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Coastal ecosystems provide critical storm and flood protection but are rapidly degrading worldwide, making their restoration urgent. We evaluated whether successional facilitation, where pioneers facilitate climax species, could be leveraged to accelerate coastal dune revegetation. A survey spanning 270 km of Southeast U.S. coastline revealed that Panicum amarum (bitter panicum) supported higher plant richness than Uniola paniculata (sea oats) and that sea oat cover was 230% greater on mature dunes than disturbed dunes, suggesting bitter panicum functions as a pioneer and sea oats as a climax species. A reciprocal transplant experiment confirmed this interpretation: bitter panicum stem production and height fell by 37% and >20 cm, respectively, when planted proximate to sea oats versus in isolation, whereas sea oats produced 38% more and >12 cm taller stems when planted proximate to bitter panicum versus in isolation. A second experiment evaluating the density‐dependence of this facilitative interaction revealed that sea oats transplanted into low densities of bitter panicum grew >15% taller than isolated and high‐density treatments. However, within 7 months, wave inundation eliminated over 60% of propagules in both experiments. To explore foredune inundation frequency and its implications for dune revegetation, we applied empirical wave runup models at 101 locations throughout Volusia County, Florida. While disturbance frequency varied seasonally and annually, sites with low dune crests and steep beach slopes experienced frequent inundation (>50 events/year). Given the interactions between geomorphology and vegetation success, we present a decision matrix to guide managers in determining optimal revegetation methods tailored to project goals and site conditions. [ABSTRACT FROM AUTHOR]

Objectives: In Italy, asbestos was used intensively until its ban in 1992, which was extended for asbestos cement factories until 1994. The aim of this study was to evaluate the dose–response between asbestos exposure and asbestosis mortality across a pool of Italian occupational cohorts, taking into account the presence of competing risks. Methods: Cohorts were followed for vital status and the cause of death was ascertained by a linkage with mortality registers. Cause‐specific (CS) Cox‐regression models were used to evaluate the dose‐exposure relationship between asbestosis mortality and the time‐dependent cumulative exposure index (CEI) to asbestos. Fine and Gray regression models were computed to assess the effect of competing risks of death. Results: The cohort included 12,963 asbestos cement workers. During the follow‐up period (1960−2012), of a total of 6961 deaths, we observed 416 deaths attributed to asbestosis, 879 to lung cancer, 400 to primary pleural cancer, 135 to peritoneal cancer, and 1825 to diseases of the circulatory system. The CS model showed a strong association between CEI and asbestosis mortality. Dose–response models estimated an increasing trend in mortality even below a CEI of 25 ff/mL‐years. Lung cancer and circulatory diseases were the main competing causes of death. Conclusions: Asbestos exposure among Italian asbestos‐cement workers has led to a very high number of deaths from asbestosis and asbestos‐related diseases. The increasing risk trend associated with excess deaths, even at low exposure levels, suggests that the proposed limit values would not have been adequate to prevent disability and mortality from asbestosis. [ABSTRACT FROM AUTHOR]

Neuromorphic computing aims to leverage physical phenomena of adaptive materials for emulating information processing capabilities and effectiveness of biological neuronal circuits. In this framework, memristors (resistors with memory) based on 2D materials are demonstrated for the hardware implementation of highly integrated artificial neural networks. All the works reported thus far exploited electrical properties of 2D materials to emulate neuromorphic functionalities. Here, a 2D memitter (emitter with memory) is reported on that exploits the stimuli‐responsive photoluminescence of a monolayer WS2 for neuromorphic‐type of data processing. A combined experimental and modeling approach reveals that photoluminescent dynamics triggered by optical stimulation emulates Short‐Term synaptic Plasticity and Visual Short‐Term Memory typical of biological systems. While spatio‐temporal processing capabilities of input signals can be used for information processing in the context of reservoir computing, the capability of the 2D memitter of sensing, processing, and memorizing‐forgetting optical inputs in the same physical substrate can be utilized for in‐sensor computing. [ABSTRACT FROM AUTHOR]

Interaction with fishing gears represents the main anthropogenic threat at sea for sea turtles worldwide, and identifying the hotspots of turtle bycatch is a priority knowledge gap.Turtle stranding data represent a source of information about mortality areas at sea that are not fully exploited. This study aims to infer turtle mortality areas of turtles stranded along the Italian Adriatic Coast in the period 2019–2021 (1432 records), through backtrack modelling of carcasses. Specifically, the decomposition process of eight loggerhead carcasses was monitored, and the relationship between floating period (FP), turtle size and sea temperature was modelled through a generalized additive model. Oceanographic information was then used to track the routes of floating carcasses back, knowing their size and decomposition stage, and finally estimate the likely area of mortality. A complementary numerical experiment of connectivity between coastal and offshore areas gave indication that areas of potential mortality are relatively close to the coast, particularly in the northern Adriatic.Stranded turtles probably represent just a small fraction (17%–25%) of total at‐sea mortalities in the study area (Italian Adriatic waters), with decomposition rates, season and distance from shore influencing their stranding likelihood. Hence, strandings can inform only about spatio‐temporal variability of coastal mortality hotspots.Inferred areas of turtle mortality were most likely located in the North and Central Adriatic all over the year and overlap with heatmaps of fishing effort, obtained from vessel monitoring system (VMS) and automatic identification system (AIS) data, in the Gulf of Manfredonia and in the North‐West Adriatic in the cold (September–December) and warm (May–August) periods, respectively. [ABSTRACT FROM AUTHOR]

Background: In the last few years, percutaneous LAA occlusion (LAAO) has become a plausible alternative in atrial fibrillation (AF) patients with contraindications to anticoagulation therapy. Nevertheless, the optimal antiplatelet strategy following percutaneous LAAO remains to be defined. Methods: Studies comparing single antiplatelet therapy (SAPT) versus dual antiplatelet therapy (DAPT) following LAAO were systematically searched and screened. The outcomes of interest were ischemic stroke, device‐related thrombus (DRT) and major bleeding. A random‐effect meta‐analysis was performed comparing outcomes in both groups. The moderator effect of baseline characteristics on outcomes was evaluated by univariate meta‐regression analyses. Results: Sixteen observational studies with 3255 patients treated with antiplatelet therapy (SAPT, n = 1033; DAPT, n = 2222) after LAAO were included. Mean age was 74.5 ± 8.3 years, mean CHA2DS2‐VASc and HAS‐BLED scores were 4.3 ± 1.5 and 3.2 ± 1.0, respectively. At a weighted mean follow‐up of 12.7 months, the occurrence of stroke (RR 1.33; 95% CI 0.64–2.77; p =.44), DRT (RR 1.52; 95% CI 0.90–2.58; p =.12), and the composite of stroke and DRT (RR 1.26; 95% CI 0.67–2.37; p =.47) did not differ significantly between SAPT and DAPT groups. The rate of major bleedings was also not different between groups (RR 1.41; 95% CI 0.64–3.12; p =.39). Conclusions: Among AF patients at high bleeding risk undergoing percutaneous LAAO, a post‐procedural minimalistic antiplatelet strategy with SAPT did not significantly differ from DAPT regimens regarding the rate of stroke, DRT and major bleeding. [ABSTRACT FROM AUTHOR]

SUMMARY: Polyamines are involved in several plant physiological processes. In Arabidopsis thaliana, five FAD‐dependent polyamine oxidases (AtPAO1 to AtPAO5) contribute to polyamine homeostasis. AtPAO5 catalyzes the back‐conversion of thermospermine (T‐Spm) to spermidine and plays a role in plant development, xylem differentiation, and abiotic stress tolerance. In the present study, to verify whether T‐Spm metabolism can be exploited as a new route to improve stress tolerance in crops and to investigate the underlying mechanisms, tomato (Solanum lycopersicum) AtPAO5 homologs were identified (SlPAO2, SlPAO3, and SlPAO4) and CRISPR/Cas9‐mediated loss‐of‐function slpao3 mutants were obtained. Morphological, molecular, and physiological analyses showed that slpao3 mutants display increased T‐Spm levels and exhibit changes in growth parameters, number and size of xylem elements, and expression levels of auxin‐ and gibberellin‐related genes compared to wild‐type plants. The slpao3 mutants are also characterized by improved tolerance to drought stress, which can be attributed to a diminished xylem hydraulic conductivity that limits water loss, as well as to a reduced vulnerability to embolism. Altogether, this study evidences conservation, though with some significant variations, of the T‐Spm‐mediated regulatory mechanisms controlling plant growth and differentiation across different plant species and highlights the T‐Spm role in improving stress tolerance while not constraining growth. [ABSTRACT FROM AUTHOR]

