In a context of increasingly necessary energy transition, precise modelling of profiles for low-voltage (LV) network consumers is crucial to enhance hosting capacity. Typically, load curves for these consumers are estimated through measurement campaigns conducted by Distribution System Operators (DSO) for a representative subset of customers or through the aggregation of load curves from household appliances within a residence. With the instrumentation of smart meters becoming more common, a new approach to modelling profiles for residential customers is proposed to make the most of the measurements from these meters. The disaggregation model estimates the load profile of customers on a low-voltage network by disaggregating the load curve measured at the secondary substation level. By utilizing only the maximum power measured by Linky smart meters, along with the load curve of the secondary substation, this model can estimate the daily profile of customers. For 48 secondary substations in our dataset, the model obtained an average symmetric mean average percentage error (SMAPE) error of 4.91% in reconstructing the load curve of the secondary substation from the curves disaggregated by the model. This methodology can allow the estimation of the daily consumption behaviors of the low-voltage customers. In this way, we can safely envision solutions that enhance the grid hosting capacity.

Bacterial collections are invaluable tools for microbiologists. However, their practical use is compromised by imprecise taxonomical assignation of bacterial strains. This is particularly true for soft rotting plant pathogens of the Pectobacterium genus. To solve this difficulty, we analyzed the taxonomic status of 265 Pectobacterium strains deposited at CIRM-CFBP collection from 1944 to 2020. This collection gathered Pectobacterium strains isolated in 27 countries from 32 plant species representing 17 botanical families or from non-host environments. MLSA approach completed by genomic analysis of 15 strains was performed to update the taxonomic status of these 265 strains. Results showed that the CIRM-CFBP Pectobacterium collection harboured at least one strain of each species to the exception of P. polonicum. Yet, 6 strains could not be assigned to any of the described species and may represent at least two new species. Surprisingly, the P. versatile species, recently described in 2019, is the most prevalent species among CIRM-CFBP strains. Analysis of P. versatile strains revealed that this species is endemic all over the world on various host plants and environments. At the opposite, other species gathered strains isolated from only one botanical family or exclusively from fresh water environment. Our work also revealed new host plants for several Pectobacterium spp.

Cyanobacteria are photosynthetic microorganisms that colonize diverse environments worldwide, ranging from ocean to freshwaters, soils, and extreme environments. Their adaptation capacities and the diversity of natural products (molecules, metabolites, or compounds) that they synthesize support the cyanobacterial success for the colonization of their respective ecological niches. Although cyanobacteria are well-known for their toxin production and their relative deleterious consequences, they also produce a large variety of molecules that exhibit beneficial properties with high potential for various fields of application (e.g., synthetic analog of the dolastatin 10 used against Hodgkin lymphoma). The present review specially focuses on the beneficial activities of cyanobacterial molecules described so far. Based on an analysis of 670 papers, it appears that more than 90 genera of cyanobacteria have been found to produce compounds with potential beneficial activities, most of them belonging to the orders Oscillatoriales, Nostocales Chroococcales, and Synechococcales. The rest of the cyanobacterial orders (i.e., Pleurocapsales, Chroococcidiopsales, and Gloeobacterales) remain poorly explored in terms of their molecular diversity and relative bioactivity. The diverse cyanobacterial molecules presenting beneficial bioactivities belong to 10 different chemical classes (alkaloids, depsipeptides, lipopeptides, macrolides/lactones, peptides, terpenes, polysaccharides, lipids, polyketides, and others) that exhibit 14 major kinds of bioactivity. However, no direct relation between the chemical class and the bioactivity of these molecules has been demonstrated. We further selected and specifically described 50 molecule families according to their specific bioactivities and their potential uses in pharmacology, cosmetology, agriculture, or other specific fields of interest. This up-to-date review takes advantage of the recent progresses in genome sequencing and biosynthetic pathway elucidation, and presents new perspectives for the rational discovery of new cyanobacterial metabolites with beneficial bioactivity.

Cyanobacteria are microorganisms able to adapt to a wide variety of environmental conditions and abiotic stresses. They produce a very large number of metabolites that can participate in the adaptation of cyanobacteria to a large range of resources such as light, temperature, or nutrient. The metabolites variation is one way to understand the physiological status and adaptation of cells. In this study, we aim to understand how the diversity and the dynamics of the whole metabolome is dependent of the growth phases and under control of abiotic factors (e.g. light intensity and temperature). The cyanobacteria Aliinostoc sp. PMC 882.14 was selected for its large number of biosynthetic gene clusters. Metabolomes were analyzed by using mass spectrometry (qTOF-MS/MS) combined with untargeted analysis to investigate the metabolite dynamics. Significant variations were characterized between exponential and stationary phases, whatever the culture conditions (“control”, “higher light”, or “higher temperature”). ”Higher light” and “higher temperature” favored the synthesis of metabolites belonging to the same molecular families. Among highly regulated metabolites, we observe the presence of mycosporine-like amino acids (MAAs), and various variants of somamides, microginins, and microviridins. Through Aliinostoc sp. PMC 882.14, this study shows the importance of knowing the physiological state of cyanobacteria for comparative global metabolomics and questions the regulation processes involve into metabolite families production. Our results also open up new perspectives in the context of the production of targeted bioactive metabolites.

Human milk is recommended for feeding preterm infant. Yet the potential impact of specific breast-milk lipid components on the initial growth rate of very-preterm infants has received scant attention. The current pilot study aims to determine whether breast-milk lipidome had any impact on the early growth pattern of preterm infants fed their own mother’s milk. A prospective monocentric observational birth cohort was established, enrolling 147 preterm infants, who received their own mother’s breast-milk throughout hospital stay. Among that cohort, infants who experienced slow (n=15) or fast (n=11) growth were selected, based on the change in their weight Z-score between birth and hospital discharge (-1.54± 0.42 and -0.48± 0.19 Z-score, respectively). Liquid chromatography-high resolution-mass spectrometry was used to obtain lipidomic signatures in breast-milk. Multivariate analyses made it possible to identify breast-milk lipid species that allowed clear-cut discrimination between the 2 infants’ groups. Validation of the selected biomarkers was performed by means of various multidimensional statistical techniques, false-discovery rate and ROC curve computation. Breast-milk associated with fast growth contained more medium chain-saturated fatty acid and -sphingomyelin, dihomo-γ-linolenic acid (DGLA)-containing phosphethanolamine, and less oleic acid-containing triglyceride and DGLA-oxylipin. Their predictive ability of preterm early-growth rate was validated in presence of confounding clinical factors.

Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neurological disorder, defined by progressive deterioration of the peripheral nerves. Clinical manifestations of CMT mutations are typically limited to peripheral neurons, the longest cells in the body. Currently, mutations in at least 80 different genes are associated with CMT and new mutations are regularly being discovered. A large portion of the proteins mutated in axonal CMT have documented roles in mitochondrial mobility. This suggests that trafficking defects may be a common underlying mechanism in CMT. This review will focus on the potential role of altered mitochondrial mobility in the pathogenesis of axonal CMT, highlighting the challenges and opportunities to this “impaired mobility” model of the disease.

Africa’s water needs are often supported by eutrophic waterbodies dominated by cyanobacteria posing health threats to riparian populations from cyanotoxins, and Lake Victoria is no exception. In two embayments of the lake (Murchison Bay and Napoleon Gulf), cyanobacterial surveys were conducted to characterize the dynamics of cyanotoxins in lake water and water treatment plants. Forty-six cyanobacterial taxa were recorded and out of these 14 were considered potentially toxigenic (i.e., from the genera Dolichospermum, Microcystis, Oscillatoria, Pseudanabaena and Raphidiopsis). A higher concentration (ranging from 5-10 µg MC-LR equiv. L-1) of microcystins (MCs) was detected in Murchison Bay compared to Napoleon Gulf, with a declining gradient from the inshore (max. 15 µg MC-LR equiv. L-1) to the open lake. In Murchison Bay, an increase either in Microcystis sp. biovolume and MC was observed over the last two decades. Despite high cell densities of toxigenic Microcystis and high MC concentrations, the water treatment plant in Murchison Bay efficiently removed the cyanobacterial biomass, intracellular and dissolved MC to below the lifetime guideline value for exposure via drinking water (< 1.0 µg MC-LR equiv. L-1). Thus, the potential health threats stem from the consumption of untreated water and recreational activities, along the shores of the lake embayments. MC concentrations were predicted from Microcystis cell numbers regulated by environmental factors such as solar radiation, wind speed in the N-S direction and turbidity. Thus, an early warning through microscopical counting of Microcystis cell numbers is proposed to better manage health risks from toxigenic cyanobacteria in Lake Victoria.

Cyanobacteria constitute pioneer colonizer of specific environments whom settlement in new biotopes precedes the establishment of composite microbial consortia. Some heterotrophic bacteria constitute cyanobacterial partners that are considered as their cyanosphere, being potentially involved in mutualistic relationships through exchange and recycling of key nutrients, and sharing of common goods. Several non-axenic cyanobacterial strains have been recently isolated along with their associated cyanosphere from the thermal mud of Balaruc-les-Bains (France) and the biofilms of the retention basin where they develop. The community structure and relationships among members of the isolated cyanobacterial strains were characterized using a metagenomic approach combined with taxonomic and microscopic description of the microbial consortia. Results provide insights into the potential role and metabolic capabilities of microorganisms of thermal mud-associated cyanobacterial biofilms. Thus, the physical proximity, host-specificity and complimentary functions advocate for their complementarity between cyanobacteria and their associated microbiota. Besides these findings, our results also highlight the great influence of the reference protein database chosen when performing functional annotation of the metagenomes from organisms of the cyanosphere and the difficulty of selecting one unique database that appropriately cover both autotroph and heterotroph metabolic specificities.

Charcot–Marie–Tooth disease (CMT) and associated neuropathies constitute the most predominant genetically transmitted neuromuscular conditions; however, effective pharmacological treatments remain elusive. The extensive genetic heterogeneity of CMT, which impacts the peripheral nerves and results in a lifelong disability, presents a significant barrier to the development of comprehensive treatments. An estimated 100 loci within the human genome are linked to various forms of CMT and its related inherited neuropathies. This review delves into prospective therapeutic strategies used for the most frequently encountered CMT variants, namely CMT1A, CMT1B, CMTX1, and CMT2A. Compounds such as PXT3003, which are currently under clinical and preclinical investigation, and a broad array of therapeutic agents and their corresponding mechanisms have been discussed in this review. Furthermore, the progress in established gene therapy techniques, including gene replacement via viral vectors, exon skipping using antisense oligonucleotides, splicing modification, and gene knockdown, has been appraised. Each of these gene therapies has the potential for substantial advancements in future research.

Background: The Balaruc-les-Bains’ thermal mud was found to be colonized predominantly by microorganisms, with cyanobacteria constituting the primary organism in the microbial biofilm observed on the mud surface. The success of cyanobacteria in colonizing this specific ecological niche can be explained in part by their taxa-specific adaptation capacities, and also the diversity of bioactive natural products that they synthesize. This array of components has physiological and ecological properties that may be exploited for various applications.

The bacterial wilt pathogen, first known as Bacillus solanacearum, has undergone numerous taxonomic changes since its first description in 1896. The history and significance of this pathogen is covered in this review with an emphasis on the advances in technology that were used to support each reclassification that finally led to the current separation of Ralstonia solanacearum into three genomic species. Frequent name changes occurred as methodology transitioned from phenotypic, biochemical, and molecular studies, to genomics and functional genomics. The diversity, wide host range and geographical distribution of R. solanacearum has resulted in its inclusion in a “species complex” as genomic analyses of elucidated phylogenetic relationships among strains. Current advances in phylogenetics and functional genomics now open new avenues for research into the epidemiology and control of the devastating bacterial wilt disease.

In this work we introduce an end-to-end multi-modal neural network to segment the Gross Tumor Volume (GTV) from 3D-CBCT’s during radiotherapy. We improve the tumor segmentation by using a U-net which takes additional information such as the tumor mask generated at the planning phase along with the CBCT volume. The mask contains relevant information about the tumor’s location and can guide the model to use this knowledge appropriately to give a better prediction. This technique could become an alternative to produce segmentation masks of GTV in CBCT automatically during radiotherapy as in the traditional RT-pipeline, they are not segmented. We have evaluated our model on a dataset of 82 patients who have undergone radiotherapy. We compare the results of registered target volumes from planning CT as mask seed with 2 different types of multi-modal architectures. Our model shows a DSC of 0.706±0.002 with Late Fusion and 0.702±0.015 with Early Fusion using the GTV Mask. The performance of the two models on this mask is similar, so we perform further experiments with different types of masks which suggest that Late Fusion model produces a better segmentation of the tumor than the Early Fusion model. We also provide an ablation study consisting of a single modality U-net and a metric based on the Planning CT mask registration. It indicates a clear advantage of using our model to produce segmentation for this type of imaging.

