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Abstract Abemaciclib demonstrated clinical benefit in women affected by HR+/HER2− advanced breast cancer (aBC). Drug-drug interactions (DDIs) can lead to reduced treatment efficacy or increased toxicity. This retro-prospective study aimed to evaluate outcomes, DDIs’ impact, and toxicities of abemaciclib combined with endocrine therapy in a real-world setting. Patients from 12 referral Italian hospitals with HR+/HER2− aBC who received abemaciclib were included. Clinical data about comorbidities, concurrent medications, outcomes, and adverse events (AE) were collected. Drug-PIN® (Personalized Interactions Network) is a tool recognizing the role of multiple interactions between active and/or pro-drug forms combined with biochemical and demographic patient data. The software was used to define the Drug-PIN score and Drug-PIN tier (green, yellow, dark yellow, and red) for each patient. Univariate and multivariate analyses were performed to identify predictors of patients’ PFS or toxicity. One hundred seventy-three patients were included. 13% of patients had >75years. The overall response rate (ORR) was 63%. The general population’s median PFS (mPFS) was 22 months (mo), while mOS were not reached. Patients treated with abemaciclib in combination with AI and fulvestrant had a mPFS of 36 and 19 mo, respectively. The most common toxicities were diarrhea, asthenia, and neutropenia detected in 63%,49%, and 49% of patients. The number of concomitant medications and comorbidities were not associated with survival outcomes (22 vs 17 mo, p = 0.068, p = 0.99). Drug-PIN tier from dark yellow to red and Drug-PIN score >12 were associated with shorter PFS compared to no/low-risk DDIs and score

Lung transplantation offers a lifesaving option for patients with end-stage lung disease, but it is marred by a high risk of post-transplant infections, particularly involving multidrug-resistant bacteria, Cytomegalovirus, and fungal pathogens. This elevated infection rate, the highest among solid organ transplants, poses a significant challenge for clinicians, particularly within the first year post-transplantation, where infections are the leading cause of mortality. The direct exposure of lung allografts to the external environment exacerbates this vulnerability leading to constant immune stimulation and consequently to an elevated risk of triggering alloimmune responses to the lung allograft. The necessity of prolonged immunosuppression to prevent allograft rejection further complicates patient management by increasing susceptibility to infections and neoplasms, and complicating the differentiation between rejection and infection, which require diametrically opposed management strategies. This review explores the intricate balance between preventing allograft rejection and managing the heightened infection risk in lung transplant recipients.

Abstract In this study, the deep learning algorithm of Convolutional Neural Network long short-term memory (CNN–LSTM) is used to classify various jewelry rocks such as agate, turquoise, calcites, and azure from various historical periods and styles related to Shahr-e Sokhteh. Here, the CNN–LSTM architecture includes utilizing CNN layers for the extraction of features from input data mixed with LSTMs for supporting sequence forecasting. It should be mentioned that interpretable deep learning-assisted laser induced breakdown spectroscopy helped achieve excellent performance. For the first time, this paper interprets the Convolutional LSTM effectiveness layer by layer in self-adaptively obtaining LIBS features and the quantitative data of major chemical elements in jewelry rocks. Moreover, Lasso method is applied on data as a factor for investigation of interoperability. The results demonstrated that LIBS can be essentially combined with a deep learning algorithm for the classification of different jewelry songs. The proposed methodology yielded high accuracy, confirming the effectiveness and suitability of the approach in the discrimination process.

