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Several interdisciplinary studies have investigated the impact of Connected and Autonomous Vehicles (CAVs) on the performance of traffic networks, which expect positive effects. Nevertheless, there will be a transitional period during which both Human-Driven Vehicles (HDVs) and CAVs shall operate simultaneously. Adequate modeling of the interactions between CAVs and HDVs is vital to understand the mixed traffic dynamics. We propose a second-order macroscopic model by reconstructing the backward propagation speed of perturbation based on the dynamic headway distance between vehicles in mixed traffic. The proposed model is validated using microscopic simulations, and it replicates the given traffic scenarios subjected to assorted Penetration Rate (PR) of CAVs. The proposed model is employed to investigate the dynamics of mixed traffic. The results demonstrate that the average traffic velocity and the Level of Service (LOS) significantly improve with the increase in the PR of CAVs. Additionally, the performance of the proposed model is compared with the well-known Jiang-Qing-Zhu (JQZ) model, and it outperforms the JQZ model. The proposed model can be employed in traffic forecasting and real-time traffic control.

Summary: The transcription factor EB (TFEB) has emerged as a master regulator of lysosomal biogenesis, exocytosis, and autophagy, promoting the clearance of substrates stored in cells. c-Abl is a tyrosine kinase that participates in cellular signaling in physiological and pathophysiological conditions. In this study, we explored the connection between c-Abl and TFEB. Here, we show that under pharmacological and genetic c-Abl inhibition, TFEB translocates into the nucleus promoting the expression of its target genes independently of its well-known regulator, mammalian target of rapamycin complex 1. Active c-Abl induces TFEB phosphorylation on tyrosine and the inhibition of this kinase promotes lysosomal biogenesis, autophagy, and exocytosis. c-Abl inhibition in Niemann-Pick type C (NPC) models, a neurodegenerative disease characterized by cholesterol accumulation in lysosomes, promotes a cholesterol-lowering effect in a TFEB-dependent manner. Thus, c-Abl is a TFEB regulator that mediates its tyrosine phosphorylation, and the inhibition of c-Abl activates TFEB promoting cholesterol clearance in NPC models.

Purpose: To evaluate the potential of synthetic radiomic data generation in addressing data scarcity in radiomics/radiogenomics models., Methods: This study was conducted on a retrospectively collected cohort of 386 colorectal cancer patients (n = 2570 lesions) for whom matched contrast-enhanced CT images and gene TP53 mutational status were available. The full cohort data was divided into a training cohort (n = 2055 lesions) and an independent and fixed test set (n = 515 lesions). Differently sized training sets were subsampled from the training cohort to measure the impact of sample size on model performance and assess the added value of synthetic radiomic augmentation at different sizes. Five different tabular synthetic data generation models were used to generate synthetic radiomic data based on "real-world" radiomics data extracted from this cohort. The quality and reproducibility of the generated synthetic radiomic data were assessed. Synthetic radiomics were then combined with "real-world" radiomic training data to evaluate their impact on the predictive model's performance., Results: A prediction model was generated using only "real-world" radiomic data, revealing the impact of data scarcity in this particular data set through a lack of predictive performance at low training sample numbers (n = 200, 400, 1000 lesions with average AUC = 0.52, 0.53, and 0.56 respectively, compared to 0.64 when using 2055 training lesions). Synthetic tabular data generation models created reproducible synthetic radiomic data with properties highly similar to "real-world" data (for n = 1000 lesions, average Chi-square = 0.932, average basic statistical correlation = 0.844). The integration of synthetic radiomic data consistently enhanced the performance of predictive models trained with small sample size sets (AUC enhanced by 9.6%, 11.3%, and 16.7% for models trained on n_samples = 200, 400, and 1000 lesions, respectively). In contrast, synthetic data generated from randomised/noisy radiomic data failed to enhance predictive performance underlining the requirement of true signal data to do so., Conclusion: Synthetic radiomic data, when combined with real radiomics, could enhance the performance of predictive models. Tabular synthetic data generation might help to overcome limitations in medical AI stemming from data scarcity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Inflammatory Bowel Diseases (IBD), Crohn's Disease (CD), and Ulcerative Colitis (UC) may have extraintestinal manifestations, including disorders of the urinary tract. The prevalence of lower urinary tract symptoms (LUTS) in IBD patients remains unclear., Aims: Assess the prevalence of LUTS in patients with CD or UC, evaluate the variables implicated in any difference in LUTS prevalence between CD or UC, and assess any relationship between disease activity and LUTS METHODS: LUTS were evaluated in 301 IBD patients through standardised questionnaires: Bristol Female Lower Urinary Tract Symptoms (BFLUTS), NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), and International Prostate Symptom Score (IPSS). IBD activity was determined through the Crohn's Disease Activity Index (CDAI), Partial Mayo Score (PMS), and Total Mayo Score (TMS)., Results: BFLUTS total score for females was 6 (3-11). Patients with a higher age at diagnosis had worse filling symptoms (p = 0.049) and a worse quality of life (p = 0.005). In males, 67.1% had mild, 28.5% moderate, and 4.4% severe IPSS symptom grades. The overall NIHCPSI prevalence of chronic prostatitis-like symptoms was 26.8%. The questionnaires revealed some significant differences in the subgroups analysed., Conclusion: LUTS should be evaluated in IBD patients by urologic-validated questionnaires for prompt diagnosis and early treatment., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest to disclose., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aims: We assessed the cumulative incidence of recurrent stroke, major bleeding and all-cause mortality associated with restarting antithrombotic treatment, in patients experiencing an anticoagulation-related event (stroke or major bleeding), occurred during anticoagulation therapy for AF., Methods and Results: We performed a retrospective population-based analysis on linked claims data of patients resident in the Veneto Region, treated with DOACs for AF and discharged (2013-2020) from the hospital for stroke, intracranial haemorrhage (ICH), and major bleeding. To adjust for competing risk of death and reduce confounding, we started the follow up after a 120-days blanking period, counting events in patients resuming oral anticoagulation versus those that did not. Risks of all-cause mortality, ischemic stroke (IS)intracranial haemorrhage (ICH), and other major bleeding events (MB) were estimated with multivariable Cox proportional hazard models and propensity score to adjust for differences in baseline characteristics. Overall, 1029 patients (mean age 77 years) were included in the final cohort: 23% experienced an IS, 18% an ICH, and 59% MB. Of these, 77% resumed anticoagulation. The cumulative incidence of events was significantly lower in patients resuming therapy. In the multivariable analysis considering age, sex and propensity score as covariates, resumption of anticoagulation significantly reduced the risk of a cumulative event (HR 0.45, 95%CI 0.35-0.57, p < 0.01). Stratifying for the index event, among patients with IS (92% resumed therapy), we observed a risk reduction of 81%; in patients with ICH (64% resumed therapy), we observed a risk reduction of 64% and for patients with MB (76% resuming therapy), we observed a risk reduction of 49%., Conclusions: In patients with AF who experienced an anticoagulation-related event, resuming oral anticoagulation was associated with better outcomes for all-cause mortality and subsequent events as compared with patients who did not resume treatment., Competing Interests: Conflict of interest None to declare. Authorship: VP and GD made substantial contributions to the conception and design of the study. NG, EF and MZ contributed to acquisition and interpretation of data; VP and GD made the first draft and NG, EF and MZ revised it critically; all authors gave final approval of the version to be published; authors agreed to be accountable for all aspects of the work., (Copyright © 2023. Published by Elsevier B.V.)

Background: Desmoid-Type Fibromatosis (DTF) is a rare mesenchymal neoplasm with a locally invasive pattern and high risk of local recurrence after surgery. Historically, the standard treatment for DTF was surgical resection. However, considering the difficulty of achieving surgical eradication, the possible unnecessary morbidity and the unpredictability of the natural history, a wait-and-see approach has been proposed for asymptomatic DTF., Methods: We analyzed 87 consecutive patients with histologically-proven sporadic primary DTF, first recurrence or residual disease managed at our institution between 2000 and 2018. Patients and tumor-related variables were reviewed and analyzed. Two different treatment strategies were adopted according to different time periods: in the "early period" (2000-2010) patients underwent surgical treatment irrespective of the clinical presentation, whereas in the "late period" (2012-2018) asymptomatic patients used to undergo a wait-and-see strategy. The event-free survival (EFS) was compared trough a pre-post comparison., Results: In the early period, surgery was performed in 51 (94.4%) patients and watchful waiting in 3 (5.6%). In the late period, the watchful waiting group accounted for 24 (72.7%) patients and the surgical group for 9 (27.3%). No statistically independent prognostic factors were found. EFS did not show statistically significant differences between early and late period groups., Conclusion: Wait-and-see policy has shown to be equivalent to upfront surgery in terms of EFS; therefore, a conservative approach is recommended in asymptomatic patients diagnosed with DTF that can be followed through watchful waiting., Competing Interests: Declaration of competing interest All the Authors declare they have no conflict of interest and there were no funding sources regarding this paper., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) global pandemic has strikingly high mortality rate with hypercoagulability state being part of the imputed mechanisms. We aimed to compare the rates of in hospital mortality in propensity score matched cohorts of COVID-19 patients in chronic anticoagulation versus those that were not., Methods: In this population-based study in the Veneto Region, we retrospectively reviewed all patients aged 65 years or older, with a laboratory-confirmed COVID-19 