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Graph generative models often lack a proper reconstruction loss to evaluate the distance between the generated graph and the target graph. This is particularly important for molecular graph generators based on autoencoders, which should reconstruct the input graphs as precisely as possible. Though, the distance estimation can be useful for any graph generator based on reconstruction, including sequential methods relying on Graph Neural Networks. Since graphs are discrete entities by nature, general graph spaces lack a reliable, general, and computationally affordable distance function. Graph Edit Distance is of course an exact, general, and permutation–invariant method for evaluating the difference between two graphs defined in the same graph space. Since it needs all the possible combinations of pairs of nodes from the two graphs, its exact computation is a NP-complete problem and cannot be carried out for graphs larger than ten nodes. As a consequence, a comprehensive soft–estimation method for Graph Edit Distance based on siamese Graph Neural Networks is proposed. A theoretical discussion is carried out, showing that the proposed method can provide a reliable and precise soft–estimation of the Graph Edit Distance on molecular graphs. Molecular graph generators can therefore use this distance estimation as a powerful non–permutation–invariant reconstruction loss. Moreover, the experimental results show that the distance estimation is accurate, with a very low Mean Squared Error loss value. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma is the second most common primary tumor of the liver. The incidence and mortality of its intrahepatic form has been increasing over the past 2 decades. Currently, the only available curative treatment for intrahepatic cholangiocarcinoma is surgical resection. There is still no prospective evidence to support neoadjuvant systemic treatments in resectable disease, while adjuvant chemotherapy with Capecitabine is currently the only recommended systemic treatment after liver resection based on the results of randomised trial. Despite the implementation of perioperative treatments and improvements in resective surgery, intrahepatic cholangiocarcinoma remains a disease characterized by high incidence of recurrence and poor long-term survival. Lymph node metastases can be found in 45–65% of patients and are one of the most impacting prognostic factors after surgical resection. Preoperative imaging is not always sufficient in assessing lymph node status, thus hepatic pedicle lymphadenectomy can be important to ensure precise staging in surgical patients. An increasing trend in performing lymph node dissection during liver resection for intrahepatic cholangiocarcinoma has been observed in the last 20 years, although its actual efficacy compared to the potential complications remains debated. The current evidence on the prognostic role of the lymph node status, its preoperative predictability, the basis for a correct hepatic pedicle lymphadenectomy and its prognostic role in the surgical treatment of intrahepatic cholangiocarcinoma are presented. [ABSTRACT FROM AUTHOR]

Rare diseases affect a growing number of individuals. One key problem for patients and their caregivers is the difficulty in reaching experts and associations competent on a particular disease. As a consequence, caregivers, often family members of the patient, learn much about the disease from their own experience. CaregiverMatcher is a proof of concept providing a smart solution to build a network of caregivers, linked by a matching mechanism based on graph neural networks. The caregivers and their experience with rare diseases are described by node features. Associations and care centers are invited to share their knowledge on the platform. [ABSTRACT FROM AUTHOR]

• Half of the banks of our sample suffered a profitability shock. • Only 30% of these banks managed to return to the previous profitability levels. • Profitability shocks are mainly caused by credit risk. • Recovering banks adopt a more conservative lending policy after the shock. This paper contributes to the existing literature on bank crisis and bank profitability by shedding light on "profitability shock" (i.e. a sudden and sizeable decline in profitability) and "profitability recovery" (i.e. returning to the previous level). Using a sample of 109 European bank holding companies over the years 2006-2016, we investigate the main drivers of these profitability shocks and the factors allowing banks to regain profitability and avoid a more severe crisis. Our findings show that (1) the profitability crisis has its roots in the lending activity and in the deterioration of the loan portfolio caused by a strong risk appetite that is not counterbalanced by adequate loan loss provisions and capitalization; (2) banks that recover after the profit shock adopt a more conservative lending policy, reduce their credit offer and tackle more effectively the NPL issue. [ABSTRACT FROM AUTHOR]

Highlights • Bank interconnectedness decreased due to the global financial crisis. • Regulatory initiatives aimed at containing systemic risk were also effective. • Within the global banking network, G-SIBs present different patterns of behaviors. Abstract This study shows that interconnections in the global banking network decreased due to the global financial crisis and subsequent regulatory initiatives. It also proves the effectiveness of the regulations of global systemically important banks in inducing these banks to contain their systemic nature. [ABSTRACT FROM AUTHOR]

• Although the insurance industry has a significant economic role, few studies investigate the determinants of individuals' insurance purchase decisions. • Along with age, marital status, education, employment status and having children, insurance literacy also influences insurance purchase decisions. • Insurance literacy has a positive relationship with both life and non-life insurance products purchase. • Individuals with higher basic and product insurance literacy show higher number of insurance products owned. Using a representative sample and a measure of insurance literacy developed and validated by an insurance supervisor, this study tests the impact of insurance literacy on the holding of insurance products in Italy. We show that insurance literacy influences insurance purchase decisions along with age, marital status, education, employment status, and having children. The greater the literacy, the higher the individual's participation in the insurance market. Given the lower level of insurance literacy compared to financial literacy, policymakers and institutions must provide more insurance education. [ABSTRACT FROM AUTHOR]

