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Abstract Background Radiomics is a quantitative approach that allows the extraction of mineable data from medical images. Despite the growing clinical interest, radiomics studies are affected by variability stemming from analysis choices. We aimed to investigate the agreement between two open-source radiomics software for both contrast-enhanced computed tomography (CT) and contrast-enhanced magnetic resonance imaging (MRI) of lung cancers and to preliminarily evaluate the existence of radiomic features stable for both techniques. Methods Contrast-enhanced CT and MRI images of 35 patients affected with non-small cell lung cancer (NSCLC) were manually segmented and preprocessed using three different methods. Sixty-six Image Biomarker Standardisation Initiative-compliant features common to the considered platforms, PyRadiomics and LIFEx, were extracted. The correlation among features with the same mathematical definition was analyzed by comparing PyRadiomics and LIFEx (at fixed imaging technique), and MRI with CT results (for the same software). Results When assessing the agreement between LIFEx and PyRadiomics across the considered resampling, the maximum statistically significant correlations were observed to be 94% for CT features and 95% for MRI ones. When examining the correlation between features extracted from contrast-enhanced CT and MRI using the same software, higher significant correspondences were identified in 11% of features for both software. Conclusions Considering NSCLC, (i) for both imaging techniques, LIFEx and PyRadiomics agreed on average for 90% of features, with MRI being more affected by resampling and (ii) CT and MRI contained mostly non-redundant information, but there are shape features and, more importantly, texture features that can be singled out by both techniques. Relevance statement Identifying and selecting features that are stable cross-modalities may be one of the strategies to pave the way for radiomics clinical translation. Key points • More than 90% of LIFEx and PyRadiomics features contain the same information. • Ten percent of features (shape, texture) are stable among contrast-enhanced CT and MRI. • Software compliance and cross-modalities stability features are impacted by the resampling method. Graphical Abstract

Acute myeloid leukemia (AML) is an aggressive hematologic neoplasia with a complex polyclonal architecture. Among driver lesions, those involving the FLT3 gene represent the most frequent mutations identified at diagnosis. The development of tyrosine kinase inhibitors (TKIs) has improved the clinical outcomes of FLT3-mutated patients (Pt). However, overcoming resistance to these drugs remains a challenge. To unravel the molecular mechanisms underlying therapy resistance and clonal selection, we conducted a longitudinal analysis using a single-cell DNA sequencing approach (MissionBioTapestri® platform, San Francisco, CA, USA) in two patients with FLT3-mutated AML. To this end, samples were collected at the time of diagnosis, during TKI therapy, and at relapse or complete remission. For Pt #1, disease resistance was associated with clonal expansion of minor clones, and 2nd line TKI therapy with gilteritinib provided a proliferative advantage to the clones carrying NRAS and KIT mutations, thereby responsible for relapse. In Pt #2, clonal architecture was less complex, and 1st line TKI therapy with midostaurin was able to eradicate the leukemic clones. Our results corroborate previous findings about clonal selection driven by TKIs, highlighting the importance of a deeper characterization of individual clonal architectures for choosing the best treatment plan for personalized approaches aimed at optimizing outcomes.

Terrestrial ecosystems play a crucial role in global carbon cycling by sequestering carbon from the atmosphere and storing it primarily in living biomass and soil. Monitoring terrestrial carbon stocks is essential for understanding the impacts of changes in land use on carbon sequestration. This study investigates the potential of remote sensing techniques and the Google Earth Engine to map and monitor changes in the forests of Calabria (Italy) over the past two decades. Using satellite-sourced Corine land cover datasets and the InVEST model, changes in Land Use Land Cover (LULC), and carbon concentrations are analyzed, providing insights into the carbon dynamics of the region. Furthermore, cellular automata and Markov chain techniques are used to simulate the future spatial and temporal dynamics of LULC. The results reveal notable fluctuations in LULC; specifically, settlement and bare land have expanded at the expense of forested and grassland areas. These land use and land cover changes significantly declined the overall carbon stocks in Calabria between 2000 and 2024, resulting in notable economic impacts. The region experienced periods of both decline and growth in carbon concentration, with overall losses resulting in economic impacts up to EUR 357.57 million and carbon losses equivalent to 6,558,069.68 Mg of CO 2 emissions during periods of decline. Conversely, during periods of carbon gain, the economic benefit reached EUR 41.26 million, with sequestered carbon equivalent to 756,919.47 Mg of CO 2 emissions. This research aims to highlight the critical role of satellite data in enhancing our understanding and development of comprehensive strategies for managing carbon stocks in terrestrial ecosystems.

