Non-invasive assessment of portal hypertension in patients with primary biliary cholangitis is affected by severity of cholestasis.

Background&aims: Non-invasive tests (NITs) for ruling-out clinical significant portal hypertension (CSPH) and high-risk varices (HRV) in patients with primary biliary cholangitis(PBC) and compensated advanced chronic liver disease (cACLD) are lacking. We evaluated NITs in these patients and the influence of cholestasis on their performance.

Methods: Consecutive patients from the "Italian PBC registry" and two UK large-volume PBC referral centres with upper endoscopy within 6 months from biochemical evaluation and transient elastography were included.

Atomic Structure and 3D Shape of a Multibranched Plasmonic Nanostar from a Single Spatially Resolved Electron Diffraction Map.

Despite the interest in improving the sensitivity of optical sensors using plasmonic nanoparticles (NPs) (rods, wires, and stars), the full structural characterization of complex shape nanostructures is challenging. Here, we derive from a single scanning transmission electron microscope diffraction map (4D-STEM) a detailed determination of both the 3D shape and atomic arrangement of an individual 6-branched AuAg nanostar (NS) with high-aspect-ratio legs. The NS core displays an icosahedral structure, and legs are decahedral rods attached along the 5-fold axes at the core apexes.

Liver-related aspects of valoctocogene roxaparvovec gene therapy for hemophilia A: expert guidance for clinical practice.

Adeno-associated virus-based gene therapy (valoctocogene roxaparvovec) is an attractive treatment for hemophilia A. Careful clinical management is required to minimize the risk of hepatotoxicity, including assessment of baseline liver condition to determine treatment eligibility and monitoring liver function after gene therapy. This article describes recommendations (developed by a group of hemophilia experts) on hepatic function monitoring before and after gene therapy.

Urinary mRNA-based biomarkers for non-muscle-invasive bladder cancer: a mini-review.

Bladder cancer (BC) is the second most common type of cancer of the urinary system. Approximately 75% of the cases are non-muscle invasive bladder cancer (NMIBC), which has a high recurrence and progression rate. Current diagnosis and surveillance methods present challenges, including risks to the patients.

Procoagulant phenotype of virus-infected pericytes is associated with portal thrombosis and intrapulmonary vascular dilations in fatal COVID-19.

Background & Aims: The underlying mechanisms and clinical impact of portal microthrombosis in severe COVID-19 are unknown. Intrapulmonary vascular dilation (IPVD)-related hypoxia has been described in severe liver diseases. We hypothesised that portal microthrombosis is associated with IPVD and fatal respiratory failure in COVID-19.

Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease.

Background: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy.

Methods: Patients with a diagnosis of pCCA between 1997-2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry.

Long term follow-up of heart rate variability in healthcare workers with mild COVID-19.

Introduction: Prior investigations into post-COVID dysautonomia often lacked control groups or compared affected individuals solely to healthy volunteers. In addition, no data on the follow-up of patients with SARS-CoV-2-related autonomic imbalance are available.

Methods: In this study, we conducted a comprehensive clinical and functional follow-up on healthcare workers (HCWs) with former mild COVID-19 (group 1, n = 67), to delineate the trajectory of post-acute autonomic imbalance, we previously detected in a case-control study.

Discrimination of Genetic Biomarkers of Disease through Machine-Learning-Based Hypothesis Testing of Direct SERS Spectra of DNA and RNA.

Cancer is globally a leading cause of death that would benefit from diagnostic approaches detecting it in its early stages. However, despite much research and investment, cancer early diagnosis is still underdeveloped. Owing to its high sensitivity, surface-enhanced Raman spectroscopy (SERS)-based detection of biomarkers has attracted growing interest in this area.

The Effect of Geoclimatic Factors on the Distribution of Paracoccidioidomycosis in Mato Grosso do Sul, Brazil.

The incidence of paracoccidioidomycosis (PCM) varies in Latin America, and it is influenced by environmental factors. This study evaluated the distribution of PCM acute/subacute form (AF) cases and their correlation with geoclimatic factors in the Mato Grosso do Sul (MS) state. The study included 81 patients diagnosed with the PCM/AF at the University Hospital of the Federal University of Mato Grosso do Sul between January 1980 and February 2022.

Angiopoietin-2 and the Vascular Endothelial Growth Factor Promote Migration and Invasion in Hepatocellular Carcinoma- and Intrahepatic Cholangiocarcinoma-Derived Spheroids.

