Experimental Detection of Entanglement with Polarized Photons

We report on the first experimental realization of the entanglement witness for polarization entangled photons. It represents a recently discovered significant quantum information protocol which is based on few local measurements. The present demonstration has been applied to the so-called Werner states, a family of ''mixed'' quantum states that include both entangled and non entangled states. These states have been generated by a novel high brilliance source of entanglement which allows to continuously tune the degree of mixedness

The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma

Cholangiocarcinoma (CCA) is an aggressive cancer with high resistance to chemotherapeutics. CCA is enriched in cancer stem cells, which correlate with aggressiveness and prognosis. FXR, a member of the metabolic nuclear receptor family, is markedly down-regulated in human CCA. Our aim was to evaluate, in primary cultures of human intrahepatic CCA (iCCA), the effects of the FXR agonist obeticholic acid (OCA), a semisynthetic bile acid derivative, on their cancerogenic potential. Primary human iCCA cell cultures were prepared from surgical specimens of mucinous or mixed iCCA subtypes. Increasing concentrations (0–2.5 μM) of OCA were added to culture media and, after 3–10 days, effects on proliferation (MTS assay, cell population doubling time), apoptosis (annexin V-FITC/propidium iodide), cell migration and invasion (wound healing response and Matrigel invasion assay), and cancerogenic potential (spheroid formation, clonogenic assay, colony formation capacity) were evaluated. Results: FXR gene expression was downregulated (RT-qPCR) in iCCA cells vs normal human biliary tree stem cells (p < 0.05) and in mucinous iCCA vs mixed iCCA cells (p < 0.05) but was upregulated by addition of OCA. OCA significantly (p < 0.05) inhibited proliferation of both mucinous and mixed iCCA cells, starting at a concentration as low as 0.05 μM. Also, CDCA (but not UDCA) inhibited cell proliferation, although to a much lower extent than OCA, consistent with its different affinity for FXR. OCA significantly induced apoptosis of both iCCA subtypes and decreased their in vitro cancerogenic potential, as evaluated by impairment of colony and spheroid formation capacity and delayed wound healing and Matrigel invasion. In general, these effects were more evident in mixed than mucinous iCCA cells. When tested together with Gemcitabine and Cisplatin, OCA potentiated the anti-proliferative and pro-apoptotic effects of these chemotherapeutics, but mainly in mixed iCCA cells. OCA abolished the capacity of both mucinous and mixed iCCA cells to form colonies when administered together with Gemcitabine and Cisplatin. In subcutaneous xenografts of mixed iCCA cells, OCA alone or combined with Gemcitabine or Cisplatin markedly reduced the tumor size after 5 weeks of treatment by inducing necrosis of tumor mass and inhibiting cell proliferation. In conclusion, FXR is down-regulated in iCCA cells, and its activation by OCA results in anti-cancerogenic effects against mucinous and mixed iCCA cells, both in vitro and in vivo. The effects of OCA predominated in mixed iCCA cells, consistent with the lower aggressiveness and the higher FXR expression in this CCA subtype. These results, showing the FXR-mediated capacity of OCA to inhibit cholangiocarcinogenesis, represent the basis for testing OCA in clinical trials of CCA patients

Proteomic Modulation in TGF-β-Treated Cholangiocytes Induced by Curcumin Nanoparticles

Curcumin is a natural polyphenol that exhibits a variety of beneficial effects on health, including anti-inflammatory, antioxidant, and hepato-protective properties. Due to its poor water solubility and membrane permeability, in the present study, we prepared and characterized a water-stable, freely dispersible nanoformulation of curcumin. Although the potential of curcumin nanoformulations in the hepatic field has been studied, there are no investigations on their effect in fibrotic pathological conditions involving cholangiocytes. Exploiting an in vitro model of transforming growth factor-  (TGF- )-stimulated cholangiocytes, we applied the Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS)-based quantitative proteomic approaches to study the proteome modulation induced by curcumin nanoformulation. Our results confirmed the well-documented anti-inflammatory properties of this nutraceutic, highlighting the induction of programmed cell death as a mechanism to counteract the cellular damages induced by TGF- . Moreover, curcumin nanoformulation positively influenced the expression of several proteins involved in TGF- -mediated fibrosis. Given the crucial importance of deregulated cholangiocyte functions during cholangiopathies, our results provide the basis for a better understanding of the mechanisms associated with this pathology and could represent a rationale for the development of more targeted therapies

