PD-L1 ≥ 50% lung cancer refractory to PD-1 inhibition: The role of salvage chemo-immunotherapy combination

Novel treatment strategies incorporating PD-1/PD-L1 inhibitors in the first-line setting of advanced non-small-cell lung cancer (NSCLC) provided relevant improvements in survival outcomes. Among NSCLC patients with PD-L1 tumor proportion score ≥50%, identifying the ones to be addressed to pembrolizumab monotherapy or chemo-immunotherapy combinations is a matter of debate, taking into account the risks of overtreatment and toxicity. Here we report the clinical stories of four NSCLC patients with PD-L1 tumor proportion score ≥50% and good performance status, sharing high tumor burden including serosal involvement. After having rapidly progressed on first-line PD-1/PD-L1 inhibitors, they achieved major clinical and radiological response to pembrolizumab-chemotherapy combination. These cases prove the feasibility and effectiveness of salvage chemo-immunotherapy in pembrolizumab-refractory NSCLC patients

Astrocyte function is affected by aging and not Alzheimer's disease: A preliminary investigation in hippocampi of 3xTg-AD mice

Old age is a risk factor for Alzheimer's disease (AD), which is characterized by hippocampal impairment together with substantial changes in glial cell functions. Are these alterations due to the disease progression or are they a consequence of aging? To start addressing this issue, we studied the expression of specific astrocytic and microglial structural and functional proteins in a validated transgenic model of AD (3×Tg-AD). These mice develop both amyloid plaques and neurofibrillary tangles, and initial signs of the AD-like pathology have been documented as early as three months of age. We compared male 3×Tg-AD mice at 6 and 12 months of age with their wild-type age-matched counterparts. We also investigated neurons by examining the expression of both the microtubule-associated protein 2 (MAP2), a neuronal structural protein, and the brain-derived neurotrophic factor (BDNF). The latter is indeed a crucial indicator for synaptic plasticity and neurogenesis/ neurodegeneration. Our results show that astrocytes are more susceptible to aging than microglia, regardless of mouse genotype. Moreover, we discovered significant agedependent alterations in the expression of proteins responsible for astrocyte-astrocyte and astrocyte-neuron communication, as well as a significant age-dependent decline in BDNF expression. Our data promote further research on the unexplored role of astroglia in both physiological and pathological aging

Aqueye optical observations of the Crab Nebula pulsar

We observed the Crab pulsar in October 2008 at the Copernico Telescope in Asiago - Cima Ekar with the optical photon counter Aqueye (the Asiago Quantum Eye) which has the best temporal resolution and accuracy ever achieved in the optical domain (hundreds of picoseconds). Our goal was to perform a detailed analysis of the optical period and phase drift of the main peak of the Crab pulsar and compare it with the Jodrell Bank ephemerides. We determined the position of the main peak using the steepest zero of the cross-correlation function between the pulsar signal and an accurate optical template. The pulsar rotational period and period derivative have been measured with great accuracy using observations covering only a 2 day time interval. The error on the period is 1.7 ps, limited only by the statistical uncertainty. Both the rotational frequency and its first derivative are in agreement with those from the Jodrell Bank radio ephemerides archive. We also found evidence of the optical peak leading the radio one by ~230 microseconds. The distribution of phase-residuals of the whole dataset is slightly wider than that of a synthetic signal generated as a sequence of pulses distributed in time with the probability proportional to the pulse shape, such as the average count rate and background level are those of the Crab pulsar observed with Aqueye. The counting statistics and quality of the data allowed us to determine the pulsar period and period derivative with great accuracy in 2 days only. The time of arrival of the optical peak of the Crab pulsar leads the radio one in agreement with what recently reported in the literature. The distribution of the phase residuals can be approximated with a Gaussian and is consistent with being completely caused by photon noise (for the best data sets).Comment: 7 pages, 7 figures. Accepted for publication in Astronomy and Astrophysic

Environment modelling for the robust motion planning and control of planar rigid robot manipulators

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Dataspaces: Concepts, Architectures and Initiatives

Despite not being a new concept, dataspaces have become a prominent topic due to the increasing availability of data and the need for efficient management and utilization of diverse data sources. In simple terms, a dataspace refers to an environment where data from various sources, formats, and domains can be integrated, shared, and analyzed. It aims to provide a unified view of heterogeneous data by bridging the gap between different data silos, enabling interoperability. The concept of dataspaces promotes the idea that data should be treated as a cohesive entity, rather than being fragmented across different systems and applications. Dataspaces often involve the integration of structured and unstructured data, including databases, documents, sensor data, social media feeds, and more. The goal is to enable organizations to harness the full potential of their data assets by facilitating data discovery, access, and analysis. By bringing together diverse data sources, dataspaces can offer new insights, support decision-making processes, and drive innovation. In the context of European Commission-funded research projects, dataspaces are often explored as part of initiatives focused on data management, data sharing, and the development of data-driven technologies. These projects aim to address challenges related to data integration, data privacy, data governance, and scalability. The goal is to advance the state of the art in data management and enable organizations to leverage data more effectively for societal, economic, and scientific advancements. It is important to notice that while dataspaces offer potential benefits, they also come with challenges. These challenges include data quality assurance, data privacy and security, semantic interoperability, scalability, and the need for appropriate data governance frameworks. Overall, dataspaces represent an approach to managing and utilizing data that emphasizes integration, interoperability, and accessibility. The concept is being explored and researched to develop innovative solutions that can unlock the value of data in various domains and sectors

A Framework for Automatic Generation of Fuzzy Evaluation Systems for Embedded Applications

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Systemic thromboembolism from a misdiagnosed non-bacterial thrombotic endocarditis in a patient with lung cancer: A case report

Thromboembolic events are frequent in patients with cancer, commonly involving the venous and pulmonary circulation. The arterial system is rarely implicated in embolism and, when involved, a cardiogenic origin should always be excluded. In the present study, a case of a patient who developed multiple embolic events concomitantly with the diagnosis of locally-advanced non-small cell lung cancer with high expression levels of programmed death-ligand 1 (PD-L1) in >50% of tumor cells is reported. A cardiac defect interpreted as a patent foramen ovale required low molecular weight heparin administration. Despite the anti-coagulant therapy, before first-line anticancer treatment with pembrolizumab immunotherapy could be administered due to high PD-L1 expression levels, a new hospitalization was required due to the onset of novel ischemic manifestation. New transthoracic and transesophageal echocardiography revealed a previously misdiagnosed vegetation of the mitral valve that caused systemic embolization. The lack of any sign of infection led to the diagnosis of a non-bacterial thrombotic endocarditis (NBTE), whose embolic sprouting gave rise to the widespread ischemic events. No active anticancer treatment was feasible due to the rapid progression of the disease. NBTE can evolve quickly, eventually preventing any chance of treatment targeting the primary cause, which in the present study was lung cancer. If NBTE can be correctly diagnosed sooner then there may be the potential for anticancer therapy that does not worsen the hypercoagulability state, thus improving cancer-associated survival