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We used inelastic x-ray scattering methods to measure the terahertz spectrum of density fluctuations of ethanol in both liquid and solid phases. The results of a Bayesian inference-based lineshape analysis with a multiple excitation model and the comparison with a previous similar analysis on water indicate that the different structures induced by hydrogen bonds in ethanol and water have a profound influence on the respective dynamic responses, the latter being characterized by longer living and better resolved high-frequency acoustic excitations. In addition, we compare these findings with those obtained with an alternative approach based on the exponential expansion theory and ensuring sum rules fulfillment, demonstrating that the model's choice directly impacts the number of spectral modes detected. [ABSTRACT FROM AUTHOR]

In a global context, the identification of frameworks and assessment tools for achieving sustainable development requires the study of urban sustainability at different scales. While sustainability can be quantified more precisely on a larger scale, it is challenging to adapt these accounting techniques to smaller sites. Measuring becomes more challenging when researching urban sustainability from several viewpoints, especially when constructing an acceptable set of measurements while taking into account the several issues of the unique decision-making apparatus from theoretical and geographical perspectives. Which sorts of indicators should be prioritized above others? How many indicators should be used? Which criteria should be employed to choose the best indicators for the location of interest? This study addresses the aforementioned research problems by proposing a systematic, multidirectional approach to defining an adequate collection of indicators for sustainability accounting in urban situations. A top-down strategy, which provides a literature study to identify regularly used indicators in essential sustainability categories, is joined by a bottom-up approach, which creates indicators based on real-world circumstances. The combination of these two methodologies seeks to produce a set of relevant sustainability measurements. A neighborhood rehabilitation project for public housing in Le Lignon (Switzerland) serves as a pilot case for calibrating the proposed multidirectional technique. The final findings can support the public and private parties involved in sustainable urban planning procedures in assessing urban projects based on location-specific features. [ABSTRACT FROM AUTHOR]

The advent of immunotherapy and antibody–drug conjugates (ADCs) have revolutionized breast cancer treatment, offering new hope to patients. However, challenges, such as resistance and limited efficacy in certain cases, remain. Recently, the combination of these therapies has emerged as a promising approach to address these challenges. ADCs play a crucial role by delivering cytotoxic agents directly to breast cancer cells, minimizing damage to healthy tissue and enhancing the tumor-killing effect. Concurrently, immunotherapies harness the body's immune system to recognize and eliminate cancer cells. This integration offers potential to overcome resistance mechanisms and significantly improve therapeutic outcomes. This review explores the rationale behind combining immunotherapies with ADCs, recent advances in this field, and the potential implications for breast cancer treatment. [ABSTRACT FROM AUTHOR]

In light of the ever‐increasing demand for lightweight materials suitable for heat transport applications, many efforts are devoted to enhancing the thermal properties of polymer‐based nanocomposites via nanofillers. In the present study, nanocomposites based on epoxy resin, including 3 wt% of multiwalled carbon nanotubes (MWCNTs), are prepared and then thermally characterized. More in detail, it is investigated the temperature increase over time, due to the Joule heating effect, when different voltage values (70, 80, and 90 V) are applied to the specimens. These experimental measures validate a simulation study performed with commercial software (COMSOL Multiphysics®), which allows the investigation of several thermal aspects of the Joule heating. A perfect agreement between experimental and modeling data is found. This means that, in support of experimental activities, modern computational methods can add knowledge in materials science to discover new advanced materials or investigate the existing ones in depth. The present case study examines the potential use of nano‐reinforced polymeric materials for thermal applications involving the Joule effect. [ABSTRACT FROM AUTHOR]

This study investigates the role of individual and contextual factors as potential concurrent predictors of bullying and victimization in male and female high school students. The sample included 517 adolescents and their teachers. With a multi‐informant approach, measures of bullying and victimization, personality traits, psychopathological symptoms, peer ratings of popularity, loneliness, bothersomeness, as well as school climate, were collected. A series of regression analyses showed gender differences in the dysfunctional personality traits resulted as predictors of bullying (e.g., impulsivity for males and deceitfulness for females). As for victimization, also the role of contextual predictors (i.e., negative relations with peers and safety problems) was significant, with some differences between males and females. These results highlight the importance of a multi‐informant and multifactor (i.e., individual, contextual) approach when investigating the dynamics of bullying and victimization. Practitioner points: Different patterns of concurrent predictors are related to bullying and victimization in males and females.Both individual and contextual factors predict victimization; only individual factors predict bullying.A school climate with negative school relations (males and females) and safety problems (females) concurrently predicts victimization. [ABSTRACT FROM AUTHOR]

A recent simulation study of the transverse current autocorrelation of the Lennard-Jones fluid [Guarini et al., Phys. Rev. E 107, 014139 (2023)] revealed that this function can be perfectly described within the exponential expansion theory [Barocchi et al., Phys. Rev. E 85, 022102 (2012)]. However, above a certain wavevector Q, not only transverse collective excitations were found to propagate in the fluid, but a second oscillatory component of unclear origin (therefore called X) must be considered to fully account for the time dependence of the correlation function. Here, we present an extended investigation of the transverse current autocorrelation of liquid Au as obtained by ab initio molecular dynamics in the very wide range of wavevectors 5.7 ≤ Q ≤ 32.8 nm−1 in order to also follow the behavior of the X component, if present, at large Q values. A joint analysis of the transverse current spectrum and its self-portion indicates that the second oscillatory component arises from the longitudinal dynamics, as suggested by its close resemblance with the previously determined component accounting for the longitudinal part of the density of states. We conclude that such a mode, albeit featuring a merely transverse property, fingerprints the effect of longitudinal collective excitations on single-particle dynamics, rather than arising from a possible coupling between transverse and longitudinal acoustic waves. [ABSTRACT FROM AUTHOR]

