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This paper presents the mathematical modelling and numerical simulation of the turbulent, two-phase flow of liquid and gas in a gas-induced agitated stirred-tank reactor, using Computational Fluid Dynamics (CFD) techniques. The reactor used as an application demonstration of the developed model is the ozone-induced one, first designed and modeled by Yang et al. (1999). A three-dimensional (3D), transient, Euler-Euler two-phase flow model is developed and used to investigate the turbulent flow and mixing of liquid and bubbles in the stirred-tank reactor, applying the sliding mesh approach. Turbulence is simulated by means of several available models, the Renormalization Group (RNG) k-ε model being the one finally recommended as the most appropriate of the ones studied, for the present application. Two-way coupling between the two phases is modeled by means of appropriate inter-phase interaction relations. The study focused on bubbles of one size group (mean aerodynamic diameter of 2.5E-03 m), but it is easily extended to any number of sizes. It is concluded that the predicted overall flow field pattern and the mixing of both phases around the two blades of the simulated baffled stirred vessel, as well as inside and outside of the main tube of the reactor, are physically plausible, appear reasonably accurate, and are, therefore, satisfying. Keywords: Computational Fluid Dynamics, Two-phase flow, Dispersed flow, Reactor mixing, Sliding mesh, Baffled stirred-tank reactor

Land abandonment in European mountains threatens habitats shaped for centuries by low-intensity agriculture and grazing. Hence, it is important to identify spatiotemporal patterns in rural abandonment, and relate them to biophysical and socioeconomic drivers. We pursued these goals in the theoretical context of transitions from traditional to productivist and then to post-productivist agriculture. We conducted a case study in a representative of southern Europe sub-mountainous marginal area that was once traditionally exploited (Pindus range, Epirus, Greece). Land cover was mapped from the outset of abandonment (years 1945, 1970, 1996 and 2015), and we subsequently calculated landscape metrics. An Intensity Analysis facilitated the comparison of rates of land cover change between time periods. By employing random forest modelling, we related socioeconomic, physiographic, geological and climatic predictors to land type occurrence and succession intensity. We found that farmland decreased from 30% to 3% during the 70 years of the study period, and that forest increased from 22% to 63%. The landscape’s heterogeneity, ecotone diversity, and spatial aggregation decreased. Abandonment and succession accelerated and relocated to lower elevation, especially during the latest time period, which was related to a second depopulation wave and livestock decrease. The remaining lowland farmlands were of productivist agriculture, and no widespread post-productivist regime was found. Thus, our study supports the view that policies, which have been mainly based on the linear transition of agricultural regimes in northern Europe, must take into account southern European mountains, where widespread abandonment can coexist with limited intensification and extensification.

Abstract Understanding the ecological mechanisms behind biological invasions remains a major focus of conservation biology and ecosystem management. Several hypotheses highlight that different facets of native biodiversity affect the establishment and spread of alien species. Here, we approach this question by examining the spatiotemporal relationship between alien bird species richness and different facets of biodiversity (taxonomic, functional, and phylogenetic) using breeding bird atlases for three U.S. states and for two time periods in each state. We associated native species richness, and functional and phylogenetic diversity with alien species richness, using generalized least squares models. Our results show that, consistently, across the three states and two time periods examined, alien species richness is positively associated with native diversity, and particularly with phylogenetic diversity. The relative importance of biodiversity metrics reflecting the functional or phylogenetic range occupied by the assemblage seems to advocate in favor of the importance of resource diversity as a main driver of both native and alien diversity. The secondary importance of biodiversity facets reflecting species functional or phylogenetic similarity, along with the lack of importance of functional or phylogenetic clustering or overdispersion, implies that if this relationship is shaped by biotic interactions, then biotic interactions facilitating coexistence (including even processes like predator‐mediated coexistence) are far more important than adversarial interactions like competition, at least at the scale of our analysis. Finally, the dominance of phylogenetic metrics over functional ones highlights the adaptive potential of a community accumulated over long lineage history may play an additional role as a source of information on evolutionary processes driving diversity patterns.

