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Giacomo Pascarella,1 Matteo Rossi,2 Emma Montella,3 Arturo Capasso,2 Gianfranco De Feo,1 Gerardo Botti Snr,1 Antonio Nardone,3 Paolo Montuori,3 Maria Triassi,3 Stefania D’Auria,4 Alessandro Morabito5 1Scientific Directorate, Istituto Nazionale Tumori “Fondazione G. Pascale”, IRCCS, Napoli, Italy; 2Wroclaw School of Banking Wyższa Szkoła Bankowa, Wrocalw, Poland; 3Department of Public Health, Università Federico II, Napoli, Italy; 4Department of Health Management, Istituto Nazionale Tumori, “Fondazione G. Pascale”, IRCCS, Napoli, Italy; 5Thoracic Department, Istituto Nazionale Tumori “Fondazione G. Pascale” IRCCS, Napoli, ItalyCorrespondence: Giacomo PascarellaScientific Directorate, Istituto Nazionale Tumori “Fondazione G. Pascale”, IRCCS, Via Mariano Semmola, 52, Napoli, 80131, ItalyEmail g.pascarella@istitutotumori.na.itPurpose: A risk assessment matrix is a widely used tool for analyzing, assessing and setting priorities in risk management in many fields. This paper overviews critical variables, advantages, disadvantages, strengths and weaknesses of this tool, according to the ISO 31000 risk management framework.Results: Risk assessment is one of the key stages in the Risk Management Process and involves specific steps: identifying hazards, analyzing and evaluating all possible risks. Several methods are developed to assess risks in the literature. A risk matrix method, also called “decision matrix risk assessment (DMRA) technique”, is a systematic approach used to determine the risk level and to compare different risks and define which threats need to be controlled first. The actors involved in risk assessment are called on to manage different issues related to the choice of the most appropriate methodological approach, the assessment of the adequacy of the existing control measures, the articulation of risk consequence domains, the definition of the impact-consequences, the explanation of risk likelihood scales and the development of a risk matrix.Conclusion: We highlighted a number of recommendations in order to address these issues, especially useful when healthcare organizations provide insufficient guidance on how to use risk matrices as well as what to do in response to the existing criticisms on their use.Keywords: healthcare risk analysis, risk matrix, consequences-likelihood analysis

Abstract Background X-linked acrogigantism (X-LAG; MIM: 300942) is a severe form of pituitary gigantism caused by chromosome Xq26.3 duplications involving GPR101. X-LAG-associated duplications disrupt the integrity of the topologically associating domain (TAD) containing GPR101 and lead to the formation of a neo-TAD that drives pituitary GPR101 misexpression and gigantism. As X-LAG is fully penetrant and heritable, duplications involving GPR101 identified on prenatal screening studies, like amniocentesis, can pose an interpretation challenge for medical geneticists and raise important concerns for patients and families. Therefore, providing robust information on the functional genomic impact of such duplications has important research and clinical value with respect to gene regulation and triplosensitivity traits. Methods We employed 4C/HiC-seq as a clinical tool to determine the functional impact of incidentally discovered GPR101 duplications on TAD integrity in three families. After defining duplications and breakpoints around GPR101 by clinical-grade and high-density aCGH, we constructed 4C/HiC chromatin contact maps for our study population and compared them with normal and active (X-LAG) controls. Results We showed that duplications involving GPR101 that preserved the centromeric invariant TAD boundary did not generate a pathogenic neo-TAD and that ectopic enhancers were not adopted. This allowed us to discount presumptive/suspected X-LAG diagnoses and GPR101 misexpression, obviating the need for intensive clinical follow-up. Conclusions This study highlights the importance of TAD boundaries and chromatin interactions in determining the functional impact of copy number variants and provides proof-of-concept for using 4C/HiC-seq as a clinical tool to acquire crucial information for genetic counseling and to support clinical decision-making in cases of suspected TADopathies.

Treatment of rectal cancer has improved over the years thanks to a multidisciplinary approach. A correct staging has a fundamental role for risk stratification and to define the best treatment for each patient. Unfortunately, approximately 30% of patients with locally advanced rectal cancers will experience tumor recurrence. Thus, the identification of novel clinical-pathological and radiological prognostic factors represents an urgent unmet clinical need. Here we report the case of a patient with radically resected localized rectal cancer who developed an impressive early pelvic recurrence. To better understand the clinical scenario, we have studied the possible factors related to the aggressiveness of the disease. The only poor prognosticfactor that was evidenced at histological report was perineural invasion. Therefore, we questioned whether we could evaluate perineural invasion with imaging, similar to head and neck tumors. Learning from this clinical case, we believe that improving the risk stratification and radiology reporting is necessary to provide the best care for the patient and allow for a better prognosis prediction. Of course, our data should be considered as hypothesis generating and should be further investigated and validated in larger and prospective studies.

