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Background: Prostate cancer (PCa) is a highly heterogeneous disease, making tailored treatment approaches challenging. Magnetic resonance imaging (MRI), notably diffusion‐weighted imaging (DWI) and the derived Apparent Diffusion Coefficient (ADC) maps, plays a crucial role in PCa characterization. In this context, radiomics is a very promising approach able to disclose insights from MRI data. However, the sensitivity of radiomic features to MRI settings, encompassing DWI protocols and multicenter variations, requires the development of robust and generalizable models. Purpose: To develop a comprehensive radiomics framework for noninvasive PCa characterization using ADC maps, focusing on identifying reliable imaging biomarkers against intra‐ and inter‐institution variations. Materials and methods: Two patient cohorts, including an internal cohort (118 PCa patients) used for both training (75%) and hold‐out testing (25%), and an external cohort (50 PCa patients) for independent testing, were employed in the study. DWI images were acquired with three different DWI protocols on two different MRI scanners: two DWI protocols acquired on a 1.5‐T scanner for the internal cohort, and one DWI protocol acquired on a 3‐T scanner for the external cohort. One hundred and seven radiomics features (i.e., shape, first order, texture) were extracted from ADC maps of the whole prostate gland. To address variations in DWI protocols and multicenter variability, a dedicated pipeline, including two‐way ANOVA, sequential‐feature‐selection (SFS), and ComBat features harmonization was implemented. Mann–Whitney U‐tests (α = 0.05) were performed to find statistically significant features dividing patients with different tumor characteristics in terms of Gleason score (GS) and T‐stage. Support‐Vector‐Machine models were then developed to predict GS and T‐stage, and the performance was assessed through the area under the curve (AUC) of receiver‐operating‐characteristic curves. Results: Downstream of ANOVA, two subsets of 38 and 41 features stable against DWI protocol were identified for GS and T‐stage, respectively. Among these, SFS revealed the most predictive features, yielding an AUC of 0.75 (GS) and 0.70 (T‐stage) in the hold‐out test. Employing ComBat harmonization improved the external‐test performance of the GS model, raising AUC from 0.72 to 0.78. Conclusion: By incorporating stable features with a harmonization procedure and validating the model on an external dataset, model robustness, and generalizability were assessed, highlighting the potential of ADC and radiomics for PCa characterization. [ABSTRACT FROM AUTHOR]

Electrical storm (ES) is among the most fearsome events in patients in waiting list for heart transplantation (HT) and catheter ablation (CA) demonstrated to be effective in reduce the arrhythmic burden. However, selection criteria for CA suitability in this specific population have never been addressed before. We retrospectively enrolled 36 patients (mean age 51 ± 8 years; 83% men) waiting HT referred to our department for ES resistant to antiarrhythmic drugs and percutaneous stellate ganglion blockade. Twenty patients were judged suitable for VT ablation according to specific criteria including absence of increased arrhythmic burden secondary to volume overload and hemodynamic decompensation; expected CA outcome favorable due to etiology of the cardiomyopathy, no need for coronary revascularization and technical feasibility of the procedure. The pre‐emptive use of mechanical circulatory supports (MCS) were discussed integrating the PAINESD score with additional clinical and hemodynamic parameters. Acute procedural success was accounted in 85% of cases with only two major complications. The CA group reported lower length of in‐hospital stay after CA suitability evaluation (56 ± 17 vs. 131 ± 64 days, p =.004). Furthermore, at a mean follow‐up of 703 ± 145 days, this group showed reduction of ventricular arrhythmia (VA) recurrence leading to implantable cardioverter defibrillator shock (4 vs. 8, p =.051) and underwent HT with a lower level of urgency (0 vs. 6 patients needed for UNOS1 status upgrade). Respectively, one patient of the CA group and two patients of the conservative group died (p =.839). At the end of follow‐up, eight patients underwent heart transplantation (p =.964) while four patients underwent Left Ventricular Assist device (LVAD) implantation (p =.440). This pilot study should be a proof for further studies exploring CA of VAs as a possible bridge therapy to HT. [ABSTRACT FROM AUTHOR]

This report evaluates the thyroid‐related effects of various active substances and metabolites, categorizing them into Cumulative Assessment Groups (CAGs) based on indicators of hypothyroidism and C‐cell effects. 21 active substances and six metabolites were scrutinized resulting in 18 substances and three metabolites for hypothyroidism (CAG‐TCF) and two substances for C‐cell hypertrophy, hyperplasia, and neoplasia (CAG‐TCP). Detailed NOAEL and LOAEL values were derived for each substance, highlighting differences between current findings and previous assessments. The analysis reveals uncertainties due to variations in data quality and study durations. Overall, the report provides a comprehensive hazard characterization of substances affecting thyroid function, contributing to cumulative risk assessment update for effects on the thyroid. [ABSTRACT FROM AUTHOR]

A new metallohybrid silsesquioxane (S) was synthesized herein from copper and ferricyanide via a cyanide bridge to produce a new electroactive hybrid material (SCuH), which was then characterized by spectroscopic and microscopic techniques and cyclic voltammetry. The voltammetric behavior of SCuH employing a graphite paste electrode indicates a well‐defined redox couple with formal potential Eθ′=0.76±0.01 V. The electrode exhibited high sensitivity to nitrite and was successfully tested for nitrite detection. The linearity of the analytical curve was 2.0×10−4 mol L−1 − 1.0×10−3 mol L−1, with a limit of detection of 2.65×10−5 mol L−1, and sensitivity amperometric value of 57.63 mA/mol L−1. These findings suggest that this material displays exceptional potential for application in electrochemical sensors designed for nitrite detection. [ABSTRACT FROM AUTHOR]

Our society largely relies on inorganic semiconductor devices which are, so far, fabricated using expensive and complex processes requiring ultra‐high vacuum equipment. Here we report on the possibility of growing a p–n junction taking advantage of electrochemical processes based on the use of aqueous solutions. The growth of the junction has been carried out using the Electrochemical Atomic Layer Deposition (E‐ALD) technique, which allowed to sequentially deposit two different semiconductors, CdS and Cu2S, on an Ag(111) substrate, in a single procedure. The growth process was monitored in situ by Surface X‐Ray Diffraction (SXRD) and resulted in the fabrication of a thin double‐layer structure with a high degree of crystallographic order and a well‐defined interface. The high‐performance electrical characteristics of the device were analysed ex‐situ and show the characteristic feature of a diode. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) may have a heterogeneous response to medical/surgical treatments based on endotypes. Data correlating biomarkers and severity of the disease are lacking. We aimed to determine if IL‐5 and calprotectin may be useful in defining severity of disease and identifying uncontrolled patients. Methods: This was a case–control study including 81 patients with diffuse CRSwNP who underwent at least one previous surgery and treated with intranasal steroids. We enrolled 39 uncontrolled patients (SNOT‐22 ≥ 40 and two or more cycles of systemic corticosteroids in last year) (Group A) and 42 controlled one (SNOT‐22 < 40 and less than two cycles of systemic corticosteroids in last year) (Group B). We analyzed IL‐5 and calprotectin in both nasal secretions and nasal polyp tissue. Results: Calprotectin and IL‐5 were significantly higher in Group A in both secretions and tissue, and the higher the number of previous surgeries, the higher the levels detected in nasal secretions. At univariate analyses, smoking, asthma, non‐steroidal anti‐inflammatory drugs‐exacerbated respiratory disease (NSAID‐ERD), blood eosinophilia, neutrophils, and eosinophils at nasal cytology were significantly associated with uncontrolled disease. Multivariate analyses showed that asthma, NSAID‐ERD, and IL‐5 in nasal secretion/polyp tissue were significantly related to the risk of uncontrolled disease. Conclusions: Our data suggest that asthma, NSAID‐ERD, and IL‐5 in nasal secretions/tissue may be helpful to identify more severe patients, as they are related to the risk of uncontrolled disease. Nonetheless, high levels of calprotectin and neutrophilia were also observed in uncontrolled patients, especially after multiple surgeries. [ABSTRACT FROM AUTHOR]

