Search

We aimed to evaluate whether progression-directed radiation therapy (PDRT) can prolong the initiation of a subsequent systemic therapy regimen in a cohort of patients with oligoprogressive NSCLC. A retrospective analysis was conducted on NSCLC patients who underwent PDRT for extracranial oligoprogressive NSCLC, defined as limited (up to five) progressing lesions following initial complete, partial, or stable response to systemic therapy according to REC1ST 1.1 and/or PERCIST 1.0 criteria. Cox proportional hazard regressions were performed to identify factors influencing time to next treatment (TTNT), which was considered the primary endpoint. Forty patients were analyzed. First, second, and ≥3 lines of systemic therapy were administered in 22 (58.2%), 14 (27.2%), and 4 (14.6%) cases, respectively. The median total dose was 36 Gy (range: 12–60) in five fractions (1–10), with a median biological effective dose for tumor control (BED10) of 52 Gy (26.4–151.2). After a median follow-up of 11 months (2–50), PDRT delayed further systemic therapy in 32 (80.0%) treatments. Median TTNT was not reached at 8 months (1–47) with a one-year Kaplan–Meier estimate of 81.4% (95% CI: 75.0% to 87.8%). No >grade 3 adverse event was observed. On multivariate analysis, patients with ≥3 lines of systemic therapy and/or with larger CTV volumes did not benefit from PDRT. Despite the use of sub-ablative doses, our findings show that PDRT represents an effective, safe, and viable option for oligoprogressive NSCLC. Patients irradiated early during their systemic treatment course, with a low volume of disease and nonmetastatic oligoprogression, could derive substantial benefits from PDRT.

The manuscript provides an overview of the mid-term results of the citizen science campaign activities conducted within the Life CONCEPTU MARIS project (LIFE20 NAT/IT/001371) whose aim is to improve the conservation status of cetaceans and pelagic sea turtles by addressing information gaps, setting up an internationally agreed-upon approach for surveillance, and identifying appropriate conservation measures. It fosters a cooperative effort by engaging the scientific community, stakeholders, policy makers and citizens in a common effort to support biodiversity.

Abstract Traditional philosophical inquiry, and more recently neuroscientific studies, have investigated the sources of artworks' aesthetic appeal. A substantial effort has been made to isolate the objective features contributing to aesthetic appreciation. While variables such as contrast or symmetry have been shown to robustly impact aesthetic judgment, they only account for a small portion of the intersubjective variability in aesthetic ratings. Recent multiprocess model of aesthetic appreciation could accommodate this finding by proposing that evaluative processes based on self-reference underpin the idiosyncrasy of aesthetic judgment. We tested this hypothesis in two behavioral studies, that were basically conceptual replications of our previous work, in which we took advantage of the self-reference effect on memory. We also tried to disentangle the role of self-reference and emotional reaction to artworks in guiding aesthetic judgments, by comparing an aesthetic judgment encoding condition to a self-reference condition (Study 1), and an emotional evaluation condition (Study 2). We show that artworks encoded in an aesthetic judgment condition exhibit a similar mnesic advantage compared to both the self-reference and the emotional evaluation encoding conditions. Moreover, retrospective emotional judgment correlates with both self-reference and aesthetic judgments ratings. These results suggest that a basic mechanism, appraisal of self-relevance, could ground aesthetic judgments.

Abstract Organic electrochemical transistors have emerged as a promising alternative to traditional 2/3 electrode setups for sensing applications, offering in-situ transduction, electrochemical amplification, and noise reduction. Several of these devices are designed to detect potentiometric-derived signals. However, potentiometric sensing should be performed under open circuit potential conditions, allowing the system to reach thermodynamic equilibrium. This criterion is not met by conventional organic electrochemical transistors, where voltages or currents are directly applied to the sensing interface, that is, the gate electrode. In this work, we introduce an organic electrochemical transistor sensing configuration called the potentiometric‑OECT (pOECT), which maintains the sensing electrode under open circuit potential conditions. The pOECT exhibits a higher response than the 2-electrode setup and offers greater accuracy, response, and stability compared to conventional organic electrochemical transistors. Additionally, it allows for the implementation of high-impedance electrodes as gate/sensing surfaces, all without compromising the overall device size.