Maria Triassi,1 Elena Giancotti,2 Antonio Nardone,1 Giulia Mancini,3 Fabiana Rubba1 1Public, Preventive and Social Medicine School, University Federico II of Naples, Naples, Italy; 2Procurement and Transplantation Coordination, Naples, Italy; 3Sociology Unit, G D'annunzio University, Chieti-Pescara, Italy Introduction: The growing disparity between organ availability for transplantation and the number of patients in need has challenged the donation and transplantation community to develop innovative processes, ideas, and techniques to bridge this gap. Advances in the sharing of best practices in the donation community have contributed greatly to this aim over the past 5 years. Studies published during the past five years (2010–2014) were analyzed to gain insight on the evolving organizational areas and tools that the procurement and transplantation pathways have been focused on. The hypothesis assessed is that networking and efficacious handling of this complex path may be ameliorated by an adaptive organizational toolbox. Methods: A thorough search has been conducted using various databases, ie, Cochrane library, PubMed, EMBASE, Federico II University Open Archive. The evidence was considered following the Effective Practice and Organization of Care Group checklist. Prevalent organizational attitudes and areas were assessed, and various scenarios were analyzed. Initially, all titles and abstracts were screened. In the next phase, the full text of all abstracts considered potentially relevant by at least one of the reviewers was evaluated. Inconsistencies in decision-making within this second phase were solved based on consensus between both reviewers. In this phase, for every study we defined whether the organization was considered relevant and what the scenario was. The information was extracted from each study based on bibliographic details (author, journal, year of publication, and language). As many as 1,071 studies were analyzed, and 81 were selected as potentially relevant. Results: We found three prevalent areas of interest focused on organizational elements: global organizational strategies scenario, clinical hospital organization, and citizenship and social scenario. Conclusion: We reached the conclusion that organization has a central role in different scenarios of procurement and transplantation in a continuum from government to hospital (the core of the system) and finally among citizens. A standardized hospital pathway definitely remains the essential step in order to ameliorate either procurement or transplantation. Keywords: transplant procurement, management, organizational tool, network

We present a case of a 70-year-old male who presented with left-sided weakness and dysarthria. Cranial imaging was suggestive of a cerebellar infarct and the patient was treated with aspirin and clopidogrel. Two months later a fall prompted further cranial imaging, which was concerning for an intracranial mass with vasogenic edema. Computed tomography angiogram (CTA) was negative for vascular lesion. Ultimately, a DSA revealed a Borden III dAVF between the right occipital artery and the posterior cerebellar vein that was treated with endovascular embolization.

The integration of multidisciplinary tumor boards (MTBs) is fundamental in delivering state-of-the-art cancer treatment, facilitating collaborative diagnosis and management by a diverse team of specialists. Despite the clear benefits in personalized patient care and improved outcomes, the increasing burden on MTBs due to rising cancer incidence and financial constraints necessitates innovative solutions. The advent of artificial intelligence (AI) in the medical field offers a promising avenue to support clinical decision-making. This review explores the perspectives of clinicians dedicated to the care of cancer patients—surgeons, medical oncologists, and radiation oncologists—on the application of AI within MTBs. Additionally, it examines the role of AI across various clinical specialties involved in cancer diagnosis and treatment. By analyzing both the potential and the challenges, this study underscores how AI can enhance multidisciplinary discussions and optimize treatment plans. The findings highlight the transformative role that AI may play in refining oncology care and sustaining the efficacy of MTBs amidst growing clinical demands.

Abstract In the Summer 2021 a seismic passive survey was carried out at Mefite d’Ansanto (Italy), well-known for the cold non-volcanic and lethal CO2 emissions. Mefite is located close to that part of Irpinia region hosting the large historical earthquakes’ faults, that generated the destructive magnitude 6.8 earthquake of 1980 and have been related to the CO2 leakage by the scientific community. The survey was conducted by installing a small short-period seismic array with the purpose of determining the wavefield features and detecting the possible signature of the regional stress variations. By analyzing the acquired data, we have determined the properties of the seismic wavefield associated with the emission vents, in the intermediate frequency band, 1–15 Hz, which was found to be composed of a stationary background component and an intermittent higher energy one. Basing on our results, considerations on the medium properties and the deep source available information, we have depicted a schematic model of the shallow seismic source: the background components are linked to the shallower activity of the hydrothermal system, e.g. the bubbling, while the intermittent ones are likely generated by the passage of the overpressured gas, trapped in the first-tens-meters’ layers, after overcoming the internal cohesion charge. The characteristics of the wavefield that we have defined, refer to a condition in which no regional earthquakes occurred and could be considered as a basis to identify possible significant variations linked to CO2 emissions and to the regional stress changes.

