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Wastewater Treatment Plants (WWTPs) present complex biochemical processes of high variability and difficult prediction. This study presents an innovative approach using Machine Learning (ML) models to predict wastewater quality parameters. In particular, the models are applied to datasets from both a simulated wastewater treatment plant (WWTP), using DHI WEST software (WEST WWTP), and a real-world WWTP database from Santa Catarina Brewery AMBEV, located in Lages/SC - Brazil (AMBEV WWTP). A distinctive aspect is the evaluation of predictive performance in continuous data scenarios and the impact of changes in WWTP operations on predictive model performance, including changes in plant layout. For both plants, three different scenarios were addressed, and the quality of predictions by random forest (RF), support vector machine (SVM), and multilayer perceptron (MLP) models were evaluated. The prediction quality by the MLP model reached an R2 of 0.72 for TN prediction in the WEST WWTP output, and the RF model better adapted to the real data of the AMBEV WWTP, despite the significant discrepancy observed between the real and the predicted data. Techniques such as Partial Dependence Plots (PDP) and Permutation Importance (PI) were used to assess the importance of features, particularly in the simulated WEST tool scenario, showing a strong correlation of prediction results with influent parameters related to nitrogen content. The results of this study highlight the importance of collecting and storing high-quality data and the need for information on changes in WWTP operation for predictive model performance. These contributions advance the understanding of predictive modeling for wastewater quality and provide valuable insights for future practice in wastewater treatment.

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Doxorubicin (DOXO)-cardiotoxicity is a limiting factor for breast cancer chemotherapy. The relationship between microparticles (MPs) and cardiotoxicity remains unclear. MPs can be released under varying pathophysiological conditions. Thereby, this study aimed to assess MPs derived from cardiomyocytes (CardioMPs), platelets (PMPs) and those that expresses tissue factor (TFMPs) in 80 women with breast cancer undergoing DOXO-based chemotherapy, with or without cardiotoxicity in a one-year follow-up. We observed in the cardiotoxicity group higher count of total-MPs at T0 (prior chemotherapy) (p = 0.034), CardioMPs at T0 and T1 (just after chemotherapy) (p = 0.009 and p = 0.0034) and TFMPs at T0 (p = 0.011) compared to non-cardiotoxicity group. The results suggest that MPs could be associated to cardiotoxicity due to DOXO treatment in breast cancer patients.

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Resumo Fundamento As doenças cardiovasculares (DCV) são relevantes para o manejo do tratamento do câncer de mama, uma vez que um número significativo de pacientes desenvolve essas complicações após a quimioterapia. Objetivo Este estudo teve como objetivo avaliar novos biomarcadores cardiovasculares, sendo eles CXCL-16 (ligante de motivo C-X-C 16), FABP3 (proteína de ligação a ácidos graxos 3), FABP4 (proteína de ligação a ácidos graxos 4), LIGHT (membro da superfamília do fator de necrose tumoral 14/TNFS14), GDF-15 (fator de crescimento/diferenciação 15) , sCD4 (forma solúvel de CD14) e ucMGP (matriz Gla-proteína não carboxilada) em pacientes com câncer de mama tratadas com doxorrubicina (DOXO). Métodos Este estudo de caso-controle foi realizado em uma clínica oncológica, incluindo 34 mulheres com diagnóstico de câncer de mama tratadas com quimioterapia com DOXO e 34 mulheres controle, sem câncer ou DCV. Os marcadores foram determinados imediatamente após o último ciclo de quimioterapia. O nível de significância estatística adotado foi de 5%. Resultados O grupo com câncer de mama apresentou níveis mais elevados de GDF-15 (p<0,001), enquanto os indivíduos controle apresentaram níveis mais elevados de FABP3 (p=0,038), FABP4 (p=0003), sCD14 e ucMGP (p<0,001 para ambos). Correlações positivas foram observadas entre FABPs e IMC no grupo com câncer. Conclusão GDF15 é um biomarcador emergente com potencial aplicabilidade clínica neste cenário. FABPs são proteínas relacionadas à adiposidade, potencialmente envolvidas na biologia do câncer de mama. sCD14 e ucMGP estão envolvidos na calcificação inflamatória e vascular. Acima de tudo, a avaliação destes novos biomarcadores cardiovasculares pode ser útil no tratamento da quimioterapia do câncer de mama com DOXO.