Abstract: Age-related macular degeneration (AMD) is the leading cause of central blindness in developed countries. It affects people mainly over the age of 50 years. It is a disease of the macula, an area of the retina responsible for sharp central vision. It particularly affects the Bruch’s membrane (BM); a layer in the retina that acts as the basement upon which retinal pigment epithelial cells (RPE) attach and survive. The pathology of AMD is not fully understood, but age is considered the main risk factor. There are two forms; nonexudative, leading to the end-stage of the disease, called nonexudative (or dry) AMD (90% of cases) where fatty deposits called drusen form under the RPE on top of the BM lifting off the RPE, and neovascular (or wet) AMD (10% of cases) where abnormal new blood vessels grow and push through the BM, bleeding in and disrupting the RPE. Neovascular AMD is well controlled with regular antiangiogenic drug injections of anti-vascular endothelial growth factor (anti-VEGF) into the eye, whereas there is no current treatment for nonexudative AMD. Many research groups across the world are working on a treatment for nonexudative AMD. This review discusses the research currently being conducted including cell therapies, development of cell transplantation membranes, targeting other disease structures in affected retina (i.e. drusen), and drug delivery to the retina using nanoparticles. Finally, we include our research contributing to the field; developing a bioactive membrane intended to function two-fold: target diseased structures and transplant healthy RPE to the desired area.

Capsaicin, a lipophilic, volatile compound, is responsible for the pungent properties of chili peppers. In recent years, a significant increase in investigations into its properties has allowed the production of new formulations and the development of tools with biotechnological, diagnostic, and potential therapeutic applications. In this way, the possible clinical application of such compound is expanding every year. This opinion article aims to provide a synthesis of recent findings regarding the mechanisms by which capsaicin participates in the control of non-communicable diseases such as obesity, diabetes, and dyslipidemia. This opinion review also discusses the recent findings and clinical studies of the use of capsaicin in body weight control.

The aim of this study was to develop a basic model to predict enteric methane emission from dairy cows and to update operational calculations for the national inventory in Norway. Basic models were developed using a database with 63 treatment means from 19 studies. The database included records for enteric CH4 production (MJ/day), dry matter intake (DMI), and dietary nutrient composition. The basic models were evaluated against an external database (n=36, from ten studies) along with other extant models. When evaluated by low root mean square prediction errors and high concordance correlation coefficients, the developed basic models that included DMI, dietary concentrations of fatty acids and neutral detergent fiber performed slightly better in predicting CH4 emissions than extant models. In order to propose country-specific values for the CH4 conversion factor Ym (% of gross energy intake partitioned into CH4) and thus to carry out the national inventory for Norway, the existing operational model was updated for the prediction of Ym over a wide range of feeding situations using energy corrected milk and dietary concentrate share as predictor variables. Input values of Ym were updated based on the results from the basic models. The predicted Ym ranged from 6.22 to 6.72%. In conclusion, the prediction of CH4 production from dairy cows was improved with the help of newly published data, which enabled an update of the operational model for calculating the national inventory of CH4 in Norway.

In recent years, it has become common for individuals to juggle employment and unpaid care work. This is just as true for the England-based academic workforce, our focus in this article. We discuss how, in the context of English HE, support for carers is enacted and negotiated through policies and practices of care. Our focus on academics with a diverse range of caring responsibilities is unusual insofar as the literature on care in academia is overwhelmingly concerned with parents, usually mothers. The article is informed primarily by critical and post-structuralist feminist perspectives. We draw on a corpus of 47 interviews conducted with academics representing a broad range of caring responsibilities, subjects, and positions. A thematic analysis reveals how carers’ relationship with the provision and policies of care support at institutional level is characterised by ambiguity. On the one hand, participants approve of societal and institutional policy support for carers. On the other hand, they are often reluctant to position themselves as the beneficiary of such policies, expressing instead a general preference for support from outside the workplace or for workplace-based inter-individual and informal care arrangements. This resistance is particularly noticeable in the case of participants with caring responsibilities other than the parenting of healthy, able-bodied children and of those whose gender, class, racial, or sexual identity do not conform with the figure of the ‘ideal academic’, contributing to their othering in the academic realm. These findings have significant implications for policies supporting carers, pointing to the need for greater visibility and recognition of caring responsibilities in academia, especially in terms of their diverse identities.

The diagnosis and treatment of autoimmune diseases are major challenges. Their signs, symptoms, and their clinical severity change throughout the course of the disease. The available treatments for these conditions do not result in complete remission, and their long-term use generates several side effects. The main challenges in this field are the development of more sensitive diagnostic tools, and effective treatments. Studies in patients and animal models reported alterations in monocyte phenotype, activation, and function. These cells play an essential role in the pathogenesis of chronic inflammatory states and have become a target for extracorporeal monitoring and specific intervention. Nanoparticles (NPs) are ultrafine particles that can be used as contrast agents in diagnostic imaging techniques to detect specific cells in inflammatory infiltrates in tissues that are not easily accessible by biopsy. In addition, NPs can be designed to deliver drugs to a cell population or tissue. This review describes several experimental pieces of evidence demonstrating that monocytes and macrophages can specifically uptake various types of NPs, thus becoming detectable in vivo by magnetic resonance imaging and susceptible to be modulated by therapeutic agents. Hence, nanoparticles targeting mononuclear phagocytes represent promising tools for diagnosing and treatment.

The expression "Follow the water" is used in order to recognize inside the universe, life as it exists on Earth. It is shown here that the expression "Follow the water in its high-subcritical state" can be used in order to recognize the components of life which form prior to the emergence of life. This specific state of water leaves signatures inside the minerals which are produced during high-subcritical water/rock interaction.

During the last years, the increasing evidence of dietary antioxidant compounds and reducing chronic diseases and the relationship between diet and health have promoted an important innovation on the baked product sector, aiming at healthier formulations. This study aims to develop a tool based on mathematical models to predict baked goods total antioxidant capacity (TAC). The high variability of antioxidant properties of flours based on the aspects related to type of grains, varieties, proximal composition and processing, among others, makes very difficult to innovate on food product development without specific analysis. Using Total phenol content (TP), Oxygen radical absorbance capacity (ORAC) and Ferric reducing antioxidant power assay (FRAP) as proxies of antioxidant capacity. Three Bayesian-type models are proposed based on a double exponential parameterised curve that reflects the initial decrease and subsequent increase as a consequence of the observed processes of degradation and generation, respectively, of the antioxidant compounds. Once the values of the main parameters of each curve have been determined, support vector machines (SVR) with exponential kernel were used to predict, based on the temperature and duration of baking as well as the values of proteins and fibers of each native grain, the values of TAC during the baking time.

Tourism is the main economic sector in the Balearic Islands (Spain) and hotel housekeepers (HHs) are a large occupational group, in which stress is becoming a major issue. This study aims at exploring in-depth factors perceived as stressors by HHs and key-informants, and their effects on work-life balance (WLB). A qualitative design with phenomenological approach was used, conducting six focus groups with 34 HHs and 10 individual interviews with key-informants. Results were analyzed adopting the job demands-resources model and a gender perspective. High demands –e.g work overload, time pressure, physical burden...-, lack of enough resources and little control –derived from role conflict, unexpected events...- were the most important factors explaining HHs’ stress. Additionally, this imbalance was perceived as leading to health problems –mainly musculoskeletal disorders-. Working schedule was mentioned as a facilitator to WLB, whereas an imbalance between job demands and resources led to work-home conflict –preventing them from enjoying leisure time-. Multiple roles at work and at home increased their stress. HHs experienced their job as invisible and unrecognised. Regarding practical implications, our recommendations for hotel organization include reducing workload and increasing resources, which would improve the job demands-resource balance, diminish negative mental and physical outcomes and improve WLB.

Anthropomorphism is a natural tendency in humans, but it is also influenced by many characteristics of the observer (the human) and the observed entity (here, the animal species). This study asked participants to complete an online questionnaire about three videos showing epimeletic behaviours in three animal species. In the videos, an individual (a sparrow, an elephant and a macaque, respectively) displayed behaviours towards an inanimate conspecific that suddenly regained consciousness at the end of the footage. A fourth video showed a robot dog being kicked by an engineer to demonstrate its stability. Each video was followed by a series of questions designed to evaluate the degree of anthropomorphism of participants, from mentaphobia (no attribution of intentions and beliefs, whatever the animal species) to full anthropomorphism (full attribution of intentions and beliefs by animals, to the same extent as in humans) and to measure how far the participants had correctly assessed each situation in terms of biological reality (current scientific knowledge of each species). There is a negative correlation (about 61%) between the mental states attributed to animals by humans to animals and the real capability of animals. The heterogeneity of responses proved that humans display different forms of anthropomorphism, from rejecting all emotional or intentional states in animals to considering animals to show the same intentions as humans. However, the scores participants attributed to animals differed according to the species shown in the video and to human sociodemographic characteristics. Understanding the potential usefulness of these factors can lead to better relationships with animals and encourage a positive view of human-robot interactions. Indeed, reflective or critical anthropomorphism can increase our humanity.

In this study, we asked participants to answer an online questionnaire about videos showing animal epimeletic behaviours: an individual (a sparrow, an elephant and a macaque) displayed behaviours towards an inanimate conspecific who suddenly got back to conscious at the end of the footage. A fourth video showed a dog-robot kicked by an engineer to demonstrate its stability. After each video, questions were asked to score the degree of anthropomorphism of participants, from mentophobia (no attribution whatever the species) to full anthropomorphism and to measure how close participants are to biological reality (actual scientific knowledge). A first important result is that there is a negative correlation (about 61%) between the anthropomorphism score (AS) and the biological reality one (BRS) showing a wrong statement. The heterogeneity of responses proved that all levels of anthropomorphism are covered from mentaphobia to full anthropomorphism. However, the scores participants attributed to animals differ according to the species shown in the video and to human characteristics. Understanding how one can play with these factors can conduct to better relationships with animals as encourage human-robot interactions. Finally, such reflective anthropomorphism can lead to an increase of human empathy and sociality, finally increasing our humanity.

: Healthcare workers are affected by mental health issues, burnout and turnover, and this burden is even greater during epidemics and pandemics, such as COVID-19. The purpose of this research is to provide an overview of the measures introduced or supported in the institutions of Quebec’s health and social services network during the COVID-19 pandemic with the aim of protecting healthcare workers’ mental health. An online questionnaire survey was administered in 2021 among human resources department personnel in health and social services network institutions involved in workplace mental health in Quebec. A total of 223 key informants representing 31 of the 34 public health and social services institutions in the province of Quebec in Canada responded to the questionnaire. Measures that focus on the needs of staff, involve all levels of authority and the ones that provide flexibility, support and recognition at work were more successful, according to the advisors surveyed. Future research into whether the same measures are considered effective or ineffective outside of a pandemic context is needed.

Introduction: Intimate partner violence occurring during pregnancy has a similar prevalence as usual obstetrical disorders routinely screened for. Referenced publications insist on the importance of adequate screening but the proper course of action has yet to be defined. Aim of study: We qualitatively explored the different resources and concepts that emerge from the discourse of maternity staff across professions. Material and methods: We led a semi structured interview with professionals included following their involvement with preselected patients. Nine professionals provided a sample of 19 interviews. The data was analysed using IPA methodology. Results We highlight the investigative importance of navigating the patient’s initial demand or lack thereof and the baby’s importance within, mindful of mechanisms of maternal disqualification. Creating an atmosphere prone to patient empowerment was the final theme to emerge from the study as the most beneficial tactic both in the short and long term. Conclusion: HCPs need to enable patients’ trust on a personal and an institutional level. As well as empowering the patient in the moment and respecting their values and choices, HCPs also convey the stability of the institution that has to become a reference of refuge and assistance for patients from their pregnancy onwards.