An outbreak species exhibits extreme, rapid population fluctuations that can be qualified as discrete events within a continuous dynamic. When outbreaks occur they may appear novel and disconcerting because the limiting factors of their dynamics are not readily identifiable. We present the first population hybrid dynamic model that combines continuous and discrete processes, designed to simulate marine species outbreaks. The deterministic framework was tested using the case of an unexploited benthic invertebrate species: the small, serpulid polychaete Ditrupa arietina. This species is distributed throughout the northeast Atlantic Ocean and Mediterranean Sea; it has a life cycle characterised by a pelagic dispersive larval stage, while juveniles and adults are sedentary. Sporadic reports of extremely high, variable densities (from <10 to >10,000 i n d. m − 2 ) have attracted attention from marine ecologists for a century. However, except for one decade-long field study from the Bay of Banyuls (France, Gulf of Lions, Mediterranean Sea), observations are sparse. Minimal formulations quantified the processes governing the population dynamics. Local population continuous dynamics were simulated from a size-structured model with a null immigration–emigration flux balance. The mathematical properties, based on the derived hybrid model, demonstrated the possibilities of reaching an equilibrium for the population using a single number of recruits per reproducer. Two extrapolations were made: (1) local population dynamics were simulated over 180 years using North Atlantic Oscillation indices to force recruitment variability and (2) steady-state population densities over the Gulf of Lions were calculated from a connectivity matrix in a metapopulation. The dynamics reach a macroscopic stability in both extrapolations, despite the absence of density regulating mechanisms. This ensures the persistence of D. arietina, even when strong, irregular oscillations characteristic of an outbreak species are observed. The hybrid model suggests that a macroscopic equilibrium for a population with variable recruitment conditions can only be characterised for time periods which contain several outbreak occurrences distributed over a regional scale. [ABSTRACT FROM AUTHOR]

In their 2023 book, "The Blue Compendium: From Knowledge to Action for a Sustainable Ocean Economy", Lubchenko and Haugan invoked alternate stable (AS) states marginally as an undesired consequence of sources of disturbance on populations, communities and ecosystems. They did not provide detailed arguments, but considered the existence of AS states as a given. Conversely, May, in his 1977 Nature article, pointed out that, when applied to systems that are complex, "the [AS states] theory remains largely metaphorical". This is the starting point of this critical review, which aims to re-examine the general theory behind AS states in ecological systems and its applications to marine ecology and conservation. The focus is first on theory, taking as examples communities that sustain competition and studying the relative importance of the fluxes of individuals between simple low-dimension, interconnected systems. We find that a minimal formulation of fluxes is sufficient to obtain a set of non-null multiple stable (MS) states and to trigger shifts between AS states when fluxes become large enough. This provides new insights into the theory of rescue and mass effects by distinguishing them through a threshold at which the system dynamics shift from one stable equilibrium to another. Then, we consider how the theoretical framework of AS states has been applied in marine environments. It appears that many applications have confounded shifts between AS states and changes in the structure of systems, particularly when the complexity of the systems increases. The main difficulty for any application remains that the concepts of MS and AS states can only be established and validated for low-dimension systems and simplified experiments. This is because the mathematical properties of models that describe large-dimension, complex systems deviate from the observed characteristics of their real-world counterparts. There are many intriguing scientific challenges around the plausible shifts between AS states, but a deeper understanding and characterization of their occurrence in nature would require a significant investment in modeling to formulate predictive ecosystem models. [ABSTRACT FROM AUTHOR]

Understanding how molecules engage in collective motions in a liquid where a network of bonds exists has both fundamental and applied relevance. On the one hand, it can elucidate the "ordering" role of long-range correlations and inspire new avenues to control such order to implement sound manipulation. Water represents an ideal investigation case to unfold these general aspects, and, across the decades, it has been the focus of thorough scrutiny. Despite this investigative effort, the spectrum of terahertz density fluctuations of water largely remains a puzzle for condensed matter physicists. To unravel it, we compare previous scattering measurements of water spectra with new ones on ice. Owing to the unique asset of Bayesian inference, we draw a more detailed portrayal of the phonon response of ice. The comparison with the one of liquid water challenges the current understanding of density fluctuations in water, or more in general, of any networked liquid. [ABSTRACT FROM AUTHOR]

Due to their remarkable intrinsic physical properties, carbon nanotubes (CNTs) can enhance mechanical properties and confer electrical and thermal conductivity to polymers currently being investigated for use in advanced applications based on thermal management. An epoxy resin filled with varying concentrations of CNTs (up to 3 wt%) was produced and experimentally characterized. The electrical percolation curve identified the following two critical filler concentrations: 0.5 wt%, which is near the electrical percolation threshold (EPT) and suitable for exploring mechanical and piezoresistive properties, and 3 wt% for investigating thermo-electric properties due to the Joule effect with applied voltages ranging from 70 V to 200 V. Near the electrical percolation threshold (EPT), the CNT concentration in epoxy composites forms a sparse, sensitive network ideal for deformation sensing due to significant changes in electrical resistance under strain. Above the EPT, a denser CNT network enhances electrical and thermal conductivity, making it suitable for Joule heating applications. Numerical models were developed using multiphysics simulation software. Once the models have been validated with experimental data, as a perfect agreement is found between numerical and experimental results, a simulation study is performed to investigate additional physical properties of the composites. Furthermore, a statistical approach based on the design of experiments (DoE) was employed to examine the influence of certain thermal parameters on the final performance of the materials. The purpose of this research is to promote the use of contemporary statistical and computational techniques alongside experimental methods to enhance understanding of materials science. New materials can be identified through these integrated approaches, or existing ones can be more thoroughly examined. [ABSTRACT FROM AUTHOR]

Simple Summary: With the increase in the mastectomy rate, the number of patients opting for postmastectomy reconstruction has been rising, with implant-based procedures being the most commonly used method. One of the most feared complications is the loss of reconstruction, often caused by implant infection. This can lead to prolonged antibiotic treatments, additional surgical procedures, capsular contracture, and unsatisfactory aesthetic results, with a significant psychological impact on patients. This study analyzed infection rates at our institution and evaluated the effectiveness of our prevention protocol introduced in 2020, comparing the data on surgical site infections (SSIs) between Trieste Hospital (with the protocol) and another center in Gorizia (without the protocol). We enrolled 396 patients, divided into the experimental group (Trieste) and the control group (Gorizia). Infected patients were 5 in the first group (1.7%) and 8 in the second group (7.9%), with an overall infection rate of 3.2%. We conclude that the prevention protocol has reduced the incidence of postoperative infections. Background: With the rise in the mastectomy rate, the number of patients who choose to undergo postmastectomy reconstruction has been increasing, and implant-based procedures are the most performed methods for postmastectomy breast reconstruction. Among the possible complications, the most feared is the loss of reconstruction. It can be related to several reasons, but one of the most common is infection of the implant, which can lead to prolonged antibiotic treatment, undesired additional surgical procedures, increased incidence of capsular contracture, and unsatisfactory aesthetics results, with a huge psychological impact on patients. Aims: The primary intent of this study is to analyze the status of infection rates at our institution and evaluate the effectiveness of our prevention protocol since its introduction. Secondly, we compared data of the surgical site infections (SSIs) after implant-based breast reconstruction at Trieste Hospital, where the protocol has been employed since 2020, and in another center, where plastic surgeons of our team are involved, with different prevention procedures. Methods and Results: We enrolled 396 female patients, who underwent implant-based breast reconstruction, using definitive mammary implants or breast tissue expanders, with or without ADM (acellular dermal matrix), both for breast cancer and risk-reducing surgery in BRCA1/2 patients. Patients treated at the Hospital of Trieste, with the use of the prevention protocol, were considered the experimental group (group 1), while patients treated in Gorizia by the same breast team with standardized best-practice rules, but without the use of the prevention protocol, were considered the control group (group 2). Infected patients were 5 in the first group (1.7%) and 8 in the second one (7.9%), with a global infection rate of 3.2%. Conclusion: After the introduction of our prevention protocol, we faced a lower incidence of infection after breast surgery with implants or tissue expanders. [ABSTRACT FROM AUTHOR]

