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Extra virgin is the most valuable commercial category among olive oils, and its quality is influenced by various factors, among which the olive fruit plays a fundamental role. The olives that enter the mill exhibit significant variability in physical and chemical characteristics, potentially impacting the quality of the extracted oil. Therefore, selecting the olives in post‐harvest could be a crucial step, especially for differentiating the final product and producing high‐quality oil. This work aimed to conduct post‐harvest densimetric sorting of the olives. For this purpose, a saline solution was used with different concentrations of salt over the 3 days of harvesting, which made it possible to divide the initial olive batch into two sub‐batches with different densities. The respective oil was extracted from each sub‐batch, called low‐ and high‐density oils, respectively, and then appropriate physical–chemical analyses were performed to characterize both the olives and the oils. Although both oils were classified as extra virgin, significant differences were observed, with higher concentrations of phenolic and volatile compounds associated with positive sensory attributes in the low‐density oils. Densimetric sorting of olives could represent a novel approach in the field of extra virgin olive oil production, enabling potential differentiation of the final product. Practical Applications: The results obtained in the study could be applied at an industrial level to classify olives in the post‐harvest phase. This could allow to produce extra virgin olive oils (EVOOs) with different chemical and sensory characteristics, particularly in terms of volatile and phenolic compounds. This would make it possible to diversify the production of EVOO, satisfy the diverse needs of consumers, allow producers to be more competitive in the market, and, in general, improve the overall quality of the final product. [ABSTRACT FROM AUTHOR]

Aim: This review is intended to adapt the current conceptual framework in dental education based on four domains to propose a set of competences, learning outcomes and methods of teaching, learning and assessment for undergraduate education in periodontology. Review: Based on the current framework of competences and learning outcomes recommended by the Association for Dental Education in Europe (ADEE), undergraduate education in periodontology has been updated using the classification and clinical practice guidelines for the diagnosis and treatment of periodontal and peri‐implant diseases. Conclusions: Specific learning outcomes have been proposed within each competence area, that is in Domain I (n = 10), Domain II (n = 13), Domain III (n = 33) and Domain IV (n = 12). Teaching methods and learning activities based on the different dimensions of the cognitive process have been proposed. Additionally, 10 key learning outcomes have been proposed as exit outcomes, which implies their accomplishment within the final assessment of any graduating student. [ABSTRACT FROM AUTHOR]

Efficient identification of human monoclonal antibodies targeting specific antigenic sites is pivotal for advancing vaccines and immunotherapies against infectious diseases and cancer. Existing screening techniques, however, limit our ability to discover monoclonal antibodies with desired specificity. In this study, we introduce a novel method, blocking of binding (BoB) enzyme‐linked immunoassay (ELISA), enabling the detection of high‐avidity human antibodies directed to defined epitopes. Leveraging BoB‐ELISA, we analyzed the antibody response to known epitopes of influenza A hemagglutinin (HA) in the serum of vaccinated donors. Our findings revealed that serum antibodies targeting head epitopes were immunodominant, whereas antibodies against the stem epitope, although subdominant, were highly prevalent. Extending our analysis across multiple HA strains, we examined the cross‐reactive antibody response targeting the stem epitope. Importantly, employing BoB‐ELISA we identified donors harboring potent heterosubtypic antibodies targeting the HA stem. B‐cell clonal analysis of these donors revealed three novel, genealogically independent monoclonal antibodies with broad cross‐reactivity to multiple HAs. In summary, we demonstrated that BoB‐ELISA is a sensitive technique for measuring B‐cell epitope immunogenicity, enabling the identification of novel monoclonal antibodies with implications for enhanced vaccine development and immunotherapies. [ABSTRACT FROM AUTHOR]

Ge4+ substitution into the recently discovered superionic conductor Li7Si2S7I is demonstrated by synthesis of Li7Si2–xGexS7I, where x≤1.2. The anion packing and tetrahedral silicon location of Li7Si2S7I are retained upon substitution. Single crystal X‐ray diffraction shows that substitution of larger Ge4+ for Si4+ expands the unit cell volume and further increases Li+ site disorder, such that Li7Si0.88Ge1.12S7I has one Li+ site more (sixteen in total) than Li7Si2S7I. The ionic conductivity of Li7Si0.8Ge1.2S7I (x=1.2) at 303 K is 1.02(3)×10−2 S cm−1 with low activation energies for Li+ transport demonstrated over a wide temperature range by AC impedance and 7Li NMR spectroscopy. All sixteen Li+ sites remain occupied to temperatures as low as 30 K in Li7Si0.88Ge1.12S7I as a result of the structural expansion. This differs from Li7Si2S7I, where the partial Li+ site ordering observed below room temperature reduces the ionic conductivity. The suppression of Li+ site depopulation by Ge4+ substitution retains the high mobility to temperatures as low as 200 K, yielding low temperature performance comparable with state‐of‐the‐art Li+ ion conducting materials. [ABSTRACT FROM AUTHOR]

The Gal(α1‐3)Gal is the terminal disaccharide unit of the α‐Gal epitope [Gal(α1‐3)Gal(β1‐4)GlcNAc], an exogenous antigenic determinant with several clinical implications, found in all non‐primate mammals and in several dangerous pathogens, including certain protozoa and mycobacteria. Its absence in humans makes the α‐Gal epitope an interesting target for several infectious diseases. Here we present the development of a macrocyclic tweezers‐shaped receptor, resulting from the combination of the structural features of two predecessors belonging to the family of diaminocarbazole receptors, which exhibits binding properties in the low millimolar range toward the Gal(α1‐3)Gal disaccharide of the α‐Gal antigen. [ABSTRACT FROM AUTHOR]

