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Metabolic reprogramming is a k`ey hallmark of tumors, developed in response to hypoxia and nutrient deficiency during tumor progression. In both cancer and immune cells, there is a metabolic shift from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, also known as the Warburg effect, which then leads to lactate acidification, increased lipid synthesis, and glutaminolysis. This reprogramming facilitates tumor immune evasion and, within the tumor microenvironment (TME), cancer and immune cells collaborate to create a suppressive tumor immune microenvironment (TIME). The growing interest in the metabolic reprogramming of the TME, particularly its significance in colorectal cancer (CRC)—one of the most prevalent cancers—has prompted us to explore this topic. CRC exhibits abnormal glycolysis, glutaminolysis, and increased lipid synthesis. Acidosis in CRC cells hampers the activity of anti-tumor immune cells and inhibits the phagocytosis of tumor-associated macrophages (TAMs), while nutrient deficiency promotes the development of regulatory T cells (Tregs) and M2-like macrophages. In CRC cells, activation of G-protein coupled receptor 81 (GPR81) signaling leads to overexpression of programmed death-ligand 1 (PD-L1) and reduces the antigen presentation capability of dendritic cells. Moreover, the genetic and epigenetic cell phenotype, along with the microbiota, significantly influence CRC metabolic reprogramming. Activating RAS mutations and overexpression of epidermal growth factor receptor (EGFR) occur in approximately 50% and 80% of patients, respectively, stimulating glycolysis and increasing levels of hypoxia-inducible factor 1 alpha (HIF-1α) and MYC proteins. Certain bacteria produce short-chain fatty acids (SCFAs), which activate CD8+ cells and genes involved in antigen processing and presentation, while other mechanisms support pro-tumor activities. The use of immune checkpoint inhibitors (ICIs) in selected CRC patients has shown promise, and the combination of these with drugs that inhibit aerobic glycolysis is currently being intensively researched to enhance the efficacy of immunotherapy.

A synthetic review of the application of multi-objective optimization models to the design of climate-responsive buildings and neighbourhoods is carried out. The review focused on the software utilized during both simulation and optimization stages, as well as on the objective functions and the design variables. The hereby work aims at identifying knowledge gaps and future trends in the research field of automation in the design of buildings. Around 140 scientific journal articles, published between 2014 and 2021, were selected from Scopus and Web of Science databases. A three-step selection process was applied to refine the search terms and to discard works investigating mechanical, structural, and seismic topics. Meta-analysis of the results highlighted that multi-objective optimization models are widely exploited for (i) enhancing building’s energy efficiency, (ii) improving thermal and (iii) visual comfort, minimizing (iv) life-cycle costs, and (v) emissions. Reviewed workflows demonstrated to be suitable for exploring different design alternatives for building envelope, systems layout, and occupancy patterns. Nonetheless, there are still some aspects that need to be further enhanced to fully enable their potential such as the ability to operate at multiple temporal and spatial scales and the possibility of exploring strategies based on sector coupling to improve a building’s energy efficiency.

Triple-negative breast cancer (TNBC) is associated with high recurrence rates, high incidence of distant metastases, and poor overall survival (OS). Taxane and anthracycline-containing chemotherapy (CT) is currently the main systemic treatment option for TNBC, while platinum-based chemotherapy showed promising results in the neoadjuvant and metastatic settings. An early arising of intrinsic or acquired CT resistance is common and represents the main hurdle for successful TNBC treatment. Numerous mechanisms were uncovered that can lead to the development of chemoresistance. These include cancer stem cells (CSCs) induction after neoadjuvant chemotherapy (NACT), ATP-binding cassette (ABC) transporters, hypoxia and avoidance of apoptosis, single factors such as tyrosine kinase receptors (EGFR, IGFR1), a disintegrin and metalloproteinase 10 (ADAM10), and a few pathological molecular pathways. Some biomarkers capable of predicting resistance to specific chemotherapeutic agents were identified and are expected to be validated in future studies for a more accurate selection of drugs to be employed and for a more tailored approach, both in neoadjuvant and advanced settings. Recently, based on specific biomarkers, some therapies were tailored to TNBC subsets and became available in clinical practice: olaparib and talazoparib for BRCA1/2 germline mutation carriers larotrectinib and entrectinib for neurotrophic tropomyosin receptor kinase (NTRK) gene fusion carriers, and anti-trophoblast cell surface antigen 2 (Trop2) antibody drug conjugate therapy for heavily pretreated metastatic TNBC (mTNBC). Further therapies targeting some pathologic molecular pathways, apoptosis, miRNAS, epidermal growth factor receptor (EGFR), insulin growth factor 1 receptor (IGF-1R), and androgen receptor (AR) are under investigation. Among them, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and EGFR inhibitors as well as antiandrogens showed promising results and are under evaluation in Phase II/III clinical trials. Emerging therapies allow to select specific antiblastics that alone or by integrating the conventional therapeutic approach may overcome/hinder chemoresistance.