Current cellular facts allow us to follow the link from chemical to biochemical metabolites, from the ancient to the modern world. In this context, the "RNA world" hypothesis proposes that early in the evolution of life, the ribozyme was responsible for the storage and transfer of genetic information and for the catalysis of biochemical reactions. Accordingly, the hammerhead ribozyme (HHR) and the hairpin ribozyme, belong to a family of endonucleolytic RNAs performing self-cleavage that might occur during replication. Furthermore, regarding the ultraconserved occurrence of HHR in several genomes of modern organisms (from mammals to small parasites and elsewhere), these small ribozymes have been regarded as living fossils of a primitive RNA world. They fold into 3D structures that generally require long-range intramolecular interactions to adopt the catalytically active conformation under specific physicochemical conditions. By studying viroids as plausible remains of ancient RNA, we recently demonstrated that they replicate in non-specific hosts, emphasizing their adaptability to different environments, which enhanced their survival probability over the ages. All these results exemplify ubiquitously features of life. Those are the versatility and efficiency of small RNAs, viroids and ribozymes, as well as their diversity and adaptability to various extreme conditions. All these traits must have originated in early life to generate novel RNA populations.

Wearable antennas are increasingly vital in modern healthcare, facilitating continuous monitoring and communication for medical purposes. These antennas are integrated into wearable devices, allowing for the transmission and reception of vital health data, such as heart rate, body temperature, and blood pressure, to medical professionals or monitoring systems in real time. This instantaneous data transmission enables timely interventions, thus improving the quality of healthcare services. This review aims to comprehensively synthesize recent research from reputable databases, focusing on the functionality and effectiveness of wearable antennas in medical applications. The primary objectives of each study were categorized, including antenna design and integration, the performance of medical wearable antenna technology, safety considerations in wearable antenna biomedicine, and the use of antennas in clinical applications and their impact. This synthesis provides valuable insights for researchers and practitioners aiming to develop and deploy wearable antennas in medical settings, ultimately enhancing healthcare delivery and patient outcomes.

Abstract: The broad clinical use of synthetic vascular grafts for vascular diseases is limited by their thrombogenicity and low patency rate, especially for vessels with a diameter inferior to 6 mm. Alternatives such as tissue-engineered blood grafts (TEBGs) have gained increasing interest. Among the different manufacturing approaches, 3D bioprinting presents numerous advantages and enables the fabrication of multi-scale, multi-material, and multicellular tissues with heterogeneous and functional intrinsic structures. Extrusion-, inkjet- and light-based 3D printing techniques have been used for the fabrication of TEBG out of hydrogels, cells, and/or solid polymers. This review discusses the state-of-the-art research on the use of 3D printing for TEBG with a focus on the biomaterials and deposition methods.

The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, mass spectrometry analyses must therefore interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct MHC I presentation but poor substrates for cross-presentation. This is an important caveat because cancer cells are poor antigen-presenting cells and the immune system therefore depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We therefore postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs represent an attractive strategy for cancer treatment.

The objective of this was to evaluate the effects of organic fertilization on biomass production in Urochloa spp. pastures, and the soil biological and physical properties in the Colombian Amazon region. Three pastures crops (Urochloa decumbens, Urochloa humidicola and Urochloa brizantha) with 5 years old were examined in a hill landscape. A randomized complete blocks design covering an area of 5005 m2, with 1 m separation between units to minimize edge effects. Highly significant differences in Urochloa spp. biomass production were observed before and after organic fertilization (i.e., initial time: 992.19±97.66 kg DM ha-1 vs. final time: 1920.94±155.44 kg DM ha-1 vs.), but not between different fertilization treatments. The interaction between the treatment and time was significant for total density (p=0.0300) and richness (p=0.0300) of soil macrofauna. Furthermore, the interaction between treatment and soil depth was significant for bulk density (p=0.0187). The linear mixed effects analysis showed that soil bulk density and penetration resistance were lower in 0 - 10 cm depth than that observed in 10 - 20 depth and 20 - 30 cm depth. Overall, the application of organic fertilizers had a significant and positive effect on Urochloa spp. forage biomass and on the physical and biological properties of soils that had historically been affected by extensive livestock farming in a deforested hill landscape in the Colombian Amazon region.

The importance of genome organization at the supranucleosomal scale in the control of gene expression is increasingly recognized today. In mammals, Topologically Associating Domains (TADs) and the active / inactive chromosomal compartments are two of the main nuclear structures that contribute to this organization level. However, recent works reviewed here indicate that, at specific loci, chromatin interactions with nuclear bodies could also be crucial to regulate genome functions, in particular transcription. They moreover suggest that these nuclear bodies are membrane-less organelles dynamically self-assembled and disassembled through mechanisms of phase separation. We have recently developed a novel genome-wide experimental method, High-salt Recovered Sequences sequencing (HRS-seq), which allows the identification of chromatin regions associated with large ribonucleoprotein (RNP) complexes and nuclear bodies. We argue that the physical nature of such RNP complexes and nuclear bodies appears to be central in their ability to promote efficient interactions between distant genomic regions. The development of novel experimental approaches, including our HRS-seq method, is opening new avenues to understand how self-assembly of phase separated nuclear bodies possibly contributes to mammalian genome organization and gene expression.

Acute myeloid leukaemia (AML) is characterized by the accumulation of undifferentiated blast cells in the bone marrow and blood. In most AMLs, relapse frequently occurs due to resistance to chemotherapy. Compelling research results indicate that drug resistance in cancer cells is highly dependent on the intracellular levels of reactive oxygen species (ROS). Modulating ROS levels is therefore a valuable strategy to overcome the chemotherapy resistance of leukemic cells. In this study, we evaluated the efficiency of diphenyleneiodonium (DPI), a well-known inhibitor of ROS production, in targeting AML cells. Results showed that although inhibiting cytoplasmic ROS production, DPI triggered an increase in the mitochondrial ROS levels caused by the disruption of the mitochondrial respiratory chain. We also demonstrated that DPI blocks the mitochondrial oxidative respiration (OxPhos) in a dose-dependent manner and that AML cells with high OxPhos status were highly sensitive to treatment with DPI, which synergizes with the chemotherapeutic agent cytarabine (Ara-C). Thus, our results suggest that targeting mitochondrial function by DPI might be exploited to target AML cells with high OxPhos status.

The pathogenesis of porcine circovirus type 2b (PCV2b) and swine influenza A virus (SwIV) during co-infection in swine respiratory cells is poorly understood. To elucidate the impact of PCV2b/SwIV co-infection, newborn porcine tracheal epithelial cells (NPTr) and immortalized porcine alveolar macrophages (iPAM 3D4/21) were co-infected with PCV2b and SwIV (H1N1 or H3N2 genotype). Viral replication, cell viability and cytokine mRNA expression were determined and compared between single-infected and co-infected cells. Finally, 3’mRNA sequencing was performed to identify the modulation of gene expression and cellular pathways in co-infected cells. It was found that PCV2b significantly decreased and improved SwIV replication, in co-infected NPTr and iPAM 3D4/21 cells respectively, compared to single infected cells. Interestingly, PCV2b/SwIV co-infection synergistically up-regulated IFN expression in NPTr cells whereas in iPAM 3D4/21 cells, PCV2b impaired the SwIV IFN induced response, both correlating with SwIV replication modulation. RNA-sequencing analyses revealed that the modulation of gene expression and enriched cellular pathways during PCV2b/SwIV H1N1 co-infection is regulated in a cell type-dependent-manner. This study revealed different outcomes of PCV2b/SwIV co-infection in porcine epithelial cells and macrophages and provides new insights on porcine viral co-infections pathogenesis.

Mutations in the SACS gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of Charcot-Marie-Tooth disease (CMT). This study aimed to identify SACS mutations in a Korean CMT cohort with cerebellar ataxia and spasticity. As a result, eight pathogenic SACS mutations in four families were identified as the underlying causes of these complex phenotypes. The prevalence of CMT families with SACS mutations was determined to be 0.3%. All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was done in four patients, and all had fatty replacements. Of note, they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without SACS mutations who had distal dominant fatty involvement. Therefore, these findings were considered a characteristic feature in CMT patients with SACS mutations. Although further studies with more cases are needed, our results highlight lower extremity MRI findings in CMT patients with SACS mutations and broaden the clinical spectrum. We suggest screening for SACS in recessive CMT patients with complex phenotypes of ataxia and spasticity.

During chronic liver injury, inflammation leads to liver fibrosis— particularly due to the activation of hepatic stellate cells (HSCs). However, the involvement of inflammatory cytokines in HSC activation and the relationship among different liver cells is unclear. To examine their interactions, many in vitro liver models are performed in organoid or spheroid culture with random 3D structure, complicating analysis. Herein, we demonstrated the hierarchical coculture of primary rat hepatocytes with non-parenchymal cells such as the human-derived HSC line (LX-2) and liver sinusoidal endothelial cell line (TMNK-1). The cocultured tissue had high usability with simple operation of separating solid and liquid phases with improved liver functions such as albumin production and hepatic cytochrome P450 3A4 activity. We also studied the effects of stimulation by both oxygen tension and the key pro-fibrogenic cytokine, transforming growth factor beta (TGF-β), on HSC activation. Gene expression analysis revealed that lower oxygen tension and TGF-β1 stimulation enhanced collagen type I and alpha-smooth muscle actin expression from LX-2 cells in the hierarchical coculture. Therefore, this hierarchical in vitro cocultured liver tissue could provide an improved platform as a disease model for elucidating the interactions of various liver cell types and biochemical signals in future liver fibrogenesis studies.

Health innovations are generally oriented on a techno-economic vision. In this perspective, technologies are seen as an end in themselves, and there is no arrangement between the technical and the social values of innovation. This vision prevails in sanitary crises, in which management is carried out based on the search for punctual, reactive, and technical solutions to remedy a specific problem without a systemic/holistic, sustainable, or proactive approach. This paper attempts to contribute to the literature on the epistemological orientation of innovations in the field of public health. Taking the Covid-19 and Ebola crises as examples, the primary objective is to show how innovation in health is oriented towards a techno-economic paradigm. Second, we propose a repositioning of public health innovation towards a social paradigm that will put more emphasis on the interaction between social and health dimensions in the perspective of social change.

Anthracnose stands as the primary obstacle to lupin cultivation, impeding development despite the considerable agronomic, ecological, and economic potential of such legume crops. This review explores recent efforts to unravel the complexities of anthracnose in domesticated lupins, focusing on both the plant perspective and the causative pathogenic agent, Colletotrichum lupini. Leveraging cutting-edge technologies has yielded crucial insights into various facets of this devastating disease, encompassing plant and pathogen biology, genetic and molecular regulations of the interaction, fungal diversity and population dynamics, and screening of plant genetic resources for anthracnose resistance. The lack of effective disease control measures, relying primarily on the use of disease-free seeds, highlights the need to develop anthracnose-resistant varieties. However, challenges arise from the intricacy of lupin's response to the disease, influenced by polygenic inheritance, in spite of loci with major effects, and environmental factors. The slow pace of genetic improvement underscores the need for more efficient breeding processes, including biotechnological approaches. This review offers a comprehensive overview of current progress and knowledge gaps, stressing the urgent need to further enhance understanding of C. lupini pathogenic mechanisms and lupin‘s resistance. Integrating advanced technologies and accelerated research efforts is paramount for achieving efficient disease management and sustainable lupin cultivation in the face of anthracnose challenges.

In this study, we propose an augmentation method for machine learning based on relabeling data in caregiving and nursing staff indoor localization with Bluetooth Low Energy (BLE) technology. Indoor localization is used to monitor staff to patient assistance in caregiving and to gain insights into workload management. However, improving accuracy is challenging when there is a limited amount of sensor data available for training. In this paper, we propose a data augmentation method to reuse the Received Signal Strength (RSS) from different sensors by relabeling to the sensors with less samples resolving data imbalance. Standard deviation and Kullback-Leibler divergence between minority and majority class are used to measure signal pattern to find matching sensors to relabel. By matching sensors between classes, two variation of relabeling are implemented specifically full and partial matching. The performance is evaluated using real world dataset we collected for five days in a nursing care facility installed with 25 BLE beacons. Random Forest model is utilized for location recognition, and performance is compared using the weighted F1-score to account for class imbalance. By increasing the sensor data with our proposed relabeling method for data augmentation, we achieved higher minority class F1-score as compared to augmentation with Random Sampling, Synthetic Minority Oversampling Technique (SMOTE) and Adaptive Synthetic Sampling (ADASYN). Our proposed method utilizes collected sensor data by leveraging majority class samples. Full matching demonstrated a 6 to 8% improvement from the original baseline overall weighted F1-score.