The present work deals with the modeling of the response to neutrons of heteronuclear diatomic liquids, with special interest in the case of hydrogen deuteride (HD), as a possible candidate for the moderation process required in the production of cold neutrons. Preliminary evaluations of the model giving the neutron double differential cross section of a heteronuclear vibrating rotor were performed in the recent past by using, as a first approximation, the ideal gas law for the center-of-mass translational dynamics. Here, the state-of-the-art methodology (based on the use of quantum simulations of the velocity autocorrelation function) for predicting the neutron response of moderately quantum fluids (like molecular hydrogen and deuterium at low temperatures) is applied to the heteronuclear form of this molecular liquid. The unavailability of the double differential cross section experimental data on liquid HD still compels us to test the calculations only at an integral level, i.e., against the only available measurements of the total neutron cross section of HD. Despite the well-tested and parameter-free computational approach, which includes proper consideration of the quantum effects, the present findings on HD indicate the evident need for more accurate measurements of its total cross section in extended ranges of incident energy, as well as of an experimental determination of the double differential cross section of this mild quantum liquid. For further applicative purposes, a very useful by-product of this study is the determination of the self diffusion coefficient D of the HD in the liquid phase. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer presents significant therapeutic challenges, driving the exploration of novel treatment strategies. Programmed cell death (PCD) mechanisms, including apoptosis, autophagy, and programmed necrosis, are crucial in lung cancer pathogenesis and treatment response. Dysregulation of these pathways contributes to tumor progression and therapy resistance. Immunonutrition, using specific nutrients to modulate immune function, and metabolic reprogramming, a hallmark of cancer cells, offer promising intervention avenues. Nutritional interventions, such as omega-3 fatty acids, modulate PCD pathways in cancer cells, while targeting metabolic pathways implicated in apoptosis regulation presents a compelling therapeutic approach. Clinical evidence supports the role of immunonutritional interventions, including omega-3 fatty acids, in enhancing PCD and improving treatment outcomes in lung cancer patients. Additionally, synthetic analogues of natural compounds, like resveratrol, show promising anticancer properties by modulating apoptotic signaling pathways. This review highlights the convergence of immunonutrition, metabolism, and PCD pathways in lung cancer biology, emphasizing the potential for therapeutic exploration. Further elucidation of the specific molecular mechanisms governing these interactions is crucial for translating these findings into clinical practice and enhancing lung cancer management. Lung cancer presents significant therapeutic challenges, motivating the exploration of novel treatment strategies. Programmed cell death (PCD) mechanisms, encompassing apoptosis, autophagy, and programmed necrosis, are pivotal in lung cancer pathogenesis and the treatment response. Dysregulation of these pathways contributes to tumor progression and therapy resistance. Immunonutrition, employing specific nutrients to modulate immune function, and metabolic reprogramming, a hallmark of cancer cells, offer promising avenues for intervention. Nutritional interventions, such as omega-3 fatty acids, exert modulatory effects on PCD pathways in cancer cells, while targeting metabolic pathways implicated in apoptosis regulation represents a compelling therapeutic approach. Clinical evidence supports the role of immunonutritional interventions, including omega-3 fatty acids, in augmenting PCD and enhancing treatment outcomes in patients with lung cancer. Furthermore, synthetic analogs of natural compounds, such as resveratrol, demonstrate promising anticancer properties by modulating apoptotic signaling pathways. This review underscores the convergence of immunonutrition, metabolism, and PCD pathways in lung cancer biology, emphasizing the potential for therapeutic exploration in this complex disease. Further elucidation of the specific molecular mechanisms governing these interactions is imperative for translating these findings into clinical practice and improving lung cancer management. [ABSTRACT FROM AUTHOR]

Modal properties of dynamically tested wind turbine blades (WTBs) of a utility-scale wind turbine are identified. A comprehensive experimental program including free vibration and short- and long-term forced vibrations representing resonance and simplified fatigue conditions was carried out to investigate vibration-based features for damage diagnosis and prognosis. A set of 12 undamaged WTBs were tested to study the variability of the identified modal parameters. Results indicate that the variability of the natural frequencies was rather low, while the obtained damping ratios exhibited significant differences. Forced vibration tests were then conducted. To reach the failure of the blades, approximately 1.9 × 104 and 4.2 × 107 cycles were induced in the short- and long-term tests, respectively. Modal properties identified during testing protocols suggest that natural frequencies correlate well with damage. A linear finite element model was also developed, and its modal properties are compared to the identified modal parameters of the undamaged blades. [ABSTRACT FROM AUTHOR]

The aim of this paper is to evaluate the usefulness of educational software among teachers in Italy (N = 559). The evaluation of usefulness was conducted on the latest and most popular web-based software used by European teachers, namely: Quizizz, Mentimeter, Wakelet, Padlet, Canva, Emaze, Answergarden, Jamboard, Coggle, Createley, Wordwall, LearningApps, Prezi, Kahoot, Plickers, Trimino, Dobble, Genial.ly, ClassDojo, Explain Everything, KhanAcademy, and Easelly. Based on data collected in the first half of 2022 using an online survey, it was noted that: 1) The majority of teachers are not able to evaluate modern software because they do not use such teaching resources as those listed; 2) About 9.3% of teachers rate the listed software highly; 3) Most commonly teachers use and also rate highly: Canva, Wordwall, Padlet, LearningApps, Kahoot, Coggle, Jamboard, and Prezi; 4) Seniority and workplace does not always differentiate the evaluation of educational software. [ABSTRACT FROM AUTHOR]

