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Background: Metastatic HR+/HER2- breast cancer is commonly treated with CDK4/6 inhibitors in combination with endocrine therapy. However, the efficacy and safety of this approach in elderly patients (≥70 years) remain unclear, particularly in the context of real-world clinical practice. This study aims to evaluate the clinical outcomes and tolerability of CDK4/6 inhibitor treatments in this fragile population, which is often under-represented in randomized clinical trials., Patients and Methods: This retrospective multicenter study included elderly patients with metastatic HR+/HER2-negative breast cancer receiving first-line CDK4/6 inhibitors. The primary endpoint was progression-free survival (PFS). The secondary endpoints focused on the overall survival (OS), safety, and tolerability, considering variables such as tumor subtype, age, comorbidities, and treatment specifics., Results: The median PFS and OS were slightly lower than those reported in clinical trials, reflecting the inclusion of a more fragile population. The luminal B subtype was linked to a poorer PFS, while other factors like age, BMI, and ECOG status did not significantly affect the outcomes. A safety analysis indicated a higher incidence of grade 3 or higher toxicities, especially in frail patients, leading to dose reductions. Despite these challenges, CDK4/6 inhibitors were generally well-tolerated, allowing most patients to continue therapy., Conclusions: CDK4/6 inhibitors with endocrine therapy are effective in elderly patients with metastatic HR+/HER2- breast cancer, though careful management is crucial to balance efficacy and minimize adverse events.

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., Competing Interests: The authors declare no conflicts of interest.

The aim of the SYRIACA project was to test the capability of a social robot to perform specific tasks in healthcare settings, reducing infection risks for patients and caregivers. The robot was piloted in an Intensive Hematological Unit, where the patients' and healthcare operators' acceptability of the robot was evaluated. The robot's functions, including logistics, surveillance, entertainment, and remote visits, were well accepted. Patients expressed interest in having multiple interactions with the robot, which testifies to its engaging potential and that it provides useful services. During remote visits, the robot reduced perceived stress among patients, alleviating feelings of isolation. The successful implementation of the robot suggests its potential to enhance safety and well-being in healthcare settings.

(1) Background: Venous thromboembolism (VTE) is a frequent complication in ambulatory lung cancer patients during chemotherapy and is associated with increased mortality. (2) Methods: We analyzed 568 newly diagnosed metastatic lung cancer patients prospectively enrolled in the HYPERCAN study. Blood samples collected before chemotherapy were tested for thrombin generation (TG) and a panel of hemostatic biomarkers. The Khorana risk score (KRS), new-Vienna CATS, PROTECHT, and CONKO risk assessment models (RAMs) were applied. (3) Results: Within 6 months, the cumulative incidences of VTE and mortality were 12% and 29%, respectively. Patients with VTE showed significantly increased levels of D-dimer, FVIII, prothrombin fragment 1 + 2, and TG. D-dimer and ECOG performance status were identified as independent risk factors for VTE and mortality by multivariable analysis and utilized to generate a risk score that provided a cumulative incidence of VTE of 6% vs. 25%, death of 19% vs. 55%, and in the low- vs. high-risk group, respectively ( p < 0.001). While all published RAMs significantly stratified patients for risk of death, only the CATS and CONKO were able to stratify patients for VTE. (4) Conclusions: A new prediction model was generated to stratify lung cancer patients for VTE and mortality risk, where other published RAMs failed.

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.

Assistive devices could promote independent living and support the active and healthy aging of an older population; however, several factors can badly influence the long-term use of new technologies. In this context, this paper presents a two-step methodology called “pre-validation” that aims to identify the factors that can bias the use of new services, thus minimizing the risk of an unsuccessful longer trial. The proposed pre-validation methodology is composed of two main phases that aim to assess the usability and the reliability of the technology assessed in a laboratory environment and the usability, acceptability, user experience, and reliability of the technology in real environments. The tested services include the socialization scenario, in which older adults are better connected to the community via technological solutions (i.e., socialization applications), and the monitoring scenario, which allows for the introduction of timely interventions (technologies involved include environmental monitoring sensors, a telepresence robot, wearable sensors, and a personalized dashboard). The obtained results underline an acceptable usability level (average System Usability Scale score > 65) for the tested technologies (i.e., socialization applications and a telepresence robot). Phase Two also underlines the good acceptability, user experience, and usability of the tested services. The statistical analysis underlines a correlation between the stress related to the use of technology, digital skills, and intention of use, among other factors. Qualitative feedback also remarks on a correlation between older adults with low digital skills and an anxiety about using technology. Positive correlation indexes were highlighted between the trust and usability scores. Eventually, future long-term trials with assistive technology should rely on motivated caregivers, be founded on a strong recruitment process, and should reassure older adults—especially the ones with low digital literacy—about the use of technology by proposing personalized training and mentoring, if necessary, to increase the trust.