diagnosis. We compared, after propensity score matching, those who received chronic anticoagulation for atrial fibrillation with those who did not., Results: Overall, 4697 COVID-19 patients fulfilled inclusion criteria, and the propensity score matching yielded 559 patients per arm. All-cause mortality rate ratio was significantly higher among non-anticoagulated patients (32.2% vs 26.5%, p = 0.036). On time to event analysis, all-cause mortality was found lower among anticoagulated patients, although the estimate was not statistically significant. (HR 0.81, 95%CI 0.65-1.01, p = 0.054)., Conclusion: Among elderly patients with COVID-19, those on chronic oral anticoagulant treatment for atrial fibrillation seem to be at lower risk of all-cause mortality compared to their propensity score matched non-anticoagulated counterpart. This finding needs to be confirmed in further studies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Anticoagulation therapy is central for the management of stroke in patients with non-valvular atrial fibrillation (NVAF). Persistence with oral anticoagulation is essential to prevent thromboembolic complications., Methods: We performed a population-based retrospective cohort study in the Veneto Region (north-eastern Italy, about 5 million inhabitants) using the regional health system databases. Naïve patients initiating direct oral anticoagulants (DOACs) for stroke prevention in NVAF from July 2013 to September 2017 were included in the study. Patients were identified using Anatomical Therapeutic Chemical (ATC) codes, excluding other indications for anticoagulation therapy using ICD-9CM codes. Treatment persistence was defined as the time from initiation to discontinuation of the therapy, including any therapeutic switching among DOACs. Baseline characteristics and comorbidities associated to the persistence of therapy with DOACs were explored by means of Kaplan-Meier curves and assessed through Cox regression., Results: Naïve patients initiating direct oral anticoagulants for stroke prevention in NVAF identified in a 4.25-year period are 17,920. After one year, the persistence to the DOACs is 72.9%. Approximately 9.8% of the discontinuations are due to switch to vitamin k antagonists (VKAs). On multivariate analysis, factors negatively affecting persistence were female gender, age <65 years, renal disease and history of bleeding. On the other hand, persistence was better in patients with hypertension, previous cerebral ischemic events, and previous acute myocardial infarction., Conclusion: In this study of real world data, one out four naive patients stopped treatment with DOACs within 12 months. Some characteristics may identify patients with poor persistence., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Failure to rescue (FTR) patients from postoperative complications could contribute to the variability in surgical mortality seen among hospitals with different volumes. We sought to examine the impact of complications and FTR on mortality following rectal surgery., Methods: The National Italian Hospital Discharge Dataset allowed to identify 75,280 patients who underwent rectal surgery between 2002 and 2014. Hospital volume was stratified into tertiles. Rates of major complications, FTR from complications and mortality following rectal surgery were compared., Results: During the study period, both the incidence of complications (2002, 23.7% versus 2014, 21.2%), and FTR decreased overtime (2002, 6.9% versus 2014, 3.8%) (both P < 0.001). The complication rate was 24.4% in low-, 21.6% in intermediate- and 20.4% in high-volume hospitals (P < 0.001). Complications were less common in minimally invasive surgery (MIS) versus open cases (18.2% versus 23.2%; P < 0.001). The most frequent complications included prolonged ileus or small bowel obstruction (5.3%), and anemia requiring blood transfusions (5.3%). The rate of FTR was 5.5%, 5.6% and 3.7% for low-, intermediate- and high-volume hospitals, respectively (P < 0.001). FTR after MIS was 2.6% vs. 5.5% after open surgery (P < 0.001). After accounting for patient and hospital characteristics, patients treated at low-volume hospitals were 23% more likely to die after a complication, compared to patients at high-volume hospitals (OR 1.23, 95%CI 1.13-1.33)., Conclusions: Hospital volume is the strongest predictor of complication and FTR. The reduction in mortality in high-volume hospitals could be determined by the better ability to rescue patients. These findings support the centralization policy of rectal cancer treatment., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Growing evidence suggests that colorectal cancer (CRC) screening based on the fecal immunochemical test (FIT) reduces CRC incidence and surgical resection rates., Aims: To compare trends in surgery for proximal and distal CRC among Italian regions at different stages of screening implementation., Methods: From the National Hospital Discharge Database we selected hospitalizations with CRC resection of residents aged 50-74 years during 2002-2014, and computed surgery rates for the 8 most populous Italian regions with/without a screening program., Results: In regions with screening, implemented around 2006-2007, the annual percent change (APC) of distal CRC resection was +1.7 (95% confidence interval -1.0, 4.4) during 2002-2007 and -9.1 (-10.6, -7.7) during 2007-2014. No significant change was observed in regions without screening. The APC for proximal colon resection in regions with screening was +5.8 (2.5, 9.0) during 2002-2007 and -4.1 (-5.8, -2.4) during 