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Engineering materials to include nanoscale porosity or other nanoscale structures has become a well-established strategy for enhancing the thermoelectric performance of dielectrics. However, the approach is only considered beneficial for materials where the intrinsic phonon mean-free path is much longer than that of the charge carriers. As such, the approach would not be expected to provide significant performance gains in polycrystalline semiconducting alloys, such as SixGe1-x, where mass disorder and grains provide strong phonon scattering. In this manuscript, we demonstrate that the addition of nanoscale porosity to even ultrafine-grained Si 0.8 Ge 0.2 may be worthwhile. The semiclassical Boltzmann transport equation was used to model electrical and phonon transport in polycrystalline Si 0.8 Ge 0.2 containing prismatic pores perpendicular to the transport current. The models are free of tuning parameters and were validated against experimental data. The models reveal that a combination of pores and grain boundaries suppresses phonon conductivity to a magnitude comparable with the electronic thermal conductivity. In this regime, ZT can be further enhanced by reducing carrier concentration to the electrical and electronic thermal conductivity and simultaneously increasing thermopower. Although increases in ZT are modest, the optimal carrier concentration is significantly lowered, meaning semiconductors need not be so strongly supersaturated with dopants. [ABSTRACT FROM AUTHOR]

The combined use of Lecce-University AERONET-photometer measurements and PM2.5, PM10, NO2, CO, and SO2 concentrations from different sites of Apulia-Region Air-Quality Agency represents the peculiarity of this study, which evaluates the impact of COVID-19 lockdown (LD) measures on aerosol and gaseous pollutants. Monthly-averaged columnar and surface parameters of the 2020-year were compared with corresponding monthly parameters of the ref-year obtained by averaging 2017, 2018, and 2019 measurements in order to evaluate LD measure impacts by Average Percent Departure (APD%). Photometer measurements showed that LD measures were likely responsible for the decrease in Aerosol Optical Depth (AOD). The APD% estimated between the 2020- and ref-year AOD (at 440 nm) was characterized by negative values from June to August, reaching the smallest mean value (−46%) in June. Moreover, the columnar aerosol load appeared less affected by continental urban/industrial particles than previous years in the summer of 2020. The PM-concentration-APD% calculated at ten sites was characterized by monthly trends similar to those of AOD-APD%. PM-APD% values varied from site to site and smaller values (up to −57% in June) were on average detected at urban/suburban sites than at background sites (up to −37%). The impact of LD measures on gaseous pollutants was observed from the onset of LD. [ABSTRACT FROM AUTHOR]

Postcopulatory sexual selection is credited as a principal force behind the rapid evolution of reproductive characters, often generating a pattern of correlated evolution between interacting, sex-specific traits. Because the female reproductive tract is the selective environment for sperm, one taxonomically widespread example of this pattern is the co-diversification of sperm length and female sperm-storage organ dimension. In Drosophila, having testes that are longer than the sperm they manufacture was believed to be a universal physiological constraint. Further, the energetic and time costs of developing long testes have been credited with underlying the steep evolutionary allometry of sperm length and constraining sperm length evolution in Drosophila. Here, we report on the discovery of a novel spermatogenic mechanism—sperm cyst looping—that enables males to produce relatively long sperm in short testis. This phenomenon (restricted to members of the saltans and willistoni species groups) begins early during spermatogenesis and is potentially attributable to heterochronic evolution, resulting in growth asynchrony between spermatid tails and the surrounding spermatid and somatic cyst cell membranes. By removing the allometric constraint on sperm length, this evolutionary innovation appears to have enabled males to evolve extremely long sperm for their body mass while evading delays in reproductive maturation time. On the other hand, sperm cyst looping was found to exact a cost by requiring greater total energetic investment in testes and a pronounced reduction in male lifespan. We speculate on the ecological selection pressures underlying the evolutionary origin and maintenance of this unique adaptation. [ABSTRACT FROM AUTHOR]

In Plato's corpus, the Greek word ἐξαίφνης appears precisely thirty-six times. Translated generally as "all of a sudden" or "the instant" in his Parmenides, ἐξαίφνης emerges in some of the most significant passages of Plato's dialogues. Put simply, ἐξαίφνης connotes illumination of the highest realities and philosophical conversion experience. In addition to providing a review of Plato's conception and use of ἐξαίφνης in Parmenides, Republic, Symposium, and the Seventh Letter, our paper brings an ancillary link to light. Namely, the appearance of ἐξαίφνης as a mark for conversion experiences in the New Testament's Acts of the Apostles and Plotinus's Enneads. We reveal how the same pattern and employment of ἐξαίφνης established by Plato emerge in both Acts and the Enneads. This pattern suggests a prolonged period of thinking and training, followed by a flash of understanding. Thus ἐξαίφνης, as evidenced by our survey of its strange instantiation in Plato's dialogues and then subsequently in Acts and the Enneads, becomes a sign for enlightenment, assimilation with the divine, and conversion experience. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims at using a multi-technique approach to detect and analyze the effects of high dose rate spatially fractionated radiation therapies and to compare them to seamless broad beam irradiation targeting healthy and glioblastoma-bearing rat brains and delivering three different doses per each irradiation geometry. Brains were analyzed post mortem by multi-scale X-ray phase contrast imaging–computed tomography, histology, immunohistochemistry, X-ray fluorescence, and small- and wide-angle X-ray scattering to achieve detailed visualization, characterization and classification in 3D of the radio-induced effects on brain tissues. The original results bring new insights to the understanding of the response of cerebral tissue and tumors treated with high dose rate spatially fractioned radiotherapies and put the basis for channeling studies of in-vivo applications for monitoring RT effects. The purpose of this study is to use a multi-technique approach to detect the effects of spatially fractionated X-ray Microbeam (MRT) and Minibeam Radiation Therapy (MB) and to compare them to seamless Broad Beam (BB) irradiation. Healthy- and Glioblastoma (GBM)-bearing male Fischer rats were irradiated in-vivo on the right brain hemisphere with MRT, MB and BB delivering three different doses for each irradiation geometry. Brains were analyzed post mortem by multi-scale X-ray Phase Contrast Imaging–Computed Tomography (XPCI-CT), histology, immunohistochemistry, X-ray Fluorescence (XRF), Small- and Wide-Angle X-ray Scattering (SAXS/WAXS). XPCI-CT discriminates with high sensitivity the effects of MRT, MB and BB irradiations on both healthy and GBM-bearing brains producing a first-time 3D visualization and morphological analysis of the radio-induced lesions, MRT and MB induced tissue ablations, the presence of hyperdense deposits within specific areas of the brain and tumor evolution or regression with respect to the evaluation made few days post-irradiation with an in-vivo magnetic resonance imaging session. Histology, immunohistochemistry, SAXS/WAXS and XRF allowed identification and classification of these deposits as hydroxyapatite crystals with the coexistence of Ca, P and Fe mineralization, and the multi-technique approach enabled the realization, for the first time, of the map of the differential radiosensitivity of the different brain areas treated with MRT and MB. 3D XPCI-CT datasets enabled also the quantification of tumor volumes and Ca/Fe deposits and their full-organ visualization. The multi-scale and multi-technique approach enabled a detailed visualization and classification in 3D of the radio-induced effects on brain tissues bringing new essential information towards the clinical implementation of the MRT and MB radiation therapy techniques. [ABSTRACT FROM AUTHOR]

