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Abstract Perturbations in complex media, due to their own dynamical evolution or to external effects, are often seen as detrimental. Therefore, a common strategy, especially for telecommunication and imaging applications, is to limit the sensitivity to those perturbations in order to avoid them. Here, instead, we consider enhancing the interaction between light and perturbations to produce the largest change in the output intensity distribution. Our work hinges on the use of tensor-based techniques, presently at the forefront of machine learning explorations, to study intensity-based measurements where its quadratic relationship to the field prevents the use of standard matrix methods. With this tensor-based framework, we can identify the maximum-information intensity channel which maximizes the change in its output intensity distribution and the Fisher information encoded in it about a given perturbation. We further demonstrate experimentally its superiority for robust and precise sensing applications. Additionally, we derive the appropriate strategy to reach the precision limit for intensity-based measurements, leading to an increase in Fisher information by more than four orders of magnitude compared to the mean for random wavefronts when measured with the pixels of a camera.

Abstract Background Data on the factors affecting blood ionized calcium concentration (ciCa2+) and diagnostic performance of serum total calcium concentration (ctCa) measurements to detect abnormal blood iCa2+ status are lacking in sick adult cattle. Objective Assess the association of ciCa2+ with venous blood pH, plasma concentrations of chloride (cCl), sodium (cNa), and potassium (cK), and ctCa, and total protein, albumin, and globulin concentrations in sick adult cattle. Animals Two‐hundred and sixty‐five adult cattle (≥1‐year‐old) with different diseases. Methods Prospective study. Whole blood pH, ciCa2+, cNa, cK, and cCl were measured using a blood gas and electrolyte analyzer, whereas ctCa, and total protein, and albumin concentrations were determined using an autoanalyzer. The relationship between ciCa2+ and venous blood pH, plasma cCl, cNa, cK, and ctCa, and total protein, albumin, and globulin concentrations was investigated. Sensitivity and specificity were calculated for ctCa for diagnosis of abnormal ciCa2+. Results Sensitivity of ctCa measurements to detect abnormal ciCa2+ was 66.0% whereas specificity of ctCa measurements was 72.3%. Serum total calcium concentration measurements accounted for 42% of adjusted blood ionized calcium (iCa2+7.40) concentration variance. Plasma cCl, and cK had explanatory power of ciCa2+7.40, accounting for an additional 21% and 9% of the variance, respectively. Conclusions and Clinical Importance Serum tCa measurements failed to accurately predict blood iCa2+ status in ill adult cattle. Serum tCa concentrations and plasma cCl were the strongest predictors of ciCa2+ in sick adult cattle.

In an ideal perfectly straight multimode fiber with a circular core, the symmetry ensures that rotating the input wave front leads to a corresponding rotation of the output wave front. This invariant property, known as the rotational memory effect (RME), remains independent of the typically unknown output profile. The RME thus offers significant potential for imaging and telecommunication applications. However, in real-life fibers, this effect is degraded by intrinsic imperfections and external perturbations, and is challenging to observe because of its acute sensitivity to misalignments and aberrations in the optical setup. Building on a previously established method for precisely estimating fiber transmission properties, we demonstrate an accurate extraction of RME properties. Additionally, we introduce a comprehensive theoretical framework for both qualitative and quantitative analysis, which specifically links the angular-dependent correlation of the RME to the core deformation’s geometrical properties and the fiber’s mode characteristics. Our theoretical predictions align well with experimental data and simulations for various amounts of fiber distorsion. Finally, we demonstrate the ability to engineer wave fronts with significantly enhanced correlation across all rotation angles. This work enables accurate characterization of distributed disorder from the fabrication process and facilitates calibration-free imaging in multimode fibers.

Multimode optical fibers support low-loss transmission of multiple spatial modes, allowing for the transport of high-dimensional, spatially encoded information. In particular, encoding quantum information in the transverse shape of photons may boost the capacity of quantum channels while using existing infrastructure. However, when photons propagate through a multimode fiber, their transverse shape gets scrambled because of mode mixing and modal interference. This is usually corrected using free-space spatial light modulators, inhibiting a robust all-fiber operation. In this work, we demonstrate an all-fiber approach for controlling the shape of single photons and the spatial correlations between entangled photon pairs, using carefully controlled mechanical perturbations of the fiber. We optimize these perturbations to localize the spatial distribution of a single photon or the spatial correlations of photon pairs in a single spot, enhancing the signal in the optimized spot by over an order of magnitude. Using the same approach, we show a similar enhancement for coupling light from a multimode fiber into a single-mode fiber.

Digital micromirror devices have gained popularity in wavefront shaping, offering a high frame rate alternative to liquid crystal spatial light modulators. They are relatively inexpensive, offer high resolution, are easy to operate, and a single device can be used in a broad optical bandwidth. However, some technical drawbacks must be considered to achieve optimal performance. These issues, often undocumented by manufacturers, mostly stem from the device’s original design for video projection applications. Herein, we present a guide to characterize and mitigate these effects. Our focus is on providing simple and practical solutions that can be easily incorporated into a typical wavefront shaping setup.

Multimode optical fibers support the dense, low-loss transmission of many spatial modes, making them attractive for technologies such as communications and imaging. However, information propagating through multimode fibers is scrambled, due to modal dispersion and mode mixing. This is usually rectified using wavefront shaping techniques with devices such as spatial light modulators. Recently, we demonstrated an all-fiber system for controlling light propagation inside multimode fibers using mechanical perturbations, called the fiber piano. In this tutorial we explain the design considerations and experimental methods needed to build a fiber piano, and review applications where fiber pianos have been used.

First derivations of the functional response were mechanistic, but subsequent uses of these functions tended to be phenomenological. Further understanding of the mechanisms underpinning predator-prey relationships might lead to novel insights into functional response in natural systems. Because recent consideration of the physical properties of the environment has improved our understanding of predator-prey interactions, we advocate the use of physics-based approaches for the derivation of the functional response from first principles. These physical factors affect the functional response by constraining the ability of both predators and prey to move according to their size. A physics-based derivation of the functional response should thus consider the movement of organisms in relation to their physical environment. One recent article presents a model along these criteria. As an initial validation of our claim, we use a slightly modified version of this model to derive the classical parameters of the functional response (i.e., attack rate and handling time) of aquatic organisms, as affected by body size, buoyancy, water density and viscosity. We compared the predictions to relevant data. Our model provided good fit for most parameters, but failed to predict handling time. Remarkably, this is the only parameter whose derivation did not rely on physical principles. Parameters in the model were not estimated from observational data. Hence, systematic discrepancies between predictions and real data point immediately to errors in the model. An added benefit to functional response derivation from physical principles is thus to provide easy ways to validate or falsify hypotheses about predator-prey relationships.