High concentrations of urinary calcium counteract vasopressin action via the activation of the Calcium‐Sensing Receptor (CaSR) expressed in the luminal membrane of the collecting duct cells, which impairs the trafficking of aquaporin‐2 (AQP2). In line with these findings, we provide evidence that, with respect to wild‐type mice, CaSR knock‐in (KI) mice mimicking autosomal dominant hypocalcaemia, display a significant decrease in the total content of AQP2 associated with significantly higher levels of AQP2 phosphorylation at Ser261, a phosphorylation site involved in AQP2 degradation. Interestingly, KI mice also had significantly higher levels of phosphorylated p38MAPK, a downstream effector of CaSR and known to phosphorylate AQP2 at Ser261. Moreover, ATF1 phosphorylated at Ser63, a transcription factor downstream of p38MAPK, was significantly higher in KI. In addition, KI mice had significantly higher levels of AQP2‐targeting miRNA137 consistent with a post‐transcriptional downregulation of AQP2. In vivo treatment of KI mice with the calcilytic JTT‐305, a CaSR antagonist, increased AQP2 expression and reduced AQP2‐targeting miRNA137 levels in KI mice. Together, these results provide direct evidence for a critical role of CaSR in impairing both short‐term vasopressin response by increasing AQP2‐pS261, as well as AQP2 abundance, via the p38MAPK‐ATF1‐miR137 pathway. Key points: Calcium‐Sensing Receptor (CaSR) activating mutations are the main cause of autosomal dominant hypocalcaemia (ADH) characterized by inappropriate renal calcium excretion leading to hypocalcaemia and hypercalciuria. Current treatments of ADH patients with parathyroid hormone, although improving hypocalcaemia, do not improve hypercalciuria or nephrocalcinosis.In vivo treatment with calcilytic JTT‐305/MK‐5442 ameliorates most of the ADH phenotypes of the CaSR knock‐in mice including hypercalciuria or nephrocalcinosis and reverses the downregulation of the vasopressin‐sensitive aquaporin‐2 (AQP2) expression, providing direct evidence for a critical role of CaSR in impairing vasopressin response.The beneficial effect of calcilytic in reducing the risk of renal calcification may occur in a parathyroid hormone‐independent action through vasopressin‐dependent inhibition of cAMP synthesis in the thick ascending limb and in the collecting duct.The amelioration of most of the abnormalities in calcium metabolism including hypercalciuria, renal calcification, and AQP2‐mediated osmotic water reabsorption makes calcilytic a good candidate as a novel therapeutic agent for ADH. [ABSTRACT FROM AUTHOR]

Bivalves are becoming an increasingly popular tool to counteract eutrophication, particularly in vegetated coastal ecosystems where synergistic interactions between bivalves and plants can govern important N sequestration pathways. In turn, new calls to evaluate how bivalve densities modify N pools and processes across multiple scales have surfaced.Ribbed mussels, Geukensia demissa, and their relationship with smooth cordgrass present a classic demonstration of positive bivalve‐plant interactions and offer a useful model for assessing density dependence. We measure porewater ammonium concentrations, N stable isotope signatures in cordgrass tissue, and sediment N fluxes in mussel aggregations and in cordgrass‐only plots across a southeastern U.S. salt marsh.In addition to measuring the effect of mussel presence, we evaluate mussel density dependence through a multiscale approach. At the patch scale, we quantify mussel density effects within their aggregations (individuals m−2) while at a larger landscape scale, we quantify mussel density effects on the cordgrass‐only areas they neighbour (individuals ~30 m−2).Porewater ammonium concentrations were halved in mussel biodeposits relative to sediments in cordgrass‐only areas and negatively related to mussel density within aggregations. Leaf clip ẟ15N signatures were nearly 2‰ higher in cordgrass growing among mussel aggregations and increased with increasing patch mussel density. Microcosm incubations showed that mussels enhanced N2 flux (i.e., nitrogen removal) and DIN flux (i.e., N regeneration) into the water column, where only nitrogen removal increased with increasing patch‐scale mussel density. Across the marsh landscape, mussel coverage drove ammonium accumulation and N2 flux in sediments.Synthesis. Our results suggest that, at the patch scale, mussels stimulate the microbial metabolism of N, the assimilation of this bioavailable N by cordgrass, and nitrogen removal in a positive, density‐dependent manner. Tidal currents redistribute mussel biodeposits from mussel aggregations to surrounding areas, influencing biogeochemical transformations at scales beyond their physical footprint. We emphasize that the N regeneration potential of bivalve populations is a significant metric contributing to their mitigation potential and that bivalve density effects may be non‐linear, vary across patch to ecosystem scales, and have differing implications for the plants with which they interact. [ABSTRACT FROM AUTHOR]

Macrocycles offer an attractive format for drug development due to their good binding properties and potential to cross cell membranes. To efficiently identify macrocyclic ligands for new targets, methods for the synthesis and screening of large combinatorial libraries of small cyclic peptides were developed, many of them using thiol groups for efficient peptide macrocyclization. However, a weakness of these libraries is that invariant thiol‐containing building blocks such as cysteine are used, resulting in a region that does not contribute to library diversity but increases molecule size. Herein, we synthesized a series of structurally diverse thiol‐containing elements and used them for the combinatorial synthesis of a 2,688‐member library of small, structurally diverse peptidic macrocycles with unprecedented skeletal complexity. We then used this library to discover potent thrombin and plasma kallikrein inhibitors, some also demonstrating favorable membrane permeability. X‐ray structure analysis of macrocycle‐target complexes showed that the size and shape of the newly developed thiol elements are key for binding. The strategy and library format presented in this work significantly enhance structural diversity by allowing combinatorial modifications to a previously invariant region of peptide macrocycles, which may be broadly applied in the development of membrane permeable therapeutics. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune degenerative disease targeting white matter in the central nervous system. The most common animal model that mimics MS is experimental autoimmune encephalomyelitis (EAE) and it plays a crucial role in pharmacological research, from the identification of a therapeutic target to the in vivo validation of efficacy. Magnetic resonance imaging (MRI) is largely used to detect MS lesions, and resting‐state functional MRI (rsfMRI) to investigate alterations in the brain functional connectivity (FC). MRI was mainly used in EAE studies to detect lesions in the spinal cord and brain. The current longitudinal MRI study aims to validate rsfMRI as a biomarker of the disease progression in the myelin oligodendrocyte glycoprotein 35–55 induced EAE animal model of MS. MR images were acquired 14, 25, and 50 days postimmunization. Seed‐based analysis was used to investigate the whole‐brain FC with some predefined areas, such as the thalamic regions, cerebellum, motor and somatosensory cortex. When compared with the control group, the EAE group exhibited a slightly altered FC and a decreasing trend in the total number of activated voxels along the disease progression. The most interesting result regards the whole‐brain FC with the cerebellum. A hyperconnectivity behavior was found at an early phase and a significant reduced connectivity at a late phase. Moreover, we found a negative correlation between the total number of activated voxels during the late phase and the cumulative disease index. The results obtained provide a clinically relevant experimental platform that may be pivotal for the elucidation of the key mechanisms of accumulation of irreversible disability, as well as the development of innovative therapies for MS. Moreover, the negative correlation between the disease severity and the size of the activated area suggests a possible research pathway to follow for the resolution of the clinico‐radiological paradox. [ABSTRACT FROM AUTHOR]