Abstract Background Immune Checkpoint Inhibitors (ICIs) lead to durable response and a significant increase in long-term survival in patients with advanced malignant melanoma (MM) and Non-Small Cell Lung Cancer (NSCLC). The identification of serum cytokines that can predict their activity and efficacy, and their sex interaction, could improve treatment personalization. Methods In this prospective study, we enrolled immunotherapy-naïve patients affected by advanced MM and NSCLC treated with ICIs. The primary endpoint was to dissect the potential sex correlations between serum cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, GM-CSF, MCP-1, TNF-ɑ, IP-10, VEGF, sPD-L1) and the objective response rate (ORR). Secondly, we analyzed biomarker changes during treatment related to ORR, disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Blood samples, collected at baseline and during treatment until disease progression (PD) or up to 2 years, were analyzed using Luminex xMAP or ELLA technologies. Results Serum samples from 161 patients (98 males/63 females; 92 MM/69 NSCLC) were analyzed for treatment response. At baseline, IL-6 was significantly lower in females (F) versus males (M); lower levels of IL-4 in F and of IL-6 in both sexes significantly correlated with a better ORR, while higher IL-4 and TNF-ɑ values were predictive of a lower ORR in F versus M. One hundred and sixty-five patients were evaluable for survival analysis: at multiple Cox regression, an increased risk of PD was observed in F with higher baseline values of IL-4, sPD-L1 and IL-10, while higher IL-6 was a negative predictor in males. In males, higher levels of GM-CSF predict a longer survival, whereas higher IL-1β predicts a shorter survival. Regardless of sex, high baseline IL-8 values were associated with an increased risk of both PD and death, and high IL-6 levels only with shorter OS. Conclusions Serum IL-1β, IL-4, IL-6, IL-10, GM-CSF, TNF-ɑ, and sPD-L1 had a significant sex-related predictive impact on ORR, PFS and OS in melanoma and NSCLC patients treated with ICIs. These results will potentially pave the way for new ICI combinations, designed according to baseline and early changes of these cytokines and stratified by sex.

Viscoelasticity (VE) is the intrinsic mechano-dynamic property enabling red blood cells (RBCs) to undergo prompt and repeated deformations while maintaining structural integrity. Assessing RBC VE and how different stressors can affect it is of great interest. Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) is a technology exploiting high-frequency acoustic waves to probe soft matter rheological properties. In the present study, a QCM-D method is reported for in vitro monitoring of cell VE in viable RBCs. The method is based on casting a sensor-adherent cell monolayer and modeling it as an effective viscoelastic medium, and allows to extrapolate proxy values of both the elastic and the viscous cell shear moduli. Real-time VE changes induced by the known cell VE stressors temperature, medium tonicity, glutaraldehyde, methyl-β-cyclodextrin and cytochalasin D have been reliably identified. The method is relatively simple and inexpensive, non-invasive, and able to seize subtle changes of cell biomechanics. Hence, it could be usefully exploited for in vitro assessment of RBC rheological properties and their alterations induced by external chemico-physical stimuli.

Italy’s demographic setting is rapidly evolving and is characterized by a substantial increase in the older population segment. This trend, driven by prolonged life expectancy and declining birth rates, positions Italy as a leader in global aging patterns. The 38th National Congress of the Società Italiana di Geriatria Ospedale e Territorio (SIGOT), held in Rome, underlined the importance of addressing the health needs of this aging population, particularly focusing on preventing sarcopenia and cardiovascular diseases. Recent data challenge the notion of functional decline as an inevitable consequence of aging, highlighting the interplay of genetic, environmental, and lifestyle factors in modulating health outcomes. Sarcopenia, a prevalent condition and biological substrate of frailty, significantly impacts physical function and mortality rates, necessitating behavioral interventions to mitigate its effects. Physical exercise emerges as a key strategy for maintaining cardiovascular health and reducing the risk of arrhythmias, prevalent in older age groups. However, the complex relationship between physical activity intensity, age, and cardiovascular risk underlines the importance of tailored interventions and preliminary screenings. Looking ahead, proactive measures such as enhanced screening, promoting lifelong healthy habits, research and innovation, robust community support systems, and adaptable policies are essential to address the multifaceted challenges posed by an aging population. With this consensus paper, we aimed to summarize the key messages from the three intensive days of the SIGOT National Congress.

Mutual interactions between the diaphragm and lung transplantation (LTx) are known to exist. Before LTx, many factors can exert notable impact on the diaphragmatic function, such as the underlying respiratory disease, the comorbidities, and the chronic treatments of the patient. In the post-LTx setting, even the surgical procedure itself can cause a stressful trauma to the diaphragm, potentially leading to morphological and functional alterations. Conversely, the diaphragm can significantly influence various aspects of the LTx process, ranging from graft-to-chest cavity size matching to the long-term postoperative respiratory performance of the recipient. Despite this, there are still no standard criteria for evaluating, defining, and managing diaphragmatic dysfunction in the context of LTx to date. This deficiency hampers the accurate assessment of those factors which affect the diaphragm and its reciprocal influence on LTx outcomes. The objective of this narrative review is to delve into the complex role the diaphragm plays in the different stages of LTx and into the modifications of this muscle following surgery.