This study evaluates inequalities in the use of dental services according to place of birth before and after the economic crisis in Spain. A cross-sectional study was performed in the population aged 18 to 65 years in Spain. We used data from three Spanish National Health Surveys for years 2006 (before the crisis), 2014 and 2017 (after the crisis). Log-binomial regression was used to quantify the association between region of origin and use of dental care services before and after controlling for the selected covariates. In 2006, we found a greater probability of not using dental care services in immigrants from Asia (PR:1.36, 95% CI:1.10–1.67) and Africa (PR:1.16; 95% CI:1.05–1.28) compared to the natives. For 2014, the probability of not using dental care services was greater for all immigrants compared to the natives, with the greatest odds for those from Africa (PR:1.71; 95% CI:1.46–2.01) and Asia (PR:1.3; 95% CI:1.23–1. 47). The associations for 2017 were weaker in magnitude than the ones observed for 2014, although stronger than for 2006. This study suggests that the economic recovery did not have the same impact for natives and immigrants regardless of regions of origin, given the observed inequalities in use of dental services.

Abstract: This comprehensive review seeks to deepen our comprehension of the African plant Momordica balsamina L. by elucidating its therapeutically important molecules and micronutrient composition. Commonly referred to as the balsam apple, this plant species is extensively harnessed for its diverse therapeutic potentials across its various organs including leaves, fruits, roots, and stems. Numerous bioactive molecules have been isolated or identified within this plant, notably encompassing polyphenols, flavonoids, terpenes, and carotenoids. These compounds exhibit a wide array of biological activities, ranging from antioxidative, anti-inflammatory, anti-diabetic, anti-carcinogenic, to anti-malarial properties, among others. Furthermore, the leaves of Momordica balsamina L. stand out for their abundant micronutrients, proteins, and amino acids. This investigation aims to shed light not only on the botanical characteristics of the Momordica balsamina plant and its potential applications in traditional medicine, but also on its chemical composition, biological functionalities, and physicochemical attributes, thus accentuating its nutritional advantages. Nonetheless, an intriguing avenue presents itself for the exploration of strategies to conserve this species, delve deeper into its potential within the cosmetics industry, and innovate methodologies for the synthesis or biosynthesis of these bioactive molecules.

Understanding molecular mechanisms of neurological disorders is required for development of personalized medicine. When the diagnosis considers not only the disease symptoms, but also their molecular basis, the treatments tailored for individual patients may be suggested. The vitamins-responsive neurological disorders are induced by deficiencies in the vitamin-dependent processes. The deficiencies may occur due to genetic impairments of proteins whose functions are involved with the vitamins. This review considers the enzymes encoded by DHTKD1, PDK3 and PDXK genes, whose mutations are observed in patients with Charcot-Marie-Tooth (CMT) disease. The enzymes bind or produce the coenzyme forms of vitamins B1 (thiamine diphosphate, ThDP) and B6 (pyridoxal-5’-phosphate, PLP). Alleviation of such disorders by administration of the lacking vitamin or its derivative calls upon a better introduction of the mechanistic knowledge to medical diagnostics and therapies. Recent data on lower levels of the vitamin B3 derivative, NAD+, in the blood of patients with CMT disease, compared to the control subjects, are also considered in view of the NAD-dependent mechanisms of pathological axonal degeneration, suggesting therapeutic potential of vitamin B3. Thus, improved diagnostics of the underlying causes of the CMT disease may allow the patients with the vitamin-responsive disease forms to benefit from the administration of the vitamins B1, B3, B6, their natural derivatives or pharmacological forms.

The current focus on afforestation in climate policy runs the risk of compromising both longterm carbon storage and human adaptation. It also works against efforts to stem the tide of biodiversity loss. We outline why an emphasis on diverse, intact natural ecosystems—as opposed to tree plantations with fast-growing exotic species—will help nations deliver the goals of the Paris Agreement and much more.

The number of families sheltered in the Paris region (France) increased by a factor of 5 between 1999 and 2009. In 2013, a survey was performed on homeless families in order to characterize their living conditions, their health needs and the developmental problems in children. This random survey was conducted in 17 languages among homeless families sheltered in emergency centers for asylum-seekers, emergency housing centers, social rehabilitation centers and social hotels in the Paris region. The situation was particularly worrying regarding their food security. Indeed, only 14.0% of people were with food security, whereas 43.3% were with low food security and 9.8% very low food security (a situation where children are also affected). Stratified multivariate robust Poisson models showed that some characteristics can lead homeless families to be at higher risk of food insecurity and/or at higher risk of falling into very low food security, such as residential instability, single parenthood, having more than 3 children, depressive symptoms, housing in social hostels, difficult access to cheap or free food locally. These harmful situations are intolerable in such a wealthy region as the Paris region. They argue for a better detection of these families, a closer social follow-up and an increase in food aid.

Artificial neural networks are a powerful tool for managing data that is difficult to process and interpret. This paper presents the study of artificial neural networks for information processing generated by an optical encoder based on the polarization of light. A machine learning technique is proposed to train the neural networks, such that the system can predict with remarkable accuracy the angular position in which the rotating element of the neuro-encoder is located, based on information provided by light’s phase shifting arrangements. The proposed neural designs show excellent performance in small angular intervals, and a methodology is proposed to avoid losing this remarkable characteristic in measurements from 0 to 180o or even to 360o. The neuro-encoder is implemented in simulation stage to obtain performance results. This study can be useful to improve capabilities of resolvers or other polyphasic sensors.

Group B Streptococcus (GBS), a commensal in the body, causes a wide range of infectious diseases. The colonisation levels of GBS and its resistance profile to antibiotics provide important information useful for orienting prevention strategies. There is little data available on the subject with determination of resistance phenotypes in Cameroon. We therefore aimed to determine the prevalence of colonization, antibiotic resistance, including patterns of inducible resistance to clindamycin of GBS in Yaounde. To achieve this goal, a prospective cross-sectional study with an analytical component was carried out from the 28th June to the 29th August 2020 at the BIOSANTE laboratory and the Yaounde Gynaeco-Obstetrics and Paediatrics hospital. Vaginal swabs and urine were collected on 163 women. This samples were analysed using 5% defibrinated sheep blood agar and chocolate plus polyvitex agar. The isolates were identified using the morphology of the colony, Gram staining, haemolysis, catalase test and latex grouping test. Antibiotic susceptibility testing was done by disk diffusion method following the recommendations of the ACFSM 2019. The double disk diffusion method was used to identify isolates with clindamycin inducible resistance. Our data was analysed by the software SPSS version 2.1. The results obtained showed that the global prevalence of colonization by GBS was 37% (57/163), 40.35% in non-pregnant women and 59.65% in pregnant women. Pregnancy (P-value = 0.019) and gestational age (P-value = 0.025) constituted the risk factors of maternal colonization by GBS. In addition, the strains of GBS were resistant to all antibiotics tested. A D test showcased that 64.7% of GBS were resistant in a constitutive manner to clindamycin. We also note the presence of M phenotypes. As a whole, our results demonstrate that the rate of GBS colonization in this study was similar or higher than those in the previous report in Cameroon. All this indicates that attention should be paid to this bacterium in the monitoring of antimicrobial resistance and in the care of pregnant women and newborns.

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here we studied the effect of 12 weeks drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males with slightly higher adipocyte area values in both males and females under clozapine medication. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine medication. IR-ß expression changed sex-specifically in the clozapine medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-medicated females. Taken together, clozapine and haloperidol have a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined and probably in their effect on liver metabolism.

We report the treatment of a 21-year-old female Covid-19 patient by a novel combination of minocycline and a guanosine-restricted diet. Minocycline is an antibiotic with well documented broad spectrum anti-viral effects, including evidence of activity against SARS-CoV-2. Deprivation of guanosine has been documented as an effective anti-viral modality in vitro and in animal models, and specific in vitro activity against CoV-SARS-2 has been reported. The patient's symptoms resolved rapidly.

The Life Cycle Analysis (LCA) was used to assess the impact of biomethane plant of the “La Católica” in Pedregal-Majes-Arequipa farm, fed with cow manure and holding a production of 60 Nm3/day of purified biogas. Life cycle inventory, impact assessment and interpretation were performed. The functional unit established was 1 MJ of energy produced; the study was modeled with SimaPro software, Ecoinvent Database and ReCiPe Midpoint (H) impact assessment methodology, according to the impact categories of climate change and fossil resource depletion. The impact analysis was limited to the Well to Tank (WTT) approach, which involves feedstock transport, substrate mixed, anaerobic digestion, biogas purification, storage and injection of the fuel into transport vehicles. The digestion process generated the highest amount of CO2 emissions (1.79E-02 kg CO2 eq/MJ-biomethane) and the highest depletion of fossil resources (6.58E-03 kg oil eq/MJ-biomethane), compared to the other fuel production, due to energy consumption and transport infrastructure. Biomethane was then compared to fossil fuels, resulting in natural gas generating the least amount of CO2 emissions, followed by diesel and finally biomethane. For the fossil resource depletion category, biomethane presented the lowest amount of fossil fuel consumption (1.37E-02 kg oil eq/MJ-biomethane), followed by natural gas and diesel.

Genotypic testing is often recommended to improve the management of patients infected with human immunodeficiency virus (HIV). To help combat this major pandemic, next-generation sequencing (NGS) techniques are widely used to analyse resistance to antiretroviral drugs. In this study, we used a Vela Sentosa kit, which is usually used for the Ion Torrent personal genome machine (PGM) platform, to sequence HIV using the Illumina Miseq platform. After RNA extraction and reverse transcriptase-polymerase chain reaction (RT-PCR), minor modifications were applied to the Vela Sentosa kit to adapt it to Illumina Miseq platform. Analysis of the results showed the same mutations present in the samples using both sequencing platforms. The total number of reads varied from 185,069 to 752,343 and from 642,162 to 2,074,028 in the Ion Torrent PGM platform and the Illumina Miseq platform, respectively. The average depth was 21955 and 46856 for Ion Torrent PGM and Illumina Miseq platforms, respectively. The cost of sequencing a run of eight samples was closely similar between the two platforms (about 1 790 United States dollars [USD] for Illumina Miseq and about 1833 USD for Ion Torrent PGM platform). We have shown for the first time that it is possible to adapt and use the Vela Sentosa kit for the Illumina Miseq platform to obtain high quality results with a similar cost.

Nature-based solutions (NbS) are increasingly recognised for their potential to address both the climate and biodiversity crises. These outcomes are interdependent, and both rely on the capacity of NbS to support and enhance the health of an ecosystem: its biodiversity, the condition of its abiotic and biotic elements, and its capacity to function normally despite environmental change. However, while understanding of ecosystem health outcomes of nature-based interventions for climate change mitigation is growing, the outcomes of those implemented for adaptation remain poorly understood with evidence scattered across multiple disciplines. To address this, we conducted a systematic review of the outcomes of 109 nature-based interventions for climate change adaptation using 33 indicators of ecosystem health across eight broad categories (e.g. diversity, biomass, ecosystem functioning and population dynamics). We showed that 88% of interventions with positive outcomes for climate change adaptation also reported measurable benefits for ecosystem health. We also showed that interventions were associated with a 67% average increase in local species richness. All eight studies that reported benefits in terms of both climate change mitigation and adaptation also supported ecosystem health, leading to a triple win. However, there were also trade-offs, mainly for forest management and creation of novel ecosystems such as monoculture plantations of non-native species. Our review highlights two major limitations of research to date. First, only a limited selection of metrics are used to assess ecosystem health and these rarely include key aspects such as functional diversity and habitat connectivity. Second, taxonomic coverage is poor: 67% of outcomes assessed only plants and 57% did not distinguish between native and non-native species. Future research addressing these issues will allow the design and adaptive management of NbS to support healthy and resilient ecosystems, and thereby enhance their effectiveness for meeting both climate and biodiversity targets.

The German Constitutional Court’s climate verdict provides a re-interpretation of liberal- democratic core concepts and is highly relevant for liberal constitutional law in general – including EU and international law. The verdict accepts human rights as intertemporal and globally applicable; it applies the precautionary principle to these rights and frees them from the misleading causality debate. However, the court fails to address the most important violations of human rights, and it categorised climate policy as a greater threat to freedom than climate change. And the court does not make it clear that the Paris 1.5-degree limit implies a radically smaller carbon budget. Furthermore, little attention has so far been paid to the fact that the ruling implies an obligation for more EU climate protection, especially since most emissions are regulated supranationally. To be effective, the EU emissions trading system demands a reform, which should go well beyond the existing EU proposals to enable societal transformation to sustainability.

