Structured population balances to support microalgae-based processes: Review of the state-of-art and perspectives analysis

Design and optimization of microalgae processes have traditionally relied on the application of unsegregated mathematical models, thus neglecting the impact of cell-to-cell heterogeneity. However, there is experimental evidence that the latter one, including but not limited to variation in mass/size, internal composition and cell cycle phase, can play a crucial role in both cultivation and downstream processes. Population balance equations (PBEs) represent a powerful approach to develop mathematical models describing the effect of cell-to-cell heterogeneity. In this work, the potential of PBEs for the analysis and design of microalgae processes are discussed. A detailed review of PBE applications to microalgae cultivation, harvesting and disruption is reported. The review is largely focused on the application of the univariate size/mass structured PBE, where the size/mass is the only internal variable used to identify the cell state. Nonetheless, the need, addressed by few studies, for additional or alternative internal variables to identify the cell cycle phase and/or provide information about the internal composition is discussed. Through the review, the limitations of previous studies are described, and areas are identified where the development of more reliable PBE models, driven by the increasing availability of single-cell experimental data, could support the understanding and purposeful exploitation of the mechanisms determining cell-to-cell heterogeneity

Electrochemical synthesis of nanowire anodes from spent lithium ion batteries

A novel process is proposed to produce nanostructured batteries anodes from spent lithium-ion batteries. The electrodic powder recovered by the mechanical treatment of spent batteries was leached and the dissolved metals were precipitated as cobalt carbonates. Two different precipitation routes were separately tested producing cobalt carbonates with different Cu and Fe contents. Nanowire anodes were produced by electrodeposition into nanoporous alumina templates from the electrolytic baths prepared by dissolution of the precipitated carbonates. The electrochemical performances of the produced anodes were evaluated as compared to nanowire anodes produced with the same electrodeposition method but using a synthetic cobalt bath. The application of the carbonates produced by directly precipitating all the leached metals gave nanowires with capacity about halved as compared to the nanowires electrodeposited from the synthetic bath. Selectively removing Cu and Fe prior cobalt carbonate precipitation yielded, in contrast, nanowires with capacity initially larger and then gradually approaching that attained by the nanowire electrodeposited from the synthetic bath. A detailed analysis is presented describing the role of metallic impurities in determining the capacity of the produced nanowires. The impact of the illustrated results for the development of sustainable recycling processes of lithium-ion batteries is discussed

Gene expression landscape of sdh-deficient gastrointestinal stromal tumors

Background: About 20–40% of gastrointestinal stromal tumors (GISTs) lacking KIT/PDGFRA mutations show defects in succinate dehydrogenase (SDH) complex. This study uncovers the gene expression profile (GEP) of SDH-deficient GIST in order to identify new signaling pathways or molecular events actionable for a tailored therapy. Methods: We analyzed 36 GIST tumor samples, either from formalin-fixed, paraf-fin-embedded by microarray or from fresh frozen tissue by RNA-seq, retrospectively collected among KIT-mutant and SDH-deficient GISTs. Pathway analysis was performed to highlight enriched and depleted transcriptional signatures. Tumor microenvironment and immune profile were also evaluated. Results: SDH-deficient GISTs showed a distinct GEP with respect to KIT-mutant GISTs. In particular, SDH-deficient GISTs were characterized by an increased expression of neural markers and by the activation of fibroblast growth factor receptor signaling and several biological pathways related to invasion and tumor progression. Among them, hypoxia and epithelial-to-mesenchymal transition emerged as features shared with SDH-deficient pheochromocytoma/paraganglioma. In addition, the study of immune landscape revealed the depletion of tumor microenvironment and inflammation gene signatures. Conclusions: This study provides an update of GEP in SDH-deficient GISTs, highlighting differences and similarities compared to KIT-mutant GISTs and to other neoplasm carrying the SDH loss of function. Our findings add a piece of knowledge in SDH-deficient GISTs, shedding light on their putative histology and on the dysregulated biological processes as targets of new therapeutic strategies

Correlation of molecular alterations with pathological features in hepatocellular carcinoma: Literature review and experience of an Italian center

Hepatocellular carcinoma (HCC) represents the primary carcinoma of the liver and the fourth leading cause of cancer-related deaths. The World Health Organization estimates an increase in cases in the coming years. The risk factors of HCC are multiple, and the incidence in different countries is closely related to the different risk factors to which the population is exposed. The molecular mechanisms that drive HCC tumorigenesis are extremely complex, but understanding this multistep process is essential for the identification of diagnostic, prognostic, and therapeutic markers. The development of multigenic nextgeneration sequencing panels through the parallel analysis of multiple markers can provide a landscape of the genomic status of the tumor. Considering the literature and our preliminary data based on 36 HCCs, the most frequently altered genes in HCCs are TERT, CTNNB1, and TP53. Over the years, many groups have attempted to classify HCCs on a molecular basis, but a univocal classification has never been achieved. Nevertheless, statistically significant correlations have been found in HCCs between the molecular signature and morphologic features, and this leads us to think that it would be desirable to integrate the approach between anatomic pathology and molecular laboratories