The Aegean archipelago has long been the main research area of numerous biogeographers, plant ecologists and taxonomists due to its intricate palaeogeography and high environmental and topographical heterogeneity. Nevertheless, some parts of this archipelago are essentially unexplored and the processes driving spatial variation in species composition remain unaddressed. Aiming to fill these gaps, we investigated the flora and plant diversity patterns of the Northern Sporades island group, as well as its biogeographical relationships. The study area lies in the biogeographical region of the West Aegean islands and comprises 23 islands and islets. The total flora of the study area consists of 1202 infrageneric taxa, belonging to 517 genera and 120 families, reflecting its geographical and bioclimatic characteristics. The endemic element consists of 41 taxa (3.4% of the flora), eight of which are restricted to the West Aegean islands and two are single island endemics. Area emerged as the most important variable in shaping plant species richness, while niche-based processes played a lesser role in driving these patterns. Regarding the taxonomic and phylogenetic beta-diversity patterns, environmental filtering and not dispersal limitation seems to shape the plant assemblages of the Northern Sporades islets. Biogeographically, the Northern Sporades island group seems to be closer connected to the Kiklades rather than to Evvia or the adjacent mainland, due to their longer isolation and separate palaeogeographical history during the Quaternary. [ABSTRACT FROM AUTHOR]

Calcific aortic valve stenosis (CAVS) is a common age-related disease characterized by active calcification of the leaflets of the aortic valve. How innate immune cells are involved in disease pathogenesis is not clear. In this study we investigate the role of the pattern recognition receptor Toll-like receptor 7 (TLR7) in CAVS, especially in relation to macrophage subtype. Human aortic valves were used for mRNA expression analysis, immunofluorescence staining, or ex vivo tissue assays. Response to TLR7 agonist in primary macrophages and valvular interstitial cells (VICs) were investigated in vitro. In the aortic valve, TLR7 correlated with M2 macrophage markers on mRNA levels. Expression was higher in the calcified part compared with the intermediate and healthy parts. TLR7+ cells were co-stained with M2-type macrophage receptors CD163 and CD206. Ex vivo stimulation of valve tissue with the TLR7 ligand imiquimod significantly increased secretion of IL-10, TNF-α, and GM-CSF. Primary macrophages responded to imiquimod with increased secretion of IL-10 while isolated VICs did not respond. In summary, in human aortic valves TLR7 expression is associated with M2 macrophages markers. Ex vivo tissue challenge with TLR7 ligand led to secretion of immunomodulatory cytokine IL-10. These results connect TLR7 activation in CAVS to reduced inflammation and improved clearance.

Calcification, a key feature of advanced human atherosclerosis, is positively associated with vascular disease burden and adverse events. We showed that macrocalcification can be a stabilizing factor for carotid plaque molecular biology, due to inverse association with immune processes. Mast cells (MCs) are important contributors to plaque instability, but their relationship with macrocalcification is unexplored. With a hypothesis that MC activation negatively associates with carotid plaque macrocalcification, we aimed to investigate the link between MCs and carotid plaque vulnerability, and study MC role in plaque calcification via smooth muscle cells (SMCs). Pre-operative computed tomography angiographies of patients (n = 40) undergoing surgery for carotid stenosis were used to characterize plaque morphology. Plaque microarrays (n = 40 and n = 126) were used for bioinformatic deconvolution of immune cell populations. Tissue microarrays (n = 103) were used to histologically validate the contribution of activated and resting MCs in plaques. Activated MCs and their typical markers were negatively correlated with macrocalcification. The ratio of activated vs. resting MCs was increased in low-calcified plaques from symptomatic patients. There was no modulating effect of medication on MC ratios. In vitro experiments showed that SMC calcification attenuated MC activation, while both active and resting MCs stimulated SMC calcification and induced dedifferentiation towards a pro-inflammatory-, osteochondrocyte-like phenotype, without modulating their migro-proliferative function. Integrative analyses from human plaques showed that MC activation is inversely associated with macrocalcification and positively with parameters of plaque vulnerability. Mechanistically, MCs induce SMC osteogenic reprograming, while matrix calcification in turn attenuates MC activation, offering new therapeutic avenues for exploration. Schematic representation of the mechanism by which MCs mediate macrocalcification formation in human plaques via SMCs, and the proposed feedback mechanism by which established macrocalcification ultimately attenuates MC activation [Display omitted] • Activated MCs correlate negatively with human carotid plaque macrocalcification. • There is no modulating effect of patient medication on MC ratios in plaques. • MCs induce SMC osteogenic reprograming in calcified plaques. • Calcified extracellular matrix in turn attenuates further MC activation. [ABSTRACT FROM AUTHOR]