The morphology and maturation process of gonads of 70 Burmeister´s porpoises, with body lengths ranging 135–183 cm (n= 34 females) and 64.5-182 cm (n= 36 males) were described. Samples were collected in six ports of central and northern Peru in 1987-1999. In the field, females were classified as immature, mature (resting, lactating, pregnant) and males as immature, pubescent and mature based on, respectively, the presence of ovarian corpora and the relative quantity of semen in cut epididymides. The ovaries of P. spinipinnis are ovoid or bean-shaped and flattened, with corpora modifying surface appearance. In the laboratory, ovaries were examined macro- and microscopically, measured, weighed and sliced in 1-3 mm sections. The number of corpora ovarica (lutea, albicantia, atretica) found in each ovary as well as their macroscopic and microscopic characteristics were documented in some detail. The follicles, their oocytes and nucleus were measured. Follicular development in P. spinipinnis is predominantly left-sided, but occurs in both ovaries in 16.3% of females, mainly in those with numerous corpora. Macroscopically, several corpora atretica with luteinization had characteristics similar to those of corpora albicantia, making microscopic determination essential. Inconclusive evidence of recent ovulation was found in January. Two of three immature females showed good follicular development in March and April. The body length at 50% sexual maturity in females was estimated at 152.7 cm. There was no evidence of reproductive senescence. The testes of P. spinipinnis are elongated and cylindrical. Of the 36 males examined macroscopically, 7 were immature, 5 pubescent and 24 mature. The histological analysis determining the presence and abundance of Sertoli cells, spermatogonia, spermatocytes, spermatids and spermatozoa, the relative amount of interstitial tissue, the elongation and mean diameter of the seminiferous tubules and the relative size of the lumen allowed to confidently determine sexual maturity status. The field evaluation of maturity based on the presence of sperm in the epididymides is a useful but, in 8.3% of cases, not exact method. For males the body length at 50% sexual maturity was estimated at 157 cm. No histological evidence of male reproductive seasonality was found. Spermatogenesis was perceptible year-round and tubule diameters had non-specific variations for each month.

Wellness tourism is a growing segment that destinations can rely on to increase tourism flows and revive underdeveloped rural areas. This study elicits tourists' preferences for wellness tourism products and the redevelopment of a wellness destination in a depopulated rural area. The re-search included 595 participants in Central Greece using on-site, face-to-face surveys. The survey data was analyzed using a two-step process. First, conjoint analysis was applied to determine the combination of wellness tourism product attributes that maximize visitors’ utility. In the second step, we elicited visitors' willingness to pay (WTP) for improvements in tourism product attributes using the contingent valuation method. Findings indicate that the combination of attributes that maximizes the preference structure of respondents includes time of visit from September to Oc-tober, duration of visit from 1 to 7 days, wellness tourism as the primary purpose of the visit, and wellness activities that contain both physical activities and training as well as spiritual and emo-tional enhancement. Using binary logistic regression, the analysis indicates that respondents are willing to pay 47.33€ per visit on average further to develop wellness tourism products in the study area. Empirical results confirmed that sustainability issues, quality, and entrepreneurship factors positively impact visitors' WTP for revitalizing wellness products. In contrast, a longer duration of stay in the area and respondents' age negatively impact their WTP. These findings suggest that structuring a customer-driven tourism product will enhance the rural destination's efforts to attract high-yield visitors and advance the rural economy. Furthermore, practical im-plications reveal that Destination Management Organizations will benefit from research results to foster targeted management plans.

Respiratory syncytial virus (RSV) RNA synthesis takes place in cytoplasmic viral factories also called inclusion bodies (IBs), which are membrane-less organelles concentrating the viral RNA polymerase complex. IBs assembly is driven by liquid-liquid phase separation promoted by interactions between the viral nucleoprotein N and the phosphoprotein P. We recently demonstrated that cyclopamine (CPM) inhibits RSV multiplication by disorganizing and hardening IBs. Although a single mutation in the viral transcription factor M2-1 induced resistance to CPM, the mechanism of action of CPM still remains to be characterized. Here, using FRAP experiments on reconstituted pseudo-IBs both in cellula and in vitro, we first demonstrated that CPM activity depends on the presence of M2-1 together with N and P. We show that CPM impairs the competition between P and RNA binding to M2-1. As mutations on both P and M2-1 induced resistance against CPM activity, we suggest that CPM may affect the dynamics of the M2-1−P interaction, thereby affecting the relative mobility of proteins contained in RSV IBs. Overall, our results reveal that stabilizing viral protein-protein interactions is an attractive new antiviral approach. They pave the way for the rational chemical optimization of new specific anti-RSV molecules.

Dog Assisted Therapy is hypothesized to lower stress in children with Autism Spectrum Disorder (ASD) and children with Down Syndrome (DS), which may be visible on a physiological level. In this study, we measured Heart Rate Variability (HRV) and salivary cortisol of 20 children with DS or ASD at the beginning and end of 6 weekly sessions of Dog-Assisted Therapy. We found a decrease of cortisol levels during single sessions, but no overall effect after 6 sessions (6 weeks). The effect of Dog Assisted Therapy on the increase of HRV could not be confirmed. This study is one of the first to use physiological measurements to test the effects of DAT.

Objective: In this pilot study, we described the gross motor development of infants aged 4 to 24 months with congenital heart disease (CHD) and assessed through a systematic develop­mental screening programme, with individualised motor interventions. Methods: Thirty infants who had cardiac repair underwent gross motor evaluations using the AIMS at 4 months, and the Bayley-III at 12 and 24 months. Results: Based on AIMS, 80% of 4-month-old infants had a delay in gross motor development and required physical therapy. Gross motor abilities significantly improved by 24 months. Infants who benefited from regular physiotherapy tended to show better improvement in motor scores. Conclusion: Our study highlights the importance of early motor screening in infants with CHD and suggests a potential benefit of early physical therapy in those at-risk. Further research is needed to assess the effectiveness of systematic developmental screening and individualized inter­vention programmes at identifying at risk patients, and their impact on developmental outcomes.

Cuba is struggling with a growing environmental problem: the uncontrolled spread of the allochthonous weed species marabou (Dichrostachys cinerea) throughout the country. Over the last 70 years, marabou has become a formidable invasive species that poses a threat to Cuban biodiversity and agricultural productivity. In this paper, we present a free and affordable method for regularly mapping the spatial distribution of the marabou based on the Google Earth Engine platform and ecological surveys. To test its accuracy, we develop an 18-year analysis (2000–2018) of marabou dynamics using the Valle de los Ingenios, a Cuban UNESCO World Heritage Site, as an experimental model. Our spatial analysis reveals clear patterns of marabou distribution and highlights areas of concentrated growth. Temporal trends illustrate the dynamic nature of the species, identifying periods of expansion and decline. In addition, our system is able to detect specific, large-scale human interventions against the marabou plague in the area. The results highlight the urgent need for remedial strategies to maintain the fragile balance in the region.

Cerebral palsy (CP) is the most common movement disorder in children with a prevalence rang-ing from 1.5 to 4 per 1000 live births. CP is caused by a non-progressive lesion of the developing brain, leading to progressive alterations of the musculoskeletal system, including spasticity, often leading to the development of fixed contractures, necessitating tendon lengthening surgery. Total RNA-sequencing analysis was performed on semitendinosus tendons from diplegic and tetraple-gic CP patients subjected to tendon lengthening surgery compared to control patients undergoing anterior cruciate ligament reconstructive surgery. Tetraplegic CP patients showed increased ex-pression of genes implicated in collagen synthesis and extracellular matrix (ECM) turnover, while only minor changes were observed in diplegic CP patients. In addition, tendons from tetra-plegic CP patients showed an enrichment for upregulated genes involved in vesicle-mediated transport and downregulated genes involved in cytokine and apoptotic signaling. Overall, our results indicate increased ECM turnover with increased net synthesis of collagen in tetraplegic CP patients without activation of inflammatory and apoptotic pathways similar to observations in athletes where ECM remodeling results in increased tendon stiffness and tensile strength. Never-theless, the resulting increased tendon stiffness is an important issue in clinical practice, where surgery is often required to restore joint mobility.

The pre-pregnancy BMI and the gestational weight gain are two important determinants of pregnancy outcomes. The aim of this study was to determine obstetric outcomes associated with insufficient gestational weight gain in women with a pre-pregnancy BMI < 18.5 kg/m2. This study was based on observational routinely-collected data from a University Hospital Maternity. The participants were allocated to the group sufficient or insufficient gestational weight gain: ≥ 12.5 kg and < 12.5 kg respectively. Primary outcomes were the adjusted birth weight in percentiles (%) and the proportion of SGA newborns. Secondary outcomes were obstetric and perinatal outcomes. A total of 135 participants with a median age of 28±8 years were included. The adjusted birth weight in percentiles was significantly lower in the insufficient gestational weight gain group (27.2±45.4 vs 42.6±48.8 %; P<0.001). Moreover, the insufficient gestational weight gain is associated with a higher risk of SGA (28.1% vs 11.3%; P=0.017). Our study also showed increased risks of premature rupture of membranes, anaemia and intrauterine growth restriction in women with an insufficient weight gain. Future studies should explore the risk factors associated with insufficient weight gain, in order to develop specific care for underweight pregnant women.

Recent reports suggest that dysregulation of lipid metabolism is a key feature of the most invasive cancers. To identify potential biomarkers of tumor aggressiveness, we compared the proteomes of two experimental models of malignant mesothelioma in rats exhibiting different invasive properties. Quantitative changes between the most invasive, M5-T1, versus the least invasive, F4-T2, first led to a list of 424 proteins. A second step, cross-comparing this list with 433 proteins distinguishing invasive vs non-invasive tumors, led to identifying 88 proteins that specifically increased and 157 that decreased, respectively, characterizing the most aggressive M5-T1 tumor. Among the 15 mitochondrial proteins found in these lists, the very long-chain specific acyl-CoA dehydrogenase, encoded by the Acadvl gene and involved in fatty acid beta oxidation, appeared to play an important role in the metabolic reprogramming of the tumor microenvironment. Immunohistochemical staining of tumor sections confirmed increased expression of Acadvl in the M5-T1 tumor. Finally, the dramatic increase and decrease, observed in 25 and 17 proteins, respectively, suggested the existence of a strong link between mitochondrial events and modifications of the extracellular matrix, immune cell components or other subcellular compartments. These findings highlight some important aspects of the tumor microenvironment changes linked to aggressiveness.

Cyclooxygenases (COX), or prostaglandin endoperoxide synthases (PTGS), are key enzimes in the synthesis of prostaglandins, which are chemical species critical in mediating inflammatory processes. There are two highly homologous COX isoforms: COX-1 and COX-2. COX-1 is involved in the production of prostaglandins, chemical compuounds that take part in physiological processes such as: protection of the gastric epithelium, maintenance of renal flow, platelet aggregation, neutrophil migration and, also, are expressed in the vascular endothelium. Meanwhile, COX-2 is induced by proinflammatory stimuli. It is very frequent the use of nonsteroidal antiinflammatory drugs (NSAIDs) to counteract the symptoms of inflammatory processes. These drugs, in addition to its benefits, can cause side effects on people’s health, such as cardiovascular and respiratory problems, among others. In the past years, it has been recognized the potential of plants secondary metabolites as pharmacological agents, prompting the need for investigations that shed light into its mechanism of action. In this work we have applied computational techniques, based on quantum chemistry and mechanical statistics, to study the protein-ligand interaction involving COX’s and secondary metabolites from natural sources. Our aim is to determine the structure activity interplay in processes involving the participation of secondary plant metabolites such as luteolin, galangin, kaempferol, apigenin, morine and quercetin on the inactivation of COX’s. From molecular docking analysis, we have extracted the energetics of the COX-(1,2)/metabolite coupling. By defining energy based factors, we have determined a procedure that predicts the chemical species with highest stability and selectivity towards inactivation of COX-2 over COX-1. The results are discussed with regard to conformational features of the selected ligands and its intermolecular strong/weak interactions inside the active-sites of the COX’s hosts.

