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This research study's principal objective is to explain the relationship between corruption and political attitudes regarding sustainable development, also from the perspective of Peruvian students. The sample consisted of 616 university students who were from the cities of Lima and Piura. They responded to two instruments: The Attitude Scale Toward Politics and the Attitude Scale Toward Corruption. Among the most representative results, it was found that institutional corruption has a highly significant and direct relationship with political attitudes from the perspective of university students (0.720. Sig.0.000). Nine out of ten dimensions of attitudes toward politics achieved highly significant correlations (p = 0.001) with attitudes toward corruption. Among the conclusions, it is observed that attitudes toward politics and attitudes toward corruption show a systematic interdependence of modification. It is necessary implement strategies for political participation without corruption is emphasized to improve the education that sustains the future governance of the country. [ABSTRACT FROM AUTHOR]

Holotomography (HT) is a cutting‐edge fast live‐cell quantitative label‐free imaging technique. Based on the principle of quantitative phase imaging, it combines holography and tomography to record a three‐dimensional map of the refractive index, used as intrinsic optical and quantitative imaging contrast parameter of biological samples, at a sub‐micrometer spatial resolution. In this study HT has been employed for the first time to analyze the changes of fibroblasts differentiating towards myofibroblasts – recognized as the main cell player of fibrosis – when cultured in vitro with the pro‐fibrotic factor, namely transforming growth factor‐β1. In parallel, F‐actin, vinculin, α‐smooth muscle actin, phospho‐myosin light chain 2, type‐1 collagen, peroxisome proliferator‐activated receptor‐gamma coactivator‐1α expression and mitochondria were evaluated by confocal laser scanning microscopy. Plasmamembrane passive properties and transient receptor potential canonical channels' currents were also recorded by whole‐cell patch‐clamp. The fluorescence images and electrophysiological results have been compared to the data obtained by HT and their congruence has been discussed. HT turned out to be a valid approach to morphologically distinguish fibroblasts from well differentiated myofibroblasts while obtaining objective measures concerning volume, surface area, projection area, surface index and dry mass (i.e., the mass of the non‐aqueous content inside the cell including proteins and subcellular organelles) of the entire cell, nuclei and nucleoli with the major advantage to monitor outer and inner features in living cells in a non‐invasive, rapid and label‐free approach. HT might open up new research opportunities in the field of fibrotic diseases. Research Highlights: Holotomography (HT) is a label‐free laser interferometric imaging technology exploiting the intrinsic optical property of cells namely refractive index (RI) to enable a direct imaging and analysis of whole cells or intracellular organelles.HT turned out a valid approach to distinguish morphological features of living unlabeled fibroblasts from differentiated myofibroblasts.HT provided quantitative information concerning volume, surface area, projection area, surface index and dry mass of the entire fibroblasts/myofibroblasts, nuclei and nucleoli. [ABSTRACT FROM AUTHOR]

The method of short‐loop recycling of Nd–Fe–B magnets is implemented, with end‐of‐life (EoL) magnets used as a source of heavy rare earth (HRE). Partially recycled magnets are fabricated by co‐sintering HRE‐free powders obtained from strip casted alloys, blended with HRE‐rich powders obtained from EoL magnets. The impact of several process parameters (blending ratio, sintering cycle, and HRE‐rich recycled particle sizes) on the microstructure and magnetic properties is discussed. A coercivity gain up to 160 kA m−1 wt%−1 of Dy with respect to the HRE‐free magnets is reported, even though impurities are incorporated. Microstructural characterizations show a heterogeneous Dy localization in core–shell/anticore–shell structures, and thus a nonoptimal use of HRE. The experimental results are compared with finite element simulations of the Dy diffusion transport performed using existing data of bulk Dy diffusion coefficients. The simulation model consists of a network of square grains separated by a liquid phase, whose fraction is based on the ternary Nd–Fe–B phase diagram. Results show similarities with the observed microstructures, and point to the interest of reducing the Dy‐rich particle size with respect to the main powder. This study provides new insights into the Dy transport mechanisms at stake in an efficient short‐loop recycling of HRE. [ABSTRACT FROM AUTHOR]

In order to examine the progressive chemical evolution of halogens (F, Cl, Br, I) in altered ocean crust (AOC) during prograde subduction, this study compares bulk and in situ halogen concentrations in mafic samples from three petrogenetically related exhumed terrains in the Western Alps (the Chenaillet ophiolite, the Queyras ophiolites of the Schistes Lustrés, and the Monviso ophiolite). Samples from the Chenaillet ophiolite represent oceanic crust unaffected by metamorphic halogen loss and define a protolith halogen content (122 μg/g F, 29 μg/g Cl, 82 ng/g Br, and 98 ng/g I). Samples from the Queyras ophiolites experienced blueschist facies conditions, undergoing recrystallization and halogen loss (74 μg/g F, 19 μg/g Cl, 70 ng/g Br, and 63 ng/g I). Eclogite facies samples from the Monviso meta‐ophiolite exhibit markedly reduced Cl (8 μg/g Cl) and Br (42 ng/g Br) contents relative to samples from Chenaillet and Queyras. Using electron probe microanalysis (EPMA), F and Cl host minerals (e.g., amphibole, chlorite, epidote) are identified and characterized in selected samples, showing a broad distribution of F and Cl, lending support to the view that halogen devolatilization in the subducting slab occurs continuously and is not dependent on the breakdown of a particular phase. In situ Cl concentrations decrease significantly between sub‐greenschist and blueschist assemblages. Fluorine is retained within subducting AOC and is decoupled from the heavy halogens (Cl, Br, I), which undergo continuous devolatilization during prograde metamorphism. Plain Language Summary: Halogens are volatile elements found predominantly in the Earth's oceans and sediments. During hydrothermal processes, they bond with other elements to form volatile‐bearing minerals. Tectonic processes can bring halogen‐enriched rocks into subduction zones, regions where one tectonic plate submerges beneath another. Subduction governs the transport of material from Earth's surface to its interior, influencing the chemical evolution of the crust, atmosphere, hydrosphere, and mantle. As the subducting plate carries rocks to greater depths beneath the surface, volatile‐bearing minerals destabilize, releasing volatile components as fluids. Halogens alter the properties of subduction‐derived fluids and impact the behavior of other biologically, climatically, and economically important elements (e.g., H2O, CO2, Au). Due to the influential role of halogens in subduction zone environments, the timing and extent of halogen loss must be constrained. This study investigates metamorphic rock samples from the Western Alps which underwent halogen‐enrichment followed by subduction and devolatilization. Results show that halogens behave differently from each other. Fluorine is not removed; it is retained until deep in the subduction zone and is returned to the Earth's mantle. The efficient removal of the other halogens occurs early in subduction (<60 km depth) and is not linked to the destabilization of a specific mineral. Key Points: Exhumed ophiolites in the Western Alps record prograde subduction zone metamorphism and halogen devolatilization of altered ocean crustResults show halogen decoupling. Fluorine is retained, whereas heavy halogens are mobilized from mafic rocks in the subducting slabDevolatilization of altered ocean crust occurs early in subduction; a significant portion of Cl, Br, and I is lost prior to eclogite facies [ABSTRACT FROM AUTHOR]

