free surgical margin of <5 mm could be achieved on the main surgical specimen. This discriminatory capacity remained constant when examining pT1‐pT2 categories only. Importantly, the MPP score could successfully define cases at risk in terms of metastatic disease in pT1‐pT2 cancer where tumor thickness failed to exhibit a significant predictive value. Machine learning (ML) models incorporating the MPP score could predict the 5‐year TCSS efficiently. Furthermore, we demonstrated that machine learning models that predict occult cervical lymph node involvement can benefit from including the MPP score. Conclusions We introduced an objective, quantifiable, and observer‐independent parameter, the MPP score, representing the aggressiveness of tumor growth and infiltration in TSCC. We showed its prognostic relevance especially in pT1‐pT2 category TSCC, and its possible use in ML models predicting TCSS and occult lymph node metastases

Specifics of young gastric cancer patients: a population-based analysis of 46,110 patients with gastric cancer from the German Clinical Cancer Registry Group

Introduction: 2–8% of all gastric cancer occurs at a younger age, also known as early-onset gastric cancer (EOGC). The aim of the present work was to use clinical registry data to classify and characterize the young cohort of patients with gastric cancer more precisely. Methods: German Cancer Registry Group of the Society of German Tumor Centers—Network for Care, Quality and Research in Oncology (ADT)was queried for patients with gastric cancer from 2000–2016. An approach that stratified relative distributions of histological subtypes of gastric adenocarcinoma according to age percentiles was used to define and characterize EOGC. Demographics, tumor characteristics, treatment and survival were analyzed. Results: A total of 46,110 patients were included. Comparison of different groups of age with incidences of histological subtypes showed that incidence of signet ring cell carcinoma (SRCC) increased with decreasing age and exceeded pooled incidences of diffuse and intestinal type tumors in the youngest 20% of patients. We selected this group with median age of 53 as EOGC. The proportion of female patients was lower in EOGC than that of elderly patients (43% versus 45%; p < 0.001). EOGC presented more advanced and undifferentiated tumors with G3/4 stages in 77% versus 62%, T3/4 stages in 51% versus 48%, nodal positive tumors in 57% versus 53% and metastasis in 35% versus 30% (p < 0.001) and received less curative treatment (42% versus 52%; p < 0.001). Survival of EOGC was significantly better (five-years survival: 44% versus 31% (p < 0.0001), with age as independent predictor of better survival (HR 0.61; p < 0.0001). Conclusion: With this population-based registry study we were able to objectively define a cohort of patients referred to as EOGC. Despite more aggressive/advanced tumors and less curative treatment, survival was significantly better compared to elderly patients, and age was identified as an independent predictor for better survival

Machine Learning-assisted immunophenotyping of peripheral blood identifies innate immune cells as best predictor of response to induction chemo-immunotherapy in head and neck squamous cell carcinoma – knowledge obtained from the CheckRad-CD8 trial

Purpose: Individual prediction of treatment response is crucial for personalized treatment in multimodal approaches against head-and-neck squamous cell carcinoma (HNSCC). So far, no reliable predictive parameters for treatment schemes containing immunotherapy have been identified. This study aims to predict treatment response to induction chemo-immunotherapy based on the peripheral blood immune status in patients with locally advanced HNSCC. Methods: The peripheral blood immune phenotype was assessed in whole blood samples in patients treated in the phase II CheckRad-CD8 trial as part of the pre-planned translational research program. Blood samples were analyzed by multicolor flow cytometry before (T1) and after (T2) induction chemo-immunotherapy with cisplatin/docetaxel/durvalumab/tremelimumab. Machine Learning techniques were used to predict pathological complete response (pCR) after induction therapy. Results: The tested classifier methods (LDA, SVM, LR, RF, DT, and XGBoost) allowed a distinct prediction of pCR. Highest accuracy was achieved with a low number of features represented as principal components. Immune parameters obtained from the absolute difference (lT2-T1l) allowed the best prediction of pCR. In general, less than 30 parameters and at most 10 principal components were needed for highly accurate predictions. Across several datasets, cells of the innate immune system such as polymorphonuclear cells, monocytes, and plasmacytoid dendritic cells are most prominent. Conclusions: Our analyses imply that alterations of the innate immune cell distribution in the peripheral blood following induction chemo-immuno-therapy is highly predictive for pCR in HNSCC