Aggressive hepatocellular carcinoma (HCC) overexpressing Angiopoietin-2 (ANG-2) (a protein linked with angiogenesis, proliferation, and epithelial-mesenchymal transition (EMT)), shares 95% of up-regulated genes and a similar poor prognosis with the proliferative subgroup of intrahepatic cholangiocarcinoma (iCCA). We analyzed the pro-invasive effect of ANG-2 and its regulator vascular endothelial growth factor (VEGF) on HCC and CCA spheroids to uncover posUsible common ways of response. Four cell lines were used: Hep3B and HepG2 (HCC), HuCC-T1 (iCCA), and EGI-1 (extrahepatic CCA).

Measurement of Electron-Neutrino Charged-Current Cross Sections on ^{127}I with the COHERENT NaIνE Detector.

Using an 185-kg NaI[Tl] array, COHERENT has measured the inclusive electron-neutrino charged-current cross section on ^{127}I with pion decay-at-rest neutrinos produced by the Spallation Neutron Source at Oak Ridge National Laboratory. Iodine is one the heaviest targets for which low-energy (≤50  MeV) inelastic neutrino-nucleus processes have been measured, and this is the first measurement of its inclusive cross section. After a five-year detector exposure, COHERENT reports a flux-averaged cross section for electron neutrinos of 9.

The impact of SARS-CoV-2 on healthcare workers of a large University Hospital in the Veneto Region: risk of infection and clinical presentation in relation to different pandemic phases and some relevant determinants.

Aim: The aim of this study is to evaluate the incidence of SARS-CoV-2 infection and the prevalence of COVID-19-related symptoms in relation to pandemic phases and some relevant variables in a cohort of 8,029 HCWs from one of the largest Italian University Hospitals.

Methods: A single-center retrospective study was performed on data collected during SARS-CoV-2 infection surveillance of HCWs. Cox's multiple regression was performed to estimate hazard ratios of SARS-CoV-2 infection.

The evil relationship between liver fibrosis and cardiovascular disease in metabolic dysfunction-associated fatty liver disease (MAFLD): Looking for the culprit.

Metabolic dysfunction-associated fatty liver disease (MAFLD), the hepatic component of the metabolic syndrome caused by insulin resistance, is a major public health problem, affecting about the 25 % of the general population in Western countries. Morbidity and mortality of MAFLD patients is increased primarily due to cardiovascular disease (CVD). Liver fibrosis, the byproduct of hepatic repair, is the main determinant of MAFLD progression and the strongest predictor for overall mortality.

FXR agonists INT-787 and OCA increase RECK and inhibit liver steatosis and inflammation in diet-induced ob/ob mouse model of NASH.

Background And Aims: We have previously shown in a model of hepatic ischaemia/reperfusion injury that the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) restores reversion-inducing-cysteine-rich protein with Kazal motifs (RECK), an inverse modulator of metalloproteases (MMPs) and inhibitor of the sheddases ADAM10 and ADAM17 involved in inflammation and fibrogenesis. Here, the effects of FXR agonists OCA and INT-787 on hepatic levels of RECK, MMPs, ADAM10 and ADAM17 were compared in a diet-induced ob/ob mouse model of non-alcoholic steatohepatitis (NASH).

Methods: Lep ob/ob NASH mice fed a high-fat diet (HFD) or control diet (CD) for 9 weeks (wks) were treated with OCA or INT-787 0.

A TGFβ-ECM-integrin signaling axis drives structural reconfiguration of the bile duct to promote polycystic liver disease.

The formation of multiple cysts in the liver occurs in a number of isolated monogenic diseases or multisystemic syndromes, during which bile ducts develop into fluid-filled biliary cysts. For patients with polycystic liver disease (PCLD), nonsurgical treatments are limited, and managing life-long abdominal swelling, pain, and increasing risk of cyst rupture and infection is common. We demonstrate here that loss of the primary cilium on postnatal biliary epithelial cells (via the deletion of the cilia gene ) drives ongoing pathological remodeling of the biliary tree, resulting in progressive cyst formation and growth.

17β-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer.

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor-positive (ER+) BC, we hypothesized that 17β-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17β-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2.

A multifidelity approach coupling parameter space reduction and nonintrusive POD with application to structural optimization of passenger ship hulls.

Nowadays, the shipbuilding industry is facing a radical change toward solutions with a smaller environmental impact. This can be achieved with low emissions engines, optimized shape designs with lower wave resistance and noise generation, and by reducing the metal raw materials used during the manufacturing. This work focuses on the last aspect by presenting a complete structural optimization pipeline for modern passenger ship hulls which exploits advanced model order reduction techniques to reduce the dimensionality of both input parameters and outputs of interest.