In the European Union (EU), where architectural heritage is significant, enhancing the energy performance of historical buildings is of great interest. Constraints such as the lack of space, especially within the historical centers and architectural peculiarities, make the application of technologies for renewable energy production and storage a challenging issue. This study presents a prototype system consisting of using the renewable energy from a photovoltaic (PV) array to compress air for a later expansion to produce electricity when needed. The PV-integrated small-scale compressed air energy storage system is designed to address the architectural constraints. It is located in the unoccupied basement of the building. An energy analysis was carried out for assessing the performance of the proposed system. The novelty of this study is to introduce experimental data of a CAES (compressed air energy storage) prototype that is suitable for dwelling applications as well as integration accounting for architectural constraints. The simulation, which was carried out for an average summer day, shows that the compression phase absorbs 32% of the PV energy excess in a vessel of 1.7 m3, and the expansion phase covers 21.9% of the dwelling energy demand. The electrical efficiency of a daily cycle is equal to 11.6%. If air is compressed at 225 bar instead of 30 bar, 96.0% of PV energy excess is stored in a volume of 0.25 m3, with a production of 1.273 kWh, which is 26.0% of the demand.

In ER+ breast cancer, usually seen as the low immunogenic type, the main mechanisms favouring the immune response or tumour growth and immune evasion in the tumour microenvironment (TME) have been examined. The principal implications of targeting the oestrogen-mediated pathways were also considered. Recent experimental findings point out that anti-oestrogens contribute to the reversion of the immunosuppressive TME. Moreover, some preliminary clinical data with the hormone-immunotherapy association in a metastatic setting support the notion that the reversion of immune suppression in TME is likely favoured by the G0-G1 state induced by anti-oestrogens. Following immune stimulation, the reverted immune suppression allows the boosting of the effector cells of the innate and adaptive immune response. This suggests that ER+ breast cancer is a molecular subtype where a successful active immune manipulation can be attained. If this is confirmed by a prospective multicentre trial, which is expected in light of the provided evidence, the proposed hormone immunotherapy can also be tested in the adjuvant setting. Furthermore, the different rationale suggests a synergistic activity of our proposed immunotherapy with the currently recommended regimen consisting of antioestrogens combined with cyclin kinase inhibitors. Overall, this lays the foundation for a shift in clinical practice within this most prevalent molecular subtype of breast cancer.

Natural gas hydrates are the largest reservoir of natural gas worldwide. This paper proposes and analyzes the CH4-CO2 replacement in the hydrate phase and pure methane collection through the use of membrane-based separation. The investigation uses a 1 L lab reactor, in which the CH4 hydrates are formed in a quartz sand matrix partially saturated with water. CH4 is subsequently dissociated with a CO2 stream supplied within the sediment inside the reactor. An energy and environmental analysis was carried out to prove the sustainability of the process. Results show that the process energy consumption constitutes 4.75% of the energy stored in the recovered methane. The carbon footprint of the CH4-CO2 exchange process is calculated as a balance of the CO2 produced in the process and the CO2 stored in system. Results provide an estimated negative value, equal to 0.004 moles sequestrated, thus proving the environmental benefit of the exchange process.

This research study aimed to investigate the influences of angular-selective retro-reflective (AS-RR) and retro-reflective (RR) materials on the urban equivalent albedo (αeq). Full ray tracing solar analyses were conducted through the Monte Carlo-based numerical model validated in a previous work. Different geometry scenarios with different patterns of urban density were modelled. AS-RR and RR materials were alternately applied to the street and to the most irradiated façade. AS-RR materials were proposed to enhance the αeq of the urban environment particularly during summer. Solar analyses were reiterated for three latitudes (i.e., Oslo, Milan, Cairo). RR pavements and façades were capable of increasing the αeq throughout the year. However, implementing an angular-selective behavior allowed for a reduction of the mitigation potential of RR materials during the winter season. In their best application, RR and AS-RR materials enabled higher αeq in summer (122%) with negligible effects during the winter (7%). Finally, the study highlighted the need for exploiting numerical models capable of conducting full ray tracing solar analyses when investigating materials whose optical properties depend on the angle of incidence of the sunrays (such as RR materials).