Central Afar is shaped by the interaction between the Red Sea (RS) and Gulf of Aden (GoA) rifts. While there have been several studies conducted in the region, we know surprisingly little about the mechanism of connection between these two rift branches. Here we use high‐resolution 3D lithospheric scale geodynamic modeling to capture the evolution of linkage between the RS and GoA rifts in central Afar. Our results demonstrate that the two rifts initially overlap and interact across a broad zone of faulting and vertical axis block rotation. However, through time, rift overlap is abandoned in favor of direct linkage which generates a series of localized en‐echelon basins. The present‐day direct linkage between the two rifts is supported by geodetic observations. Our study reconciles previously proposed models for the RS and GoA rift connection by considering spatial and temporal evolution of the rifts. Plain Language Summary: Rifts are places where tectonic plates move away from each other. They normally start as short, isolated features, and then grow and connect together to eventually form oceans. Central Afar in East Africa is a great location to study how these rifts form and grow by connecting with other rifts. In this area, the Red Sea (RS) and Gulf of Aden (GoA) rifts interact, but it is not clear how this happened through time. Some studies suggest that the two rifts form an overlap zone where blocks within the overlap rotate, while others argue that the two rifts directly link and form a continuous rift zone. To resolve this debate, we conducted a high‐resolution computer simulation of the evolution of the RS and GoA rifts in central Afar. We compared our model results with earthquake positions and satellite data that constrain the present‐day motion of the plates. Our results demonstrate that the RS and GoA rifts first overlapped for a few millions of years, and then formed a direct linkage. Our study suggests that both conceptual models can be reconciled when we consider the temporal evolution of the two rifts through geological times. Key Points: Analyzing the spatiotemporal evolution of rifts can address the controversial issue on the connection between propagating riftsWe present results from InSAR and geodynamic models to describe the connection between Red Sea (RS) and Gulf of Aden (GoA) rifts in central AfarThe connection between the two rifts evolves from rift overlap to direct linkage elucidating the observed deformation in the region [ABSTRACT FROM AUTHOR]

The paper explores the use of the magnetic control strategy for the output power regulation of an LCC‐S compensated inductive wireless power transfer system. The magnetic control is implemented through a controlled variable inductor whose magnetization state is actively regulated by an auxiliary DC–DC converter. The principles for the design and regulation of the system are discussed, and the experimental setup for the validation of the regulation method is implemented. Several measurement results highlight the effectiveness and potential improvements of the magnetic control strategy for inductive wireless power transfer systems. [ABSTRACT FROM AUTHOR]

This paper introduces a novel approach for designing a Wireless Power Transfer (WPT) system with LCC‐S compensation. Since WPT systems operate under resonant conditions, even small deviations of the components from the nominal values can result in a significant reduction of the power transferred to the load, and in an increment of the circulating currents, reducing the system efficiency. The design techniques available today in the literature provide a unique combination of passive components capable of transferring a certain power to the load. This is a limitation, because, in practice, there are several combinations that allow reaching the desired output power, but they are usually neglected because they are extremely difficult to compute analytically. For this reason, in this paper, the authors present an innovative design procedure that enables, through a Genetic Algorithm, the identification of multiple feasible combinations of the LCC‐S components capable of achieving the desired output power. Moreover, the authors evaluate the effects of the component tolerances on the output power to determine which combinations are more robust to component variations. This task is performed by calculating the probability that a particular combination yields the desired output power, once the tolerances have been considered, following a Monte Carlo approach. This information is utilized to decide whether it is possible to reduce the component quality (worsening the tolerance) without affecting the performance. Finally, an optimal solution granting both low‐cost and robustness against component tolerances can be individuated. The proposed design procedure is applied to a case study and validated experimentally. [ABSTRACT FROM AUTHOR]

The High Magnetic Passive Loop (HMCPL) technique is proposed as an innovative passive shielding system to mitigate the undesired dispersion of the magnetic field produced by a wireless power transfer (WPT) system, thus reducing the risk of hazardous human exposure. The magnetic structure is described both in terms of lumped parameters circuit, useful for sizing, and in terms of a geometrical representation solved by finite element method, useful to assess the field attenuation effects. Sizing of the resonance capacitors in the shielded WPT structure is approached as a Pareto optimization problem and solved via genetic algorithm. HMCPL shielding design guidance is provided to reduce the magnetic field emission in the surrounding environment. Furthermore, the influence of the shielding on the performance of the WPT system is also evaluated. [ABSTRACT FROM AUTHOR]

Multiple strategies are continuously being explored to expand the drug target repertoire in solid tumors. We devised a novel computational workflow for transcriptome‐wide gene expression outlier analysis that allows the systematic identification of both overexpression and underexpression events in cancer cells. Here, it was applied to expression values obtained through RNA sequencing in 226 colorectal cancer (CRC) cell lines that were also characterized by whole‐exome sequencing and microarray‐based DNA methylation profiling. We found cell models displaying an abnormally high or low expression level for 3533 and 965 genes, respectively. Gene expression abnormalities that have been previously associated with clinically relevant features of CRC cell lines were confirmed. Moreover, by integrating multi‐omics data, we identified both genetic and epigenetic alternations underlying outlier expression values. Importantly, our atlas of CRC gene expression outliers can guide the discovery of novel drug targets and biomarkers. As a proof of concept, we found that CRC cell lines lacking expression of the MTAP gene are sensitive to treatment with a PRMT5‐MTA inhibitor (MRTX1719). Finally, other tumor types may also benefit from this approach. [ABSTRACT FROM AUTHOR]

Serine/threonine‐protein kinase B‐raf (BRAF) mutations are found in 8–15% of colorectal cancer patients and identify a subset of tumors with poor outcome in the metastatic setting. We have previously reported that BRAF‐mutant human cells display a high rate of protein production, causing proteotoxic stress, and are selectively sensitive to the proteasome inhibitors bortezomib and carfilzomib. In this work, we tested whether carfilzomib could restrain the growth of BRAF‐mutant colorectal tumors not only by targeting cancer cells directly, but also by promoting an immune‐mediated antitumor response. In human and mouse colorectal cancer cells, carfilzomib triggered robust endoplasmic reticulum stress and autophagy, followed by the emission of immunogenic‐damage‐associated molecules. Intravenous administration of carfilzomib delayed the growth of BRAF‐mutant murine tumors and mobilized the danger‐signal proteins calreticulin and high mobility group box 1 (HMGB1). Analyses of drug‐treated samples revealed increased intratumor recruitment of activated cytotoxic T cells and natural killers, concomitant with the downregulation of forkhead box protein P3 (Foxp3)+ T‐cell surface glycoprotein CD4 (CD4)+ T cells, indicating that carfilzomib promotes reshaping of the immune microenvironment of BRAF‐mutant murine colorectal tumors. These results will inform the design of clinical trials in BRAF‐mutant colorectal cancer patients. [ABSTRACT FROM AUTHOR]

