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Abstract Background Access to quality Home Palliative Care (HPC) is a public health priority. This study analyzed HPC services in Piedmont, a large, diverse Italian region (4.3 million inhabitants), as a case study to understand organizational variations in complex settings and inform equity-focused policies. Methods A cross-sectional survey covered Piedmont's 12 Local Health Authorities (LHAs) and 35 districts. Pre-pandemic data for 2019 were collected in 2023 via in-person questionnaires and interviews with HPC managers/directors. Key structural, process, and outcome indicators were analyzed descriptively. 2022 data were collected for comparison. Results Substantial heterogeneity was found across LHAs in 2019. Formal Local Palliative Care Networks existed in only 8/12 LHAs. Dedicated HPC units were present in 11/12 LHAs, but with varying structures and staffing (physician Full-Time Equivalents, or FTEs, range 0.59-3.00 per 100,000 inhabitants; regional average 1.71, below standards). Nurse FTE data faced challenges. Care pathways showed fragmentation and coordination with emergency services were limited, but psychological support was guaranteed. Large disparities emerged in care intensity (ratio of actual assistance days to total care days range 0.09-0.64) and place of death for cancer patients (home deaths range 6.26%-44.03%). Fragmented data systems hindered monitoring. The 2019-2022 comparison showed improvements (hospital deaths decreased from 23.6% to 16.0%) but confirmed persistent heterogeneity. Conclusions Mapping revealed marked variability in Piedmont's HPC organization, resourcing, delivery, and outcomes. Key challenges identified include network gaps, resource disparities (esp. physicians), fragmented models/pathways, poor care continuity, and inadequate monitoring. Addressing these disparities requires understanding a complex, often poorly documented system lacking systematic data. This study offers a valuable methodology applicable in similar contexts. Key messages • Mapping regional Home Palliative Care reveals significant disparities in organization, resources, and outcomes, impacting equity of access and quality. • Detailed regional analysis provides an evidence base for targeted policies and standardized improvements towards equitable, high-quality HPC across Europe.

RadioLab is an Italian project, addressed to school-age people, and designed for the dissemination of scientific culture on the theme of environmental radioactivity, with particular regards to the importance of knowledge of radon gas exposure. The project is a nationwide initiative promoted by the National Institute of Nuclear Physics- INFN. First tool used by the project, and of immediate impact to assess the public awareness on radon, is the administration of the survey “do you know the radon gas?”. In the survey, together with the knowledge of radon and of its sources, information on personal, cultural and territorial details regarding the interviewees are also taken. Reasonably, the survey invests not only young people, but also their relatives, school workers and, gradually, the public. The survey is administrated during exhibitions or outreach events devoted to schools, but also open to the public. The survey is in dual form: printed and online. The online mode clearly leads RadioLab project even outside the school environment. Based on the results of the survey, several statistical analyses have been performed and many conclusions are drawn about the knowledge of the population on the radon risk. The RadioLab benefit and the requirement to carry on the project goals, spreading awareness of environmental radioactivity from radon, emerge. The dataset involves all twenty Italian regions and consists of 28,612 entries covering the 5-year period 2018–2022.

We identified a discrete number of microRNAs differentially expressed in benign or malignant mesothelial tissues. We focused on mir-145 whose levels were significantly downregulated in malignant mesothelial tissues and malignant pleural mesothelioma (MPM) cell lines as compared to benign tissues (pleura, peritoneum or cysts). We show that promoter hyper-methylation caused very low levels in MPM cell lines and specimens. Treatment of MPM cell lines with mir-145 agonists negatively modulated some protumorigenic properties of MPM cells, such as clonogenicity, cell migration and resistance to pemetrexed treatment. The main effector mechanism of the clonogenic death induced by mir-145 was that of accelerated senescence. We found that mir-145 targeted OCT4 via specific binding to its 3′-UTR. Increased intracellular levels of mir-145 decreased the levels of OCT4 and its target gene ZEB1, thereby counteracting the increase of OCT4 induced by pemetrexed treatment which is known to favor the development of chemoresistant cells. In line with this, reintroduction of OCT4 into mimic-145 treated cells counteracted the effects on clonogenicity and replicative senescence. This further supports the relevance of the mir-145-OCT4 interaction for the survival of MPM cells. The potential use of mir-145 expression levels to classify benign vs malignant mesothelial tissues and the differences between pemetrexed-induced senescence and that induced by the re-expression of mir-145 are discussed.