Acute myeloid leukemia (AML) is an aggressive heterogeneous disease characterized by several alterations of the immune system prompting disease progression and treatment response. The therapies available for AML can affect lymphocyte function, limiting the efficacy of immunotherapy while hindering leukemia-specific immune reactions. Recently, the treatment based on Venetoclax (VEN), a specific B-cell lymphoma 2 (BCL-2) inhibitor, in combination with hypomethylating agents (HMAs) or low-dose cytarabine, has emerged as a promising clinical strategy in AML. To better understand the immunological effect of VEN treatment, we characterized the phenotype and immune checkpoint (IC) receptors’ expression on CD4+ and CD8+ T cells from AML patients after the first and second cycle of HMA in combination with VEN. HMA and VEN treatment significantly increased the percentage of naïve CD8+ T cells and TIM-3+ CD4+ and CD8+ T cells and reduced cytokine-secreting non-suppressive T regulatory cells (Tregs). Of note, a comparison between AML patients treated with HMA only and HMA in combination with VEN revealed the specific contribution of VEN in modulating the immune cell repertoire. Indeed, the reduction of cytokine-secreting non-suppressive Tregs, the increased TIM-3 expression on CD8+ T cells, and the reduced co-expression of PD-1 and TIM-3 on both CD4+ and CD8+ T cells are all VEN-specific. Collectively, our study shed light on immune modulation induced by VEN treatment, providing the rationale for a novel therapeutic combination of VEN and IC inhibitors in AML patients.

Rockslides are one of the most dangerous hazards in mountainous and hilly areas. In this study, a rockslide that occurred on 30 November 2022 in Castrocucco, a district located in the Italian municipality of Maratea (Potenza province) in the Basilicata region, was investigated by using pre- and post-event high-resolution 3D models. The event caused a great social alarm as some infrastructures were affected. The main road to the tourist hub of Maratea was, in fact, destroyed and made inaccessible. Rock debris also affected a beach club and important boat storage for sea excursions to Maratea. This event was investigated by using multiscale and multisensor close-range remote sensing (LiDAR and SfM) to determine rockslide characteristics. The novelty of this work lies in how these data, although not originally acquired for rockslide analysis, have been integrated and utilized in an emergency at an almost inaccessible site. The event was analyzed both through classical geomorphological analysis and through a quantitative comparison of multi-temporal DEMs (DoD) in order to assess (i) all the morphological features involved, (ii) detached volume (approximately 8000 m3), and (iii) the process of redistributing and reworking the landslide deposit in the depositional area.

Manna, a well-known herbal drug has multiple traditional and pharmaceutical uses and the entire composition, sugar derivatives and polyphenols, gives rise to a very interesting bioactive complex with versatile therapeutic and benefic properties such as antioxidant and anti-inflammatory activities. The aim of this research was to investigate a F. ornus manna extract loaded in a pectin hydrogel as a synergic vehicle to evaluate the potential use of the complex for cosmetic and dermatological applications. In particular, the study set out to disclose manna properties as a wound healing agent with antimicrobial and reparative activity on infected tissues. Moreover, considering the correlation between antioxidant activity and antiaging potential, the extract was investigated in regard to the anti-elastase activity and skin whitening potential. The total phenolic content of each extract was also determined and a safe profile by in vitro cytotoxicity studies was verified. The hydrogel complex, containing the manna extract and pectin as the gelling agent, exhibited suitable properties in terms of pH (from 5.50 to 6.80), rheological behavior and ability of preserving the antioxidant activity of the manna exudate (around 10%). All the peculiarities that make the pectin hydrogels ideal systems for skin disease, as wound dressings and for antiaging cosmetic formulations.

Orchids are experiencing wide success in ornamental, medicinal, and food fields. The reason for their success is correlated with both their morphology and metabolomics, the latter linked to their taste and biological effects. Despite many orchids having already been the subject of chemotaxonomic works, some of them are still untapped, like the case of Orchis purpurea. O. purpurea is one of the most common species of the genus Orchis, present in hedgerows, verges, and light woodland, where it is one of the few herbaceous plants able to be unpleasant to herbivorous animals. Essential oil from roots, stems, leaves, and flowers were analyzed via GC/MS analyses, revealing the presence of 70 compounds, with a clear prevalence of coumarin. The high concentration of this metabolite may explain the resistance of O. purpurea to herbivores, being associated with appetite-suppressing properties and a bitter taste. Non-volatile fractions were analyzed via UHPLC-MS analysis revealing the presence of hydroxycinnamic acid derivatives, polyphenols, and glycosidic compounds, probably responsible for their color and fragrance. Taken together, the herein presented results shed light on both the defensive strategy and the chemotaxonomy of O. purpurea.

Treatment of borderline acetabular dysplasia (lateral center edge angle ≥18°) remains controversial, and there is a paucity of literature focusing on outcomes in adolescent patients. The purpose of this study was to evaluate the outcomes of a periacetabular osteotomy (PAO) as surgical management of borderline acetabular dysplasia in adolescent patients. We performed a retrospective review of prospectively collected data and included patients ≤ 21 years of age that underwent PAO for borderline acetabular dysplasia. All patients had a minimum of 1-year follow-up. Outcomes were assessed using modified Harris Hip Scores (mHHS), Hip Outcome Scores (HOS) and international Hip Outcome Tool (iHOT-33). Descriptive and univariate statistical analyses were performed. This study included 33 adolescent patients (35 hips) with symptomatic, borderline acetabular dysplasia. The majority of patients was female (32 patients, 97%); half of all patients reported a history of hip pain for over 1 year; and seven patients had previous hip arthroscopy. In addition to PAO, seven hips (20%) underwent a concurrent hip arthroscopy at the time of surgery. There were significant improvements in mean mHHS, HOS-activities of daily living (ADL), HOS-Sport and iHOT-33 scores after surgery (P

In this work the authors report atomically detailed computer simulations revealing the binding mechanisms of small molecule drugs to an intrinsically disordered region of the androgen receptor, a castration-resistant prostate cancer drug target.