Background: Patients with hormone receptor-positive (HR+)/HER2- metastatic breast cancer (mBC) generally receive hormonal therapy (HT) combined with CDK4/6 inhibitors (CDK4/6i). Despite this treatment, resistance mechanisms to CDK4/6i emerge and the majority of these patients experience disease progression (PD). This highlight the necessity to uncover the resistance mechanism to CDK4/6i through the identification of specific biomarkers. The primary objective is to assess the accuracy and feasibility of a novel multi-gene target panel NGS assay on circulating tumor DNA (ctDNA) to detect molecular alterations of AKT1, ERBB2, ESR1, KRAS, PIK3CA, and TP53 genes in women with BC undergoing HT plus CDK4/6i treatment. Secondarily, the study aims to explore the relationship between genomic profiling and clinical outcomes. Materials and Methods: Plasma samples were collected from 16 patients diagnosed with advanced/locally advanced HR+/HER2- BC at 2 time points: T0 (baseline) and at T1 (3 months after CDK4/6i treatment). Starting from 2 mL of plasma, ctDNA was isolated and libraries were set up using the Plasma-SeqSensei (PQS)® Breast Cancer IVD Kit, sequenced on Nextseq 550 and analyzed using the Plasma-SeqSensei™ IVD Software®. Results: Among the five patients who presented PD, three had PIK3CA mutations and, of these, two showed a higher mutant allele frequency (MAF) at T1. In three patients with stable disease and in eight patients with partial response, the MAF of the detected alterations decreased dramatically or disappeared during CDK4/6i treatment. Conclusions: Based on our findings, the liquid biopsy analysis using the PQS panel seems to be both feasible and accurate, demonstrating a strong sensitivity in detecting mutations. This exploratory analysis of the clinical outcome associated to the mutational status of patients highlights the potential of molecular analysis on liquid biopsy for disease monitoring, although further validation with a larger patient cohort is necessary to confirm these preliminary observations.

In an eye-tracking during reading experiment, we examined how rapidly two types of photo-sentence relations impact sentence comprehension. The relation between a photo of a cultural figure and a year in an ensuing sentence (either the cultural figure in the photo was either alive in that year or not) was contrasted with relations between the same photo and achievements or facts about the cultural figure (e.g., a film they had vs. had not starred in). Longer reading times were observed at the regions containing mismatching year or fact, with more robust effects when data were filtered to include only trials in which participants had accurate prior knowledge about the cultural figure, their accomplishments, and their lifetime. These findings indicate that specific long-term knowledge is activated by a picture of a known figure and is rapidly available during language processing.

We present a case of breast cancer metastases superimposed on epidural lipomatosis and although none of these findings are considered rare, their coexistence leads to unique image findings, and as far as we know there are no other cases like this in literature.

In two self-paced reading experiments, we investigated the integration of knowledge about cultural figures during language processing. Experiment 1 investigated how contextually-defined lifetime information (dead/alive) was integrated with temporal verb morphology (English Present Perfect and Past Simple). Experiment 2 investigated how long-term knowledge about a cultural figure, prompted by their picture, is integrated with two types of linguistic input in German: temporal phrases containing a year, and biographical information (e.g., Joaquin Phoenix: "In the year 2013 / *1960, I starred in the film ‘Her’ / *‘Psycho’"). Experiment 1 revealed longer reading times and higher rejection rates when life status mismatched tense (i.e., dead – Present Perfect, alive – Past Simple). In Experiment 2, shorter reading times and higher accuracy rates emerged in conditions containing lifetime-year mismatches. No effects were found for biographical information violations. Together, the two experiments provide cross-linguistic evidence that knowledge of a referent’s lifetime is integrated during language processing.

