Nanodynamo quantifies subcellular RNA dynamics revealing extensive coupling between steps of the RNA life cycle.

The coordinated action of transcriptional and post-transcriptional machineries shapes gene expression programs at steady state and determines their concerted response to perturbations. We have developed Nanodynamo, an experimental and computational workflow for quantifying the kinetic rates of nuclear and cytoplasmic steps of the RNA life cycle. Nanodynamo is based on mathematical modelling following sequencing of native RNA from cellular fractions and polysomes.

Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer.

Unlabelled: Cancer cells exhibit metabolic plasticity to meet oncogene-driven dependencies while coping with nutrient availability. A better understanding of how systemic metabolism impacts the accumulation of metabolites that reprogram the tumor microenvironment (TME) and drive cancer could facilitate development of precision nutrition approaches. Using the Hi-MYC prostate cancer mouse model, we demonstrated that an obesogenic high-fat diet (HFD) rich in saturated fats accelerates the development of c-MYC-driven invasive prostate cancer through metabolic rewiring.

Lessons Learned from the COVID-19 Vaccination Campaigns in Veneto Region: Population Vaccination Centers as Support for the Traditional Outpatient Model.

The extraordinary vaccination campaigns of the COVID-19 pandemic era put organizational and operational systems to the test in numerous territorial contexts. In the Veneto region, the activation of population vaccination centers (CVPs) guaranteed the provision of vaccines to mountain areas. These centers, drive-in and building-based, improved the efficiency of dose administration in relation to similar conditions where healthcare workers (HCWs) were routinely involved in clinics.

Improving the Quality of Healthcare Provision Regarding HPV Immunization for Women with CIN2+ Lesions: The Experience of the Veneto Region in Italy.

HPV is the most common cause of sexually-transmitted infections the world over. The aim of this study was to assess the impact of a healthcare quality improvement strategy designed to increase the rate of vaccination against HPV in women diagnosed with cervical lesions graded as CIN2 or higher (CIN2+) during routine screening. The Veneto Regional Health Service developed a 22-item questionnaire to measure the gap between ideal procedure and real practice regarding the offer of vaccination against HPV for women undergoing routine cervical screening.

Cost-effectiveness analysis of the new oncological drug durvalumab in Italian patients with stage III non-small cell lung cancer.

Background: The monoclonal antibody durvalumab, an immune-checkpoint inhibitor (ICI) antiprogrammed death ligand 1 (PD-L1), is available for unresectable stage III NSCLC patients as consolidation therapy following induction chemoradiotherapy, with very promising overall survival (OS) and progression-free survial (PFS) results in registration trials. The purpose of this study was to provide policymakers with an estimate of the cost-effectiveness of durvalumab in the treatment of non-small cell lung cancer (NSCLC).

Methods: The study developed a Markov model covering a 5-year period to compare costs and outcomes of treating PD-L1 positive patients with or without durvalumab.

MYC drives aggressive prostate cancer by disrupting transcriptional pause release at androgen receptor targets.

c-MYC (MYC) is a major driver of prostate cancer tumorigenesis and progression. Although MYC is overexpressed in both early and metastatic disease and associated with poor survival, its impact on prostate transcriptional reprogramming remains elusive. We demonstrate that MYC overexpression significantly diminishes the androgen receptor (AR) transcriptional program (the set of genes directly targeted by the AR protein) in luminal prostate cells without altering AR expression.

Halting the pandemic outside 'CORTINA2021' alpine world ski championships: a challenge for sport and public health in times of COVID-19.

Background: In February 2021 the "Cortina2021" Alpine World Ski Championships took place in the mountain town of Cortina d'Ampezzo (Italy), thus gaining the definition of "first sporting event of global significance in the time of covid-19 pandemic". Though the event took place behind closed doors and in a context of national public health restrictive measures, it counted almost 6,000 participants.

Methods: A rigorous "Covid-19 Prevention and Hygiene Protocol" was drawn up by the local and regional health authorities together with the organizing committee, in order to contain the risk of viral circulation within the venue.

Using Failure Mode, Effect and Criticality Analysis to Improve Safety in the COVID Mass Vaccination Campaign.