Abstract Adhesive Capsulitis of the shoulder is a painful pathology limiting shoulder movements, commonly known as “Frozen Shoulder”. Since this pathology limits movement, it is important to make an early diagnosis. Diagnosing capsulitis relies on clinical assessment, although diagnostic imaging, such as Magnetic Resonance Imaging, can provide predictive or supportive information for specific characteristic signs. However, its diagnosis is not so simple nor so immediate, indeed it remains a difficult topic for many general radiologists and expert musculoskeletal radiologists. This study aims to investigate whether it is possible to use disease signs within a medical image to automatically diagnose Adhesive Capsulitis. To this purpose, we propose an automatic Model Checking-based approach to quickly diagnose the Adhesive Capsulitis taking as input the radiomic feature values from the medical images. Furthermore, we compare the performance achieved by our method with diagnostic results obtained by professional radiologists with different levels of experience. To the best of our knowledge, this is the first method for the automatic diagnosis of Adhesive Capsulitis of the Shoulder.

Abstract The ESR1 ligand binding domain activating mutations are the most prevalent genetic mechanism of acquired endocrine resistance in metastatic hormone receptor-positive breast cancer. These mutations confer endocrine resistance that remains estrogen receptor (ER) dependent. We hypothesized that in the presence of the ER mutations, continued ER blockade with endocrine therapies that target mutant ER is essential for tumor suppression even with chemotherapy treatment. Here, we conducted comprehensive pre-clinical in vitro and in vivo experiments testing the efficacy of adding fulvestrant to fluorouracil (5FU) and the 5FU pro-drug, capecitabine, in models of wild-type (WT) and mutant ER. Our findings revealed that while this combination had an additive effect in the presence of WT-ER, in the presence of the Y537S ER mutation there was synergy. Notably, these effects were not seen with the combination of 5FU and selective estrogen receptor modulators, such as tamoxifen, or in the absence of intact P53. Likewise, in a patient-derived xenograft (PDX) harboring a Y537S ER mutation the addition of fulvestrant to capecitabine potentiated tumor suppression. Moreover, multiplex immunofluorescence revealed that this effect was due to decreased cell proliferation in all cells expressing ER and was not dependent on the degree of ER expression. Taken together, these results support the clinical investigation of the combination of ER antagonists with capecitabine in patients with metastatic hormone receptor-positive breast cancer who have experienced progression on endocrine therapy and targeted therapies, particularly in the presence of an ESR1 activating mutation.

IntroductionThis study examined user behavior, e-cigarette dependence, and device characteristics on nicotine intake among users of pod-mod e-cigarettes.Aims and methodsIn 2019-2020, people who use pod-mods in the San Francisco Bay Area completed questionnaires and provided a urine sample for analysis of total nicotine equivalents (TNE). The relationship between TNE and e-cigarette use, e-cigarette brands, e-liquid nicotine strength, e-cigarette dependence, and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), as a measure of combustible cigarette exposure, were examined.ResultsOf 100 participants (64% male, 71% in the 18-34 age group, 45% white), 53 used JUUL primarily, 12 used Puff Bar primarily, and 35 used other brands, including Suorin; 48 participants reported current cigarette smoking. Participants most often reported use of e-liquid with 4.5%-6.0% nicotine (68%), fruit (35%), tobacco (28%), and menthol or mint flavors (26%), used e-cigarettes on 25.5 (SD = 6.3) days a month, 10.2 (SD = 14.2) times a day, and 40% used 1-2 pods/cartridges per week. In bivariate analysis, urinary TNE was higher with greater frequency (days used) and intensity (number of pods used) of e-cigarette use, e-cigarette dependence, and combustible cigarette use. In multivariable analysis, days of e-cigarette use in the last 30 days, number of pods used per week, and NNAL levels were significantly associated with TNE. There was no significant impact of e-liquid nicotine strength on TNE.ConclusionsNicotine intake among people who used pod-mod e-cigarettes increased with e-cigarette consumption and e-cigarette dependence, but not with e-liquid nicotine strength. Our findings may inform whether FDA adopts a nicotine standard for e-cigarettes.ImplicationsThe study examined how device and user characteristics influence nicotine intake among pod-mod e-cigarette users. Nicotine intake increased with frequency (days of e-cigarette use in past 30 days) intensity of use (number of pods used per day) and e-cigarette dependence but not with the flavor or nicotine concentration of the e-liquids. Regulation of nicotine concentration of e-liquids is unlikely to influence nicotine exposure among adult experienced pod-mod users.