Linear immunoglobulin (Ig) A disease (LAD) is a rare autoimmune blistering dermatosis caused by linear deposition of IgA1 along the dermoepidermal junction of skin and mucosae. It can affect both children and adults. Although idiopathic in most cases, it can also be associated with infections, malignancies, or drug administration. Among medications, antibiotics are most commonly responsible, particularly vancomycin. We report the case of a 51-year-old female patient who developed mucocutaneous LAD after oral metronidazole administration, which was confirmed by histopathological examination and direct immunofluorescence of one of the bullous lesions. Lesions rapidly cleared after metronidazole discontinuation and a short course of oral methylprednisolone and dapsone. To our knowledge, this is the third reported case of metronidazole-induced LAD, and the first in which metronidazole was not administered in combination with other antibiotics such as ceftriaxone.

Natural deep eutectic solvents (NaDES) represent a new generation of green, non-flammable solvents, useful as an efficient alternative to the well-known ionic liquids. They can be easily prepared and exhibit unexpected solubilizing power for lipophilic molecules, although those of a hydrophilic nature are mostly used. For their unique properties, they can be recommend for different cosmetic and pharmaceutical applications, ranging from sustainable extraction, obtaining ready-to-use ingredients, to the development of biocompatible drug delivery responsive systems. In the biomedical field, NaDES can be used as biopolymer modifiers, acting as delivery compounds also known as “therapeutic deep eutectic systems”, being able to solubilize and stabilize different chemical and galenical formulations. The aim of this review is to give an overview of the current knowledge regarding natural deep eutectic solvents specifically applied in the cosmetic and pharmaceutical fields. The work could help to disclose new opportunities and challenges for their implementation not only as green alternative solvents but also as potential useful pathways to deliver bioactive ingredients in innovative formulations.

Nowadays, the availability of affordable multi-constellation multi-frequency receivers has broadened access to accurate positioning. The abundance of satellite signals coupled with the implementation of ground- and satellite-based correction services has unlocked the potential for achieving real-time centimetre-level positioning with low-cost instrumentation. Most of the current and future applications cannot exploit well-consolidated satellite positioning techniques such as Network Real Time Kinematic (RTK) and Precise Point Positioning (PPP); the former is inapplicable for large user bases due to the necessity of a two-way communication link between the user and the NRTK service provider, while the latter necessitates long convergence times that are not in keeping with kinematic application. In this context, the hybrid PPP-RTK technique has emerged as a potential solution to meet the demand for real-time, low-cost, accurate, and precise positioning. This paper presents an Internet of Things (IoT) GNSS device developed with low-cost hardware; it leverages a commercial PPP-RTK correction service which delivers corrections via IP. The main target is to obtain both horizontal and vertical decimetre-level accuracies in urban kinematic tests, along with other requisites such as solution availability and the provision of connection ports for interfacing an IoT network. A vehicle-borne kinematic test has been conducted to evaluate the device performance. The results show that (i) the IoT device can deliver horizontal and vertical positioning solutions at decimetre-level accuracy with the targeted solution availability, and (ii) the provided IoT ports are feasible for gathering the position solutions over an internet connection.

Hand hygiene plays a pivotal role in preventing Healthcare-Associated Infections (HAIs). Nevertheless, the quality of hand disinfection techniques remains suboptimal, and the reliability of assessment methodologies is notably lacking. This study aimed to evaluate hand disinfection techniques using an automated system in an Italian research hospital. Hospital employees underwent automated hand-disinfection technique assessment, according to the World Health Organization’s six-step protocol, at a basal time and two further times. Detection was carried out with a scanner that evaluated the effective hand disinfectant coverage through a fluorescent dye present in the hydro-alcoholic gel rub. The hand-hygiene technique of 222 employees was analyzed by HandInScan®. At the initial assessment of hand coverage with the hydro-alcoholic gel, the mean palm coverage was 82.2%, mean back coverage was 66.8%, and overall mean hand coverage was 74.5%. Then, two measurements were performed in June (t1) and December 2022 (t2). The third measurement showed an increase in hand coverage, with a mean palm coverage of 97.2%, a mean back coverage of 91.8%, and a mean hand coverage of 94.5% (p < 0.05). Moreover, the mean coverage of the hand-back was lower than that of the hand-palm at all times (p < 0.001). The automated scanner provided evidence supporting its effectiveness in enhancing hand hygiene among hospital employees. These findings have motivated researchers to conduct long-term studies, given the potential effects on HAI prevention—including their impact on HAI trends.