In antiquity, Pb was a common element added in the production of large bronze artifacts, especially large statues, to impart fluidity to the casting process. As Pb does not form a solid solution with pure Cu or with the Sn–Cu alloy phases, it is normally observed in the metal matrix as globular droplets embedded within or in interstitial positions among the crystals of Sn‐bronze (normally the α phase) as the last crystallizing phase during the cooling process of the Cu–Sn–Pb ternary melt. The disequilibrium Sn content of the Pb droplets has recently been suggested as a viable parameter to detect modern materials [Shilstein, Berner, Feldman, Shalev & Rosenberg (2019). STAR Sci. Tech. Archaeol. Res.5, 29–35]. The application assumes a time‐dependent process, with a timescale of hundreds of years, estimated on the basis of the diffusion coefficient of Sn in Pb over a length of a few micrometres [Oberschmidt, Kim & Gupta (1982). J. Appl. Phys.53, 5672–5677]. Therefore, Pb inclusions in recent Sn‐bronze artifacts are actually a metastable solid solution of Pb–Sn containing ∼3% atomic Sn. In contrast, in ancient artifacts, unmixing processes and diffusion of Sn from the micro‐ and nano‐inclusions of Pb to the matrix occur, resulting in the Pb inclusions containing a substantially lower or negligible amount of Sn. The Sn content in the Pb inclusions relies on accurate measurement of the lattice parameter of the phase in the Pb–Sn solid solution, since for low Sn values it closely follows Vegard's law. Here, several new measurements on modern and ancient samples are presented and discussed in order to verify the applicability of the method to the detection of modern artwork pretending to be ancient. [ABSTRACT FROM AUTHOR]

We study the effect of economic conditions early in life on the occurrence of type-2 diabetes in adulthood using contextual economic indicators and withinsibling pair variation. We use data from Lifelines: a longitudinal cohort study and biobank including 51,270 siblings born in the Netherlands from 1950 onward. Sibling fixed-effects account for selective fertility. To identify type-2 diabetes we use biomarkers on the hemoglobin A1c concentration and fasting glucose in the blood. We find that adverse economic conditions around birth increase the probability of type-2 diabetes later in life both in males and in females. Inference based on self-reported diabetes leads to biased results, incorrectly suggesting the absence of an effect. The same applies to inference that does not account for selective fertility. [ABSTRACT FROM AUTHOR]

Introduction: Social media are widely used by adolescents and young adults as a mean to maintain interpersonal relationships. Recent studies have found that young individuals with high levels of social anxiety feel more confident in communicating online. However, little is known about the role of perceived social media characteristics that could minimize the distress they experienced in face‐to‐face interactions. In this study, we rely on the tenets of the Transformation Framework, according to which social media, with its own features, may transform social relationships, including disclosing emotions and communicating with others online, in ways that may differ across individuals with or without specific vulnerability (e.g., social anxiety). Therefore, this cross‐sectional study aims at examining the contribution of three specific social media features (i.e., asynchronicity, cue absence, and visualness) in explaining perceived breadth and depth of online communication, both directly and via e‐motional processes (i.e., expression and facilitating use of e‐motions), across groups of individuals with high versus low levels of social anxiety. Methods: Participants were 1046 Italian adolescents and young adults (61.4% females; Mage = 17.9, SD = 3.23) who completed an anonymous self‐report questionnaire between 2021 and 2022. Participants with very high scores on social anxiety (above the 90th percentile; socially anxious), were distinguished from all others (socially nonanxious) and a multigroup analysis (MGA) was run to compare the pattern of associations across the two different groups. Results and Conclusion: Results from the MGA showed significant differences between the two groups, partially confirming our hypotheses. Specifically, among socially anxious individuals, perceived cue absence was found to benefit perceived breadth and depth of online communication, and asynchronicity to enhance online emotional processes; conversely, these associations were negative in the group of socially nonanxious. Thus, these findings underly the contribution of social media in explaining youngsters' online experiences and support the potential beneficial role of some social media features for those more socially vulnerable. [ABSTRACT FROM AUTHOR]

Background and Objectives: Deficiencies of protein C (PC) or protein S (PS) are rare diseases, characterized by mutations in the PC or PS genes, which encode plasma serine proteases with anti‐coagulant activity. Severe PC or PS deficiencies manifest in early life as neonatal purpura fulminans, a life‐threatening heamorrhagic condition requiring immediate treatment. First‐line treatment involves replacement therapy, followed by maintenance with anti‐coagulants. Replacement therapy with specific protein concentrates is currently only limited to PC, and therefore, a PC + PS concentrate represents a useful addition to therapeutic options, particularly for severe PS deficiency. Further, the production of a PC + PS concentrate from unused plasma fractionation intermediates would impact favourably on manufacturing costs, and consequently therapy prices for patients and health systems. Materials and Methods: Several chromatographic runs were performed on the same unused plasma fractionation intermediates using different supports to obtain a PC/PS concentrate. The best chromatographic mediums were chosen, in terms of specific activity and recovery. A full process of purification including virus inactivation/removal and lyophilization steps was set up. Results: The final freeze‐dried product had a mean PC concentration of 47.75 IU/mL with 11% of PS, and a mean specific activity of 202.5 IU/mg protein, corresponding to over 12,000‐fold purification from plasma. Conclusion: The development of a novel concentrated PC/PS mixture obtained from a waste fraction of other commercial products could be used for its potential therapeutic role in the management of neonatal purpura fulminans pathology. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is the most prevalent gynecological cancer in high‐income countries. Its incidence is skyrocketing due to the increase in risk factors such as obesity, which represents a true pandemic. This study aimed to evaluate microRNA (miRNA) expression in obesity‐related EC to identify potential associations between this specific cancer type and obesity. miRNA levels were analyzed in 84 EC patients stratified based on body mass index (BMI; ≥30 or <30) and nine noncancer women with obesity. The data were further tested in The Cancer Genome Atlas (TCGA) cohort, including 384 EC patients, 235 with BMI ≥30 and 149 with BMI <30. Prediction of miRNA targets and analysis of their expression were also performed to identify the potential epigenetic networks involved in obesity modulation. In the EC cohort, BMI ≥30 was significantly associated with 11 deregulated miRNAs. The topmost deregulated miRNAs were first analyzed in 84 EC samples by single miRNA assay and then tested in the TCGA dataset. This independent validation provided further confirmation about the significant difference of three miRNAs (miR‐199a‐5p, miR‐449a, miR‐449b‐5p) in normal‐weight EC patients versus EC patients with obesity, resulting significantly higher expressed in the latter. Moreover, the three miRNAs were significantly correlated with grade, histological type, and overall survival. Analysis of their target genes revealed that these miRNAs may regulate obesity‐related pathways. In conclusion, we identified specific miRNAs associated with BMI that are potentially involved in modulating obesity‐related pathways and that may provide novel implications for the clinical management of obese EC patients. [ABSTRACT FROM AUTHOR]

A systematic and extensive analytical study was carried out on the loose inlays discovered in the Ptolemaic workshop of Tebtynis (Fayum oasis, Egypt). This paper presents data derived from the multi‐methodological archaeometric investigations (optical microscopy, scanning electron microscopy–energy‐dispersive spectroscopy, electron probe microanalysis, micro‐Raman spectroscopy) performed on a set of intentionally colored and opacified glasses. In particular, we will discuss the textural, chemical, and mineralogical results related to the study of the yellow, yellowish‐orange, red, and brown inlays and semi‐finished/waste products now preserved at the Museo Egizio, Torino. The results highlight the presence of natron (low‐magnesium glasses, LMG) and plant ash (high‐magnesium glasses, HMG) base glass, coexisting with intermediate composition. Yellow samples are opacified using lead antimonates doped with iron and sometimes tin; conversely, yellowish‐orange specimens and the only brown sample are characterized by nanocrystals of cuprite. Red glasses are found in two variants: Dull reds are HMG with colloidal metallic copper particles, while sealing‐wax reds show LMG composition, associated with dendritic cuprite dispersed in a transparent, greenish matrix. [ABSTRACT FROM AUTHOR]

The pharmacokinetic properties of small biotherapeutics can be enhanced via conjugation to cross‐reactive albumin‐binding ligands in a process that improves their safety and accelerates testing through multiple pre‐clinical animal models. In this context, the small and stable heavy‐chain‐only nanobody NbAlb1, capable of binding both human and murine albumin, has recently been successfully applied to improve the stability and prolong the in vivo plasma residence time of multiple small therapeutic candidates. Despite its clinical efficacy, the mechanism of cross‐reactivity of NbAlb1 between human and murine serum albumins has not yet been investigated. To unveil the molecular basis of such an interaction, we solved the crystal structure of human serum albumin (hSA) in complex with NbAlb1. The structure was obtained by harnessing the unique features of a megabody chimeric protein, comprising NbAlb1 grafted onto a modified version of the circularly permutated and bacterial‐derived protein HopQ. This structure showed that NbAlb1 contacts a yet unexplored binding site located in the peripheral region of domain II that is conserved in both human and mouse serum albumin proteins. Furthermore, we show that the binding of NbAlb1 to both serum albumin proteins is retained even at acidic pH levels, thus explaining its extended in vivo half‐life. The elucidation of the molecular basis of NbAlb1 cross‐reactivity to human and murine albumins might guide the design of novel nanobodies with broader reactivity toward a larger panel of serum albumins, thus facilitating the pre‐clinical and clinical phases in humans. [ABSTRACT FROM AUTHOR]

