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The Trp53 gene encodes several isoforms of elusive biological significance. Here, we show that mice lacking the Trp53 alternatively spliced (AS) exon, thereby expressing the canonical p53 protein but not isoforms with the AS C-terminus, have unexpectedly lost a male-specific protection against Myc-induced B-cell lymphomas. Lymphomagenesis was delayed in Trp53+/+Eμ-Myc males compared to Trp53ΔAS/ΔAS Eμ-Myc males, but also compared to Trp53+/+Eμ-Myc and Trp53ΔAS/ΔAS Eμ-Myc females. Pre-tumoral splenic cells from Trp53+/+Eμ-Myc males exhibited a higher expression of Ackr4, encoding an atypical chemokine receptor with tumor suppressive effects. We identified Ackr4 as a p53 target gene whose p53-mediated transactivation is inhibited by estrogens, and as a male-specific factor of good prognosis relevant for murine Eμ-Myc-induced and human Burkitt lymphomas. Furthermore, the knockout of ACKR4 increased the chemokine-guided migration of Burkitt lymphoma cells. These data demonstrate the functional relevance of alternatively spliced p53 isoforms and reveal sex disparities in Myc-driven lymphomagenesis.

Mesoporous germanium (MP-Ge) emerges as a very appealing material for many applications such as anode material for Lithium-Ion batteries due to it high specific area and large void spaces or, in optoelectronics as sacrificial layer for III-V materials growth and detachment, allowing notably several uses of a single Ge substrate. These porous nanostructures are distinguished by a large specific surface area and are prone to degradation with time due to exposure to the environment. To understand and be able to reduce this effect, we studied the chemical and morphological evolution of porous germanium layers under various ambient storage conditions for 3 months to identify the main parameters responsible for material degradation. This study demonstrates that the ambient air environment leads to the growth of native oxide, leading to major morphology changes. Scanning electrons microscope (SEM) showed the formation of clusters and the enlargement of the pores after 90 days. These structural modifications are caused by the oxidation of Ge, and more specifically by the creation of GeO2 matrices due to the synergy of dioxygen (O2) and humidity (H2O(g)). The energy brought by light can exacerbate these phenomena and thus accelerate the degradation rate of the pore morphology. Based on these experimental results, we propose efficient solutions to limit the GeO2 proportions and the clusters' appearance, by storing them under a dry neutral atmosphere (Ar) or by adding a hydrogen halide pre-treatment (10s 1% HBr solution).

Over recent years, positive airway pressure (PAP) remote monitoring has transformed the management of OSA and produced a large amount of data. Accumulated PAP data provide valuable and objective information regarding patient treatment adherence and efficiency. However, the majority of studies that have analyzed longitudinal PAP remote monitoring have summarized data trajectories in static and simplistic metrics for PAP adherence and the residual apnea-hypopnea index by the use of mean or median values. The aims of this article are to suggest directions for improving data cleaning and processing and to address major concerns for the following data science applications: (1) conditions for residual apnea-hypopnea index reliability, (2) lack of standardization of indicators provided by different PAP models, (3) missing values, and (4) consideration of treatment interruptions. To allow fair comparison among studies and to avoid biases in computation, PAP data processing and management should be conducted rigorously with these points in mind. PAP remote monitoring data contain a wealth of information that currently is underused in the field of sleep research. Improving the quality and standardizing data handling could facilitate data sharing among specialists worldwide and enable artificial intelligence strategies to be applied in the field of sleep apnea.

In the Michoacán region of central-western Mexico, the village of Turícuaro has for centuries been a center for metate production based on andesites exploited on the slopes of Hoya Urutzen and 'El Metate' volcanoes. Surveys have been conducted in this volcanic landscape, with the invaluable help of one of the last metateros (craftsmen) family of the village, the Vidalès, in order to reconstruct the strategies adopted through time to extract this andesite over a large territory. It has been possible to propose a first mapping as well as a relative dating of the various quarrying areas. Different types of exploitations have been described, from ancient quarries, associated with archaeological occupations, to current extraction sites. The morphology of the outcrops (walls, isolated blocks) partly conditioned the organization of the quarries (flat, organized on terraces, etc). It has also been possible to observe the different strategies and organization of work associated with this activity, through the observation of the abandoned blocks, waste and roughouts. Finally, this work offers a new perspective on Mesoamerican metate quarrying strategies.