As the size and distance from shore of new offshore wind power plants (OWPPs) increase, connection to shore using high-voltage (HV) direct-current (DC) technology becomes more cost-effective. Currently, every offshore wind power plant has a collection system based on medium-voltage alternating-current technology. Such systems rely on heavy and bulky low-frequency (i.e., 50 or 60 Hz) transformers: a drawback offshore, where equipment weight and space are restricted. Consequently, there is growing interest in medium-voltage direct-current collection systems, in which low-frequency transformers are replaced with DC/DC converters equipped with lighter and smaller medium-frequency transformers. However, the deployment of all-DC OWPPs still faces several challenges. Based on a very comprehensive and critical literature review, three of them are identified and discussed in this paper. The first challenge is the technological gap at component level. In this work, the DC/DC converter topologies most suitable for application to OWPPs are described and compared. The second challenge is the controllability of DC collection systems. Parallel, series and hybrid DC collection system layouts are presented and discussed. The third challenge is the compliance of all-DC OWPPs with current requirements for their connection to the onshore grids. The three challenges are discussed to highlight current research gaps and potential future directions. [ABSTRACT FROM AUTHOR]

Toxic tumour syndrome (TTS) is a particularly aggressive form of secondary vasculopathy occurring after radiation therapy of uveal melanoma due to the persistence of the necrotic tumour mass inside the eye. The development of TTS confers a particularly unfavourable functional and anatomical ocular prognosis, ultimately requiring enucleation in most cases if untreated. Vitreoretinal (VR) surgery has been successfully applied for treatment and prevention of TTS using both resecting and non-resecting techniques. In this systematic review, we aim to define characteristics of uveal melanomas benefiting the most from secondary VR surgery and to outline the optimal type and timing of VR intervention in such cases. Analysis of the literature reveals that endoresection should be performed within 3 months after radiotherapy to tumours thicker than 7 mm and with a largest basal diameter between 8 mm and 15 mm with post-equatorial location, especially after proton beam treatment. Alternatively, endodrainage remains a valid therapeutic option in eyes with macula-off retinal detachment, tumour diameter larger than 15 mm or ciliary body involvement. VR surgery can be successful in the management of TTS following radiotherapy for uveal melanoma when timing and indication are appropriately evaluated. [ABSTRACT FROM AUTHOR]

In recent decades, endogenous nanocarrier-exosomes have received considerable scientific interest as drug delivery systems. The unique proteo-lipid architecture allows the crossing of various natural barriers and protects exosomes cargo from degradation in the bloodstream. However, the presence of this bilayer membrane as well as their endogenous content make loading of exogenous molecules challenging. In the present work, we will investigate how to promote the manipulation of vesicles curvature by a high-pressure microfluidic system as a ground-breaking method for exosomes encapsulation. Exosomes isolated from Uppsala 87 Malignant Glioma (U87-MG) cell culture media were characterized before and after the treatment with high-pressure homogenization. Once their structural and biological stability were validated, we applied this novel method for the encapsulation in the lipidic exosomal bilayer of the chemotherapeutic Irinotecan HCl Trihydrate-CPT 11. Finally, we performed in vitro preliminary test to validate the nanobiointeraction of exosomes, uptake mechanisms, and cytotoxic effect in cell culture model. [ABSTRACT FROM AUTHOR]

In this manuscript, an optically passive fiber Bragg grating (FBG) interrogation system able to perform high-frequency measurement is proposed. The idea is mainly based on the use of an arrayed waveguide grating (AWG) device which is used to discriminate the fiber optic sensor (FOS) wavelength encoded response under test in function of its output channels. As made clear by the theoretical model studied in the proposed manuscript, the Bragg wavelength shift can be detected as in linear dependence with the proposed interrogation function which changes with the voltage produced by two (or more) adjacent AWG output channels. To prove the feasibility of the system, some experimental analyses are conducted with a custom electrical module characterized by high-speed and low-noise operational amplifiers. As static measurements, three FBGs with different full width at half maximum (FWHM) have been monitored under wide-range wavelength variation; while, as dynamic measurement, one FBG, glued onto a metal plate, in order to sense the vibration at low and high frequency, was detected. The output signals have been processed by a digital acquisition (DAQ) board and a graphical user interface (GUI). The presented work highlights the characteristics of the proposed idea as competitor among the entire class of interrogation systems currently used. This is because here, the main device, that is the AWG, is passive and reliable, without the need to use modulation signals, or moving parts, that affect the speed of the system. In addition, the innovative multi-channel detection algorithm allows the use of any type of FOS without the need to have a perfectly match of spectra. Moreover, it is also characterized by a high dynamic range without loss of sensitivity. [ABSTRACT FROM AUTHOR]

Low aqueous solubility and poor oral bioavailability are limiting factors in the oral delivery of voxelotor, an antisickling agent. To overcome these limitations, a voxelotor self-nanoemulsifying drug delivery system was developed. Various oils, surfactants, and cosurfactants were screened for their solubilization potential for the drug. The area of nanoemulsification was identified using a ternary phase diagram. An experimental mixture design and a desirability function were applied to select SNEDDSs that contain a maximum amount of lipids and a minimum amount of surfactant, and that possess optimal emulsification properties (i.e., droplet sizes, polydispersity index (PDI), emulsification time, and transmittance percentage). The optimized SNEDDS formulation was evaluated for the self-emulsifying time (32 s), droplet size (35 nm), and zeta potential (−8 mV). In vitro dissolution studies indicated a 3.1-fold improvement in drug solubility from the optimized SNEDDS over pure drug powder. After 60 min of in vitro lipolysis, 88% of the voxelotor loaded in the SNEDDS remained in the aqueous phase. Cytotoxicity evaluation, using Caco-2 cells, indicated the safety of the formulation at 0.9 mg/mL. The transport of the voxelotor SNEDDS across Caco-2 monolayers was significantly enhanced compared to that of the free drug. Compared to the drug suspension, the developed SNEDDS enhanced the oral bioavailability (1.7-fold) of voxelotor in rats. The results suggest that further development of SNEDDSs for the oral delivery of voxelotor is needed. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBDs) are chronic relapsing inflammatory conditions of the gastrointestinal tract, encompassing Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBD-U). They are currently considered as systemic disorders determined by a set of genetic predispositions, individual susceptibility and environmental triggers, potentially able to involve other organs and systems than the gastrointestinal tract. A large number of patients experiences one or more extraintestinal manifestations (EIMs), whose sites affected are mostly represented by the joints, skin, bones, liver, eyes, and pancreas. Pancreatic abnormalities are not uncommon and are often underestimated, encompassing acute and chronic pancreatitis, autoimmune pancreatitis, exocrine pancreatic insufficiency and asymptomatic elevation of pancreatic enzymes. In most cases they are the result of environmental triggers. However, several genetic polymorphisms may play a role as precipitating factors or contributing to a more severe course. The aim of this paper is to provide an updated overview on the available evidence concerning the etiology, pathogenesis and clinical presentation of pancreatic diseases in IBD pediatric patients. [ABSTRACT FROM AUTHOR]

The present paper provides theoretical insights regarding the determinants of firms' incentives to invest in a Circular Economy. The analysis relies on a Cournot model disaggregating the disposal cost in the production function. In a non-simultaneous sequential game, two risk-neutral firms are endowed with a green innovation project that, if successful, would reduce the overall production costs and implement a Circular Economy. Firms are plagued by asymmetric information about the exact value of the other firm's innovation. In this setting, the R&D investment in a Circular Economy, by affecting the distribution of production and disposal costs, influences the production decisions of both the innovating and the rival firms. The sign of the impact depends on the firms' strategy in the product market. Furthermore, the analysis points out that cooperation in R&D of firms competing in the product market reinforces incentives to invest in green innovation. This suggests that governments aimed to advance a Circular Economy should encourage firms' cooperation. [ABSTRACT FROM AUTHOR]