Post‐translational modifications of lysine in histones, as methylation and acetylation, have well established functions in epigenetics and are emerging as important actors in broader biological regulation. Currently, the detection of acetylated lysine (Kac) in water solution as free amino acid or protein residue remains challenging. Acetylated lysine is a neutral amino acid, and the lack of ion–dipole interactions causes the decrease in binding affinity displayed by synthetic molecular receptors with respect to the other lysine modifications. Here, we report molecular modeling calculations and 1H NMR experiments to investigate the binding properties of two different calix[4]pyrrole receptors towards Kac. Computational analyses reveal that tetra‐aryl‐extended calix[4]pyrrole (1) preferentially binds the cis‐Kac conformer over the trans one due to steric considerations and more favorable interactions. Experimental 1H NMR titration experiments confirm the formation of a 1 : 1 complex between receptor 1 and cis‐Kac, with a Ka exceeding 103 M−1. Conversely, the super‐aryl‐extended calix[4]pyrrole 2 is less efficient in binding Kac, due to unfavorable solvation/desolvation effects, as proven by 1H NMR experiments. Moreover, receptor 1 showed a higher affinity for Kac over other lysine modifications, such as methylated lysines. [ABSTRACT FROM AUTHOR]

Summary: The green solvents and eco‐extraction methods are gaining increasing interest in chemical analysis for bioactive compounds in food matrices. Deep Eutectic Solvents (DES) developed as a greener and more sustainable alternative to organic solvents, owing to their non‐toxic, highly stable, and biodegradation‐friendly nature. DES application for polyphenols and antioxidant compounds extraction in dark chocolate samples has been evaluated in an integrated study for sustainability assessment, based on multivariate analysis and Life Cycle Assessment (LCA) methodology. A green extraction method based on DES was proposed testing different HBA:HBD pairs (ChCl:Fru, ChCl:Teg, Bet:Fru, and Bet:Teg). DES Bet:Fru resulted in the highest extraction yield in terms of both total polyphenols (0.34–3.37 g GAE/100 g) and flavonoids (1.13–8.32 g RUT/100 g), P < 0.05. Furthermore, the environmental performances of green and conventional solvents (MeOH:H2O, H2O, and MeOH) were evaluated by applying a comparative LCA (c‐LCA). The c‐LCA study highlighted that conventional extraction for polyphenols in dark chocolate was 60% more impactful than DES. DES pairs analysed quantitatively lowest impacted than conventional methods, considering the macro‐categories Human Health (9.99 × 10–8 ÷ 1.54 × 10–7 DALYs), Ecosystem (2.29 × 10–10 ÷ 3.57 × 10–10 species.yr), and Resources (6.57 × 10–3 ÷ 8.96 × 10–3 USD2013). [ABSTRACT FROM AUTHOR]

High‐resolution grid digital elevation models (DEMs) are increasingly used by scientists and engineers to describe the current state and evolution of Earth and planetary topography. These data, however, are commonly altered by depression filling and grid coarsening procedures. Alteration of observed topographic data may cause significant information loss and limit the capabilities of models. This study shows that physically meaningful thalweg and ridge networks can be extracted automatically from any unaltered high‐resolution grid DEM, and that these networks can be used as bases for terrain partitioning. The slopeline network connecting grid cell centers is used to identify ridge points as those grid cell border midpoints and vertices that are not crossed by slopelines. From each ridge point, the average length of the two slopelines extending on the opposite slopes of the ridge until they rejoin is then computed. Based on these lengths, exorheic and endorheic basins are identified. Thalwegs of exorheic and endorheic basins are finally connected through spilling saddles to form the thalweg network. The related ridge network is identified based on neighboring relationships between ridge points. Thalweg and ridge networks are hierarchized using the well‐known concept of drainage area and an extended concept of dispersal area to inform terrain partitioning at any level of detail. Observed topographic features are well reproduced by extracted networks. The impact of preserving depressions over mountain areas is evaluated, and the benefits from unstructured terrain partitioning based on thalweg and ridge networks in the description of flood plain inundation are illustrated. Plain Language Summary: Detailed topographic data are increasingly used by scientists and engineers to describe the current state and evolution of Earth and planetary topography. In current models, however, depressions are commonly filled for model simplicity, and grids are normally coarsened for computational efficiency. Alteration of observed topographic data may cause a significant information loss and limit the capabilities of models. In this study, it is shown that the lines following the lowest part of a valley or channel (thalwegs) and the lines of intersection at the top between opposite slopes (ridges) are the essential topographic features (bases) that need to be extracted from observed topographic data and retained when terrain is partitioned. New terrain analysis methods are developed to extract thalweg networks connecting depression (endorheic) and drainage (exorheic) basins, and to identify physically meaningful ridge networks. Observed topographic features are well reproduced by extracted networks. The impact of preserving depressions over mountain areas is evaluated, and the benefits from unstructured terrain partitioning based on thalweg and ridge networks in the description of flood plain inundation are illustrated. The developed methods provide a new pathway for scientists and engineers to rigorously incorporate detailed topographic data into their descriptions of Earth surface processes. Key Points: Physically meaningful thalweg and ridge networks can be extracted automatically from any high‐resolution grid digital elevation modelDepressions and nested systems of exorheic and endorheic basins are handled without the need to alter the observed topographic dataThalweg and ridge networks can be obtained at the desired level of detail and are presented here as novel bases for terrain partitioning [ABSTRACT FROM AUTHOR]

Aims: Anaphylaxis guidelines recommend intramuscular adrenaline, commonly 300 μg administered using an auto‐injector device. However, overweight/obese patients may require a higher adrenaline dose for adequate cardiovascular (CV) response. This study evaluated the pharmacokinetics (PK) and pharmacodynamic (PD) CV profiles after a single 500 μg adrenaline injection via Anapen auto‐injector in healthy normal weight males and otherwise healthy, overweight or obese females. Methods: In this exploratory open‐label, single‐centre study, 54 healthy volunteers aged 18‐50 years received a single 500 μg adrenaline injection (Anapen auto‐injector) in the thigh (antero‐lateral middle third [18 males] or antero‐inferior third [36 females]). Assessments included depot depth (ultrasonography), plasma adrenaline levels (liquid chromatography‐tandem mass spectrometry) and heart rate (HR; ECG Holter monitor). Results: Ultrasonography showed that 82.4% of normal weight males received intramuscular injections; all overweight and obese females received subcutaneous injections. Anapen injection produced rapid increases in circulating adrenaline levels and significant increases in systolic blood pressure (SBP) and HR. Second peak plasma adrenaline concentrations (Cmax2) were reduced, and time to Cmax2 increased in overweight and obese females compared with males with normal body mass index; area under the curve (0–240 min) (AUC(0‐240)) was increased in overweight and obese females. Obese females had reduced maximal SBP values compared with normal weight males or overweight females; overweight and obese females had markedly different HR time courses compared with normal weight males. Conclusion: A 500 μg adrenaline injection via Anapen produced rapid PK/PD changes in normal weight, overweight and obese subjects, irrespective of intramuscular or subcutaneous injection, and was well tolerated. [ABSTRACT FROM AUTHOR]