Teodorico Borgognoni was born in Lucca in 1205 and was appointed bishop of Bitonto and Cervia in 1262 and 1270. Following his father, he learned the art of surgery and collected relevant recipes in his most important work, entitled Cyrurgia seu filia principis. Among the disciplines reported in this work, the most interesting and innovative is anesthesia. The recipes in this field contribute to Borbognoni’s consideration as the forerunner of modern anesthesia. Such recipes have been reported in other manuscripts from the Middle Ages, like Manuscript No. 1939. In the present work, we investigate the traditional preparations handed down in this manuscript, focusing on type of preparation and botanical ingredients. The results highlight that exploited ingredients can be divided into three groups: the first comprises plants already known for their narcotic effects, the second includes ingredients acting as an adjuvant for absorption or reducing the metabolism, and the last group includes ingredients not associated with biological activity to explain their presence in anesthetic recipes. This third group is of particular interest for future biological investigations. Our goal is to rekindle attention to the work of Teodorico Borgognoni on traditional preparation for anesthetic purposes: a topic often underestimated by ethnobotanical surveys.

Shelter caves serve as crucial repositories that provide valuable insights into Late Pleistocene–Holocene depositional mechanisms and environmental changes. In this study, we conducted a stratigraphic analysis of the easternmost cave-fill succession within the Santuario della Madonna cave, located along the Tyrrhenian coasts of southern Italy. By examining the cave-fill deposits and their relationship with archaeological successions from previous excavation campaigns, we aimed to enhance our understanding of sedimentary evolution, specifically, the interplay between local and global environmental factors. A comprehensive sedimentological analysis was conducted, enabling the identification of three distinct sedimentary facies within the clastic succession that overlays the calcareous cave roof. Our findings reveal a noticeable shift in cave sedimentation processes, characterized by a gap in detritus accumulation followed by the deposition of flowstones. Furthermore, the presence of oversized boulders within the succession was attributed to failures from the cliffs that overhang the cave opening. We interpret these boulders as possible evidence of cave collapses induced by earthquakes, similarly to rockfall phenomena observed in the archaeological test pits within the shelter, which show a strong correlation with paleoseismic events.

Continuous and unplanned urbanization, combined with negative alterations in land use land cover (LULC), leads to a deterioration of the urban thermal environment and results in various adverse ecological effects. The changes in LULC and thermal characteristics have significant implications for the economy, climate patterns, and environmental sustainability. This study focuses on the Province of Naples in Italy, examining LULC changes and the Urban Thermal Field Variance Index (UTFVI) from 1990 to 2022, predicting their distributions for 2030. The main objectives of this research are the investigation of the future seasonal thermal characteristics of the study area by characterizing land surface temperature (LST) through the UTFVI and analyzing LULC dynamics along with their correlation. To achieve this, Landsat 4-5 Thematic Mapper (TM) and Landsat 9 Operational Land Imager (OLI) imagery were utilized. LULC classification was performed using a supervised satellite image classification system, and the predictions were carried out using the cellular automata-artificial neural network (CA-ANN) algorithm. LST was calculated using the radiative transfer equation (RTE), and the same CA-ANN algorithm was employed to predict UTFVI for 2030. To investigate the multi-temporal correlation between LULC and UTFVI, a cross-tabulation technique was employed. The study’s findings indicate that between 2022 and 2030, there will be a 9.4% increase in built-up and bare-land areas at the expense of the vegetation class. The strongest UTFVI zone during summer is predicted to remain stable from 2022 to 2030, while winter UTFVI shows substantial fluctuations with a 4.62% decrease in the none UTFVI zone and a corresponding increase in the strongest UTFVI zone for the same period. The results of this study reveal a concerning trend of outward expansion in the built-up area of the Province of Naples, with central northern regions experiencing the highest growth rate, predominantly at the expense of vegetation cover. These predictions emphasize the urgent need for proactive measures to preserve and protect the diminishing vegetation cover, maintaining ecological balance, combating the urban heat island effect, and safeguarding biodiversity in the province.

GNSS has become ubiquitous in high-precision applications, although the cost of high-end GNSS receivers remains a major obstacle for many applications. Recent advances in GNSS receiver technology have led to the development of low-cost GNSS receivers, making high-precision positioning available to a wider range of users. One such technique for achieving high-precision positioning is Precise Point Positioning-Real Time Kinematic (PPP-RTK). It is a GNSS processing technique that combines the PPP and RTK approaches to provide high-precision positioning in real time without the need for a base station. In this work, we aim to assess the performance of the low-cost u-blox ZED-F9P GNSS module in PPP-RTK mode using the low-cost u-blox ANN-MB antenna. The experiment was designed to investigate both the time it takes the receiver to resolve the phase ambiguity and to determine the positioning accuracies achievable. Results showed that the u-blox ZED-F9P GNSS module could achieve centimeter-level positioning accuracy in about 60 s in PPP-RTK mode. These results make the PPP-RTK technique a good candidate to fulfill the demand for mass-market accurate and robust navigation since uses satellite-based corrections to provide accurate positioning information without the need for a local base station or network. Furthermore, due to its rapid acquisition capabilities and accurate data georeferencing, the technique has the potential to serve as a valuable method to improve the accuracy of the three-S techniques (GIS, remote sensing, and GPS/GNSS).