Background & Aims Outcomes of liver transplantation for hepatocellular carcinoma (HCC) are determined by cancer-related and non-related events. Treatments for hepatitis C virus infection have reduced non-cancer events among patients receiving liver transplants, so reducing HCC-related death might be an actionable end point. We performed a competing-risk analysis to evaluate factors associated with survival of patients with HCC and developed a prognostic model based on features of HCC patients before liver transplantation. Methods We performed multivariable competing-risk regression analysis to identify factors associated with HCC-specific death of patients who underwent liver transplantation. The training set comprised 1018 patients who underwent liver transplantation for HCC from January 2000 through December 2013 at 3 tertiary centers in Italy. The validation set comprised 341 consecutive patients who underwent liver transplantation for HCC during the same period at the Liver Cancer Institute in Shanghai, China. We collected pretransplantation data on etiology of liver disease, number and size of tumors, patient level of α-fetoprotein (AFP), model for end-stage liver disease score, tumor stage, numbers and types of treatment, response to treatments, tumor grade, microvascular invasion, dates, and causes of death. Death was defined as HCC-specific when related to HCC recurrence after transplantation, disseminated extra- and/or intrahepatic tumor relapse and worsened liver function in presence of tumor spread. The cumulative incidence of death was segregated for hepatitis C virus status. Results In the competing-risk regression, the sum of tumor number and size and of log 10 level of AFP were significantly associated with HCC-specific death ( P < .001), returning an average c-statistic of 0.780 (95% confidence interval, 0.763−0.798). Five-year cumulative incidence of non−HCC-related death was 8.6% in HCV-negative patients and 18.1% in HCV-positive patients. For patients with HCC to have a 70% chance of HCC-specific survival 5 years after transplantation, their level of AFP should be <200 ng/mL and the sum of number and size of tumors (in centimeters) should not exceed 7; if the level of AFP was 200−400 ng/mL, the sum of the number and size of tumors should be ≤5; if their level of AFP was 400−1000 ng/mL, the sum of the number and size of tumors should be ≤4. In the validation set, the model identified patients who survived 5 years after liver transplantation with 0.721 accuracy (95% confidence interval, 0.648%−0.793%). Our model, based on patients’ level of AFP and HCC number and size, outperformed the Milan; University of California, San Francisco; Shanghai-Fudan; Up-to-7 criteria ( P < .001); and AFP French model ( P = .044) to predict which patients will survive for 5 years after liver transplantation. Conclusions We developed a model based on level of AFP, tumor size, and tumor number, to determine risk of death from HCC-related factors after liver transplantation. This model might be used to select end points and refine selection criteria for liver transplantation for patients with HCC. To predict 5-year survival and risk of HCC-related death using an online calculator, please see www.hcc-olt-metroticket.org/ . ClinicalTrials.gov ID NCT02898415 . [ABSTRACT FROM AUTHOR]

Background: Death of patients presenting with bleeding events to the Emergency Department still represent a major problem. We sought to analyze clinical characteristics associated with worse outcomes including short- and long-term death, beyond antithombotic treatment strategy.Methods: Patients presenting with any bleeding events during 2016-2017years were enrolled. Clinical parameters, site of bleeding, major bleeding, ongoing anti-thrombotic treatment strategy and death were collected. Hard 5:1 propensity score matching was performed to adjust dead patients in baseline characteristics. Endpoints were one-month and one-year death.Results: Out of 166,000 visits to the Emergency Department, 3.050 patients (1.8%) were enrolled and eventually 429 were analyzed after propensity. Overall, anticoagulants or antiplatelets were given to 234(54%). Major bleeding account for 111(26%) patients, without differences between those taking anticoagulants or antiplatelets versus others. Death at one-month and one-year was 26(6%) and 72(17%), respectively. Independent predictors of one-month death were major bleeding (Odds Ratio, OR 26, p<0.001), female gender (OR 7, p<0.001) and white blood cells (OR 1.2, p=0.01); of one-year were major bleeding (OR 7, p<0.001), age (OR 1.1, p<0.001) and female gender (OR 2.3, p=0.043). Of note, death rate of gastrointestinal and intracranial bleeding where higher than others (p<0.001). Overall mortality was approximately 40% on one-month; 60% in older patients and 80% in female gender with CHA2D2VASC-score≥2. Receiver operator characteristics analysis showed larger areas for major bleeding and age (0.75 and 0.72, respectively) over others; p<0.05 on C-statistic.Conclusions: In patients with bleeding events, death rate was driven by major bleeding on short-term and older age on long-term. Among dead patients mortality was approximately 40% on one-month; 60% in older patients, and 80% in female gender. [ABSTRACT FROM AUTHOR]