Objectives: Hepatokines are proteins secreted by the liver that impact the functions of the liver and various tissues through autocrine, paracrine, and endocrine signaling. Recently, Tsukushi (TSK) was identified as a new hepatokine that is induced by obesity and cold exposure. It was proposed that TSK controls sympathetic innervation and thermogenesis in brown adipose tissue (BAT) and that loss of TSK protects against diet-induced obesity and improves glucose homeostasis. Here we report the impact of deleting and/or overexpressing TSK on BAT thermogenic capacity, body weight regulation, and glucose homeostasis. Methods: We measured the expression of thermogenic genes and markers of BAT innervation and activation in TSK-null and TSK-overexpressing mice. Body weight, body temperature, and parameters of glucose homeostasis were also assessed in the context of TSK loss and overexpression. Results: The loss of TSK did not affect the thermogenic activation of BAT. We found that TSK-null mice were not protected against the development of obesity and did not show improvement in glucose tolerance. The overexpression of TSK also failed to modulate thermogenesis, body weight gain, and glucose homeostasis in mice. Conclusions: TSK is not a significant regulator of BAT thermogenesis and is unlikely to represent an effective target to prevent obesity and improve glucose homeostasis. Keywords: Tsukushi, Hepatokine, Brown adipose tissue, Thermogenesis, Glucose homeostasis, Obesity

Abstract Recent research indicates that attentional stimulus selection could be a rhythmic process. In monkey, neurons in V4 and IT exhibit rhythmic spiking activity in the theta range in response to a stimulus. When two stimuli are presented together, the rhythmic neuronal responses to each occur in anti-phase, a result indicative of competitive interactions. In addition, it was recently demonstrated that these alternating oscillations in monkey V4 modulate the speed of saccadic responses to a target flashed on one of the two competing stimuli. Here, we replicate a similar behavioral task in humans (7 participants, each performed 4000 trials) and report a pattern of results consistent with the monkey findings: saccadic response times fluctuate in the theta range (6 Hz), with opposite phase for targets flashed on distinct competing stimuli.

Multimode optical fibers (MMFs) have gained renewed interest in the past decade, emerging as a way to boost optical communication data rates in the context of an expected saturation of current single-mode fiber-based networks. They are also attractive for endoscopic applications, offering the possibility to achieve a similar information content as multicore fibers, but with a much smaller footprint, thus reducing the invasiveness of endoscopic procedures. However, these advances are hindered by the unavoidable presence of disorder that affects the propagation of light in MMFs and limits their practical applications. We introduce here a general framework to study and avoid the effect of disorder in wave-based systems and demonstrate its application for multimode fibers. We experimentally find an almost complete set of optical channels that are resilient to disorder induced by strong deformations. These deformation principal modes are obtained by only exploiting measurements for weak perturbations harnessing the generalized Wigner-Smith operator. We explain this effect by demonstrating that, even for a high level of disorder, the propagation of light in MMFs can be characterized by just a few key properties. These results are made possible thanks to a precise and fast estimation of the modal transmission matrix of the fiber which relies on a model-based optimization using deep learning frameworks.

Objective: The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions into distinct protein complexes (mTORC1 and mTORC2) that regulates growth and metabolism. DEP-domain containing mTOR-interacting protein (DEPTOR) is part of these complexes and is known to reduce their activity. Whether DEPTOR loss affects metabolism and organismal growth in vivo has never been tested. Methods: We have generated a conditional transgenic mouse allowing the tissue-specific deletion of DEPTOR. This model was crossed with CMV-cre mice or Albumin-cre mice to generate either whole-body or liver-specific DEPTOR knockout (KO) mice. Results: Whole-body DEPTOR KO mice are viable, fertile, normal in size, and do not display any gross physical and metabolic abnormalities. To circumvent possible compensatory mechanisms linked to the early and systemic loss of DEPTOR, we have deleted DEPTOR specifically in the liver, a tissue in which DEPTOR protein is expressed and affected in response to mTOR activation. Liver-specific DEPTOR null mice showed a reduction in circulating glucose upon fasting versus control mice. This effect was not associated with change in hepatic gluconeogenesis potential but was linked to a sustained reduction in circulating glucose during insulin tolerance tests. In addition to the reduction in glycemia, liver-specific DEPTOR KO mice had reduced hepatic glycogen content when fasted. We showed that loss of DEPTOR cell-autonomously increased oxidative metabolism in hepatocytes, an effect associated with increased cytochrome c expression but independent of changes in mitochondrial content or in the expression of genes controlling oxidative metabolism. We found that liver-specific DEPTOR KO mice showed sustained mTORC1 activation upon fasting, and that acute treatment with rapamycin was sufficient to normalize glycemia in these mice. Conclusion: We propose a model in which hepatic DEPTOR accelerates the inhibition of mTORC1 during the transition to fasting to adjust metabolism to the nutritional status. Keywords: DEPTOR, mTOR, Liver, Glucose, Fasting

Background/Objective: The mechanistic target of rapamycin (mTOR) is a serine–threonine kinase that functions into distinct protein complexes (mTORC1 and mTORC2) that regulate energy homeostasis. DEP-domain containing mTOR-interacting protein (DEPTOR) is part of these complexes and is known to dampen mTORC1 function, consequently reducing mTORC1 negative feedbacks and promoting insulin signaling and Akt/PKB activation in several models. Recently, we observed that DEPTOR is expressed in several structures of the brain including the mediobasal hypothalamus (MBH), a region that regulates energy balance. Whether DEPTOR in the MBH plays a functional role in regulating energy balance and hypothalamic insulin signaling has never been tested. Methods: We have generated a novel conditional transgenic mouse model based on the Cre-LoxP system allowing targeted overexpression of DEPTOR. Mice overexpressing DEPTOR in the MBH were subjected to a metabolic phenotyping and MBH insulin signaling was evaluated. Results: We first report that systemic (brain and periphery) overexpression of DEPTOR prevents high-fat diet-induced obesity, improves glucose metabolism and protects against hepatic steatosis. These phenotypes were associated with a reduction in food intake and feed efficiency and an elevation in oxygen consumption. Strikingly, specific overexpression of DEPTOR in the MBH completely recapitulated these phenotypes. DEPTOR overexpression was associated with an increase in hypothalamic insulin signaling, as illustrated by elevated Akt/PKB activation. Conclusion: Altogether, these results support a role for MBH DEPTOR in the regulation of energy balance and metabolism. Keywords: mTOR, DEPTOR, Hypothalamus, Energy balance, Glucose metabolism