Background & Aims: Chronic hepatitis D virus (HDV) often leads to end-stage liver disease and hepatocellular carcinoma (HCC). Comprehensive data pertaining to large populations with HDV and HCC are missing, therefore we sought to assess the characteristics, management, and outcome of these patients, comparing them to patients with hepatitis B virus (HBV) infection. Methods: We analysed the Italian Liver Cancer database focusing on patients with positivity for HBV surface antigen and anti-HDV antibodies (HBV/HDV, n = 107) and patients with HBV infection alone (n = 588). Clinical and oncological characteristics, treatment, and survival were compared in the two groups. Results: Patients with HBV/HDV had worse liver function [Model for End-stage Liver Disease score: 11 vs. 9, p<.0001; Child-Turcotte-Pugh score: 7 vs. 5, p<.0001] than patients with HBV. HCC was more frequently diagnosed during surveillance (72.9% vs. 52.4%, p = .0002), and the oncological stage was more frequently Milan-in (67.3% vs. 52.7%, p = .005) in patients with HBV/HDV. Liver transplantation was more frequently performed in HBV/HDV than in HBV patients (36.4% vs. 9.5%), while the opposite was observed for resection (8.4% vs. 20.1%, p<.0001), and in a competing risk analysis, HBV/HDV patients had a higher probability of receiving transplantation, independently of liver function and oncological stage. A trend towards longer survival was observed in patients with HBV/HDV (50.4 vs. 44.4months, p = .106). Conclusions: In patients with HBV/HDV, HCC is diagnosed more frequently during surveillance, resulting in a less advanced cancer stage in patients with more deranged liver function than HBV alone. Patients with HBV/HDV have a heightened benefit from liver transplantation, positively influencing survival. [ABSTRACT FROM AUTHOR]

Background: Late‐onset pain is frequent following COVID‐19, and many pathogenetic mechanisms have been proposed. Identifying the main features of patients may help in designing tailored rehabilitative interventions. Methods: We enrolled post‐COVID‐19 patients with an increase in pain intensity of two points on the COVID‐19 Yorkshire Rehabilitation Scale (C19‐YRS) at 52 weeks compared to the pre‐COVID‐19 condition. All subjects were retrospectively monitored at 12, 26, and 52 weeks. A specific pain assessment was performed to determine the characteristics and mechanisms of pain. Catastrophizing, kinesiophobia, and other psychological symptoms were evaluated. The pressure pain threshold (PPT) and temporal summation (TS) were measured and compared in age‐ and sex‐matched healthy controls to analyse pain characteristics. Results: A total of 67 patients were recruited, with 20 of them presenting an increase in pain at 52 weeks. Subjects of the two subgroups were similar in demographic and clinical characteristics at baseline; significant differences in fatigue, anxiety, mobility, ability to perform daily activities, and general health perception were recorded at 26 weeks. Fatigue significantly predicted pain onset (β = 0.54, p = 0.002). Sixteen different body regions were identified as painful, with a pain intensity of 6.0 ± 1.9. Most of the samples did not show neuropathic or nociplastic mechanisms. No differences in PPT and TS were recorded between patients and healthy controls. Conclusions: Almost one out of three patients hospitalized for COVID‐19 developed pain 1 year later, and fatigue seems responsible for chronicity. An overlapping of conditions may explain late‐onset post‐COVID‐19 pain, and a comprehensive approach must be considered for patient management. Significance: Late‐onset pain is frequent in post‐COVID‐19 syndrome and an overlapping of different mechanisms seems to be responsible for its development. Among many predisposing factors, fatigue in the months before seems to be one of the primary causes of pain one year following infection and its management may help to identify new strategies for prevention and treatment of late‐onset pain. [ABSTRACT FROM AUTHOR]

A new full model of the atmospheric transport of cosmogenic 10Be is presented based on the specialized SOCOL‐AERv2‐BE chemistry‐climate model coupled with the CRAC:10Be isotope production model. The model includes all the relevant atmospheric processes and allows computing the isotope concentration at any given location and time. The full model is directly compared with 10Be isotope measurements in five Antarctic and Greenland ice cores for the period 1980–2007. The model reasonably well reproduces the average concentration and solar‐cycle dependency or the lack of it for most observational sites but does not perfectly catch the interannual variability at sites with complex orography likely due to the coarse model grid. This implies that the model correctly reproduces the large‐scale atmospheric dynamics but effectively averages out synoptic‐scale variability. It is found that the dominant source of 10Be is located in the middle stratosphere (25–40 km), in the tropical (<30° latitudes) and polar (>60°) regions, as produced by galactic cosmic rays and solar energetic particles, respectively. It is shown that >60% (90%) of 10Be produced in the atmosphere reaches the Earth's surface within one (two) years, respectively. For practical purposes, a simple parameterization of the full‐model results is presented which agrees with the full model within 20% in polar regions. This parameterization allows one to make a quick estimate of near‐ground 10Be concentrations based only on production rates without heavy calculations. This practical approach can be applied to studies of solar and geomagnetic variability using cosmogenic isotopes. Key Points: A full model of production and atmospheric transport of 10Be produced by galactic cosmic ray (GCR) and solar energetic particles (SEP) is presented and validatedThe dominant source regions of 10Be in polar ice are identified as tropical and polar stratosphere for GCR and SEPs, respectivelyAn easy‐to‐use parameterization of the full model is proposed to study cosmic‐ray variability with 10Be data [ABSTRACT FROM AUTHOR]

Objective: Although disparities have been described in epilepsy care, their contribution to status epilepticus (SE) and associated outcomes remains understudied. Methods: We used the 2010–2019 National Inpatient Sample to identify SE hospitalizations using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM)/ICD‐10‐CM codes. SE prevalence was stratified by demographics. Logistic regression was used to assess factors associated with electroencephalographic (EEG) monitoring, intubation, tracheostomy, gastrostomy, and mortality. Results: There were 486 861 SE hospitalizations (2010–2019), primarily at urban teaching hospitals (71.3%). SE prevalence per 10 000 admissions was 27.3 for non‐Hispanic (NH)‐Blacks, 16.1 for NH‐Others, 15.8 for Hispanics, and 13.7 for NH‐Whites (p <.01). SE prevalence was higher in the lowest (18.7) compared to highest income quartile (18.7 vs. 14, p <.01). Older age was associated with intubation, tracheostomy, gastrostomy, and in‐hospital mortality. Those ≥80 years old had the highest odds of intubation (odds ratio [OR] = 1.5, 95% confidence interval [CI] = 1.43–1.58), tracheostomy (OR = 2, 95% CI = 1.75–2.27), gastrostomy (OR = 3.37, 95% CI = 2.97–3.83), and in‐hospital mortality (OR = 6.51, 95% CI = 5.95–7.13). Minority populations (NH‐Black, NH‐Other, and Hispanic) had higher odds of tracheostomy and gastrostomy compared to NH‐White populations. NH‐Black people had the highest odds of tracheostomy (OR = 1.7, 95% CI = 1.57–1.86) and gastrostomy (OR = 1.78, 95% CI = 1.65–1.92). The odds of receiving EEG monitoring rose progressively with higher income quartile (OR = 1.47, 95% CI = 1.34–1.62 for the highest income quartile) and was higher for those in urban teaching compared to rural hospitals (OR = 12.72, 95% CI = 8.92–18.14). Odds of mortality were lower (compared to NH‐Whites) in NH‐Blacks (OR =.71, 95% CI =.67–.75), Hispanics (OR =.82, 95% CI =.76–.89), and those in the highest income quartiles (OR =.9, 95% CI =.84–.97). Significance: Disparities exist in SE prevalence, tracheostomy, and gastrostomy utilization across age, race/ethnicity, and income. Older age and lower income are also associated with mortality. Access to EEG monitoring is modulated by income and urban teaching hospital status. Older adults, racial/ethnic minorities, and populations of lower income or rural location may represent vulnerable populations meriting increased attention to improve health outcomes and reduce disparities. [ABSTRACT FROM AUTHOR]