Liver transplantation (LT) is the only curative treatment for patients with unresectable perihilar cholangiocarcinoma (pCC). Before listing, patients undergo neoadjuvant chemoradiation (CT-RT) according to the Mayo Clinic protocol (radiosensitizing chemotherapy + brachytherapy). In 2020, at our center we substituted brachytherapy with stereotactic beam radiotherapy (SBRT). To compare pretransplant toxicity and post-transplant outcomes of LT for pCC after brachytherapy versus SBRT. We performed a retrospective analysis of patients who underwent LT for pCC at our center between 2011 and 2023. Pre-LT adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Eight patients underwent LT: 4 after brachytherapy and 4 after SBRT (4, 50% women, median age 52 in brachytherapy and 62.5 in SBRT). CT-RT-related adverse events ≥ grade 3 occurred in all after brachytherapy and in one patient after SBRT (p=0.028). Median post-LT length of stay was 16.5 days (range, 9 - 25) for brachytherapy and 12 (range, 10-12) for SBRT. Post-LT 90-day complications occurred in 2 (50%) patients after brachytherapy (Clavien Dindo grade II and IVa) and one after SBRT (grade IIIa). In the brachytherapy group, one patient had microfoci of pCC on the bile duct margin; all LT in the SBRT group were R0. One brachytherapy patient and one SBRT patient had positive lymph nodes at histology. Overall survival at 1-, 3- and 5- years for the entire cohort was 100%, 80% and 40. No differences in survival were observed between the two groups. After a median follow-up of 146 months for brachytherapy and 12 months for SBRT, recurrences were 3 for brachytherapy and one for SBRT. Two deaths occurred in the brachytherapy group, none in the SBRT group. Preliminary data suggest that neoadjuvant SBRT is comparable to brachytherapy regarding post-LT outcomes, but with lower pre-LT toxicity. [ABSTRACT FROM AUTHOR]

In the last two decades, the number of oncological "exceptions" equated or even exceeded the number of non-oncological indications to liver transplantation (LT) in many countries. However, the prioritization of oncological patients within common waiting lists (WL) is still an unmet need. The aim of this study is to define and grade the factors that influence WL priority amongst all oncologic indications to liver transplant. A literature search was made to define which factors influence urgency, utility and transplant benefit principles in oncologic indications to LT. Those factors found to be shared by all oncological indications were then defined and qualitatively graded. For each grade, an evaluation of priority according to the three allocation principles was assessed, and priority for each grade (from 1 to 5) was given according to a blended principle. The following factors were identified: time on treatment before WL, response to therapy, availability of maintenance therapies while on WL, presence of alternative curative treatments, expected progression-free survival on WL, tumor burden with respect to transplant criteria, age and liver function. Each factor was graded according to a blended principle that takes into account urgency, utility and transplant benefit. A scale was then derived, summing a minimum of 15 and a maximum of 36 points, that allows for grading priority within oncologic indications to LT and with non-oncologic indications. We propose a prioritization scheme of oncologic indications to LT according to the principle of transplant benefit blended with those of urgency and utility. Its feasibility should be discussed within the transplant community and prospectively tested. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) patients treated with combinatorial immunotherapy (CIT) including anti-angiogenics and immune checkpoint inhibitors (atezolizumab and bevacizumab) can achieve tumor downstaging and become eligible to liver transplantation (LT). While CIT may increase the risk of graft rejection, LT-associated immunosuppression may exert detrimental effects on anti-tumor immunity. Patients with intermediate-advanced HCC downstaged to accepted LT criteria, underwent circulating anti-tumor cell immunomonitoring. Here we show the behaviour of memory and effector T cell subsets during treatment, during the washout phase, at early and late post-LT follow-up, with the aim of uncovering immune responses that regulate tumor immunosurveillance. Four HCC patients undergoing LT after CIT downstaging (median 120 days on treatment) followed by a 2 month (median 70.5 days) wash-out phase underwent peripheral blood sampling at different time points (end of treatment, during the wash-out phase and up to 5 months after LT). High resolution flow cytometry was performed on whole blood to quantify cells expressing lymphoid markers, with particular regards to CD8+ memory and effector T cell subsets. Flow cytometry data show that CIT induced a boost of naïve, effector memory (TEM) and terminally differentiated effector memory (TEMRA) T cells that decreases rapidly within the first 30 days of the wash-out phase with a further reduction at early post-LT time points (3-7 days) because of the enhanced immunosuppressive regimen. Nevertheless, within the first month and even more at a five-month post-LT follow-up, most of the effector and memory T cell subsets encompassing anti-tumor responses, regain levels even higher than on-treatment values. The post-liver transplant regaining of anti-tumor immune cell levels, despite immunosuppression, at levels higher than on-CIT treatment, justifies further investigation in the field and suggests a possible role of organ transplantation as an endogenous adjuvant to aid in adaptive immune responses. [ABSTRACT FROM AUTHOR]