We report on a 63-year-old woman, previously in good health, who had undergone nephrectomy for clear cell renal cell carcinoma in 2002. Because of systemic relapse with multiple lung metastases in 2006, the patient was treated with sunitinib 50 mg daily on a 4-weeks on-/2-weeks off-schedule. After 3 years of treatment, she developed a purpuric rash on her feet and trunk. Biopsy revealed leukocytoclastic vasculitis. No other organ involvement was diagnosed. She was started on oral prednisone 30 mg daily with rapid resolution of the vasculitic skin lesions. Sunitinib was temporally discontinued and reintroduced at the same dose level. Reappearance of a less serious vasculitis after 2 cycles of re-treatment was resolved in the weeks off-treatment and by reducing the dose of sunitinib along with 5 mg of prednisone daily. One year after the diagnosis, the patient is still on this therapy. Oncology providers should be aware of this rare but potentially serious, possible adverse effect of sunitinib.

Ovarian cancer is one of the leading causes of cancer-related death among women. Resistance to the disease occurs in more than 70% of the cases even after treated with chemotherapy agents such as paclitaxel- and platinum-based agents. The immune system is increasingly becoming a target for intense research in order to study the host's immune response against ovarian cancer. T cell populations, including NK T cells and Tregs, and cytokines have been associated with disease outcome, indicating their increasing clinical significance, having been associated with prognosis and as markers of disease progress, respectively. Harnessing the immune system capacity in order to induce antitumor response remains a major challenge. This paper examines the recent developments in our understanding of the mechanisms of development of the immune response in ovarian cancer as well as its prognostic significance and the existing experience in clinical studies.

A multiresolution source/filter model for coding of audio source signals (spot recordings) is proposed. Spot recordings are a subset of the multimicrophone recordings of a music performance, before the mixing process is applied for producing the final multichannel audio mix. The technique enables low bitrate coding of spot signals with good audio quality (above 3.0 perceptual grade compared to the original). It is demonstrated that this particular model separates the various microphone recordings of a multimicrophone recording into a part that mainly characterizes a specific microphone signal and a part that is common to all signals of the same recording (and can thus be omitted during transmission). Our interest in low bitrate coding of spot recordings is related to applications such as remote mixing and real-time collaboration of musicians who are geographically distributed. Using the proposed approach, it is shown that it is possible to encode a multimicrophone audio recording using a single audio channel only, with additional information for each spot microphone signal in the order of 5 kbps, for good-quality resynthesis. This is verified by employing both objective and subjective measures of performance.

Extra skeletal Ewing Sarcoma (EES) is a rare entity which predominantly occurs in adolescents and young adults. It usually arises from the soft tissues of the trunk or the extremities. We present a case of EES arising from the left visceral pleura in a 21 year old female patient who presented to the emergency room of our institution with fever, productive cough and sternal pain radiating to the back for the last 3 days. Chest radiograph was firstly performed, followed by chest CT examination. Finally open lung biopsy revealed a small round cell malignancy. The mass was resected and the histological examination revealed Extra skeletal Ewing Sarcoma (EES) of the visceral pleura without involvement of the adjacent lung. Secondary multiple nodules at the lateral wall of the pleura were also noticed and so postoperative multiagent chemotherapy was performed. EES should be considered in the differential diagnosis of any patient, especially adolescents or young adults, with a soft tissue mass of the trunk or the extremities. Hippokratia 2011; 15 (4): 363-365 [ABSTRACT FROM AUTHOR]