Background: Robotic C‐arm cone‐beam computed tomography (CBCT) scanners provide fast in‐room imaging in radiotherapy. Their mobility extends beyond performing a gantry rotation, but they might encounter obstructions to their motion which limit the gantry angle range. The axial field‐of‐view (FOV) of a reconstructed CBCT image depends on the acquisition geometry. When imaging a large anatomical location, such as the thorax, abdomen, or pelvis, a centered cone beam might be insufficient to acquire untruncated projection images. Some CBCT scanners can laterally displace their detector and collimate the beam to increase the FOV, but the gantry must then perform a 360∘$360^{\circ}$ rotation to provide complete data for reconstruction. Purpose: To extend the FOV of a CBCT image with a single short scan (gantry angle range of 180∘+$180^{\circ}+$ fan angle) using two complementary short scans. Methods: We defined an acquisition protocol using two short scans during which the source follows the same trajectory and where the detector has equal and opposite tilt and/or offset between the two scans, which we refer to as complementary scans. We created virtual acquisitions using a Monte Carlo simulator on a digital anthropomorphic phantom and on a computed tomography (CT) scan of a patient abdomen. For our proposed method, each simulation produced two complementary sets of projections, which were weighted for redundancies and used to reconstruct one CBCT image. We compared the resulting images to the ground truth phantoms and simulations of conventional scans. Results: Reconstruction artifacts were slightly more prominent in the complementary scans w.r.t. a complete scan with untruncated projections but matched those in a single short scan without truncation. When analyzing reconstructed scans from simulated projections with scatter and corrected with prior CT information, we found a global agreement between complementary and conventional scan approaches. Conclusions: When dealing with a limited range of motion of the gantry of a CBCT scanner, two complementary short scans are a technically valid alternative to a full 360∘$^{\circ}$ scan with equal FOV. This approach enables FOV extension without collisions or hardware upgrades. [ABSTRACT FROM AUTHOR]

Background: Left ventricular assist device (L‐VAD) implantation is increasingly used in patients with heart failure (HF) and most patients also have an implantable cardioverter defibrillator (ICD). Limited data are available on the incidence of ICD therapies and complications in this special setting. The aim of this study was to analyze the real‐world incidence and predictors of ICD therapies, complications and interactions between ICD and L‐VAD. Methods: We conducted a multicenter retrospective observational study in patients with advanced HF implanted with ICD and a continuous‐flow L‐VAD, followed‐up in five advanced HF centers in Northern Italy. Results: A total of 234 patients (89.7% male, median age 59, 48.3% with ischemic etiology) were enrolled. After a median follow‐up of 21 months, 66 patients (28.2%) experienced an appropriate ICD therapy, 22 patients (9.4%) an inappropriate ICD therapy, and 17 patients (7.3%) suffered from an interaction between ICD and L‐VAD. The composite outcome of all ICD‐related complications was reported in 41 patients (17.5%), and 121 (51.7%) experienced an L‐VAD‐related complication. At multivariable analysis, an active ventricular tachycardia (VT) zone and a prior ICD generator replacement were independent predictors of ICD therapies and of total ICD‐related complications, respectively. Conclusions: Real‐world patients with both L‐VAD and ICD experience a high rate of ICD therapies and complications. Our findings suggest the importance of tailoring device programming in order to minimize the incidence of unnecessary ICD therapies, thus sparing the need for ICD generator replacement, a procedure associated to a high risk of complications. [ABSTRACT FROM AUTHOR]

Key Clinical Message: A 46‐year‐old woman with congenitally corrected transposition of the great arteries (ccTGA) associated with dextrocardia, situs viscerus inversus, and left superior vena cava persistence presented with an incessant supraventricular tachycardia. Electrophysiological study was not conclusive in differential diagnosis of atrial tachycardia versus atypical atrioventricular (AV) nodal reentrant tachycardia, also due to the unconventional anatomy of the coronary sinus. By a comprehensive mapping of cardiac chambers, a double side slow‐pathway was localized in both atrial chambers and subsequently ablated by radiofrequency delivery without tachycardia changes. Aortic root and cusps were devoid of electrical activity. The muscular part of the sub‐pulmonary ventricle at the level of interatrial septum showed an earliest activation signal of −90 ms and ablation of this site was effective in abolish the tachycardia. This is the first case to report technical concerns of septal atrial tachycardia ablation in ccTGA associated with multiple anatomical malformations. Moreover, some peculiarities have been reported for the first time including the presence of double‐side AV nodal slow‐pathway and atypical localization of the tachycardia origin into the muscular part of the sub‐pulmonary ventricle instead of posterior pulmonary cusp. [ABSTRACT FROM AUTHOR]

Background: Although antioxidants are largely used in subfertile men with oligo‐astheno‐teratozoospermia (OAT), the choice among different molecules is challenged by the lack of comparative head‐to‐head studies. The network meta‐analysis (NMA) can overcome limitations of pairwise meta‐analyses, since it incorporates direct and indirect evidence into a single model generating an effectiveness hierarchy. Objective: To assess with a NMA the effects of antioxidants in improving seminal parameters in idiopathic OAT. Materials and methods: PubMed, Scopus, Cinahl, and Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing any antioxidant treatment to each other or placebo in men with at least one idiopathic seminal abnormality. Data were included in a random‐effects NMA, where efficacy of treatments was ranked by surface under the cumulative ranking curve (SUCRA). Results: 29 RCTs provided information on 2045 men (mean age: 33.5 years) with idiopathic OAT and 19 antioxidant preparations. Compared to placebo, l‐carnitine, especially in combination with l‐acetyl‐carnitine (LAC), had the highest SUCRA for sperm concentration, progressive motility, and morphology. Folate was the only other compound effective on sperm concentration. Vitamin E+selenium or zinc had the highest SUCRA for total motility. A contribution on progressive motility was revealed for pentoxifylline and vitamin E+CoQ10. [ABSTRACT FROM AUTHOR]

Context: Mortality in type 2 diabetes is twice that of the normoglycemic population. Unravelling biomarkers that identify high‐risk patients for referral to the most aggressive and costly prevention strategies is needed. Objective: To validate in type 2 diabetes the association with all‐cause mortality of a 14‐metabolite score (14‐MS) previously reported in the general population and whether this score can be used to improve well‐established mortality prediction models. Methods: This is a sub‐study consisting of 600 patients from the "Sapienza University Mortality and Morbidity Event Rate" (SUMMER) study in diabetes, a prospective multicentre investigation on all‐cause mortality in patients with type 2 diabetes. Metabolic biomarkers were quantified from serum samples using high‐throughput proton nuclear magnetic resonance metabolomics. Results: In type 2 diabetes, the 14–MS showed a significant (p < 0.0001) association with mortality, which was lower (p < 0.0001) than that reported in the general population. This difference was mainly due to two metabolites (histidine and ratio of polyunsaturated fatty acids to total fatty acids) with an effect size that was significantly (p = 0.01) lower in diabetes than in the general population. A parsimonious 12‐MS (i.e. lacking the 2 metabolites mentioned above) improved patient discrimination and classification of two well‐established mortality prediction models (p < 0.0001 for all measures). Conclusions: The metabolomic signature of mortality in the general population is only partially effective in type 2 diabetes. Prediction markers developed and validated in the general population must be revalidated if they are to be used in patients with diabetes. [ABSTRACT FROM AUTHOR]

Introduction: We examined data from a large, high acuity, pediatric psychiatric emergency department (ED) to assess both the immediate and longer‐term impact of the pandemic on ED visits for suicidal thoughts and behaviors (STBs) among youth. Methods: Youth ages 5–17 years presenting at a pediatric psychiatric ED in New York, NY from March 2019–November 2021 were included in this study. Visits were categorized as pre‐pandemic, pandemic year 1, or pandemic year 2. We examined changes in demographic and clinical characteristics among patients presenting across the three time periods, as well as multivariable associations between these characteristics and STBs. Results: Over 32 months, 2728 patients presented at 4161 visits. The prevalence of a discharge diagnosis of STBs increased from 21.2% pre‐pandemic to 26.3% (p < 0.001) during pandemic year 1, and further increased to 30.1% (p = 0.049) during pandemic year 2. Youth were 21% more likely to receive a discharge diagnosis of STBs in pandemic year 1 (RR 1.21, 95% CI 1.07, 1.36) and 35% more likely in pandemic year 2 (RR 1.35, 95% CI 1.19, 1.52) compared to pre‐pandemic baseline. Conclusions: In a large, high‐acuity ED, STBs continued to increase 20 months after the initial COVID‐19 lockdown. These findings highlight the persistent detrimental impact of the pandemic on youth mental health. [ABSTRACT FROM AUTHOR]