The opto-electronic properties of semiconducting 2D materials can be flexibly manipulated by engineering the atomic-scale environment. This can be done by including 2D materials in tailored van der Waals (vdW) stacks, whose optical response is a function of the number and the type of adjacent 2D layers. This work reports a systematic investigation of the dielectric function of 2D semiconducting WS2 in various stacking configurations: monolayer, 3R/2H homobilayer, and WS2/MoS2 heterobilayer. Reliable, Kramers-Kronigconsistent dielectric functions are obtained for WS2 in each configuration by means of spectroscopic ellipsometry (SE) and related parametric optical modeling in a wide spectral range (1.55-3.10 eV). The results of SE are combined with photoluminescence and absorbance spectra to identify the spectral position of the main excitonic features in WS2, which manifest sizable redshifts depending on the stacking configuration. These results represent a consistent reference set for the dielectric function of WS2 in vdW stacking configurations of particular interest for the scientific and technological field, and can be fruitfully exploited for reliable predictions of the optical response of WS2-containing systems. [ABSTRACT FROM AUTHOR]

Summary: In this study, the phytochemical profile of commercial pollen samples was investigated using different analytical approaches. The samples pollen composition was monitored by optical microscopy. The infrared spectrum of the ethanol extractable material form different pollen samples indicated the specific presence of an aromatic portion in samples dominated by pollens from arboreal species of sweet chestnut pollen grains (e.g. Castanea sativa Mill. and Prunus). In addition, the UPLC‐PDA analysis showed the ubiquitarian presence of an array of different derivatives confirmed as hydroxylated cinnamoyl derivatives of spermidine (major) and of spermine (minor). This profile appeared to be associated with the sample botanical origin. Samples dominated by chestnut honey pollen grains showed the highest content in total amount of these derivatives, with a peculiar profile dominated by the presence of N1, N5, N10‐tricaffeoyl spermidine. The results showed that their average chemical composition is quantitatively and qualitatively correlated to their botanical origin, suggesting the feasibility of this approach as a practical tool to monitor plant population using honeybee pollen as a bioindicator of the impact of natural and anthropic processes at the local and global level. [ABSTRACT FROM AUTHOR]

Background: Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is associated with late complications that can impair the quality of life (QoL) of patients for years after transplant. The purpose of the present study was to determine the difference in the QoL of adults that underwent allo‐HSCT in childhood and adolescence compared with not transplanted adults. Methods: In this prospective case–control cross‐sectional study, we included patients aged ≥18 years that received an allo‐HSCT during childhood or adolescence and subsequently survived at least 2 years after transplantation. The control group consisted of blood donors matched for age and sex. QoL assessment was performed using the Short Form‐36 (SF‐36) Health Survey, Portuguese version 2. Results: Thirty‐four transplanted patients and controls were included. 58.8% were male, and the median age at transplant was 13.5 years (range, 4–17 years). The median follow‐up was 11.5 years (range, 2.0–23.0 years). The most common late effect was skeletally followed by endocrine complications. Patients with these late complications had the worst QOL in the following dimensions: physical functioning, role physical, bodily pain, general health, and mental health. When compared to the control group, patients had a lower score in two dimensions: physical functioning and role physical. Conclusions: Although skeletal and endocrine complications of transplant patients in childhood have an impact on physical functioning, most parameters of QoL of these patients in adulthood are similar to healthy individuals of the same age and gender. Early detection and long‐term monitoring of late complications can prevent impairment of the QoL. [ABSTRACT FROM AUTHOR]

Aims: To examine clinical and social correlates of health‐related quality of life (HRQL) in patients with heart failure (HF) from high‐ (HIC), upper middle‐ (UMIC), lower middle‐ (LMIC) and low‐income (LIC) countries. Methods and results: Between 2017 and 2020, 23 292 patients with HF (32% inpatients, 61% men) from 40 countries were enrolled in the Global Congestive Heart Failure study. HRQL was recorded at baseline using the Kansas City Cardiomyopathy Questionnaire (KCCQ)‐12. In a cross‐sectional analysis, we compared age‐ and sex‐adjusted mean KCCQ‐12 summary scores (SS: 0–100, higher = better) between patients from different country income levels. We used multivariable linear regression examining correlations (estimated coefficients) of KCCQ‐12‐SS with sociodemographic, comorbidity, treatment and symptom covariates. The adjusted model (37 covariates) was informed by univariable findings, clinical importance and backward selection. Mean age was 63 years and 40% of patients were in New York Heart Association (NYHA) class III–IV. Average HRQL was 55 SD 27. It was 62.5 (95% confidence interval [CI] 62.0–63.1) in HIC, 56.8 (56.1–57.4) in UMIC, 48.6 (48.0–49.3) in LMIC, and 38.5 (37.3–39.7) in LICs (p < 0.0001). Strong correlates (estimated coefficient [95% CI]) of KCCQ‐12‐SS were NYHA class III versus class I/II (−12.1 [−12.8 to −11.4] and class IV versus class I/II (−16.5 [−17.7 to −15.3]), effort dyspnoea (−9.5 [−10.2 to −8.8]) and living in LIC versus HIC (−5.8 [−7.1 to −4.4]). Symptoms explained most of the KCCQ‐12‐SS variability (partial R2 = 0.32 of total adjusted R2 = 0.51), followed by sociodemographic factors (R2 = 0.12). Results were consistent in populations across income levels. Conclusion: The most important correlates of HRQL in HF patients relate to HF symptom severity, irrespective of country income level. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?It is a challenge to discover effective therapies for fibrosis. Increasing evidence supports the antifibrotic potential of platelet‐rich plasma (PRP) as a source of bioactive molecules, such as vascular endothelial growth factor (VEGF)‐A. However, the effects and mechanisms of action of PRP need to be clarified.What is the main finding and its importance?This report clarifies the mechanisms mediating the antifibrotic action of PRP, strengthening the role of VEGF‐A/VEGF receptor, and identifies gap junction currents and connexin 43 as novel targets of this pathway in the fibroblast‐to‐myofibroblast transition induced by the transforming growth factor‐β1. Despite increasing experimental evidence, the antifibrotic potential of platelet‐rich plasma (PRP) remains controversial, and its mechanisms of action are not fully clarified. This short report extends our previous research on the capability of PRP to prevent the in vitro differentiation of fibroblasts toward myofibroblasts, the key effectors of fibrosis, induced by the profibrotic agent transforming growth factor‐β1 (TGF‐β1). In particular, we focused on the involvement of signalling mediated by vascular endothelial growth factor (VEGF)‐A/VEGF receptor (VEGFR) in the PRP‐induced fibroblast response, highlighting gap junction features. Electrophysiological and morphological analyses revealed that PRP hindered morphofunctional differentiation of both murine NIH/3T3 and human primary adult skin fibroblasts toward myofibroblasts as judged by the analysis of membrane phenomena, α‐smooth muscle actin and vinculin expression and cell morphology. Neutralization of VEGF‐A by blocking antibodies or pharmacological inhibition of VEGFR by KRN633 in TGF‐β1‐treated fibroblasts prevented the PRP‐promoted effects, such as the reduction of voltage‐dependent transjunctional currents in cell pairs and a decreased expression of connexin 43, the typical connexin isoform forming voltage‐dependent connexons. The role of VEGF‐A in inhibiting these events was confirmed by treating TGF‐β1‐stimulated fibroblasts with soluble VEGF‐A. The results obtained when cells were differentiated using KRN633 alone suggest an antagonistic cross‐talk between TGF‐β1 and VEGFR. In conclusion, this study identifies, for the first time, gap junction currents as crucial targets in the VEGF‐A/VEGFR‐mediated antifibrotic pathway and provides new insights into mechanisms behind the action of PRP in preventing differentiation of fibroblasts to myofibroblasts. [ABSTRACT FROM AUTHOR]