Lung cancer treatment and patient care are constantly improving, but it remains doubtful whether this applies equally to all socioeconomic groups. It is nowadays well established that there are socioeconomic inequalities regarding lung cancer incidence, screening, effective treatment, overall survival, and prognosis. One of the key contributing factors to low socioeconomic status is low education. Low educational level is correlated with several factors, such as smoking habits, bad lifestyle behaviors, lower paid and unhealthier occupations, polluted neighborhoods, and genetic-familial risk, that lead to increased lung cancer incidence. The disparities regarding lung cancer care are further enhanced by stigma. On this basis and inspired by the gap in health equality among the Greek population, the Greek Society of Lung Cancer initiated a campaign, "MIND THE GAP", to help increase awareness and minimize the gap associated with lung cancer, both in Greece and across Europe. The aim of this review is to explore the gap of health inequalities regarding lung cancer incidence and prognosis between patients of different SES and its root of causality. Key pivotal actions towards bridging this gap are reviewed as well., Competing Interests: The authors declare no conflicts of interest.

Background/aim: Real-world data on the EGFR mutational profile upon progression after first/second-generation EGFR-TKI treatment in patients with advanced non-small-cell lung cancer (NSCLC) and treatment strategies employed thereon are needed., Patients and Methods: This observational study was conducted in 23 hospital-based lung cancer Centers in Greece (protocol code: D133FR00126). Ninety-six eligible patients were consecutively enrolled between July-2017 and September-2019. Re-biopsy was performed in 18 of 79 patients who tested T790M-negative in liquid biopsy after progression in the first-line (1L) setting., Results: Of the study population, 21.9% tested T790M-positive, while 72.9% proceeded to 2L treatment, mainly comprising of a third-generation EGFR-TKI (48.6%), a switch to chemotherapy (30.0%), or chemo-immunotherapy (17.1%). The objective response rate (ORR) in 2L was 27.9% in T790M-negative and 50.0% in T790M-positive patients. Of evaluable patients, 67.2% experienced disease progression; median progression-free survival (PFS) was 5.7 and 10.0 months among T790M-negative and positive patients, respectively. Among T790M-negative patients, longer median PFS and post-progression survival were observed with third-generation EGFR-TKI treatment., Conclusion: Mutational status and treatment strategy were identified as critical determinants of clinical outcomes in the 2L-setting of EGFR-mutated NSCLC patients in real-world settings in Greece, with early diagnosis, appropriate molecular testing and high-efficacy treatments at first lines positively affecting ORR and PFS., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Neurodegenerative diseases are a group of disorders characterised by progressive loss of brain function. The most common of these is Alzheimer's disease, a form of dementia. Intake of macro- and micro-nutrients impacts brain function, including memory, learning, mood, and behaviour. Lipids, particularly phospholipids and sphingolipids, are crucial structural components of neural tissues and significantly affect cognitive function. The importance of functional foods in preventing cardiovascular disease is well-documented in the current literature. However, the significance of such foods for central nervous system health and neurodegenerative diseases is less recognized. Gut microbiome composition affects cognitive health and function, and dietary lipids are known to influence gut health. Thus, this review will discuss different sources of dietary lipids and their effect on cognitive functioning and their interaction with the gut microbiome in the context of neurodegenerative disease.

The immune system regulates angiogenesis in cancer with both pro- and antiangiogenic activities. The induction of angiogenesis is mediated by tumor-associated macrophages and myeloid-derived suppressor cells (MDSC) which produce proinflammatory cytokines, endothelial growth factors (VEGF, bFGF…), and protease (MMP9) implicated in neoangiogenesis. Some cytokines (IL-6, IL-17…) activated Stat3 which also led to the production of VEGF and bFGF. In contrast, other cytokines (IFN, IL-12, IL-21, and IL-27) display an antiangiogenic activity. Recently, it has been shown that some antiangiogenic molecules alleviates immunosuppression associated with cancer by decreasing immunosuppressive cells (MDSC, regulatory T cells), immunosuppressive cytokines (IL-10, TGFβ), and inhibitory molecules on T cells (PD-1). Some of these broad effects may result from the ability of some antiangiogenic molecules, especially cytokines to inhibit the Stat3 transcription factor. The association often observed between angiogenesis and immunosuppression may be related to hypoxia which induces both neoangiogenesis via activation of HIF-1 and VEGF and favors the intratumor recruitment and differentiation of regulatory T cells and MDSC. Preliminary studies suggest that modulation of immune markers (intratumoral MDSC and IL-8, peripheral regulatory T cells…) may predict clinical response to antiangiogenic therapy. In preclinical models, a synergy has been observed between antiangiogenic molecules and immunotherapy which may be explained by an improvement of immune status in tumor-bearing mice after antiangiogenic therapy. In preclinical models, antiangiogenic molecules promoted intratumor trafficking of effector cells, enhance endogenous anti-tumor response, and synergyzed with immunotherapy protocols to cure established murine tumors. All these results warrant the development of clinical trials combining antiangiogenic drugs and immunotherapy.