Coronal mass ejections (CMEs) can create significant disruption to human activities and systems on Earth, much of which can be mitigated with prior warning of the upstream solar wind conditions. However, it is currently extremely challenging to accurately predict the arrival time and internal structure of a CME from coronagraph images alone. In this study, we take advantage of a rare opportunity to use Solar Orbiter, at 0.5 au upstream of Earth, as an upstream solar wind monitor. In combination with low‐latency images from STEREO‐A, we successfully predicted the arrival time of two CME events before they reached Earth. Measurements at Solar Orbiter were used to constrain an ensemble of simulation runs from the ELEvoHI model, reducing the uncertainty in arrival time from 10.4 to 2.5 hr in the first case study. There was also an excellent agreement in the Bz profile between Solar Orbiter and Wind spacecraft for the second case study, despite being separated by 0.5 au and 10° longitude. The opportunity to use Solar Orbiter as an upstream solar wind monitor will repeat once a year, which should further help assess the efficacy upstream in‐situ measurements in real time space weather forecasting. Plain Language Summary: Coronal mass ejections (CMEs) are large eruptions of plasma from the Sun that can significantly disrupt human technology when directed toward Earth. Much like weather on Earth, the consequences of these "space weather" events can be lessened with warning of their arrival, for example, putting satellites into safe mode. This is usually done by identifying a CME in telescope images, and then predicting if and when it will arrive at Earth. However, the current forecasting models have large uncertainties in arrival time, and struggle to predict the in situ properties of the CME, which can significantly alter the severity of the event. In this paper, by taking advantage of a period in March 2022, we were able to use real time measurements from halfway between the Sun and the Earth taken by the Solar Orbiter spacecraft. This allowed us to predict the arrival time of a CME more than a day before it arrived at Earth, a significant improvement on the current capabilities. We also show that the Solar Orbiter measurements can be used to constrain a CME propagation model, significantly improving the accuracy and precision of the forecasted arrival time. Key Points: Real time data from Solar Orbiter and STEREO‐A were used to predict the arrival time of two coronal mass ejections before arrival at EarthFor one event, in situ measurements at 0.5 au were used to reduce the error in arrival time from 10.4 to 2.5 hr with the ELEvoHI modelThe in situ Bz profile was comparable to the geomagnetic response at Earth, despite being separated by 0.5 au and 10° longitude [ABSTRACT FROM AUTHOR]

Highly oxygenated cyclohexanes, including (amino)cyclitols, are featured in natural products possessing a notable range of biological activities. As such, these building blocks are valuable tools for medicinal chemistry. While de novo synthetic strategies have provided access to select compounds, challenges including stereochemical density and complexity have hindered the development of a general approach to (amino)cyclitol structures. This work reports the use of arenophile chemistry to access dearomatized intermediates which are amenable to diverse downstream transformations. Practical guidelines were developed for the synthesis of natural and non‐natural (amino)cyclitols from simple arenes through a series of strategic functionalization events. [ABSTRACT FROM AUTHOR]

Aims: Latitudinal gradients in plant communities are well studied, yet how these fundamental ecological patterns influence ecosystem recovery after extreme weather events remains largely unknown. In coastal foredunes, we investigated how the cover of a key dune‐building grass (Uniola paniculata), vegetation diversity and vegetation cover vary along a short latitudinal gradient during recovery from hurricane disturbance. Location: Southeastern USA. Methods: We surveyed 24 sites, from central Florida to north Georgia (>400 km), four times over 18 months. General linear mixed‐effect models were used to unravel patterns of vegetation responses across latitude. Results: Vegetation properties showed countervailing patterns across the latitudinal gradient. While vegetation richness, functional diversity and total cover generally declined, Uniola cover increased with increasing latitude. Further, the latitude–richness relationship strengthened while the latitude–functional diversity relationship was invariant with increasing time since the hurricane disturbance. Meanwhile, the latitude–Uniola association was seasonally dependent and strongest in the summer. Latitude also influenced diversity–cover relationships: vegetation cover was positively related to species richness at lower latitudes, while it was positively associated with functional diversity only at northern sites. We found no relationship between species richness or functional diversity and increases in cover between time steps; however, recruitment of new species and functional groups was associated with increases in vegetation cover between time steps at northern sites. Conclusions: Our study highlights the temporal dynamism and contrasting patterns along latitudinal gradients exhibited by key engineering species and overall plant diversity in foredunes — a crucial line of coastal protection — exposed to hurricane disturbances. These results suggest a need for greater integration of latitudinal and diversity effects into our understanding of coastal dune resilience. They also highlight the potential benefits of enhancing dune plant biodiversity, particularly in areas where the dune‐building grasses that are classically employed in restoration (e.g., Uniola) are unfavoured, to accelerate the re‐establishment of well‐vegetated dunes. [ABSTRACT FROM AUTHOR]

Preterm infants cannot counteract excessive reactive oxygen species (ROS) production due to preterm birth, leading to an excess of lipid peroxidation with malondialdehyde (MDA) production, capable of contributing to brain damage. Melatonin (ME), an endogenous brain hormone, and its metabolites, act as a free radical scavenger against ROS. Unfortunately, preterms have an impaired antioxidant system, resulting in the inability to produce and release ME. This prospective, multicenter, parallel groups, randomized, double‐blind, placebo‐controlled trial aimed to assess: (i) the endogenous production of ME in very preterm infants (gestational age ≤ 29 + 6 WE, 28 infants in the ME and 26 in the placebo group); (ii) the exogenous hormone availability and its metabolization to the main metabolite, 6‐OH‐ME after 15 days of ME oral treatment; (iii) difference of MDA plasma concentration, as peroxidation marker, after treatment. Blood was collected before the first administration (T1) and after 15 days of administration (T2). ME and 6‐OH‐ME were detected by liquid chromatography tandem mass spectrometry, MDA was measured by liquid chromatograph with fluorescence detection. ME and 6‐OH‐ME were not detectable in the placebo group at any study time‐point. ME was absent in the active group at T1. In contrast, after oral administration, ME and 6‐OH‐ME resulted highly detectable and the difference between concentrations T2 versus T1 was statistically significant, as well as the difference between treated and placebo groups at T2. MDA levels seemed stable during the 15 days of treatment in both groups. Nevertheless, a trend in the percentage of neonates with reduced MDA concentration at T2/T1 was 48.1% in the ME group versus 38.5% in the placebo group. We demonstrated that very preterm infants are not able to produce endogenous detectable plasma levels of ME during their first days of life. Still, following ME oral administration, appreciable amounts of ME and 6‐OH‐ME were available. The trend of MDA reduction in the active group requires further clinical trials to fix the dosage, the length of ME therapy and to identify more appropriate indexes to demonstrate, at biological and clinical levels, the antioxidant activity and consequent neuroprotectant potential of ME in very preterm newborns. [ABSTRACT FROM AUTHOR]

Background: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers. Methods: Cancer risk was studied among a pool of formerly asbestos‐exposed workers in Italy. Fifty‐two Italian asbestos cohorts (asbestos‐cement, rolling‐stock, shipbuilding, and other) were pooled and their mortality follow‐up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period. Results: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow‐up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03−1.05; women = 1.15, 95% CI 1.11−1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18−1.23; women = 1.29, 95% CI 1.22−1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86−11.09 and 4.29, 95% CI 3.66−5.00; women: SMR = 27.13, 95% CI 23.29−31.42 and 7.51, 95% CI 5.52−9.98), lung (SMR: men = 1.28, 95% CI 1.24−1.32; women = 1.26, 95% CI 1.02−1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08−1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter. Conclusions: Analyses by time‐dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time. [ABSTRACT FROM AUTHOR]