Vaccination against SARS-CoV-2 will likely be the most promising way to combat the pandemic. Even if mass vaccination is urgent, it should still always be supported by appropriate patient safety management. The aim of this study, based on failure mode, effects and criticality analysis (FMECA), was to identify possible failures and highlight measures that can be adopted to prevent their occurrence.

Non-Small-Cell Lung Cancer: Real-World Cost Consequence Analysis.

Purpose: The present work aimed at conducting a real-world data analysis on the management costs and survival analysis comparing data from non-small-cell lung cancer (NSCLC) cases diagnosed in the Veneto region before (2015) and after (2017) the implementation of a regional diagnostic and therapeutic pathway including all new diagnostic and therapeutic strategies.

Method: This study considered 254 incidental cases of NSCLC in 2015 and 228 in 2017 within the territory of the Padua province (Italy), as recorded by the Veneto Cancer Registry. Tobit regression analysis was performed to verify if total and each item costs (2 years after NSCLC diagnosis) are associated with index year, adjusting by year of diagnosis, sex, age, and stage at diagnosis.

Drive-through vaccinations prove successful in immunizing mountain communities against tick-borne encephalitis during the COVID-19 pandemic.

In March 2020, the COVID-19 pandemic disrupted most of the routine outpatient activities in Italian hospitals and Prevention Departments, including those vaccinations which were not urgent and/or scheduled for children aged 0-6 years. Since June 2020, when the pandemic entered a milder phase, in the alpine Province of Belluno (Veneto, North-Eastern Italy), 12,152 doses of vaccine against tick-borne encephalitis have been administered by means of the innovative "drive-through" modality. No significant adverse events have occurred and popular demand has steadily grown, proving the "drive-through" approach to be safe, efficient and successful.

Diet-Dependent Metabolic Regulation of DNA Double-Strand Break Repair in Cancer: More Choices on the Menu.

Despite several epidemiologic and preclinical studies supporting the role of diet in cancer progression, the complexity of the diet-cancer link makes it challenging to deconvolute the underlying mechanisms, which remain scantly elucidated. This review focuses on genomic instability as one of the cancer hallmarks affected by diet-dependent metabolic alterations. We discuss how altered dietary intake of metabolites of the one-carbon metabolism, including methionine, folate, and vitamins B and C, can impact the methylation processes and thereby tumorigenesis.

Estimated direct costs of non-small cell lung cancer by stage at diagnosis and disease management phase: A whole-disease model.

Background: Non-small cell lung cancer (NSCLC) is the first cause of cancer-related death among men and the second among women worldwide. It also poses an economic threat to the sustainability of healthcare services. This study estimated the direct costs of care for patients with NSCLC by stage at diagnosis, and management phase of pathway recommended in local and international guidelines.

Safety in Wine Production: A Pilot Study on the Quality Evaluation of Wine in the Framework of UE Regulation.

In Italy, wine production is considered a sector of excellence, where the wines' appreciable sensory features are favored by environmental factors, including weather and climate conditions, which benefit territories with a specific vocation. The whole chain involves many economic and agri-food sector operators, and requires an in-depth assessment of specific risks for identifying critical points, keeping the entire production process under control, and ensuring product traceability. This article describes the results of a pilot study conducted in the Prosecco DOCG (Designations of Controlled and Guaranteed Origin) area, concerning the detection of residues of plant protection products in fifty wine bottles.

[From the traces in the wells of the urban aqueduct network to the subsequent prohibition of the use of glyphosate: the case of an area of high-intensity wine production in the province of Treviso, Veneto].

Glyphosate is the best-selling herbicide in the world and in 2015 the International Agency for Research on Cancer listed it among the "probable carcinogens for humans", opening a scientific debate that is still going on. On these premises, in 2016, extraordinary samplings of glyphosate, its metabolite AMPA, and a similar compound, ammonium glufosinate, were carried out in 12 wells of the water network intended for domestic consumption in the territory of the Local Health Unit 2 - District of Pieve di Soligo, Province of Treviso, Veneto region, Italy. The area includes 13 municipalities at high-intensity "Prosecco d.

Differences in direct costs of patients with stage I cutaneous melanoma: A real-world data analysis.