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative motor neuron disease and remains misunderstood with difficult diagnosis and prognosis. The implication of the immune system is recognized in ALS pathophysiology, hence the interest in leucocytes count as lymphocytes and neutrophils. The neutrophil to lymphocyte ratio (NLR) has recently been used as a prognosis factor to assess the progression of ALS. Thus, the aim of this study was to analyze the evolution of the NLR during disease evolution in a French cohort of ALS patients and its relation with survival. Clinical parameters and NLR were collected in ALS patients followed at the University Hospital of Tours (France). ALS patients were subdivided into three groups in regard to their NLR value at inclusion: group 1 (NLR < 2); group 2 (NLR: 2-3); group 3 (NLR > 3). Comparison of qualitative and quantitative clinical and biological variables between NLR groups was performed. Then Cox-regressions were carried out to determine the association of NLR with survival. We observed a significant correlation of NLR with ALSFRS-r score (p<0.0001) and with vital forced capacity (p=0.0004) at inclusion. We observed that increased NLR at diagnosis is associated with decreased ALS patients’ survival.

Data on helminth parasites and epizoites is presented for the long-beaked and short-beaked common dolphins from the Southeast Pacific. Sampling in 1985-2000 was conducted mainly at six fishing ports in Peru and Ecuador where cetaceans were landed. From a total of 473 common dolphins sampled, we identified helminths including three species of Trematoda: Nasitrema globicephalae, Pholeter gastrophilus and Braunina cordiformis; three species of Nematoda, which includes Anisakis spp., Crassicauda sp. and Halocercus sp.; and two cestodes Tetrabothrius forsteri and Clistobothrium delphini (formerly Phyllobothrium delphini). No acanthocephalans were observed. No statistically significant sexual and ontogenetic variation in helminth prevalence was detected after which samples were pooled. The highest prevalence in the long-beaked common dolphin (n=440) was observed for N. globicephalae (96.3%) in cranial sinuses, Crassicauda sp. (83.3%) in mammary glands, Crassicauda sp. (78.8%) infesting the cranial sinuses, followed by Cl. delphini (28.6%) in the blubber and P. gastrophilus and B. cordiformis (20.4%) in the digestive tract. Although comparative testing was unfeasible due to minimal samples of short-beaked common dolphin (n=33), several of the same helminth species were found, but not N. globicephalae nor B. cordiformis. No cyamids were encountered while pseudo-stalked barnacles Xenobalanus globicipitis were common. No new (global) helminth host records are revealed for common dolphins, but this study presents a first checklist of parasites separately for the Southeast Pacific long-beaked and short-beaked common dolphins. Future work should include exhaustive laboratory-based necropsies, enhanced sampling of the short-beaked form, focus on intermediate hosts and parasitic pathology, including potential human health impact from consumption of small cetaceans.

Landscapes evolve due to climatic conditions, tectonic activity, geological features, biological activity, and sedimentary dynamics. These processes link geological processes at depth to surface features. Consequently, the study of landscapes can reveal essential information about the geochemical footprint of ore deposits at depth. Advances in satellite imaging and computing power have enabled the creation of large geospatial datasets, the sheer size of which necessitates automated processing. We describe a methodology to enable the automated mapping of landscape pattern domains using machine learning (ML) algorithms. From a freely available Digital Elevation Model, derived data, and sample landclass boundaries provided by domain experts, our algorithm produces a dense map of the model region in Western Australia. Both random forest and support vector machine classification achieve about 98\% classification accuracy with reasonable runtime of 48 minutes on a single core. We discuss computational resources and study the effect of grid resolution. Larger tiles result in a more contiguous map, while smaller tiles result in a more detailed, and at some point, noisy map. Diversity and distribution of landscapes mapped in this study support previous results. In addition, our results are consistent with the geological trends and main basement features in the region.

This review presents an updated overview of research concerning Leishmania protein structures, primarily sourced from the Protein Data Bank (PDB), that play a role in the metabolic pathways of the Leishmania parasite. Furthermore, we assess the current progress in the identification and development of bioactive chemical agents aimed at addressing this substantially overlooked tropical disease. We have analyzed experimental data obtained from in vitro, in vivo and in silico sources. This data has been categorized into four main areas: a) vector taxonomy and geographic distribution; b) parasite taxonomy and geographic distribution; c) enzymatic functions of proteins engaged in parasite/host interactions throughout various developmental stages (such as oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases, and cytokines); and d) established and experimental treatments employing bioactive chemical compounds. Our objective is to establish a foundational point of reference for research efforts concentrating on the elucidation of interaction mechanisms and the processes of ligand-protein activation/inactivation, specifically linked to Leishmania infections. Consequently, we emphasize enzymes recognized for their involvement in the biochemical pathways incited during Leishmania infection episodes. This review encapsulates the current understanding, offering insights to inform and direct future explorations aimed at targeting proteins and pathways to enhance the management of Leishmania-related diseases.

Still, the most common in vitro model for absorption, distribution, metabolism and excretion (ADME) purposes is the Caco-2 cell line. However, clear differences in gene- and protein expression towards the small intestine and an at best fair prediction accuracy of intestinal drug absorption restrict the usefulness as model for intestinal epithelial cells. To overcome these limitations, we evaluated a panel of low-passaged patient-derived colorectal cancer cell lines of the HROC collection concerning similarities to small intestinal epithelial cells and their potential to predict intestinal drug absorption. After initial screen of a larger panel, ten cell lines with confluent outgrowth and long-lasting barrier forming potential were further characterized in close detail. Tight junctional complexes and microvilli structures were detected in all lines, differentiated epithelial cells were abundant in 7/10. All lines expressed multiple transporter molecules, with expression levels in three lines being close to those of small intestinal epithelial cells. Compared to the Caco-2 model, three HROC lines demonstrated both higher similarity to jejunal epithelial tissue cells and higher regulatory potential of relevant drug transporters. In sum, these lines would be better suited human small intestinal epithelium models for basic and translational research; especially for ADME studies.

Introduction: OS2966 is a fist-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin. CD29 expression is highly upregulated in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy. Here, we present a novel Phase I clinical trial design addressing several factors plaguing effective treatment of high-grade gliomas (HGG). Study Design: This 2-part, ascending-dose, Phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinically-indicated resection. In Study Part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which will be used for intratumoral, convection-enhanced delivery (CED) of OS2966. Subsequently, patients will undergo their clinically-indicated tumor resection followed by CED of OS2966 to the surrounding tumor-infiltrated brain. Matched pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. Dose escalation will be achieved using a unique concentration-based accelerated titration design. Discussion: The present study design leverages multiple innovations including: 1) the latest CED technology, 2) 2-part design including neoadjuvant intratumoral administration, 3) a first-in-class investigational therapeutic, and 4) concentration-based dosing. Trial registration: A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active. A Phase I trial is registered at clinicialtrials.gov (NCT04608812).

Skin ageing is a progressive but modifiable, multi-factorial disorder that involves all skin tissues. Pertaining to its wide range of physiological and psychosocial complications, skin ageing requires rigorous clinical attention. Topical retinoids and per-oral proteoglycans are promising, non-invasive, therapeutic modalities. To overcome the low bioavailability of conventional free retinoids, Nourella® cream with Retilex-A® (Pharma Medico, Aarhus, Denmark) was developed using a proprietary nano-encapsulation technology. The nano-encapsulation is a sophisticated ‘permeation/penetration enhancer’ that optimises topical drug delivery by increasing surface availability and net absorption ratio. Treatment adherence is also improved by minimising skin irritation. Interventional evidence supports the higher efficacy of Retilex-A® in improving skin thickness and elasticity compared with conventional free forms. It is also reported that the rejuvenating efficacy of Retilex-A® and tretinoin are comparable. Another skin anti-ageing approach is proteoglycan replacement therapy (PRT) with Vercilex®. Vercilex® in Nourella® tablet has the potential to ameliorate proteoglycan dysmetabolism in the aged skin by activating skin cells and improving collagen/elastin turnover. Replicated clinical trials evidenced that PRT can significantly enhance the density, elasticity and thickness of both intrinsically aged and photoaged skin. Evidently, Vercilex® and Retilex-A® share a range of bioactivities, which underlies their synergistic activity observed in a clinical trial. Dual therapy with Nourella® tablets and cream produced higher effect sizes on skin characteristics than monotherapy with each of the two treatments. In conclusion, Nourella® cream and tablets are safe and effective treatments for skin ageing; however, combining the two in a ‘dual skin rejuvenation system’ significantly improves treatment outcomes.

This article aims to delve into the Equity, Diversity and Inclusivity (EDI) issues prevalent in the engineering disciplines in Canada and Spain, shedding light on the common obstacles faced by underrepresented individuals and highlighting potential strategies to foster a more inclusive and diverse engineering community in these nations. Two strategic lines have been identified: (a) facilitating university education access to underrepresented and minority groups, and (b) Accompanying and guiding such students during university training, setting them up for successful future careers. The article also shows the sets of strategies employed in Canada and Spain, clearly distinguishing the approach taken in the two countries. While in Canada, there is a more decentralized approach wherein the universities device their strategies and agenda to address EDI issues, in Spain there is a stronger and direct involvement of the government to ensure a comprehensive, system-wide approach to tackling EDI issues in academia.

Charcot-Marie-Tooth disease is a hereditary polyneuropathy caused by mutations in Mitofusin-2 (MFN2), a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. Autosomal-dominant inheritance of a R94Q mutation in MFN2 causes the axonal subtype 2A2A which is characterized by early onset and progressive atrophy of distal muscles caused by motoneuronal degeneration. Here, we studied mitochondrial shape, respiration, cytosolic and mitochondrial ATP content as well as mitochondrial quality control in MFN2-deficient fibroblasts stably expressing wildtype or R94Q MFN2. Under normal culture conditions, R94Q cells had slightly more fragmented mitochondria but a similar mitochondrial oxygen consumption, membrane potential and ATP production as wildtype cells. However, when inducing mild oxidative stress 24 h before analysis using 100 µM hydrogen peroxide, R94Q cells exhibited significantly increased respiration but decreased mitochondrial ATP production. This was accompanied by increased glucose uptake and an upregulation of hexokinase 1 and pyruvate kinase M2 suggesting increased pyruvate shuttling into mitochondria. As these changes coincided with decreased levels of PINK1/Parkin-mediated mitophagy in R94Q cells, we conclude that the disease-causing R94Q mutation in MFN2 causes uncoupling of mitochondrial respiration from ATP production by a less efficient mitochondrial quality control triggered by oxidative stress.

The present study contributes to bridging the gap on research related to the presence and distribution patterns of carnivore mammals in the western state of Michoacán, highlighting the importance and need to increase efforts aimed at the study and monitoring of wildlife present in this region. The distribution of carnivore in western Mexico was modeled through the application a two-scale approach: a large, modeled region, corresponding to the western part of the country, for which models were obtained that represent the distribution potential of the species, and, the second modeled study area that includes only the western portion of the state of Michoacán, in which models of the current distribution of the species for this region were proposed. A series of predictive models were generated on the current distribution of 11 species of carnivore species (Canis latrans, Urocyon cinereoargenteus, Herpailurus yagouaroundi, Leopardus pardalis, Leopardus wiedii, Puma concolor, Panthera onca, Conepatus leuconotus, Bassariscus astutus, Nasua narica, Procyon lotor), from which, prioritization exercises were carried out on important areas for the conservation of these species, as well as the comparison and analysis of the existing natural protected areas (NPA) in the study area. The different exercises for prioritizing areas for conservation yielded similar results and show the potential percentages of the landscape that can be subjected to protection and conservation programs.

Background: Real-world data (RWD) related to the health status and care of cancer patients reflect the ongoing medical practice, and their analysis yields essential real-world evidence. Advanced information technologies are vital for their collection, qualification, and reuse in research projects. Methods: UNICANCER, the French federation of comprehensive cancer centres, has innovated a unique research network : Consore. This potent federated tool enables the analysis of data from millions of cancer patients across eleven French hospitals. Results: Currently operational within eleven French cancer centres, Consore employs natural language processing to structure the therapeutic management data of approximately 1.3 million cancer patients. This data originates from their electronic medical records, encompassing about 65 millions of medical records. Thanks to the structured data, which is harmonized within a common data model, and its federated search tool, Consore can create patient cohorts based on patient or tumor characteristics, and treatment modalities. This ability to derive larger cohorts is particularly attractive when studying rare cancers. Conclusions: Consore serves as a tremendous data mining instrument that propels French cancer centres into the big data era. With its federated technical architecture and unique shared data model, Consore facilitates compliance to regulations and acceleration of cancer research projects.