Introduction: Telemedicine has been successfully employed in a wide range of conditions, such as such as chronic lung disease and COVID-19. This study evaluate the role of telemonitoring for the early diagnosis of acute lung allograft dysfunction in cystic fibrosis adults who underwent lung transplant (LuTx). Quality of life and functional level achieved during a 12 months follow up were assessed. Methods: Patients were randomized into two groups; control group received traditional hospital-based follow-up, whereas patients in the intervention group received, on top of standard care, a telemonitoring device, with a pulse oximeter and a spirometer integrated. Telemonitoring data were digitally transmitted to our centre. Results: Sixteen patients were enrolled in each group. No statistically significant difference was found between the two groups in terms of incidence of allograft dysfunction, time from onset of symptoms to diagnosis and time of occurrence from LuTx. Moreover, both groups achieved similar quality of life and functional level. With reference to the telemonitoring group: 1) hospital reported data were consistent with those being remotely registered; 2) adherence to telemonitoring decreased during the follow up; 3) the majority of patients reported a high degree of satisfaction. Conclusion: The COVID19 pandemic highlighted the necessity to investigate alternative practices to treat chronically ill individuals. Telemonitoring is a valuable tool to improve quality care to LuTx recipients.

The present eye-tracking reading study investigated the real-time processing of the so-called Lifetime Effect, which involvesthe integration of temporal verb morphology and knowledge ofa referent’s lifetime (alive vs. dead). Critical stimuli containedfamous referents, meaning that their lifetime status is widelyknown. In addition, context sentences mentioned their lifetimestatus and occupation. Tense/aspect was manipulated in a fol-lowing target sentence to contain either the present perfect orthe simple future (e.g., She has performed / will perform...).For dead referents, the target sentence was infelicitous giventhe tense/aspectual marking; for living referents, the mark-ing was felicitous. This design permitted us to examine ef-fects of lifetime status conveyed via world knowledge and lin-guistic context on the processing of tense/aspect morphology.Eye-tracking reading times revealed longer total reading timesat the critical (verb) and post-critical regions for the presentperfect when following a deceased context, while the dead-simple future condition had shorter overall reading times thanany other condition. Naturalness ratings revealed the dead-simple future to be quickly and reliably rejected, while thedead-present perfect was deemed acceptable. However, thelatter was rated significantly lower than the living/present per-fect condition. Taken together, the results imply that worldknowledge and an immediate context defining a real-world ref-erent as being dead or alive can jointly modulate the processingof subsequent verb tense/aspect, but with striking differencesbetween the present perfect and simple future.

In this paper, we discuss a new approach to the analysis of multi/hyper-spectral data sets, based on the Interesting Features Finder (IFF) method. The IFF is a simple algorithm recently proposed in the framework of Laser-Induced Breakdown Spectroscopy (LIBS) spectral analysis for detecting ‘interesting’ spectral features independently of the variance they represent in a set of spectra. To test the usefulness of this method to multispectral analysis, we show in this paper the results of its application on the recovery of a ‘lost’ painting from the Etruscan hypogeal tomb of the Volumni (3rd century BCE—1st century CE) in Perugia, Italy. The results obtained applying the IFF algorithm are compared with the results obtained by applying Blind Source Separation (BSS) techniques and Self-Organized Maps (SOM) to a multispectral set of 17 fluorescence and reflection images. From this comparison emerges the possibility of using the IFF algorithm to obtain rapidly and simultaneously, by varying a single parameter in a range from 0 to 1, several sets of elaborated images all containing the ‘interesting’ features and carrying information comparable to what could have been obtained by BSS and SOM, respectively.

Several samples coming from the recently discovered (February 2019) Late Bronze Age/Early Iron Age Chovdar necropolis in Azerbaijan were analysed using the X-ray fluorescence (XRF) technique. The analysis allowed a preliminary classification of the samples in eight groups based on their composition, obtained from the XRF spectra using the fundamental parameter method. A more detailed classification was then obtained using the graph clustering method.