TP53 is conventionally thought to prevent cancer formation and progression to metastasis, while mutant TP53 has transforming activities. However, in the clinic, TP53 mutation status does not accurately predict cancer progression. Here we report, based on clinical analysis corroborated with experimental data, that the p53 isoform Δ133p53β promotes cancer cell invasion, regardless of TP53 mutation status. Δ133p53β increases risk of cancer recurrence and death in breast cancer patients. Furthermore Δ133p53β is critical to define invasiveness in a panel of breast and colon cell lines, expressing WT or mutant TP53. Endogenous mutant Δ133p53β depletion prevents invasiveness without affecting mutant full-length p53 protein expression. Mechanistically WT and mutant Δ133p53β induces EMT. Our findings provide explanations to 2 long-lasting and important clinical conundrums: how WT TP53 can promote cancer cell invasion and reciprocally why mutant TP53 gene does not systematically induce cancer progression.

Observers can rapidly perform a variety of visual tasks such as categorizing a scene as open, as outdoor, or as a beach. Although we know that different tasks are typically associated with systematic differences in behavioral responses, to date, little is known about the underlying mechanisms. Here, we implemented a single integrated paradigm that links perceptual processes with categorization processes. Using a large image database of natural scenes, we trained machine-learning classifiers to derive quantitative measures of task-specific perceptual discriminability based on the distance between individual images and different categorization boundaries. We showed that the resulting discriminability measure accurately predicts variations in behavioral responses across categorization tasks and stimulus sets. We further used the model to design an experiment, which challenged previous interpretations of the so-called "superordinate advantage." Overall, our study suggests that observed differences in behavioral responses across rapid categorization tasks reflect natural variations in perceptual discriminability.

Object-substitution masking (OSM) occurs when a briefly presented target in a search array is surrounded by small dots that remain visible after the target disappears. The reduction of target visibility occurring after OSM has been suggested to result from a specific interference with reentrant visual processing while the initial feedforward processing is thought to be left intact. We tested a prediction derived from this hypothesis: the fastest responses, being triggered before the beginning of reentrant processing, should escape the OSM interference. In a saccadic choice reaction time task, which gives access to very early stages of visual processing, target visibility was reduced either by OSM, conventional backward masking, or low stimulus contrast. A general reduction of performance was observed in all three conditions. However, the fastest saccades did not show any sign of interference under either OSM or backward masking, as they did under the low-contrast condition. This finding supports the hypothesis that masking interferes mostly with reentrant processing at later stages, while leaving early feedforward processing largely intact.

Brown adipose tissue (BAT) represents a remarkable heat-producing tissue. The thermogenic potential of BAT is conferred by uncoupling protein 1, a protein found uniquely in the brown adipocytes. The physiological control of BAT activity and capacity is ensured by the sympathetic nervous system (SNS), which densely innervates brown fat depots. SNS-mediated BAT thermogenesis is essentially governed by hypothalamic and brainstem neurons. BAT is not only controlled by the brain thermoregulatory circuits but also by brain energy balance pathways including the very significant brain melanocortin system, which speaks in favor of the genuine involvement of SNS-mediated BAT thermogenesis in energy homeostasis. The use of positron emission tomography/computed tomography (PET/CT) scanning has further revealed the presence of well-defined BAT depots in the cervical, clavicular, and paraspinal areas in adult humans. The prevalence of these depots was reported to be higher in subjects exposed to low temperature and was also higher in women than men. Moreover, the prevalence of BAT was shown to decrease with age and body fat mass, which suggests that BAT could not only be involved in cold-induced non shivering thermogenesis but also in the energy balance regulation and obesity in humans. This short review summarizes recent progress made in our understanding of the control of SNS-mediated BAT thermogenesis and of the determinants of BAT prevalence or detection in humans.

The processes underlying object recognition are fundamental for the understanding of visual perception. Humans can recognize many objects rapidly even in complex scenes, a task that still presents major challenges for computer vision systems. A common experimental demonstration of this ability is the rapid animal detection protocol, where human participants earliest responses to report the presence/absence of animals in natural scenes are observed at 250-270 ms latencies. One of the hypotheses to account for such speed is that people would not actually recognize an animal per se, but rather base their decision on global scene statistics. These global statistics (also referred to as spatial envelope or gist) have been shown to be computationally easy to process and could thus be used as a proxy for coarse object recognition. Here, using a saccadic choice task, which allows us to investigate a previously inaccessible temporal window of visual processing, we showed that animal - but not vehicle - detection clearly precedes scene categorization. This asynchrony is in addition validated by a late contextual modulation of animal detection, starting simultaneously with the availability of scene category. Interestingly, the advantage for animal over scene categorization is in opposition to the results of simulations using standard computational models. Taken together, these results challenge the idea that rapid animal detection might be based on early access of global scene statistics, and rather suggests a process based on the extraction of specific local complex features that might be hardwired in the visual system.

Research progress in machine vision has been very significant in recent years. Robust face detection and identification algorithms are already readily available to consumers, and modern computer vision algorithms for generic object recognition are now coping with the richness and complexity of natural visual scenes. Unlike early vision models of object recognition that emphasized the role of figure-ground segmentation and spatial information between parts, recent successful approaches are based on the computation of loose collections of image features without prior segmentation or any explicit encoding of spatial relations. While these models remain simplistic models of visual processing, they suggest that, in principle, bottom-up activation of a loose collection of image features could support the rapid recognition of natural object categories and provide an initial coarse visual representation before more complex visual routines and attentional mechanisms take place. Focusing on biologically-plausible computational models of (bottom-up) pre-attentive visual recognition, we review some of the key visual features that have been described in the literature. We discuss the consistency of these feature-based representations with classical theories from visual psychology and test their ability to account for human performance on a rapid object categorization task.