2007-2014, while in regions without screening surgical rates increased through the whole study period. Compared to 2002, in 2014 distal CRC resection rates were greatly reduced in regions with screening, reaching values similar to proximal CRC resection., Conclusion: Following the implementation of screening programs surgery rates steeply decreased, confirming the deep impact of FIT-based screening on the burden of CRC., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The global real-life impact of non-vitamin K antagonist oral anticoagulants (NOACs) introduction in the healthcare system in a setting of well-managed vitamin K antagonist (VKA) therapy has not been specifically addressed., Methods: We did a population-based retrospective cohort study in naïve patients initiating oral anticoagulants for stroke prevention in atrial fibrillation in a region with a well-managed VKA therapy. NOAC and VKA cohorts were identified using Anatomical Therapeutic Chemical (ATC) codes, while excluding other indications for anticoagulation therapy using ICD-9CM codes. Propensity score was conducted using two different approaches: stratification and 1:1 matching. Event-rates were assessed using both an intention to treat (ITT) and as treated analyses., Results: Of the 137,800 selected patients, 40,411 (6923 treated with NOACs and 33,488 with VKAs) were identified (June 2013-December 2015). Overall ischaemic stroke and major bleeding risk did not significantly differ between the groups both in the ITT and as treated analyses. Noteworthy, intracranial bleeding risk was lower with NOACs (stratified model HR=0.69; 95%CI 0.48-0.99; 1:1 matched model HR=0.73; 95%CI 0.47-1.13) reaching statistical significance in the as treated analysis in both stratified and 1:1 matched models (HR=0.51; 95%CI 0.32-0.80 and HR=0.52; 95%CI 0.30-0.90, respectively)., Conclusion: Despite well-managed anticoagulation with VKAs, NOACs' introduction has a positive global impact in the public healthcare system in terms of effectiveness and safety especially by lowering intracranial bleeding., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Context: Frequent end-of-life health care setting transitions can lead to an increased risk of fragmented care and exposure to unnecessary treatments., Objectives: We assessed the relationship between the presence and the intensity of an Integrated Cancer Palliative Care (ICPC) plan and the occurrence of multiple transitions during the last month of life., Methods: Decedents of cancer aged 18-85 years residents in two regions of Italy were investigated accessing their integrated administrative data (death certificates, hospital discharges, hospice, and home care records). The principal outcome was defined as having 3+ health care setting transitions during the last month of life. The ICPC plans instituted 90-31 days before death represented the main exposure of interest., Results: Of the 17,604 patients, 6698 included in an ICPC, although spending in hospital a median number of only two days (interquartile range 1-2), experienced 1+ (59.8%), 2+ (21.1%), or 3+ (5.9%) health care transitions. Among the latter group, the most common trajectory of care is home-hospital-home-hospital (36.0%). The intensity of the ICPC plan showed a marked protective effect toward the event of 3+ health care setting transitions; the effect is already evident from an intensity of at least one home visit/week (odds ratio 0.73; 95% confidence interval 0.62-0.87)., Conclusion: A well-integrated palliative care approach can be effective in further reducing the percentage of patients who spent many days in hospital and/or undergo frequent and inopportune changes of their care setting during their last month of life., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The simultaneous assessment of multiple indicators for quality of care is essential for comparisons of performance between hospitals and health care systems. The aim of this study was to assess the rates of in-hospital mortality and 30-day readmission and length of hospital stay (LOS) in patients who underwent surgical procedures for colorectal cancer between 2005 and 2014 in Italy., Methods: All patients in the National Italian Hospital Discharge Dataset who underwent a surgical procedure for colorectal cancer during the study period were included. The adjusted odd ratios for risk factors for in-hospital mortality, 30-day readmission, and LOS were calculated using multilevel multivariable logistic regression., Results: Among the 353 941 patients, rates of in-hospital mortality and 30-day readmission were 2.5% and 6%, respectively, and the median LOS was 13 days. High comorbidity, emergent/urgent admission, male gender, creation of a stoma, and an open approach increased the risks of all the outcomes at multivariable analysis. Age, hospital volume, hospital geographic location, and discharge to home/non-home produced different effects depending on the outcome considered. The most frequent causes of readmission were infection (19%) and bowel obstruction (14.6%)., Conclusions: We assessed national averages for mortality, LOS and readmission and related trends over a 10-year time. Laparoscopic surgery was the only one that could be modified by improving surgical education. Higher hospital volume was associated with a LOS reduction, but our findings only partially support a policy of centralization for colorectal cancer procedures. Surgical site infection was identified as the most preventable cause of readmission., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)