Alzheimer’s disease (AD) predominantly occurs as a late-onset form (LOAD), involving neurodegeneration and cognitive decline with progressive memory loss. Over time, risk factors and aging promote accumulation of well-known AD pathologies in oxidative stress, amyloid-beta and tau protein pathology, as well as inflammation. Homeostatic glial functions regulate and suppress these AD pathologies; however, other glial states involve increased pro-inflammatory cytokine release and further pathology accumulation. Different stresses can additionally induce cellular senescence, or an irreversible differentiation process resulting in decreased supportive functions and increased, pro-inflammatory cytokine release. While these pathophysiological underpinnings all contribute to LOAD, they require temporal and mechanistic integration. This perspective hypothesizes that when individuals have threshold senescent glia accumulation, they transition from healthy cognition into mild cognitive impairment and LOAD diagnosis. Particularly, senescent microglia are predicted to represent a final threshold required for the tau pathology burden and spreading that corresponds to sustained neurodegeneration and dementia severity. We first explore age-related decline in glia that promote increases in AD pathologies, and then discuss emerging evidence linking oxidative stress, neurons containing tau pathology, and amyloid-beta to microglia, oligodendrocyte progenitor cell, and astrocyte senescence. Our hypothesis proposes that senescent astrocytes and oligodendrocyte progenitors pressure microglia to phagocytose neurons containing tau pathology. The resulting senescent microglia would form neuritic plaques and induce paracrine senescence transitioning into a progressive clinical dementia presentation. This predictive hypothesis can potentially account for why medications used to treat LOAD fail, as previous treatments have not reduced senescent glial burden. It is also coherent with the predominant hypotheses surrounding LOAD, generates testable hypotheses about LOAD, and increases rationale in testing senolytics as targeted treatments for LOAD arrest and reversal.

The Canal of Aragon and Catalonia (CAC) is 134 km long and irrigates 105,000 ha (131 irrigation user communities) and it is own by the River Ebro’s Water Agency. The aqueducts are located between km 67 and 71 of the canal and were designed by the Civil Engineer Félix de los Ríos Martín in 1907. The cross-section of both aqueducts, Coll de Foix and Capedevila, was extended within the framework of the project by Fernando Hué Herrero in 1962 in order to reach design flows of 26.1 m3/s and 25.7 m3/s, respectively. The structural performance of the aqueducts has been satisfactory, nevertheless the hydraulic capacity has reduced over the years. As a result, the irrigation user communities have expressed the need to extend the cross-section of the aqueducts to meet the irrigation demands. Given the age of the structure and the different design considerations at the time, it is paramount to verify the structural reliability of the aqueducts in the new load configuration. Therefore, the objective of the paper is to present the structural safety analysis conducted and describe the new extended cross-section for both aqueducts (maintaining the original structural typology).

Combining the Job Demands-Resourses model and the Work Adjustment theory, this research aims to create a theoretical model that considers Leader-Member Exchange (LMX) and Work Adjustment as protective factors, capable of reducing job exhaustion and turnover intention. A convenience sample of 257 Italian employees filled an online self-report questionnaire. A sequential mediation model was tested, which showed that the relationship between LMX and turnover intention is mediated by Work Adjustment and Job Exhaustion. The results show that the higher the LMX, the higher the work adjustment of the workers and the less they will perceive job exhaustion and, consequently, intent to leave the organisation. With a view to primary prevention, the aim was to investigate possible protective factors at work and the risk factors to look out for in order to move in the direction of preventing a malaise phenomenon before it develops with the aim of promoting wellbeing in organisations.

Background. To determine the effectiveness and safety of meropenem in routine clinical practice, in terms of clinical and microbiological response. Methods. A real-world, observational, descriptive, longitudinal study with daily monitoring of clinical history records was conducted on all patients who were medically prescribed meropenem during a period between October 2015 and March 2016 at a university hospital in Bucaramanga (Colombia). Results. The study evaluated 84 patients with an average age of 63.2 years, mostly older adults with multiple comorbidities, of whom 54.8% were men. A positive clinical or microbiological response was obtained in 98.8% of the patients. At the end of the treatments, significant improvements in dysthermia (0% vs 29% at the beginning, p = 0.000), tachycardia (13% vs 47%, p = 0.049) and leukocytosis (39% vs 15% at the beginning, p = 0.008) were evidenced. The improvement in the indicator that combines all the SIRS criteria was also significant (p = 0.000). The treatment was well tolerated, although we identified some non-serious and expected adverse reactions. Conclusions. Generic meropenem proved to be effective and well tolerated for different types of infection in routine clinical practice. The results are consistent with the findings of the clinical studies with the innovator drug.

As new treatment modalities are being explored in neuro-oncology, viruses are emerging as a promising class of therapeutics. Virotherapy consists of introduction of either wild-type or engineered viruses to the site of disease, where they exert anti-tumor effect. These viruses can either be non-lytic, in which case they are used to deliver gene therapy, or lytic, which induce tumor cell lysis and subsequent host immunologic response. Replication-competent viruses can then go on to further infect and lyse neighboring glioma cells. This treatment paradigm is being explored extensively in both preclinical and clinical studies for a variety of indications. Virus-based therapies are advantageous due to the natural susceptibility of glioma cells to viral infection, which improves therapeutic selectivity. Furthermore, lytic viruses expose glioma antigens to the host immune system and subsequently stimulate an immune response that specifically targets tumor cells. This review surveys the current landscape of oncolytic virotherapy clinical trials in high-grade glioma, summarizes preclinical experiences, identifies challenges associated with this modality across multiple trials, and highlights potential to integrate this therapeutic strategy into promising combinatory approaches.

This study assesses attitudes of young adults' (18-30 years old) consumption on local and traditional products in7 European countries. A clustered sample (n=836) from natives of Greece, Bulgaria, Romania, Slovenia, Croatia, Denmark and France was collected, by distributing questionnaires through social media and university mail services. Sample was examined by implementing Principal Component Analysis (PCA) in three different samples; overall and two subgroups, Eastern and Western European countries. Six major factors revealed: consumer behavior, health issues, cost, influence from media and close environment and availability on store. As a result, young adults have a positive attitude to local and traditional food products but they express insecurity for health issues. Cost factor influences less people from Eastern European countries than those from the overall sample (3rd and 5th factor accordingly). Influence of close environment is a different factor in Eastern countries comparing to Western ones that it common with influence from media. Females and older people (25-30 years old) doubt less about TFPs, while media have high influence on consumers’ decisions. Aim of this survey is to create consumer profiles of young adults and create different promotion strategies of local and traditional products among the two groups of countries.

Conservation of wildlife depends on precise and unbiased knowledge on the abundance and distribution of species. It is challenging to choose appropriate methods to obtain a sufficiently high detectability and spatial coverage matching the species characteristics and spatiotemporal use of the landscape. In remote regions, such as in the Arctic, monitoring efforts are often resource-intensive and there is a need for cheap and precise alternative methods. Here, we compare an uncrewed aerial vehicle (UAV; quadcopter) pilot-survey of the non-gregarious Svalbard reindeer to traditional population abundance surveys from ground and helicopter to investigate whether UAVs can be an efficient alternative technology. We found that the UAV survey underestimated reindeer abundance compared to the traditional abundance surveys when used at management relevant spatial scales. Observer variation in reindeer detection on UAV imagery was influenced by the RGB greenness index and mean blue channel. In future studies, we suggest to test long-range fixed-wing UAVs to increase the sample size of reindeer and area coverage and incorporate detection probability in animal density models from UAV imagery. In addition, we encourage focus on more efficient post-processing techniques, including automatic animal object identification with machine learning and analytical methods that account for uncertainties.

Evolutionary psychology theories propose that contact with green, natural environments may benefit physical health, but little comparable evidence exists for brown, natural environments, such as the desert. In this study, we examined the association between “brownness” and “greenness” with fasting glucose among young residents of El Paso, Texas. We defined brownness as the surface not covered by vegetation or impervious land within Euclidian buffers around participants’ homes. Fasting glucose along with demographic and behavioral data was obtained from the Nurse Engagement and Wellness Study (N = 517). We found that residential proximity to brownness was not associated with fasting glucose when modeled independently. In contrast, we found that residential greenness was associated with decreased levels of fasting glucose, despite the relatively low levels of greenness within the predominantly desert environment of El Paso. A difference between the top and bottom greenness exposure quartiles within a 250 m buffer was associated with a 3.5 mg/dL decrease in fasting glucose levels (95% confidence interval: -6.2, -0.8). Our results suggest that within the understudied context of the desert, green vegetation may be health-promoting to a degree that is similar to other, non-desert locations in the world that have higher baselines levels of green.

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.

As AI models become more and more common in business and even in our daily lives, it is important to understand what the carbon impact of these models is. Recent papers have shown that this impact can be quite great, i.e., the training of a single high-end model can result in emissions of more than 500t of CO2eq. In this paper we discuss the factors that influence the carbon footprint of AI models, explore what impact different decisions have, and show how the footprint can be reduced. We also examine the footprint of different models to give a guideline on how urgent action is for different organizations.

Social and spatial characteristics of a population often interact to influence health outcomes, suggesting a need to jointly analyze both to offer useful insights in community health. However, researchers have used either social or spatial analyses to examine community-based health issues and inform intervention programs. We propose a combined socio-spatial analytic approach to develop a social network with spatial weights and a spatial statistic with social weights, and apply them to an ongoing study of mental and physical well-being of rural Latino immigrants in North Florida, USA. We demonstrate how this approach can be used to calculate measures, such as social network centrality, support contact dyads, and spatial kernel density based on a health survey data. Findings reveal that the integrated approach accurately reflected interactions between social and spatial elements, and identified community members (who) and locations (where) that should be prioritized for community-based health interventions.

Maternal obesity is increasingly prevalent and is associated with elevated morbidity and mortality rates in both mothers and children. As the interface between the mother and fetus, the placenta has mediates the impact of the maternal environment on fetal development. Most of the literature data on the effects of maternal obesity on placental functions do not exclude potential confounding factors like metabolic diseases (e.g. gestational diabetes). Moreover, it is now clear that the placental response to maternal environment depends on the fetal sex. In this context, we reviewed how maternal obesity (in the absence of gestational diabetes) affects the human placenta in terms of (i) endocrine function, (ii) morphological characteristics, (iii) nutrient exchanges and metabolism, (iv) inflammatory/immune status, (v) oxidative stress, and (vi) transcriptome, with a focus on fetal sex specificities. A better understanding of sex-specific placental responses to maternal obesity is crucial for improving pregnancy outcomes and the health of mothers and children.

For more than twenty years chemists use peptidic organocatalysts to transfer acyl groups onto alcohols. The goal was and still is the increase of selectivity towards the substrate of choice. One carefully designed example is a highly enantioselective tetrapeptide organocatalyst for the kinetic resolution of trans-cycloalkane-1,2-diols. Until now, the intermediate responsible for the acyl transfer of this tetrapeptide has never been directly observed. It was proposed computationally that a π-methylhistidine moiety is acylated as an intermediate step in the catalytic cycle. In this study we set out to investigate whether we can detect and characterize this key intermediate using NMR-spectroscopy and mass spectrometry. Different mass spectrometric experiments using a nano-ElectroSpray Ionization (ESI) source and tandem MS-techniques allowed the identification of tetrapeptide acylium ions using different acylation reagents. The complexes of trans-cyclohexane-1,2-diols with the tetrapeptide were also detected. Additionally, we were able to detect acylated tetrapeptides in solution using NMR-spectroscopy and monitor the acetylation reaction of a trans-cyclohexane-1,2-diol. These findings are important steps towards the understanding of this organocatalyst and its high enantioselectivity.

Human papillomavirus (HPV) is associated with cellular changes of the cervix leading to cancer, which highlights the importance of vaccination in preventing HPV infections and subsequent cellular changes. Women undergoing treatment (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2+) remain at risk for recurrence. This study assesses the effect of post-conization HPV vaccination on the viral status of women six months post-conization, aiming to evaluate the vaccine's effectiveness in preventing recurrence of CIN2+. A retrospective cohort study was conducted among women in Troms and Finnmark who underwent conization in 2022. Using the SymPathy database and the national vaccination register (SYSVAK), we analyzed the vaccination status and HPV test results of women born before 1991, who had not received the HPV vaccine prior to conization. Out of 419 women undergoing conization, 243 met the inclusion criteria. A significant association was found between post-conization HPV vaccination and a negative HPV test at six months follow-up (ARR = 12.1%, P = 0.039). Post-conization HPV vaccination significantly reduced the risk of a positive HPV test at the first follow-up, suggesting its potential in preventing recurrence of high-grade cellular changes. The retrospective design and the insufficient control of confounding variables underscore the necessity for further studies to confirm these findings.