Self‐assembly of proteinaceous biomolecules into functional materials with ordered structures that span length scales is common in nature yet remains a challenge with designer peptides under ambient conditions. This report demonstrates how charged side‐chain chemistry affects the hierarchical co‐assembly of a family of charge‐complementary β‐sheet‐forming peptide pairs known as CATCH(X+/Y−) at physiologic pH and ionic strength in water. In a concentration‐dependent manner, the CATCH(6K+) (Ac‐KQKFKFKFKQK‐Am) and CATCH(6D−) (Ac‐DQDFDFDFDQD‐Am) pair formed either β‐sheet‐rich microspheres or β‐sheet‐rich gels with a micron‐scale plate‐like morphology, which were not observed with other CATCH(X+/Y−) pairs. This hierarchical order was disrupted by replacing D with E, which increased fibril twisting. Replacing K with R, or mutating the N‐ and C‐terminal amino acids in CATCH(6K+) and CATCH(6D−) to Qs, increased observed co‐assembly kinetics, which also disrupted hierarchical order. Due to the ambient assembly conditions, active CATCH(6K+)‐green fluorescent protein fusions could be incorporated into the β‐sheet plates and microspheres formed by the CATCH(6K+/6D−) pair, demonstrating the potential to endow functionality. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial membrane protein‐associated neurodegeneration (MPAN) is caused by mutations in the C19orf12 gene. MPAN typically appears in the first two decades of life and presents with progressive dystonia‐parkinsonism, lower motor neuron signs, optic atrophy, and abnormal iron deposits predominantly in the basal ganglia. MPAN, initially considered as a strictly autosomal recessive disease (AR), turned out to be also dominantly inherited (AD). Objectives: Our aim was to better characterize the clinical, molecular, and functional spectra associated with such dominant pathogenic heterozygous C19orf12 variants. Methods: We collected clinical, imaging, and molecular information of eight individuals from four AD‐MPAN families and obtained brain neuropathology results for one. Functional studies, focused on energy and iron metabolism, were conducted on fibroblasts from AD‐MPAN patients, AR‐MPAN patients, and controls. Results: We identified four heterozygous C19orf12 variants in eight AD‐MPAN patients. Two of them carrying the familial variant in mosaic displayed an atypical late‐onset phenotype. Fibroblasts from AD‐MPAN showed more severe alterations of iron storage metabolism and autophagy compared to AR‐MPAN cells. Conclusion: Our data add strong evidence of the realness of AD‐MPAN with identification of novel monoallelic C19orf12 variants, including at the mosaic state. This has implications in diagnosis procedures. We also expand the phenotypic spectrum of MPAN to late onset atypical presentations. Finally, we demonstrate for the first time more drastic abnormalities of iron metabolism and autophagy in AD‐MPAN than in AR‐MPAN. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Interest in leveraging suspension feeders, such as marine bivalves, to exert top‐down control on organic matter (OM) loading in estuaries is gaining momentum. Not only can these faunal engineers alleviate the consequences of nutrient pollution, but they may also bolster the critical blue carbon services provided by coastal ecosystems—a potential dual, mitigating effect on cultural eutrophication and climate change. Ribbed mussels, Geukensia demissa, offer a useful model for assessing faunally driven carbon (C) and nitrogen (N) processes in these systems and their relationships with faunal density. Combining bulk geochemical analyses with Bayesian stable isotope mixing model frameworks (MixSIAR), we quantified the effect of mussels on the source and amount of organic C and N deposited to the benthic floor (i.e., sedimentation), accumulated in surface sediments, and stored in aboveground Spartina alterniflora in Georgia salt marshes. Relative to areas without mussels, mussel presence shifted the source of deposited and accumulated OM to a more allochthonous makeup; amplified the amount of deposited, but not accumulated, allochthonous and autochthonous OM; and enhanced aboveground storage of C and N. Both sources of OM accumulated in sediments as well as standing stocks of C and N were highly and positively correlated with local mussel density (ind. m−2) but unrelated to neighboring mussel density (ind. ∼25 m−2) in adjacent, non‐mussel areas. This work provides new evidence that suspension feeders, through their faunal engineering activities, can interact powerfully and synergistically with primary producers to enhance the blue carbon services of marshes and counteract coastal eutrophication. Plain Language Summary: Coastal ecosystems regulate carbon and nitrogen generated both inside and outside of their physical extents—important ecosystem services that can help combat the consequences of pollution and climate change. Suspension‐feeding animals living in these ecosystems, like mussels, may enhance this regulation by feeding on algae suspended in the overlying tidewater and depositing their waste to the habitat bottom. There, these deposits can accumulate in sediments or be taken up by plants. We studied how ribbed mussel presence and density influence carbon and nitrogen regulation processes in Georgia, USA salt marshes. By comparing deposits in marsh areas with and without mussel aggregations with elemental and stable isotope analyses, we found that mussels amplify the reclamation and import of marsh‐derived and marine‐derived carbon and nitrogen, respectively. We took a similar approach to sediment and found that concentrations of both sources of carbon and nitrogen increase as mussel density increases within their aggregations. Finally, we found that mussel presence and density boosted cordgrass biomass and, in turn, carbon and nitrogen storage. Mussel populations are disproportionately augmenting the role of salt marshes in regulating carbon and nitrogen pollution and should be incorporated into coastal management decisions related to these challenges. Key Points: Through suspension feeding and biodeposition, mussels augment sedimentation of organic matter (OM) produced inside and outside of salt marshesOM accumulation in sediments and aboveground storage increases with increasing mussel densityMussels bolster the capacity of salt marshes to counteract coastal eutrophication and provide blue carbon services [ABSTRACT FROM AUTHOR]

Sporotrichosis is a neglected fungal zoonosis with significant impacts on human and animal health. Accurate diagnosis, treatment, and understanding of the transmission dynamics of Sporothrix species are essential for mitigating the spread of sporotrichosis. This study aimed to identify the Sporothrix species involved in the ongoing outbreaks of animal sporotrichosis in the metropolitan region of Belo Horizonte, Minas Gerais, Brazil, and analyse the phylogenetic relationships between pathogenic species to investigate the outbreak origin. Additionally, to better understand the evolution of the disease, we conducted a retrospective survey of positive feline and canine cases from November 2017 to July 2021 with proven cultures for Sporothrix. A significant increase in animal cases over the last 4 years was observed, with cats being the most affected host. Sporothrix brasiliensis was the predominant agent in 100% of the clinical isolates (n = 180) molecularly identified. Phylogenetic and haplotype analysis points towards the cases isolated from Minas Gerais sharing the haplotype originating from a long‐lasting outbreak of cat‐transmitted sporotrichosis in Rio de Janeiro, however, with a secondary contribution from genotypes circulating in other outbreaks in Brazil. Thus, we present clear evidence of the circulation of different S. brasiliensis genotypes associated with animal sporotrichosis in the metropolitan region of Belo Horizonte. Genetic monitoring can contribute to understanding the causal agent for zoonotic sporotrichosis in epidemiological processes and help to implement disease prevention and control measures. [ABSTRACT FROM AUTHOR]

Tailor‐made poly(vinyl alcohol)‐b‐poly(styrene) copolymers (PVA‐b‐PS) for separation membranes are synthesized by the combination of reversible‐deactivation radical polymerization techniques. The special features of these di‐block copolymers are the high molecular weight (>70 kDa), the high PVA content (>80 wt%), and the good film‐forming property. They are soluble only in hot dimethyl sulfoxide, but by the "solvent‐switch" technique, they self‐assemble in aqueous media to form micelles. When the self‐assembled micelles are cast on a porous substrate, thin‐film membranes with higher water permeance than that of PVA homopolymer are obtained. Thus, by using these tailor‐made PVA‐b‐PS copolymers, it is demonstrated that chemical cross‐linkers and acid catalysts can no longer be needed to produce PVA membranes, since the PS nanodomains within the PVA matrix act as cross‐linking points. Lastly, subsequent thermal annealing of the thin film enhances the membrane selectivity due to the improved microphase separation. [ABSTRACT FROM AUTHOR]