In adolescence individuals enlarge their social relationships and peer groups acquire a strong importance for their identity. Moreover, adolescents can experiment negative relationships with peers, i.e., bullying/cyberbullying. The present study aims to investigate the relationship between the feeling of belonging to a specific group, social identification, the distance that adolescents maintain interacting with others, interpersonal distance, and bullying/cyberbullying behaviors. Adolescents (age range 10–15 years) completed online measures of group identification (social identification with classmates, friends and family), interpersonal distance, and bullying and cyberbullying (perpetration and victimization). Results showed that adolescents with low social identification with classmates and friends chose larger interpersonal distance. Additionally, low scores in social identification with classmates were associated with higher victimization in cyberbullying. In contrast, adolescents with low scores in social identification with family were more involved as bullies in bullying and as victims in cyberbullying. Male adolescents were more likely to be victimized in bullying than females. This study underlines how social identification with peers and family works as a buffer in interfacing strangers, adjusting the distance maintained with them, and as a protective factor against aggressive relationships in adolescence. This study provides new opportunities for psychologists in understanding the psychological dynamics that shape social interactions among adolescents. [ABSTRACT FROM AUTHOR]

Plasma membrane (PM) H+-ATPases of the P-type family are highly conserved in yeast, other fungi, and plants. Their main role is to establish an H+ gradient driving active transport of small ions and metabolites across the PM and providing the main component of the PM potential. Furthermore, in both yeast and plant cells, conditions have been described under which active H+-ATPases promote activation of TORC1, the rapamycin-sensitive kinase complex controlling cell growth. Fungal and plant PM H+-ATPases are self-inhibited by their respective cytosolic carboxyterminal tails unless this domain is phosphorylated at specific residues. In the yeast H+-ATPase Pma1, neutralization of this autoinhibitory domain depends mostly on phosphorylation of the adjacent Ser911 and Thr912 residues, but the kinase(s) and phosphatase(s) controlling this tandem phosphorylation remain unknown. In this study, we show that S911-T912 phosphorylation in Pma1 is mediated by the largely redundant Ptk1 and Ptk2 kinase paralogs. Dephosphorylation of S911-T912, as occurs under glucose starvation, is dependent on the Glc7 PP1 phosphatase. Furthermore, proper S911-T912 phosphorylation in Pma1 is required for optimal TORC1 activation upon H+ influx coupled amino-acid uptake. We finally show that TORC1 controls S911-T912 phosphorylation in a manner suggesting that activated TORC1 promotes feedback inhibition of Pma1. Our results shed important new light on phosphoregulation of the yeast Pma1 H+-ATPase and on its interconnections with TORC1. Author summary: In all eukaryotic cells, the plasma membrane contains an abundant pump which catalyzes transport of specific ions at the expense of ATP. These ATPases of the P-type superfamily are crucial, as the ion gradient they establish across the membrane supports active uptake of nutrients and export of waste products of cell metabolism. Fungal and plant cells differ from animal cells in that the ion gradient that energizes their plasma membrane is composed of protons (H+) instead of sodium (Na+). The H+-ATPases establishing this H+ gradient are highly conserved and also contribute to regulating a kinase complex called TORC1 (Target of Rapamycin Complex 1), which plays a central role in controlling cell growth. The activity of plant and fungal H+-ATPases is regulated by a mechanism of self-inhibition mediated by their cytosol-facing C-terminal extremity. The inhibitory effect of this regulatory domain is neutralized by phosphorylation of specific residues. In the yeast Saccharomyces cerevisiae, two adjacent C-terminal residues, Ser911 and Thr912, are particularly important in controlling the activity of the main plasma membrane H+-ATPase, known as Pma1. This report describes identification of the long-sought kinases and phosphatases modulating phosphorylation of these two residues and reveals a potential contribution of TORC1 to feedback control of this double modification. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to analyze the impact of environmental regulation on innovation and international competitiveness. We test the weak, narrow, and strong versions of Porter's hypotheses by looking at the impact of environmental regulation on exports both directly and indirectly through innovation and by introducing the role of pollution intensity in moderating the impact of stringent regulation on innovation and international competitiveness. Green policies are measured with the OECD Environmental Stringency Policy Index, distinguishing between market, non-market instruments, and technology support policies. Differently from previous papers, we adopt the technology gap approach to trade, which is suitable for relating environmental regulation to trade competitiveness and we apply the simultaneous-equation system econometric model with a moderating factor represented by pollution intensity. The results support the weak and strong versions of Porter's hypotheses and find that the positive impact of regulation on innovation and exports increases with a country's pollution intensity, suggesting that green policies, if properly coordinated, can represent a win–win strategy, fostering, at the same time, sustainability and international competitiveness. [ABSTRACT FROM AUTHOR]

There is sufficient evidence on the negative consequences of cyberbullying victimisation depending on the coping styles. Social support seeking is among the most effective strategies for coping with cybervictimisation, but it is scarcely used. The robust Maximum Likelihood (ML) method was used to test the potential mediating role of individual (self-awareness, and responsible decision-making) and contextual variables (self-perceived parental and peer support) in the relationship between cybervictimisation and social support seeking in boys and girls. This cross-sectional study collected data from 1,276 Spanish secondary school students (51.2% boys, 48.8% girls) aged 11–18 (M = 13.88, SD = 1.42). Structural equation modelling (SEM) results pointed out responsible decision-making and self-perceived parental support as relevant mediating factors for girls. By contrast, the model was not significant for boys. These findings highlight the importance of both individual and contextual variables in helping adolescents cope with cyberaggressions, considering gender differences. [ABSTRACT FROM AUTHOR]

Hormone receptor-positive (HR+) breast cancer (BC) accounts for about 60–70% of all diagnosed BCs, and endocrine therapy has long been the hallmark of systemic treatment for this tumor subtype. However, the therapeutic paradigm of luminal BC has been overcome due to recent evidence of antibody–drug conjugate (ADC) activity (such as trastuzumab deruxtecan and sacituzumab govitecan) in pretreated metastatic HR+ BC patients. Therefore, nowadays, the identification of patients who can benefit more from this approach represents a new challenge, as does the management of new toxicities and the integration of these drugs into the therapeutic algorithm of HR+ metastatic BC patients. [ABSTRACT FROM AUTHOR]

Summary: Blinatumomab is the first bi‐specific T‐cell engager approved for relapsed or refractory B‐cell precursor acute lymphoblastic leukaemia (B‐ALL). Despite remarkable clinical results, the effects of blinatumomab on the host immune cell repertoire are not fully elucidated. In the present study, we characterized the peripheral blood (PB) and, for the first time, the bone marrow (BM) immune cell repertoire upon blinatumomab treatment. Twenty‐nine patients with B‐ALL received blinatumomab according to clinical practice. Deep multiparametric flow cytometry was used to characterize lymphoid subsets during the first treatment cycle. Blinatumomab induced a transient redistribution of PB effector T‐cell subsets and Treg cells with a persistent increase in cytotoxic NK cells, which was associated with a transient upregulation of immune checkpoint receptors on PB CD4 and CD8 T‐cell subpopulations and of CD39 expression on suppressive Treg cells. Of note, BM immune T‐cell subsets showed a broader post‐treatment subversion, including the modulation of markers associated with a T‐cell‐exhausted phenotype. In conclusion, our study indicates that blinatumomab differentially modulates the PB and BM immune cell repertoire, which may have relevant clinical implications in the therapeutic setting. [ABSTRACT FROM AUTHOR]

