Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus

Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett's metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett's esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyzed for BE diagnosis. Quantitative Real-time PCR was used to compare miRNA expression levels in serum and 60 disease/ normal-paired tissues from 30 patients diagnosed with esophagitis, columnar-lined oesophagus (CLO) or BE. MiRNA expression analysis showed that miR-143, miR-145, miR-194 and miR-215 levels were significantly higher, while miR-203 and miR-205 were lower in BE tissues compared with their corresponding normal tissues. Esophageal mucosa analysis of patients with CLO and esophagitis showed that these miRNAs were similarly deregulated but to a lesser extent keeping the same trend and CLO appeared as intermediate step between esophagitis and BE. Analysis on circulating miRNA levels confirmed that miR-194 and miR-215 were significantly upregulated in both BE and CLO compared to esophagitis, while miR-143 was significantly upregulated only in the Barrett group. These findings suggest that miRNAs may be involved in neoplastic/ metaplastic progression and miRNA analysis might be useful for progression risk prediction as well as for monitoring of BE/CLO patients

An IXPE-led X-Ray Spectropolarimetric Campaign on the Soft State of Cygnus X-1: X-Ray Polarimetric Evidence for Strong Gravitational Lensing

We present the first X-ray spectropolarimetric results for Cygnus X-1 in its soft state from a campaign of five IXPE observations conducted during 2023 May–June. Companion multiwavelength data during the campaign are likewise shown. The 2–8 keV X-rays exhibit a net polarization degree PD = 1.99% ± 0.13% (68% confidence). The polarization signal is found to increase with energy across the Imaging X-ray Polarimetry Explorer’s (IXPE) 2–8 keV bandpass. The polarized X-rays exhibit an energy-independent polarization angle of PA = −25.°7 ± 1.°8 east of north (68% confidence). This is consistent with being aligned to Cyg X-1’s au-scale compact radio jet and its parsec-scale radio lobes. In comparison to earlier hard-state observations, the soft state exhibits a factor of 2 lower polarization degree but a similar trend with energy and a similar (also energy-independent) position angle. When scaling by the natural unit of the disk temperature, we find the appearance of a consistent trend line in the polarization degree between the soft and hard states. Our favored polarimetric model indicates that Cyg X-1’s spin is likely high (a * ≳ 0.96). The substantial X-ray polarization in Cyg X-1's soft state is most readily explained as resulting from a large portion of X-rays emitted from the disk returning and reflecting off the disk surface, generating a high polarization degree and a polarization direction parallel to the black hole spin axis and radio jet. In IXPE’s bandpass, the polarization signal is dominated by the returning reflection emission. This constitutes polarimetric evidence for strong gravitational lensing of X-rays close to the black hole

Immunohistochemistry analysis of PSMA expression at prostatic biopsy in high-risk prostate cancer: potential implications for PSMA-PET patient selection

IntroductionProstate-specific membrane antigen (PSMA) is a transmembrane protein expressed by normal prostatic tissue. Therefore, molecular imaging targeting PSMA (PSMA-PET) has gained particular interest and diffusion for PCa staging and restaging. Several factors may affect PSMA-PET results, and many tools have been proposed to improve patient selection. Furthermore, PSMA expression is not homogeneous among different tissues and within the prostate itself. The aims of this study were to evaluate immunohistochemistry (IHC) features of prostate biopsy samples and to assess their correlation with whole-mount specimens and PSMA-PET parameters.MethodsWe included consecutive high-risk PCa patients who underwent PSMA-PET for staging proposal at our institution from January 2022 to December 2022. The PET parameters selected were SUVmax, total volume (TV), and total lesion activity (TL). Each patient underwent multiparametric MRI (mpMRI) and fusion-targeted prostate biopsy prior to surgery. IHC analyses were performed on the index lesion cores. IHC visual score (VS) (1, 2, 3) and visual pattern (VP) (membranous, cytoplasmic, and combined) and the percentage of PSMA-negative tumor areas (PSMA%neg) within biopsy cores were evaluated.ResultsForty-three patients who underwent robotic radical prostatectomy after PSMA-PET were available for analyses. Concordance between VS and VP at biopsy and final pathology showed a Cohen’s kappa coefficient of 0.39 and 0.38, respectively. Patients with PSMA%neg <20% had a higher concordance in VS and VP (Cohen’s kappa 0.49 and 0.4, respectively). No difference emerged in terms of median PSMA-TV (p = 0.3) and PSMA-TL (p = 0.9) according to VS at biopsy, while median SUVmax was higher in patients with VS 3 (p = 0.04). Higher SUVmax was associated with membranous and combined VP expression (p = 0.008). No difference emerged between patients with PSMA%neg <20% or PSMA%neg >20% on biopsy cores in terms of SUVmax, PSMA-TL, and PSMA-TV (p = 0.5, p = 0.5, and p = 0.9 respectively).ConclusionsWe found a correlation between IHC VS and VP on targeted biopsy cores and SUVmax at PSMA-PET. However, the correlation between the IHC parameters of biopsy cores and final pathology was not as high as expected. Nevertheless, the presence of PSMA%neg <20% seems to have a better concordance in terms of visual score