A common requirement in the military, law enforcement, and forensic mission space is the need to collect trace samples from surfaces using a method that not only readily captures the sample but also retains its integrity for downstream identification and characterization. Additionally, collecting samples from three‐dimensional objects (e.g., shell casings) is a challenge for which there is currently no validated standardized approach. Recently, hydrogels have been shown to have the potential for surface collection of trace bacterial spores, amino acids, and DNA. To test whether these hydrogels can serve as a viable collection medium for sampling DNA from surfaces, we carried out a series of preliminary tests examining collection efficiency and suitability of hydrogel material to recover samples of diluted, dried human DNA on a smooth polycarbonate surface. The recovery of surface DNA using a commercially available hydrogel was examined, and the efficiency compared to samples collected using a standard foam collection swab. DNA collected using the hydrogel and swab methods was then examined using quantitative polymerase chain reaction (qPCR) and short tandem repeat (STR) analysis to determine whether the collection material was compatible with these downstream processes. The hydrogel material used for this study collected the experimental DNA with comparable efficiency to standard collection swabs. In addition, qPCR and STR analyses demonstrated compatibility with the hydrogel collection and extraction process. These data suggest that hydrogels have the potential to be used as sample collection materials and deserve further characterization to elucidate their utility in collection from irregularly shaped, three‐dimensional surfaces/materials. [ABSTRACT FROM AUTHOR]

Inlays range among the most aesthetically pleasing and technically challenging glasses produced in the Ptolemaic period. Despite the central role of this phase in the history of glass technology, little is known about the recipes and the technological knowledge of the Egyptian artisans. This paper will thus focus on the study of the materials from the secondary workshop of Tebtynis (Fayum oasis, Egypt). We report the first multi‐methodological study comprising textural, chemical, and mineralogical analyses (optical microscopy, scanning electron microscopy coupled with energy‐dispersive system, electron probe microanalysis, and μ‐Raman spectroscopy) on a set of 81 colorless, white, blue, and green samples carefully selected among the 800+ glasses from the craft area now stored at the Museo Egizio, Turin (Italy). Our study offers the biggest compositional database of well‐dated Ptolemaic glasses currently available in the literature, highlighting some interesting novelties regarding the silica and alkali sources, and the coloring and opacifying techniques employed. The results suggest a specialized craft of traditional origin, but open to innovation and experimentation, as expected from transitional phases. [ABSTRACT FROM AUTHOR]

Cardiomyopathy is a progressive disease of the myocardium leading to impaired contractility. Genotoxic cancer therapies are known to be potent drivers of cardiomyopathy, whereas causes of spontaneous disease remain unclear. To test the hypothesis that endogenous genotoxic stress contributes to cardiomyopathy, we deleted the DNA repair gene Ercc1 specifically in striated muscle using a floxed allele of Ercc1 and mice expressing Cre under control of the muscle‐specific creatinine kinase (Ckmm) promoter or depleted systemically (Ercc1−/D mice). Ckmm‐Cre+/−;Ercc1−/fl mice expired suddenly of heart disease by 7 months of age. As young adults, the hearts of Ckmm‐Cre+/−;Ercc1−/fl mice were structurally and functionally normal, but by 6‐months‐of‐age, there was significant ventricular dilation, wall thinning, interstitial fibrosis, and systolic dysfunction indicative of dilated cardiomyopathy. Cardiac tissue from the tissue‐specific or systemic model showed increased apoptosis and cardiac myocytes from Ckmm‐Cre+/‐;Ercc1−/fl mice were hypersensitive to genotoxins, resulting in apoptosis. p53 levels and target gene expression, including several antioxidants, were increased in cardiac tissue from Ckmm‐Cre+/−;Ercc1−/fl and Ercc1−/D mice. Despite this, cardiac tissue from older mutant mice showed evidence of increased oxidative stress. Genetic or pharmacologic inhibition of p53 attenuated apoptosis and improved disease markers. Similarly, overexpression of mitochondrial‐targeted catalase improved disease markers. Together, these data support the conclusion that DNA damage produced endogenously can drive cardiac disease and does so mechanistically via chronic activation of p53 and increased oxidative stress, driving cardiac myocyte apoptosis, dilated cardiomyopathy, and sudden death. [ABSTRACT FROM AUTHOR]

Pedometricians have spent a lot of effort on mapping soil types and basic soil properties. However, end‐users typically need a more elaborate soil quality index for land management. Soil quality indices are typically derived from multiple individual soil properties by evaluating whether specific criteria are met. If this is based on individually mapped soil properties, then an important consequence is that cross‐correlations between soil properties are ignored. This makes it impossible to quantify the uncertainties associated with the mapped indices. The objective of this study was to map a soil potential multifunctionality index for agriculture (Agri‐SPMI) over a 12,125 km2 study region located along the French Mediterranean coast to help urban planners preserve soils of the highest quality. The index considered the ability of soils to fulfil four functions under five land use scenarios. A binary map represented each soil function fulfilment for a given scenario. The final soil quality index map was the sum of the 20 binary maps. A regression cokriging model was developed to map the basic soil properties first individually from legacy soil data and spatial soil covariates using a random forest algorithm, and next, interpolate the residuals using cokriging and the linear model of coregionalisation. The mapping uncertainties of soil properties were propagated by calculating the soil quality index over 300 stochastic simulations of soil properties derived from the linear models of coregionalisation. Results showed a poor prediction accuracy of the quality index, mainly because some soil properties were poorly predicted (notably available water capacity and coarse fragments) and used in combination with extreme thresholds that defined land suitability. Overall, the uncertainty was correctly quantified because the stochastic simulations reproduced the width of the observed distribution well, but the shapes of the distributions differed considerably from those of the observations. We envisage some ways for improvement, such as creating probability maps instead of the mean from simulations, and changing the prediction support from point to area. Highlights: The study mapped a soil quality index (Agri‐SPMI) to help preserve soils of highest quality along the French Mediterranean coast.The Agri‐SPMI considered the ability of soils to fulfill four functions under five land use scenarios, derived from multiple individual soil properties.A regression cokriging model was developed to map the basic soil properties, followed by interpolating the residuals using cokriging and the linear model of coregionalisation.The study accurately quantified mapping uncertainties using stochastic simulations, but the soil quality index prediction accuracy was poor, with suggestions for improvement. [ABSTRACT FROM AUTHOR]

Background and purpose: Essential tremor (ET) is a common and heterogeneous disorder characterized by postural/kinetic tremor of the upper limbs and other body segments and by non‐motor symptoms, including cognitive and psychiatric abnormalities. Only a limited number of longitudinal studies have comprehensively and simultaneously investigated motor and non‐motor symptom progression in ET. Possible soft signs that configure the ET‐plus diagnosis are also under‐investigated in follow‐up studies. We aimed to longitudinally investigate the progression of ET manifestations by means of clinical and neurophysiological evaluation. Methods: Thirty‐seven ET patients underwent evaluation at baseline (T0) and at follow‐up (T1; mean interval ± SD = 39.89 ± 9.83 months). The assessment included the clinical and kinematic evaluation of tremor and voluntary movement execution, as well as the investigation of cognitive and psychiatric disorders. Results: A higher percentage of patients showed tremor in multiple body segments and rest tremor at T1 as compared to T0 (all p‐values < 0.01). At T1, the kinematic analysis revealed reduced finger‐tapping movement amplitude and velocity as compared to T0 (both p‐values < 0.001). The prevalence of cognitive and psychiatric disorders did not change between T0 and T1. Female sex, absence of family history, and rest tremor at baseline were identified as predictive factors of worse disease progression. Conclusions: ET progression is characterized by the spread of tremor in multiple body segments and by the emergence of soft signs. We also identified possible predictors of disease worsening. The results contribute to a better understanding of ET classification and pathophysiology. [ABSTRACT FROM AUTHOR]

The ability to establish a connection between the direction of the other's gaze and the object that is observed has important implications in the development of social cognition and learning. In this study, we analyzed alpha and theta band oscillations in one group of 9‐month‐old infants by implementing a face‐to‐face live paradigm, which presented the infants with a triadic social interaction with a real human being. We compared neural activations in two experimental conditions: Congruent and Incongruent gaze shift following the appearance of an object. In the Incongruent object‐gaze shift condition, we observed an increase of the theta power in comparison with the Congruent condition. We also found an enhancement of the alpha activity during the Congruent versus the Incongruent object‐gaze condition. These findings confirm the involvement of the theta and alpha band activity in the detection of the gaze of others when it shifts toward a referential target. We consider that the theta band modulation could be associated with the processing of unexpected events. Furthermore, the increase of the alpha band activity during the Congruent object‐gaze condition seems to be in agreement with prior findings on the mechanisms of internally controlled attention that emerge before the first year of life. The implementation of a live paradigm elicited a partially different oscillatory pattern in comparison with non‐live standard paradigms, supporting the importance of an ecological set‐up reproducing real‐life conditions to study the development of social cognition. Our article addresses a key question in the development of social cognition and learning in infants: understanding the neural mechanisms involved in object‐gaze processing. The novel aspect of our work regards the use of a live face‐to‐face paradigm, which could greatly contribute to obtain more reliable information on how infants process referential gaze in a real‐life context. [ABSTRACT FROM AUTHOR]

