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Acute kidney injury following trauma impacts patient recovery critically, necessitating an integrated approach to emergency care and nephrology. This review aims to provide a comprehensive understanding of trauma-induced nephropathy, highlighting recent advancements in pathophysiological insights, diagnostic techniques, and strategic interventions. Our key findings emphasize the role of biomarkers, like Neutrophil Gelatinase-Associated Lipocalin and Liver Fatty Acid-Binding Protein, and imaging techniques, such as contrast-enhanced ultrasound, in early AKI detection. Preventive strategies, including aggressive fluid resuscitation, avoidance of nephrotoxic agents, and hemodynamic optimization, are essential for mitigating AKI progression. Integrating these approaches into trauma care frameworks aims to enhance patient outcomes and set a foundation for future research and clinical improvements.

Lamellar ichthyosis (LI) is a chronic disease, mostly caused by mutations in the TGM1 gene, marked by impaired skin barrier formation. No definitive therapies are available, and current treatments aim at symptomatic relief. LI mouse models often fail to faithfully replicate the clinical and histopathological features of human skin conditions. To develop advanced therapeutic approaches, such as combined ex vivo cell and gene therapy, we established a human cellular model of LI by efficient CRISPR-Cas9-mediated gene ablation of the TGM1 gene in human primary clonogenic keratinocytes. Gene-edited cells showed complete absence of transglutaminase 1 (TG1) expression and recapitulated a hyperkeratotic phenotype with most of the molecular hallmarks of LI in vitro . Using a self-inactivating γ-retroviral (SINγ-RV) vector expressing transgenic TGM1 under the control of its own promoter, we tested an ex vivo gene therapy approach and validate the model of LI as a platform for pre-clinical evaluation studies. Gene-corrected TGM1 -null keratinocytes displayed proper TG1 expression, enzymatic activity, and cornified envelope formation and, hence, restored proper epidermal architecture. Single-cell multiomics analysis demonstrated proviral integrations in holoclone-forming epidermal stem cells, which are crucial for epidermal regeneration. This study serves as a proof of concept for assessing the potential of this therapeutic approach in treating TGM1 -dependent LI., Competing Interests: M.D.L. is a consultant for J-TEC-Japan Tissue Engineering, Ltd., (© 2024 The Author(s).)

Epidermal stem cells orchestrate epidermal renewal and timely wound repair through a tight regulation of self-renewal, proliferation, and differentiation. In culture, human epidermal stem cells generate a clonal type referred to as holoclone, which give rise to transient amplifying progenitors (meroclone and paraclone-forming cells) eventually generating terminally differentiated cells. Leveraging single-cell transcriptomic data, we explored the FOXM1-dependent biochemical signals controlling self-renewal and differentiation in epidermal stem cells aimed at improving regenerative medicine applications. We report that the expression of H1 linker histone subtypes decrease during serial cultivation. At clonal level we observed that H1B is the most expressed isoform, particularly in epidermal stem cells, as compared to transient amplifying progenitors. Indeed, its expression decreases in primary epithelial culture where stem cells are exhausted due to FOXM1 downregulation. Conversely, H1B expression increases when the stem cells compartment is sustained by enforced FOXM1 expression, both in primary epithelial cultures derived from healthy donors and JEB patient. Moreover, we demonstrated that FOXM1 binds the promotorial region of H1B, hence regulates its expression. We also show that H1B is bound to the promotorial region of differentiation-related genes and negatively regulates their expression in epidermal stem cells. We propose a novel mechanism wherein the H1B acts downstream of FOXM1, contributing to the fine interplay between self-renewal and differentiation in human epidermal stem cells. These findings further define the networks that sustain self-renewal along the previously identified YAP-FOXM1 axis., (© 2024. The Author(s).)

Background: West Nile virus (WNV) is an emerging mosquito-borne pathogen in Serbia, where it has been detected as a cause of infection in humans since 2012. We analyzed and modelled WNV transmission patterns in the country between 2012 and 2023., Methods: We applied a previously developed modelling approach to quantify epidemiological parameters of interest and to identify the most important environmental drivers of the force of infection (FOI) by means of statistical analysis in the human population in the country., Results: During the study period, 1,387 human cases were recorded, with substantial heterogeneity across years. We found that spring temperature is of paramount importance for WNV transmission, as FOI magnitude and peak timing are positively associated with it. Furthermore, FOI is also estimated to be greater in regions with a larger fraction of older adult people, who are at higher risk to develop severe infections., Conclusion: Our results highlight that temperature plays a key role in shaping WNV outbreak magnitude in Serbia, confirming the association between spring climatic conditions and WNV human transmission risk and thus pointing out the importance of this factor as a potential early warning predictor for timely application of preventive and control measures., Competing Interests: WW was employed by Environmental Research Group Oxford Ltd, c/o Dept Biology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Marini, Drakulovic, Jovanovic, Dagostin, Wint, Tagliapietra, Vasic and Rizzoli.)