Background: Gastric pH changes by proton-pump-inhibitors (PPIs) were found to affect progression-free survival (PFS) in metastatic breast cancer (mBC) patients treated with palbociclib. The current study was aimed at investigating whether the same effect could occur in patients treated with ribociclib. Patients and methods: Patients with hormone-positive/HER-2-negative mBC candidates for first-line treatment with ribociclib were enrolled in this retrospective-cohort study. Patients were classified as “no concomitant PPIs” or “concomitant PPIs”; PPI administration covered the entire or not less than 2/3 of treatment with ribociclib. All clinical interventions were made according to clinical practice. Results: A total of 128 patients were consecutively enrolled in the study; 78 belonged to the “no concomitant PPIs” group and 50 to the “concomitant PPIs” group. One hundred and six patients were endocrine-sensitive and received ribociclib and letrozole, while 22 were endocrine-resistant and were treated with ribociclib and fulvestrant. The most prescribed PPI was lansoprazole. According to PFS, patients taking PPIs had a PFS almost superimposable to those assuming ribociclib and endocrine therapy alone (35.3 vs. 49.2 months, p = 0.594). No difference in PFS was observed in estrogen-sensitive or estrogen-resistant mBC in the presence or absence of concomitant PPI treatment (p = 0.852). No correlation with adverse events was found including grade>2 hematological toxicities. Conclusions: The present study supports the hypothesis that the concomitant use of PPIs does not compromise the efficacy of ribociclib in a real-life setting.

Abstract Bariatric surgery (BS) is an effective intervention for severe obesity and associated comorbidities. Although several studies have addressed the clinical and metabolic effects of BS, an integrative analysis of the complex body response to surgery is still lacking. We conducted a longitudinal data study with 36 patients with severe obesity who were tested before, 6 and 12 months after restrictive BS for more than one hundred blood biomarkers, including clinical, oxidative stress and metabolic markers, peptide mediators and red blood cell membrane lipids. By using a synthetic data-driven modeling based on principal component and correlation analyses, we provided evidence that, besides the early, well-known glucose metabolism- and weight loss-associated beneficial effects of BS, a tardive, weight-independent increase of the hepatic cholesterol metabolism occurs that is associated with potentially detrimental inflammatory and metabolic effects. Canonical correlation analysis indicated that oxidative stress is the most predictive feature of the BS-induced changes of both glucose and lipids metabolism. Our results show the power of multi-level correlation analysis to uncover the network of biological pathways affected by BS. This approach highlighted potential health risks of restrictive BS that are disregarded with the current practice to use weight loss as surrogate of BS success.

Abstract Max Ernst was one of the most influential artists associated with both the Dada and Surrealist movements. However, until now, only few scientific studies have been devoted to his works. This paper presents the results of a multi-analytical investigation on six oil paintings, made between 1927 and 1942, belonging to the Peggy Guggenheim Collection in Venice (Solomon R. Guggenheim Foundation, New York). Through a combined art historical and scientific approach, this study aims at understanding Ernst’s painting techniques, including frottage, grattage, dripping, and decalcomania, the used materials, and the state of conservation of the artworks. Non-invasive in situ investigations were performed by means of Vis–NIR multi-spectral imaging, X-ray fluorescence, external reflection FTIR and Raman spectroscopy. Imaging analysis revealed important information about Ernst’s painting methods while the other techniques provided useful information about the ground layer, the painting materials and the presence of alteration products. Ernst’s palette discloses great freedom in his use of materials and evolution during the time. This investigation demonstrates that an integrated, non-invasive, diagnostic approach provides a thorough analysis of materials and execution techniques of Ernst’ masterworks allowing an in-depth knowledge of his highly skilled work.

The classical light interactions of nanosilicon, which is a dielectric material, are exceedingly weak for radius r ≪ λ (wavelength), scaling as r6. It exhibits geometrical anisotropy-based depolarization, which is the basis for the very weak response in isotropic structures (nanosphere). Recently, surface enhanced Raman scattering (SERS) in DNA decorated with ultrasmall Si nanoparticles has been demonstrated, affording an effective alternative to plasmon–metal particles. In this paper, we execute fundamental quantum atomistic computation of 1 nm hydrogenated Si particles, with different surface reconstruction and termination, including Si–H, H–Si–Si–H (dimer molecules), or oxygenated dimer bridges (H–Si–O–Si–H). We obtain the mechanical vibrational modes of the particles. Our results show that by changing the surface configuration one can control the symmetry and normal vibration modes, and enhance the polarizability, polarity, and light interactions (scattering, absorption, and depolarization/memory). The low frequency polarizability (Raman scattering) shifts spatially from the interior to the surface, while the infrared polarity remains on the surface, but its bandwidth narrows spectrally. The results support previous infrared absorption and light scattering and depolarization measurements, as well recent SERS, which enable Si nanoparticles to be an effective alternative to plasmonic metal particles. Molecular surface reconstruction in terms of Si dimers and bridges were suggested as the source of the novel nonlinear and anisotropic luminescence and photonic properties of Si nanoparticles. Such control affords potential for optimizing the design and operation of a wide range of opto-electronic advanced scattering and luminescence devices.