Indocyanine green (ICG) is one of the most commonly used fluorophores in near-infrared fluorescence-guided techniques. However, the molecule is prone to form aggregates in saline solution with a limited photostability and a moderate fluorescence yield. ICG was thus formulated using protein-based nanoparticles of H-ferritin (HFn) in order to generate a new nanostructure, HFn-ICG. In this study, an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) system was employed to develop and validate the quantitative analysis of ICG in liver tissue samples from HFn-ICG-treated mice. To precipitate HFn, cold acetone in acidic solution at pH 5.0 was used. The processed liver samples were injected into the UHPLC-MS/MS system for analysis using the positive electrospray ionization mode. Chromatographic separation was achieved on a Waters Acquity UPLC® HSS T3 Column (1.8 μm, 2.1 × 100 mm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. The selected reaction monitoring transitions of m/z 753 →m/z 330 and m/z 827 →m/z 330 were applied for ICG and IR-820 (the internal standard, IS), respectively. The method was selective and linear over a concentration range of 50–1,500 ng/ml. The method was validated for sensitivity, accuracy, precision, extraction recovery, matrix effect, and stability in liver tissue homogenates. ICG extraction recoveries ranged between 85 and 108%. The intra- and inter-day precisions were less than 6.28%. The method was applied to a bio-distribution study to compare the amount of ICG levels from mice treated with HFn-ICG and free ICG. The analyses of the homogenate samples from the two types of treatment showed that the concentration levels of ICG is approximately six-fold higher than those of free ICG (1,411 ± 7.62 ng/ml vs. 235 ± 26.0 ng/ml) at 2 h post injection.

Abstract Heterogeneities in the magnetic signature along intraplate shear zones complicate their correlation with the physical processes that are involved in the geodynamic evolution of megathrusts. Isolating the preferred orientation of different magnetic minerals may provide insights into faulting processes, tectonics, and strain partitioning. Studies of exhumed analogs are fundamental to constrain variations in the magnetic properties with respect to a geodynamic context of intraplate shear zones. This study uses a combined statistical and magnetic approach to separate the contribution of coexisting petrofabrics to better interpret the heterogeneities in the magnetic signature. The main results indicate that there is a strong dependency among the variation in the magnetic properties and their anisotropy with the distance from the thrust faults and strain localization within the shear zone. Close to the main thrust, we observed a shear‐related fabric, indicating a high degree of non‐coaxial strain. Away from the thrust faults, the degree of anisotropy and the ellipsoids' oblateness gradually diminishes and subfabrics related to previous tectonic events or less intense deformation become dominant. Our observations also indicate strain decoupling across the basal thrust with dominant vertical uniaxial strain within the footwall. In contrast characterization of the anisotropy of magnetic remanence provides significant information on the variable response of different subpopulations of ferromagnetic minerals to shearing, indicating different degree of reworking or independent deformation processes.

Volatile Organic Compounds (VOCs) are produced by plants to address a variety of physiological and ecological tasks (among others, stress resistance, and pollinator attraction). Genetics is a key factor in determining plants’ VOCs content and emission, nevertheless, environment strongly influences VOCs profiles in plants. Orchids are a widespread group of plants that colonize diverse environments and rely on complex and refined pollination mechanisms to reproduce. Orchids VOCs are rarely studied and discussed in relation to growing conditions. In the present study, we compare the volatile profiles of inflorescences of Himantoglossum robertianum (Loisel.) P. Delforge sampled in six ecologically diverse populations on Sardinia Island (Italy). The essential oils obtained by steam distillation were characterized by GC-FID and GC-MS analysis. A total of 79 compounds were detected, belonging to the chemical classes of saturated hydrocarbons, esters, alcohols, ketones, unsaturated hydrocarbons, sesquiterpenes, oxygenated terpenes, terpenes, acids, and aldehydes. Multivariate statistics separated H. robertianum populations based on their chemical profiles. Differences were positively linked to the distance separating populations and reflected climatological features of the sampling sites. Interestingly, our results differed from those available in the literature, pointing out the high variability of VOCs profiles in this food-deceptive orchid.

ObjectivePrior reports suggest that autism spectrum disorder (ASD) is associated with atypically excessive early brain growth. Recent cross-sectional studies suggest that later cortical development during adolescence/adulthood might also be aberrant, although longitudinal designs are required to evaluate atypical growth trajectories. The present study sought to examine longitudinal changes in cortical thickness and surface area among adolescents and young adults with ASD.MethodTwo high-resolution anatomic magnetic resonance imaging scans approximately 2 years apart were acquired from 17 adolescents with ASD and 18 typically developing (TD) adolescents, matched on age (range = 14-24 years), IQ, sex ratio, and handedness (70 scans total). The FreeSurfer image analysis suite was used to quantify longitudinal changes in cortical thickness and surface area.ResultsAccelerated cortical thinning for the ASD group as compared to the TD group was found in 2 areas in the left hemisphere, the posterior portion of ventral temporal cortex and superior parietal cortex (cluster corrected p < .01). For ventral temporal cortex, cortical thinning was associated with everyday executive function impairments, and thinner cortex at time 2 was correlated with ASD social symptoms. Differences in surface area changes were not detected.ConclusionThe present longitudinal study extends prior cross-sectional research by demonstrating increased cortical thinning (in portions of temporal and parietal cortex) but comparable surface area growth rates in participants with ASD compared to TD controls during adolescence and into young adulthood. These findings provide further evidence for atypical cortical development beyond the early years in ASD, marked by increased cortical thinning in late adolescence/young adulthood.