A software for the Master Sintering Curve (MSC) approach has been developed using Python language. An interface with simple steps allows the user to insert data from shrinkage results followed for conversion to densification view and built curves based on MSC theory. The simple software language allows easy adaptation to external users and their specific issues, aiming to improve the sintering phenomena investigation. Finally, three ceramic materials have been analyzed, demonstrating the software operation. [ABSTRACT FROM AUTHOR]

Mammal bioerosion is an emergent threat to the functionality of levees. In the present paper, the problem of assessing the failure probability of levees affected by mammal bioerosion is addressed. A fully bivariate description of peak flow discharge and flood duration is combined with a deterministic unsteady seepage flow model to obtain a suitable model of variably disturbed levee response to the observed natural variability of floods. Monte Carlo analysis is also implemented to evaluate the epistemic uncertainty connected to the description of the river system. The obtained model is tested with respect to a real‐world levee located along the Secchia River in northern Italy, which underwent a disastrous failure caused by mammal bioerosion in 2014. The convex linear combination of two Archimedean copulas is found to fit the empirical dependence structure between peak flow discharge and flood duration. The reliability of the unsteady seepage flow model is tested against detailed numerical simulations of the seepage occurring through the levee body. A limit state function is obtained by comparing the maximum extent of the seepage front to the distance between the den end and the riverside levee slope, and the corresponding levee safety and failure regions are delimited. Results obtained from the developed model reveal a significant impact of mammal dens located near the levee crest in terms of failure probability and related return period. This impact is consistent with failures observed in the study area. Plain Language Summary: Burrowing mammals often find in levees a suitable habitat. Unfortunately, mammal dens can significantly compromise the functionality of levees by creating preferential flow paths for flood water seeping through the levee bodies, and by causing ultimately levee failures due to excessive seepage and internal erosion. In fact, many levee failures have been connected to the levee weakening caused by mammal dens. Mammal bioerosion significantly increases the failure probability of levees and the related flood risk in densely populated floodplains. Estimating the failure probability of levees affected by mammal bioerosion is therefore a relevant societal need. In the present study levee, safety and failure conditions are estimated by combining a fully bivariate statistical description of peak flow discharge and flood duration with a computationally efficient unsteady seepage flow model. The resulting modeling framework incorporates the natural variability of floods and the essential hydraulic properties of disturbed/undisturbed levees. Model results reveal that the return period of levee failure due to excessive seepage reduces from 100 to 9 years, namely of −91%, when the mammal den extends for 84% of levee thickness. These results can be used to inform levee design and maintenance programs for the safety of societies living in floodplains worldwide. Key Points: Fully bivariate analysis of peak flow discharge and flood duration is used to describe the hydrologic forcing to leveesVorogushyn et al.'s unsteady seepage flow model is extended to derive the failure probability of variably disturbed leveesReturn period of levee failure due to excessive seepage reduces from 100 to 9 years when the mammal den extends for 84% of levee thickness [ABSTRACT FROM AUTHOR]

Objectives: Endoscopic sphincterotomy (ES) and papillectomy (EP) are associated with a non‐negligible risk of post‐procedural bleeding. Despite first‐line endoscopic hemostasis being achieved by several methods, patients may experience bleeding persistence or recurrence. In such cases, fibrin glue (FG) injection may be used as a rescue therapy before more invasive approaches. The aim of this study was to evaluate the efficacy and safety of endoscopic FG injection to treat refractory post‐ES and post‐EP bleeding. Methods: Data were collected retrospectively from patients with refractory immediate or delayed bleeding following ES or EP, between October 2007 and November 2019, at a single institution. Clinical success was defined as bleeding control after FG injection. Results: Overall, 70 patients were included. Clinical success was reached in 64 (91.4%) patients after one session of FG injection. Of six (8.6%) patients in whom the treatment failed, one required subsequent insertion of a fully covered self‐expanding metal stent (FC‐SEMS) due to immediate massive bleeding, while five experienced bleeding recurrence. Such events were managed with an additional session of FG injection that failed in two cases. Therefore, one patient underwent FC‐SEMS plus selective embolization, whereas the other underwent diagnostic arteriography. No severe periprocedural complications occurred. Two cases of intrabiliary glue migration were treated by endoscopic removal with a retrieval basket. Conclusions: Rescue therapy with endoscopic FG injection appears to be effective and safe to treat refractory post‐ES and post‐EP bleeding. Further studies are required to confirm these preliminary data. [ABSTRACT FROM AUTHOR]

The outbreak of COVID‐19 coronavirus disease around the end of 2019 has become a pandemic. The preferred method for COVID‐19 detection is the real‐time polymerase chain reaction (RT‐PCR)‐based technique; however, it also has certain limitations, such as sample‐dependent procedures with a relatively high false negative ratio. We propose a safe and efficient method for screening COVID‐19 based on Raman spectroscopy. A total of 177 serum samples are collected from 63 confirmed COVID‐19 patients, 59 suspected cases, and 55 healthy individuals as a control group. Raman spectroscopy is adopted to analyze these samples, and a machine learning support‐vector machine (SVM) method is applied to the spectrum dataset to build a diagnostic algorithm. Furthermore, 20 independent individuals, including 5 asymptomatic COVID‐19 patients and 5 symptomatic COVID‐19 patients, 5 suspected patients, and 5 healthy patients, were sampled for external validation. In these three groups—confirmed COVID‐19, suspected, and healthy individuals—the distribution of statistically significant points of difference showed highly consistency for intergroups after repeated sampling processes. The classification accuracy between the COVID‐19 cases and the suspected cases is 0.87 (95% confidence interval [CI]: 0.85–0.88), and the accuracy between the COVID‐19 and the healthy controls is 0.90 (95% CI: 0.89–0.91), while the accuracy between the suspected cases and the healthy control group is 0.68 (95% CI: 0.67–0.73). For the independent test dataset, we apply the obtained SVM model to the classification of the independent test dataset to have all the results correctly classified. Our model showed that the serum‐level classification results were all correct for independent test dataset. Our results suggest that Raman spectroscopy could be a safe and efficient technique for COVID‐19 screening. [ABSTRACT FROM AUTHOR]