Objective: Second-line treatment options in advanced urothelial cancer are limited. We investigated the efficacy of a methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) combination after failure of gemcitabine/platinum chemotherapy., Patients and Methods: Twenty-five patients with advanced urothelial cancer, who received second-line MVAC after first-line gemcitabine/cisplatin (n = 9) or gemcitabine/carboplatin (n = 16), were included in this retrospective analysis., Results: Twenty-two patients (88%) relapsed within 6 months after first-line treatment. Following MVAC, there were 5 (20%) objective responses. Median follow-up was 20.2 months. Median progression-free survival (PFS) was 3.8 months (95% CI: 2.3-5.2), and median overall survival (OS) was 9 months (95% CI: 6.6-11.4). Eastern Cooperative Oncology Group performance status 0.1 versus 2 was associated with longer PFS (5 months versus 3.3 months, P = 0.049). Response or stabilization of disease during second-line chemotherapy predicted for a significantly longer PFS and OS (7.4 versus 3.5, P = 0.005; 15.5 versus 7, P = 0.046)., Conclusions: Second-line MVAC chemotherapy may result in prolonged survival in some patients with refractory disease. Further research in this field is necessary.

Testicular cancer is a highly curable neoplasm, even in the case of extragonadal disease. Nevertheless, patients with adverse prognostic features or relapsing after first-line cisplatin-based chemotherapy have a worse prognosis with a death rate greater than 50%. High-dose chemotherapy (HDC) has long been used in this group of patients. The introduction of stem cells, instead of bone marrow, as the source of hemopoietic cells and the use of leukocyte growth factors have substantially reduced the mortality and morbidity of this procedure although the role of HDC is not well defined. This review summarizes the available data, focusing on published randomized studies. The problems associated with the design of these studies and the interpretation of data are discussed. Currently this HDC approach is mainly used in patients who relapse after first-line chemotherapy. Nevertheless, selection of patients likely to benefit from this treatment remains an issue of intense clinical research.

Background: Serum CD105 has been associated with angiogenic activity in cancer, and low CD105 expression has been associated with improved prognosis. The present study evaluated the prognostic significance of serum levels of CD105 and related factors in patients with epithelial ovarian cancer (EOC) after cytoreductive surgery and chemotherapy., Patients and Methods: Eighty-six patients with stages IIC to IV EOC treated postoperatively with platinum-based chemotherapy were included. The enzyme-linked immunosorbent assay was used to measure prechemotherapy serum levels of CD105, transforming growth factor beta1/2 (TGF-beta1/2), angiopoietin 2, vascular endothelial growth factor, and tumor necrosis factor-alpha., Results: High levels of TGF-beta2 (>8908.86 pg/mL) and CD105 (>4.25 ng/mL) were independently associated with improved overall survival (not reached vs 39 months, P = 0.009 and 75 vs 39 months, P = 0.029, respectively), whereas a high level of TGF-beta2 and a low level of vascular endothelial growth factor (<219.04 pg/mL) were independently associated with improved progression-free survival (49 vs 17 months, P = 0.022 and 57 vs 16 months, P = 0.023, respectively). Among patients with favorable (>4.25 ng/mL) CD105 levels, only patients with low TGF-beta1 levels (<177.1 ng/mL) had superior survival than patients with low CD105 levels., Conclusions: Our study confirms the prognostic significance of angiogenesis in EOC and supports a biological interaction between CD105 and TGF-beta1. High angiogenic activity may be associated by increased efficacy of postoperative chemotherapy.