Background: the tight and reciprocal interaction between cancer and hemostasis has stimulated investigations on the possible role of hemostatic biomarkers in predicting specific cancer outcomes, such as disease progression (DP) and overall survival (OS). In a prospective cohort of newly diagnosed metastatic gastrointestinal (GI) cancer patients from the HYPERCAN study, we aimed to assess whether the hemostatic biomarker levels measured before starting any anticancer therapy may specifically predict for 6-months DP (6m-DP) and for 1-year OS (1y OS). Methods: plasma samples were collected and tested for thrombin generation (TG) as global hemostatic assay, and for D-dimer, fibrinogen, and prothrombin fragment 1 + 2 as hypercoagulation biomarkers. DP and mortality were monitored during follow-up. Results: A prospective cohort of 462 colorectal and 164 gastric cancer patients was available for analysis. After 6 months, DP occurred in 148 patients, providing a cumulative incidence of 24.8% (21.4−28.4). D-dimer and TG endogenous thrombin potential (ETP) were identified as independent risk factors for 6m-DP by multivariate Fine−Gray proportional hazard regression model corrected for age, cancer site, and >1 metastatic site. After 1 year, we observed an OS of 75.7% (71.9−79.0). Multivariate Cox regression analysis corrected for age, site of cancer, and performance status identified D-dimer and ETP as independent risk factors for 1y OS. Patients with one or both hemostatic parameters above the dichotomizing threshold were at higher risk for both 6m-DP and 1-year mortality. Conclusion.: in newly diagnosed metastatic GI cancer patients, pretreatment ETP and D-dimer appear promising candidate biomarkers for predicting 6m-DP and 1y OS. In this setting, for the first time, the role of TG as a prognostic biomarker emerges in a large prospective cohort.

As a consequence of the COVID-19 emergency, frail citizens felt isolated because of social isolation, suspended and/or strongly reduced home assistance, and limited access to hospitals. In this sense, assistive technology could play a pivotal role in empowering frail older adults reducing their isolation, as well as in reinforcing the work of formal caregivers and professionals. In this context, the goal of this paper is to present four pilot studies-conducted from March 2020 to April 2021-to promptly react to COVID-19 by providing assistive technology solutions, aiming to (1) guarantee high-quality service to older adults in-home or in residential facility contexts, (2) promote social inclusion, and (3) reduce the virus transmission. In particular, four services, namely, telepresence service, remote monitoring service, virtual visit, and environmental disinfection, were designed, implemented, and tested in real environments involving 85 end-users to assess the user experience and/or preliminary assess the technical feasibility. The results underlined that all the proposed services were generally accepted by older adults and professionals. Additionally, the results remarked that the use of telepresence robots in private homes and residential facilities increased enjoyment reducing anxiety, whereas the monitoring service supported the clinicians in monitoring the discharged COVID-19 patients. It is also worth mentioning that two new services/products were developed to disinfect the environment and to allow virtual visits within the framework of a hospital information system. The virtual visits service offered the opportunity to expand the portfolio of hospital services. The main barriers were found in education, technology interoperability, and ethical/legal/privacy compliance. It is also worth mentioning the key role played by an appropriate design and customer needs analysis since not all assistive devices were designed for older persons.

Background: Emotion recognition skills are predicted to be fundamental features in social robots. Since facial detection and recognition algorithms are compute-intensive operations, it needs to identify methods that can parallelize the algorithmic operations for large-scale information exchange in real time. The study aims were to identify if traditional machine learning algorithms could be used to assess every user emotions separately, to relate emotion recognizing in two robotic modalities: static or motion robot, and to evaluate the acceptability and usability of assistive robot from an end-user point of view., Methods: Twenty-seven hospital employees (M = 12; F = 15) were recruited to perform the experiment showing 60 positive, negative, or neutral images selected in the International Affective Picture System (IAPS) database. The experiment was performed with the Pepper robot. Concerning experimental phase with Pepper in active mode, a concordant mimicry was programmed based on types of images (positive, negative, and neutral). During the experimentation, the images were shown by a tablet on robot chest and a web interface lasting 7 s for each slide. For each image, the participants were asked to perform a subjective assessment of the perceived emotional experience using the Self-Assessment Manikin (SAM). After participants used robotic solution, Almere model questionnaire (AMQ) and system usability scale (SUS) were administered to assess acceptability, usability, and functionality of robotic solution. Analysis wasperformed on video recordings. The evaluation of three types of attitude (positive, negative, andneutral) wasperformed through two classification algorithms of machine learning: k-nearest neighbors (KNN) and random forest (RF)., Results: According to the analysis of emotions performed on the recorded videos, RF algorithm performance wasbetter in terms of accuracy (mean ± sd = 0.98 ± 0.01) and execution time (mean ± sd = 5.73 ± 0.86 s) than KNN algorithm. By RF algorithm, all neutral, positive and negative attitudes had an equal and high precision (mean = 0.98) and F-measure (mean = 0.98). Most of the participants confirmed a high level of usability and acceptability of the robotic solution., Conclusions: RF algorithm performance was better in terms of accuracy and execution time than KNN algorithm. The robot was not a disturbing factor in the arousal of emotions.