Glycogen is a biologically essential macromolecule that is directly involved in multiple human diseases. While its primary role in carbohydrate storage and energy metabolism in the liver and muscle is well characterized, recent research has highlighted critical metabolic and non-metabolic roles for glycogen in the brain. In this review, the emerging roles of glycogen homeostasis in the healthy and diseased brain are discussed with a focus on advancing our understanding of the role of glycogen in the brain. Innovative technologies that have led to novel insights into glycogen functions are detailed. Key insights into how cellular localization impacts neuronal and glial function are discussed. Perturbed glycogen functions are observed in multiple disorders of the brain, including where it serves as a disease driver in the emerging category of neurological glycogen storage diseases (n-GSDs). n-GSDs include Lafora disease (LD), adult polyglucosan body disease (APBD), Cori disease, Glucose transporter type 1 deficiency syndrome (G1D), GSD0b, and late-onset Pompe disease (PD). They are neurogenetic disorders characterized by aberrant glycogen which results in devastating neurological and systemic symptoms. In the most severe cases, rapid neurodegeneration coupled with dementia results in death soon after diagnosis. Finally, we discuss current treatment strategies that are currently being developed and have the potential to be of great benefit to patients with n-GSD. Taken together, novel technologies and biological insights have resulted in a renaissance in brain glycogen that dramatically advanced our understanding of both biology and disease. Future studies are needed to expand our understanding and the multifaceted roles of glycogen and effectively apply these insights to human disease. [ABSTRACT FROM AUTHOR]

Objectives: Mandatory newborn screening (NBS) for spinal muscular atrophy (SMA) was implemented for the first time in Italy at the end of 2021, allowing the identification and treatment of patients at an asymptomatic stage. Methods: DNA samples extracted from dried blood spot (DBS) from newborns in Apulia region were analysed for SMA screening by using a real‐time PCR‐based assay. Infants harbouring homozygous deletion of SMN1 exon 7 confirmed by diagnostic molecular tests underwent clinical and neurophysiological assessment and received a timely treatment. Results: Over the first 20 months since regional NBS introduction, four out of 42,492 (0.009%) screened children were found to carry a homozygous deletion in the exon 7 of SMN1 gene, with an annual incidence of 1:10,623. No false negatives were present. Median age at diagnosis was 7 days and median age at treatment was 20.5 days. Three of them had two copies of SMN2 and received gene therapy, while the one with three SMN2 copies was treated with nusinersen. All but one were asymptomatic at birth, showed no clinical signs of disease after a maximum follow‐up of 16 months and reached motor milestones appropriate with their age. The minimum interval between diagnosis and the treatment initiation was 9 days. Interpretation: The timely administration of disease‐modifying therapies prevented presymptomatic subjects to develop disease symptoms. Mandatory NBS for SMA should be implemented on a national scale. [ABSTRACT FROM AUTHOR]

Charcot–Marie‐Tooth type 2A (CMT2A) is an inherited sensorimotor neuropathy associated with mutations within the Mitofusin 2 (MFN2) gene. These mutations impair normal mitochondrial functioning via different mechanisms, disturbing the equilibrium between mitochondrial fusion and fission, of mitophagy and mitochondrial axonal transport. Although CMT2A disease causes a significant disability, no resolutive treatment for CMT2A patients to date. In this context, reliable experimental models are essential to precisely dissect the molecular mechanisms of disease and to devise effective therapeutic strategies. The most commonly used models are either in vitro or in vivo, and among the latter murine models are by far the most versatile and popular. Here, we critically revised the most relevant literature focused on the experimental models, providing an update on the mammalian models of CMT2A developed to date. We highlighted the different phenotypic, histopathological and molecular characteristics, and their use in translational studies for bringing potential therapies from the bench to the bedside. In addition, we discussed limitations of these models and perspectives for future improvement. [ABSTRACT FROM AUTHOR]

This work describes the self‐assembly behavior of heterochiral, aliphatic dipeptides, l‐Leu‐d‐Xaa (Xaa = Ala, Val, Ile, Leu), in green solvents such as acetonitrile (MeCN) and buffered water at neutral pH. Interestingly, water plays a structuring role because at 1% v/v, it enables dipeptide self‐assembly in MeCN to yield organogels, which then undergo transition towards crystals. Other organic solvents and oils were tested for gelation, and metastable gels were formed in tetrahydrofuran, although at high peptide concentration (80 mM). Single‐crystal X‐ray diffraction revealed the dipeptides' supramolecular packing modes in amphipathic layers, as opposed to water channels reported for the homochiral Leu–Leu, or hydrophobic columns reported for homochiral Leu–Val and Leu–Ile. [ABSTRACT FROM AUTHOR]

This study provides a metataxonomic analysis of the fungal communities in soils under slash‐and‐burn agroforestry system and offers new insights into the relationships between fungal populations and soil physicochemical features such as pH, the particle size distribution, easily oxidizable organic carbon, total nitrogen, available phosphorus, and the mineralogical composition. Soils from three locations in central Mozambique—Vanduzi, Sussundenga, and Macate—that are subjected to slash‐and‐burn were considered to assess the effects of the forest fallow length (temporal variation) and of the land use (charcoal kiln, crop field, and forest; meaning horizontal variation) on the fungal community. The fungi of the genetic horizons (vertical variation) were also considered. Most of the detected fungi were decomposers, antagonists of plant pathogens, and plant‐growth promoters; they were differently distributed in relation to the soil's physicochemical properties and the soil use. The variations in the fungi distribution among the locations and between the horizons were considerable, while there were few variations between the different land‐use types. The limited differences between land uses indicate the inability of a forest fallow period shorter than 50 years to improve soil fertility and induce changes in the fungal community. The pedological approach used to identify and sample soil horizons allowed us to clearly distinguish the fungal community of the A horizons, those richest in organics and nutrients, and that of the Bo horizons, which have poor fertility. [ABSTRACT FROM AUTHOR]