Effective bone substitute biomaterials remain an important challenge in patients with large bone defects. Glass ceramics produced by different synthesis routes may result in changes in the material physicochemical properties and consequently affect the success or failure of the bone healing response. To investigate the differences in the orchestration of the inflammatory and healing process in bone grafting and repair using different glass–ceramic routes production. Thirty male Wistar rats underwent surgical unilateral parietal defects filled with silicate glass–ceramic produced by distinct routes: BS – particulate glass–ceramic produced via the fusion/solidification route, and BG – particulate glass–ceramic produced via the sol–gel route. After 7, 14, and 21 days from biomaterial grafting, parietal bones were removed to be analyzed under H&E and Massons' Trichome staining, and immunohistochemistry for CD206, iNOS, and TGF‐β. Our findings demonstrated that the density of lymphocytes and plasma cells was significantly higher in the BS group at 45, and 7 days compared to the BG group, respectively. Furthermore, a significant increase of foreign body giant cells (FBGCs) in the BG group at day 7, compared to BS was found, demonstrating early efficient recruitment of FBGCs against sol–gel‐derived glass–ceramic particulate (BS group). According to macrophage profiles, CD206+ macrophages enhanced at the final periods of both groups, being significantly higher at 45 days of BS compared to the BG group. On the other hand, the density of transformation growth factor beta (TGF‐β) positive cells on 21 days were the highest in BG, and the lowest in the BS group, demonstrating a differential synergy among groups. Noteworthy, TGF‐β+ cells were significantly higher at 21 days of BG compared to the BS group. Glass–ceramic biomaterials can act differently in the biological process of bone remodeling due to their route production, being the sol–gel route more efficient to activate M2 macrophages and specific FBGCs compared to the traditional route. Altogether, these features lead to a better understanding of the effectiveness of inflammatory response for biomaterial degradation and provide new insights for further preclinical and clinical studies involved in bone healing. [ABSTRACT FROM AUTHOR]

Background and Aims: Hepatocellular carcinoma (HCC) recurrence is common in patients treated with liver resection (LR). In this study, we aimed to evaluate the incidence and preoperative predictors of non‐transplantable recurrence in patients with single HCC ≤5 cm treated with frontline LR. Methods: From the Italian Liver Cancer (ITA.LI.CA) database, 512 patients receiving frontline LR for single HCC ≤5 cm were retrieved. Incidence and predictors of recurrence beyond Milan criteria (MC) and up‐to‐seven criteria were compared between patients with HCC <4 and ≥4 cm. Results: During a median follow‐up of 4.2 years, the overall recurrence rate was 55.9%. In the ≥4 cm group, a significantly higher proportion of patients recurred beyond MC at first recurrence (28.9% vs. 14.1%; p < 0.001) and overall (44.4% vs. 25.2%; p < 0.001). Similar results were found considering recurrence beyond up‐to‐seven criteria. Compared to those with larger tumours, patients with HCC <4 cm had a longer recurrence‐free survival and overall survival. HCC size ≥4 cm and high alpha‐fetoprotein (AFP) level at the time of LR were independent predictors of recurrence beyond MC (and up‐to‐seven criteria). In the subgroup of patients with available histologic information (n = 354), microvascular invasion and microsatellite lesions were identified as additional independent risk factors for non‐transplantable recurrence. Conclusions: Despite the high recurrence rate, LR for single HCC ≤5 cm offers excellent long‐term survival. Non‐transplantable recurrence is predicted by HCC size and AFP levels, among pre‐operatively available variables. High‐risk patients could be considered for frontline LT or listed for transplantation even before recurrence. [ABSTRACT FROM AUTHOR]

Glycated haemoglobin in the first year after diagnosis of type 1 diabetes is an independent risk factor for diabetic retinopathy: The IMDIAB 25 years follow-up study Effect of intensive diabetes therapy on the progression of diabetic retinopathy in patients with type 1 diabetes: 18 years of follow-up in the DCCT/EDIC. Keywords: HbA1c; metabolic memory; retinopathy; type 1 diabetes EN HbA1c metabolic memory retinopathy type 1 diabetes 3415 3419 5 10/05/23 20231101 NES 231101 BACKGROUND Intensive glycaemic control lowers the risk of microvascular complications.[1] This effect has been shown to persist for up to 18 years of follow-up.[[2], [4]] Whether the glycaemic control obtained during the first months after type 1 diabetes (T1D) onset has an impact on the future risk of chronic complications has not been clarified. Linear regression models were used to test the presence of any association between HbA1c at diabetes onset, mean-first-year HbA1c and HbA1c measured at last follow-up and to test baseline features associated with first-year HbA1c. [Extracted from the article]

Background and Purpose: Nociplastic pain due to central sensitization (CS) is common in people suffering from chronic pain, but no clinical practice guideline is available in rehabilitative settings for patients' management. The aim of this study is to achieve expert consensus on physiotherapy competencies in the management of people with nociplastic pain and suspected CS mechanisms. Methods: A web‐based Delphi process was employed. Experts in the rehabilitation field were recruited following pre‐defined eligibility criteria. Following completion of three Delphi rounds, the final list of competencies was generated. Results: In all, 23 participants were recruited. They all completed Round 1 (23/23, 100%), twenty Round 2 and Round 3 (20/23, 87%). Following Round 1, seven areas were identified by the panel as crucial for CS physiotherapy management; 19 competencies out of 40 reached the consensus between experts, and nine additional competencies were added to Round 2 following literary review. Round 2 identified the agreement for all the 29 competencies. During Round 3, all the experts confirmed the final list generated through the consensus process. Discussion: An agreement between experts was found for the final list of competencies that a physiotherapist should implement every time it approaches people with suspected CS mechanisms. Further research is needed to support the clinical utility of our findings and their applicability in daily practice. [ABSTRACT FROM AUTHOR]

Background: Although selective estrogen receptor modulators have been proposed as a treatment for men with central functional hypogonadism, only a few data have been produced in men with obesity‐related functional androgen deficiency. Objective: To determine whether and to what extent selective estrogen receptor modulators are an effective and safe therapy in men with obesity‐related functional androgen deficiency. Materials and methods: A thorough search of PubMed, Web of Science, Scopus, and Cochrane Library databases was performed to identify studies comparing testosterone levels before and after treatment. Mean differences with 95% coefficient intervals were combined using random effects models. Funnel plot, Egger's test, and trim‐and‐fill analysis were used to assess publication bias. Results: Seven studies met the inclusion criteria providing information on 292 men with obesity‐related functional androgen deficiency treated with clomiphene citrate (12.5–50 mg daily) or enclomiphene citrate (12.5–25 mg daily) for 1.5–4 months. The pooled estimates indicated a significant increase in testosterone levels both with clomiphene (mean difference: 11.56 nmol/L; 95% coefficient interval: 9.68, 13.43; I2 = 69%, pfor heterogeneity = 0.01) and enclomiphene citrate (mean difference: 7.50 nmol/L; 95% coefficient interval: 6.52, 8.48; I2 = 4%, pfor heterogeneity = 0.37). After the exclusion of one study on severely obese men, who exhibited the highest response rate to clomiphene citrate, the heterogeneity disappeared (mean difference: 10.27 nmol/L; 95% coefficient interval: 9.39, 11.16; I2 = 0%, pfor heterogeneity = 0.66). No publication bias was revealed by Egger's test and trim‐and‐fill analysis. No treatment‐related unexpected findings regarding safety profile were registered. Discussion and conclusion: Treatment with clomiphene citrate and enclomiphene citrate may be an effective and safe alternative to testosterone replacement therapy in men with obesity‐related functional androgen deficiency. Further long‐term studies are warranted to define clinical reflections of the selective estrogen receptor modulators‐induced increase in testosterone levels and to better clarify the safety profile. [ABSTRACT FROM AUTHOR]

Background: Triple‐negative breast cancer (TNBC) is the neoplasia most associated with BRCA1 germline pathogenic variants (PV) and is more likely to develop metastases than the other breast cancer (BC) subtypes, mainly in the lungs and the central nervous system (CNS). Recently, BRCA2 carriers were shown to have a higher risk for developing CNS metastases. However, the patterns of recurrence and metastases of BRCA2 carriers with TNBC are unknown. Methods: TNBC patient data attending the A.C. Camargo Cancer Center, from 1998 through 2020, were verified either by medical records or by BRCA1/2 genetic testing carried out. Multivariable logistic regression models were fit to the data to assess the independent factors for bone and CNS metastases. Adjustment was done using all independent variables with p < 0.2 in the univariable Cox model to describe the relationship between the independent variables until time of death. Results: A total of 388 TNBC patients were evaluated. We identified PV in BRCA1/2 genes in 21% (82/388), being 17.7% (69/388) in BRCA1 and only 3.3% (13/388) in BRCA2. A total of 120 patients (31%) developed distant metastases. Bone or CNS metastases were observed in 40% and 60% of BRCA2 PV carriers (p = 0.155), respectively. The BRCA2 carriers tended to have a higher likelihood of developing bone metastases (OR, 4.06; 95% CI, 0.82–20.01; p = 0.085), when compared to BRCA1 carriers (OR, 0.6; 95% CI, 0.12–2.87; p = 0.528). BRCA2 carriers had an OR of 1.75 (95% CI, 0.33–9.14; p = 0.503) for CNS metastasis development, while BRCA1 carriers had an OR of 0.72 (95% CI, 0.23–2.23; p = 0.574). Conclusions: Patients with TNBC and PV in the BRCA2 gene had higher frequencies of secondary bone involvement and CNS in the course of the disease. However, the BRCA2 PV did not represent an independent outcome predictor of metastases and overall survival. Efforts to increase the number of BRCA2 carriers among TNBC patients are crucial for determining their risk of developing bone and CNS metastases compared to BRCA2 noncarriers. [ABSTRACT FROM AUTHOR]