Following electrification of automotive transport, studies on the penetration of electric vehicles (EVs) are widespread, especially in defined contexts. As major transport hubs, airports fall within contexts worthy of interest. In this work, a forecast of the demand for electric mobility in an Italian international airport (Rome–Fiumicino) is presented. The main goal of the research is to build up a methodology that allows evaluating the penetration index of EVs that will access the airport parks in 2025 and 2030, to be able to have a preliminary assessment of the number of charging points necessary for serving them. In the paper, first, a wide review of proposed scenarios on the penetration of EVs at international and national level and available data on local automotive transport are presented, as a preliminary study for the definition of reference scenarios for the local context. Then, the proposed methodology is presented and applied to the specific case study. Finally, a preliminary sizing of the required charging infrastructure is reported. The results show that a significant impact on the airport electricity network can be foreseen, and it requires proper planning of adaptation/upgrading actions. The proposed approach can be considered as a reference for similar studies on electrical mobility in other airport areas around the world. [ABSTRACT FROM AUTHOR]

Image Coregistration for InSAR processing is a time-consuming procedure that is usually processed in batch mode. With the availability of low-energy GPU accelerators, processing at the edge is now a promising perspective. Starting from the individuation of the most computationally intensive kernels from existing algorithms, we decomposed the cross-correlation problem from a multilevel point of view, intending to design and implement an efficient GPU-parallel algorithm for multiple settings, including the edge computing one. We analyzed the accuracy and performance of the proposed algorithm—also considering power efficiency—and its applicability to the identified settings. Results show that a significant speedup of InSAR processing is possible by exploiting GPU computing in different scenarios with no loss of accuracy, also enabling onboard processing using SoC hardware. [ABSTRACT FROM AUTHOR]

The aim of the study was to compare the clinical phenotype of patients with familial Mediterranean fever (FMF)-related AA amyloidosis, according to the age of FMF diagnosis and E148Q genotype. Patients with biopsy-confirmed FMF-related AA amyloidosis were included in the study. Tel-Hashomer criteria were applied in the diagnosis of FMF. All patients had detailed baseline assessment of clinical features, renal functions, genetic testing, histopathological diagnosis of amyloidosis, and treatment received. Multiple comparisons were performed according to the age of diagnosis, disease phenotype, mutation, and mortality. Our study included 169 patients with a diagnosis of AA amyloidosis. There were 101 patients diagnosed with FMF < 18 years of age and 68 patients diagnosed who were ≥18 years of age. The three most common clinical manifestations were fever (84.6%), abdominal pain (71.6%), and arthritis (66.9%). The most common allele among FMF patients was M694V (60.6%), followed by E148Q (21.4%), and M680I (10.3%). The most frequent genotypes were M694V/M694V (45.0%), M694V/E148Q (14.8%), and E148Q/E148Q (11.2%) among 169 patients in our cohort. During the follow-up period, 15 patients (10 male, 5 female) died, of whom 14 had M694V homozygous genotype and one was homozygous for E148Q. Clinicians should be aware of patients with homozygous E148Q genotype for close monitoring and further evaluation. The possible relationship between E148Q and AA amyloidosis needs to be confirmed in other ethnicities. [ABSTRACT FROM AUTHOR]

Epigenetic regulators play a crucial role in establishing and maintaining gene expression states. To date, the main efforts to study cellular heterogeneity have focused on elucidating the variable nature of the chromatin landscape. Specific chromatin organisation is fundamental for normal organogenesis and developmental homeostasis and can be affected by different environmental factors. The latter can lead to detrimental alterations in gene transcription, as well as pathological conditions such as cancer. Epigenetic marks regulate the transcriptional output of cells. Centromeres are chromosome structures that are epigenetically regulated and are crucial for accurate segregation. The advent of single-cell epigenetic profiling has provided finer analytical resolution, exposing the intrinsic peculiarities of different cells within an apparently homogenous population. In this review, we discuss recent advances in methodologies applied to epigenetics, such as CUT&RUN and CUT&TAG. Then, we compare standard and emerging single-cell techniques and their relevance for investigating human diseases. Finally, we describe emerging methodologies that investigate centromeric chromatin specification and neocentromere formation. [ABSTRACT FROM AUTHOR]

In this paper, we propose a highly sensitive temperature sensor based on two cascaded Mach–Zehnder interferometers (MZIs) that work using the Vernier effect. The all-fiber MZIs were assembled by splicing a segment of capillary hollow-core fiber (CHCF) between two sections of multimode fibers (MMFs). This cascaded configuration exhibits a temperature sensitivity of 1.964 nm/°C in a range from 10 to 70 °C, which is ~67.03 times higher than the sensitivity of the single MZI. Moreover, this device exhibits a high-temperature resolution of 0.0153 °C. A numerical analysis was carried out to estimate the devices' temperature sensitivity and calculate the magnification of the sensitivity produced by the Vernier effect. The numerical results have an excellent agreement with the experimental results and provide a better insight into the working principle of the MZI devices. The sensor's performance, small size, and easy fabrication make us believe that it is an attractive candidate for temperature measurement in biological applications. [ABSTRACT FROM AUTHOR]

Repurposing of remdesivir and other drugs with potential antiviral activity has been the basis of numerous clinical trials aimed at SARS-CoV-2 infection in adults. However, expeditiously designed trials without careful consideration of dose rationale have often resulted in treatment failure and toxicity in the target patient population, which includes not only adults but also children. Here we show how paediatric regimens can be identified using pharmacokinetic-pharmacodynamic (PKPD) principles to establish the target exposure and evaluate the implications of dose selection for early and late intervention. Using in vitro data describing the antiviral activity and published pharmacokinetic data for the agents of interest, we apply a model-based approach to assess the exposure range required for adequate viral clearance and eradication. Pharmacokinetic parameter estimates were subsequently used with clinical trial simulations to characterise the probability target attainment (PTA) associated with enhanced antiviral activity in the lungs. Our analysis shows that neither remdesivir, nor anti-malarial drugs can achieve the desirable target exposure range based on a mg/kg dosing regimen, due to a limited safety margin and high concentrations needed to ensure the required PTA. To date, there has been limited focus on suitable interventions for children affected by COVID-19. Most clinical trials have defined doses selection criteria empirically, without thorough evaluation of the PTA. The current results illustrate how model-based approaches can be used for the integration of clinical and nonclinical data, providing a robust framework for assessing the probability of pharmacological success and consequently the dose rationale for antiviral drugs for the treatment of SARS-CoV-2 infection in children. [ABSTRACT FROM AUTHOR]

Cyanobacteria are microorganisms with photosynthetic mechanisms capable of colonizing several distinct environments worldwide. They can produce a vast spectrum of bioactive compounds with different properties, resulting in an improved adaptative capacity. Their richness in secondary metabolites is related to their unique and diverse metabolic apparatus, such as Non-Ribosomal Peptide Synthetases (NRPSs). One important class of peptides produced by the non-ribosomal pathway is anabaenopeptins. These cyclic hexapeptides demonstrated inhibitory activity towards phosphatases and proteases, which could be related to their toxicity and adaptiveness against zooplankters and crustaceans. Thus, this review aims to identify key features related to anabaenopeptins, including the diversity of their structure, occurrence, the biosynthetic steps for their production, ecological roles, and biotechnological applications. [ABSTRACT FROM AUTHOR]