Covalently linked peptide-porphyrin compounds are most suitable systems for fundamental studies aiming to the comprehension of the mechanisms driving photoinduced energy/electron transfer processes. Mimicking photosynthetic units, the porphyrin groups act as antenna moieties while the peptide chain is the active medium through which energy and/or electron funneling occur. In this contribution we studied the transfer of excitation between two identical tetraphenylporphyrin groups connected by short peptide chains of different length formed by non-coded conformationally constrained α-amino acids, i.e., Cα-methylvaline. The photophysical events following porphyrin photoexcitation were characterized from the microsecond to the picosecond time region by time-resolved spectroscopy techniques. Ultrafast transient absorption measurements revealed the presence of a transient species that we assign to a self-trapped exciton migrating through the peptide chain. The exciton species propagates the electronic coupling between the two porphyrin groups giving rise to a characteristic bisignate band measured by circular dichroism experiments. Molecular dynamics simulations strongly suggest that the long lifetime (hundreds of picoseconds) of the exciton species is determined by the rigidity of the Cα-methylvaline residues, that inhibited energy relaxation pathways coupled to torsional motions of the peptide chain.

Background: Cyclin-dependent kinase 4 and 6 (CDK4 and CDK6) inhibitors have changed the therapeutic management of hormone receptor-positive (HR+) metastatic breast cancer (mBC) by targeting the cell cycle machinery and overcoming endocrine resistance. However, a large number of patients present disease progression due to cancer cells resisting CDK4/6 inhibitors. Our research considers which clinicopathological characteristics could be useful in identifying patients who might respond to CDK4/6 inhibitors by analyzing a retrospective case series of patients with HR+ mBC who were treated with hormone therapy plus CDK4/6 inhibitors. Methods: Approximately 177 mBC patients were enrolled, of whom 66 were treated with CD4/6 inhibitors plus letrozole and 111 were treated with CDK4/6 inhibitors and fulvestrant. A multistate model was used. Results: A low body surface area and older age were associated with an increased risk of developing neutropenia. A high Ki67 index, the presence of visceral metastases, and not having previously undergone adjuvant chemotherapy were prognostic factors of disease progression/death. As expected, some of the neutropenic patients who had previously undergone multiple lines of treatment were at a higher risk of disease progression/death. Furthermore, neutropenia status was associated with a more than doubled risk of progression/death compared to patients without neutropenia (HR = 2.311; p = 0.025). Conclusions: Having identified certain factors that could be associated with the development of neutropenia and considering that neutropenia itself is associated with an increased risk of progression, we believe that the baseline characteristics should be taken into account to reduce cases of neutropenia and disease progression.

Field handheld/portable instrumentations, such as in-situ geochemical analyzers, have the potential to assist efficiently targeted geochemical archaeometry campaigns in detecting and quantifying specific elements. Non-destructive portable energy dispersive x-ray fluorescence and micro-destructive handheld laser-induced breakdown spectroscopy (LIBS) instrumentation were utilized to investigate the elemental composition, internal stratigraphy by depth profiling and microscale compositional mapping of five copper and two iron alloy artefacts collected from various ancient graves in the Minervino Murge area, Apulia, Italy. The primary elements identified by both techniques included Cu, Sn and Pb in copper alloys, and Fe with minor amounts of Cu and Pb in iron alloys. Furthermore, the elements Al, Ca, Si, Mg, Na and K, mostly originated from soil contamination, and the trace elements Sb, Ni and Zn were detected. The satisfactory performance of both techniques was assessed by their capacity to provide reproducible elemental composition data. Finally, the depth profile and mapping achieved by LIBS contributed to understanding the metal processing and history of the objects studied, so confirming both techniques to be robust analytical tools in outdoor archaeology and archaeometry campaigns.