Within the research along the European Fusion Roadmap, water-cooled divertor PFCs are foreseen in the design of a first fusion demonstration power plant (DEMO) in order to provide reliable heat removal capability. In the frame of this concerted attempt, the Max Planck Institute for Plasma Physics is concentrating on the development and testing of composite materials based on tungsten (W, preferred armour material) and copper (Cu, preferred heat sink material). W fibres (W f ) as monofilaments and yarns as reinforcement play a central role in these investigations due to their extraordinary properties concerning ductility already at room temperature and high tensile strength. Recent investigations on the impact of radiation damage suggest that the fibres retain their ductility upon irradiation. W reinforced with W fibres (W f /W) allows to overcome the intrinsic brittleness of W. Quantitative mechanical fracture tests of W f /W confirm the basic mechanisms of fibre reinforcement and the increased resistance to mechanical fatigue. The good wettability of W with liquid Cu and the absence of any metallurgical solubility make up an ideal material pairing for composite production. W fibre-reinforced Cu (W f /Cu) cooling tubes provide a rather high thermal conductivity (> 250 W mK −1 ) and at least twice the strength of CuCrZr in hoop direction in the temperature range up to at least 500 °C. Very recent neutron irradiation experiments confirm the sustainment of ductility of the W f /Cu composite. Numerical simulations suggest that thermal stresses in W-Cu PFCs could be strongly reduced by tailoring the local W and Cu volume fraction. This ‘freely’ distributed material composition can be achieved by means of additively manufactured W skeletons consecutively infiltrated by Cu. Investigations with W preforms produced by Laser Beam Powder Bed Fusion and infiltrated by Cu demonstrate the feasibility of this approach while testing of specifically prepared specimen is ongoing.

Background Patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) are becoming essential parts of a learning health system, and using these measures is a promising approach for value-based healthcare. However, evidence regarding healthcare professional and patient organizations’ knowledge, use and perception of PROMs and PREMs is lacking. Objectives The objectives of the study were to: 1- Describe the current knowledge and use of PROMs and PREMs by healthcare professional and patient organizations, 2- Describe the determinants of PROMs and PREMs implementation according to healthcare professional and patient organizations. Methods We conducted an environmental scan using semi-structured interviews with representatives from healthcare professional and patient organizations. Interviews were recorded and live coded based on the Franklin framework. We used inductive and deductive thematic analysis to extract information about the main themes addressed during the interview (awareness of PROMs and PREMs, examples of implementation and use of PROMs and PREMs, tools used, vision for future implementation, barriers and facilitators to implementation and the best way to collect PROMs and PREMs data). Results 63% of healthcare professional organizations ( n  = 19) and 41% of patient organizations ( n  = 9) that were contacted agreed to have a representative interviewed. The representatives from both the healthcare professional and patient organizations acknowledged the importance of assessing patients’ experience and outcomes. However, they considered the implementation of PROMs and PREMs tools to be scarce within their organizations, in clinical practice and in the education system. Patient organizations were worried that overuse of PROMs and PREMs could lead to depersonalization of practice. Barriers to implementing PROMs and PREMs included lack of awareness of tools, resistance to change and lack of motivation to complete or explain the questionnaire. Barriers also included factors such as lack of financial, technological and human resources and issues with integration of data and inconsistency of digital platforms. Conclusions This environmental scan revealed a lack of awareness of tools by healthcare professional and patient organizations’ representatives and limited implementation. Adequate training, technological integration, and demonstration of PROMs and PREMs benefits to foster broader adoption in clinical and organizational settings is dearly needed. Addressing these challenges is essential for enhancing value-based care.

Background Lung cancer represents the most frequent cause of death for cancer. In non-small cell lung cancer (NSCLC), which accounts for the vast majority of this disease, only early detection and treatment, when possible, may significantly affect patient's prognosis. An important role in NSCLC malignancy is attributed to the signal transduction pathways involving PI3Kinase, with consequent activation of the AKT family factors. The serum and glucocorticoid kinase (SGK) factors, which share high structural and functional homologies with the AKT factors, are a family of ubiquitously expressed serine/threonine kinases under the control of cellular stress and hormones. SGK1 is the most represented SGK member. Methods By means of immunohistochemistry and quantitative real-time PCR, we determined SGK1 protein and mRNA expression in a cohort of 66 formalin-fixed, paraffin-embedded NSCLC surgical samples. All samples belonged to patients with a well-documented clinical history. Results mRNA expression was significantly higher in squamous cell carcinomas, and correlated with several clinical prognostic indicators, being elevated in high-grade tumors and in tumors with bigger size and worse clinical stage. No correlation was found between SGK1 protein expression and these clinical parameters. Conclusions This explorative analysis of SGK1 expression in NSCLC samples highlights the potential role of this factor in NSCLC patients' prognosis. Moreover, the higher expression in the squamous cell carcinoma subtype opens new therapeutic possibilities in this NSCLC subtype by designing specific kinase inhibitors.