Although battery electric vehicles (BEVs) are locally emission-free and assist automakers in reducing their carbon footprint, two major disadvantages are their shorter range and higher production costs compared to combustion engines. These drawbacks are primarily due to the battery, which is generally the heaviest and most expensive component of a BEV. Lightweight measures (strategies to decrease vehicle mass, e.g., by changing materials or downsizing components) lower energy consumption and reduce the amount of battery energy required (and in turn battery costs). Careful selection of lightweight measures can result in their costs being balanced out by a commensurate reduction in battery costs. This leads to a higher efficiency vehicle, but without affecting its production and development costs. In this paper, we estimate the lightweight potential of BEVs, i.e., the cost limit below which a lightweight measure is fully compensated by the cost savings it generates. We implement a parametric energy consumption and mass model and apply it to a set of BEVs. Subsequently, we apply the model to quantify the lightweight potential range (in €/kg) of BEVs. The findings of this paper can be used as a reference for the development of cheaper, lighter, and more energy-efficient BEVs. [ABSTRACT FROM AUTHOR]

Respiratory monitoring is receiving growing interest in different fields of use, ranging from healthcare to occupational settings. Only recently, non-contact measuring systems have been developed to measure the respiratory rate ( f R ) over time, even in unconstrained environments. Promising methods rely on the analysis of video-frames features recorded from cameras. In this work, a low-cost and unobtrusive measuring system for respiratory pattern monitoring based on the analysis of RGB images recorded from a consumer-grade camera is proposed. The system allows (i) the automatized tracking of the chest movements caused by breathing, (ii) the extraction of the breathing signal from images with methods based on optical flow (FO) and RGB analysis, (iii) the elimination of breathing-unrelated events from the signal, (iv) the identification of possible apneas and, (v) the calculation of f R value every second. Unlike most of the work in the literature, the performances of the system have been tested in an unstructured environment considering user-camera distance and user posture as influencing factors. A total of 24 healthy volunteers were enrolled for the validation tests. Better performances were obtained when the users were in sitting position. FO method outperforms in all conditions. In the f R range 6 to 60 breaths/min (bpm), the FO allows measuring f R values with bias of −0.03 ± 1.38 bpm and −0.02 ± 1.92 bpm when compared to a reference wearable system with the user at 2 and 0.5 m from the camera, respectively. [ABSTRACT FROM AUTHOR]

The moment-based M 2 M 4 signal-to-noise (SNR) estimator was proposed for a complex sinusoidal signal with a deterministic but unknown phase corrupted by additive Gaussian noise by Sekhar and Sreenivas. The authors studied its performances only through numerical examples and concluded that the proposed estimator is asymptotically efficient and exhibits finite sample super-efficiency for some combinations of signal and noise power. In this paper, we derive the analytical asymptotic performances of the proposed M 2 M 4 SNR estimator, and we show that, contrary to what it has been concluded by Sekhar and Sreenivas, the proposed estimator is neither (asymptotically) efficient nor super-efficient. We also show that when dealing with deterministic signals, the covariance matrix needed to derive asymptotic performances must be explicitly derived as its known general form for random signals cannot be extended to deterministic signals. Numerical examples are provided whose results confirm the analytical findings. [ABSTRACT FROM AUTHOR]

The purpose of this randomized controlled study was to evaluate the clinical efficacy of a novel oral spray containing resveratrol (RV) in controlling bacterial biofilm and gingival inflammation in early childhood. RV, a natural polyphenol, known for its anti-inflammatory and anti-infective activities, was included in a nanovector of 2-hydroxypropyl-beta-cyclodextrins (HPβCD) to improve its bioavailability. A total of 64 children between two and five years of age with plaque-induced gingivitis were randomly included in two equal groups. Both groups were enrolled in a mechanical plaque control program for a period of four weeks, while the test group was also instructed to use the RV-HPβCD mouthwash (in spray formulation) once daily, after toothbrushing. All children underwent three oral hygiene motivation sessions, 14 days apart, during which the full-mouth presence of bacterial plaque, gingival inflammation, dental stain and salivary pH were recorded. At two-week appointment, they also received professional plaque removal. The use of RV-based oral spray significantly reduced the amount of dental plaque and the percentage of bleeding sites and improved salivary pH compared to the control group at both two- and four-week examinations. Based on these promising results, the local delivery of RV-HPβCD via oral spray could enhance the control of dental biofilm in early childhood, when antiseptic mouthwashes are not recommended. [ABSTRACT FROM AUTHOR]

Thyroid cancer is the most common malignancy of the endocrine system, encompassing different entities with distinct histological features and clinical behavior. The diagnostic definition, therapeutic approach, and follow-up of thyroid cancers display some controversial aspects that represent unmet medical needs. Liquid biopsy is a non-invasive approach that detects and analyzes biological samples released from the tumor into the bloodstream. With the use of different technologies, tumor cells, free nucleic acids, and extracellular vesicles can be retrieved in the serum of cancer patients and valuable molecular information can be obtained. Recently, a growing body of evidence is accumulating concerning the use of liquid biopsy in thyroid cancer, as it can be exploited to define a patient's diagnosis, estimate their prognosis, and monitor tumor recurrence or treatment response. Indeed, liquid biopsy can be a valuable tool to overcome the limits of conventional management of thyroid malignancies. In this review, we summarize currently available data about liquid biopsy in differentiated, poorly differentiated/anaplastic, and medullary thyroid cancer, focusing on circulating tumor cells, circulating free nucleic acids, and extracellular vesicles. [ABSTRACT FROM AUTHOR]

Water infiltration rate (WIR) into the soil profile was investigated through a comprehensive study harnessing spectral information of the soil surface. As soil spectroscopy provides invaluable information on soil attributes, and as WIR is a soil surface-dependent property, field spectroscopy may model WIR better than traditional laboratory spectral measurements. This is because sampling for the latter disrupts the soil-surface status. A field soil spectral library (FSSL), consisting of 114 samples with different textures from six different sites over the Mediterranean basin, combined with traditional laboratory spectral measurements, was created. Next, partial least squares regression analysis was conducted on the spectral and WIR data in different soil texture groups, showing better performance of the field spectral observations compared to traditional laboratory spectroscopy. Moreover, several quantitative spectral properties were lost due to the sampling procedure, and separating the samples according to texture gave higher accuracies. Although the visible near-infrared–shortwave infrared (VNIR–SWIR) spectral region provided better accuracy, we resampled the spectral data to the resolution of a Cubert hyperspectral sensor (VNIR). This hyperspectral sensor was then assembled on an unmanned aerial vehicle (UAV) to apply one selected spectral-based model to the UAV data and map the WIR in a semi-vegetated area within the Alento catchment, Italy. Comprehensive spectral and WIR ground-truth measurements were carried out simultaneously with the UAV–Cubert sensor flight. The results were satisfactorily validated on the ground using field samples, followed by a spatial uncertainty analysis, concluding that the UAV with hyperspectral remote sensing can be used to map soil surface-related soil properties. [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is diagnosed by a combination of specific serology and typical duodenal lesions. The histological confirmation of CD, mandatory in the majority of patients with suspected CD, is based on invasive and poorly tolerated procedures, such as upper gastrointestinal endoscopy. In this study we propose an alternative and non-invasive methodology able to confirm the diagnosis of CD based on the analysis of serum samples using the Raman spectroscopy technique. Three different bands centered at 1650, 1450 and 1003 cm−1 have been considered and the A1450/A1003 and A1650/A1003 ratios have been computed to discriminate between CD and non-CD subjects. The reliability of the methodology was validated by statistical analysis using receiver operating characteristic (ROC) curves. The Youden index was also determined to obtain optimal cut-off points. The obtained results highlighted that the proposed methodology was able to distinguish between CD and non-CD subjects with 98% accuracy. The optimal cut-off points revealed, for both the A1450/A1003 and A1650/A1003 ratios, high values of sensitivity and specificity (>95.0% and >92.0% respectively), confirming that Raman spectroscopy may be considered a valid alternative to duodenal biopsy and demonstrates spectral changes in the secondary structures of the protein network. [ABSTRACT FROM AUTHOR]