Abstract Background Cardiovascular diseases (CVDs) are relevant to the management of breast cancer treatment since a substantial number of patients develop these complications after chemotherapy. Objective This study aims to evaluate new cardiovascular biomarkers, namely CXCL-16 (C-X-C motif ligand 16), FABP3 (fatty acid binding protein 3), FABP4 (fatty acid binding protein 4), LIGHT (tumor necrosis factor superfamily member 14/TNFS14), GDF-15 (Growth/differentiation factor 15), sCD4 (soluble form of CD14), and ucMGP (uncarboxylated Matrix Gla-Protein) in breast cancer patients treated with doxorubicin (DOXO). Methods This case-control study was conducted in an oncology clinic that included 34 women diagnosed with breast cancer and chemotherapy with DOXO and 34 control women without cancer and CVD. The markers were determined immediately after the last cycle of chemotherapy. The statistical significance level adopted was 5%. Results The breast cancer group presented higher levels of GDF-15 (p<0.001), while control subjects had higher levels of FABP3 (p=0.038), FABP4 (p=0003), sCD14, and ucMGP (p<0.001 for both). Positive correlations were observed between FABPs and BMI in the cancer group. Conclusion GDF15 is an emerging biomarker with potential clinical applicability in this scenario. FABPs are proteins related to adiposity, which are potentially involved in breast cancer biology. sCD14 and ucMGP engage in inflammatory and vascular calcification. The evaluation of these novel cardiovascular biomarkers could be useful in the management of breast cancer chemotherapy with DOXO.

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Venous thromboembolism (VTE) is an important cause of morbidity/mortality in cancer patients, and COMPASS-CAT score must be used to VTE-risk prediction. There is a relationship between cytokines and thrombus formation and/or resolution. This study aimed to investigate the VTE risk and cytokines level in breast cancer patients prior to chemotherapy with doxorubicin (DOXO). Eighty women with breast cancer and indication for DOXO treatment were selected. TNF, IL-1ß, IL-6, and IL-10 were measured after the diagnosis and immediately before DOXO treatment. All 80 patients presented a high risk for VTE when evaluated by COMPASS-CAT model (score ≥7). A positive correlation was observed between IL-10 plasma levels and VTE risk score. Our data showed that higher IL-10 levels before chemotherapy are associated to increased risk of VTE in breast cancer patients. This finding suggests that IL-10 levels and the combination with COMPASS-CAT score could be good markers to predict increased risk of VTE in these patients.

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BACKGROUND: Central Illustration : New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy. Cardiovascular diseases (CVDs) are relevant to the management of breast cancer treatment since a substantial number of patients develop these complications after chemotherapy. OBJECTIVE: This study aims to evaluate new cardiovascular biomarkers, namely CXCL-16 (C-X-C motif ligand 16), FABP3 (fatty acid binding protein 3), FABP4 (fatty acid binding protein 4), LIGHT (tumor necrosis factor superfamily member 14/TNFS14), GDF-15 (Growth/differentiation factor 15), sCD4 (soluble form of CD14), and ucMGP (uncarboxylated Matrix Gla-Protein) in breast cancer patients treated with doxorubicin (DOXO). METHODS: This case-control study was conducted in an oncology clinic that included 34 women diagnosed with breast cancer and chemotherapy with DOXO and 34 control women without cancer and CVD. The markers were determined immediately after the last cycle of chemotherapy. The statistical significance level adopted was 5%. RESULTS: The breast cancer group presented higher levels of GDF-15 (p<0.001), while control subjects had higher levels of FABP3 (p=0.038), FABP4 (p=0003), sCD14, and ucMGP (p<0.001 for both). Positive correlations were observed between FABPs and BMI in the cancer group. CONCLUSION: GDF15 is an emerging biomarker with potential clinical applicability in this scenario. FABPs are proteins related to adiposity, which are potentially involved in breast cancer biology. sCD14 and ucMGP engage in inflammatory and vascular calcification. The evaluation of these novel cardiovascular biomarkers could be useful in the management of breast cancer chemotherapy with DOXO.

FUNDAMENTO: Figura Central: Novos Biomarcadores Cardiovasculares em Pacientes com Câncer de Mama Submetidas a Quimioterapia à Base de Doxorrubicina. As doenças cardiovasculares (DCV) são relevantes para o manejo do tratamento do câncer de mama, uma vez que um número significativo de pacientes desenvolve essas complicações após a quimioterapia. OBJETIVO: Este estudo teve como objetivo avaliar novos biomarcadores cardiovasculares, sendo eles CXCL-16 (ligante de motivo C-X-C 16), FABP3 (proteína de ligação a ácidos graxos 3), FABP4 (proteína de ligação a ácidos graxos 4), LIGHT (membro da superfamília do fator de necrose tumoral 14/TNFS14), GDF-15 (fator de crescimento/diferenciação 15) , sCD4 (forma solúvel de CD14) e ucMGP (matriz Gla-proteína não carboxilada) em pacientes com câncer de mama tratadas com doxorrubicina (DOXO). MÉTODOS: Este estudo de caso-controle foi realizado em uma clínica oncológica, incluindo 34 mulheres com diagnóstico de câncer de mama tratadas com quimioterapia com DOXO e 34 mulheres controle, sem câncer ou DCV. Os marcadores foram determinados imediatamente após o último ciclo de quimioterapia. O nível de significância estatística adotado foi de 5%. RESULTADOS: O grupo com câncer de mama apresentou níveis mais elevados de GDF-15 (p<0,001), enquanto os indivíduos controle apresentaram níveis mais elevados de FABP3 (p=0,038), FABP4 (p=0003), sCD14 e ucMGP (p<0,001 para ambos). Correlações positivas foram observadas entre FABPs e IMC no grupo com câncer. CONCLUSÃO: GDF15 é um biomarcador emergente com potencial aplicabilidade clínica neste cenário. FABPs são proteínas relacionadas à adiposidade, potencialmente envolvidas na biologia do câncer de mama. sCD14 e ucMGP estão envolvidos na calcificação inflamatória e vascular. Acima de tudo, a avaliação destes novos biomarcadores cardiovasculares pode ser útil no tratamento da quimioterapia do câncer de mama com DOXO.