Modelling approaches play a crucial role in supporting local public health agencies by estimating and forecasting vector abundance and seasonality. However, the reliability of these models is contingent on the availability of standardized, high-quality data. Addressing this need, our study focuses on collecting and harmonizing egg count observations of the mosquito Aedes albopictus, obtained through ovitraps in monitoring and surveillance efforts across Albania, France, Italy, and Switzerland from 2010 to 2022. We processed the raw observations to obtain a continuous time series of ovitraps observations allowing for an extensive geographical and temporal coverage of Ae. albopictus population dynamics. The resulting post-processed observations are stored in the open-access database VectAbundance.This initiative addresses the critical need for accessible, high-quality data, enhancing the reliability of modelling efforts and bolstering public health preparedness., (© 2024. The Author(s).)

Photoexcited GeTe undergoes a nonthermal phase transition from a rhombohedral to a rocksalt crystalline phase. The microscopic mechanism and the nature of the transition are unclear. By using constrained density functional perturbation theory and by accounting for quantum anharmonicity within the stochastic self-consistent harmonic approximation, we show that the nonthermal phase transition is strongly first order and does not involve phonon softening, at odds with the thermal one. The transition is driven by the closure of the single particle gap in the photoexcited rhombohedral phase. Finally, we show that ultrafast x-ray diffraction data are consistent with a coexistence of the two phases, as expected in a first order transition. Our results are relevant for the understanding of phase transitions and bonding in phase change materials.

The photoluminescence spectrum of a single-layer boron nitride remains elusive, marked by enigmatic satellites that hint at significant but unidentified exciton-phonon coupling. Here, by employing a first-principles approach based on the many-body cumulant expansion of the charge response, we calculate the optical absorption and photoluminescence of a single-layer boron nitride. We identify the specific exciton-phonon scattering channels and unravel their impact on the optical absorption and photoluminescence spectra, thereby providing an interpretation of the experimental features. Finally, we show that, even in a strongly polar material such as h-BN monolayer, the electron-hole interaction responsible for the excitonic effect results in the cancellation of the Frölich interaction at small phonon momenta. This effect is captured only if the invariance of the exciton-phonon matrix elements under unitary transformations in the Bloch function manifold is preserved in the calculation.

Screening, a ubiquitous phenomenon associated with the shielding of electric fields by surrounding charges, has been widely adopted as a means to modify a material's properties. While most studies have relied on static changes of screening through doping or gating thus far, here we demonstrate that screening can also drive the onset of distinct quantum states on the ultrafast timescale. By using time- and angle-resolved photoemission spectroscopy, we show that intense optical excitation can drive 1T-TiSe 2 , a prototypical charge density wave material, almost instantly from a gapped into a semimetallic state. By systematically comparing changes in band structure over time and excitation strength with theoretical calculations, we find that the appearance of this state is likely caused by a dramatic reduction of the screening length. In summary, this work showcases how optical excitation enables the screening-driven design of a nonequilibrium semimetallic phase in TiSe 2 , possibly providing a general pathway into highly screened phases in other strongly correlated materials.

This paper investigates the role of institutional quality in explaining cross-regional variation in population health status in Italy. We first introduce a composite Regional Health Status Indicator summarizing life expectancy, mortality and morbidity data. Then, we study the empirical relationship between this indicator and a set of socioeconomic, health system and institutional controls at the Italian regional level over the period of 2011-2019. We find that institutional quality is a driver of population health. Furthermore, well-functioning local institutions and regions compliant with national standards in terms of public healthcare services (Essential Levels of Care) make socioeconomic context no longer relevant for population health, potentially reducing inequalities., (© 2024. The Author(s).)