Analysis and performance assessment of the use of ammonia-based nano additive for lean combustion

In recent years, considerable progress has been made in exploring new applications of fuel additives to reduce emissions. Reduction of total nitrogen oxide (NOx) emissions can be achieved by decreasing the flame temperature by using fuel emulsified with water and/or using ammonia-based nano additives such as urea. The use of water as part of the hydrocarbon fuel is also one of the prospective directions in the development of new types of fuel systems. For the preparation of emulsified fuel, it is desirable to achieve greater stability of the emulsified fuel with minimum expenditure of chemicals and energy, so that the emulsified fuel can be used for a longer period. The paper analyzed the influence of nano-dispersed urea particles, water, and surfactant (Span 80/ Tween 80) on the combustion stability and emission characteristics of aviation fuel. The experimental campaign was conducted on a test stand (a 300kW liquid vortex combustor of 300 kW) consisting of a cylindrical combustion chamber with four optical windows and equipped with high-precision pressure sensors, thermocouples, and an exhaust gas analyzer for acquiring emissions. The experimental campaign was conducted at a constant fuel/air ratio (Φ). One of the main focus is related to the stability of the emulsion. Chemiluminescence imaging was performed to characterize the effects of the additive on flame emissions. In addition, a statistical and spectral analysis was performed using the pressure sensor for instability analysis. Exhaust gas analysis was performed both with the additive described above and without additive for a constant Φ condition. The analysis was performed for NOx, carbon monoxide (CO) and carbon dioxide (CO2) and oxygen (O 2)

Comorbidity and in-hospital mortality in peritoneal dialysis patients: data of the Emilia Romagna region of Italy

Objective: Kidney failure increases in-hospital mortality (IHM); however, comorbidity is crucial for predicting mortality in dialysis patients. Our aim was to evaluate the impact of comorbidity, assessed by modified Elixhauser index (mEI), Charlson Comorbidity Index (CCI), and age-adjusted CCI, on IHM in a cohort of peritoneal dialysis patients admitted to hospitals of the Emilia Romagna region (ERR) of Italy. Patients and methods: All hospital admissions of peritoneal dialysis patients recorded between 2007 and 2021 in the ERR database were analyzed. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) was used for detecting diagnoses and procedures, and the inclusion criterion was code 5498. Comorbidity burden was evaluated by three different scores, and hemodialysis (HD) treatment need was considered. IHM was our outcome. Results: During the 15 years of the study, 3,242 hospitalized peritoneal dialysis patients (62.7% males) were evaluated. Mean age was 62.8±20.6 years, 9.6% underwent HD, and IHM was 5.9% (n=192). IHM mortality was stable throughout the study period. Deceased subjects were older, were hospitalized longer, had a higher comorbidity burden, and had a higher percentage of HD treatment needs than survivors. Age, male sex, comorbidity burden, and HD treatment were predictors of IHM. Receiver operating characteristics (ROC) analysis confirmed the impact of comorbidity burden on IHM, especially when age was considered. Conclusions: We conclude that in male, elderly hospitalized peritoneal dialysis patients with failing dialysis technique, comorbidity burden should be considered being a predictor of IHM

Tumor-Infiltrating Lymphocyte Recognition in Primary Melanoma by Deep Learning Convolutional Neural Network

The presence of tumor-infiltrating lymphocytes (TILs) is associated with a favorable prognosis of pri-mary melanoma (PM). Recently, artificial intelligence (AI)-based approach in digital pathology was proposed for the standardized assessment of TILs on hematoxylin and eosin-stained whole slide images (WSIs). Herein, the study applied a new convolution neural network (CNN) analysis of PM WSIs to automatically assess the infiltration of TILs and extract a TIL score. A CNN was trained and validated in a retrospective cohort of 307 PMs including a training set (237 WSIs, 57,758 patches) and an inde-pendent testing set (70 WSIs, 29,533 patches). An AI-based TIL density index (AI-TIL) was identified after the classification of tumor patches by the presence or absence of TILs. The proposed CNN showed high performance in recognizing TILs in PM WSIs, showing 100% specificity and sensitivity on the testing set. The AI-based TIL index correlated with conventional TIL evaluation and clinical outcome. The AI-TIL index was an independent prognostic marker associated directly with a favorable prognosis. A fully automated and standardized AI-TIL appeared to be superior to conventional methods at differentiating the PM clinical outcome. Further studies are required to develop an easy-to-use tool to assist pathologists to assess TILs in the clinical evaluation of solid tumors. (Am J Pathol 2023, 193: 2099-2110; https://doi.org/10.1016/j.ajpath.2023.08.013