Reducing the carbon footprint of energy production is one of the most pressing challenges facing humanity today. Lignocellulosic biomass residues from fruit production industries show promise as a viable energy source. This paper presents a study of the Italian context concerning the utilization of orchard lignocellulosic residues for energy production as electricity or bioethanol. The potential of various orchard residues was assessed through chemical and physical analyses, and an equivalent electrical energy of about 6441.62 GWh or an amount of 0.48 Mt/y of bioethanol was obtained based on the average annual dry residue mass availability of about 3.04 Mt/y. These data represent 9.30% of the national electrical energy production from renewable sources, as well as 6.21% of the Italian demand for gasoline in 2022. Electricity generation from these residues has shown its potential as a reliable and sustainable baseload power source, as well as a source of renewable transportation fuel. The studied process could be a valuable reference to expand these concepts on a global scale to achieve a greener and more sustainable energy future.

The nursing role significantly changed following reforms in the nurse training process. Nowadays, nurses are increasingly trained to promote and improve the quality of clinical practice and to provide support in the assistance of patients and communities. Opportunities and threats are emerging as a consequence of the introduction of new disruptive technologies in public health, which requires the health care staff to develop new digital skills. The aim of this paper is to review and define the role of nurses and the skills they are asked to master in terms of new methodological approaches and digital knowledge in a continuously evolving health care scenario that relies increasingly more on technology and digital solutions. This scoping review was conducted using a thematic summary of previous studies. Authors collected publications through a cross-database search (PubMed, Web of Science, Google Scholar) related to new telemedicine approaches impacting the nurses' role, considering the time span of 2011-2021 and therefore including experiences and publications related to the first phase of the COVID-19 pandemic. The assessment was completed between April and July 2021. After a cross-database search, authors reviewed a selection of 60 studies. The results obtained were organized into 5 emerging macro areas: (1) leadership (nurses are expected to show leadership capabilities when introducing new technologies in health care practices, considering their pivotal role in coordinating various professional figures and the patient), (2) soft skills (new communication skills, adaptiveness, and problem solving are needed to adapt the interaction to the level of digital skills and digital knowledge of the patient), (3) training (specific subjects need to be added to nursing training to boost the adoption of new communication and technological skills, enabling health care professionals to largely and effectively use new digital tools), (4) remote management of COVID-19 or chronic patients during the pandemic (a role that has proved to be fundamental is the community and family nurse and health care systems are adopting novel assistance models to support patients at home and to enable decentralization of services from hospitals to the territory), and (5) management of interpersonal relationships with patients through telemedicine (a person-centered approach with an open and sensitive attitude seems to be even more important in the framework of telemedicine where a face-to-face session is not possible and therefore nonverbal indicators are more problematic to be noticed). Further advancing nurses' readiness in adopting telemedicine requires an integrated approach, including combination of technical knowledge, management abilities, soft skills, and communication skills. This scoping review provides a wide-ranging and general-albeit valuable-starting point to identify these core competences and better understand their implications in terms of present and future health care professionals' roles.

The environmental impacts of sport events have been growing during the last decades, which has led to the organizing associations developing adequate countermeasures to both reduce carbon emissions due to construction and operational stages compensate for the emissions. This work aims at proposing an approach to stadiums energy enhancement that includes strategies largely recognized as effective and applicable to several building typologies (residential, commercial, academic, etc.). The selected case study is the Dacia Arena in northern Italy that has been recently refurbished and renovated. The proposed workflow has as a goal minimizing the increment of the operational emissions, caused by new heated areas in the stadium. Firstly, the energy consumption was estimated in dynamic state for Scenario 0 (current state) and Scenario 1 (refurbished state) to quantify the new plant’s energy demand. Secondly, two hypothetical system layouts were proposed and evaluated. In the first, the power for lighting, cooling and heating is supplied by a system that couples photovoltaic panels with heat pump. In the second, the same photovoltaic plant is integrated with a biomass plant and an absorption chiller. The comparison highlights the suitability of those interventions and the environmental advantages deriving from their exploitation.