Background: Clinical factors, such as tumor thickness, ulceration and growth phase have a role as prognostic factors for stage I melanoma. However, it is still under debate whether these variables influence the related direct costs. We aimed to investigate which clinical factors represent direct health care "cost drivers" for stage I melanoma.

The importance of sex as a risk factor for hospital readmissions due to pulmonary diseases.

Background: Pulmonary diseases are a common and costly cause of 30-day readmissions. Few studies have focused on the difference in risk for rehospitalization between men and women in older patients. In this study we analyzed the association between sex and the risk of readmission in a cohort of patients admitted to the hospital for chronic obstructive pulmonary disease (COPD) exacerbation and other major pulmonary diseases.

A functional interplay between Δ133p53 and ΔNp63 in promoting glycolytic metabolism to fuel cancer cell proliferation.

Although ΔNp63 is known to promote cancer cell proliferation, the underlying mechanism behind its oncogenic function remains elusive. We report here a functional interplay between ΔNp63 and Δ133p53. These two proteins are co-overexpressed in a subset of human cancers and cooperate to promote cell proliferation.

AXL receptor signalling suppresses p53 in melanoma through stabilization of the MDMX-MDM2 complex.

Deregulation of the tyrosine kinase signalling is often associated with tumour progression and drug resistance, but its underlying mechanisms are only partly understood. In this study, we investigated the effects of the receptor tyrosine kinase AXL on the stability of the MDMX-MDM2 heterocomplex and the activity of p53 in melanoma cells. Our data demonstrated that AXL overexpression or activation through growth arrest-specific 6 (Gas6) ligand stimulation increases MDMX and MDM2 protein levels and decreases p53 activity.

MDMX under stress: the MDMX-MDM2 complex as stress signals hub.

The tumor suppressor p53 plays a central role in safeguarding cellular homeostasis. Upon various types of stress signals such as DNA damage or oncogenic stress, p53 is promptly activated to prevent and repair damages that can threaten the genome stability. The two major negative regulators of p53 are MDM2 and MDMX, two homolog proteins that control p53 activity and turnover, hence keeping it in check during normal cell cycling.

Human epidermal growth factor receptor 4 (Her4) Suppresses p53 Protein via Targeting the MDMX-MDM2 Protein Complex: IMPLICATION OF A NOVEL MDMX SER-314 PHOSPHOSITE.

Deregulated receptor tyrosine kinase (RTK) signaling is frequently associated with tumorigenesis and therapy resistance, but its underlying mechanisms still need to be elucidated. In this study, we have shown that the RTK human epidermal growth factor receptor 4 (Her4, also known as Erbb4) can inhibit the tumor suppressor p53 by regulating MDMX-mouse double minute 2 homolog (MDM2) complex stability. Upon activation by either overexpression of a constitutively active vector or ligand binding (Neuregulin-1), Her4 was able to stabilize the MDMX-MDM2 complex, resulting in suppression of p53 transcriptional activity, as shown by p53-responsive element-driven luciferase assay and mRNA levels of p53 target genes.

Quantitative cross-species extrapolation between humans and fish: the case of the anti-depressant fluoxetine.

Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case.

A new role for carbonic anhydrase 2 in the response of fish to copper and osmotic stress: implications for multi-stressor studies.

The majority of ecotoxicological studies are performed under stable and optimal conditions, whereas in reality the complexity of the natural environment faces organisms with multiple stressors of different type and origin, which can activate pathways of response often difficult to interpret. In particular, aquatic organisms living in estuarine zones already impacted by metal contamination can be exposed to more severe salinity variations under a forecasted scenario of global change. In this context, the present study aimed to investigate the effect of copper exposure on the response of fish to osmotic stress by mimicking in laboratory conditions the salinity changes occurring in natural estuaries.

Challenges for the development of a biotic ligand model predicting copper toxicity in estuaries and seas.

An effort is ongoing to develop a biotic ligand model (BLM) that predicts copper (Cu) toxicity in estuarine and marine environments. At present, the BLM accounts for the effects of water chemistry on Cu speciation, but it does not consider the influence of water chemistry on the physiology of the organisms. We discuss how chemistry affects Cu toxicity not only by controlling its speciation, but also by affecting the osmoregulatory physiology of the organism, which varies according to salinity.