Background: Novel biomarkers of vascular disease in diabetes could help identify new mechanistic pathways. Osteocalcin, osteoprotegerin, and osteopontin are key molecules involved in bone and vascular calcification processes, both of which are compromised in diabetes. We aimed to evaluate possible associations of osteocalcin, osteoprotegerin, and osteopontin with cardiovascular disease (CVD) and diabetic retinopathy (DR) among people with type 2 diabetes (T2D). Materials and Methods: Osteocalcin, osteoprotegerin, and osteopontin concentrations were measured at enrolment in 848 participants with T2D from the Sapienza University Mortality and Morbidity Event Rate (SUMMER) Study (ClinicalTrials.gov: NCT02311244). Logistic regression models and propensity score matching were used to assess possible associations of osteocalcin, osteoprotegerin, and osteopontin with a history of CVD and with evidence of any grade of DR adjusting for confounders. Results: Previous CVD was reported in 139 (16.4%) participants, while 144 (17.0%) had DR. After adjusting for possible confounders, osteocalcin but not osteoprotegerin or osteopontin concentrations were associated with a history of CVD (Odds Ratio [OR] and 95% CI for one standard deviation (SD) increase in osteocalcin concentrations (natural log): 1.35 (1.06–1.72), p = 0.014). Associations with prevalent DR were seen for osteoprotegerin (OR for one SD increase in osteoprotegerin concentrations (natural log): 1.25 (1.01–1.55), p = 0.047) and osteopontin (OR for one SD increase in osteopontin concentrations (natural log): 1.25 (1.02–1.53), p = 0.022), but not osteocalcin. Conclusions: In T2D, higher serum osteocalcin concentrations are associated with macrovascular complications and higher osteoprotegerin and osteopontin concentrations with microvascular complications, suggesting that these osteokines might be involved in pathways directly related to vascular disease. [ABSTRACT FROM AUTHOR]

Purpose: To define an optimal set of b‐values for accurate derivation of diffusion MRI parameters in the brain with segmented Intravoxel Incoherent Motion (IVIM) model. Methods: Simulations of diffusion signals were performed to define an optimal set of b‐values targeting different perfusion regimes, by relying on an optimization procedure which minimizes the total relative error on estimated IVIM parameters computed with a segmented fitting procedure. Then, the optimal b‐values set was acquired in vivo on healthy subjects and skull base chordoma patients to compare the optimized protocol with a clinical one. Results: The total relative error on simulations decreased of about 40% when adopting the optimal set of 13 b‐values (0 10 20 40 50 60 200 300 400 1200 1300 1400 1500 s/mm2), showing significant differences and increased precision on D and f estimates with respect to simulations with a non‐optimized b‐values set. Similarly, in vivo acquisitions demonstrated a dependency of IVIM parameters on the b‐values array, with differences between the optimal set of b‐values and a clinical non‐optimized acquisition. IVIM parameters were compatible to literature values, with D (0.679/0.701 [0.022/0.008] ·10−3mm2/s), f (5.49/5.80 [0.70/1.14] %), and D* (8.25/7.67 [0.92/0.83] ·10−3mm2/s) median [interquartile range] estimates for white matter/gray matter in volunteers and D (0.709/0.715/1.06 [0.035/0.023/0.271] ·10−3mm2/s), f (7.08/7.84/21.54 [1.20/1.06/6.05] %), and D* (10.85/11.84/2.32 [1.38/2.32/4.94] ·10−3mm2/s) for white matter/gray matter/Gross Tumor Volume in patients with skull‐base chordoma tumor. Conclusions: The definition of an optimal b‐values set can improve the estimation of quantitative IVIM parameters. This allows setting up an optimized approach that can be adopted for IVIM studies in the brain. [ABSTRACT FROM AUTHOR]

Background: Quantitative imaging such as Diffusion‐Weighted MRI (DW‐MRI) can be exploited to non‐invasively derive patient‐specific tumor microstructure information for tumor characterization and local recurrence risk prediction in radiotherapy. Purpose: To characterize tumor microstructure according to proliferative capacity and predict local recurrence through microstructural markers derived from pre‐treatment conventional DW‐MRI, in skull‐base chordoma (SBC) patients treated with proton (PT) and carbon ion (CIRT) radiotherapy. Methods: Forty‐eight patients affected by SBC, who underwent conventional DW‐MRI before treatment and were enrolled for CIRT (n = 25) or PT (n = 23), were retrospectively selected. Clinically verified local recurrence information (LR) and histological information (Ki‐67, proliferation index) were collected. Apparent diffusion coefficient (ADC) maps were calculated from pre‐treatment DW‐MRI and, from these, a set of microstructural parameters (cellular radius R, volume fraction vf, diffusion D) were derived by applying a fine‐tuning procedure to a framework employing Monte Carlo simulations on synthetic cell substrates. In addition, apparent cellularity (ρapp) was estimated from vf and R for an easier clinical interpretation. Histogram‐based metrics (mean, median, variance, entropy) from estimated parameters were considered to investigate differences (Mann‐Whitney U‐test, α = 0.05) in estimated tumor microstructure in SBCs characterized by low or high cell proliferation (Ki‐67). Recurrence‐free survival analyses were also performed to assess the ability of the microstructural parameters to stratify patients according to the risk of local recurrence (Kaplan‐Meier curves, log‐rank test α = 0.05). Results: Refined microstructural markers revealed optimal capabilities in discriminating patients according to cell proliferation, achieving best results with mean values (p‐values were 0.0383, 0.0284, 0.0284, 0.0468, and 0.0088 for ADC, R, vf, D, and ρapp, respectively). Recurrence‐free survival analyses showed significant differences between populations at high and low risk of local recurrence as stratified by entropy values of estimated microstructural parameters (p = 0.0110). Conclusion: Patient‐specific microstructural information was non‐invasively derived providing potentially useful tools for SBC treatment personalization and optimization in particle therapy. [ABSTRACT FROM AUTHOR]

Introduction: Thoracic impedance (TI) drops measured by implantable cardioverter‐defibrillators (ICDs) have been reported to correlate with ventricular tachycardia/fibrillation (VT/VF). The aim of our study was to assess the temporal association of decreasing TI trends with VT/VF episodes through a longitudinal analysis of daily remote monitoring data from ICDs and cardiac resynchronization therapy defibrillators (CRT‐Ds). Methods and Results: Retrospective data from 2384 patients were randomized 1:1 into a derivation or validation cohort. The TI decrease rate was defined as the percentage of rolling weeks with a continuously decreasing TI trend. The derivation cohort was used to determine a TI decrease rate threshold for a ≥99% specificity of arrhythmia prediction. The associated risk of VT/VF episodes was estimated in the validation cohort by dividing the available follow‐up into 60‐day assessment intervals. Analyses were performed separately for 1354 ICD and 1030 CRT‐D patients. During a median follow‐up of 2.0 years, 727 patients (30.4%) experienced 3298 confirmed VT/VF episodes. In the ICD group, a TI decrease rate of >60% was associated with a higher risk of VT/VF episode in a 60‐day assessment interval (stratified hazard ratio, 1.42; 95% confidence interval (CI), 1.05–1.92; p =.023). The TI decrease preceded (40.8%) or followed (59.2%) the VT/VF episodes. In the CRT‐D group, no association between TI decrease and VT/VF episodes was observed (p =.84). Conclusion: In our longitudinal analysis, TI decrease was associated with VT/VF episodes only in ICD patients. Preventive interventions may be difficult since episodes can occur before or after TI decrease. [ABSTRACT FROM AUTHOR]