Background: The Pilots for Healthy and Active Ageing (PHArA-ON) project aimsto ensure reality smart and active living for Europe's ageing population by creating a set of integrated and highly customizable interoperable open platforms with advanced services, devices, and technologies and tools. The aim of the present study was to determine the needs and preferences of older people and their caregivers for improving healthy and active aging and guiding the technological development of thePHArA-ON system., Methods: A pre-structured interview was administered to older adults, informal caregivers and professional caregivers (including social operators) taking part in the piloting sessions., Results: Interviews were carried out in Umana Persone Social Enterprise R&D Network (UP) in Tuscany, and Ospedale Casa SollievodellaSofferenza (CSS) in Apulia. A total of 22 older adults, 22 informal caregivers, 13 professional caregivers and 4 social operators were recruited. A prioritization analysis of services, according to the stakeholder's needs, has determined two fundamental need categories: Heath Management (i.e., stimulation and monitoring), and Socialisation (i.e., promoting social inclusion)., Conclusions: The main scientific contributions to this study are the following: to design and evaluate technology in the context of healthy and active ageing, to acquire relevant knowledge on user needs to develop technologies that can handle the real life situations of older people, obtain useful insights about the attitude and availability of end-users in using technologies in clinical practice, and to provide important guidelines to improve the PHArA-ON system. Specific experimentation stages were also carried out to understand which kind of technology is more acceptable, and to obtain feedback regarding the development priority related to the impact of the proposed services. Research through fruitful and continuous interaction with the different subjects involved in the development process of the system, as well as with stakeholders, enabled the implementation of a platform which could be further and easily integrated and improved.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease for which there is currently no cure. Progress in the characterization of other neurodegenerative mechanisms has shifted the spotlight onto an intracellular structure called mitochondria-endoplasmic reticulum (ER) contacts (MERCs) whose ER portion can be biochemically isolated as mitochondria-associated membranes (MAMs). Within the central nervous system (CNS), these structures control the metabolic output of mitochondria and keep sources of oxidative stress in check via autophagy. The most relevant MERC controllers in the ALS pathogenesis are vesicle-associated membrane protein-associated protein B (VAPB), a mitochondria-ER tether, and the ubiquitin-specific chaperone valosin containing protein (VCP). These two systems cooperate to maintain mitochondrial energy output and prevent oxidative stress. In ALS, mutant VAPB and VCP take a central position in the pathology through MERC dysfunction that ultimately alters or compromises mitochondrial bioenergetics. Intriguingly, both proteins are targets themselves of other ALS mutant proteins, including C9orf72, FUS, or TDP-43. Thus, a new picture emerges, where different triggers cause MERC dysfunction in ALS, subsequently leading to well-known pathological changes including endoplasmic reticulum (ER) stress, inflammation, and motor neuron death.

Body height is considered to be one of the most important reproductive signals. However, there are only a few publications on what influences the sense of whether we assess ourselves as tall or short. In the present contribution, the psychological impact of money on the evaluation of a person's own height was tested. We performed two experimental studies in which the respondents had contact with different amounts of money and were asked to evaluate their body height with the use of a laser pointer. The first experiment ( N = 61) showed that contact with money significantly increased subjective height evaluation, and the effect was independent of participants' real body height. The second experiment ( N = 120) replicated the effect of money manipulation. Moreover, it was shown that higher amounts of money increased one's own height estimation more than smaller amounts. Our research shows that money can be used for building one's social position, which is an attractiveness signal that can influence one's own height evaluation.

The molecular mechanisms underlying bipolar disorder (BPD) have remained largely unknown. Postmortem brain tissue studies comparing BPD patients with healthy controls have produced a heterogeneous array of potentially implicated protein-coding RNAs. We hypothesized that dysregulation of not only coding, but multiple classes of RNA (coding RNA, long non-coding (lnc) RNA, circular (circ) RNA, and/or alternative splicing) underlie the pathogenesis of BPD. Using non-polyadenylated libraries we performed RNA sequencing in postmortem human medial frontal gyrus tissue from BPD patients and healthy controls. Twenty genes, some of which not previously implicated in BPD, were differentially expressed (DE). PCR validation and replication confirmed the implication of these DE genes. Functional in silico analyses identified enrichment of angiogenesis, vascular system development and histone H3-K4 demethylation. In addition, ten lncRNA transcripts were differentially expressed. Furthermore, an overall increased number of alternative splicing events in BPD was detected, as well as an increase in the number of genes carrying alternative splicing events. Finally, a large reservoir of circRNAs populating brain tissue not affected by BPD is described, while in BPD altered levels of two circular transcripts, cNEBL and cEPHA3, are reported. cEPHA3, hitherto unlinked to BPD, is implicated in developmental processes in the central nervous system. Although we did not perform replication analyses of non-coding RNA findings, our findings hint that RNA dysregulation in BPD is not limited to coding regions, opening avenues for future pharmacological investigations and biomarker research.