This paper estimates the effect of in utero exposure to adverse events on late life diabetes, cardiovascular disease risks and cognition deficiency. We merge data on the regional violence during the Cultural Revolution and the excessive death rates during the Chinese Great Famine with data from the China Health and Retirement Longitudinal Study survey. Results show that female babies who were exposed in utero to the famine have higher diabetes risks, while male babies who were exposed to the Cultural Revolution are shown to have lower cognitive abilities. [ABSTRACT FROM AUTHOR]

The development of dimorphic adult sexes is a critical process for most animals, one that is subject to intense selection. Work in vertebrate and insect model species has revealed that sex determination mechanisms vary widely among animal groups. However, this variation is not uniform, with a limited number of conserved factors. Therefore, sex determination offers an excellent context to consider themes and variations in gene network evolution. Here we review the literature describing sex determination in diverse insects. We have screened public genomic sequence databases for orthologs and duplicates of 25 genes involved in insect sex determination, identifying patterns of presence and absence. These genes and a 3.5 reference set of 43 others were used to infer phylogenies and compared to accepted organismal relationships to examine patterns of congruence and divergence. The function of candidate genes for roles in sex determination (virilizer, female‐lethal‐2‐d, transformer‐2) and sex chromosome dosage compensation (male specific lethal‐1, msl‐2, msl‐3) were tested using RNA interference in the milkweed bug, Oncopeltus fasciatus. None of these candidate genes exhibited conserved roles in these processes. Amidst this variation we wish to highlight the following themes for the evolution of sex determination: (1) Unique features within taxa influence network evolution. (2) Their position in the network influences a component's evolution. Our analyses also suggest an inverse association of protein sequence conservation with functional conservation. RESEARCH HIGHLIGHTS: We review sex determination, a well‐studied process in Drosophila and one increasingly explored in diverse insects. Structural conservation in sex determination candidate genes masks mechanistic variation in this process. More functionally conserved genes in the sex determination network are paradoxically more divergent in their protein sequence. Knockdown of several candidate genes in Oncopeltus does not support their function in sex determination or dosage compensation in this species. [ABSTRACT FROM AUTHOR]

Human activity anomaly detection plays a crucial role in the next generation of surveillance and assisted living systems. Most anomaly detection algorithms are generative models and learn features from raw images. This work shows that popular state‐of‐the‐art autoencoder‐based anomaly detection systems are not capable of effectively detecting human‐posture and object‐positions related anomalies. Therefore, a human pose‐driven and object‐detector‐based deep learning architecture is proposed, which simultaneously leverages human poses and raw RGB data to perform human activity anomaly detection. It is demonstrated that pose‐driven learning overcomes the raw RGB based counterpart limitations in different human activities classification. Extensive validation is provided by using popular datasets. Then, it is demonstrated that with the aid of object detection, the human activities classification can be effectively used in human activity anomaly detection. Moreover, novel challenging datasets, that is, BMbD, M‐BMbD and JBMOPbD, are proposed for single and multi‐target human posture anomaly detection and joint human posture and object position anomaly detection evaluations. [ABSTRACT FROM AUTHOR]

We estimate government spending and tax multipliers in the United States via a flexible proxy‐SVAR model, where identification is achieved by combining fiscal and non‐fiscal instruments with additional parametric restrictions. We find that, while the spending multiplier is robustly estimated to be larger than one across different models, the estimate of the tax multiplier is sensitive to the combination of instruments that we use. We unveil that the key factor behind these heterogeneous estimates is the assumption of orthogonality between total factor productivity (our main non‐fiscal proxy) and the tax shock. If this assumption is imposed, the tax multiplier is around one. If it is not imposed, the tax multiplier is three times as large. Our results point to the need of accounting for the large uncertainty surrounding the tax multiplier for the design of optimal fiscal policies. [ABSTRACT FROM AUTHOR]

The use and creation of machine‐learning‐based solutions to solve problems or reduce their computational costs are becoming increasingly widespread in many domains. Deep Learning plays a large part in this growth. However, it has drawbacks such as a lack of explainability and behaving as a black‐box model. During the last few years, Visual Analytics has provided several proposals to cope with these drawbacks, supporting the emerging eXplainable Deep Learning field. This survey aims to (i) systematically report the contributions of Visual Analytics for eXplainable Deep Learning; (ii) spot gaps and challenges; (iii) serve as an anthology of visual analytical solutions ready to be exploited and put into operation by the Deep Learning community (architects, trainers and end users) and (iv) prove the degree of maturity, ease of integration and results for specific domains. The survey concludes by identifying future research challenges and bridging activities that are helpful to strengthen the role of Visual Analytics as effective support for eXplainable Deep Learning and to foster the adoption of Visual Analytics solutions in the eXplainable Deep Learning community. An interactive explorable version of this survey is available online at https://aware‐diag‐sapienza.github.io/VA4XDL. [ABSTRACT FROM AUTHOR]

Oxygen‐ozone (O2‐O3) therapy is an adjuvant/complementary treatment based on the activation of antioxidant and cytoprotective pathways driven by the nuclear factor erythroid 2‐related factor 2 (Nrf2). Many drugs, including dimethyl fumarate (DMF), that are used to reduce inflammation in oxidative‐stress‐related neurodegenerative diseases, act through the Nrf2‐pathway. The scope of the present investigation was to get a deeper insight into the mechanisms responsible for the beneficial result of O2‐O3 treatment in some neurodegenerative diseases. To do this, we used an integrated approach of multimodal microscopy (bright‐field and fluorescence microscopy, transmission and scanning electron microscopy) and biomolecular techniques to investigate the effects of the low O3 concentrations currently used in clinical practice in lipopolysaccharide (LPS)‐activated microglial cells human microglial clone 3 (HMC3) and in DMF‐treated LPS‐activated (LPS + DMF) HMC3 cells. The results at light and electron microscopy showed that LPS‐activation induced morphological modifications of HMC3 cells from elongated/branched to larger roundish shape, cytoplasmic accumulation of lipid droplets, decreased electron density of the cytoplasm and mitochondria, decreased amount of Nrf2 and increased migration rate, while biomolecular data demonstrated that Heme oxygenase 1 gene expression and the secretion of the pro‐inflammatory cytokines, Interleukin‐6, and tumor necrosis factor‐α augmented. O3 treatment did not affect cell viability, proliferation, and morphological features of both LPS‐activated and LPS + DMF cells, whereas the cell motility and the secretion of pro‐inflammatory cytokines were significantly decreased. This evidence suggests that modulation of microglia activity may contribute to the beneficial effects of the O2‐O3 therapy in patients with neurodegenerative disorders characterized by chronic inflammation. Highlights: Low‐dose ozone (O3) does not damage activated microglial cells in vitroLow‐dose O3 decreases cell motility and pro‐inflammatory cytokine secretion in activated microglial cells in vitroLow‐dose O3 potentiates the effect of an anti‐inflammatory drug on activated microglial cells [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is a complex multisystemic inflammatory disorder and part of the inflammatory bowel diseases (IBDs). About 20% of the subjects affected by IBDs are paediatric patients and 21% of them present extraintestinal manifestations. Among the extraintestinal manifestations of CD, oral manifestations are rather frequent (20–50% of affected people) and can be difficult to identify, being frequently aspecific and not pathognomonic. Their early diagnosis by the dentist is extremely important, because extraintestinal manifestations can precede intestinal symptoms, in all patients but especially in children. The aim of this paper is to report the case of a CD adolescent patient that presented a gingival manifestation. [ABSTRACT FROM AUTHOR]