Summary: Acute chest syndrome (ACS) is a frequent cause of hospitalization in sickle cell disease (SCD). Despite advances in acute care, many settings still lack knowledge about ACS best practices. After the AIEOP Guidelines were published in 2012, suggesting standardized management in Italy, a retrospective study was performed to assess the diagnostic and therapeutic pathways of ACS in children. From 2013 to 2018, 208 ACS episodes were presented by 122/583 kids in 11 centres. 73 were male, mean age 10.9 years, 85% African, 92% HbSS or Sβ°. In our hub‐and‐spoke system, a good adherence to Guidelines was documented, but discrepancies between reference centres and general hospitals were noted. Improvement is needed for timely transfer to reference centres, use of incentive spirometry, oxygen therapy and pain management. [ABSTRACT FROM AUTHOR]

The increasing diffusion of timber as a structural material asks for major detailing concerning numerical modelling; timber is commonly used with other construction materials in order to create hybrid structures exploiting each material's strengths and smoothing less efficient features. In this way – combining timber and steel – structural performances are guaranteed while lightness and sustainability of only‐timber structures are maintained. Some specific issues linked to timber material – e.g., orthotropic behaviour – and contact with steel are specifically addressed, exploring different techniques according to the scale of the problem. Finally, a complete steel‐timber hybrid beam‐to‐column joint is assembled, with a clear understanding of each interaction and insights for future adjustments to the benchmark model. [ABSTRACT FROM AUTHOR]

Summary: Haemochromatosis (HC) encompasses a range of genetic disorders. HFE‐HC is by far the most common in adults, while non‐HFE types are rare due to mutations of HJV, HAMP, TFR2 and gain‐of‐function mutations of SLC40A1. HC is often unknown to paediatricians as it is usually asymptomatic in childhood. We report clinical and biochemical data from 24 paediatric cases of HC (10 cases of HFE‐, 5 TFR2‐, 9 HJV‐HC), with a median follow‐up of 9.6 years. Unlike in the adult population, non‐HFE‐HC constitutes 58% (14/24) of the population in our series. Transferrin saturation was significantly higher in TFR2‐ and HJV‐HC compared to HFE‐HC, and serum ferritin and LIC were higher in HJV‐HC compared to TFR2‐ and HFE‐HC. Most HFE‐HC subjects had relatively low ferritin and LIC at the time of diagnosis, so therapy could be postponed for most of them after the age of 18. Our results confirm that HJV‐HC is a severe form already in childhood, emphasizing the importance of early diagnosis and treatment to avoid the development of organ damage and reduce morbidity and mortality. Although phlebotomies were tolerated by most patients, oral iron chelators could be a valid option in early‐onset HC. [ABSTRACT FROM AUTHOR]

The presence of pre‐existing fabrics at all lithospheric scales has been proven to be of primary importance in controlling the evolution of continental rifts. Indeed, observations from natural examples show that even in conditions of orthogonal rifting, when extension should result in simple fault patterns dominated by normal faults orthogonal to extension vectors, inherited fabrics induce complex arrangements of differently‐oriented extension‐related structures. This paper explored the influence of inherited fabrics on rift‐related structures by using a series of analog models deformed in a centrifuge. The models reproduced a brittle‐ductile crustal system and considered the presence of pre‐existing discrete fabrics in the brittle crust in conditions of orthogonal narrow rifting. These fabrics were reproduced by cutting the brittle layer at different orientations with respect to the extension direction. Modeling shows pre‐existing fabrics have a significant influence on rift‐related faults, provided that the angle between inherited fabrics and the rift trend is less than 45°. In these conditions, fabrics cause prominent segmentation of rift‐related faults and induce the development of isolated depocenters. Pre‐existing fabrics strongly influence the geometry of extension‐related structures, resulting in curved fault patterns and en‐echelon arrangement of oblique faults. These findings provide insights into the development of continental rift systems in nature: our modeling shows indeed significant similarities (i.e., peculiar fault architecture and geometries) with the faults in different sectors of the East African Rift System (e.g., the Magadi and Bogoria basin, Kenya Rift), testifying that reactivation of inherited fabrics is a paramount process in shaping continental rifts. Key Points: Centrifuge analog models show that inherited fabrics strongly influence rift structures when their angle to the rift trend is <45°Inherited fabrics affect the top‐view geometry of rifts, leading to curvature and segmentation of faults as well as isolated depocentersOur models display strong similarities with different examples in the East African Rift System, well explaining the fault pattern evolution [ABSTRACT FROM AUTHOR]

The issue of the presence of dissolved oxygen (DO) in virgin olive oil (VOO) is neglected in literature. Available information is limited to the extraction stage of the product life cycle, and studies focused on the subsequent stages from extraction to bottling are virtually absent. The present work aims to fill this gap through a dissolved oxygen monitoring experiment performed at industrial scale. Seven different unit‐operations of the routine working procedure of an Italian industrial company specializing in the marketing of VOO were studied: oil discharge from tanker truck; blend formation; oil transferring to filtration; oil transferring to bottling; precoat‐bodyfeed filtration; polishing filtration; bottling. The overall concentration of DO averages to 2.2 mg L–1, while the oil incoming the company was at 1.5 mg L–1. The unit‐operations can be ordered as "mixing‐for‐blend > precoat‐bodyfeed filtration > transfer‐to‐bottling > bottling," with a decreasing oxygenation effect. Polishing filtration does not determine a significant DO variation. In the immediate term, the increase in DO does not result in oxidative deterioration of the oil, at least detectable with the peroxides value. Practical Applications: The results provide important information for the management of virgin olive oil on an industrial scale in the postproduction stages up to bottling. First, it was clearly demonstrated that bulk transport operations led to oxygenation of the oil. From this point on, the oil underwent further oxygenation, the extent of which depends on the specific processing operation considered. The oxygenation effect of each operation is different, which means that different interventions with varying intensity in terms of complexity and cost could be applied on a case‐by‐case basis to preserve the oil from oxygenation. [ABSTRACT FROM AUTHOR]