Residual effects of mental fatigue on subjective fatigue, reaction time and cardiac responses

Este estudio investigó los efectos residuales de la fatiga mental inducidos por 30 minutos Test de Stroop con palabra con color incongruente sobre la fatiga percibida subjetivamente, el tiempo de reacción y la variabilidad de la frecuencia cardíaca (HRV) en 20 voluntarios adultos (10 hombres, 10 mujeres). Las variables dependientes se evaluaron antes, inmediatamente después y a los 15, 30, 45 y 60 minutos después de dos condiciones: (a) Test de Stroop con palabra con color incongruente de 30 minutos (condición de fatiga mental); o (b) condición de control de 30 minutos. En la pre condiciones, no hubo diferencias significativas entre las condiciones experimentales para ninguna variable. Sin embargo, hubo un efecto residual de la fatiga mental en las respuestas psicológicas durante hasta ~ 15 minutos después de la manipulación experimental (p < 0,01). Para la tarea de tiempo de reacción, se observaron diferencias significativas solo inmediatamente después de la fatiga mental, en comparación con la condición de control (p < 0,0001). No hubo diferencias significativas entre las condiciones experimentales para ningún parámetro de HRV en ningún período. Además, no hubo diferencias significativas relacionadas con el género en ningún período ni en ninguna de las condiciones para ninguna variable. Los datos sugieren que la fatiga mental puede alterar las respuestas psicológicas hasta ~ 15 min después de su inducción, y la fatiga mental puede afectar el rendimiento del tiempo de reacción cognitiva sin cambiar las respuestas cardíacas autónomas.This study investigated the residual effects of mental fatigue induced by the 30-minute incongruent Stroop Color Word task on subjectively perceived fatigue, reaction time, and heart rate variability (HRV) in 20 adult volunteers (10 men; 10 women). Dependent variables were assessed before, immediately after, and at 15, 30, 45, and 60 minutes after two conditions: (a) a 30-minute incongruent Stroop Color Word task (mental fatigue condition); or (b) a 30-minute control condition. At pre-testing, there were no significant differences between experimental conditions for any variable. However, there was a residual effect of mental fatigue on psychological responses for up to ~15 minutes after the experimental manipulation (p < 0.01). For the reaction time task, significant differences were observed only immediately after the mental fatigue, compared to the control condition (p < 0.0001). There were no significant differences between experimental conditions for any parameters of HRV at any testing period. In addition, there were no significant gender related differences at any period or in either condition for any variable. The data suggest that mental fatigue can alter psychological responses for up to ~15 min after its induction, and mental fatigue may impair cognitive reaction time performance without changing autonomic cardiac responses.Este estudo investigou os efeitos residuais da fadiga mental induzida por 30 minutos do teste de Stroop com a palavra de cor incongruente na fadiga percebida de maneira subjetiva, tempo de reação e variabilidade da frequência cardíaca (VFC) em 20 voluntários adultos (10 homens; 10 mulheres). As variáveis dependentes foram avaliadas antes, imediatamente após e aos 15, 30, 45 e 60 minutos após duas condições: (a) teste de Stroop com a palavra de cor incongruente de 30 minutos (condição fadiga mental); ou (b) uma condição controle de 30 minutos. No pré-teste, não houve diferenças significativas entre as condições experimentais para qualquer variável. No entanto, houve um efeito residual da fadiga mental nas res-postas psicológicas por até ~ 15 minutos após a manipulação experimental (p <0,01). Para o teste de tempo de reação, foram observadas diferenças significativas apenas imediatamente após a fadiga mental, em comparação com a condição controle (p <0,0001). Não houve diferenças significativas entre as condições experimentais para quaisquer parâmetros da VFC em qualquer período. Além disso, não houve diferenças significativas relacionadas ao gênero em qualquer período ou em qualquer condição para qualquer variável. Os dados sugerem que a fadiga mental pode alterar as respostas psico-lógicas por até 15 minutos após sua indução, e a fadiga mental pode prejudicar o desempenho cognitivo pela piora tempo de reação sem alterar as respostas autonômicas cardíacas

Improvement in insulin sensitivity, but without changes in liver enzymes in obese women after 12 weeks of a walking exercise program with self-selected intensity