In systemic sclerosis (SSc), abnormalities in microvessel morphology occur early and evolve into a distinctive vasculopathy that relentlessly advances in parallel with the development of tissue fibrosis orchestrated by myofibroblasts in nearly all affected organs. Our knowledge of the cellular and molecular mechanisms underlying such a unique relationship between SSc-related vasculopathy and fibrosis has profoundly changed over the last few years. Indeed, increasing evidence has suggested that endothelial-to-mesenchymal transition (EndoMT), a process in which profibrotic myofibroblasts originate from endothelial cells, may take center stage in SSc pathogenesis. While in arterioles and small arteries EndoMT may lead to the accumulation of myofibroblasts within the vessel wall and development of fibroproliferative vascular lesions, in capillary vessels it may instead result in vascular destruction and formation of myofibroblasts that migrate into the perivascular space with consequent tissue fibrosis and microvessel rarefaction, which are hallmarks of SSc. Besides endothelial cells, other vascular wall-resident cells, such as pericytes and vascular smooth muscle cells, may acquire a myofibroblast-like synthetic phenotype contributing to both SSc-related vascular dysfunction and fibrosis. A deeper understanding of the mechanisms underlying the differentiation of myofibroblasts inside the vessel wall provides the rationale for novel targeted therapeutic strategies for the treatment of SSc. [ABSTRACT FROM AUTHOR]

The aim of this paper was to assess the differences in tissue response to implantation during 15, 30 and 45 days in the subcutaneous connective tissue of Wistar rats from three biomaterials: Angelus MTA®, Theracal LC®, and Angelus MTA® to which 25% bioglass G3 was added. Twenty-four Wistar rats were used, the materials were inserted into the rat's dorsal area in silicone tubes 5 mm long by 1.5 mm diameter. Histological reaction was assessed at 15, 30, and 45 days after implantation. They were then stained with hematoxylin eosin and evaluated by two observers. Data were analyzed using Fisher's exact test and Mann–Whitney's U test was used to determine the association between variables. Angelus MTA induced the formation of dystrophic calcifications twice as much as Theracal LC (p < 0.05). The addition of G3 did not affect the greater or lesser occurrence of calcifications (p > 0.05). Theracal LC and MTA plus G3 caused an inflammatory reaction, which was chronic at 15 days and decreased in intensity, almost disappearing after 45 days. Theracal LC, as well as Angelus MTA plus G3, were well tolerated when implanted in the subcutaneous connective tissue of rat. Histologically, no inconvenience was found for the use by direct contact of Theracal LC, and the mixture of MTA with 25% bioactive glass G3, in the tissue of Wistar rats. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral squamous cell carcinoma (OSCC) accounts for 90–95% of malignant tumors of the lip and oral cavity and is associated with high mortality in the advanced stages. Early diagnosis is a challenge for oral pathologists and dentists, due to the ambiguous appearance of early OSCC, which is often misdiagnosed, mistreated, and associated with diagnostic delay. The gold standards for OSCC diagnosis are biopsy and histopathological assessment, but these procedures are invasive and time-consuming. Adjunctive noninvasive techniques allow the definition of the malignant features of a suspicious lesion in real time and noninvasively, thus improving the diagnostic procedure. The present review aimed to focus on some of the main promising noninvasive imaging techniques, to highlight their perspective adoption in a three-step diagnosis, which is idealistically faster and better, as well as enables the patient's compliance. Oral squamous cell carcinoma (OSCC) is the most prevalent form of cancer of lips and oral cavity, and its diagnostic delay, caused by misdiagnosis at the early stages, is responsible for high mortality ratios. Biopsy and histopathological assessment are the gold standards for OSCC diagnosis, but they are time-consuming, invasive, and do not always enable the patient's compliance, mainly in cases of follow-up with the need for more biopsies. The use of adjunctive noninvasive imaging techniques improves the diagnostic approach, making it faster and better accepted by patients. The present review aims to focus on the most consolidated diagnostic techniques, such as vital staining and tissue autofluorescence, and to report the potential role of some of the most promising innovative techniques, such as narrow-band imaging, high-frequency ultrasounds, optical coherence tomography, and in vivo confocal microscopy. According to their contribution to OSCC diagnosis, an ideal three-step diagnostic procedure is proposed, to make the diagnostic path faster, better, and more accurate. [ABSTRACT FROM AUTHOR]

Lactobionic acid (LBA) is widely used in different industrial sectors owing to its biocompatibility characteristics as well as antioxidant and antimicrobial properties. In this study, mixtures of the protein zein with LBA and with the addition of oleic acid (OA) as a ternary system were investigated as drug delivery films for the release of LBA. The chosen combinations exploit the vast difference in water solubility between LBA and the other two components (zein and OA). DSC thermograms and dynamic mechanical spectra, alongside electron microscopy images, were used to describe the microstructural features of the films and were found to provide insights for the release of LBA from the two examined zein-based films immersed in an aqueous physiological solution. For both film systems, a burst release behavior was observed, followed by a rapid and total extraction of LBA. The required immersion time for the total extraction of LBA was greatly reduced when oleic acid was added to the precursor solution mixture for producing the films. The LBA released from the zein-based films was found to exhibit both the expected antioxidant properties as well as exerting bacteriostatic effects towards Escherichia coli and Staphylococcus epidermidis. [ABSTRACT FROM AUTHOR]

One of the main questions facing precision agriculture is the evaluation of different algorithms for the delineation of homogeneous management zones. In the present study, a new approach based on the use of time series of satellite imagery, collected during two consecutive growing seasons, was proposed. Texture analysis performed using the Gray-Level Co-Occurrence Matrix (GLCM) was used to integrate and correct the sum of the vegetation indices maps (NDVI and MCARI2) and define the homogenous productivity zones on ten durum wheat fields in southern Italy. The homogenous zones identified through the method that integrates the GLCM indices with the spectral indices studied showed a greater accuracy (0.18–0.22 Mg ha−1 for ∑NDVIs + GLCM and 0.05–0.49 Mg ha−1 for ∑MCARI2s + GLCM) with respect to the methods that considered only the sum of the indices. Best results were also obtained with respect to the homogeneous zones derived by using yield maps of the previous year or vegetation indices acquired in a single day. Therefore, the survey methods based on the data collected over the entire study period provided the best results in terms of estimated yield; the addition of clustering analysis performed with the GLCM method allowed to further improve the accuracy of the estimate and better define homogeneous productivity zones of durum wheat fields. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is among the most devastating digestive tract cancers worldwide. This cancer is characterized by poor diagnostic detection, lack of therapy, and difficulty in predicting tumorigenesis progression. Although mutations of key oncogenes and oncosuppressor involved in tumor growth and in immunosurveillance escape are known, the underlying mechanisms that orchestrate PC initiation and progression are poorly understood or still under debate. In recent years, the attention of many researchers has been concentrated on the role of extracellular vesicles and of a particular subset of extracellular vesicles, known as exosomes. Literature data report that these nanovesicles are able to deliver their cargos to recipient cells playing key roles in the pathogenesis and progression of many pancreatic precancerous conditions. In this review, we have summarized and discussed principal cargos of extracellular vesicles characterized in PC, such as miRNAs, lncRNAs, and several proteins, to offer a systematic overview of their function in PC progression. The study of extracellular vesicles is allowing to understand that investigation of their secretion and analysis of their content might represent a new and potential diagnostic and prognostic tools for PC. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease represents an increasing cause of chronic hepatic disease in recent years. This condition usually arises in patients with multiple comorbidities, the so-called metabolic syndrome. The therapeutic options are multiple, ranging from lifestyle modifications, pharmacological options, to liver transplantation in selected cases. The choice of the most beneficial one and their interactions can be challenging. It is mandatory to stratify the patients according to the severity of their disease to tailor the available treatments. In our contribution, we review the most recent pharmacological target therapies, the role of bariatric surgery, and the impact of liver transplantation on the NAFLD outcome. [ABSTRACT FROM AUTHOR]