Ambulatory blood pressure monitoring during pregnancy: an Italian experience

Objective: To describe the impact of a collaborative Italian diagnostic pathway offering ambulatory blood pressure (BP) monitoring (ABPM) in High Risk Antenatal Clinic (HRAC) pregnant women. The study included 395 pregnant women evaluated at HRAC between 2012 and 2016, while analyzing demographic, clinical characteristics, and prescription of ABPM. Pregnant women were firstly seen when gestational age was 19.6 +/- 9.6 weeks. In at least one-third of cases, ABPM was followed by medical intervention aiming to modify the preexisting therapeutic treatment. Hypertension and overweight were the main reasons for performing ABPM. WCH: white-coat hypertension

Nuclear accumulation of mRNAs underlies G4C2-repeat-induced translational repression in a cellular model of C9orf72 ALS

A common feature of non-coding repeat expansion disorders is the accumulation of RNA repeats as RNA foci in the nucleus and/or cytoplasm of affected cells. These RNA foci can be toxic because they sequester RNA-binding proteins, thus affecting various steps of post-transcriptional gene regulation. However, the precise step that is affected by C9orf72 GGGGCC (G4C2) repeat expansion, the major genetic cause of amyotrophic lateral sclerosis (ALS), is still poorly defined. In this work, we set out to characterise these mechanisms by identifying proteins that bind to C9orf72 RNA. Sequestration of some of these factors into RNA foci was observed when a (G4C2)31 repeat was expressed in NSC34 and HeLa cells. Most notably, (G4C2)31 repeats widely affected the distribution of Pur-alpha and its binding partner fragile X mental retardation protein 1 (FMRP, also known as FMR1), which accumulate in intra-cytosolic granules that are positive for stress granules markers. Accordingly, translational repression is induced. Interestingly, this effect is associated with a marked accumulation of poly(A) mRNAs in cell nuclei. Thus, defective trafficking of mRNA, as a consequence of impaired nuclear mRNA export, might affect translation efficiency and contribute to the pathogenesis of C9orf72 ALS

Severe Aortic Stenosis and Myocardial Function: Diagnostic and Prognostic Usefulness of Ultrasonic Integrated Backscatter Analysis

Background— The aim of this study was to assess the myocardial reflectivity pattern in severe aortic valve stenosis through the use of integrated backscatter (IBS) analysis. Patients with aortic stenosis (AS) were carefully selected in the Department of Cardiology. Methods and Results— Thirty-five subjects (AS: valve orifice ≤1 cm2; 12 female; mean age, 71.8±6.2 years) and 25 healthy subjects were studied. All subjects of the study had conventional 2D-Doppler echocardiography and IBS. Backscatter signal was sampled at the septum and posterior wall levels. Patients with AS were divided into 2 groups: 16 patients with initial signs of congestive heart failure and a depressed left ventricular systolic function (DSF) (ejection fraction [EF] range, 35% to 50%) and 19 asymptomatic patients with normal left ventricular systolic function (NSF) (EF >50%). Myocardial echo intensity (pericardium related) was significantly higher at the septum and posterior wall levels in DSF than in NSF and in control subjects. IBS variation, as an expression of variation of the signal, appeared to be significantly lower in AS with DSF than in NSF and in control subjects, at both the septum and posterior wall levels. Patients with DSF underwent aortic valve replacement, and, during surgical intervention, a septal myocardial biopsy was made for evaluation of myocardium/fibrosis ratio. Abnormally increased echo intensity was detected in left ventricular pressure overload by severe aortic stenosis and correlated with increase of myocardial collagen content (operating biopsy). Conclusions— One year after aortic valve replacement, we observed a significant reduction of left ventricular mass, and, only if pericardial indexed IBS value (reduction of interstitial fibrosis) decreased, it was possible to observe an improvement of EF and of IBS variation