Purpose and background: The magnetic resonance (MR)‐only radiotherapy workflow is urged by the increasing use of MR image for the identification and delineation of tumors, while a fast generation of synthetic computer tomography (sCT) image from MR image for dose calculation remains one of the key challenges to the workflow. This study aimed to develop a neural network to generate the sCT in brain site and evaluate the dosimetry accuracy. Materials and methods: A generative adversarial network (GAN) was developed to translate T1‐weighted MRI to sCT. First, the "U‐net" shaped encoder‐decoder network with some image translation‐specific modifications was trained to generate sCT, then the discriminator network was adversarially trained to distinguish between synthetic and real CT images. We enrolled 37 brain cancer patients acquiring both CT and MRI for treatment position simulation. Twenty‐seven pairs of 2D T1‐weighted MR images and rigidly registered CT image were used to train the GAN model, and the remaining 10 pairs were used to evaluate the model performance through the metric of mean absolute error. Furthermore, the clinical Volume Modulated Arc Therapy plan was calculated on both sCT and real CT, followed by gamma analysis and comparison of dose‐volume histogram. Results: On average, only 15 s were needed to generate one sCT from one T1‐weighted MRI. The mean absolute error between synthetic and real CT was 60.52 ± 13.32 Housefield Unit over 5‐fold cross validation. For dose distribution on sCT and CT, the average pass rates of gamma analysis using the 3%/3 mm and 2%/2 mm criteria were 99.76% and 97.25% over testing patients, respectively. For parameters of dose‐volume histogram for both target and organs at risk, no significant differences were found between both plans. Conclusion: The GAN model can generate synthetic CT from one single MRI sequence within seconds, and a state‐of‐art accuracy of CT number and dosimetry was achieved. [ABSTRACT FROM AUTHOR]

Triclocarban (TCC) is an antimicrobial compound widely used in personal care products such as soaps, toothpaste, and shampoo. This agent is incompletely removed by wastewater treatment and represents an environmental contaminant. Recent studies have shown that TCC is associated with some endocrine disruptions. The aim of the present study was to evaluate if TCC exposure during critical periods of development (gestation and lactation) could lead to adverse effects on reproductive and behavior parameters of female offspring. Pregnant female Wistar rats were divided into four groups (n = 8–11/group): Control; TCC 0.3 mg/kg (TCC 0.3); TCC 1.5 mg/kg; TCC 3.0 mg/kg (TCC 3.0); and treated daily by oral gavage from gestational day 0 to lactational day 21. The female pups (F1 generation) were weaned on post‐natal day 21 and included in the study. No litter‐mates were used for the same group. There was a decrease in estradiol levels in the TCC 0.3 and TCC 3.0 groups. Moreover, there was a decrease in progesterone levels and an increase in pre‐implantation loss in the TCC 3.0 group in adulthood. It is suggested, in this study, that the decrease in progesterone biosynthesis could interfere with implantation process. The exposure window to TCC is an important factor, as we found alterations only in the offspring. Triclocarban (TCC), an antimicrobial compound, could act as an endocrine disruptor. We evaluated whether maternal exposure to TCC could interfere with reproductive and behavior parameters of female rat offspring. Dams were treated with TCC (0.3; 1.5 and 3.0 mg/kg) and treated from gestational day 0 to lactational day 21. There was a decrease in estradiol (TCC 0.3 and TCC 3.0 groups) and progesterone levels, and an increase in pre‐implantation loss (TCC 3.0 group) in adult female offspring. [ABSTRACT FROM AUTHOR]

Oral lichen planus (OLP) is a common chronic inflammatory disease of unknown etiology that mainly affects middle-aged women, with no racial predilection.[1] Based on the modified World Health Organization (WHO) diagnostic criteria for OLP proposed by van der Meij and van der Waal,[2] definitive diagnosis depends on the clinicopathological correlation, and requires the presence of bilateral, more or less symmetrical reticular lesions, a well-defined band-like zone of lymphocytes, and signs of liquefaction degeneration of the basal cell epithelial layer. Histopathological examination of all OLP patients (29/29; 100%) and nine OLL patients (32.1%) showed liquefactive degeneration of basal cell layer and a band-like lymphocytic infiltrate in the subepithelial connective tissue (Figure). Hyperparakeratinization was observed in 21 OLP patients (72.4%) and 17 OLL patients (60.7%), and apoptotic bodies were found in five OLP (17.2%) and five OLL patients (17.8%), particularly in the basal epithelial cell layer. [Extracted from the article]

Postmastectomy radiation therapy is technically difficult and can be considered one of the most complex techniques concerning patient setup reproducibility. Slight patient setup variations — particularly when high‐conformal treatment techniques are used — can adversely affect the accuracy of the delivered dose and the patient outcome. This research aims to investigate the inter‐fraction setup variations occurring in two different scenarios of clinical practice: at the reference and at the current patient setups, when an image‐guided system is used or not used, respectively. The results were used with the secondary aim of assessing the robustness of the patient setup procedure in use. Forty eight patients treated with volumetric modulated arc and intensity modulated therapies were included in this study. EPID‐based in vivo dosimetry (IVD) was performed at the reference setup concomitantly with the weekly cone beam computed tomography acquisition and during the daily current setup. Three indices were analyzed: the ratio R between the reconstructed and planned isocenter doses, γ% and the mean value of γ from a transit dosimetry based on a two‐dimensional γ‐analysis of the electronic portal images using 5% and 5 mm as dose difference and distance to agreement gamma criteria; they were considered in tolerance if R was within 5%, γ% > 90% and γmean < 0.4. One thousand and sixteen EPID‐based IVD were analyzed and 6.3% resulted out of the tolerance level. Setup errors represented the main cause of this off tolerance with an occurrence rate of 72.2%. The percentage of results out of tolerance obtained at the current setup was three times greater (9.5% vs 3.1%) than the one obtained at the reference setup, indicating weaknesses in the setup procedure. This study highlights an EPID‐based IVD system's utility in the radiotherapy routine as part of the patient's treatment quality controls and to optimize (or confirm) the performed setup procedures' accuracy. [ABSTRACT FROM AUTHOR]

A UV exclusion experiment was conducted on durum wheat (Triticum durum Desf. var. Claudio) grown in pots. Plants were grown under three different radiative treatments in greenhouses covered with plastic filters: Teflon, transparent to the entire region of natural UV‐visible sunlight (TEF); polyester, transparent above 312 nm (MYL, excluding UVB) and Lee, transparent above 400 nm (LEE, excluding both UVA and UVB). Analyses have been carried out to determine the concentration of photosynthetic pigments in leaves, UV‐absorbing compounds, nitrogen and carbon in leaves, culms and spikes and proteins and gluten in grains. In particular, plants grown under UV exclusion showed a reduction in protein and dry gluten content (consequently without variation in the ratio dry gluten/protein), but at the same time, a significant increase of gluten index, which is a parameter to define the quality of gluten, was observed. The results highlighted the influence played by UV radiation on some biochemical parameters, mainly UV‐absorbing compounds, leaf nitrogen and grain protein characteristics of durum wheat cultivated under Mediterranean conditions. In particular, natural level of UV in the Mediterranean improves the characteristics of durum wheat flour important for pasta production (high dry gluten level), while the UV exclusion could improve characteristics of flour important for bread production (high gluten index). [ABSTRACT FROM AUTHOR]

