Metformin: a modulator of bevacizumab activity in cancer? A case report.

Recurrent type I endometrial cancer ((EC)) has poor prognosis and demands novel therapeutic approaches. Bevacizumab, a VEGF-A neutralizing monoclonal antibody, has shown clinical activity in this setting. To our knowledge, however, although some diabetic cancer patients treated with bevacizumab may also take metformin, whether metformin modulates response to anti-VEGF therapy has not yet been investigated. Here, we report the case of a patient with advanced (EC) treated, among other drugs, with bevacizumab in combination with metformin. The patient affected by relapsed (EC) G3 type 1, presented in march 2010 with liver, lungs and mediastinic metastases. After six cycles of paclitaxel and cisplatin she underwent partial response. Later on, she had disease progression notwithstanding administration of multiple lines of chemotherapy. In march 2013, due to brain metastases with coma, she began steroid therapy with development of secondary diabetes. At this time, administration of Bevacizumab plus Metformin improved her performance status. CT scans performed in this time window showed reduced radiologic density of the lung and mediastinic lesions and of liver disease, suggestive of increased tumor necrosis. Strong F-18-FDG uptake by PET imaging along with high levels of monocarboxylate transporter 4 and lack of liver kinase B1 expression in liver metastasis, highlighted metabolic features previously associated with response to anti-VEGF therapy and phenformin in preclinical models. However, clinical benefit was transitory and was followed by rapid and fatal disease progression. These findingsalbeit limited to a single casesuggest that tumors lacking LKB1 expression and/or endowed with an highly glycolytic phenotype might develop large necrotic areas following combined treatment with metformin plus bevacizumab. As metformin is widely used among diabetes patients as well as in ongoing clinical trials in cancer patients, these results deserve further clinical investigation

Atypical ageing defect in Pinot Blanc wines: a comparison between organic and conventional production management systems

Atypical ageing (ATA) is an aroma defect that occurs in white wines and entails a loss of varietal aromas as well as scents of wet mop, shoe polish and dish rag. 2-Aminoacetophenone (2AAP) - a degradation product of indole-3-acetic acid (IAA) - has been described as the main odour-active compound and chemical marker responsible for this off-flavour. A stress reaction in the vineyard triggered by climatic, pedological and viticultural factors can ultimately cause ATA development in wines and remarkably affect wine quality. The aim of this research was to investigate the influence of three grapevine management systems on the occurrence of ATA. The experiments were carried out on Pinot Blanc grape samples from vines cultivated using one conventional and two organic approaches. The management systems mainly differed for the fertilisation regime and the weed control

Impact of Smoking Status on Mortality in STEMI Patients Undergoing Mechanical Reperfusion for STEMI : Insights from the ISACS–STEMI COVID-19 Registry

The so-called “smoking paradox”, conditioning lower mortality in smokers among STEMI patients, has seldom been addressed in the settings of modern primary PCI protocols. The ISACS– STEMI COVID-19 is a large-scale retrospective multicenter registry addressing in-hospital mortality, reperfusion, and 30-day mortality among primary PCI patients in the era of the COVID-19 pandemic. Among the 16,083 STEMI patients, 6819 (42.3%) patients were active smokers, 2099 (13.1%) previous smokers, and 7165 (44.6%) non-smokers. Despite the impaired preprocedural recanalization (p < 0.001), active smokers had a significantly better postprocedural TIMI flow compared with nonsmokers (p < 0.001); this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. Active smokers had a significantly lower in-hospital (p < 0.001) and 30-day (p < 0.001) mortality compared with non-smokers and previous smokers; this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. In conclusion, in our population, active smoking was significantly associated with improved epicardial recanalization and lower in-hospital and 30-day mortality compared with previous and non-smoking histor

Impact of chronic obstructive pulmonary disease on short-term outcome in patients with ST-elevation myocardial infarction during COVID-19 pandemic: insights from the international multicenter ISACS-STEMI registry

Background Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study. Methods In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents. Results A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658-1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620-1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups. Conclusion This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity. Trial registration number: NCT 04412655 (2nd June 2020)

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Advances in Computational Social Science and Social Simulation