Background: Obesity is related to negative changes in insulin resistance and liver enzymes and is associated with the risk factor for the development of type II diabetes mellitus and nonalcoholic fatty liver disease. A number of studies have demonstrated that aerobic exercise shows promise for disease prevention and treatment in this population. Aim: The objective of the present study was to evaluate the effect of a walking exercise program with self-selected intensity on insulin resistance and liver enzymes in obese women. Methods: Forty-eight obese women (47.8 ± 8.4 years; 88.1 ± 12.0 kg; 158.0 ± 0.1 cm) were divided into two groups: control group (CG; n = 23) and self-selected walking group (SSWG; n = 25). Before and after the exercise program, all subjects underwent anthropometric measurements and blood samples were collected. The intervention consisted of a walking exercise program with self-selected intensity for 12 weeks (3 times/week, totalizing 36 sessions). Results: After the exercise program, fasting glucose, fasting insulin, and HOMA improved only in the SSWG (p 0.05). In addition, there were no differences in liver enzymes after the intervention in both groups (p > 0.05). Conclusions: The results support that a walking exercise program with self-selected intensity improved insulin resistance in obese women. Thus, exercise programs with self-selected intensity seem to be an interesting alternative for improving health and preventing diseases

Clinical relevance of gene mutations and rearrangements in advanced differentiated thyroid cancer

Background: Tumor genotyping is becoming crucial to optimize the clinical management of patients with advanced differentiated thyroid cancer (DTC); however, its implementation in clinical practice remains undefined. We herein report our single-center experience on molecular advanced DTC testing by next-generation sequencing approach, to better define how and when tumor genotyping can assist clinical decision making. Materials and methods: We retrospectively collected data on all adult patients with advanced DTC who received molecular profiling at the IRCSS Sant'Orsola-Malpighi Hospital from 2008 to 2022. The genetic alterations were correlated with radioactive iodide refractory (RAI-R), RAI uptake/disease status, and time to RAI resistance (TTRR) development. Results: A significant correlation was found between RAI-R development and genetic alterations (P&nbsp;= 0.0001). About 48.7% of RAI-R cases were positive for TERT/TP53 mutations (as both a single event and comutations with other driver gene alterations, such as BRAF mutations, RAS mutations, or gene fusions), while the great majority of RAI-sensitive cases carried gene fusions (41.9%) or were wild type (WT; 41.9%). RAI uptake/disease status and time to TTRR were significantly associated with genetic alterations (P&nbsp;= 0.0001). In particular, DTC with TERT/TP53 mutations as a single event or as comutations displayed a shorter median TTRR of 35.4 months (range 15.0-55.8 months), in comparison to the other molecular subgroups. TERT/TP53 mutations as a single event or as comutations remained independently associated with RAI-R after Cox multivariate analysis (hazard ratio 4.14, 95% CI 1.51-11.32; P&nbsp;= 0.006). Conclusions: Routine testing for genetic alterations should be included as part of the clinical workup, for identifying both the subset of more aggressive tumors and the subset of tumors harboring actionable gene fusions, thus ensuring the appropriate management for all patients with advanced DTC

Detection of EGFR-Activating and T790M Mutations Using Liquid Biopsy in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer Whose Disease Has Progressed During Treatment With First- and Second-Generation Tyrosine Kinase Inhibitors: A Multicenter Real-Life Retrospective Study

Epidermal growth factor receptor T790M detection using liquid biopsy was evaluated in a real-life setting in 120 advanced non–small-cell lung cancer patients whose disease had progressed during first- or second-generation tyrosine kinase inhibitors. The T790M detection rate was 25.8% using liquid biopsy and 49.2% after tissue rebiopsy. Liquid biopsies performed before disease progression according to Response Evaluation Criteria In Solid Tumors were all negative for T790M and T790M positivity was higher in cases of extrathoracic metastatic sites

A novel mutation in the tyrosine kinase domain of ERBB2 in hepatocellular carcinoma

BACKGROUND: Several studies showed that gain-of-function somatic mutations affecting the catalytic domain of EGFR in non-small cell lung carcinomas were associated with response to gefitinib and erlotinib, both EGFR-tyrosine kinase inhibitors. In addition, 4% of non-small cell lung carcinomas were shown to have ERBB2 mutations in the kinase domain. In our study, we sought to determine if similar respective gain-of-function EGFR and ERBB2 mutations were present in hepatoma and/or biliary cancers. METHODS: We extracted genomic DNA from 40 hepatoma (18) and biliary cancers (22) samples, and 44 adenocarcinomas of the lung, this latter as a positive control for mutation detection. We subjected those samples to PCR-based semi-automated double stranded nucleotide sequencing targeting exons 18–21 of EGFR and ERBB2. All samples were tested against matched normal DNA. RESULTS: We found 11% of hepatoma, but no biliary cancers, harbored a novel ERBB2 H878Y mutation in the activating domain. CONCLUSION: These newly described mutations may play a role in predicting response to EGFR-targeted therapy in hepatoma and their role should be explored in prospective studies

The SSM at 1

On February 3-4, 2016 SUERF – The European Money and Finance Forum –, Deutsche Bundesbank and Stiftung Geld und Währung jointly organized a Colloquium/Conference in Frankfurt in order to evaluate the experience with the SSM – the Single Supervisory Mechanism – during the first year of its existence. The present issue of SUERF Conference Proceedings includes a selection of papers based on the authors’ contributions to the Frankfurt event