Background & Aims: Among the reprogrammed metabolic pathways described in cancer stem cells, aberrant lipid metabolism has recently drawn increasing attention. Our study explored the contribution of fatty acids (FA) in the regulation of stem-like features in intrahepatic cholangiocarcinoma (iCCA). Methods: We previously identified a functional stem-like subset in human iCCA by using a three-dimensional sphere (SPH) model in comparison to parental cells grown as monolayers (MON). In this study, quantification of intracellular free FA and lipidomic analysis (triacylglycerol [TAG] composition, de novo synthesis products) was performed by Liquid chromatography–mass spectrometry (LC–MS); quadrupole time-of-flight liquid chromatography/mass spectrometry (Q-TOF LC/MS), respectively, in both SPH and MON cultures. Results: Stem-like SPH showed a superior content of free FA (citric, palmitic, stearic, and oleic acids) and unsaturated TAG. Molecularly, SPH showed upregulation of key metabolic enzymes involved in de novo FA biosynthesis (AceCS1, ACLY, ACAC, FASN, ACSL1) and the mTOR signalling pathway. In patients with iCCA (n = 68), tissue expression of FASN, a key gene involved in FA synthesis, correlated with 5-year overall survival. Interference with FASN activity in SPH cells through both specific gene silencing (siRNA) or pharmacological inhibition (orlistat) decreased sphere-forming ability and expression of stem-like markers. In a murine xenograft model obtained by injection of iCCA-SPH cells, FASN inhibition by orlistat or injection of FASN-silenced cells significantly reduced tumour growth and expression of stem-like genes. Conclusion: Altered FA metabolism contributes to the maintenance of a stem-like phenotype in iCCA. FASN inhibition may represent a new approach to interfere with the progression of this deadly disease. Impact and implications: Recent evidence indicates that metabolic disorders correlate with an increased susceptibility to intrahepatic cholangiocarcinoma (iCCA). Our investigation emphasises the pivotal involvement of lipid metabolism in the tumour stem cell biology of iCCA, facilitated by the upregulation of crucial enzymes and the mTOR signalling pathway. From a clinical perspective, this underscores the dual role of FASN as both a prognostic indicator and a therapeutic target, suggesting that FASN inhibitors could enhance patient outcomes by diminishing stemness and tumour aggressiveness. These findings pave the way for novel therapeutic strategies for iCCA and shed light on its relationship with metabolic disorders such as diabetes, obesity, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease.

Proceedings

Abstract Background Biliary tract cancers (BTCs) are rare and lethal cancers, with a 5-year survival inferior to 20%(1–3). The only potential curative treatment is surgical resection. However, despite complex surgical procedures that have a remarkable risk of postoperative morbidity and mortality, the 5-year survival rate after radical surgery (R0) is 20–40% and recurrence rates are up to ~ 75%(4–6). Up to ~ 40% of patients relapse within 12 months after resection, and half of these patient will recur systemically(4–6). There is no standard of care for neoadjuvant chemotherapy (NAC) in resectable BTC, but retrospective reports suggest its potential benefit (7, 8). Methods PURITY is a no-profit, multicentre, randomized phase II/III trial aimed at evaluating the efficacy of the combination of gemcitabine, cisplatin and nabpaclitaxel (GAP) as neoadjuvant treatment in patients with resectable BTC at high risk for recurrence. Primary objective of this study is to evaluate the efficacy of neoadjuvant GAP followed by surgery as compared to upfront surgery, in terms of 12-month progression-free survival for the phase II part and of progression free survival (PFS) for the phase III study. Key Secondary objectives are event free survival (EFS), relapse-free survival, (RFS), overall survival (OS), R0/R1/R2 resection rate, quality of life (QoL), overall response rate (ORR), resectability. Safety analyses will include toxicity rate and perioperative morbidity and mortality rate. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues and longitudinal ctDNA analysis are planned to identify potential biomarkers of primary resistance and prognosis. Discussion Considering the poor prognosis of resected BTC experiencing early tumor recurrence and the negative prognostic impact of R1/R2 resections, PURITY study is based on the rationale that NAC may improve R0 resection rates and ultimately patients’ outcomes. Furthermore, NAC should allow early eradication of microscopic distant metastases, undetectable by imaging but already present at the time of diagnosis and avoid mortality and morbidity associated with resection for patients with rapid progression or worsening general condition during neoadjuvant therapy. The randomized PURITY study will evaluate whether patients affected by BTC at high risk from recurrence benefit from a neoadjuvant therapy with GAP regimen as compared to immediate surgery. Trial registration PURITY is registered at ClinicalTrials.gov (NCT06037980) and EuCT(2023–503295-25–00).