The development of tailored additive manufacturing (AM) approaches is resulting in novel strategies for engineering the macro/microstructural details of potential medical devices made of biocompatible polymers. The aim of this work is the employment of a multifunctional AM machine for fabricating poly(methyl methacrylate) (PMMA) constructs with a predefined shape and porous architecture, by either melt‐ or solution‐extrusion AM. In particular, PMMA porous scaffolds are manufactured by employing fused filament fabrication (FFF) or computer‐aided wet‐spinning (CAWS). The comparative characterization of the two developed PMMA implant prototypes demonstrates significant differences in terms of porous structure, polymer surface topography, material composition, glass transition temperature, and mechanical properties. As a consequence, FFF‐printed PMMA samples support a faster in vitro proliferation of a murine fibroblast cell line in comparison to PMMA scaffolds by CAWS. The results achieved encourage further research on the developed processing protocols, aimed at the development of tailored PMMA implants for personalized surgery applications. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to provide an overview of the clinical phenotypes associated with 4 SMN2 copies. Methods: Clinical phenotypes were analyzed in all the patients with 4 SMN2 copies as part of a nationwide effort including all the Italian pediatric and adult reference centers for spinal muscular atrophy (SMA). Results: The cohort includes 169 patients (102 men and 67 women) with confirmed 4 SMN2 copies (mean age at last follow‐up = 36.9 ± 19 years). Six of the 169 patients were presymptomatic, 8 were classified as type II, 145 as type III (38 type IIIA and 107 type IIIB), and 8 as type IV. The remaining 2 patients were asymptomatic adults identified because of a familial case. The cross‐sectional functional data showed a reduction of scores with increasing age. Over 35% of the type III and 25% of the type IV lost ambulation (mean age = 26.8 years ± 16.3 SD). The risk of loss of ambulation was significantly associated with SMA type (p < 0.0001), with patients with IIIB and IV less likely to lose ambulation compared to type IIIA. There was an overall gender effect with a smaller number of women and a lower risk for women to lose ambulation. This was significant in the adult (p = 0.009) but not in the pediatric cohort (p = 0.43). Interpretation: Our results expand the existing literature on natural history of 4 SMN2 copies confirming the variability of phenotypes in untreated patients, ranging from type II to type IV and an overall reduction of functional scores with increasing age. ANN NEUROL 2023;94:1126–1135 [ABSTRACT FROM AUTHOR]

To investigate the existence of any association between new putative periodontal pathogens and periodontitis. Two independent reviewers conducted electronic literature searches in the MEDLINE (PubMed), EMBASE, DOSS and Google Scholar databases as well as a manual search to identify eligible clinical studies prior to November 2022. Studies comparing the prevalence of microorganisms other than the already‐known periodontal pathogens in subgingival plaque and/or saliva samples between subjects with periodontitis and subject with periodontal health were included. Meta‐analyses were performed on data provided by the included studies. Fifty studies including a total of 2739 periodontitis subjects and 1747 subjects with periodontal health were included. The Archaea domain and 25 bacterial species (Anaeroglobus geminatus, Bacteroidales [G‐2] bacterium HMT 274, Desulfobulbus sp. HMT 041, Dialister invisus, Dialister pneumosintes, Eubacterium brachy, Enterococcus faecalis, Eubacterium nodatum, Eubacterium saphenum, Filifactor alocis, Fretibacterium sp. HMT 360, Fretibacterium sp. HMT 362, Mogibacterium timidum, Peptoniphilaceae sp. HMT 113, Peptostreptococcus stomatis, Porphyromonas endodontalis, Slackia exigua, Streptococcus gordonii, Selenomonas sputigena, Treponema amylovorum, Treponema lecithinolyticum, Treponema maltophilum, Treponema medium, Treponema parvum and Treponema socranskii) were found to be statistically significantly associated with periodontitis. Network studies should be conducted to investigate the role of these newly identified periodontitis‐associated microorganisms through interspecies interaction and host‐microbe crosstalk analyses. [ABSTRACT FROM AUTHOR]

In this work, a microwave synthesis followed by a simple purification process produces a new type of chiral Carbon Nanodots (CNDs). These CNDs are soluble in organic solvents, exhibit amino groups on their surface and display interesting absorption and emission properties along with mirror image profiles in the electronic circular dichroism spectrum. All these features set the stage for CNDs to act as multifunctional catalytic platforms, able to promote diverse chemical transformations. In particular, the outer shell composition of CNDs was instrumental to carry out organocatalytic reactions in an enantioselective fashion. In addition, the redox and light‐absorbing properties of the material are suitable to drive photochemical processes. Finally, the photoredox and organocatalytic activations of CNDs were exploited at the same time to promote a cross‐dehydrogenative coupling. This work demonstrates that CNDs can be used as catalysts to promote multiple reactivities, previously considered exclusive domain of molecular catalysts. [ABSTRACT FROM AUTHOR]

The lentiginous spread of melanocytes into the hair follicle can be observed in a number of benign melanocytic neoplasms such as in nevi but also in sun‐induced melanocytic hyperplasia and melanoma. The follicular colonization by melanocytes in melanoma is classified into three distinct patterns: primary follicular melanoma, melanoma with folliculotropism, and invasive melanoma arising from melanoma in situ with folliculotropism. The role of follicular colonization in melanoma pathologic staging is still a matter of debate though the description of the latter has been recommended by the International Collaboration on Cancer Reporting. In this review, we will discuss the role of follicular colonization in melanoma and melanocytic nevi as well as the facts and controversies regarding this topic. [ABSTRACT FROM AUTHOR]