Background Functional well-differentiated neuroendocrine tumours (NET) with liver metastases represent a therapeutic challenge with few alternative options in guidelines. In these patients, the role of surgical resection of the primary tumour is controversial. Patients and methods From a regional registry collecting somatostatin analogue (SSA)-treated tumours from 1979 to 2005, a series of 139 patients presenting with symptomatic, liver-metastatic, well-differentiated NET (G1–G2, mitoses: ≤20, Ki-67: ≤20%) was prospectively collected and retrospectively analysed. Surgery on either the primary tumour or liver metastases was chosen: 1) when low perioperative risk was predictable; 2) in presence of an impending risk of obstruction, bleeding, or perforation; or 3) if liver metastases were suitable of curative or subtotal (>90%) tumour removal. Impact of the most relevant clinico-pathological parameters on survival was studied. Results Median follow-up was 127 months and median survival was 94 months, with 138 vs. 37 months in resected vs. non-resected primary NET (p < 0.001), respectively. In the univariate analysis, prolonged survival was significantly associated with primary tumour resection (p < 0.001), resection of liver metastases (p = 0.002), site of primary (carcinoid vs. pancreatic, p = 0.018), basal chromogranin-A (CgA) <200 ng/mL (p = 0.001), and absence of diarrhea (p = 0.012). Multivariate analysis showed that primary tumour resection was an independent positive prognostic factor (HR = 3.17; 95% CI: 1.77–5.69, p < 0.001), whereas diarrhea, basal CgA ≥200 ng/mL, and high tumour load were independent negative prognostic factors. Also, in 103 patients with non-resectable liver metastases, primary tumour resection was significantly associated with prolonged survival (median 137 vs. 32 months, p < 0.0001). Conclusions Primary tumour resection may improve survival in functional well-differentiated NET with liver metastases. [ABSTRACT FROM AUTHOR]

Security token offerings (STOs), based on blockchain technology, are attracting increasing attention as an innovative alternative means of venture financing. Information about specific STOs is generally provided in white papers. This study analyses the content of white papers using a unique sample of 188 STOs from 2017 to 2021 to identify which topic is related to campaign success. We leverage latent Dirichlet allocation (LDA) topic modelling to identify the topics and themes in white papers. Nine topics are identified through LDA: company description, distributed ledger technology components, energy and green issues, financial and legal issues, artificial intelligence, and tech applications in different industries—specifically, healthcare, manufacturing and construction, education, and financial services. We find that energy and green issues represent one of the most prominent topics among all types of projects and that their disclosure is positively related to the probability of campaign success and the amount of funding raised. Another prominent topic that affects campaign outcomes is technology in the healthcare industry, reflecting wider investment trends in this sector. Our results may help entrepreneurs to improve their campaign disclosures and present new issues for policymakers regarding investments in digital tokens. • An integrated framework of STOs success is proposed by combining topic modelling with other campaigns' indicators. • Company's energy consumption and green impact is one of the most dealt topics among all types of projects. • The technological components in the healthcare field is a topic related to the campaign success • Energy consumption and green issues must be adequately disclosed to affect campaign success. [ABSTRACT FROM AUTHOR]

Abstract: Background: Standard imaging methods in evaluating chest wall deformities, such as Pectus Excavatum (PE) in paediatric and adolescent patients, include baseline 2-view chest radiography and chest CT scan. Only few studies to date investigated the value of fast MRIin the pre operative assessment of patient affected by PE. Objective: To evaluate the efficacy of chest fast MRI in pre-operative management of patient affected by PE. To obtain the Haller Index (HI) and Asymmetry Index (AI) from chest fast MRI protecting patients from radiation exposure. Materials and Methods: We analyzed the data of 42 consecutive patients with severe PE who underwent minimally invasive repair between March 2007 and March 2010. All 42 patients received chest fast MRI, but only the first 5 in view of the results, were studied also with chest ultrafast CT scan. In both examinations, data at the deepest point of the depression were collected. Results: Severity indices of the deformity using HI and AI, collected from CT scan and fast MRI in the first 5 patients, were comparable. In the remaining 37 fast chest MRI offered good images of the chest wall deformities with no radiation exposure, detailing anatomical information such as displacement and rotation of the heart or great vessels anomalies. Conclusion: This study suggests the use of chest MRI in pre operative workup for patients with PE to obtain severity indices (Haller Index and Asymmetry Index avoiding radiation exposure to paediatric patients. [Copyright &y& Elsevier]