Objective: The Liebowitz Social Anxiety Scale‐Self Report (LSAS‐SR) is a self‐report measure of social anxiety (SA), which has shown adequate psychometric properties across cultures. However, no study has systematically evaluated its measurement invariance (MI) between (a) individuals with and without a diagnosis of social anxiety disorder (SAD) and (b) males and females. The current study addresses this issue. Methods: We collected data on 257 (158 females) Italian individuals diagnosed with SAD and 356 (232 females) community‐dwelling adults. Results: We initially found support for the unidimensionality of the Italian LSAS‐SR measurement model in all samples. Using the Graded Response Model, we obtained evidence of partial MI and differential item functioning between community‐dwelling and SAD‐diagnosed individuals and evidence of strong MI between male and female participants. Conclusions: The results of this study suggest that the Italian LSAS‐SR measures the same trait in the same way across the symptom continuum and sexes, making it a psychometrically sound tool for assessment, screening, and research purposes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the static magnetic field generated by a proton pencil beam as a candidate for range verification bymeans of Monte Carlo simulations, thereby improving upon existing analytical calculations. We focus on the impact of statistical current fluctuations and secondary protons and electrons. Methods:We considered a pulsed beam (10 µs pulse duration) during the duty cycle with a peak beam current of 0.2 µA and an initial energy of 100 MeV. We ran Geant4-DNA Monte Carlo simulations of a proton pencil beam in water and extracted independent particle phase spaces. We calculated longitudinal and radial current density of protons and electrons, serving as an input for a magnetic field estimation based on a finite element analysis in a cylindrical geometry. We made sure to allow for non-solenoidal current densities as is the case of a stopping proton beam. Results: The rising proton charge density toward the range is not perturbed by energy straggling and only lowered through nuclear reactions by up to 15%, leading to an approximately constant longitudinal current. Their relative low density however (at most 0.37 protons/mm3 for the 0.2 µA current and a beam cross-section of 2.5 mm), gives rise to considerable current density fluctuations. The radial proton current resulting from lateral scattering and being two orders of magnitude weaker than the longitudinal current is subject to even stronger fluctuations. Secondary electrons with energies above 10 eV, that far outnumber the primary protons, reduce the primary proton current by only 10% due to their largely isotropic flow. A small fraction of electrons (< 1%), undergoing head-on collisions, constitutes the relevant electron current. In the far-field, both contributions to the magnetic field strength (longitudinal and lateral) are independent of the beam spot size. We also find that the nuclear reaction-related losses cause a shift of 1.3mmto the magnetic field profile relative to the actual range, which is further enlarged to 2.4 mm by the electron current (at a distance of = 50 mm away from the central beam axis). For 1 > 45 mm, the shift increases linearly. While the current density variations cause significant magnetic field uncertainty close to the central beam axis with a relative standard deviation (RSD) close to 100%, they average out at a distance of 10 cm, where the RSD of the total magnetic field drops below 2%. Conclusions: With the small influence of the secondary electrons together with the low RSD, our analysis encourages an experimental detection of the magnetic field through sensitive instrumentation, such as optical magnetometry or SQUIDs. Conclusions: With the small influence of the secondary electrons together with the low RSD, our analysis encourages an experimental detection of the magnetic field through sensitive instrumentation, such as optical magnetometry or SQUIDs. [ABSTRACT FROM AUTHOR]

Proteolysis‐targeting chimeras (PROTACs) are novel therapeutics for the treatment of human disease. They exploit the enormous potential of the E3 ligases, a class of proteins that mark a target protein for degradation via the ubiquitin–proteasome system. Despite the existence of several E3 ligase‐related databases, the choice of the functioning ligase is limited to only 1.6% of those available, probably due to the fragmentary understanding of their structures and their known ligands; in fact, none of the existing databases report detailed studies covering their 3D structure or their pockets. Here, we report ELIOT (E3 LIgase pocketOme navigaTor), an accurate and complete platform containing the E3 ligase pocketome to enable navigation and selection of new E3 ligases and new ligands for the design of new PROTACs. All E3 ligase pockets were characterized with innovative 3D descriptors including their PROTAC‐ability score, and similarity analyses between E3 pockets are presented. Tissue specificity and their degree of involvement in patients with specific cancer types are also annotated for each E3 ligase, enabling appropriate selection for the design of a PROTAC with improved specificity. All data are available at https://eliot.moldiscovery.com. [ABSTRACT FROM AUTHOR]

Aims: To explore and describe perceived factors that favour or hinder the challenges faced by mothers with congenital heart disease during pregnancy and motherhood. Design: A secondary qualitative analysis, according to the interpretative phenomenological analysis approach. Methods: A previous study by Flocco et al., 2020 led us to identify that this population share risks, fear, worries and challenges related to pregnancy. To better understand two a priori themes, barriers and facilitators, we adopted The Standards for Reporting Qualitative Research guidelines, and the processes of credibility, transferability and dependability guaranteed the rigour. Results: The perceived barriers that were identified from the twelve semi‐structured interviews were mainly identified in clinical and psychological risks, uncertainty about the future. The main facilitators were identified in positive mental attitude, self‐motivation, trust in support by clinicians and nurses. Conclusion: The study results confirmed two main a priori themes, revealing that CHD women perceive considerable obstacles and figure out facilitators to face the difficulties encountered in their path to become mothers. [ABSTRACT FROM AUTHOR]

Active hydrothermal travertine systems are ideal environments to investigate how abiotic and biotic processes affect mineralization mechanisms and mineral fabric formation. In this study, a biogeochemical characterization of waters, dissolved gases, and microbial mats was performed together with a mineralogical investigation on travertine encrustations occurring at the outflow channel of a thermal spring. The comprehensive model, compiled by means of TOUGHREACT computational tool from measured parameters, revealed that mineral phases were differently influenced by either abiotic conditions or microbially driven processes. Microbial mats are shaped by light availability and temperature gradient of waters flowing along the channel. Mineralogical features were homogeneous throughout the system, with euhedral calcite crystals, related to inorganic precipitation induced by CO2 degassing, and calcite shrubs associated with organomineralization processes, thus indicating an indirect microbial participation to the mineral deposition (microbially influenced calcite). The microbial activity played a role in driving calcite redissolution processes, resulting in circular pits on calcite crystal surfaces possibly related to the metabolic activity of sulfur‐oxidizing bacteria found at a high relative abundance within the biofilm community. Sulfur oxidation might also explain the occurrence of gypsum crystals embedded in microbial mats, since gypsum precipitation could be induced by a local increase in sulfate concentration mediated by S‐oxidizing bacteria, regardless of the overall undersaturated environmental conditions. Moreover, the absence of gypsum dissolution suggested the capability of microbial biofilm in modulating the mobility of chemical species by providing a protective envelope on gypsum crystals. [ABSTRACT FROM AUTHOR]

Recent theoretical advances, based on a combination of concepts from Thouless' topological theory of adiabatic charge transport and a newly introduced gauge‐invariance principle for transport coefficients, have permitted to connect (and reconcile) Faraday's picture of ionic transport—whereby each atom carries a well‐defined integer charge—with a rigorous quantum description of the electronic charge‐density distribution, which hardly suggests its partition into well defined atomic contributions. In this paper, these progresses are reviewed; in particular, it is shown how, by relaxing some general topological conditions, charge may be transported in ionic conductors without any net ionic displacements. After reporting numerical experiments which corroborate these findings, a new connection between the topological picture and the well‐known Marcus–Hush theory of electron transfer is introduced in terms of the topology of adiabatic paths drawn by atomic trajectories. As a significant byproduct, the results reviewed here permit to classify different regimes of ionic transport according to the topological properties of the electronic structure of the conducting material. Finally, a few recent applications to energy materials and planetary sciences are reported. [ABSTRACT FROM AUTHOR]

The newly identified low frequency elasticity of mesoscopic liquids opens the route to the identification of novel dynamic liquid properties. Two experimental examples illustrating the impact of the liquid elasticity in optics and thermodynamics are presented. It is revealed that at mesoscopic scale, liquids are able to convert the mechanical energy in optical and thermal effects. The fluids are submitted to a low frequency (∼Hz) mechanical shear strain (external stress), thus excluding a coupling with molecular time scales. The dynamic response is probed using two in situ methods accessing in real time optical response of the isotropic phase of liquid crystals and probing the thermal response upon shear deformation. In both cases, a dynamic response is identified: the isotropic phase of liquid crystals exhibits a low frequency dynamic birefringence while ordinary liquids exhibit cold and hot thermal waves synchronous to the low frequency excitation. [ABSTRACT FROM AUTHOR]