Interactions between model parameters and low spatiotemporal resolution of available data mean that conventional soil organic carbon (SOC) models are often affected by equifinality, with consequent uncertainty in SOC forecasts. Estimation of belowground C inputs is another major source of uncertainty in SOC modelling. Models are usually calibrated on SOC stocks and fluxes from long‐term experiments (LTEs), whereas other point data are not used for constraining the model parameters. We used data from an agricultural long‐term (>65 years) fertilization experiment to test a multi‐objective parameter estimation approach on the RothC model, combining SOC data from different fertilization treatments with microbial biomass, basal respiration and Zimmermann's fractions data. We also compared two methods to estimate the belowground C inputs: a conventional scaling of belowground biomass from crop harvest yield and an alternative approach based on constant belowground C for cereals measured experimentally in the field. The resulting posterior parameter distributions still suffered from some equifinality; the most stable C pool kinetic constants and composition of exogenous organic matter were the most sensitive parameters. The use of fixed belowground C inputs for cereals improved the model performance, reducing the importance of treatment‐specific parameters and processes. The introduction of microbial biomass and basal respiration data was effective for increasing determination of the calibration, but also suggested a change in the model structure: the microbial biomass pool, which is proportional to the C inputs in the traditional models, could be represented by different microbial physiology functions. Highlights: Multi‐objective calibration with SOC and microbial or soil fractionation data can reduce model uncertainty.We compared different methods to estimate belowground C inputs on a long‐term trial in Switzerland.Fixed belowground C inputs measured in the field gave the best model performance.Microbial data can improve model calibration, but a change in model structure is suggested. [ABSTRACT FROM AUTHOR]

Background & Aims: Advances in direct‐acting antiviral treatment of HCV have reinvigorated public health initiatives aimed at identifying affected individuals. We evaluated the possible impact of only diagnosed and linked‐to‐care individuals on overall HCV burden estimates and identified a possible strategy to achieve the WHO targets by 2030. Methods: Using a modelling approach grounded in Italian real‐life data of diagnosed and treated patients, different linkage‐to‐care scenarios were built to evaluate potential strategies in achieving the HCV elimination goals. Results: Under the 40% linked‐to‐care scenario, viraemic burden would decline (60%); however, eligible patients to treat will be depleted by 2025. Increased case finding through a targeted screening strategy in 1948‐1978 birth cohorts could supplement the pool of diagnosed patients by finding 75% of F0‐F3 cases. Under the 60% linked‐to‐care scenario, viraemic infections would decline by 70% by 2030 but the patients eligible for treatment will run out by 2028. If treatment is to be maintained, a screening strategy focusing on 1958‐1978 birth cohorts could capture 55% of F0‐F3 individuals. Under the 80% linked‐to‐care scenario, screening limited in 1968‐1978 birth cohorts could sustain treatment at levels required to achieve the HCV elimination goals. Conclusion: In Italy, which is an HCV endemic country, the eligible pool of patients to treat will run out between 2025 and 2028. To maintain the treatment rate and achieve the HCV elimination goals, increased case finding in targeted, high prevalence groups is required. [ABSTRACT FROM AUTHOR]

2006), there was no designation of a single specimen as type, but two collections (P, BM!) of I Blanchet 2093 i as the holotype (also indicated as the holotype of the synonym I Phyllanthus flagelliformis i var. I demonstrans i ). In the publication, "(2909) Proposal to conserve the name I Phyllanthus flagelliformis i against I P. eurisladro i ( I Phyllanthaceae i )" (Orlandini & al. in Taxon 71: 911-912. Corrigendum to: (2909) Proposal to conserve the name Phyllanthus flagelliformis against P. eurisladro (Phyllanthaceae) [in Taxon 71(4): 911-912. [Extracted from the article]

OBJECTIVE: To evaluate the efficacy and safety of golimumab in biological naive and experienced patients with moderately to severely active ulcerative colitis (UC) treated at two Italian IBD centers. METHODS: We retrospectively reviewed our prospectively maintained UC database from March 2015 to March 2017. Patients received golimumab 200 mg at week 0, 100 mg at week 2, then 50 mg or 100 mg every 4 weeks. Follow‐up was recorded at 12 and 24 weeks and in March 2017, with a median follow‐up of 64 weeks. The main outcomes evaluated were clinical remission (CR) and adverse event rates. RESULTS: Of the 59 patients (44% naive and 56% experienced), CR rate was 47% at 12‐week follow‐up, 55% (among the 49 patients on treatment) at 24‐week follow‐up and 49% (among 35 patients on treatment) at the last follow‐up visit. Median treatment duration was 52 weeks (interquartile range 30–64 weeks) among patients treated for >6 months. Overall, 10 (17%) patients experienced adverse events, of whom 50% discontinued treatment. The most frequent adverse events were infections. Biological naive and experienced patients did not differ in terms of CR and adverse event rates. CONCLUSIONS: Our real‐life experience showed that CR decreased over time and was achieved by almost one‐third of the cohort at the last follow‐up visit. Golimumab showed an overall favorable safety profile and the results were not different between biological naive and experienced patients. Future research is needed to confirm our results and to identify criteria to select patients most likely to respond. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is an ultra‐rare highly malignant tumor of the skeletal system affecting mainly children and young adults and it is characterized by an extremely aggressive clinical course. OS patients are currently treated with chemotherapy and complete surgical resection of cancer tissue. However, resistance to chemotherapy and the recurrence of disease, as pulmonary metastasis, remain the two greatest challenges in the management, and treatment of this tumor. For these reasons, it is of primary interest to find alternative therapeutic strategies for OS. Dysregulated Hedgehog signalling is involved in the development of various types of cancers including OS. It has also been implicated in tumor/stromal interaction and cancer stem cell biology, and therefore presents a novel therapeutic strategy for cancer treatment. In our work, we tested the activity of five potent Smoothened (SMO) inhibitors, four acylguanidine and one acylthiourea derivatives, against an OS cell line. We found that almost all our compounds were able to inhibit OS cells proliferation and to reduce Gli1 protein levels. Our results also indicated that SMO inhibition in OS cells by such compounds, induces apoptosis with a nanomolar potency. These findings suggest that inactivation of SMO may be a useful approach to the treatment of patients with OS. [ABSTRACT FROM AUTHOR]