Background: Type 2 diabetes mellitus (T2DM) and atrial fibrillation are risk factors for stroke. The potential preventive effects of cardiovascular and antidiabetic treatments on stroke risk in patients with these diseases remain insufficiently documented. Sulfonylureas have also been reported to be associated with stroke. This study aimed to assess the risk of stroke according to the use of drugs (anticoagulants, antiplatelet agents, and oral antidiabetic drugs [OADs]) in patients with T2DM and nonvalvular atrial fibrillation (NVAF). Methods: Patients with a history of T2DM and NVAF were identified from two systematic registries: a registry of patients with stroke and a registry of patients with atrial fibrillation. Patients with stroke were randomly matched to patients without prior stroke events based on age, sex, body mass index, and index date. All treatments administered 12 months before the index date were documented. The associations between anticoagulants, antiplatelet agents, and OADs and stroke were assessed using multivariate conditional logistic models that yielded adjusted odds ratios (aORs) and 95 % confidence intervals, controlling for risk factors identified in the univariate comparison of cases and matched referents. Results: Three-hundred and fifteen patients with stroke with both diabetes and NVAF were matched to 523 referents with both diabetes and NVAF but no history of stroke. The aORs for the use of drugs and stroke were 0.24 [0.15–0.40] for direct oral anticoagulants (DOACs), 0.42 [0.27–0.67] for vitamin K agonists (VKA), 0.80 [0.52–1.24] for antiplatelet agents, and 0.68 [0.45–1.02] for OADs. No significant associations were found between individual OAD use and stroke risk. Similar results were obtained for ischemic stroke. Only VKAs were significantly associated with hemorrhagic stroke (odds ratio = 4.25 [1.16–15.64]). Conclusions: Anticoagulant use was associated with a protective effect against the risk of stroke in patients with diabetes and NVAF, with no increase in the risk of hemorrhagic stroke for DOAC. No increased risk of stroke was observed because of any OAD, including sulfonylureas.

This article examines the interplay between artificial intelligence (AI) and cybersecurity in light of future regulatory requirements on the security of AI systems, specifically focusing on the robustness of high-risk AI systems against cyberattacks in the context of the European Union’s AI Act. The paper identifies and analyses three challenges to achieve compliance of AI systems with the cybersecurity requirement: accounting for the diversity and the complexity of AI technologies, assessing AI-specific risks, and developing secure-by-design AI systems. The contribution of the article consists in providing an overview of AI cybersecurity practices and identifying gaps in current approaches to security conformity assessment for AI systems. Our analysis highlights the unique vulnerabilities present in AI systems and the absence of established cybersecurity practices tailored to these systems, and emphasises the need for continuous alignment between legal requirements and technological capabilities, acknowledging the necessity for further research and development to address the challenges. It concludes that comprehensive cybersecurity practices must evolve to accommodate the unique aspects of AI, with a collaborative effort from various sectors to ensure effective implementation and standardisation.

Since the establishment of the first eye bank in the 1940s, their role has evolved to face new challenges. With the recent development of lamellar keratoplasties, eye banks play an even bigger role in the selection and preparation of donor tissues. The increasing number of keratoplasty techniques and the high demand for “ready-to-use” tissues are challenging eye banks to improve and develop new preparation techniques. Besides necessary examinations, new approaches of tissue analysis in eye banks allow a better/optimized selection of corneal tissues. These new challenges in tissue preservation, preparation, and selection are propelling eye banks into a new era of modern eye banking.

Abstract Glaucoma is a multifactorial neurodegenerative disease characterized by the progressive and irreversible degeneration of the optic nerve and retinal ganglion cells. Despite medical advances aiming at slowing degeneration, around 40% of treated glaucomatous patients will undergo vision loss. It is thus of utmost importance to have a better understanding of the disease and to investigate more deeply its early causes. The transcriptional coactivator YAP, an important regulator of eye homeostasis, has recently drawn attention in the glaucoma research field. Here we show that Yap conditional knockout mice (Yap cKO), in which the deletion of Yap is induced in both Müller glia (i.e. the only retinal YAP-expressing cells) and the non-pigmented epithelial cells of the ciliary body, exhibit a breakdown of the aqueous-blood barrier, accompanied by a progressive collapse of the ciliary body. A similar phenotype is observed in human samples that we obtained from patients presenting with uveitis. In addition, aged Yap cKO mice harbor glaucoma-like features, including deregulation of key homeostatic Müller-derived proteins, retinal vascular defects, optic nerve degeneration and retinal ganglion cell death. Finally, transcriptomic analysis of Yap cKO retinas pointed to early-deregulated genes involved in extracellular matrix organization potentially underlying the onset and/or progression of the observed phenotype. Together, our findings reveal the essential role of YAP in preserving the integrity of the ciliary body and retinal ganglion cells, thereby preventing the onset of uveitic glaucoma-like features.