Aims: To compare the association of high serum uric acid (HUA) or metabolic syndrome (MetS) with fatty liver disease (FLD) in youths with overweight/obesity (OW/OB). Materials and Methods: Cross‐sectional study of anthropometrics, biochemical variables, and liver ultrasound of 3104 individuals with OW/OB (age 5–17 years). Metabolic syndrome was defined by ≥ 3 criteria among (1) high waist circumference; (2) high triglycerides; (3) low high‐density lipoproteins; (4) fasting glucose ≥100 mg/dl; (5) blood pressure ≥95th percentile in children, and ≥130/80 mmHg in adolescents. High serum uric acid was defined as serum UA value ≥ 75th percentile adjusted for sex. Fatty liver disease was determined by echography. Results: The sample was stratified in four categories: (1) no HUA, no MetS (reference category); (2) MetS; (3) HUA; (4) HUA and MetS (HUA + MetS). The prevalence of FLD increased across the four categories from 29.9%, 44.0%, 52.2%, to 67.1%, respectively (p < 0.0001). The ORs for the categorical variables were 1.33 (1.06–1.68) for MetS (p = 0.02), 3.19 (2.51–4.05) for HUA (p < 0.0001) and 3.72 (2.65–5.21) for HUA + MetS (p < 0.0001), versus the reference category regardless of the body mass index. Conclusions: HUA represents a useful marker of FLD in youths with OW/OB, given its greater ability to identify those at increased risk of the disease compared to MetS. The ability of both to predict incident FLD must be investigated in longitudinal study. [ABSTRACT FROM AUTHOR]

Rationale: We show evidence of cysteinylation on Cys252 of recombinant human p40 subunit of interleukin 12 (IL‐12). This was reported in 1996. However, no paper detailing this concept has been published yet. Our paper reports the quantification of Cys252 cysteinylation as well as the full disulfide bridges assignment by nonreducing peptide mapping using mass spectrometry (MS) detection. Methods: Nonreducing peptide mapping was applied for disulfide bridges assignment. This study presents an ad hoc method in which applying a neutral pH in the presence of an alkylating agent allowed to mitigate the formation of artifacts such as reshuffled disulfide bridges and permitted the detection of free cysteine. Ultra‐high‐performance liquid chromatography–MS analysis was performed on a Waters quadrupole time‐of‐flight Xevo G2‐XS mass spectrometer acquiring data in MSE mode. MS data were processed using Expressionist MS Refiner 13.5 (Genedata). Results: Scouting experiments were performed using two batches of drug substance. An in‐depth study of the LC tandem mass spectrometry profiles revealed the presence of additional species related to "free" Cys252; this cysteine residue was also detected in its S‐cysteinylated and S‐homocysteinylated forms. This result is consistent with that reported in literature so far. The relative abundance of overall "cysteinylated" species resulted in the range between 46% and 36%, which has also been confirmed using orthogonal techniques such as Ellman's assay. Conclusions: Our data clearly demonstrate that the free cysteine (Cys252) on the p40 subunit of recombinant IL‐12 is also present in its cysteinylated and homocysteinylated forms at a considerable rate. Our observations, although based on results obtained on an IL‐12‐derived fusion protein, are consistent with the current literature. [ABSTRACT FROM AUTHOR]

Integrated terrestrial system models predict the coupled water, energy and biogeochemical cycles. Simulations with these models are affected by uncertainties of model parameters, initial and boundary conditions, atmospheric forcings and the biophysical processes. Data assimilation (DA) can quantify and reduce the uncertainty. This has been tested intensively for single compartment models, but far less for integrated models with multiple compartments. We constructed a virtual reality (VR) with a coupled land surface‐subsurface model under the Terrestrial Systems Modeling Platform, which mimics the Neckar catchment in southern Germany. Soil moisture and groundwater level (GWL) data extracted from the simulated VR are used as measurements to be assimilated with state‐only/state‐hydraulic parameter estimation. Soil moisture DA improves soil moisture characterization in the vertical profile and the neighboring grid cells, with a 40 ∼ 60% reduction of root mean square error (RMSE) over the observation points. In spite of a small ensemble size of 64 members, assimilating soil moisture data improved saturated hydraulic conductivity estimation around the measurement locations. The characterization of evapotranspiration and river discharge only show limited improvements (1% at observation points and less than 0.1% in RMSE at 3 selected gauge locations respectively). GWL DA not only improves the GWL characterization (76 ∼ 88% RMSE reduction at observation locations) but also soil moisture for some cases. In addition, a clear improvement in GWL characterization is observed up to 8 km from the observations, and updating the model states of the saturated zone only instead of the complete domain gives better performance. Key Points: Groundwater level (GWL) and soil moisture data assimilation (DA) improve characterization of subsurface statesGWL DA improves GWL characterization up to 8 km from observation locationsEvapotranspiration and discharge hardly better estimated, despite better estimates of soil moisture and GWL [ABSTRACT FROM AUTHOR]

Purpose: In this study, we investigate the use of magnetic resonance imaging (MRI) for the clinical evaluation of gating treatment robustness in carbon‐ion radiotherapy (CIRT) of pancreatic cancer. Indeed, MRI allows radiation‐free repeated scans and fast dynamic sequences for time‐resolved (TR) imaging (cine‐MRI), providing information on inter‐ and intra‐fraction cycle‐to‐cycle variations of respiratory motion. MRI can therefore support treatment planning and verification, overcoming the limitations of the current clinical standard, that is, four‐dimensional computed tomography (4DCT), which describes an "average" breathing cycle neglecting breathing motion variability. Methods: We integrated a technique to generate a virtual CT (vCT) from 3D MRI with a method for 3D reconstruction from 2D cine‐MRI, to produce TR vCTs for dose recalculations. For eight patients, the method allowed evaluating inter‐fraction variations at end‐exhale and intra‐fraction cycle‐to‐cycle variability within the gating window in terms of tumor displacement and dose to the target and organs at risk. Results: The median inter‐fraction tumor motion was in the range 3.33–12.16 mm, but the target coverage was robust (‐0.4% median D95% variation). Concerning cycle‐to‐cycle variations, the gating technique was effective in limiting tumor displacement (1.35 mm median gating motion) and corresponding dose variations (‐3.9% median D95% variation). The larger exposure of organs at risk (duodenum and stomach) was caused by inter‐fraction motion, whereas intra‐fraction cycle‐to‐cycle dose variations were limited. Conclusions: This study proposed a method for the generation of TR vCTs from MRI, which enabled an off‐line evaluation of gating treatment robustness and suggested its feasibility to support treatment planning of pancreatic tumors in CIRT. [ABSTRACT FROM AUTHOR]

Measuring the variability of incoming neutrons locally would be usefull for the cosmic‐ray neutron sensing (CRNS) method. As the measurement of high energy neutrons is not so easy, alternative particles can be considered for such purpose. Among them, muons are particles created from the same cascade of primary cosmic‐ray fluxes that generate neutrons at the ground. In addition, they can be easily detected by small and relatively inexpensive detectors. For these reasons they could provide a suitable local alternative to incoming corrections based on remote neutron monitor data. The reported measurements demonstrated that muon detection system can detect incoming cosmic‐ray variations locally. Furthermore the precision of this measurement technique is considered adequate for many CRNS applications. Plain Language Summary: The measurement of the variability of the incident neutron flux is of fundamental importance for the cosmic‐ray neutron sensing technique. This type of measurement is not easy to use to have local and instantaneous values. For this reason in this work it is reported how this type of information can be obtained through the measurement of the flux of cosmic muons, which are correlated with the flux of cosmic neutrons. This type of measurement, being easier to perform, allows you to have a local and real time value in a very simple way. Key Points: Incoming correction in cosmic‐ray neutron sensing observations based on local muon measurements at ground [ABSTRACT FROM AUTHOR]

The assessment of unregulated level of enzyme activity is a crucial parameter for early diagnoses in a wide range of pathologies. In this study, we propose the use of electron paramagnetic resonance (EPR) as an easy method to probe carboxylesterase (CE) enzymatic activity in vitro. For this application, were synthesized two amphiphilic, nitroxide containing esters, namely Tempo‐C12 (T‐C12) and Tempo‐2‐C12 (T‐2‐C12). They exhibit low solubility in water and form stable micelles in which the radicals are EPR almost silent, but the hydrolysis of the ester bond yields narrows and intense EPR signals. The intensity of the EPR signals is proportional to the enzymatic activity. CEs1, CEs2 and esterase from porcine liver (PLE) were investigated. The obtained results show that T‐C12 and T‐2‐C12‐containing systems display a much higher selectivity toward the CEs2, with a Limit of Detection of the same order of those ones obtained with optical methods. [ABSTRACT FROM AUTHOR]