FMS-like tyrosine kinase 3 (FLT3) is among the most common driver genes recurrently mutated in acute myeloid leukemia (AML), accounting for approximately 30% of cases. Activating mutations of the FLT3 receptor include internal tandem duplications (ITD) that map to the auto-inhibitory juxtamembrane (JM) domain or point mutations within the tyrosine kinase domain (TKD). Several FLT3 tyrosine kinase inhibitors have been developed in the last few years, but midostaurin is currently the only one approved for the treatment of newly diagnosed patients harboring FLT3 mutations. Here we describe for the first time a novel in-frame deletion in exon 14 (JM domain) of the FLT3 gene, that we identified in a young woman with CBFb-MYH11-positive AML. We demonstrated that this novel FLT3 variant is pathogenic, since it is responsible for constitutive activation of FLT3 receptor. Finally, ex-vivo studies demonstrated that this novel mutation is sensitive to midostaurin.

In recent years, the performance of free-and-open-source software (FOSS) for image processing has significantly increased. This trend, as well as technological advancements in the unmanned aerial vehicle (UAV) industry, have opened blue skies for both researchers and surveyors. In this study, we aimed to assess the quality of the sparse point cloud obtained with a consumer UAV and a FOSS. To achieve this goal, we also process the same image dataset with a commercial software package using its results as a term of comparison. Various analyses were conducted, such as the image residuals analysis, the statistical analysis of GCPs and CPs errors, the relative accuracy assessment, and the Cloud-to-Cloud distance comparison. A support survey was conducted to measure 16 markers identified on the object. In particular, 12 of these were used as ground control points to scale the 3D model, while the remaining 4 were used as check points to assess the quality of the scaling procedure by examining the residuals. Results indicate that the sparse clouds obtained are comparable. MicMac® has mean image residuals equal to 0.770 pixels while for Metashape® is 0.735 pixels. In addition, the 3D errors on control points are similar: the mean 3D error for MicMac® is equal to 0.037 m with a standard deviation of 0.017 m, whereas for Metashape®, it is 0.031 m with a standard deviation equal to 0.015 m. The present work represents a preliminary study: a comparison between software packages is something hard to achieve, given the secrecy of the commercial software and the theoretical differences between the approaches. This case study analyzes an object with extremely complex geometry; it is placed in an urban canyon where the GNSS support can not be exploited. In addition, the scenario changes continuously due to the vehicular traffic.

Adrenomedullin (ADM) is a hypotensive and vasodilator peptide belonging to the calcitonin gene-related peptide family. It is secreted in vitro by endothelial cells and vascular smooth muscle cells, and is significantly upregulated by a number of stimuli. Moreover, ADM participates in the regulation of hematopoietic compartment, solid tumors and leukemias, such as acute myeloid leukemia (AML). To better characterize ADM involvement in AML pathogenesis, we investigated its expression during human hematopoiesis and in leukemic subsets, based on a morphological, cytogenetic and molecular characterization and in T cells from AML patients. In hematopoietic stem/progenitor cells and T lymphocytes from healthy subjects, ADM transcript was barely detectable. It was expressed at low levels by megakaryocytes and erythroblasts, while higher levels were measured in neutrophils, monocytes and plasma cells. Moreover, cells populating the hematopoietic niche, including mesenchymal stem cells, showed to express ADM. ADM was overexpressed in AML cells versus normal CD34+ cells and in the subset of leukemia compared with hematopoietic stem cells. In parallel, we detected a significant variation of ADM expression among cytogenetic subgroups, measuring the highest levels in inv(16)/t(16;16) or complex karyotype AML. According to the mutational status of AML-related genes, the analysis showed a lower expression of ADM in FLT3-ITD, NPM1-mutated AML and FLT3-ITD/NPM1-mutated cases compared with wild-type ones. Moreover, ADM expression had a negative impact on overall survival within the favorable risk class, while showing a potential positive impact within the subgroup receiving a not-intensive treatment. The expression of 135 genes involved in leukemogenesis, regulation of cell proliferation, ferroptosis, protection from apoptosis, HIF-1α signaling, JAK-STAT pathway, immune and inflammatory responses was correlated with ADM levels in the bone marrow cells of at least two AML cohorts. Moreover, ADM was upregulated in CD4+ T and CD8+ T cells from AML patients compared with healthy controls and some ADM co-expressed genes participate in a signature of immune tolerance that characterizes CD4+ T cells from leukemic patients. Overall, our study shows that ADM expression in AML associates with a stem cell phenotype, inflammatory signatures and genes related to immunosuppression, all factors that contribute to therapy resistance and disease relapse.