Internet usage is a salient developmental factor in adolescents' lives. Although relevant correlates of Internet use have been documented earlier, there is a lack of information on lower socioeconomic status groups. This is important, as these adolescents have increased risk of negative online experiences. The current survey aimed to explore Internet use and parental involvement amongst adolescents from areas of socio-economic disadvantage in 30 urban schools across five European countries. A total of 2594 students participated, of whom 90% were 14–16 years. Virtually all adolescents of socioeconomic disadvantage had Internet access, with 88.5% reporting spending more than two hours per day online, often on apps such as Instagram, Snapchat, and YouTube. Almost one-third of adolescents did not talk with their parents about their Internet use and almost two-thirds indicated that their parents were only a little or not interested in their Internet use. A consistent finding across countries was that girls more often talked with their parents about their Internet use and more often reported that their parents were interested in their Internet use than boys. The results suggest that parents have an important task in explicitly showing interest in their adolescents' Internet use, with special attention needed for boys. [ABSTRACT FROM AUTHOR]

Background: The majority of female cancer patients undergoing anticancer treatments are at risk of experiencing 'cancer treatment-related infertility', which can result in permanent damage to their reproductive prospects. Among the fertility preservation methods, ovarian tissue cryopreservation (OTC) has emerged as an alternative for these patients. The Cancer Institute of Bari initiated a research program to assess the feasibility of OTC. This study compares the viability of ovarian cortical fragments cryopreserved using slow freezing (SF) and ultra-rapid freezing (URF) methods. Methods: Ovarian cortex biopsies were obtained from 11 fertile women enrolled in our oncofertility service between June 2022 and January 2023. After tissue collection, a histological assessment was performed before cryopreservation. OTC was carried out using both SF and URF methods. Six months later, thawed samples were evaluated for follicle counts and histological integrity. Results: No statistically significant difference was observed in the proportion of intact follicles (means of 31.5% and 73.0% in the SF and URF groups, respectively; p = 0.064). However, there was a significant difference in the number of follicles between the SF group (n = 149) and the URF group (n = 37) (p = 0.046). Conclusions: We assessed the viability of ovarian cortex after freezing and thawing, focusing on the structural integrity of follicles. Our findings suggest that there are no significant differences between the SF and URF methods. [ABSTRACT FROM AUTHOR]

While both the academic literature and practice suggest that the use of accounting information is often not neutral, the factors behind a manipulative use of accounting information are under-researched—especially in the public sector context. This article is intended to stimulate the debate about ethical questions related to accounting information manipulation that are often neglected. The authors aim to increase awareness among politicians and public managers about the disputability, or even inappropriateness, of the accounting information they receive. This article explores ethical issues of accounting information manipulation (AIM) in the political arena. After conceptualizing AIM, including its drivers, techniques, contextualities and impacts, the authors discuss underlying tensions between various types of values that emerge as a trigger for applying AIM. In that respect a distinction is made between values at the societal, organizational and individual level, such as, respectively, sustainability, transparency and honesty, and additionally between private values related to personal gain and public values. [ABSTRACT FROM AUTHOR]

Background: Since the incidence of cancer increases with age, in older cancer patients important information may be missed without a Comprehensive Geriatric Assessment (CGA). On the other side, CGA is a time-consuming and complex instrument, so that Geriatric 8 (G8) has been proposed as a more feasible screening tool to identify patients who could benefit from a CGA evaluation. G8 consists of 8 questions (patient age + 7 items derived from the Mini Nutritional Assessment questionnaire). A G8 score ≤ 14 is considered associated with frailty and risk of malnutrition. Another screening test is Bioelectrical Impedance Analysis (Bioimpedentiometry, BIA), which enables to evaluate the nutritional status through a specific parameter known as Phase angle (PhA). This study is aimed at assessing the ability of G8 alone or in combination with PhA to detect elderly cancer patients at higher risk for malnutrition who cannot undergo immediate anticancer treatments. Methods: A total of 289 cancer patients (168 men and 121 women) aged ≥ 70 years old were enrolled and performed both G8 test, body mass index (BMI) and BIA assessments. A concurrent G8 score ≤ 14 and PhA < 5 defined subjects most exposed to the risk of malnutrition. Results: An association between BMI and G8 (p < 0.001, OR 1.54) and a clinically significant relationship between G8 and PhA (p = 0.013) were observed. Conclusion: G8 can be used to identify patients at risk for malnutrition who would benefit from comprehensive CGA. The concurrent use of G8 and BIA presents a higher power in discriminating subjects at higher risk of malnutrition than a single test. This study suggests the need for routine assessment of nutritional status in cancer patients using combinations of methods, in order to implement strategies for individually-tailored care before starting any treatment. [ABSTRACT FROM AUTHOR]

This original paper, based on data from the Erasmus+Blurred Lives Project, presents a new multi-dimensional categorisation model to describe negative online experiences, including forms of cyberbullying, based on a study of internet usage among over N = 2,500 adolescents with lower socio-economic status (SES) backgrounds across five European countries. The paper first sets out the rationale for the development of a new coding system, before describing the current study and nature of the survey data collected. There follows a description of the development of the new system and the series of reliability checks undertaken by the research team (N= 11, from 5 countries) and of the refinements made to the categories and codes. The resulting coding system is presented with consideration of the strengths and limitations, and description of two early pilot studies which have successfully adopted the new system. [ABSTRACT FROM AUTHOR]

(a) Cohort of Multiple Myeloma patients treated with DVd (Daratumumab + Bortezomib + Dexamethasone): OS in the subgroup of "Lenalidomide-refractory patients" (70.6% of patients). The last treatment received before the DVd regimen was Carfilzomib-Lenalidomide-Dexamethasone (KRd) (39.6%), Lenalidomide-Dexamethasone (Rd) (39.6%), Elotuzumab-Lenalidomide-Dexamethasone (EloRd) (14.6%) and Ixazomib-Lenalidomide-Dexamethasone (IxaRd) (6.2%). (range 1-34) ht 1 Hgb: hemoglobin; LDH: lactate dehydrogenase; 2M: 2microglobulin; DVd: Daratumumab-Bortezomib-Dexamethasone; KRd: Carfilzomib-Lenalidomide-Dexamethasone; Rd: Lenalidomide-Dexamethasone; EloRd: Elotuzumab-Lenalidomide-Dexamethasone; IxaRd: Ixazomib-Lenalidomide-Dexamethasone. (b) Cohort of Multiple Myeloma patients treated with DVd (Daratumumab + Bortezomib + Dexamethasone): TTP in the subgroup of "Lenalidomide-refractory patients" (70.6% of patients). [Extracted from the article]