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Multidimensional signals and analytic flexibility: Estimating degrees of freedom in human speech analyses

Recent empirical studies have highlighted the large degree of analytic flexibility in data analysis which can lead to substantially different conclusions based on the same data set. Thus, researchers have expressed their concerns that these researcher degrees of freedom might facilitate bias and can lead to claims that do not stand the test of time. Even greater flexibility is to be expected in fields in which the primary data lend themselves to a variety of possible operationalizations. The multidimensional, temporally extended nature of speech constitutes an ideal testing ground for assessing the variability in analytic approaches, which derives not only from aspects of statistical modeling, but also from decisions regarding the quantification of the measured behavior. In the present study, we gave the same speech production data set to 46 teams of researchers and asked them to answer the same research question, resulting insubstantial variability in reported effect sizes and their interpretation. Using Bayesian meta-analytic tools, we further find little to no evidence that the observed variability can be explained by analysts’ prior beliefs, expertise or the perceived quality of their analyses. In light of this idiosyncratic variability, we recommend that researchers more transparently share details of their analysis, strengthen the link between theoretical construct and quantitative system and calibrate their (un)certainty in their conclusions

La gestione delle collezioni scientifiche e storico naturalistiche: questionario sullo stato dell’arte dei Musei scientifici e di storia naturale italiani

L’ importante ruolo, affidato ai Musei di Scienze e di Storia Naturale, nella divulgazione, conservazione e studio della scienza e della biodiversità ha portato ad affrontare numerose trasformazioni e variazioni sia nell’apparato comunicativo che nella gestione. Per garantire la fruizione del patrimonio custodito è necessario adeguare gli standard minimi richiesti per sviluppare archivi e banche dati fruibili. Attraverso i risultati di questo sondaggio, condotto nel corso del 2013 nell’ambito del progetto di ricerca di dottorato “La gestione delle collezioni dei musei scientifici e storico naturalistrici mediante applicazione di tecnologie di infomobilità” (Cangemi, 2015), si vuole presentare lo stato dell’arte della conservazione e della gestione delle collezioni scientifiche e naturalistiche. In particolare l’attenzione è stata posta sull’utilizzo di strumenti di monitoraggio, sullo stato e i metodi di inventariazione e catalogazione, ed infine sulle procedure adottate per la ovimentazione interna ed esterna dei beni custoditi.The important role assigned to the Natural History and Science Museums for the dissemination, preservation and study of science and biodiversity has led to deal with many changes both in the communications and in the management strategies. In order to guarantee the future fruition of the Cultural Heritage the minimum standards required have to be upgraded for developing open archives and databases. Through the results of this survey carried out in 2013 within a PhD research entitled “Management of the Scientific and Natural History Museums collections through the application of infomobility technologies”(Cangemi, 2015), we wish to present the state of the art of the conservation and management of the natural and scientific collections. In particular, the attention has been focused on the use of monitoring tools, rank and methods of inventory and cataloging, and finally on the procedures for indoor and outdoor handling of goods stored in the museums

Management of concomitant coronary artery disease and aortic valve stenosis in the era of transcatheter aortic valve treatment

Severe calcific aortic stenosis (AS) and coronary artery disease (CAD) have common risk factors and are frequently encountered in the same patient in clinical practice. CAD has been reported in ≥ 50% of AS patients undergoing both surgical treatment and transcatheter aortic valve implantation (TAVI). In the last two decades, TAVI has been established as a less invasive alternative to surgery. Recently, more and more young and low surgical risk patients undergo TAVI. Despite the high prevalence of CAD in patients treated with TAVI, the management strategy of concomitant CAD in these patients remains an area of considerable uncertainty. This review provides an updated overview of the current knowledge about this topic and offers points for reflection about the best approach to use