In rehabilitation, the upper limb function is generally assessed using clinical scales and functional motor tests. Although the Box and Block Test (BBT) is commonly used for its simplicity and ease of execution, it does not provide a quantitative measure of movement quality. This study proposes the integration of an ecological Inertial Measurement Units (IMUs) system for analysis of the upper body kinematics during the execution of a targeted version of BBT, by able-bodied persons with subjects with Parkinson's disease (PD). Joint angle parameters (mean angle and range of execution) and hand trajectory kinematic indices (mean velocity, mean acceleration, and dimensionless jerk) were calculated from the data acquired by a network of seven IMUs. The sensors were applied on the trunk, head, and upper limb in order to characterize the motor strategy used during the execution of BBT. Statistics revealed significant differences (p < 0.05) between the two groups, showing compensatory strategies in subjects with PD. The proposed IMU-based targeted BBT protocol allows to assess the upper limb function during manual dexterity tasks and could be used in the future for assessing the efficacy of rehabilitative treatments. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma (CM) tissue represents a network constituted by cancer cells and tumor microenvironment (TME). A key feature of CM is the high structural and cellular plasticity of TME, allowing its evolution with disease and adaptation to cancer cell and environmental alterations. In particular, during melanoma development and progression each component of TME by interacting with each other and with cancer cells is subjected to dramatic structural and cellular modifications. These alterations affect extracellular matrix (ECM) remodelling, phenotypic profile of stromal cells, cancer growth and therapeutic response. The stromal fibroblast populations of the TME include normal fibroblasts and melanoma-associated fibroblasts (MAFs) that are highly abundant and flexible cell types interacting with melanoma and stromal cells and differently influencing CM outcomes. The shift from the normal microenvironment to TME and from normal fibroblasts to MAFs deeply sustains CM growth. Hence, in this article we review the features of the normal microenvironment and TME and describe the phenotypic plasticity of normal dermal fibroblasts and MAFs, highlighting their roles in normal skin homeostasis and TME regulation. Moreover, we discuss the influence of MAFs and their secretory profiles on TME remodelling, melanoma progression, targeted therapy resistance and immunosurveillance, highlighting the cellular interactions, the signalling pathways and molecules involved in these processes. [ABSTRACT FROM AUTHOR]

Broadband electromagnetic (EM) modeling increases in importance for virtual prototyping of advanced power electronics systems (PES), enabling a more accurate prediction of fast switching converter operation and its impact on energy conversion efficiency and EM interference. With the aim to predict and reduce an adverse impact of parasitics on the dynamic performance of fast switching power semiconductor devices, the circuit-oriented EM modeling based on the extraction of equivalent lumped R-L-C-G circuits is frequently selected over the Finite Element Method (FEM)-based EM modeling, mainly due to its lower computational complexity. With requirements for more accurate virtual prototyping of fast-switching PES, the modeling accuracy of the equivalent-RLCG-circuit-based EM modeling has to be re-evaluated. In the literature, the equivalent-RLCG-circuit-based EM techniques are frequently misinterpreted as the quasi-static (QS) 3-D Partial Element Equivalent Circuit (PEEC) method, and the observed inaccuracies of modeling HF effects are attributed to the QS field assumption. This paper presents a comprehensive analysis on the differences between the QS 3-D PEEC-based and the equivalent-RLCG-circuit-based EM modeling for simulating the dynamics of fast switching power devices. Using two modeling examples of fast switching power MOSFETs, a 3-D PEEC solver developed in-house and the well-known equivalent-RLCG-circuit-based EM modeling tool, ANSYS Q3D, are compared to the full-wave 3-D FEM-based EM tool, ANSYS HFSS. It is shown that the QS 3-D PEEC method can model the fast switching transients more accurately than Q3D. Accordingly, the accuracy of equivalent-RLCG-circuit-based modeling approaches in the HF range is rather related to the approximations made on modeling electric-field induced effects than to the QS field assumption. [ABSTRACT FROM AUTHOR]

This study aimed to assess the success of pulpotomy in primary molars using Biodentine, new-developed tri-calcium, di-calcium-based silicate cement, at 6 and 12 months. The hypothesis was that stages of root resorption could influence the treatment success. A novel composite score was used based on five clinical and radiographic outcomes: soft-tissue pathology, pain to percussion, pathologic mobility, radiolucency and pathologic root resorption. Patients' compliance and intraoperative pain experience were recorded using the Frankl scale and the Wong–Baker scale. A total of 22 primary molars, 9 in stage S (stability) and 13 in stage R (resorption) were submitted to pulpotomy using Biodentine and restored with composite resin. The success rate was 92.3% in the R group compared to 100% in the S group at both 6 and 12 months (p = 0.850). There was no statistically significant effect of type of molar, tooth position and type of carious lesions on the composite outcome (all p > 0.05). Overall, 73% of the children experienced no or mild/moderate pain and 77% had a cooperative attitude. Children younger than 7 years old experienced more pain (p = 0.04). Biodentine is a promising biomaterial for pulpotomy of primary teeth regardless of the stage of root resorption. [ABSTRACT FROM AUTHOR]

A preliminary local database of potential (opportunistic) airborne human and plant pathogenic and non-pathogenic species detected in PM10 samples collected in winter and spring is provided, in addition to their seasonal dependence and relationships with meteorological parameters and PM10 chemical species. The PM10 samples, collected at a Central Mediterranean coastal site, were analyzed by the 16S rRNA gene metabarcoding approach, and Spearman correlation coefficients and redundancy discriminant analysis tri-plots were used to investigate the main relationships. The screening of 1187 detected species allowed for the detection of 76 and 27 potential (opportunistic) human and plant pathogens, respectively. The bacterial structure of both pathogenic and non-pathogenic species varied from winter to spring and, consequently, the inter-species relationships among potential human pathogens, plant pathogens, and non-pathogenic species varied from winter to spring. Few non-pathogenic species and even fewer potential human pathogens were significantly correlated with meteorological parameters, according to the Spearman correlation coefficients. Conversely, several potential plant pathogens were strongly and positively correlated with temperature and wind speed and direction both in winter and in spring. The number of strong relationships between presumptive (human and plant) pathogens and non-pathogens, and meteorological parameters slightly increased from winter to spring. The sample chemical composition also varied from winter to spring. Some potential human and plant pathogens were correlated with chemicals mainly associated with marine aerosol and/or with soil dust, likely because terrestrial and aquatic environments were the main habitats of the detected bacterial species. The carrier role on the species seasonal variability was also investigated. [ABSTRACT FROM AUTHOR]

Glaucoma is a heterogeneous group of chronic neurodegenerative disorders characterized by a relatively selective, progressive damage to the retinal ganglion cells (RGCs) and their axons, which leads to axon loss and visual field alterations. To date, many studies have shown the role of various elements, mainly metals, in maintaining the balance of prooxidative and antioxidative processes, regulation of fluid and ion flow through cell membranes of the ocular tissues. Based on the earlier and current research results, their relationship with the development and progression of glaucoma seems obvious and is increasingly appreciated. In this review, we aimed to summarize the current evidence on the role of trace elements in the pathogenesis and prevention of glaucomatous diseases. Special attention is also paid to the genetic background associated with glaucoma-related abnormalities of physiological processes that regulate or involve the ions of elements considered as trace elements necessary for the functioning of the cells. [ABSTRACT FROM AUTHOR]