Introduction: Fertility preservation (FP) and monitoring has considerable relevance in the multidisciplinary approach to cancer patients. In these consensus-based practical recommendations, the scientific societies Fondazione Italiana Linfomi (FIL) and Società Italiana della Riproduzione Umana (SIRU) reviewed the main aspects and identified the optimal paths which aim to preserve and monitor fertility in patients diagnosed with lymphoma at the different phases of the disease and during long-term survivorship. Methods: For the Panel, eleven experts were selected for their expertise in research and clinical practice on onco-fertility and lymphoma. The Panel's activity was supervised by a chairman. A series of rank-ordering key questions were proposed according to their clinical relevance and discussed among the Panel, focusing on patients diagnosed with non-Hodgkin's lymphomas and Hodgkin lymphoma. Agreement among all the Panelists on the content and terminology of the statements was evaluated by a web-based questionnaire according to the Delphi methodology. Results: From the literature review a total of 78 questions or sentences, divided into the 6 areas of interest, were identified. By applying the Gwet's AC, k was: Section 1: 0,934 (Very good); Section 2: 0,958 (Very good); Section 3: 0,863 (Very good); Section 4: 0,649 (Good); Section 5: 0,936 (Very good); Section 6 raw agreement 100%. Two rounds of Delphi allowed to provide the maximum agreement. All statements were newly discussed in a round robin way and confirmed for the drafting of the final recommendations. Discussion: These recommendations would be useful for onco-hematologists, gynecologists, urologists, and general practice physicians who take care of young lymphoma patients to guarantee an evidence-based oncofertility assessment and treatment during the oncologic pathway. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) in elderly women is an increasing health issue due to demographic changes. BC tends to present later and may receive less than standard treatment options. More often, BC in elderly patients is endocrine-positive (HR+). The treatment of elderly patients with metastatic BC (mBC) represents a therapeutic challenge. In recent years, the treatment landscape of patients that are HR+/Her2-negative has changed due to the introduction in clinical practice of new targeted drugs, which have improved patient outcomes. Elderly patients are a small percentage of all patients enrolled in clinical trials and, to date, there are no standardized guidelines that define the best treatment option for this patient population. This can lead to undertreatment or overtreatment, impacting patient morbidity and mortality. Geriatric Assessment tools to tailor the treatment in elderly patients are underused because they are long and difficult to apply in a busy routine clinical practice. For all these reasons, there is an urgent need to produce data about the best treatment for elderly patients with HR+ mBC. Herein, we report data from randomized clinical trials and real-world evidence on the therapeutic options for HR+ Her2-negative mBC elderly patients and explore future treatment directions. [ABSTRACT FROM AUTHOR]

There is ample evidence of bullying victimization-perpetration association. However, little is known about the role of socioemotional variables in reinforcing or mitigating it. There is a need to delve deeper into what victims feel and do that leads them to bully. This study aimed to analyze the moderating role of peer relationship management and anger regulation in the victimization-perpetration association, controlling gender and age. This cross-sectional study involved 874 Spanish middle school students (47.8% girls) aged 11 to 18 years (M = 13.92, SD = 1.45). The results revealed that the perpetration was positively related to victimization and negatively related to peer relationship management and anger regulation. In addition, peer relationship management can moderate the victimization-perpetration association, acting as a protective factor, when the ability of victims to regulate anger is sufficiently trained. These findings highlight the importance of designing effective prevention based on socio-emotional development to fully curb bullying. [ABSTRACT FROM AUTHOR]

Summary: We explored the relevance of genomic microarrays (GM) in the refinement of prognosis in newly diagnosed low‐risk chronic lymphocytic leukaemia (CLL) patients as defined by isolated del(13q) or no lesions by a standard 4 probe fluorescence in situ hybridization (FISH) analysis. Compared to FISH, additional lesions were detected by GM in 27 of the 119 patients (22.7%). The concordance rate between FISH and GM was 87.4%. Discordant results between cytogenetic banding analysis (CBA) and GM were observed in 45/119 cases (37.8%) and were mainly due to the intrinsic characteristics of each technique. The presence of additional lesions by GM was associated with age > 65 years (p = 0.047), advanced Binet stage (p = 0.001), CLL‐IPI score (p < 0.001), a complex karyotype (p = 0.004) and a worse time‐to‐first treatment in multivariate analysis (p = 0.009). Additional lesions by GM were also significantly associated with a worse time‐to‐first treatment in the subset of patients with wild‐type TP53 and mutated IGHV (p = 0.025). In CLL patients with low‐risk features, the presence of additional lesions identified by GM helps to identify a subset of patients with a worse outcome that could be proposed for a risk‐adapted follow‐up and for early treatment including targeted agents within clinical trials. [ABSTRACT FROM AUTHOR]

High rates of lung failure have been reported in haematological patients after SARS‐CoV2 infection. An early administration of monoclonal antibodies or anti‐virals may improve the prognosis. Oral anti‐virals may have a wider use independently of the genetic variations of the virus. Prospective data on anti‐virals in haematological malignancies (HMs) are still lacking. Outpatients diagnosed with HM and early COVID‐19 infection were prospectively treated with the oral anti‐virals nirmatrelvir/ritonavir and molnupiravir. Incidence of lung failure, deaths and adverse events was analysed. Long‐term outcome at third month was evaluated. Eighty‐two outpatients were evaluable for the study objectives. All patients had been treated for their HM within 12 months. COVID‐19‐related lung failure was 23.1%. Active HM (aOR = 4.42; p = 0.038) and prolonged viral shedding (aOR = 1.04; p = 0.022) resulted independent predictors of severe infection. The vaccination with three to four doses (aOR = 0.02; p = 0.001) and with two doses (aOR = 0.06; p = 0.006) resulted protective. COVID‐19‐related deaths at 28 days were 6.1%. All‐cause mortality at 90‐day follow‐up was 13.4% (n. 11) and included opportunistic infections and cardiovascular events. In conclusion, this approach reduced the incidence of lung failure and specific mortality compared to previous cohorts, but patients remain at high risk of further complications. [ABSTRACT FROM AUTHOR]