Recent experimental work has demonstrated the existence of extremely rapid saccades towards faces in natural scenes that can be initiated only 100 ms after image onset (Crouzet, Kirchner, & Thorpe, 2010). These ultra-rapid saccades constitute a major challenge to current models of processing in the visual system because they do not seem to leave enough time for even a single feed-forward pass through the ventral stream. Here we explore the possibility that the information required to trigger these very fast saccades could be extracted very early on in visual processing using relatively low-level amplitude spectrum (AS) information in the Fourier domain. Experiment 1 showed that AS normalization can significantly alter face detection performance. However, a decrease of performance following AS normalization does not alone prove that AS-based information is used (Gaspar & Rousselet, 2009). In Experiment 2, following the Gaspar and Rousselet paper, we used a swapping procedure to clarify the role of AS information in fast object detection. Our experiment is composed of 3 conditions: (i) original images, (ii) inverted, in which the face image has the AS of a vehicle, and the vehicle has the AS of a face, and (iii) swapped, where the face has the AS of another face image, and the vehicle has the AS of another vehicle image. The results showed very similar levels of performance in the original and swapped conditions, and a clear drop in the inverted condition. This result demonstrates that, in the early temporal window offered by the saccadic choice task, the visual saccadic system does indeed rely on low-level AS information in order to rapidly detect faces. This sort of crude diagnostic information could potentially be derived very early on in the visual system, possibly as early as V1 and V2.

It has been proposed that abnormal postprandial plasma nonesterified fatty acid (NEFA) metabolism may participate in the development of tissue lipotoxicity and type 2 diabetes (T2D). We previously found that non-diabetic offspring of two parents with T2D display increased plasma NEFA appearance and oxidation rates during intravenous administration of a fat emulsion. However, it is currently unknown whether plasma NEFA appearance and oxidation are abnormal during the postprandial state in these subjects at high-risk of developing T2D.Palmitate appearance and oxidation rates and glycerol appearance rate were determined in eleven healthy offspring of two parents with T2D (positive family history, FH+), 13 healthy subjects without first-degree relatives with T2D (FH-) and 12 subjects with T2D at fasting, during normoglycemic hyperinsulinemic clamp and during continuous oral intake of a standard liquid meal to achieve steady postprandial NEFA and triacylglycerols (TG) without and with insulin infusion to maintain similar glycemia in all three groups.Plasma palmitate appearance and oxidation were higher at fasting and during the clamp conditions in the T2D group (all P

Abstract The characterisation of novel materials presents a challenge that requires new and original developments. To face some of these demands for making measurements at the nanoscale, a new microsphere-assisted white light interference nanoscope performing local reflectance mapping is presented. This technique presents the advantages of being non-destructive, full-field and label-free. A 145 μm diameter microsphere, glued to the end of an optical fiber, is inserted inside the white light interference microscope to improve the lateral resolution from 940 nm to 520 nm. The acquisition and the Fourier transform processing of a stack of interference images superimposed on the virtual image produced by the microsphere allows the extraction of the local reflectance over a wavelength range of 460 nm to 900 nm and a field of view of 8 μm in diameter. The enhancement in the lateral resolution of the reflectance is demonstrated through the spectral distinction of neighboring ripples on a laser-textured colored stainless-steel sample that cannot be resolved without the microsphere, on regions with a surface of 279 × 279 nm2 horizontally spaced 279 nm apart. Future improvements could potentially lead to a lateral resolution of reflectance measurement over a 100 nm diameter area in air, paving the way to sub-diffraction reflectance mapping.

Abstract A detailed assessment of a low energy demand, 1.5 ∘C compatible pathway is provided for Europe from a bottom-up, country scale modelling perspective. The level of detail enables a clear representation of the potential of sufficiency measures. Results show that by 2050, 50% final energy demand reduction compared to 2019 is possible in Europe, with at least 40% of it attributable to various sufficiency measures across all sectors. This reduction enables a 77% renewable energy share in 2040 and 100% in 2050, with very limited need for imports from outside of Europe and no carbon sequestration technologies. Sufficiency enables increased fairness between countries through the convergence towards a more equitable share of energy service levels. Here we show, that without sufficiency measures, Europe misses the opportunity to transform energy demand leaving considerable pressure on supply side changes combined with unproven carbon removal technologies.

Abstract Background Dengue fever is one of the most prevalent mosquito-borne diseases in Cambodia. Until now, no specific vaccine nor antiviral treatment exists the virus causing Dengue fever. Consequently, its prevention relies only on vector control strategies. However, efficient vector control in turn relies on a good knowledge of the biology of the vector species. Therefore, this study aims to provide the first review of the distribution, ecology, meteorological impacts, trophic behavior, vector competence, vector control and insecticide resistance of dengue vector species in Cambodia. Methods A systematic search of the Google Scholar and PubMed databases was conducted for relevant published articles. Of the 610 published articles originally identified, 70 articles were ultimately selected for inclusion in this review. We also included new data from unpublished research conducted in Cambodia between 2017 and 2023 related to dengue vector bionomics. Results Eleven Aedes (Stegomyia) mosquito species have been recorded in Cambodia, including a new species described in 2024. Four species are associated with dengue virus transmission, among which Aedes aegypti and Ae. albopictus are the main vectors and Ae. malayensis and Ae. scutellaris are considered to be potential vectors. Aedes aegypti and Ae. albopictus are present in all provinces of Cambodia. Aedes albopictus shows a preference for forest, rural and suburban areas, while Ae. aegypti is mostly found in urban and suburban areas. The distribution of these two species is also influenced by meteorological factors, seasonality and the availability of breeding habitats and blood meals. Both species are predominant during the rainy season, and their respective density is impacted by precipitation and temperature. Aedes aegypti is characterized as anthropophilic, while Ae. albopictus exhibits zooanthropophilic behavior, and both species have been observed to be predominantly diurnal. In addition, they were found to be highly resistant to the insecticides used in Cambodia for their control, such as temephos for larvae and deltamethrin and permethrin for adult mosquitoes. Conclusions This review provides extensive and important knowledge on dengue vectors in Cambodia. This knowledge is derived not only from published research articles but also from many recent studies in Cambodia on the bionomics of dengue vector species. The review provides valuable information for use by public health authorities on dengue virus transmission and to develop better vector control strategies in the country. Graphical Abstract

Abstract Molten silicates at depth are crucial for planetary evolution, yet their local structure and physical properties under extreme conditions remain elusive due to experimental challenges. In this study, we utilize in situ X-ray diffraction (XRD) at the Matter in Extreme Conditions (MEC) end-station of the Linear Coherent Linac Source (LCLS) at SLAC National Accelerator Laboratory to investigate liquid silicates. Using an ultrabright X-ray source and a high-power optical laser, we probed the local atomic arrangement of shock-compressed liquid (Mg,Fe)SiO3 with varying Fe content, at pressures from 81(9) to 385(40) GPa. We compared these findings to ab initio molecular dynamics simulations under similar conditions. Results indicate continuous densification of the O-O and Mg-Si networks beyond Earth’s interior pressure range, potentially altering melt properties at extreme conditions. This could have significant implications for early planetary evolution, leading to notable differences in differentiation processes between smaller rocky planets, such as Earth and Venus, and super-Earths, which are exoplanets with masses nearly three times that of Earth.