Abstract: A new grid coarsening strategy, denoted as hydrography‐driven coarsening, is developed in the present study. The hydrography‐driven coarsening is designed to retain the essential hydrographic features of valleys and channels observed in high‐resolution digital elevation models: (1) depressions are filled in the considered high‐resolution digital elevation model, (2) the obtained topographic data are used to extract a reference grid network composed of all surface flow paths, (3) the Horton order is assigned to each link of the reference grid network, and (4) within each coarse grid cell, the elevation of the point lying along the highest‐order path of the reference grid network and displaying the minimum distance to the cell center is assigned to this coarse grid cell center. The capabilities of the hydrography‐driven coarsening to provide consistent surface flow paths with respect to those observed in high‐resolution digital elevation models are evaluated over a synthetic valley and two real drainage basins located in the Italian Alps and in the Italian Apennines. The hydrography‐driven coarsening is found to yield significantly more accurate valley and channel profiles than existing coarsening strategies. In absolute terms, the obtained valleys and channels compare favorably with those observed. In addition, the proposed coarsening strategy is found to reduce drastically the impact of depression‐filling in the obtained coarse digital elevation models. The hydrography‐driven coarsening strategy is therefore advocated for all those cases in which the relief of the extracted drainage network is an important hydrographic feature. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the performance of various algorithms for deformable image registration (DIR) to propagate regions of interest (ROIs) using multiple commercial platforms. Methods and materials: Thirteen institutions participated in the study with six commercial platforms: RayStation (RaySearch Laboratories, Stockholm, Sweden), MIM (Cleveland, OH, USA), VelocityAI and Smart Adapt (Varian Medical Systems, Palo Alto, CA, USA), Mirada XD (Mirada Medical Ltd, Oxford, UK), and ABAS (Elekta AB, Stockholm, Sweden). The DIR algorithms were tested on synthetic images generated with the ImSimQA package (Oncology Systems Limited, Shrewsbury, UK) by applying two specific Deformation Vector Fields (DVF) to real patient data‐sets. Head‐and‐neck (HN), thorax, and pelvis sites were included. The accuracy of the algorithms was assessed by comparing the DIR‐mapped ROIs from each center with those of reference, using the Dice Similarity Coefficient (DSC) and Mean Distance to Conformity (MDC) metrics. Statistical inference on validation results was carried out in order to identify the prognostic factors of DIR performances. Results: DVF intensity, anatomic site and participating center were significant prognostic factors of DIR performances. Sub‐voxel accuracy was obtained in the HN by all algorithms. Large errors, with MDC ranging up to 6 mm, were observed in low‐contrast regions that underwent significant deformation, such as in the pelvis, or large DVF with strong contrast, such as the clinical tumor volume (CTV) in the lung. Under these conditions, the hybrid DIR algorithms performed significantly better than the free‐form intensity based algorithms and resulted robust against intercenter variability. Conclusions: The performances of the systems proved to be site specific, depending on the DVF type and the platforms and the procedures used at the various centers. The pelvis was the most challenging site for most of the algorithms, which failed to achieve sub‐voxel accuracy. Improved reproducibility was observed among the centers using the same hybrid registration algorithm. [ABSTRACT FROM AUTHOR]

Copulas are shown in this paper to provide an effective strategy to describe the statistical dependence between peak flow discharge and flood volume featuring hydrographs forcing a flood control reservoir. A 52 year time series of flow discharges observed in the Panaro River (Northern Italian Apennines) is used to fit an event-based bivariate distribution and to support time-continuous modeling of a flood control reservoir, located online along the river system. With regard to reservoir performances, a method aimed at estimating the bivariate return period is analytically developed, by exploiting the derived distribution theory and a simplified routing scheme. In this approach, the return period is that of the peak flow discharge released downstream from the reservoir. Therefore, in order to verify the reliability of the proposed method, a nonparametric version of its frequency distribution is assessed by means of continuous simulation statistics. Copula derived and nonparametric distributions of the downstream peak flow discharge are found to be in satisfactory agreement. Finally, a comparison of bivariate return period estimates carried out by using alternative approaches is illustrated. [ABSTRACT FROM AUTHOR]

Alkaptonuria (AKU) is an ultra-rare genetic disease, in which the accumulation of a toxic metabolite, homogentisic acid (HGA) leads to the systemic development of ochronotic aggregates. These aggregates cause severe complications mainly at the level of joints with extensive degradation of the articular cartilage. Primary cilia have been demonstrated to play an essential role in development and the maintenance of articular cartilage homeostasis, through their involvement in mechanosignaling and Hedgehog signaling pathways. Hedgehog signaling has been demonstrated to be activated in osteoarthritis (OA) and to drive cartilage degeneration in vivo. The numerous similarities between OA and AKU suggest that primary cilia Hedgehog signaling may also be altered in AKU. Thus, we characterized an AKU cellular model in which healthy chondrocytes were treated withHGA(66 µM) to replicateAKUcartilage pathology. We investigated the degree of activation of the Hedgehog signaling pathway and how treatment with inhibitors of the receptor Smoothened (Smo) influenced Hedgehog activation and primary cilia structure. The results obtained in this work provide a further step in the comprehension of the pathophysiological features of AKU, suggesting a potential therapeutic approach to modulate AKU cartilage degradation processes through manipulation of the Hedgehog pathway. [ABSTRACT FROM AUTHOR]

Apparently coincidentally, Müller (l.c. 1863: 53) established a I Phyllanthus klotzschianus i var. I robustus i as the alpha variety of his I P. klotzschianus i , briefly describing the species as "ramulis penultimis validis trigonis, ramulis ultimis densiusculis distincte tristichis v. superne sub-distichis coriaceis 5-8 cm. longis, 8-12 mm. latis obtusiusculis" without indicating a typical element. This species has erect phylloclades and flowers with five tepals (Santiago & al., l.c. 2006: 153), and, according to field observations, it presents sessile flowers, while the other phyllocladiferous species are, for the most part, distinctly pedicellate. The species name, I Phyllanthus robustus i , as well as the characteristics on its exsiccate label were written by Martius with few morphological features and data that allow a solid description of the species. I robustus i has appeared only in species lists like Bouman & al. (l.c. 2022: 47) that incorporated the species in I P i . sect. [Extracted from the article]

The species name, as well as its exsiccate label, was written by Martius with few morphological characteristics and data that would allow a clear identification of the species. In the eight years since the lectotypification by Moraes & al. (l.c.), there has been no other acceptance of the name I Phyllanthus eurisladro i as applying to I P. flagelliformis i . About 27 years separate the publications of these two species names by Colla and Müller Argoviensis, and we currently know, after consulting the exsiccate of I Phyllanthus eurisladro i deposited in TO, that I P i . [Extracted from the article]