Abstract Background This study aims to evaluate visual outcome, central corneal thickness, and re-bubbling rate in a cohort with undersized sequential Descemet Membrane Endothelial Keratoplasty (DMEK) due to endothelial graft decompensation following primary penetrating keratoplasty (PK). Methods All patients who received a sequential DMEK (n = 16) or triple DMEK (n = 2) after failed primary PK between November 2020 and June 2022 were retrospectively evaluated. Analyzed parameters were corrected distance visual acuity (CDVA), central corneal thickness (CCT), re-bubbling rate and graft survival. Results 18 eyes of 18 patients were included. All patients underwent a DMEK with undersized graft after failed PK(s). Mean time between the last PK and DMEK was 102 ± 82 weeks. Mean follow-up time was 8.9 ± 4.6 months. CDVA increased significantly from 1.12 ± 0.60 logMAR preoperatively to 0.64 ± 0.49 logMAR 6 weeks postoperatively (p = 0.013). Mean CCT decreased significantly from 807 ± 224 μm before to 573 ± 151 μm 6 weeks after DMEK (p = 0.003). Re-bubbling was necessary in eight eyes (44.4%) after a median time of 7 days. The 12-month Kaplan Meier survival was 66.7%. Conclusion In case of endothelial graft decompensation without stromal scars after primary PK, a DMEK can be performed for selected patients who had satisfying CDVA before the endothelial decompensation. Prior to DMEK indication, an AS-OCT should routinely be performed to circularly search for posterior steps at the PK graft margin, as well as shortly after DMEK to exclude a detachment of the endothelial graft. All patients should be informed about a higher re-bubbling rate in comparison to primary DMEK.

Background. It is well-established that a range of macronutrients, micronutrients and bioactive compounds found in animal-source foods play unique and important roles in human health as part of a healthy diet. Methods. This narrative review focuses on terrestrial animal source foods (TASFs). It particularly analyzes five groups: poultry eggs, milk, unprocessed meat, foods from hunting and wildlife farming, and insects. The objectives were as follows: (1) examine the nutrient composition of TASFs within and across livestock species, drawing on the country and regional food composition databases; (2) analyze the influence of intrinsic animal characteristics and production practices on TASF nutritional quality. Results. TASFs are rich in high-quality proteins and fats, as well as micronutrients such as vitamin B12, iron or zinc. This study found differences in the nutritional quality of TASFs by livestock species and animal products, as well as by characteristics of livestock production systems. Our findings suggest that there may be public health opportunities by diversifying TASF consumption across species and improving certain aspects of the production systems to provide products that are both more sustainable and of higher quality. Conclusions. Future research should adopt a more holistic approach to examining the food matrix and the dietary patterns that influence TASF digestibility. It is necessary to include meat from hunting and wildlife farming and insects in global food composition databases, as limited literature was found. In addition, scarce research focuses on low- and middle-income countries, highlighting the need for further exploration of TASF food composition analysis and how intrinsic animal characteristics and livestock production system characteristics impact their nutritional value.

Falls are very serious health concerns among older adults. Providing additional cutaneous and proprioceptive feedback to older adults may enhance their balance control and therefore reduce the incidents of falls. This study aimed to investigate the acute and acclimated effect of wearing waist-to-above-ankle compression garments (CGs) on balance control in community-dwelling older adults. Thirty-one older adults participated in the study. The Timed Up and Go, Berg Balance Scale, and the Fall Risk Test of the Biodex Balance System were used in a random order to examine balance control in three testing sessions 1 week apart. Results indicated wearing CGs had a significant impact on the Timed Up and Go test (p <.001), Berg Balance Scale (p =.001), and the Fall Risk Test (p =.001). For the Timed Up and Go test, participants exhibited significant improvement in both the acute (8.68 vs. 7.91 s) and acclimated effect (7.91 vs. 7.41 s) of wearing CGs. For the Berg Balance Scale, participants showed significant improvement after wearing CGs for 1 week in comparison to the no CGs condition (55.77 vs. 55.39 points). For the Fall Risk Test, participants showed a significant improvement in the acute effect of wearing CGs in comparison to the no CGs condition (1.55° vs. 1.31°). This exploratory study showed that wearing waist-to-above-ankle CGs provided a positive impact on balance control in healthy community-dwelling older adults. It lays the foundation for future studies with a larger sample size to investigate the potential benefits of wearing CGs in individuals with balance control deficits and/or other comorbidities. [ABSTRACT FROM AUTHOR]