Abstract Background BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy. Despite previous suggestion of pathogenicity, variant classification in public databases is still conflicting, needing additional evidence. Methods Maximum likelihood penetrance of breast/ovarian and other cancer types was estimated using full pedigree data from 53 informative Italian families. The effect of the variant on BRCA1‐ABRAXAS1 interaction was assessed using a GFP‐fragment reassembly‐based PPI assay. Results were combined with additional data from multiple sources to classify the variant according to ACMG/AMP classification rules specified for BRCA1/2. Results Variant‐carriers displayed increased risk for ovarian cancer (HR = 33.0, 95% CI = 7.0–155.0; cumulative risk at age 70 = 27.6%, 95% CI = 12.6–40.0%) but not for breast cancer (HR = 0.7, 95% CI = 0.2–2.2). An increased risk of uterine cancer (HR = 8.0, 95% CI = 1.03–61.6) emerged, warranting further evaluation. Likelihood‐ratio in favor of pathogenicity was 98898642.82 under assumption of standard BRCA1 breast and ovarian penetrance, and 104240832.84 after excluding breast cancer diagnoses (based on penetrance results). Functional analysis demonstrated that the variant abrogates the BRCA1‐ABRAXAS1 binding, supporting the PS3 code assignment within the ACMG/AMP rule‐based model. Collectively, these findings allowed to classify the variant as pathogenic. Conclusion Pathogenicity of BRCA1:c.5017_5019del(p.His1673del) has been confirmed; however, breast cancer risk in Italian families is not increased, unlike in families from other countries and in carriers of most BRCA1 pathogenic variants. The knowledge of atypical risk profiles for this and other variants will pave the way for personalized management based on specific genotype.

Background/Objectives: Although rare in the Western world, dog bites may be lethal or lead to physically severe outcomes. However, little attention is given to their psychological consequences. We aimed to review their psychological consequences in children 1–14 years of age, focusing on the prevalence and nature of psychological disorders, evaluating the impact on future mental health of children and their families, and assessing the effectiveness of preventive interventions and measures. Methods: On 23 May 2024, we investigated the PubMed, CINAHL, and PsycINFO/PsycARTICLES databases using (“dog bite” OR animal-induced OR animal-caused) AND (psychol* OR mental OR psychiatr* OR anxiety OR anxious OR depress* OR obsess* OR trauma* OR psychosis OR psychotic OR schizophren* OR schizoaffect*) filtered for ages 0–18 years. This resulted in 311 records, of which 50 were eligible. These included original research, case reports, patient surveys, and reviews/meta-analyses. Results: Findings indicate that younger children are particularly vulnerable, often suffering head/neck bites, leading to severe injuries and psychological distress, with post-traumatic stress disorder (PTSD) being a common outcome. Symptoms such as nightmares, flashbacks, anxiety, and social withdrawal were frequently reported. Positive parental support and timely psychological interventions were found to mitigate these effects. Conclusions: Interdisciplinary approaches integrating education, cognitive restructuring, and behaviour modification are needed to effectively prevent and address the psychological impacts of dog bites. Summarising, dog bites in children result in substantial psychological sequelae, necessitating robust prevention and intervention strategies to improve their quality of life and reduce the risk of chronic mental conditions.

The purpose of this clinical epidemiological investigation was to examine the oral health conditions of homeless people in the city of Rome, Italy. A total of 157 homeless subjects were subjected to a first dental visit, during which anamnestic information was recorded in a digital medical record. A diagnosis of dental disorders was performed by assessing oral hygiene conditions, periodontal health, the presence of caries and/or root residues, and the presence of partial and/or total edentulousness. Caries and missing teeth were evaluated by the DMFT index. The first major criticality was represented by poor or absent oral hygiene. The examined sample showed a major percentage of high DMFT (63.0%); the most common clinical condition was the presence of numerous root residues. Regarding periodontal health, 73.2% of patients had gingivitis, 21.6% periodontitis, while 11 patients had periodontal pathologies with tooth mobility (7%). Finally, 8.9% of patients had one or two missing elements, 22.9% had partial edentulousness, and 8.9% of the sample had total edentulism. This analysis provides an important basis for strengthening health promotion and the importance of accessible and effective care for this population. It will therefore be necessary to continue to adopt a patient-centered approach geared towards addressing the demands that this population faces in maintaining their oral health.

Antineoplastic drugs (ADs) are essential tools in cancer treatment, but their cytotoxicity poses a risk to workers involved in their handling. In a hospital environment fundamental strategies for minimising exposure involve proper use of safety cabinets and closed-circuit transfer devices, along with personnel training and increased awareness of risks. However, medical gloves remain the first line of defence. In this respect the evaluation of glove materials and best choices can improve hospital safety management and prevent potential hazards and long-term consequences. The aim of this study was to assess contamination of gloves in samples taken from AD administration and preparation units of nine Italian hospitals and to raise awareness of the importance of evaluating chemico-physical properties of gloves. Our findings show that 33 % of the analysed gloves were positive for at least one AD, with contaminations ranging from 0.6 to 20,729 pg/ cm2. We proposed the alert glove values (AGVs) for each AD as a limit value for contamination assessment and good practice evaluation. Our findings also point to multiple AD contamination (43 % of positive findings in preparation units), calculated as total AGV (AGV-T), and confirm that gloves should be replaced after 30 min of AD handling, based on cumulative permeation and area under the curve (AUC), to maintain safety and limit dermal exposure.