Abstract Germline and somatic TP53 variants play a crucial role during tumorigenesis. However, genetic variations that solely affect the alternatively spliced p53 isoforms, p53β and p53γ, are not fully considered in the molecular diagnosis of Li-Fraumeni syndrome and cancer. In our search for additional cancer predisposing variants, we identify a heterozygous stop-lost variant affecting the p53β isoforms (p.*342Serext*17) in four families suspected of an autosomal dominant cancer syndrome with colorectal, breast and papillary thyroid cancers. The stop-lost variant leads to the 17 amino-acid extension of the p53β isoforms, which increases oligomerization to canonical p53α and dysregulates the expression of p53’s transcriptional targets. Our study reveals the capacity of p53β mutants to influence p53 signalling and contribute to the susceptibility of different cancer types. These findings underscore the significance of p53 isoforms and the necessity of comprehensive investigation into the entire TP53 gene in understanding cancer predisposition.

Abstract Cytomegalovirus (CMV) infection poses risks to newborns, necessitating effective therapies. Given that the damage includes both viral infection of brain cells and immune system-related damage, here we investigate the involvement of cellular prion protein (PrP), which plays vital roles in neuroprotection and immune regulation. Using a murine model, we show the role of PrP in tempering neonatal T cell immunity during CMV infection. PrP-null mice exhibit enhanced viral control through elevated virus-specific CD8 T cell responses, leading to reduced viral titers and pathology. We further unravel the molecular mechanisms by showing CMV-induced upregulation followed by release of PrP via the metalloproteinase ADAM10, impairing CD8 T cell response specifically in neonates. Additionally, we confirm PrP downregulation in human CMV (HCMV)-infected fibroblasts, underscoring the broader relevance of our observations beyond the murine model. Furthermore, our study highlights how PrP, under the stress of viral pathogenesis, reveals its impact on neonatal immune modulation.

Abstract Background In the last decade, notable progress in mechatronics paved the way for a new generation of arm prostheses, expanding motor capabilities thanks to their multiple active joints. Yet, the design of control schemes for these advanced devices still poses a challenge, especially with the limited availability of command signals for higher levels of arm impairment. When addressing this challenge, current commercial devices lack versatility and customizing options to be employed as test-beds for developing novel control schemes. As a consequence, researchers resort to using lab-specific experimental apparatuses on which to deploy their innovations, such as virtual reality setups or mock prosthetic devices worn by unimpaired participants. Methods To meet this need for a test-bed, we developed the Smart Arm platform, a human-like, multi-articulated robotic arm that can be worn as a trans-humeral arm prosthesis. The design process followed three principles: provide a reprogrammable embedded system allowing in-depth customization of control schemes, favor easy-to-buy parts rather than custom-made components, and guarantee compatibility with industrial standards in prosthetics. Results The Smart ArM platform includes motorized elbow and wrist joints while being compatible with commercial prosthetic hands. Its software and electronic architecture can be easily adapted to build devices with a wide variety of sensors and actuators. This platform was employed in several experiments studying arm prosthesis control and sensory feedback. We also report our participation in Cybathlon, where our pilot with forearm agenesia successfully drives the Smart Arm prosthesis to perform activities of daily living requiring both strength and dexterity. Conclusion These application scenarios illustrate the versatility and adaptability of the proposed platform, for research purposes as well as outside the lab. The Smart Arm platform offers a test-bed for experimenting with prosthetic control laws and command signals, suitable for running tests in lifelike settings where impaired participants wear it as a prosthetic device. In this way, we aim at bridging a critical gap in the field of upper limb prosthetics: the need for realistic, ecological test conditions to assess the actual benefit of a technological innovation for the end-users.

Abstract Machine learning and deep learning are novel methods which are revolutionizing medical imaging. In our study we trained an algorithm with a U-Net shaped network to recognize ultrasound images of the median nerve in the complete distal half of the forearm and to measure the cross-sectional area at the inlet of the carpal tunnel. Images of 25 patient hands with carpal tunnel syndrome (CTS) and 26 healthy controls were recorded on a video loop covering 15 cm of the distal forearm and 2355 images were manually segmented. We found an average Dice score of 0.76 between manual and automated segmentation of the median nerve in its complete course, while the measurement of the cross-sectional area at the carpal tunnel inlet resulted in a 10.9% difference between manually and automated measurements. We regard this technology as a suitable device for verifying the diagnosis of CTS.

Abstract Background The change in the efficacy of antimicrobial agents due to their misuse is implicated in extensive health and mortality related concerns. The Antibiotics Use Questionnaire (AUQ) is a theory driven measure based on the Theory of Planned Behaviour (TpB) factors that is designed to investigate drivers of antibiotic use behaviour. The objective of this study is to replicate the factor structure from the pilot study within a similar Australian confirmation cohort, and to extend this through investigating if the factor structure holds in a Chinese-identifying cohort. Methods The AUQ was disseminated to two cohorts: a confirmation cohort similar to the original study, and a Chinese identifying cohort. Data analysis was completed on the two data sets independently, and on a combined data set. An orthogonal principal components analysis with varimax rotation was used to assess the factor structure, followed by general linear models to determine the influence of the TpB factors on reported antibiotic use. Results 370 participant responses from the confirmation cohort, and 384 responses from the Chinese-identifying cohort were retained for analysis following review of the data. Results showed modest but acceptable levels of internal reliability across both cohorts. Social norms, and the interaction between attitudes and beliefs and knowledge were significant predictors of self-reported antibiotic use in both cohorts. In the confirmation cohort healthcare training was a significant predictor, and in the Chinese-identifying cohort education was a significant predictor. All other predictors tested produced a nonsignificant relationship with the outcome variable of self-reported antibiotic use. Conclusions This study successfully replicated the factor structure of the AUQ in a confirmation cohort, as well as a cohort that identified as culturally or legally Chinese, determining that the factor structure is retained when investigated across cultures. The research additionally highlights the need for a measure such as the AUQ, which can identify how differing social, cultural, and community factors can influence what predicts indiscriminate antibiotic use. Future research will be required to determine the full extent to which this tool can be used to guide bespoke community level interventions to assist in the management of antimicrobial resistance.