Acetabular dysplasia has traditionally been defined using the lateral center edge angle and treated with periacetabular osteotomy (PAO). However, the recently described Ottawa classification further quantifies dysplasia in 3-dimensional terms, categorizing Ottawa A as dysplasia due to isolated, excessive acetabular anteversion or anterior acetabular under-coverage. We sought to determine if patients who have Ottawa A dysplasia can expect similar outcomes when undergoing a PAO compared to a traditional dysplasia cohort. Patients who had undergone PAO with Ottawa A hip dysplasia were selected and compared to a control group of patients who had lateral acetabular undercoverage. The modified Harris Hip Score and International Hip Outcome Tool–33 were collected preoperatively and at various follow-up points for a final follow-up average of 2.3 years (range, 0.9 to 6.2). The 17 patients (21 hips) who had Ottawa A dysplasia were compared to a control cohort of 69 patients (88 hips). Both groups saw significant improvements in modified Harris Hip Score and International Hip Outcome Tool–33 at final follow-up, P <.001. There were no differences between groups in any of the outcome measures or rates of achieving minimal clinically important difference (MCID) or substantial clinical benefit. Rates of MCID ranged from 82.4 to 100%, and rates of achieving substantial clinical benefit ranged from 47.1 to 52.9%. In patients undergoing a PAO for Ottawa A hip dysplasia, a significant improvement in patient-reported outcomes can be expected with high rates of MCID achievement. This is not significantly different for patients undergoing PAO for more traditional dysplasia parameters. [ABSTRACT FROM AUTHOR]

The Trentino-South Tyrol region is a special statute region of northeastern Italy. This territory is of particular interest for its morphology, flourishing vegetation, and history, having been a meeting area among different civilizations. Hence, Trentino is characterized by an ethnic plurality and a rich ethnobotanical knowledge, even if the available information is fragmentary, widely dispersed, and often guarded in oral popular culture. To fill this gap, in the present work 200 subjects were interviewed using an ethnobotanical survey. The resulting 817 citations referred to 64 native species, used either for human or animal health or for domestic purposes. As a second step, for each plant exploited for medicinal purposes, local importance was evaluated by calculating their relative frequency of citation. Moreover, the main traditional preparations were discussed. Among them, the most cited and exploited ones are Achillea millefolium, Arnica montana, Hypericum perforatum, Malva sylvestris, Pinus mugo, and Satureja montana, for which a deeper analysis has been performed. Lastly, the ethnobotanical knowledge of the plants growing in this territory will add a piece to the mosaic of traditional medicine in Italy and may lay the foundation for a nature-aided drug discovery process.

Rosa x damascena Mill. essential oil is mainly used in the cosmetics and perfumery industry, but it also finds application in the food industry as a flavoring agent. The chemical composition of essential oils is affected by environment, soil, harvesting technique, storage condition, and extraction methods. Nowadays, the study and design of greener, more efficient, and sustainable extractive procedures is the main and strategic focus in the chemical research and development of botanical derivatives, especially as regards fragrances and essential oils. Several technologies are available, and the best method to use depends on the desired chemicals, but conventional extractive processes are often laborious and time-consuming, involve large amounts of solvents, and may cause the partial loss of volatiles, affecting the quality of the final product. In the last decade, microwave irradiation has been successfully applied to classical techniques, often improving the general extractive efficiency and extract quality. In the present paper, as a preliminary analytical screening approach, two microwave-mediated techniques, Solvent-Free Microwave Extraction (SFME) and Microwave Hydrodiffusion and Gravity (MHG), and two conventional procedures, Hydrodistillation (HD) and Steam Distillation (SD), were applied and compared for the extraction of volatile compounds from R. x damascena fresh petals to highlight differences and advantages of the selected procedure and of the obtained extracts useful in a cosmetic context as fragrances or active ingredients. The chemical composition of the extracts was investigated by GC-MS and GC-FID. Sixty-one components, distributed in the four techniques, were identified. SD and HD are dominated by oxygenated terpenes (59.01% and 50.06%, respectively), while MHG and SFME extracts are dominated by alcohols (61.67% and 46.81%, respectively). A relevant variability in the composition of the extracts relating to the extraction techniques used was observed. To point out the correlation between the process and composition of the obtained natural products, principal component analysis (PCA) of the data extracted from GC-FID was used. Taking into account a cosmetic application, SFME shows several advantages when compared with the other procedures. The extract (obtained in a significantly higher amount) contains a meaningful lower level of potential fragrance allergenic compounds and quite a double amount of benzyl alcohol and 2-phenyl ethanol that can also enhance the preservative action in personal care products.

The Sibari Plain (northeastern Calabria) shows a well-developed stair of late Quaternary marine/coastal terraces resulting from the interaction between sea level fluctuations and tectonic uplift. This paper (i) provides a stratigraphic description of terraced deposits between the Raganello and Coscile rivers, (ii) assesses the relative controls of eustacy and uplift on the staircase formation, and (iii) unravels the Quaternary morphosedimentary evolution of the study area. A geomorphological approach was coupled with stratigraphic field surveys. Photo interpretation, topographic map analyses, and field surveys allowed us to map ten orders of terraces forming telescopically incised valley-fills. Based on the uppermost position of foreshore deposits on inner margins and an average uplift rate of ~1 mm/y, inferred from the Marine Isotope Stage (MIS) 5.5, terraces were correlated with highstands. Sedimentological and stratigraphic analyses allowed us to recognize four assemblages of genetically associated sedimentary facies related to superimposed and juxtaposed coastal and alluvial systems, showing a seaward-stepping architecture. Based on stratal geometry and facies association, we argue that alluvial/fluvial sediments and coastal depositional systems formed contemporaneously along the same terrace. Terrace arrangement resulted from repeated cycles of valley incision (sea level fall) and aggradational to progradational stacking pattern (sea level rise and highstands) in a framework of sustained uplift.