Central granular cell odontogenic tumour (CGCOT) is a rare odontogenic benign neoplasm with only 39 cases reported in the literature. This report describes an unusual case of CGCOT as it was associated with severe signs of local and systemic infection. The patient was hospitalised for sepsis, high fever and facial swelling. The intraoral examination and the radiographic images led to the clinical diagnosis of periapical abscess caused by a severely decayed left maxillary third molar. After the surgical extraction of the tooth, a periapical lesion and fragments of the alveolar process were sent for histopathologic examination and immune‐phenotypic characterisation. The pathological findings became crucial for the definitive diagnosis of CGCOT, osteonecrosis and osteomyelitis. The purpose of this report is to provide knowledge about this tumour and highlight the importance of sending samples collected during oral surgery for histopathologic examination. [ABSTRACT FROM AUTHOR]

Background: To date, only a few clinical and neurophysiological studies have assessed the features of valproate‐induced tremor (VIT), and whether valproate (VPA) affects voluntary movements is underinvestigated. Objective: To better characterize the clinical and neurophysiological features of VIT in patients with epilepsy and the effect of VPA on the execution of voluntary movement. Methods: We tested 29 patients with VIT (13 taking VPA alone and 16 taking VPA plus other antiepileptics). Patients underwent a neurological examination, video recordings and kinematic assessments of postural, kinetic, and resting upper limb tremor using a motion analysis system. Movement execution was tested by kinematic assessment of finger tapping. Data of patients with VIT were compared with those of 13 patients with epilepsy taking VPA but without tremor, 13 patients with epilepsy who were not on VPA treatment, 20 patients with Parkinson's disease (PD), and 20 healthy controls (HCs). Results: Clinical and kinematic evaluations showed that tremor in patients taking VPA alone was less severe than tremor in patients taking VPA plus other antiepileptics. All patients taking VPA, regardless of the presence of tremor, performed slower finger tapping compared with HCs, similar to what was observed in PD, although with no sequence effect. Patients with epilepsy without VPA showed a normal motor performance. Conclusions: Tremor and movement slowness are motor signs induced by VPA. VIT severity is exacerbated when VPA is taken in combination with other antiepileptics. VPA‐induced slowness occurs regardless of tremor, may precede tremor development, and is not attributed to epilepsy. [ABSTRACT FROM AUTHOR]

Background: Corsica is a large French island in the Mediterranean Sea with high human and animal migration rates, especially near wetlands where these migrations are particularly frequent. Among the livestock populations, cattle and sheep are widely present all across the entire Mediterranean region. Trade can be responsible for the circulation of numerous pathogens and their vectors, thereby representing a health and economic threat for the livestock industry. Objectives: The objective of our study was to investigate the presence of pathogens in cattle and sheep farms in the wetlands of Corsica using a high‐throughput screening technique. Methods: In our study, blood samples and ticks were collected from cattle and sheep in 20 municipalities near Corsican wetlands to screen for the presence of various types of pathogens. The samples were processed using a high‐throughput screening technique based on real‐time microfluidic PCR: 45 pathogens were screened in 47 samples simultaneously. Results: A total of 372 cattle and 74 sheep were sampled, and 444 ticks were collected from cattle. Out of the eight tick species detected, the main one was Rhipicephalus bursa (38.7% of the ticks collected). From cattle blood samples, one species and two genera were found: Anaplasma marginale, Trypanosoma sp. and Babesia sp. in respectively 61.5%, 58.3% and 12.2% of the cattle blood samples. From sheep blood samples, 74.3% were positive for Anaplasma sp, 2.7% for Anaplasma ovis and 1.4% for Anaplasma capra. This is the first report of A. ovis DNA in blood samples from sheep in Corsica. Out of 444 the tick samples, 114 were positive: 77.2% for Rickettsia aeschlimannii, 20.2% for Rickettsia sp., 3.5% for Babesia sp. and 1.8% for Anaplasma sp. Among them, 2.7% were co‐infected with R. aeschlimannii and Babesia sp. Conclusions: Our results confirm the extent of possible circulation of different pathogens near Corsican wetlands, not only in ticks collected from livestock but also directly in cattle and sheep, with two (Trypanosoma sp. and Babesia sp.) being detected for the first time in cattle, one for the first time in sheep (A. ovis) and one for the first time in Corsica (A. capra) [ABSTRACT FROM AUTHOR]

Cardiac stromal cells (CSCs) are the main players in fibrosis. Dysmetabolic conditions (metabolic syndrome—MetS, and type 2 diabetes mellitus—DM2) are strong pathogenetic contributors to cardiac fibrosis. Moreover, modulation of the oxidative state (OxSt) and autophagy is a fundamental function affecting the fibrotic commitment of CSCs, that are adversely modulated in MetS/DM2. We aimed to characterize CSCs from dysmetabolic patients, and to obtain a beneficial phenotypic setback from such fibrotic commitment by modulation of OxSt and autophagy. CSCs were isolated from 38 patients, stratified as MetS, DM2, or controls. Pharmacological modulation of OxSt and autophagy was obtained by treatment with trehalose and NOX4/NOX5 inhibitors (TREiNOX). Flow‐cytometry and real‐time quantitative polymerase chain reaction (RT‐qPCR) analyses showed significantly increased expression of myofibroblasts markers in MetS‐CSCs at baseline (GATA4, ACTA2, THY1/CD90) and after starvation (COL1A1, COL3A1). MetS‐ and DM2‐CSCs displayed a paracrine profile distinct from control cells, as evidenced by screening of 30 secreted cytokines, with a significant reduction in vascular endothelial growth factor (VEGF) and endoglin confirmed by enzyme‐linked immunoassay (ELISA). DM2‐CSCs showed significantly reduced support for endothelial cells in angiogenic assays, and significantly increased H2O2 release and NOX4/5 expression levels. Autophagy impairment after starvation (reduced ATG7 and LC3‐II proteins) was also detectable in DM2‐CSCs. TREiNOX treatment significantly reduced ACTA2, COL1A1, COL3A1, and NOX4 expression in both DM2‐ and MetS‐CSCs, as well as GATA4 and THY1/CD90 in DM2, all versus control cells. Moreover, TREiNOX significantly increased VEGF release by DM2‐CSCs, and VEGF and endoglin release by both MetS‐ and DM2‐CSCs, also recovering the angiogenic support to endothelial cells by DM2‐CSCs. In conclusion, DM2 and MetS worsen microenvironmental conditioning by CSCs. Appropriate modulation of autophagy and OxSt in human CSCs appears to restore these features, mostly in DM2‐CSCs, suggesting a novel strategy against cardiac fibrosis in dysmetabolic patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Keywords: 2D materials; memitter; neuromorphic materials; synaptic plasticity; visual memoryNeuromorphic 2D MemitterIn article number 2403158, Federico Ferrarese Lupi, GianlucaMilano, Carlo Grazianetti, and co‐workers describes the concept of 2D memitter, which exploits the stimuli‐responsive photoluminescence of a monolayer WS2 for neuromorphic‐type of data processing..By Federico Ferrarese Lupi; Gianluca Milano; Angelo Angelini; Mateo Rosero‐Realpe; Bruno Torre; Erika Kozma; Christian Martella and Carlo GrazianettiReported by Author; Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

Human in vitro models of neural tissue with tunable microenvironment and defined spatial arrangement are needed to facilitate studies of brain development and disease. Towards this end, embedded printing inside granular gels holds great promise as it allows precise patterning of extremely soft tissue constructs. However, granular printing support formulations are restricted to only a handful of materials. Therefore, there has been a need for novel materials that take advantage of versatile biomimicry of bulk hydrogels while providing high‐fidelity support for embedded printing akin to granular gels. To address this need, Authors present a modular platform for bioengineering of neuronal networks via direct embedded 3D printing of human stem cells inside Self‐Healing Annealable Particle‐Extracellular matrix (SHAPE) composites. SHAPE composites consist of soft microgels immersed in viscous extracellular‐matrix solution to enable precise and programmable patterning of human stem cells and consequent generation mature subtype‐specific neurons that extend projections into the volume of the annealed support. The developed approach further allows multi‐ink deposition, live spatial and temporal monitoring of oxygen levels, as well as creation of vascular‐like channels. Due to its modularity and versatility, SHAPE biomanufacturing toolbox has potential to be used in applications beyond functional modeling of mechanically sensitive neural constructs. [ABSTRACT FROM AUTHOR]