Abstract Cholinergic striatal interneurons (ChIs) express the vesicular glutamate transporter 3 (VGLUT3) which allows them to regulate the striatal network with glutamate and acetylcholine (ACh). In addition, VGLUT3-dependent glutamate increases ACh vesicular stores through vesicular synergy. A missense polymorphism, VGLUT3-p.T8I, was identified in patients with substance use disorders (SUDs) and eating disorders (EDs). A mouse line was generated to understand the neurochemical and behavioral impact of the p.T8I variant. In VGLUT3T8I/T8I male mice, glutamate signaling was unchanged but vesicular synergy and ACh release were blunted. Mutant male mice exhibited a reduced DA release in the dorsomedial striatum but not in the dorsolateral striatum, facilitating habit formation and exacerbating maladaptive use of drug or food. Increasing ACh tone with donepezil reversed the self-starvation phenotype observed in VGLUT3T8I/T8I male mice. Our study suggests that unbalanced dopaminergic transmission in the dorsal striatum could be a common mechanism between SUDs and EDs.

Abstract Despite being mutated in 92% of TP53 mutant cancers, how mutations on p53 isoforms affect their activities remain largely unknown. Therefore, exploring the effect of mutations on p53 isoforms activities is a critical, albeit unexplored area in the p53 field. In this article, we report for the first time a mutant Δ133p53α-specific pathway which increases IL4I1 and IDO1 expression and activates AHR, a tumor-promoting mechanism. Accordingly, while WT Δ133p53α reduces apoptosis to promote DNA repair, mutant R273H also reduces apoptosis but fails to maintain genomic stability, increasing the risks of accumulation of mutations and tumor’s deriving towards a more aggressive phenotype. Furthermore, using 2D and 3D spheroids culture, we show that WT Δ133p53α reduces cell proliferation, EMT, and invasion, while the mutant Δ133p53α R273H enhances all three processes, confirming its oncogenic potential and strongly suggesting a similar in vivo activity. Importantly, the effects on cell growth and invasion are independent of mutant full-length p53α, indicating that these activities are actively carried by mutant Δ133p53α R273H. Furthermore, both WT and mutant Δ133p53α reduce cellular senescence in a senescence inducer-dependent manner (temozolomide or radiation) because they regulate different senescence-associated target genes. Hence, WT Δ133p53α rescues temozolomide-induced but not radiation-induced senescence, while mutant Δ133p53α R273H rescues radiation-induced but not temozolomide-induced senescence. Lastly, we determined that IL4I1, IDO1, and AHR are significantly higher in GBMs compared to low-grade gliomas. Importantly, high expression of all three genes in LGG and IL4I1 in GBM is significantly associated with poorer patients’ survival, confirming the clinical relevance of this pathway in glioblastomas. These data show that, compared to WT Δ133p53α, R273H mutation reorientates its activities toward carcinogenesis and activates the oncogenic IL4I1/IDO1/AHR pathway, a potential prognostic marker and therapeutic target in GBM by combining drugs specifically modulating Δ133p53α expression and IDO1/Il4I1/AHR inhibitors.

Abstract Dysregulated epigenetic states are a hallmark of cancer and often arise from genetic alterations in epigenetic regulators. This includes missense mutations in histones, which, together with associated DNA, form nucleosome core particles. However, the oncogenic mechanisms of most histone mutations are unknown. Here, we demonstrate that cancer-associated histone mutations at arginines in the histone H3 N-terminal tail disrupt repressive chromatin domains, alter gene regulation, and dysregulate differentiation. We find that histone H3R2C and R26C mutants reduce transcriptionally repressive H3K27me3. While H3K27me3 depletion in cells expressing these mutants is exclusively observed on the minor fraction of histone tails harboring the mutations, the same mutants recurrently disrupt broad H3K27me3 domains in the chromatin context, including near developmentally regulated promoters. H3K27me3 loss leads to de-repression of differentiation pathways, with concordant effects between H3R2 and H3R26 mutants despite different proximity to the PRC2 substrate, H3K27. Functionally, H3R26C-expressing mesenchymal progenitor cells and murine embryonic stem cell-derived teratomas demonstrate impaired differentiation. Collectively, these data show that cancer-associated H3 N-terminal arginine mutations reduce PRC2 activity and disrupt chromatin-dependent developmental functions, a cancer-relevant phenotype.

Abstract Functionally characterizing the genetic alterations that drive pancreatic cancer is a prerequisite for precision medicine. Here, we perform somatic CRISPR/Cas9 mutagenesis screens to assess the transforming potential of 125 recurrently mutated pancreatic cancer genes, which revealed USP15 and SCAF1 as pancreatic tumor suppressors. Mechanistically, we find that USP15 functions in a haploinsufficient manner and that loss of USP15 or SCAF1 leads to reduced inflammatory TNFα, TGF-β and IL6 responses and increased sensitivity to PARP inhibition and Gemcitabine. Furthermore, we find that loss of SCAF1 leads to the formation of a truncated, inactive USP15 isoform at the expense of full-length USP15, functionally coupling SCAF1 and USP15. Notably, USP15 and SCAF1 alterations are observed in 31% of pancreatic cancer patients. Our results highlight the utility of in vivo CRISPR screens to integrate human cancer genomics and mouse modeling for the discovery of cancer driver genes with potential prognostic and therapeutic implications.

Abstract Inscribed on the UNESCO World Heritage list, the sub-Antarctic Crozet archipelago is located in a region facing significant environmental changes impacting a poorly known marine biodiversity. Underwater imagery constitutes a valuable non-invasive approach for gathering ecological data and improving our knowledge of ecosystems’ vulnerability. We here compiled two datasets, encompassing 17 video-imagery surveys of Crozet nearshore environments conducted in 2021 and 2022 at two sites of Ile de la Possession: Baie du Marin and Crique du Sphinx. Faunal abundance and algal cover data related to each survey are also provided. A total of 755 images were analysed, comprising 52 faunal and 14 algal taxa identified in 2021, as well as 45 faunal and 14 algal taxa identified in 2022. Video-transects were performed in shallow waters by scuba divers using a GoPro®HERO7 multiple camera set-up, and in deeper waters using a remotely operated vehicle. These data provide a first baseline for biodiversity and ecosystem studies, and for monitoring the long-term dynamics of Crozet benthic habitats facing natural and anthropogenic disturbances.