Simple Summary: RAB7A (RAs-related in Brain 7A) is a master regulator of intracellular traffic controlling transport to late endosomes and lysosomes, two organelles of the endocytic pathway important for degradation. Thanks to this function, RAB7A is also involved in cellular processes linked to cancer, such as apoptosis, cytoskeletal reorganization, and cell migration. Therefore, the interest in the role of RAB7A in cancer progression is increasing. Previously, we demonstrated that RAB7A regulates phosphorylation and assembly of vimentin, a cytoskeletal intermediate filament protein, which is also an important mesenchymal marker of cancer cells. The aim of the present study is the identification of the kinases responsible for vimentin phosphorylation whose activity is affected by the modulation of RAB7A expression. We found that RAB7A is able to regulate AKT (also called protein kinase B or PKB) and PAK1 (P21-Activated Kinase 1) and several of their downstream effectors, which control proliferation, apoptosis, survival, migration, and invasion. These data suggest that RAB7A could have a key role in cancer development. RAB7A is a small GTPase that controls the late endocytic pathway but also cell migration through RAC1 (Ras-related C3 botulinum toxin substrate 1) and vimentin. In fact, RAB7A regulates vimentin phosphorylation at different sites and vimentin assembly, and, in this study, we identified vimentin domains interacting with RAB7A. As several kinases could be responsible for vimentin phosphorylation, we investigated whether modulation of RAB7A expression affects the activity of these kinases. We discovered that RAB7A regulates AKT and PAK1, and we demonstrated that increased vimentin phosphorylation at Ser38 (Serine 38), observed upon RAB7A overexpression, is due to AKT activity. As AKT and PAK1 are key regulators of several cellular events, we investigated if RAB7A could have a role in these processes by modulating AKT and PAK1 activity. We found that RAB7A protein levels affected beta-catenin and caspase 9 expression. We also observed the downregulation of cofilin-1 and decreased matrix metalloproteinase 2 (MMP2) activity upon RAB7A silencing. Altogether these results demonstrate that RAB7A regulates AKT and PAK1 kinases, affecting their downstream effectors and the processes they regulate, suggesting that RAB7A could have a role in a number of cancer hallmarks. [ABSTRACT FROM AUTHOR]

Simple Summary: The initial treatment of early breast cancer has achieved important clinical results over time. However, late recurrences after many years of disease-free survival remain an open question, which has recently attracted the attention of a few researchers. The authors of this commentary suggest that the approach emerging from scientific meetings regarding this subject is marred by the lack of attention to recent clinical and laboratory data. The role of tumor dormancy and the dynamics of disease recurrence are presented here and a more general reflection on therapeutic approaches to cancer is proposed. The problem of late recurrence in breast cancer has recently gained attention and was also addressed in an international workshop held in Toronto (ON, Canada), in which several aspects of the question were examined. This Commentary offers a few considerations, which may be useful for the ongoing investigations. A few premises are discussed: (a) clinical recurrences, especially the late ones, imply periods of tumor dormancy; (b) a structured pattern of distant metastases appearance is detectable in both early and late follow-up times; (c) the current general paradigm underlying neoplastic treatments, i.e., that killing all cancer cells is the only way to control the disease, which is strictly sprouting from the somatic mutation theory, should be re-considered. Finally, a few research approaches are suggested. [ABSTRACT FROM AUTHOR]

Molecular docking is a key method for structure-based drug design used to predict the conformations assumed by small drug-like ligands when bound to their target. However, the evaluation of molecular docking studies can be hampered by the lack of a free and easy to use platform for the complete analysis of results obtained by the principal docking programs. To this aim, we developed PacDOCK, a freely available and user-friendly web server that comprises a collection of tools for positional distance-based and interaction-based analysis of docking results, which can be provided in several file formats. PacDOCK allows a complete analysis of molecular docking results through root mean square deviation (RMSD) calculation, molecular visualization, and cluster analysis of docked poses. The RMSD calculation compares docked structures with a reference structure, also when atoms are randomly labelled, and their conformational and positional differences can be visualised. In addition, it is possible to visualise a ligand into the target binding pocket and investigate the key receptor–ligand interactions. Moreover, PacDOCK enables the clustering of docking results by identifying a restrained number of clusters from many docked poses. We believe that PacDOCK will contribute to facilitating the analysis of docking results to improve the efficiency of computer-aided drug design. [ABSTRACT FROM AUTHOR]

Due to associated maxillofacial growth anomalies and the impairment of oral functions, macroglossia may negatively impact the oral health-related quality of life (OHRQoL) of people with Beckwith–Wiedemann syndrome (BWS). Therefore, the aim of this cross-sectional study was to determine the OHRQoL of Italian children and adolescents with BWS compared to healthy peers and to identify which symptoms related to macroglossia had the highest impact. A total of 48 patients with BWS and 48 age- and gender-matched controls completed the Italian version of OHIP-14 and a questionnaire on functional, oral and aesthetic outcomes. Parents of patients with BWS who had undergone tongue reduction surgery (TRS) answered additional questions related to surgery. The BWS group scored higher than controls on the total OHIP-14 and on the dimensions of oral function (p: 0.036) and psychosocial impact (p: 0.002), indicating a reduced OHRQoL. Neither gender nor age had an impact on OHRQoL. Scores were worse in children and adolescents treated with TRS, as most of them still had open bite malocclusion and speech difficulties. The OHRQoL of children and adolescents affected by BWS is worse than that of their healthy peers in spite of the surgical treatment of macroglossia. [ABSTRACT FROM AUTHOR]

Objectives: This review aimed to evaluate the correlation between viral infections (HPV, EBV, HSV-1, CMV) other than HCV and oral lichen planus to assess if there is sufficient evidence to establish if these viruses can play a role in the etiopathogenesis of the disease. Materials and methods: We reviewed the literature using different search engines (PubMed, ISI Web of Science, and the Cochrane Library), employing MeSH terms such as "oral lichen planus" and "OLP" in conjunction with other terms. We utilized the Population, Intervention, Comparison, Outcomes, and Study design (PICOS) method to define our study eligibility criteria. Results: A total of 43 articles of the 1219 results initially screened were included in the study. We allocated the 43 selected items into four groups, according to each related virus: HPV, EBV, HSV-1, and CMV. Conclusions: Heterogeneous results neither confirm nor exclude a direct correlation between the investigated viral infections and oral lichen planus etiopathogenesis and its feasible malignant transformation. Many viral agents can cause oral lesions and act as cancerizing agents. Future studies could be desirable to produce comparable statistical analyses and enhance the quantity and quality of the outcomes to promote the translation of research into clinical practice. [ABSTRACT FROM AUTHOR]

10.1097/ICO.0000000000002681 44 Hubschman J.P., Govetto A., Spaide R.F., Schumann R., Steel D., Figueroa M.S., Sebag J., Gaudric A., Staurenghi G., Haritoglou C. Optical coherence tomography-based consensus definition for lamellar macular hole. 10.1136/bjophthalmol-2014-305648 5 Borroni D., Romano V., Kaye S.B., Somerville T., Napoli L., Fasolo A., Gallon P., Ponzin D., Esposito A., Ferrari S. Metagenomics in ophthalmology: Current findings and future prospectives. 10.3390/jcm11133580 10 Parekh M., Leon P., Ruzza A., Borroni D., Ferrari S., Ponzin D., Romano V. Graft detachment and rebubbling rate in Descemet membrane endothelial keratoplasty. Over the last decade, ophthalmology has significantly benefited from advances in vivo non-invasive ophthalmic imaging techniques that play currently a fundamental role in the clinical assessment, diagnosis, management, and monitoring of a wide variety of conditions involving both the anterior and posterior segment [[1], [3], [5]]. [Extracted from the article]