Background: Artificial Intelligence(AI)-based solutions for Gleason grading hold promise for pathologists, while image quality inconsistency, continuous data integration needs, and limited generalizability hinder their adoption and scalability., Methods: We present a comprehensive digital pathology workflow for AI-assisted Gleason grading. It incorporates A!MagQC (image quality control), A!HistoClouds (cloud-based annotation), Pathologist-AI Interaction (PAI) for continuous model improvement, Trained on Akoya-scanned images only, the model utilizes color augmentation and image appearance migration to address scanner variations. We evaluate it on Whole Slide Images (WSI) from another five scanners and conduct validations with pathologists to assess AI efficacy and PAI., Results: Our model achieves an average F1 score of 0.80 on annotations and 0.71 Quadratic Weighted Kappa on WSIs for Akoya-scanned images. Applying our generalization solution increases the average F1 score for Gleason pattern detection from 0.73 to 0.88 on images from other scanners. The model accelerates Gleason scoring time by 43% while maintaining accuracy. Additionally, PAI improve annotation efficiency by 2.5 times and led to further improvements in model performance., Conclusions: This pipeline represents a notable advancement in AI-assisted Gleason grading for improved consistency, accuracy, and efficiency. Unlike previous methods limited by scanner specificity, our model achieves outstanding performance across diverse scanners. This improvement paves the way for its seamless integration into clinical workflows., (© 2024. The Author(s).)

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use's (ICH) renovation of Good Clinical Practice (GCP) represents a philosophical shift in the conduct of clinical research away from a one-size-fits-all application to promoting a proactive, risk-based approach. The aim of this paper is to enhance the understanding of specific topics detailed in ICH E8 based on direct feedback from TransCelerate member companies who identified Quality by Design (QbD), Critical to Quality (CtQ), Fit for Purpose, and Stakeholder Engagement, as most changed and open to interpretation. The TransCelerate framework seeks to highlight and expand each of these central topics to support utilization and implementation of a strong foundation for quality in clinical development., (© 2023. The Author(s).)

West Nile virus (WNV) is an emerging mosquito-borne pathogen in Europe where it represents a new public health threat. While climate change has been cited as a potential driver of its spatial expansion on the continent, a formal evaluation of this causal relationship is lacking. Here, we investigate the extent to which WNV spatial expansion in Europe can be attributed to climate change while accounting for other direct human influences such as land-use and human population changes. To this end, we trained ecological niche models to predict the risk of local WNV circulation leading to human cases to then unravel the isolated effect of climate change by comparing factual simulations to a counterfactual based on the same environmental changes but a counterfactual climate where long-term trends have been removed. Our findings demonstrate a notable increase in the area ecologically suitable for WNV circulation during the period 1901-2019, whereas this area remains largely unchanged in a no-climate-change counterfactual. We show that the drastic increase in the human population at risk of exposure is partly due to historical changes in population density, but that climate change has also been a critical driver behind the heightened risk of WNV circulation in Europe., (© 2024. The Author(s).)

Background: Estimates of the spatiotemporal distribution of different mosquito vector species and the associated risk of transmission of arboviruses are key to design adequate policies for preventing local outbreaks and reducing the number of human infections in endemic areas. In this study, we quantified the abundance of Aedes albopictus and Aedes aegypti and the local transmission potential for three arboviral infections at an unprecedented spatiotemporal resolution in areas where no entomological surveillance is available., Methods: We developed a computational model to quantify the daily abundance of Aedes mosquitoes, leveraging temperature and precipitation records. The model was calibrated on mosquito surveillance data collected in 115 locations in Europe and the Americas between 2007 and 2018. Model estimates were used to quantify the reproduction number of dengue virus, Zika virus, and chikungunya in Europe and the Americas, at a high spatial resolution., Findings: In areas colonised by both Aedes species, A aegypti was estimated to be the main vector for the transmission of dengue virus, Zika virus, and chikungunya, being associated with a higher estimate of R 0 when compared with A albopictus. Our estimates highlighted that these arboviruses were endemic in tropical and subtropical countries, with the highest risks of transmission found in central America, Venezuela, Colombia, and central-east Brazil. A non-negligible potential risk of transmission was also estimated for Florida, Texas, and Arizona (USA). The broader ecological niche of A albopictus could contribute to the emergence of chikungunya outbreaks and clusters of dengue autochthonous cases in temperate areas of the Americas, as well as in mediterranean Europe (in particular, in Italy, southern France, and Spain)., Interpretation: Our results provide a comprehensive overview of the transmission potential of arboviral diseases in Europe and the Americas, highlighting areas where surveillance and mosquito control capacities should be prioritised., Funding: EU and Ministero dell'Università e della Ricerca, Italy (Piano Nazionale di Ripresa e Resilienza Extended Partnership initiative on Emerging Infectious Diseases); EU (Horizon 2020); Ministero dell'Università e della Ricerca, Italy (Progetti di ricerca di Rilevante Interesse Nazionale programme); Brazilian National Council of Science, Technology and Innovation; Ministry of Health, Brazil; and Foundation of Research for Minas Gerais, Brazil., Competing Interests: Declaration of interests MA has received research funding from Seqirus. The funding is related to influenza vaccination in Italy and thus not related to this manuscript. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)