The purpose of this study is the evaluation of the histological effects of a new-generation superpulsed CO2 laser through an “ex vivo” study. A CO2 (λ = 10,600 nm) ultra-speed laser (SmartUS20D, DEKA, Florence, Italy) has been used at different parameters from 2 to 4 watt in Continuous Wave (CW) and Pulsed Wave (PW, 50 Hz) to obtain 30 samples from pig cadaver tongues. All the specimens have been subdivided into 6 groups (from A to F) and each group consisted of 5 samples. A final specimen has been taken by scalpel and used as control group. Histological analysis has been performed using an optical microscope (Leica DM 2000) at a magnification of ×40. Results showed that histological readability was optimal in all the samples. The thermal damage has been negligible in all the groups. Furthermore, the average of thermal damage was 0,095 mm in the epithelial, while it was 0.245 mm in the connective tissue. Statistical analysis using Graphpad Prism 5 software showed no significant differences among the groups. CO2 laser demonstrated a good surgical effectiveness provoking little peripheral damage onto the cut edges and allowing a safe histological diagnosis.

Tyrosine kinase inhibitors (TKIs) have shown strong activity against non-small-cell lung cancer (NSCLC) patients harboring activating epidermal growth factor receptor (EGFR) mutations. However, a fraction of EGFR wild-type (WT) patients may have an improvement in terms of response rate and progression-free survival when treated with erlotinib, suggesting that factors other than EGFR mutation may lead to TKI sensitivity. However, at present, no sufficiently robust clinical or biological parameters have been defined to identify WT-EGFR patients with greater chances of response. Therapeutics validation has necessarily to focus on lung cancer stem cells (LCSCs) as they are more difficult to eradicate and represent the tumor-maintaining cell population. Here, we investigated erlotinib response of lung CSCs with WT-EGFR and identified EGFR phosphorylation at tyrosine1068 (EGFR tyr1068 ) as a powerful biomarker associated with erlotinib sensitivity both in vitro and in preclinical CSC-generated xenografts. In contrast to the preferential cytotoxicity of chemotherapy against the more differentiated cells, in EGFR tyr1068 cells, erlotinib was even more active against the LCSCs compared with their differentiated counterpart, acquiring potential value as CSC-directed therapeutics in the context of WT-EGFR lung cancer. Although tumor growth was inhibited to a similar extent during erlotinib or chemotherapy administration to responsive tumors, erlotinib proved superior to chemotherapy in terms of higher tolerability and reduced tumor aggressiveness after treatment suspension, substantiating the possibility of preferential LCSC targeting, both in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) tumors. We conclude that EGFR tyr1068 may represent a potential candidate biomarker predicting erlotinib response at CSC-level in EGFR-WT lung cancer patients. Finally, besides its invariable association with erlotinib sensitivity in EGFR-WT lung CSCs, EGFR tyr1068 was associated with EGFR-sensitizing mutations in cell lines and patient tumors, with relevant diagnostic, clinical and therapeutic implications.

Background Fibrotic interstitial lung diseases (ILDs) are chronic and often progressive conditions resulting in substantial morbidity and mortality. Shortness of breath, a symptom often linked to oxygen desaturation on exertion, is tightly linked to worsening quality of life in these patients. Although ambulatory oxygen is used empirically in their treatment, there are no ILD-specific guidelines on its use. To our knowledge, no studies are available on the effects of ambulatory oxygen on day-to-day life in patients with ILD. Methods/design Ambulatory oxygen in fibrotic lung disease (AmbOx) is a multicentre, randomised controlled crossover trial (RCT) funded by the Research for Patient Benefit Programme of the National Institute for Health Research. The trial will compare ambulatory oxygen used during daily activities with no ambulatory oxygen in patients with fibrotic lung disease whose oxygen saturation (SaO 2 ) is ≥94% at rest, but drops to ≤88% on a 6-min Walk Test. The randomised controlled trial (RCT) will evaluate the effects on health status (measured by the King’s Brief ILD Questionnaire: K-BILD) of ambulatory oxygen used at home, at an optimal flow rate determined by titration at screening visit, and administered for a 2-week period, compared to 2 weeks off oxygen. Key secondary outcomes will include breathlessness on activity scores, as measured by the University of California San Diego Shortness of Breath Questionnaire, global patient assessment of change scores, as well as quality of life scores (St George’s Respiratory Questionnaire), anxiety and depression scores (Hospital Anxiety and Depression Scale), activity markers measured by SenseWear Armbands, pulse oximetry measurements, patient-reported daily activities, patient- and oxygen company-reported oxygen cylinder use. The study also includes a qualitative component and will explore in interviews patients’ experiences of the use of a portable oxygen supply and trial participation in a subgroup of 20 patients and carers. Discussion This is the first RCT of the effects of ambulatory oxygen during daily life on health status and breathlessness in fibrotic lung disease. The results generated should provide the basis for setting up ILD-specific guidelines for the use of ambulatory oxygen. Trial registration National Clinical Trials Registry, identifier: NCT02286063 . Registered on 8 October 2014 (retrospectively registered).