By providing financial resources, conditional to the implementation of the (social) recommendations in the Semester and the principles of the European Pillar of Social Rights, the Recovery and Resilience Facility (RRF) has opened new political and institutional opportunity windows for the multi‐level co‐production of social policies. The article first dives into how the RRF has been translated into national social policies choices, by assessing the alignment of reforms and investments with the Semester social recommendations and their capacity to address the social vulnerabilities identified in the Pillar's Social Scoreboard. Second, it sheds light on the interaction between the European Commission, in charge of assessing and monitoring the RRF, and the national governments, the key actors in setting‐up and implementing the plans. Comparing six case studies (Italy, Germany, Spain, Croatia, Belgium and Austria), the article shows that the RRF has only partially contributed to reinforcing member states' compliance with social Country Specific Recommendations and the role of the Social Pillar in the drafting of National Recovery and Resilience Plans has been very limited. This notwithstanding, the RRF has contributed to fasten‐forward the implementation of welfare reforms and initiatives which would have been remained on the paper, especially for whose countries with limited fiscal capacity. Furthermore, it provides empirical evidence of the collaborative approach between the Commission and the national government, substantiating the claim of the emergence of a new mode of coordinative Europeanization. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the prevalence, subtypes and postnatal outcomes of congenital heart defects (CHD) in a cohort of monochorionic diamniotic (MCDA) twin pregnancies complicated by selective fetal growth restriction (sFGR), and to compare this population with a cohort of uncomplicated MCDA pregnancies evaluated during the same period. Methods: This was a retrospective analysis of all consecutive MCDA pregnancies referred between 2009 and 2018, including those complicated by sFGR (Group A) and those without complications (Group B). All neonates delivered in our center were screened for CHD before discharge. Discharge letters for all those delivered elsewhere were retrieved. Pregnancies with complications other than sFGR and those without perinatal follow‐up were excluded. Pregnancies in Group A were divided into three types according to the Gratacós system of sFGR classification. Results: A total of 870 MCDA twin pregnancies were included: 296 in Group A and 574 in Group B. In Group A, the prevalence of CHD was 3.7% (22/592 twins), with no significant difference in CHD frequency between the three types of sFGR (Type I, 3.7%; Type II, 3.2%; Type III, 4.2%; P = 0.55). Of four Type‐III sFGR pregnancies with CHD, one had pulmonary stenosis (PS) in the larger twin and isolated coarctation of the aorta in the smaller cotwin, and three had PS in the larger twin only. No Type‐III sFGR pregnancies in which only the smaller twin was affected by CHD were observed. Of 11 CHD cases in the larger twin, 10 (91%) were right ventricular outflow tract abnormalities (RVOTA), and one (9%) was a ventricular septal defect. In the smaller twins, 11 cases of CHD were observed, covering a broad spectrum of cardiac abnormalities. In Group B, the CHD prevalence was 1.1% (13/1148 twins), which was similar to that in the general population, according to the EUROCAT registry for the same period and geographical area of the study (0.96%; P = 0.579). The CHD prevalence was significantly higher in Group A compared with Group B (3.7% vs 1.1%; P = 0.0002; odds ratio, 3.57 (95% CI, 1.78–7.22)). In all pregnancies with CHD in the study population, the anomaly was discordant. Conclusions: In MCDA twin pregnancy, sFGR was associated with a three‐fold higher prevalence of CHD. Women with such pregnancies should be referred to a tertiary care hospital for pre‐ and postnatal cardiac evaluation, treatment and long‐term follow‐up. In larger twins, the only major CHD observed was RVOTA, while a broad spectrum of CHD was noted in smaller twins. The higher risk of CHD in MCDA pregnancies appears to be due to the typical complications of the monochorionic pregnancy, rather than to the monochorionic nature of the pregnancy itself. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Ferroptosis is a form of regulated cell death (RCD) characterized by intracellular iron ion accumulation and reactive oxygen species (ROS)‐induced lipid peroxidation. Ferroptosis in cancer and ferroptosis‐related anticancer drugs have recently gained interest in the field of cancer treatment. Boron is an essential trace element playing an important role in several biological processes. Recent studies have described contrasting effects of boric acid (BA) in cancer cells, ranging from protective/mitogenic to damaging/antiproliferative. Interestingly, boron has been shown to interfere with critical factors involved in ferroptosis—intracellular glutathione and lipid peroxidation in the first place. Thus, the present study was aimed to verify the ability of boron to modulate the ferroptotic process in HepG2 cells, a model of hepatocellular carcinoma. Our results indicate that—when used at high, pharmacological concentrations—BA can increase intracellular ROS, glutathione, and TBARS levels, and enhance ferroptosis induced by RSL3 and erastin. Also, high BA concentrations can directly induce ferroptosis, and such BA‐induced ferroptosis can add to the cytotoxic effects of anticancer drugs sorafenib, doxorubicin and cisplatin. These observations suggest that BA could be exploited as a chemo‐sensitizer agent in order to overcome cancer drug resistance in selected conditions. However, the possibility of reaching suitably high concentrations of BA in the tumor microenvironment will need to be further investigated. [ABSTRACT FROM AUTHOR]

This paper presents an accurate averaged model of a Buck converter controlled via pulse‐skipping modulation (PSM). The derived model includes the parasitic elements of the circuit components, and it is not yet given in the literature. Output capacitor voltage and inductor current are analysed under steady‐state operation by deriving the expressions of average and ripple amplitude values. The accuracy improvements introduced by the proposed model are validated by comparison against models existing in the literature. A design procedure based on the proposed model is formulated and experimentally validated. The expressions for the control‐to‐output and the input‐to‐output network functions, both including the parasitic components of the converter circuit, are derived and utilized to exploit the circuit dynamic behaviour in the frequency domain. [ABSTRACT FROM AUTHOR]

Cross‐batch contamination in a decanter centrifuge during virgin olive oil production cannot be avoided using current technology. The extent of this contamination is investigated using industrial‐scale tests, by measuring the volatile profile and color on three consecutive oil batches, collected at the decanter outlet at different extraction times. The extent of contamination varied, pointing out qualitative consequences, as defective molecules are found. The latter are often active at low concentrations, and the measured cross‐batch contamination can lead both to the downgrading of large batches of virgin olive oils and to the adulteration of monovarietal and certified productions. An innovative method, based on the direct determination of the color (L and a* coordinates) of oil at the outlet of the decanter is able to identify the same compositional change point indicated by gas chromatography, and could be successfully used to mitigate the effects of cross‐batch contamination. Practical applications: An in‐line colorimetric system can be implemented at the decanter outlet to detect the point of change between different olive batches. Otherwise, the virgin olive oil exiting from the decanter at the beginning of one batch can be collected separately in order to avoid the contamination due to the previous batch. [ABSTRACT FROM AUTHOR]