Rocks in the continental crust are long lived and have the potential to record a wide span of tectonic history in rock fabric. Mapping rock fabric in situ at depth requires the application of seismic methods. Below depths of microcrack closure seismic anisotropy presumably reflects the shape and crystallographic preferred orientations influenced by deformation processes. Interpretation of seismic observables relevant for anisotropy requires assumptions on the symmetry and orientation of the bulk elastic tensor. We compare commonly made assumptions against a compilation of 95 bulk elastic tensors from laboratory measurements, including electron backscatter diffraction and ultrasound, on crustal rocks. The majority of samples developed fabric at pressures corresponding to middle to lower crustal condition. Tensor symmetry is a function of mineral modal composition, with mica-rich samples trending toward hexagonal symmetry, amphibole-rich samples trending toward an increased orthorhombic symmetry component, and quartz-feldspar-rich samples showing a larger component of lower symmetries. Seventy-seven percent of samples have a best fit hexagonal tensor with slow-axis symmetry, as opposed to mantle deformation fabric that usually has fast-axis symmetry. The best fit hexagonal approximation for crustal tensors is not elliptical but deviates systematically from elliptical symmetry with increasing anisotropy, an observation that affects the magnitude and orientation of anisotropy inferred from receiver function and surface wave observations. We present empirical linear relationships between anisotropy and ellipticity for crustal rocks. The maximum out-of-plane conversion amplitudes in receiver functions scale linearly with degree of anisotropy for nonelliptical symmetry. The elliptical assumption results in a bias of up to 1.4 times true anisotropy. [ABSTRACT FROM AUTHOR]

In patients with age-related macular degeneration (AMD), choroidal neovascularization is the major cause of severe visual loss. In these patients, the persistence of neovascular growth despite vascular endothelial growth factor-A blockage needs the discovery of new endothelial cell targets. The glycoprotein CD93, highly expressed in activated endothelial cells, has been recently involved in the regulation of the angiogenic process both as transmembrane and soluble protein. Choroidal neovascular membranes from patients affected by AMD were examined by immunofluorescence using anti-CD93 and anti-von Willebrand factor antibodies. Blood vessels within intraocular and extraocular neoplasias were used as controls for CD93 expression. All choroidal neovascular membranes displayed strong CD93 staining in the von Willebrand factor-positive endothelial cells, consistently with the analyses showing a high colocalization coefficient in the blood vessels. Intraocular and extraocular tumor vessels showed similar results, whereas the normal choroid displayed blood vessels with only faint CD93 staining. Additionally, the concentration of soluble CD93 was determined in the aqueous humor of patients affected by naïve neovascular AMD by enzyme-linked immunosorbent assays. Age-matched cataract patients served as controls. Soluble CD93 was significantly increased in the aqueous humor of naïve neovascular AMD patients and tended to decrease after treatment with an antiangiogenic drug. In conclusion, both transmembrane and soluble CD93 are overexpressed in patients with neovascular AMD, indicating that CD93 may represent a potential new antiangiogenic target in the treatment of choroidal neovascularization. J. Cell. Physiol. 232: 1767-1773, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Tris-( N-phenylureido)-calix[6]arene derivatives are heteroditopic non-symmetric molecular hosts that can form pseudorotaxane complexes with 4,4′-bipyridinium-type guests. Owing to the unique structural features and recognition properties of the calix[6]arene wheel, these systems are of interest for the design and synthesis of novel molecular devices and machines. We envisaged that the incorporation of photoactive units in the calixarene skeleton could lead to the development of systems the working modes of which can be governed and monitored by means of light-activated processes. Here, we report on the synthesis, structural characterization, and spectroscopic, photophysical, and electrochemical investigation of two calix[6]arene wheels decorated with three naphthyl groups anchored to either the upper or lower rim of the phenylureido calixarene platform. We found that the naphthyl units interact mutually and with the calixarene skeleton in a different fashion in the two compounds, which thus exhibit a markedly distinct photophysical behavior. For both hosts, the inclusion of a 4,4 ′-bipyridinium guest activates energy- and/or electron-transfer processes that lead to non-trivial luminescence changes. [ABSTRACT FROM AUTHOR]

X-ray radiation in macromolecular crystallography can chemically alter the biological material and deteriorate the integrity of the crystal lattice with concomitant loss of resolution. Typical alterations include decarboxylation of glutamic and aspartic residues, breaking of disulfide bonds and the reduction of metal centres. Helical scans add a small translation to the crystal in the rotation method, so that for every image the crystal is shifted to expose a fresh part. On beamline PROXIMA 2A at Synchrotron SOLEIL, this procedure has been tested with various parameters in an attempt to understand how to mitigate the effects of radiation damage. Here, the strategies used and the crystallographic metrics for various scenarios are reported. Among these, the loss of bromine from bromophenyl moieties appears to be a useful monitor of radiation damage as the carbon-bromine bond is very sensitive to X-ray irradiation. Two cases are focused on where helical scans are shown to be superior in obtaining meaningful data compared with conventional methods. In one case the initial resolution of the crystal is extended over time, and in the second case the anomalous signal is preserved to provide greater effective multiplicity and easier phasing. [ABSTRACT FROM AUTHOR]

Background The measurement of handgrip strength (HGS) has prognostic value with respect to all-cause mortality, cardiovascular mortality and cardiovascular disease, and is an important part of the evaluation of frailty. Published reference ranges for HGS are mostly derived from Caucasian populations in high-income countries. There is a paucity of information on normative HGS values in non-Caucasian populations from low- or middle-income countries. The objective of this study was to develop reference HGS ranges for healthy adults from a broad range of ethnicities and socioeconomically diverse geographic regions. Methods HGS was measured using a Jamar dynamometer in 125,462 healthy adults aged 35-70 years from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Results HGS values differed among individuals from different geographic regions. HGS values were highest among those from Europe/North America, lowest among those from South Asia, South East Asia and Africa, and intermediate among those from China, South America, and the Middle East. Reference ranges stratified by geographic region, age, and sex are presented. These ranges varied from a median (25th-75th percentile) 50 kg (43-56 kg) in men <40 years from Europe/North America to 18 kg (14-20 kg) in women >60 years from South East Asia. Reference ranges by ethnicity and body-mass index are also reported. Conclusions Individual HGS measurements should be interpreted using region/ethnic-specific reference ranges. [ABSTRACT FROM AUTHOR]

Alkaptonuria (AKU) is a rare genetic disease that affects the entire joint. Current standard of AKU treatment is palliative and little is known about its physiopathology. Neovascularization is involved in the pathogenesis of systemic inflammatory rheumatic diseases, a family of related disorders that includes AKU. Here, we investigated the presence of neoangiogenesis in AKU synovium and healthy controls. Synovium from AKU patients, who had undergone total joint replacement or arthroscopy, or from healthy patients without any history of rheumatic diseases, who underwent surgical operation following sport trauma was subjected to hematoxylin and eosin staining. Histologic grades were assigned for clinical disease activity and synovitis based on cellular content of the synovium. By immunofluorescence microscopy, using different endothelial cell markers, we observed large vascularization in AKU but not in healthy synovium. Moreover, Western blotting and quantification analyses confirmed strong expression of endothelial cell markers in AKU synovial tissues. Importantly, AKU synovium vascular endothelium expressed high levels of β-dystroglycan, a protein previously involved in the regulation of angiogenesis in osteoarthritic synovium. This is the first report providing experimental evidences that new blood vessels are formed in AKU synovial tissues, opening new perspectives for AKU therapy. [ABSTRACT FROM AUTHOR]