Aquesta conferència és la celebració conjunta de la "10th Artificial Economics Conference AE", la "10th Conference of the European Social Simulation Association ESSA" i la "1st Simulating the Past to Understand Human History SPUHH".Conferència organitzada pel Laboratory for Socio­-Historical Dynamics Simulation (LSDS-­UAB) de la Universitat Autònoma de Barcelona.Readers will find results of recent research on computational social science and social simulation economics, management, sociology,and history written by leading experts in the field. SOCIAL SIMULATION (former ESSA) conferences constitute annual events which serve as an international platform for the exchange of ideas and discussion of cutting edge research in the field of social simulations, both from the theoretical as well as applied perspective, and the 2014 edition benefits from the cross-fertilization of three different research communities into one single event. The volume consists of 122 articles, corresponding to most of the contributions to the conferences, in three different formats: short abstracts (presentation of work-in-progress research), posters (presentation of models and results), and full papers (presentation of social simulation research including results and discussion). The compilation is completed with indexing lists to help finding articles by title, author and thematic content. We are convinced that this book will serve interested readers as a useful compendium which presents in a nutshell the most recent advances at the frontiers of computational social sciences and social simulation researc

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Coupling waste heat extraction based on phase change material with steam generation: evidence from steel industry

Waste heat recovery in steel industry represents one of the greatest opportunity to reduce the consumption of primary energy while increasing the sustainability of the steelmaking processes. One of the most important and challenging source of waste heat in steelmaking process is the off gas emitted by the Electric Arc Furnace (EAF), which represents about 30% of the total energy provided to the process. Due to the dynamic of the EAF process, the off gas parameters (temperature and mass flow rate) fluctuate intensively causing large variations in thermal power. Currently, the most modern heat recovery systems face these thermal power fluctuations generating saturated steam at around 220 \ub0C and storing it in Ruth\u2019s steam accumulator to feed an Organic Rankine Cycle (ORC). Since the average temperatures of the off gas are usually around 600 \ub0C, in order to reduce exergy losses a better solution would be to generate superheated steam at higher temperature to directly feed a steam turbine. For this aim, high temperature phase change materials (PCMs) can be employed to reduce the fluctuating thermal power entering the steam generator. Previous findings have shown technical and economic performances of a PCM-based device able to smooth off gas temperature profiles. The introduction of a heat transfer fluid (HTF) to overcome overheating issues in PCM containers has also been investigated. In this paper, the opportunity of actively managing the HTF flowing through the PCM device to enhance the steam parameters level is investigated. To this end, the PCM-based device is coupled with a steam generator: the effects of both off gas temperature smoothing and extraction of stored heat in the PCM by HTF on steam parameters and performance of the related energy conversion system are analysed. An analytical model is implemented in Fortran90 to predict the thermal behaviour of the PCM device. The Fortran code is interfaced with the TRNSYS software to analyse the performance of the whole heat recovery system (PCM device, steam generator and steam turbine) and to develop a proper control strategy. All thermo-physical properties are estimated using the REFPROP 8.0 package. Calculations are carried out in transient regime, adopting off-gas flow rates and temperature profiles representative of real EAF processes. Finally, an economic performance assessment of the whole system is carried out

Coupling waste heat extraction by phase change materials with superheated steam generation in the steel industry

To allow a better exergy exploitation than the current state-of-the-art waste heat to power solutions in the steel industry, a new type of energy recovery system based on Phase Change Materials is proposed. In particular, the use of high temperature PCMs evolves from simply smoothing off gas temperature, as in the most recent studies for energy recovery from electric arc furnaces, to generating constant superheated steam able to feed the downstream turbine nearly at nominal load. This result is achieved by introducing an auxiliary section between the PCM Section and the steam generation one, which provides the auxiliary heat needed to level the thermal content of off gas. The auxiliary heat is extracted from the PCM units by a heat transfer fluid flowing across the inner tube of each PCM container. Different models to properly size and simulate the operations of the proposed energy recovery system have been developed and integrated. Results show how the size of the steam generator and the turbine can be reduced of about 41% with respect to traditional solutions, while increasing electric power production by 22% thanks to the reduced fluctuation in steam parameters at the turbine inlet, which leads to a greater overall efficiency