Introduction Tetraplegia causes extensive sensorimotor deficits affecting activity, participation and quality of life. People with C6-C7 tetraplegia can learn to grasp objects by performing wrist extension movement (ie, tenodesis grasp), and motor imagery (MI) added to rehabilitation significantly improved tenodesis grasp. We hypothesise that this improvement can be further boosted by adding neurofeedback during MI. Thus, we design a randomised controlled trial investigating the effect of MI training on grasping ability in people with C6-C7 tetraplegia.Methods and analysis We will perform a bicentric, assessor-blinded, randomised controlled study. During rehabilitation, 21 inpatients with C6-C7 tetraplegia will be allocated to MI with neurofeedback (MI training with graphical display on a computer screen based on mu (8–13 Hz) and beta (18–25 Hz) frequency rhythms measured with 32-channel electroencephalography), MI alone (only MI training) and control (watching movies and visualisation of geometric shapes). All participants will receive three 45-min training sessions per week for 5 weeks.The primary outcome measure will be wrist extension angle immediately after the intervention during tenodesis grasp measured with a 3D motion analysis system (VICON). Secondary outcomes will include a range of measures: kinematic, grip strength, upper limb range of motion, upper limb strength (manual muscle test and hand-held dynamometer measure), dexterity (box and block test, 9-hole peg test, Jebsen test, capabilities of upper extremity questionnaire), quality of life (WHOQOL-Bref), daily life autonomy (Quadriplegic Index of Function), MI capacity and brain reorganisation (magnetoencephalography only available in Lyon, n=15). We will measure all outcomes five times: during weeks 1, 3 and 5 (baseline), week 11 (immediately after the intervention end) and week 18 (8 weeks after the intervention end).Ethics and dissemination Ethical approval was granted on 29 September 2017 (CPP Nord-Ouest-IV 17/25, N°2017-A00990-53). Dissemination will occur via presentation of results in scientific meetings and publication in peer-reviewed academic journals.Trial registration number NCT03190863 (ClinicalTrials.gov).

Alzheimer's disease (AD) is characterized by progressive cognitive decline and neuropathological changes, yet the underlying neurobiological mechanisms remain elusive. Here, we employed a multimodal longitudinal neuroimaging approach, using anatomical and functional sequences on a high field magnetic resonance imaging (MRI) preclinical scanner, to investigate alterations in brain connectivity and white matter microstructure in a transgenic mouse model of AD (J20) when compared to wild-type (WT) littermates. Functional connectivity analysis revealed distinct network disruptions in J20 mice, primarily involving connections between posterior and anterior brain regions; importantly, a significant interaction between group and age highlighted an exacerbation of these connectivity changes with advancing age in J20 mice. In addition, significant reductions in fractional anisotropy (FA) were observed in the corpus callosum of J20 mice compared to WT, indicative of microstructural alterations consistent with white matter pathology. The observed alterations in brain connectivity and microstructure provide valuable insights into the spatiotemporal processes underlying AD-related decline and underscore the utility of multimodal neuroimaging in elucidating the neurobiological substrates of AD pathology in animal models.

Despite therapeutic efficacy observed with immune checkpoint blockade in advanced melanoma, many tumors do not respond to treatment, representing a need for new therapies. Here, we have generated chimeric antigen receptor (CAR) T cells targeting TYRP1, a melanoma differentiation antigen expressed on the surface of melanomas, including rare acral and uveal melanomas. TYRP1-targeted CAR T cells demonstrate antigen-specific activation and cytotoxic activity in vitro and in vivo against human melanomas independent of the MHC alleles and expression. In addition, the toxicity to pigmented normal tissues observed with T lymphocytes expressing TYRP1-targeted TCRs was not observed with TYRP1-targeted CAR T cells. Anti-TYRP1 CAR T cells provide a novel means to target advanced melanomas, serving as a platform for the development of similar novel therapeutic agents and as a tool to interrogate the immunobiology of melanomas.

Abstract is missing (Short communication)

Abstract The Scutellaris Group of Aedes comprises 47 mosquito species, including Aedes albopictus. While Ae. albopictus is widely distributed, the other species are mostly found in the Asia–Pacific region. Evolutionary history researches of Aedes species within the Scutellaris Group have mainly focused on Ae. albopictus, a species that raises significant public health concerns, neglecting the other species. In this study, we aimed to assess genetic diversity and estimate speciation times of several species within the Scutellaris Group. Mosquitoes were therefore collected from various Asia–Pacific countries. Their mitochondrial cytochrome c oxidase subunit 1 (cox1) and subunit 3 (cox3) sequences were analyzed alongside those of other Scutellaris Group species available in the GenBank database. To estimate the divergence time, we analyzed 1849 cox1 gene sequences from 21 species, using three species (Aedes aegypti, Aedes notoscriptus and Aedes vigilax) as outgroups. We found that most of the speciation dates occurred during the Paleogene and the Neogene periods. A separation between the Scutellaris Subgroup and the Albopictus Subgroup occurred approximately 64–61 million years ago (MYA). We also identified a split between species found in Asia/Micronesia and those collected in Melanesia/Polynesia approximately 36–35 MYA. Our findings suggest that the speciation of Aedes species within the Scutellaris Group may be driven by diversity in mammalian hosts, climate and environmental changes, and geological dynamics rather than human migration.