Abstract Background To investigate the capability of a not-yet commercially available fully automated lexicographic optimization (LO) planning algorithm, called mCycle (Elekta AB, Stockholm, Sweden), to further improve the plan quality of an already-validated Wish List (WL) pushing on the organs-at-risk (OAR) sparing without compromising target coverage and plan delivery accuracy. Material and Methods Twenty-four mono-institutional consecutive cervical cancer Volumetric-Modulated Arc Therapy (VMAT) plans delivered between November 2019 and April 2022 (50 Gy/25 fractions) have been retrospectively selected. In mCycle the LO planning algorithm was combined with the a-priori multi-criterial optimization (MCO). Two versions of WL have been defined to reproduce manual plans (WL01), and to improve the OAR sparing without affecting minimum target coverage and plan delivery accuracy (WL02). Robust WLs have been tuned using a subset of 4 randomly selected patients. The remaining plans have been automatically re-planned by using the designed WLs. Manual plans (MP) and mCycle plans (mCP01 and mCP02) were compared in terms of dose distributions, complexity, delivery accuracy, and clinical acceptability. Two senior physicians independently performed a blind clinical evaluation, ranking the three competing plans. Furthermore, a previous defined global quality index has been used to gather into a single score the plan quality evaluation. Results The WL tweaking requests 5 and 3 working days for the WL01 and the WL02, respectively. The re-planning took in both cases 3 working days. mCP01 best performed in terms of target coverage (PTV V95% (%): MP 98.0 [95.6–99.3], mCP01 99.2 [89.7–99.9], mCP02 96.9 [89.4–99.5]), while mCP02 showed a large OAR sparing improvement, especially in the rectum parameters (e.g., Rectum D50% (Gy): MP 41.7 [30.2–47.0], mCP01 40.3 [31.4–45.8], mCP02 32.6 [26.9–42.6]). An increase in plan complexity has been registered in mCPs without affecting plan delivery accuracy. In the blind comparisons, all automated plans were considered clinically acceptable, and mCPs were preferred over MP in 90% of cases. Globally, automated plans registered a plan quality score at least comparable to MP. Conclusions This study showed the flexibility of the Lexicographic approach in creating more demanding Wish Lists able to potentially minimize toxicities in RT plans.

Abstract Forests cover about one-third of Europe’s surface and their growth is essential for climate protection through carbon sequestration and many other economic, environmental, and sociocultural ecosystem services. However, reports on how climate change affects forest growth are contradictory, even for same regions. We used 415 unique long-term experiments including 642 plots across Europe covering seven tree species and surveys from 1878 to 2016, and showed that on average forest growth strongly accelerated since the earliest surveys. Based on a subset of 189 plots in Scots pine (the most widespread tree species in Europe) and high-resolution climate data, we identified clear large-regional differences; growth is strongly increasing in Northern Europe and decreasing in the Southwest. A less pronounced increase, which is probably not mainly driven by climate, prevails on large areas of Western, Central and Eastern Europe. The identified regional growth trends suggest adaptive management on regional level for achieving climate-smart forests.

Hereditary breast/ovarian cancer (HBOC) syndrome is caused by the inheritance of monoallelic germline BRCA1/2 gene mutations. If BRCA1/2 mutation carriers are identified before the disease develops, effective actions against HBOC can be taken, including intensive screening, risk-reducing mastectomy and salpingo-oophorectomy, and risk-reducing medications. The Italian National Prevention Plan mandates the creation of regional BRCA genetic testing programmes. So far, however, only informal data have been reported on their implementation. We have designed a study aimed at evaluating the results of a population-based programme for risk assessment and genetic counselling and testing for BRCA1/2-related HBOC that is underway in the Emilia-Romagna region (northern Italy). The programme—which is entirely free—includes basic screening with an estimate of the likelihood of carrying a BRCA1/2 mutation using a familial risk assessment tool, a closer examination of women with suspected risk increase, an assessment of the need for further genetic counselling and, if needed, genetic testing and risk-reducing interventions. In this paper, the design of the programme and the protocol of the study are presented. The study has an observational, historical cohort design. Eligible are the women found to be at an increased risk of HBOC (profile 3 women). The main objectives are (i) to determine the precision of the programme in measuring the level of risk of HBOC for profile 3 women; (ii) to determine the characteristics of profile 3 women and their association with the risk management strategy chosen; (iii) to compare the age at onset, histologic type, tumour stage, molecular subtype, and prognosis of breast/ovarian cancers observed in the cohort of profile 3 women with the features of sporadic cancers observed in the general female population; (iv) to determine the level and the determinants of adherence to recommendations; and (v) to determine the appropriateness and timing of risk-reducing surgery and medications. Investigating the quality and results of the programme is necessary because the best practices in risk assessment and genetic counselling and testing for BRCA1/2-related cancer and the challenges they encounter should be identified and shared. The study has the potential to provide sound empirical evidence for the factors affecting the effectiveness of this type of service.