The dynamical mechanical analysis of blood generally uses models inspired by conventional flows, assuming scale‐independent homogeneous flows and without considering fluid–surface boundary interactions. The present experimental study highlights the relevance of using an approach in line with physiological reality providing a strong interaction between the fluid and the boundary interface. New dynamic properties of human blood plasma are found: a finite shear elastic response (solid‐like property) is identified in nearly static conditions, which also depends on the scale (being reinforced at small scales). The elastic behavior is confirmed by the induction, without heat transfer, of local hot and cold thermodynamic states evidencing a thermo‐mechanical coupling in blood plasma so far known only in elastic materials. This finding opens new routes for medical diagnosis and device fabrication. [ABSTRACT FROM AUTHOR]

Purpose: In‐beam positron emission tomography (PET) is one of the modalities that can be used for in vivo noninvasive treatment monitoring in proton therapy. Although PET monitoring has been frequently applied for this purpose, there is still no straightforward method to translate the information obtained from the PET images into easy‐to‐interpret information for clinical personnel. The purpose of this work is to propose a statistical method for analyzing in‐beam PET monitoring images that can be used to locate, quantify, and visualize regions with possible morphological changes occurring over the course of treatment. Methods: We selected a patient treated for squamous cell carcinoma (SCC) with proton therapy, to perform multiple Monte Carlo (MC) simulations of the expected PET signal at the start of treatment, and to study how the PET signal may change along the treatment course due to morphological changes. We performed voxel‐wise two‐tailed statistical tests of the simulated PET images, resembling the voxel‐based morphometry (VBM) method commonly used in neuroimaging data analysis, to locate regions with significant morphological changes and to quantify the change. Results: The VBM resembling method has been successfully applied to the simulated in‐beam PET images, despite the fact that such images suffer from image artifacts and limited statistics. Three dimensional probability maps were obtained, that allowed to identify interfractional morphological changes and to visualize them superimposed on the computed tomography (CT) scan. In particular, the characteristic color patterns resulting from the two‐tailed statistical tests lend themselves to trigger alarms in case of morphological changes along the course of treatment. Conclusions: The statistical method presented in this work is a promising method to apply to PET monitoring data to reveal interfractional morphological changes in patients, occurring over the course of treatment. Based on simulated in‐beam PET treatment monitoring images, we showed that with our method it was possible to correctly identify the regions that changed. Moreover we could quantify the changes, and visualize them superimposed on the CT scan. The proposed method can possibly help clinical personnel in the replanning procedure in adaptive proton therapy treatments. [ABSTRACT FROM AUTHOR]

Background: Whether and to what extent an association exists between hyperuricemia and erectile dysfunction (ED) has not yet been fully determined. Objective: To define pooled prevalence estimates and correlates of erectile dysfunction in men with hyperuricemic disorders. Materials and methods: A thorough search of Medline, Scopus, and Cochrane Library databases was performed. Data were combined using random‐effects models and the between‐study heterogeneity was assessed by Cochrane's Q and I2 tests. A funnel plot was used to assess publication bias. Results: Overall, 8 studies included gave information about 85,406 hyperuricemic men, of whom 5023 complained of erectile dysfunction, resulting in a pooled erectile dysfunction prevalence estimate of 33% (95% Confidence Interval: 13–52%; I² = 99.9%). The funnel plot suggested the presence of a publication bias. At the meta‐regression analyses, among the available covariates that could affect estimates, only type 2 diabetes mellitus was significantly associated with a higher prevalence of erectile dysfunction (β = 0.08; 95% Confidence Interval: 0.01, 0.15, p = 0.025). At the sub‐group analysis, the pooled erectile dysfunction prevalence decreased to 4% (95% Confidence Interval: 0%–8%) when only the largest studies with the lowest prevalence of type 2 diabetes mellitus were included and increased up to 50% (95% Confidence Interval: 17%–84%) when the analysis was restricted to studies enrolling smaller series with higher prevalence of type 2 diabetes mellitus. Conclusions: A not negligible proportion of men with hyperuricemia can complain of erectile dysfunction. While a pathogenetic contribution of circulating uric acid in endothelial dysfunction cannot be ruled out, the evidence of a stronger association between hyperuricemia and erectile dysfunction in type 2 diabetes mellitus points to hyperuricemia as a marker of systemic dysmetabolic disorders adversely affecting erectile function. [ABSTRACT FROM AUTHOR]

Purpose: Cone beam computed tomography (CBCT) is a standard solution for in‐room image guidance for radiation therapy. It is used to evaluate and compensate for anatomopathological changes between the dose delivery plan and the fraction delivery day. CBCT is a fast and versatile solution, but it suffers from drawbacks like low contrast and requires proper calibration to derive density values. Although these limitations are even more prominent with in‐room customized CBCT systems, strategies based on deep learning have shown potential in improving image quality. As such, this article presents a method based on a convolutional neural network and a novel two‐step supervised training based on the transfer learning paradigm for shading correction in CBCT volumes with narrow field of view (FOV) acquired with an ad hoc in‐room system. Methods: We designed a U‐Net convolutional neural network, trained on axial slices of corresponding CT/CBCT couples. To improve the generalization capability of the network, we exploited two‐stage learning using two distinct data sets. At first, the network weights were trained using synthetic CBCT scans generated from a public data set, and then only the deepest layers of the network were trained again with real‐world clinical data to fine‐tune the weights. Synthetic data were generated according to real data acquisition parameters. The network takes a single grayscale volume as input and outputs the same volume with corrected shading and improved HU values. Results: Evaluation was carried out with a leave‐one‐out cross‐validation, computed on 18 unique CT/CBCT pairs from six different patients from a real‐world dataset. Comparing original CBCT to CT and improved CBCT to CT, we obtained an average improvement of 6 dB on peak signal‐to‐noise ratio (PSNR), +2% on structural similarity index measure (SSIM). The median interquartile range (IQR) Hounsfield unit (HU) difference between CBCT and CT improved from 161.37 (162.54) HU to 49.41 (66.70) HU. Region of interest (ROI)‐based HU difference was narrowed by 75% in the spongy bone (femoral head), 89% in the bladder, 85% for fat, and 83% for muscle. The improvement in contrast‐to‐noise ratio for these ROIs was about 67%. Conclusions: We demonstrated that shading correction obtaining CT‐compatible data from narrow‐FOV CBCTs acquired with a customized in‐room system is possible. Moreover, the transfer learning approach proved particularly beneficial for such a shading correction approach. [ABSTRACT FROM AUTHOR]

Incidental cystic renal masses are common, usually benign, and almost always indolent. Since 1986, the Bosniak classification has been used to express the risk of malignancy in a cystic renal mass detected at imaging. Historically, magnetic resonance imaging (MRI) was not included in that classification. The proposed Bosniak v.2019 update has formally incorporated MRI, included definitions of imaging terms designed to improve interobserver agreement and specificity for malignancy, and incorporated a variety of masses that were incompletely defined or not included in the original classification. For example, at unenhanced MRI, homogeneous masses markedly hyperintense at T2‐weighted imaging (similar to cerebrospinal fluid) and homogeneous masses markedly hyperintense at fat suppressed T1‐weighted imaging (approximately ≥2.5 times more intense than adjacent renal parenchyma) are classified as Bosniak II and may be safely ignored, even when they have not been imaged with a complete renal mass MRI protocol. MRI has specific advantages and is recommended to evaluate masses that at computed tomography (CT) 1) have abundant thick or nodular calcifications; 2) are homogeneous, hyperattenuating, ≥3 cm, and nonenhancing; or 3) are heterogeneous and nonenhancing. Although MRI is generally excellent for characterizing cystic renal masses, there are unique weaknesses of MRI that bear consideration. These details and others related to MRI of cystic renal masses are described in this review, with an emphasis on Bosniak v.2019. A website (https://bosniak-calculator.herokuapp.com/) and mobile phone apps named "Bosniak Calculator" have been developed for ease of assignment of Bosniak classes. Level of Evidence: 5 Technical Efficacy Stage: 3 [ABSTRACT FROM AUTHOR]