Background: Parvovirus is a common childhood infection that could be very dangerous to the fetus, if pregnant women become infected. The spectrum of effects range from pure red blood cell aplasia with hydrops fetalis to meningoencephalitis, with many symptoms in between. Severe anemia in the setting of pure red blood cell aplasia is one of the more common effects that neonatal experience (if infected intrapartum), with the current gold standard treatment being intrauterine or postnatal packed red blood cell (PRBC) transfusions, yet intravenous immunoglobulin (IVIG) may be a superior treatment option. Case presentation: A preterm infant was born at 26th week of gestational age via emergency Cesarean section due to hydrops fetalis, with parvovirus B19 exposure one month prior. The infant tested positive for IgM antibodies against parvovirus B19. Among many other serious complications of both hydrops fetalis and premature delivery, the infant had severe unremitting anemia, and received many PRBC transfusion over the course of his 71-day-long neonatal intensive care unit stay. During a follow up appointments as outpatient, his blood tests showed persistent high copies of parvovirus B19. He was then supported with PRBC transfusions and treated with IVIG. After three doses of IVIG, the infant's parvovirus B19 viral copy numbers have dramatically reduced and the infant did not require any more PRBC transfusions. Conclusions: IVIG infusion effectively treated the parvovirus B19 infection and restored erythropoiesis making the child transfusion independent. Furthermore, since IVIG is safe and readily crosses the placenta, further studies are needed to determine if IVIG should be considered as an alternative prenatal treatment for congenital parvovirus B19 infection. [ABSTRACT FROM AUTHOR]

Whale migrations are poorly understood. Two competing hypotheses dominate the literature: 1. moving between feeding and breeding grounds increases population fitness, 2. migration is driven by dynamic environmental gradients, without consideration of fitness. Other hypotheses invoke communication and learned behaviors. In this article, their migration was investigated with a minimal individual-based model at the scale of the Global Ocean. Our aim is to test if global migration patterns can emerge from only the local, individual perception of environmental change. The humpback whale (Megaptera novaeangliae) meta-population is used as a case study. This species reproduces in 14 zones spread across tropical latitudes. From these breeding areas, humpback whales are observed to move to higher latitudes seasonally, where they feed, storing energy in their blubber, before returning to lower latitudes. For the model, we developed a simplified ethogram that conditions the individual activity. Then trajectories of 420 whales (30 per DPS) were simulated in two oceanic configurations. The first is a homogeneous ocean basin without landmasses and a constant depth of −1000 m. The second configuration used the actual Earth topography and coastlines. Results show that a global migration pattern can emerge from the movements of a set of individuals which perceive their environment only locally and without a pre-determined destination. This emerging property is the conjunction of individual behaviors and the bathymetric configuration of the Earth's oceanic basins. Topographic constraints also maintain a limited connectivity between the 14 DPSs. An important consequence of invoking a local perception of environmental change is that the predicted routes are loxodromic and not orthodromic. In an ocean without landmasses, ecophysiological processes tended to over-estimate individual weights. With the actual ocean configuration, the excess weight gain was mitigated and also produced increased heterogeneity among the individuals. Developing a model of individual whale dynamics has also highlighted where the understanding of whales' individual behaviors and population dynamic processes is incomplete. Our new simulation framework is a step toward being able to anticipate migration events and trajectories to minimize negative interactions and could facilitate improved data collection on these movements. [ABSTRACT FROM AUTHOR]

A growing number of gamma-ray burst (GRB) afterglows is observed at very-high energies (VHE, ≳ 100 GeV). Yet, our understanding of the mechanism powering the VHE emission remains baffling. We make use of multiwavelength observations of the afterglow of GRB 180720B, GRB 190114C, and GRB 221009A to investigate whether the bursts exhibiting VHE emission share common features. We assume the standard afterglow model and microphysical parameters consistent with a synchrotron self-Compton (SSC) scenario for the VHE radiation. By requiring that the blastwave should be transparent to γ–γ pair production at the time of observation of the VHE photons and relying on typical prompt emission efficiencies and data in the radio, optical, and X-ray bands, we infer for those bursts that the initial energy of the blastwave is |$\tilde{E}_{k, \rm {iso}} \gtrsim \mathcal {O}(10^{54})$|  erg and the circumburst density is |$n_0 \lesssim \mathcal {O}(10^{-1})$|  cm−3 for a constant circumburst profile [or |$A_\star \lesssim \mathcal {O}(10^{-1})$|  cm−1 for a wind scenario]. Our findings thus suggest that these VHE bursts might be hosted in low-density environments, if the SSC radiation is responsible for the VHE emission. While these trends are based on a small number of bursts, the Cherenkov Telescope Array has the potential to provide crucial insight in this context by detecting a larger sample of VHE GRBs. In addition, due to the very poor statistics, the non-observation of high-energy neutrinos cannot constrain the properties of these bursts efficiently, unless additional VHE GRBs should be detected at distances closer than 15 Mpc when IceCube-Gen2 radio will be operational. [ABSTRACT FROM AUTHOR]

Although immunotherapy has proved to be a very efficient therapeutic strategy for many types of tumors, the results for pancreatic cancer (PC) have been very poor. Indeed, chemotherapy remains the standard treatment for this tumor in the advanced stage. Clinical data showed that only a small portion of PC patients with high microsatellite instability/mismatch repair deficiency benefit from immunotherapy. However, the low prevalence of these alterations was not sufficient to lead to a practice change in the treatment strategy of this tumor. The main reasons for the poor efficacy of immunotherapy probably lie in the peculiar features of the pancreatic tumor microenvironment in comparison with other malignancies. In addition, the biomarkers usually evaluated to define immunotherapy efficacy in other cancers appear to be useless in PC. This review aims to describe the main features of the pancreatic tumor microenvironment from an immunological point of view and to summarize the current data on immunotherapy efficacy and immune biomarkers in PC. [ABSTRACT FROM AUTHOR]

The current state of the art on material science emphasizes recent research efforts aimed at designing novel materials characterized by low-density and advanced properties. The present article reports the experimental, theoretical and simulation results on the thermal behavior of 3D printed discs. Filaments of pure poly (lactic acid) PLA and filled with 6 wt% of graphene nanoplatelets (GNPs) are used as feedstocks. Experiments indicate that the introduction of graphene enhances the thermal properties of the resulting materials since the conductivity passes from the value of 0.167 [W/mK] for unfilled PLA to 0.335 [W/mK] for reinforced PLA, which corresponds to a significantly improvement of 101%. Exploiting the potential of 3D printing, different air cavities have been intentionally designed to develop new lightweight and more cost-effective materials without compromising their thermal performances. Furthermore, some cavities are equal in volume but different in the geometry; it is necessary to investigate how this last characteristic and its possible orientations affect the overall thermal behavior compared to that of an air-free specimen. The influence of air volume is also investigated. Experimental results are supported by theoretical analysis and simulation studies based on the finite element method. The results aim to be a valuable reference resource in the field of design and optimization of lightweight advanced materials. [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) is the most common type of tumor in men. In the early stage of the disease, it is sensitive to androgen deprivation therapy. In patients with metastatic castration-sensitive prostate cancer (mHSPC), chemotherapy and second-generation androgen receptor therapy have led to increased survival. However, despite advances in the management of mHSPC, castration resistance is unavoidable and many patients develop metastatic castration-resistant disease (mCRPC). In the past few decades, immunotherapy has dramatically changed the oncology landscape and has increased the survival rate of many types of cancer. However, immunotherapy in prostate cancer has not yet given the revolutionary results it has in other types of tumors. Research into new treatments is very important for patients with mCRPC because of its poor prognosis. In this review, we focus on the reasons for the apparent intrinsic resistance of prostate cancer to immunotherapy, the possibilities for overcoming this resistance, and the clinical evidence and new therapeutic perspectives regarding immunotherapy in prostate cancer with a look toward the future. [ABSTRACT FROM AUTHOR]