Silicone oils (SO) are used as long-term intraocular tamponades and have an irreplaceable role in vitreoretinal surgery. They can, however, be associated with multiple and potentially severe complications, involving different ocular tissues, in particular retina and cornea. Recent advances in ophthalmic imaging have allowed the precise characterization of retinal and corneal microstructural changes, at a subclinical level. This detailed analysis of SO-related retinal and corneal changes has improved our understanding of their pathogenesis and offer the potential for optimized monitoring and management of patients with SO-filled eyes. This review aims to provide clinicians and ophthalmic scientists with an updated and comprehensive overview of the corneal and retinal changes associated with SO tamponade. [ABSTRACT FROM AUTHOR]

Simple Summary: Pegfilgrastim, the pegylated form of filgrastim (recombinant human GCSF) is widely adopted as supportive care for preventing neutropenia or febrile neutropenia episodes during chemotherapy. Neutropenia is directly cause of potentially severe infections and indirectly cause of treatment delivery delay. No guidelines address the pegfilgrastim role in the specific setting of Hodgkin lymphoma (HL). Since HL is a young-adult disease and shows mostly a very a favorable outcome after chemotherapy, treatment delay or dose reduction could potentially affect negatively the outcome. The aim of our review is to explore the current scientific literature on pegfilgratim use in HL, evaluating both observational than prospective trial. Moreover, analyzing the latter, we aim to define some practical suggestion about primary prophylaxis with pegfilgrastim in HL. Neutropenia and febrile neutropenia are common and potentially life-threating events associated with chemotherapy treatment in Hodgkin lymphoma (HL). Neutropenia-related infectious events could be an issue both for direct clinical consequences and for delay in treatment delivery, affecting final outcomes in a potentially highly curable disease. Pegfilgrastim is the pegylated form of filgrastim, the recombinant form of human G-CSF, capable of prevent and mitigate neutropenic effects of chemotherapy, when adopted as primary prophylaxis in several hematological malignancies. No updated version of major international guidelines provides clear indication on prophylaxis use of pegfilgrastim in HL to prevent febrile neutropenia episodes in HL. Moreover, to date, scarce and non-uniform clinical experiences evaluating pegfilgrastim as prophylaxis in HL are present in the literature. Herein, we propose a brief summary of the literature data about efficacy and safety of the use of pegfilgrastim as primary prophylaxis in HL during chemotherapy treatment. [ABSTRACT FROM AUTHOR]

Background: Leiomyosarcoma (LMS) originating from the adrenal gland is exceedingly rare, constituting a minute fraction of soft tissue sarcomas. Due to its rarity, with less than 50 documented cases in English medical literature, the diagnosis and management of adrenal LMS remain challenging. The aim of this study was to perform a review of the literature, in order to evaluate the prognosis of these rare cancers and report our specific case. Methods: A systematic review of the literature was conducted using PubMed, Web of Science, Google Scholar, and Scopus databases, up to December 2020. The search utilized MeSH terms such as "Adrenal Gland Neoplasms," "Leiomyosarcoma," "Adrenalectomy," and "Smooth Muscle Tumor." The inclusion criteria focused on studies reporting patients with a histopathological diagnosis of adrenal leiomyosarcoma. The PRISMA guidelines were followed to ensure a comprehensive analysis. Results: Out of 63 identified studies, 43 met the inclusion criteria and were reviewed. These studies highlighted the rarity and aggressive behavior of adrenal leiomyosarcoma. Surgical excision remains the cornerstone of treatment, often complemented by adjuvant therapies. The reviewed case involved a 52-year-old woman who underwent a right laparoscopic adrenalectomy for a 9 × 7 × 6 cm grade 3 leiomyosarcoma. Despite subsequent adjuvant chemotherapy, hepatic metastases were detected, illustrating the aggressive nature of the disease. The literature underscores the importance of histopathological analysis and long-term surveillance for managing disease progression. Conclusions: Optimal management of adrenal leiomyosarcoma requires a multidisciplinary approach and meticulous follow-up. The rarity of the disease poses challenges for standardizing treatment, but surgical excision and tailored adjuvant therapies show promise. Further research is essential to refine treatment strategies and improve prognosis for this rare malignancy. [ABSTRACT FROM AUTHOR]

Aberrant sialylation with overexpression of the homopolymeric glycan polysialic acid (polySia) was recently reported in fibroblasts from fibrotic skin lesions. Yet, whether such a rise in polySia levels or sialylation in general may be functionally implicated in profibrotic activation of fibroblasts and their transition to myofibroblasts remains unknown. Therefore, we herein explored whether inhibition of sialylation could interfere with the process of skin fibroblast-to-myofibroblast transition induced by the master profibrotic mediator transforming growth factor β1 (TGFβ1). Adult human skin fibroblasts were pretreated with the competitive pan-sialyltransferase inhibitor 3-Fax-peracetyl-Neu5Ac (3-Fax) before stimulation with recombinant human TGFβ1, and then analyzed for polySia expression, cell viability, proliferation, migratory ability, and acquisition of myofibroblast-like morphofunctional features. Skin fibroblast stimulation with TGFβ1 resulted in overexpression of polySia, which was effectively blunted by 3-Fax pre-administration. Pretreatment with 3-Fax efficiently lessened TGFβ1-induced skin fibroblast proliferation, migration, changes in cell morphology, and phenotypic and functional differentiation into myofibroblasts, as testified by a significant reduction in FAP, ACTA2, COL1A1, COL1A2, and FN1 gene expression, and α-smooth muscle actin, N-cadherin, COL1A1, and FN-EDA protein levels, as well as a reduced contractile capability. Moreover, skin fibroblasts pre-administered with 3-Fax displayed a significant decrease in Smad3-dependent canonical TGFβ1 signaling. Collectively, our in vitro findings demonstrate for the first time that aberrant sialylation with increased polySia levels has a functional role in skin fibroblast-to-myofibroblast transition and suggest that competitive sialyltransferase inhibition might offer new therapeutic opportunities against skin fibrosis. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease targeting the brain and spinal cord. Non-neuronal cells, including macrophages, may contribute to the disruption of motor neurons (MNs), neuromuscular junction dismantling and clinical signs of ALS. Understanding the modality and the effect of MNs–macrophage communication is pivotal. Here, we focus on extracellular vesicle (EVS)-mediated communication and, in particular, we analyze the response of macrophages. NSC-34 cells transfected with mutant SOD1 (G93A, A4V, G85R, G37R) and differentiated towards MN-like cells, and Raw 264.7 macrophages are the cellular models of the study. mSOD1 NSC-34 cells release a high number of vesicles, both large-lEVs (300 nm diameter) and small-sEVs (90 nm diameter), containing inflammation-modulating molecules, and are efficiently taken up by macrophages. RT-PCR analysis of inflammation mediators demonstrated that the conditioned medium of mSOD1 NSC-34 cells polarizes Raw 264.7 macrophages towards both pro-inflammatory and anti-inflammatory phenotypes. sEVs act on macrophages in a time-dependent manner: an anti-inflammatory response mediated by TGFβ firstly starts (12 h); successively, the response shifts towards a pro-inflammation IL-1β-mediated (48 h). The response of macrophages is strictly dependent on the SOD1 mutation type. The results suggest that EVs impact physiological and behavioral macrophage processes and are of potential relevance to MN degeneration. [ABSTRACT FROM AUTHOR]