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Cardiovascular toxicity is the main adverse effect of Doxorubicin (DOX) in cancer patients. microRNAs (miRNAs) are promising biomarkers to identify cardiac injury induced by DOX in breast cancer patients during the subclinical phase. Using RT-qPCR, we compared the expression of circulating miR-208a5p, miR-133a, miR-499a5p, miR-15a, miR-133b, and miR-49a3p in serum samples from DOX-induced cardiotoxicity (case) compared to the non-cardiotoxicity group (control). To further explore the potential roles of these circulating miRNA in cardiotoxicity, we searched the miRTarBase for experimentally validated miRNA-target interactions and performed a functional enrichment analysis based on those interactions. miR-133a was significantly upregulated in case compared to control group. The most relevant pathway regulated by miR-133a was ErbB2 signaling, whose main genes involved are EGFR, ERBB2, and RHOA, which are possibly downregulated by miR133a. The other miRNAs did not show significant differential expression when compared on both groups. The data suggest that miR-133a is associated with DOX-based cardiotoxicity during chemotherapy in breast cancer patients through ErbB2 signaling pathway. Moreover, miR-133a may be a future marker of DOX-induced cardiotoxicity in women with breast cancer.

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BACKGROUND: Myocardial toxicity is a common side effect of doxorubicin (DOXO) therapy in breast cancer patients. We hypothesized that DOXO-induced cardiotoxicity may be related to the release of inflammatory cytokines in response to the treatment. This study aimed to assess changes in plasma levels of interleukin (IL)-1ß, IL-6, IL-10 and tumor necrosis factor (TNF) after chemotherapy and to correlate these levels with cardiac biomarkers and clinical data. METHODS: Sixty-four patients with breast cancer treated with DOXO were included. Twenty-two subjects (cases) developed cardiotoxicity until one year after the end of DOXO treatment. Cytokines and cardiac markers were evaluated before starting chemotherapy (T0), up to 7 days after the last infusion (T1) and 12 months after the last infusion (T2). RESULTS: Higher IL-10 levels were observed in the case group compared to controls at T1 (p = .006) and T2 (p = .046). The IL-1ß, IL-6 and TNF levels did not change during treatment in each group (p > .05), nor between the case and control groups. The IL-10 levels were higher at T1 than at T0 and T2 (p < .05 for both) in the cardiotoxicity group. A correlation between IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at T0 and T2 in the cardiotoxicity group was observed (p = .048 and p = .004, respectively). CONCLUSION: Our study demonstrated that DOXO induced an increase in plasma IL-10 levels in patients who presented cardiotoxicity after treatment, which correlated with NT-proBNP levels.

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This study deals with the photochemical degradation of the model compound tetracycline, an aqueous pollutant derived from the degradation of the bactericide oxytetracycline (OTC), in the innovative photoreactor FluHelik, designed to promote pollutant abatement in liquid phase through H2O2/UVC and UVC processes. Computational fluid dynamics (CFD) simulations were performed to predict the behavior of the photoreactor in the laboratory scale. The simulations revealed a well-defined helicoidal flow pattern around the UVC lamp in the photoreactor, and the effect of different operational conditions (e.g., flow rate and light intensity) on the reactor's performance was evaluated, allowing to optimize the equipment.

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In this work, the performance of microreactors irradiated with conventional (fluorescent) and UV-LED light was evaluated. For this purpose, a microfluidic reactor with an equivalent diameter of 133.5 µm was used. In addition, the effect of scale variation on the performance of photochemical reactors was assessed using reactors with three internal diameters (600, 1200, and 2300 µm), 2 residence times (30 and 60 s), and two sources of UVA radiation (A with irradiance of 115 W m-2 and B with irradiance of 44 W m-2). Also, the relationship between the configuration of the photocatalyst film and the effect of the scale on the performance of photochemical reactors was experimentally and theoretically investigated. For both cases, methylene blue dye was used as a model pollutant and titanium dioxide (TiO2) as a photocatalyst deposited on the inner wall of the photocatalytic reactors. For the residence time of 30 s, the smaller the reactor diameter, the greater was the degradation (22, 18, and 6%, respectively, for lamp A and 17, 16, and 8 %, respectively, for lamp B). The influence of the diameter of the reactor was also observed for the residence time of 60 s, but only for the reactor with a 2300-µm internal diameter. The reactors with diameters 600 and 1200 µm only showed different results when illuminated with lamp B (33 and 28% of methylene blue conversion, respectively). Moreover, computational simulation results suggested higher efficiency as the reactor's diameter is decreased and an optimum thickness of photocatalyst film to maximize the performance of devices in which photocatalytic reactions are carried out.

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