Almost 17% of Western patients affected by non-small cell lung cancer (NSCLC) have an activating epidermal growth factor receptor (EGFR) gene mutation. Del19 and L858R are the most-common ones; they are positive predictive factors for EGFR tyrosine kinase inhibitors (TKIs). Currently, osimertinib, a third-generation TKI, is the standard first-line therapy for advanced NSCLC patients with common EGFR mutations. This drug is also administered as a second-line treatment for those patients with the T790M EGFR mutation and previously treated with first- (erlotinib, gefitinib) or second- (afatinib) generation TKIs. However, despite the high clinical efficacy, the prognosis remains severe due to intrinsic or acquired resistance to EGRF-TKIs. Various mechanisms of resistance have been reported including the activation of other signalling pathways, the development of secondary mutations, the alteration of the downstream pathways, and phenotypic transformation. However, further data are needed to achieve the goal of overcoming resistance to EGFR-TKIs, hence the necessity of discovering novel genetic targets and developing new-generation drugs. This review aimed to deepen the knowledge of intrinsic and acquired molecular mechanisms of resistance to EGFR-TKIs and the development of new therapeutic strategies to overcome TKIs' resistance. [ABSTRACT FROM AUTHOR]

The aim of this research was to compare the level of digital competence of future pedagogical staff (students of pedagogical faculties) in Italy and Poland. The research was conducted using original measurement tools and knowledge tests. The triangulation of techniques and research tools made possible the determination of the level of knowledge of the positive and negative features of the development of the information society, as well as the proficiency and frequency of use of the most popular websites and software. The research was conducted in the first half of 2022 using stratified sampling in both countries (N = 1209, IT = 604, PL = 605). Based on the data collected, it was noted that: (1) Pre-service teachers most often use software such as word processors and presentation creation tools; (2) This group very rarely uses software to create web pages, create visual material, or edit video; (3) The least problematic software that students use are word processors and multimedia presentations; (4) Among the typical ICT mediated activities that cause problems are: searching for and installing freeware (PL), installing and configuring parental control software (PL, IT), creating websites (PL, IT), searching for freely licensed images, and identifying plagiarism (PL); (5) Polish students have more theoretical knowledge about e-risks and the possibilities of the digital world than their Italian counterparts; (6) In most domains, the Italian future teachers rate their competences higher; (7) 53.81% of the respondents in IT and 38.68% in PL received lower results in competence tests, and handling ICT in selected areas causes problems for these students; (8) Both in PL and IT the frequency of ICT use and its seamless integration are predictors for assessing the effectiveness of ICT use in education. [ABSTRACT FROM AUTHOR]

Advances in pharmacotherapies that target cell cycle in breast cancer have transformed the therapeutic armamentarium of breast oncology leading to the approval of CDK4/6 inhibitors plus endocrine therapy as the upfront treatment in the HR+/HER2- metastatic setting. The current challenge is to evaluate the efficacy of these drugs in the early setting. The current challenge is to evaluate the efficacy of these drugs in the early setting. Research is also making progress for other breast cancer subtypes (triple negative and HER 2+ breast cancer). The aim of this review is to summarize the recent therapeutic updates regarding the efficacy of CDK4/6 inhibitors in the metastatic and early setting for the treatment of HR+/HER2- breast cancer. The review also presents data regarding the clinical role of CDK4/6 inhibitors in HER2+, triple negative breast cancer, and on therapeutic sequences in resistant tumors. A comprehensive search for the literature was conducted using MEDLINE, ASCO, ESMO, and SABCS databases. The therapeutic paradigm of breast cancer involving CDK4/6 inhibitors presents some still open discussion points. Further evidence regarding the best treatment strategy in HR+ HER2- metastatic breast cancer and the efficacy of CDK 4/6is in the early stage will be necessary in the next future. Predictive biomarkers of response or resistance need to be validated. [ABSTRACT FROM AUTHOR]

Simple Summary: We hereby report on the immunomodulatory effects induced over time in patients with advanced relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and B-lineage acute lymphoblastic leukemia (B-ALL) treated with the commercial CAR-T-cell product tisagenlecleucel. We observed that, in addition to its anti-neoplastic activity, tisagenlecleucel was capable of exerting a marked and long-lived in vivo reshaping of the host immune system, in terms of T- and NK-cell expansion and cytokine release. These results may contribute to a further understanding of the complex field of immunotherapy and intercellular crosstalk, suggesting a role for host immune modulation in the long-term control of the disease. Background: Chimeric antigen receptor (CAR)-T cells represent a potentially curative strategy for patients with relapsed or refractory (R/R) B-cell malignancies. To elucidate a possible host immune activation following CAR-T-cell infusion, we investigated the effects of tisagenlecleucel administration on the patients' immune populations in 25 patients with R/R diffuse large B-cell lymphoma (DLBCL) and B-lineage acute lymphoblastic leukemia (B-ALL). Methods: The modulation of CAR-T cells over time, the numeric changes, as well as the cytokine production capability of different lymphocyte populations and circulating cytokine levels, were analyzed. Results: Our results confirmed the ability of tisagenlecleucel to control the disease, with an overall response observed in 84.6% of DLBCL and in 91.7% of B-ALL patients at 1-month post-infusion, and showed that most patients who subsequently relapsed could undergo further treatment. Interestingly, we could document a significant increase in CD3+, CD4+, CD8+, and NK cells over time, as well as a decrease in Treg cells, and an increased IFNγ and TNFα production by T lymphocytes. Conclusions: Taken together, our results indicate that in patients with DLBCL and B-ALL, the administration of tisagenlecleucel is capable of inducing a marked and prolonged in vivo modulation/reshaping of the host immune system, both in children and adults. [ABSTRACT FROM AUTHOR]