Orchidaceae is a flowering plant family worldwide distributed known for producing volatile organic compounds (VOCs) which can act as olfactory signals for pollinators. Despite the importance of VOCs in the different reproductive strategies, in the literature there are only a few publications on the characterization of orchids’ volatile profiles. In this study, the essential oils from fresh inflorescences of sympatric orchids Anacamptis morio, Himantoglossum robertianum, Ophrys sphegodes and Orchis purpurea, naturally growing in Piedmont (Italy) were isolated by steam distillation and characterized by GC/FID and GC/MS. A number of compounds were identified, with a peculiar distribution in the species: alcohols (range 16.93–50.60%), from which p-cresol (range 12.75–38.10%) was the most representative compound; saturated hydrocarbons (range 5.81–59.29%), represented by pentacosane (range 2.22–40.17%) and tricosane (range 0.78–27.48%); long-chain monounsaturated hydrocarbons (range 0.29–5.20%) represented by 9-pentacosene, 11-tricosene, and 1-heneicosene. The structure of positional isomers in linear alkenes was elucidated by derivatization with dimethyl disulfide and MS fragmentation patterns. Coumarin (68.84%) was the dominant compound in O. purpurea and was detected in lower concentrations (range 0.21–0.26%) in the other taxa. These volatile compounds may represent a particular feature of these plant species and play an essential role in pollinator interaction.

Abstract Background Extramedullary involvement of B-cell Acute Lymphoblastic Leukemia (EM-ALL) is a rare occurrence, characterized by dismal outcome and the absence of a defined and shared therapeutic approach. In the landscape of innovative compounds, inotuzumab ozogamicin (IO) is a promising drug, whose mechanism of action relies on the killing of CD22 positive leukemic cells, through the delivery, after cell binding, of a molecule of calicheamicin. Case presentation We report two cases of CD22 positive relapsed EM-ALL treated with IO, obtained as compassionate use. Case 1, a 66 years old woman, affected by Philadelphia (Ph) negative B-ALL, relapsed with extramedullary involvement after 6 standard chemotherapy courses, who reached a complete metabolic response with IO treatment. Case 2, a 67 years old man with Ph positive B-ALL, initially treated with ponatinib, a third generation tyrosine-kinase inhibitor (TKI), obtaining a prolonged deep molecular remission. Nevertheless, for skin relapse during TKI treatment, the patient received local radiotherapy and, shortly after, standard chemotherapy, as multiple abdominal sites of relapse were detected too, with no response. The patient then received IO, obtained as compassionate use, with a good metabolic response. Conclusions These two cases suggest a possible key role of IO in the setting of advanced CD22 positive ALL, and underline its potential activity also in patients with EM involvement, relapsed after or refractory to conventional chemotherapy. Despite the well known hepatotoxic effect of the compound (Sinusoid Occlusive Syndrome), neither of them had such adverse event, moreover the second patient safely underwent allogeneic bone marrow transplantation.

Abstract Background Despite the recent progress that has been made in the understanding and treatment of acute lymphoblastic leukemia (ALL), the outcome is still dismal in adult ALL cases. Several studies in solid tumors identified high expression of WEE1 kinase as a poor prognostic factor and reported its role as a cancer-conserving oncogene that protects cancer cells from DNA damage. Therefore, the targeted inhibition of WEE1 kinase has emerged as a rational strategy to sensitize cancer cells to antineoplastic compounds, which we evaluate in this study. Methods The effectiveness of the selective WEE1 inhibitor AZD-1775 as a single agent and in combination with different antineoplastic agents in B and T cell precursor ALL (B/T-ALL) was evaluated in vitro and ex vivo studies. The efficacy of the compound in terms of cytotoxicity, induction of apoptosis, and changes in gene and protein expression was assessed using different B/T-ALL cell lines and confirmed in primary ALL blasts. Results We showed that WEE1 was highly expressed in adult primary ALL bone marrow and peripheral blood blasts (n = 58) compared to normal mononuclear cells isolated from the peripheral blood of healthy donors (p = 0.004). Thus, we hypothesized that WEE1 could be a rational target in ALL, and its inhibition could enhance the cytotoxicity of conventional therapies used for ALL. We evaluated the efficacy of AZD-1775 as a single agent and in combination with several antineoplastic agents, and we elucidated its mechanisms of action. AZD-1775 reduced cell viability in B/T-ALL cell lines by disrupting the G2/M checkpoint and inducing apoptosis. These findings were confirmed in human primary ALL bone marrow and peripheral blood blasts (n = 15). In both cell lines and primary leukemic cells, AZD-1775 significantly enhanced the efficacy of several tyrosine kinase inhibitors (TKIs) such as bosutinib, imatinib, and ponatinib, and of chemotherapeutic agents (clofarabine and doxorubicin) in terms of the reduction of cell viability, apoptosis induction, and inhibition of proliferation. Conclusions Our data suggest that WEE1 plays a role in ALL blast’s survival and is a bona fide target for therapeutic intervention. These data support the evaluation of the therapeutic potential of AZD-1775 as chemo-sensitizer agent for the treatment of B/T-ALL.