Building integrated photovoltaics (BIPV) is progressively achieving an advanced level of technical maturity and considerable market penetration. In the last kilometre for considerable market implementation, major challenges are today mostly related to improving cost‐effectiveness and product reliability. BIPV multifunctional products are still framed in complex and sometimes unclear qualification processes, in the grey area between electrotechnical and construction sectors, impacting commercialization and users' confidence. The EN 50583 part 1 and part 2 standards today represent the main regulatory framework in Europe for BIPV. However, acts in force for product certification, in the construction and electrical sectors, in most national and local contexts are not yet harmonized for BIPV and imply wide margins of interpretation. The product's qualification in the EU is therefore based on electrical standards for photovoltaics modules or, on the other hand, on standards for construction products. To overcome some of these barriers and challenges, the authors propose a newly developed procedure for testing the impact resistance of BIPV products, introducing a performance‐based approach with the goal of combining building and electrical‐related limit states and responding to the need for a harmonized assessment to ensure the product's safety in use. The methodology and preliminary findings resulting from the application of real test cases, taking also into account the effect of temperature, are presented and analysed. As a result, it is envisaged that the implementation will help operators and prospective normative upgrades, ensuring more outstanding product quality for BIPV's market and driving towards a drop in life cycle costs. [ABSTRACT FROM AUTHOR]

The emerging coronavirus pneumonia epidemic caused by the SARS‐CoV‐2 infection has spread rapidly around the world. The main routes of transmission of SARS‐CoV‐2 are currently recognised as aerosol/droplet inhalation. However, the involvement of the oral cavity in coronavirus disease 2019 (COVID‐19) is poorly known. The current data indicates the presence of viral RNA in oral samples, suggesting the implication of saliva in SARS‐CoV‐2 transmission, however, no direct observation of SARS‐CoV‐2 particles in different oral samples has been reported. In this study, we investigated whether particles of SARS‐CoV‐2 were present in oral samples collected from three symptomatic COVID‐19 patients. Using scanning electron microscopy (SEM), the correlative strategy of light microscopy and electron microscopy and immunofluorescence staining, we showed the presence of SARS‐like particles in RT‐qPCR SARS‐CoV‐2‐positive saliva, dental plaque and gingival crevicular fluid (GCF) samples. In the saliva samples, we demonstrated the presence of epithelial oral cells with morphogenetic features of SARS‐CoV‐2 infected cells. Inside those cells, vacuoles filled with nascent particles were observed, suggesting the potential infection and replication of SARS‐CoV‐2 in oral tissues. Our results corroborate previous studies and confirm that the oral cavity may be a potential niche for SARS‐CoV‐2 infection and a potential source of transmission. [ABSTRACT FROM AUTHOR]

The development of novel and effective metal‐free catalytic systems, which can drive value‐added organic transformations in environmentally benign solvents (for instance, water), is highly desirable. Moreover, these new catalysts need to be harmless, easy‐to‐prepare, and potentially recyclable. In this context, amine‐rich carbon dots (CDs) have recently emerged as promising nano‐catalytic platforms. These nitrogen‐doped nanoparticles, which show dimensions smaller than 10 nm, generally consist of carbon cores that are surrounded by shells containing numerous amino groups. In recent years, organic chemists have used these surface amines to guide the design of several synthetic methodologies under mild operative conditions. This Concept highlights the recent advances in the synthesis of amine‐rich carbon dots and their applications in organic catalysis, including forward‐looking opportunities within this research field. [ABSTRACT FROM AUTHOR]

HTT full‐penetrance pathogenic repeat expansions, the genetic cause of Huntington's disease (HD), have been recently reported in a minority of frontotemporal dementia/amyotrophic lateral sclerosis (ALS) patients (0.13%). We analyzed HTT CAG repeats in an Italian cohort of ALS patients (n = 467) by repeat‐primed polymerase chain reaction. One patient harbored two expanded alleles in the HTT gene (42 and 37 CAG repeats). The absence of HD typical symptoms and the clinical picture consistent with ALS, corroborated by the diagnostic assessment, apparently excluded a misdiagnosis of HD. [ABSTRACT FROM AUTHOR]

The first atroposelective aminocatalytic methodology for the construction of C−N atropisomers is presented. The synthesis of this class of axially chiral molecules typically encompasses substrates in which the C−N bond is pre‐formed. In contrast, this work presents the direct coupling of indole‐2‐carboxaldehydes to ortho‐quinones, to form the stereogenic C−N axis in an atroposelective way. Application of typical secondary amine catalysts furnished the desired product, however, in low yields and as a complex mixture arising from poor regiocontrol among the C3‐ and N1‐sites of the indole core. A new aminocatalyst was designed and synthesized with increased outer‐sphere steric bulk to address these challenges thereby providing good levels of regio‐ and enantioselectivity. A novel library of functionalized and enantioenriched C−N atropisomers was obtained and their synthetic utility was demonstrated by various transformations. [ABSTRACT FROM AUTHOR]

Rift‐Rift‐Rift triple junctions are key features of emergent plate boundary networks during fragmentation of a continent. A key example of such a setting is the Afar triple junction where the African, Arabian and Somalian plates interact. We performed analog and numerical models simulating continental break‐up in a Rift‐Rift‐Rift setting to investigate the resulting structural pattern and evolution. We modified the ratio between plate velocities, and we performed single‐stage (with all plates moving at the same time) and two‐stage (where one plate first moves alone and then all the plates move simultaneously) models. Additionally, the direction of extension was changed to induce orthogonal extension in one of the three rift branches. Our models suggest that differential extension velocities in the rift branches determine the localization of the structural triple junction, which is located closer to the rift branch experiencing slower extension velocities. Furthermore, imposed velocities affect the deformation resulting in end‐member fault patterns. The effect of applying similar velocities in all rift arms is to induce a symmetric fault pattern (generating a Y‐shaped geometry). In contrast, a faster plate generates structures trending orthogonal to dominant velocity vectors, while faults associated with the movement of the slower plates remain subordinate (generating a T‐shaped pattern). Two‐stage models reveal high‐angle faults interacting at the triple junction, confirming that differential extension velocities strongly affect fault patterns. These latter models show large‐scale similarities with fault patterns observed in the Afar triple junction, providing insights into the factors controlling the structural evolution of this area. Plain Language Summary: When continents break‐up a rift valley can form and eventually grow to form an ocean. For particular conditions, more than two tectonic plates can be involved in this process. In this case, a "triple junction" is formed that consists of three rift branches. This process shaped the Afar region, where the movement of the Arabian, African, and Somalian plates, which separate at different rates of motion, created the Gulf of Aden, Red Sea, and Ethiopian rifts. The way in which triple junctions work can be difficult to study due to their large extent and several million year‐long activity. Therefore, we performed physical laboratory experiments and numerical experiments on the computer to investigate how triple junction form. We performed models with different rates of motion for the three plates, simulating one or two tectonic stages. The models show that the difference in the rate of motion between the three plates is the main control on the distribution and type of faults forming at triple junctions. Our results suggest that the fault pattern at the Afar triple junction observed nowadays may be explained by two tectonic stages and a lower extension rate occurring between the African and Somalian plates. Key Points: We perform single and two‐stage analog and numerical models of Rift‐Rift‐Rift triple junctionsModels show that differential velocity of extension between the plates is key for the geometry of fault patterns at triple junctionsTwo‐stage models shed light on the geometry and evolution of the Afar triple junction [ABSTRACT FROM AUTHOR]