The data warehousing process requires an architectural revolution to settle big data challenges and address new data sources such as social networks, recommendation systems, smart cities, and the web to extract value from shared data. In this respect, the pipeline modeling community for the acquisition, storage, and processing of data for analysis purposes is enacting a wide range of technological solutions that present significant challenges and difficulties. More specifically, the choice of the most appropriate tool for the user's specific business needs and the interoperability between the different tools have become a primary challenges. From this perspective, we propose in this paper a new interactive framework based on machine learning techniques (ML) to assist experts in the process of modeling a customized pipeline for data warehousing. More precisely, we elaborate first (i) an analysis of the experts' requirements and the characteristics of the data to be processed, then (ii) we propose the most appropriate architecture to their requirements from a multitude of specific architectures instantiated from a generic one, by using (iii) several ML methods to predict the most suitable tool for each phase and task within the architecture. Additionally, our framework is validated through two real-world use cases and user feedback. [JJCIT 2024; 10(3.000): 306-318]

Abstract Tumor suppressor p53 (TP53) is frequently mutated in cancer, often resulting not only in loss of its tumor-suppressive function but also acquisition of dominant-negative and even oncogenic gain-of-function traits. While wild-type p53 levels are tightly regulated, mutants are typically stabilized in tumors, which is crucial for their oncogenic properties. Here, we systematically profiled the factors that regulate protein stability of wild-type and mutant p53 using marker-based genome-wide CRISPR screens. Most regulators of wild-type p53 also regulate p53 mutants, except for p53 R337H regulators, which are largely private to this mutant. Mechanistically, FBXO42 emerged as a positive regulator for a subset of p53 mutants, working with CCDC6 to control USP28-mediated mutant p53 stabilization. Additionally, C16orf72/HAPSTR1 negatively regulates both wild-type p53 and all tested mutants. C16orf72/HAPSTR1 is commonly amplified in breast cancer, and its overexpression reduces p53 levels in mouse mammary epithelium leading to accelerated breast cancer. This study offers a network perspective on p53 stability regulation, potentially guiding strategies to reinforce wild-type p53 or target mutant p53 in cancer.

Abstract Background Simulation-based training courses in laparoscopy have become a fundamental part of surgical training programs. Surgical skills in laparoscopy are challenging to master, and training in these skills induces stress responses in trainees. There is limited data on trainees’ stress levels, the stress responses related to training on different laparoscopic simulators, and how previous experiences influence trainees’ stress response during a course. This study investigates physiologic, endocrine and self-reported stress responses during simulation-based surgical skills training in a course setting. Methods We conducted a prospective observational study of trainees attending basic laparoscopic skills training courses at a national training centre. During the three-day course, participants trained on different laparoscopic simulators: Two box-trainers (the D-box and P.O.P. trainer) and a virtual reality simulator (LAPMentor™). Participants’ stress responses were examined through heart rate variability (HRV), saliva cortisol, and the State Trait Anxiety Inventory-6 (STAI-6). The correlation between previous laparoscopic experiences and stress response measurements was explored. Results Twenty-four surgical trainees were included in the study. Compared to resting conditions, stress measures were significantly higher during simulation-training activity (the D-box (SDNN = 58.5 ± 23.4; LF/HF-ratio = 4.58 ± 2.71; STAI-6 = 12.3 ± 3.9, P

Abstract Objectives We aimed to analyze the risk factors for management failure of BC after pediatric liver transplantation (pLT) by retrospectively analyzing primary pLT performed between 1997 and 2018 (n = 620 patients). Results In all, 117/620 patients (19%) developed BC. The median (range) follow-up was 9 (1.4–21) years. Patient survival at 1, 5 and 10 years was 88.9%, 85.7%, 84.4% and liver graft survival was 82.4%, 77.4%, and 74.3% respectively. Graft not patient survival was impaired by BC (p = 0.01). Multivariate analysis identified the number of dilatation courses > 2 (p = 0.008), prolonged cold ischemia time (p = 0.004), anastomosed multiple biliary ducts (p = 0.019) and hepatic artery thrombosis (p = 0.01) as factors associated with impaired graft survival. The number of dilatation courses > 2 (p 2) radiologic dilatation courses are associated with impaired graft survival and management failure. Overall, graft but not patient survival was impaired by BC.

Abstract Background Early hormone-positive breast cancers typically have favorable outcomes, yet long-term surveillance is crucial due to the risk of late recurrences. While many studies associate MMP-11 expression with poor prognosis in breast cancer, few focus on early-stage cases. This study explores MMP-11 as an early prognostic marker in hormone-positive breast cancers. Methods In this retrospective study, 228 women with early hormone-positive invasive ductal carcinoma, treated surgically between 2011 and 2016, were included. MMP-11 expression was measured by immunohistochemistry, and its association with clinical and MRI data was analyzed. Results Among the patients (aged 31–89, median 60, with average tumor size of 15.7 mm), MMP-11 staining was observed in half of the cases. This positivity correlated with higher uPA levels and tumor grade but not with nodal status or size. Furthermore, MMP-11 positivity showed specific associations with MRI features. Over a follow-up period of 6.5 years, only 12 oncological events occurred. Disease-free survival was linked to Ki67 and MMP-11. Conclusion MMP-11, primarily present in tumor-surrounding stromal cells, correlates with tumor grade and uPA levels. MMP-11 immunohistochemical score demonstrates a suggestive trend in association with disease-free survival, independent of Ki67 and other traditional prognostic factors. This highlights the potential of MMP-11 as a valuable marker in managing early hormone-positive breast cancer.

ABSTRACTWe present the characterization of geohazard-related features of the Ligurian Sea with the map of its physiographic domains (1:250,000 scale) and five maps (1:100,000 scale) of the morphological and morpho-bathymetric elements. These were realized in the framework of the MaGIC (Marine Geohazard along Italian Coasts) project, promoted by the Italian Civil Protection Department. The characterization of submarine geohazards along continental margins, together with mapping of marine geological features are critical for the management of coastal risks. Multibeam bathymetric data combined with high-resolution 2D reflection seismic data, allowed to identify and map the main tectono-sedimentary features related to mass movements along the Ligurian continental margin. A dense grid of seismic profiles allowed to improve the comprehension of the margin structure as well as its recent tectonic activity providing new insights concerning mass wasting processes and active tectonics relationships to plan further, focalized investigations in areas of maximum risk.

We investigated changes in primary schoolchildren's perceptions of the school climate amidst the COVID-19 pandemic and online learning shift. Data from the Modified-Delaware School Climate Survey-Student collected before (Time 1 (T1): October/November 2019) and during the pandemic's initial wave (Time 2 (T2): 12 months later) in Spain, Norway and Poland were analysed. In this repeat cross-sectional pre-post quasi-experimental study, we included a total of 1167 participants at T1 and 1209 participants at T2, ranging in age from 8 to 16 years and representing schoolchildren from fourth to last primary grades. Findings revealed a significant decline (overall OR = 0.80) in school climate perception across dimensions and countries during the pandemic's onset. Boys exhibited more negative perceptions than girls, particularly pronounced in Norway (OR = 0.59). Age also played a role, with a decline as students advanced in age, especially prominent in Poland (overall OR = 0.74). Our results emphasize the necessity of considering gender and age distinctions to enhance school climate during crises and proactively mitigate adverse effects on school climate.