Key Clinical Message Patients with intrathecal catheters for pain medication infusion should be aware of the possible complication of acute flaccid paralysis. While exceedingly rare, it should prompt immediate medical attention to rule out compressive pathology requiring intervention.

The gap between endoscopy and histology is getting closer with the introduction of sophisticated endoscopic technologies. Furthermore, unprecedented advances in artificial intelligence (AI) have enabled objective assessment of endoscopy and digital pathology, providing accurate, consistent, and reproducible evaluations of endoscopic appearance and histologic activity. These advancements result in improved disease management by predicting treatment response and long-term outcomes. AI will also support endoscopy in raising the standard of clinical trial study design by facilitating patient recruitment and improving the validity of endoscopic readings and endoscopy quality, thus overcoming the subjective variability in scoring. Accordingly, AI will be an ideal adjunct tool for enhancing, complementing, and improving our understanding of ulcerative colitis course. This review explores promising AI applications enabled by endoscopy and histology techniques. We further discuss future directions, envisioning a bright future where AI technology extends the frontiers beyond human limits and boundaries.

Abstract In this study, the origins of efficiency gains in Cu(In,Ga)Se2 (CIGS) solar cells are investigated by introducing an Al2O3 passivation layer in terms of the oxidation condition of Mo back contact, alkali‐metal diffusion, minority carrier lifetimes (τ), and charge conditions. The study reveals that introduction of an Al2O3 back‐contact passivation layer into solar cells yields multiple impacts. Al2O3 deposition enhances the oxidation of the Mo back contacts, increasing Na solubility in Mo and Na diffusion from Mo into the CIGS layer, thereby modifying the metastable properties of CIGS. The charge condition at the CIGS/Al2O3 interface is not fixed negative charge but variable, dependent on whether electrons or holes are supplied. During solar cell operation, the interfacial charge condition is expected to be neutral or positive for Al2O3 grown using plasma or thermal atomic layer deposition techniques, respectively. Moreover, the mechanical peeling off of CIGS from Mo back contact enhanced τ in a similar way as with the insertion of Al2O3. Based on this study, the enhancement of alkali metal supply and the removal of direct contact of CIGS to the metal contact (Mo) can play crucial roles in improving the performance of CIGS solar cell.

The interest in Self-Sovereign Identity (SSI) in research, industry, and governments is rapidly increasing. SSI is a paradigm where users hold their identity and credentials issued by authorized entities. SSI is revolutionizing the concept of digital identity and enabling the definition of a trust framework wherein a service provider (verifier) validates the claims presented by a user (holder) for accessing services. However, current SSI solutions primarily focus on the presentation and verification of claims, overlooking a dual aspect: ensuring that the verifier is authorized to access the holder's claims. Addressing this gap, this paper introduces an innovative SSI-based solution that integrates decentralized wallets with Ciphertext-Policy Attribute-Based Proxy Re-Encryption (CP-ABPRE). This combination effectively addresses the challenge of verifier authorization. Our solution, implemented on the Ethereum platform, enhances accountability by notarizing key operations through a smart contract. This paper also offers a prototype demonstrating the practicality of the proposed approach. Furthermore, it provides an extensive evaluation of the solution's performance, emphasizing its feasibility and efficiency in real-world applications.

Background Ventricular repolarization time (ECG QT and JT intervals) is associated with malignant arrhythmia. Genome‐wide association studies have identified 230 independent loci for QT and JT; however, 50% of their heritability remains unexplained. Previous work supports a causal effect of lower serum calcium concentrations on longer ventricular repolarization time. We hypothesized calcium interactions with QT and JT variant associations could explain a proportion of the missing heritability. Methods and Results We performed genome‐wide calcium interaction analyses for QT and JT intervals. Participants were stratified by their calcium level relative to the study distribution (top or bottom 20%). We performed a 2‐stage analysis (genome‐wide discovery [N=62 532] and replication [N=59 861] of lead variants) and a single‐stage genome‐wide meta‐analysis (N=122 393, [European ancestry N=117 581, African ancestry N=4812]). We also calculated 2‐degrees of freedom joint main and interaction and 1‐degree of freedom interaction P values. In 2‐stage and single‐stage analyses, 50 and 98 independent loci, respectively, were associated with either QT or JT intervals (2‐degrees of freedom joint main and interaction P value

Background and Aims: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. Methods: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. Results: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. Conclusions: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.