Becker muscular dystrophy (BMD) is an X‐linked neuromuscular disorder due to mutation in the DMD gene, encoding dystrophin. Despite a wide clinical variability, BMD is characterized by progressive muscle degeneration and proximal muscle weakness. Interestingly, a dysregulated expression of muscle‐specific microRNAs (miRNAs), called myomirs, has been found in patients affected with muscular dystrophies, although few studies have been conducted in BMD. We analysed the serum expression levels of a subset of myomirs in a cohort of 29 ambulant individuals affected by BMD and further classified according to the degree of alterations at muscle biopsy and in 11 age‐matched healthy controls. We found a significant upregulation of serum miR‐1, miR‐133a, miR‐133b and miR‐206 in our cohort of BMD patients, supporting the role of these miRNAs in the pathophysiology of the disease, and we identified serum cut‐off levels discriminating patients from healthy controls, confiming the potential of circulating miRNAs as promising noninvasive biomarkers. Moreover, serum levels of miR‐133b were found to be associated with fibrosis at muscle biopsy and with patients' motor performances, suggesting that miR‐133b might be a useful prognostic marker for BMD patients. Taken together, our data showed that these serum myomirs may represent an effective tool that may support stratification of BMD patients, providing the opportunity of both monitoring disease progression and assessing the treatment efficacy in the context of clinical trials. [ABSTRACT FROM AUTHOR]

Aim: To assess the effect of surgical root coverage (RC) on dentin hypersensitivity (DH) associated with gingival recession. Materials and Methods: Two independent reviewers conducted electronic literature searches in MEDLINE (PubMed), EMBASE, Cochrane Library, Web Of Science, Dentistry & Oral Sciences Source, ScienceDirect, and ClinicalTrials.gov databases as well as a manual search to identify eligible clinical studies from January 2000 to March 2022. Randomized controlled trials (RCTs) comparing two surgical RC techniques or a surgical RC technique with or without adjuvant were included. Meta‐analyses were performed on data provided by RCTs. Results: Thirteen RCTs with a total of 701 patients (1086 recessions) were included. The percentage of DH suppression was 70.8% (95% confidence interval [CI] [64.4–76.6]; I2 = 39.2% [3.5–61.8], Q‐test = 0.02) after surgical RC. Recession reduction and percentage of RC were both statistically significantly associated with DH suppression (estimate = 0.66 [0.10–1.23], p =.022, R2 = 14.45% and estimate = 0.04 [0.01–0.08], p =.012, R2 = 29.54%, respectively). Coronally advanced flap (CAF) + connective tissue graft showed results statistically more effective than CAF + xenogeneic collagen matrix in DH suppression (73.3% [65.6–79.8] and 61.4% [51.7–70.3], respectively; p =.048). Conclusions: Success of surgical RC is associated with DH suppression. [ABSTRACT FROM AUTHOR]

Biliary tract cancers (BTCs) have poor prognosis and limited therapeutic options. The impact of O6-methylguanine-DNA methyltransferase (MGMT) inactivation in advanced BTC patients is not established. We investigated the prevalence, prognostic, and predictive impact of MGMT inactivation in two multicenter cohorts. MGMT inactivation was assessed through PCR and immunohistochemistry (IHC) in an Italian cohort; the results were then externally validated using RNA sequencing (RNA-seq) data from the BTC subcohort of the Molecularly Aided Stratification for Tumor Eradication Research (MASTER) precision oncology program of the National Center for Tumor Diseases Heidelberg and the German Cancer Consortium. Among 164 Italian cases, 18% presented MGMT promoter hypermethylation (> 14%) and 73% had negative MGMT protein expression. Both were associated with worse overall survival (OS; HR 2.31; P < 0.001 and HR 1.99, P = 0.012, respectively). In the MASTER cohort, patients with lower MGMT mRNA expression showed significantly poorer OS (median OS [mOS] 20.4 vs 31.7 months, unadjusted HR 1.89; P = 0.043). Our results suggest that MGMT inactivation is a frequent epigenetic alteration in BTC, with a significant prognostic impact, and provide the rationale to explore DNA-damaging agents in MGMT-inactivated BTCs. [ABSTRACT FROM AUTHOR]

Previous attempts to address the presence of interspecific competition between domestic livestock and wild ungulates have focused largely on habitat or dietary overlaps. Although overlaps in habitat or diet create opportunities for competition to occur between species, competition only results from such overlap if it affects one or both species negatively. Less attention has been afforded to possible behavioural modifications induced in wildlife by competition with domestic livestock. Here, we investigated the effects of the presence of livestock on feeding behaviour of guanaco (Lama guanicoe) in southern Patagonia, using focal sampling of individuals during foraging bouts, with instantaneous scan samples to estimate group behavioural budgets. We recorded guanaco bite and step rates, used as proxies of foraging intake and selectivity, from four different study sites over eight consecutive seasons. We also estimated sheep and guanaco densities per site, along with vegetation biomass availability. As in other ungulates, bite rates of guanaco appear to be highly flexible and generally increased with vegetation biomass availability. However, as sheep densities and thus additional grazing pressure increased, guanaco foraging strategy compensated by increasing bite rates when foraging vegetation was scarce, indicating further likelihood of competition. Additionally, scan samples indicated that the probability of guanaco feeding occurring at any one time was higher in areas shared with domestic sheep compared to national parks, suggesting guanaco have to focus more on feeding than other behaviours when sheep are present. [ABSTRACT FROM AUTHOR]