The capability to avoid other air traffic is a fundamental component of the layered conflict management system to ensure safe and efficient operations in the National Airspace System. The evaluation of systems designed to mitigate the risk of midair collisions of manned aircraft are based on large-scale modeling and simulation efforts and a quantitative volume defined as a near midair collision (NMAC). Since midair collisions are difficult to observe in simulation and are inherently rare events, basing evaluations on NMAC enables a more robust statistical analysis. However, an NMAC and its underlying assumptions for assessing close encounters with manned aircraft do not adequately consider the different characteristics of smaller UAS-only encounters. The primary contribution of this paper is to explore quantitative criteria to use when simulating two or more smaller UASs in sufficiently close proximity that a midair collision might reasonably occur and without any mitigations to reduce the likelihood of a midair collision. The criteria assumes a historically motivated upper bound for the collision likelihood and subsequently identify the smallest possible NMAC analogs. We also demonstrate the NMAC analogs can be used to support modeling and simulation activities.

Despite the important role that the GH/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium has turned to be considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effect, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, it will be described the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy. It will be analyzed all those elements triggering the local and systemic production of GH/IGF-I and their possible role both in physiological and pathological conditions. The whole evidence will be combined with important data from the GHAS trial, in which GH or placebo were administrated to patients suffering from critical limb ischemia with no option for revascularization. We postulate that GH, alone or in combination, should be considered as a promising therapeutic agent for helping in the approach of the ischemic disease.

Pieron's and Chocholle’s seminal psychophysical work predicts that human response time to information relative to visual contrast and/or sound frequency decreases when contrast intensity or sound frequency increases. The goal of this study is to bring to the fore the ability of individuals to use visual contrast intensity and sound frequency in combination for faster perceptual decisions of relative depth (“nearer”) in planar (2D) object configurations on the basis of physical variations in luminance contrast. Computer controlled images with two abstract patterns of varying contrast intensity, one on the left and one on the right, preceded or not by a pure tone of varying frequency, were shown to healthy young humans in controlled experimental sequences. Their task (two-alternative forced-choice) was to decide as quickly as possible which of two patterns, the left or the right one, in a given image appeared to “stand out as if it were nearer” in terms of apparent (subjective) visual depth. The results show that the combinations of varying relative visual contrast with sounds of varying frequency exploited here produced an additive effect on choice response times in terms of facilitation, where a stronger visual contrast combined with a higher sound frequency produced shorter forced-choice response times. This new effect is predicted by cross-modal audio-visual probability summation.

Gut microbiota affects progression of rheumatoid arthritis (RA). The present study aims at investigating the protective potential of Bifidobacterium longum cell wall lipoproteins (Lpps) shown to modulate the intestinal microbiome and prevent osteoarthritis. Arthritis was induced by collagen (CIA) or anti-collagen antibodies (CAIA) injection. Intake of 0.5 mg Lpps /L, but not 0.25 and 1mg Lpps/L significantly alleviated RA symptoms in CIA DBA/1OOaHsd mice. Arthritis index (AI) was also reduced in CAIA mice. In CIA protected group, colon Ligilactobacillus murinus, caecal Lactobacillus johnsonii and spleen weight correlated with AI, whereas the reverse was observed with splenic CD11c+ dendritic cells (cDCs). The unprotected CIA Lpps group harbored higher caecal and colon E. coli and lower caecal L.murinus. Lpps administration to CAIA mice after arthritis induction led to lower colon E. plexicaudatum counts. Splenocytes from CIA protected mice triggered by LPS secreted higher Il-10 than control ones. However, higher IL-10 response was not elicited in gnotobiotic RA mice splenocytes with lower cDCs recruitment. Labeled bacteria with Lpps signal were detected in CIA mice bone marrow (BM) cDCs 5 and 16h post-gavage but not in Peyer’s patches and spleen. In vitro uptake of Lpps by primary BM and thymus cells was observed within 24h. FACS analysis detected the Lpps signal in the plasmacytoid cell compartment but not in cDCs. In conclusion, Lpps dosing is critical for preventing arthritis progression and appropriately modulating the microbiome. Our results also highlight the possible triggering of the immune system by Lpps.

Combined awareness about the power and limitations of bioinformatics and molecular biology enables advanced research based on high-throughput data. Despite an increasing demand for scientists with a combined background in both fields, the education in dry lab and wet lab is often separated. This work describes an example of integrated education with focus on genomics and transcriptomics. Participants learn computational and molecular biology methods in the same practical course. Peer-review is applied as a teaching method to foster cooperative learning of students with heterogeneous backgrounds. Evaluation results indicate acceptance and appreciation of this approach.

To evaluate whether the extent of cardiac damage in severe aortic stenosis (AS) might be associated with the occurrence of conduction system disorders after TAVI. A total of 153 symptomatic patients with severe AS who had a TAVI were categorized before the procedure according to the extent of cardiac damage: stage 1 (13.5%): no or LV damage; stage 2 (58.8%): left atrial/mitral valve damage, atrial fibrillation (AF); stage 3 (27.7%): low-flow state, pulmonary vasculature/tricuspid valve/RV damage. After TAVI, 34% of patients exhibited LBBB and 10% high-degree atrioventricular block (HD-AVB). No patient in group 1 developed HD-AVD whereas new LBBB was frequent in groups 2 and 3. Twenty-one patients presented with resolutive paroxysmal AF with a higher rate for each group increment (group 1: n=0, 0%; group 2: n=11,15.7%; group 3: n=10, 30.3%) (p = 0.012). Patients in group 3 had the higher rate of permanent pacemaker implantation (PPMI) (group 1: n=1, 6.3%; group 2: n=7,10%; group 3: n=9, 27.3%) (p=0.012). No patient in group 1 died during the hospital stay. In conclusion, cardiac damage staging of AS might help identify patients at higher risk of conduction disorders and PPMI requirement after TAVI.

The shortage of quantum computers, and their current state of development, constraints research in many fields that could benefit from quantum computing. Although the work of a quantum computer can be simulated with classical computing, personal computers take so long to run quantum experiments that they are not very useful for the progress of research. This manuscript presents an open quantum computing simulation platform that enables quantum computing researchers to have access to high performance simulations. This platform, called QUTE, relies on a supercomputer powerful enough to simulate general purpose quantum circuits of up to 38 qubits, and even more under particular simulations. This manuscript describes in-depth the characteristics of the QUTE platform and the results achieved in certain classical experiments in this field, which would give readers an accurate idea of the system capabilities.

The prefabricated houses supply in Chile was analyzed from web platforms, public market, social media, and Internal Revenue Service, using indicators according to regulatory compliance, complexity, and sustainability attributes, which are essential in advancing to industrialization, and climate change adaptability. The 80% is concentrated in construction, and manufacturing companies, 83% of them are legally registered,with the capacity of meeting technical requirements. To delve deeper into this, 54% has low level, 35% medium level, and 11% high level. The sustainability was measured in 5 levels: 2.7% (1), 37,5% (2), 58,6% (3), 1,1% (4) and 0% (5), which is the highest one. This attribute was determined as the weakest one. The proposed evaluation, based on indicators by attribute, is objective and relevant to consideration since there is still a lack of capacity to supply the housing deficit, and there is not attributes associated to security in habitability to address the climate change, and environment threats, with a lack of action by the state to promote this productive sector, therefore focusing more in provide products, than taking responsibility of the site, not advancing to become a real state agency, which could be improved if management, and regulation were incorporated.

Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease, for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKIs became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40-60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon re-treatment, indicating TKI discontinuation is safe. However, there is still a gap in the understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it ex-amines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.

Development of effective treatments for high-grade glioma (HGG) is hampered by 1) the blood-brain barrier (BBB), 2) an infiltrative growth pattern, 3) rapid development of therapeutic resistance, and, in many cases, 4) dose-limiting toxicity due to systemic exposure. Convec-tion-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and in-crease therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.

Background: Proteins targeted by the Ubiquitin Proteasome System (UPS) are identified for degradation by the proteasome, which has been implicated in the development of neuro-degenerative diseases. Major histocompatibility complex (MHC) molecules present peptides broken down by the proteasome and are involved in neuronal plasticity, regulating synapse number and axon regeneration in the central or peripheral nervous system during develop-ment and in brain diseases. The mechanisms governing these effects are mostly unknown, but evidence from different compartments of the cerebral cortex indicates the presence of im-mune-like MHC receptors in the central nervous system. Methods: We have used human induced pluripotent stem cells (iPSC) differentiated to neural stem cells and then to motor neurons as a developmental model to better understand the structure of the proteasome in developing motor neurons. We perform a proteomic analysis of starting human skin fibroblasts, their matching iPSC, differentiated neural stem cells and motor neurons that highlighted significant differences in the constitutive proteasome and immunoproteasome subunits during development towards motor neurons from iPSC. Results: Proteomic analysis showed that the catalytic proteasome subunits expressed in fi-broblasts differ to those in neural stem cells and motor neurons. Western blot analysis con-firmed the proteomic data, particularly the decreased expression of Beta5i (PSMB8) subunit immunoproteasome. Conclusion: The constitutive proteasome subunits are upregulated in iPSC from HFF and the immunoproteasome subunit beta 5i expression is higher in MN than NSC suggesting a im-munoproteasome phenotype in MN. The immunoproteasome may have implications on motor neuron development and neurodevelopmental diseases that warrants further investi-gation.

Over the last 15 years, the advent of high-throughput ‘omics’ techniques has revealed the multiple roles and interactions occurring among hosts, their microbial partners and their environment. This microbiome revolution has radically changed our views of biology, evolution and individuality. Sitting at the interface between a host and its environment, the microbiome is a relevant yet understudied compartment for ecotoxicology research. Various recent works confirm that the microbiome reacts to and interacts with contaminants, with consequences for hosts and ecosystems. In this paper, we thus advocate for the development of a “microbiome-aware ecotoxicology” of organisms. We emphasize its relevance and discuss important conceptual and technical pitfalls associated with study design and interpretation. We identify topics such as functionality, quantification, temporality, resilience, interactions and prediction as major challenges and promising venues for microbiome research applied to ecotoxicology.

The impact of sex in the development of long-term toxicities affecting the quality of life of cancer survivors has not been investigated experimentally. To address this issue, a series of neurologic and cardiologic endpoints were used to investigate sex-based differences triggered by paclitaxel treatment and radiotherapy exposure. Male and female WT mice were treated with Paclitaxel (150 and 300 mg/kg) administered weekly over 6 weeks or exposed to 19 Gy cardiac irradiation. Cohorts were analyzed for behavioral and neurobiologic endpoints to assess systemic toxicity of paclitaxel or cardiovascular endpoints to assess radiotherapy toxicity. Interestingly, female WT mice exhibited enhanced tolerance compared to male WT mice regardless of the treatment regimen. To provide insight into the possible sex-specific protective mechanisms, rhoB deficient animals and elderly mice (22 months) were used with a focus on the possible contribution of sex hormones including estrogen. RhoB deficiency and advanced age had no impact on neurocognitive impairment induced by Paclitaxel but reversed the cardioprotection was observed in females after radiotherapy. Conversely, rhoB deficiency protected males from radiation toxicity. In sum, rhoB was identified as a molecular determinant driving estrogen dependent cardioprotection in female mice, whereas neuroprotection was not sex-hormone dependent. To our knowledge, this study revealed for the first time sex- and organ-specific responses to paclitaxel and radiotherapy.

DIEP-based breast reconstruction necessitates wide undermining at the abdominal donor-site, creating large wound areas. Flap harvesting is usually conducted using electrosurgical dissection devices. This study sought to compare the clinical outcomes in patients after using the PEAK PlasmaBlade (PPB) versus monopolar electrocautery (MPE). This retrospective cohort study included 128 patients with DIEP-based breast reconstruction. Patient characteristics as well as information on the postoperative course were collected and a comparative evaluation was conducted. The MPE group exhibited significantly (p* = 0.0324) higher abdominal drainage volume (351.11 ± 185.96 ml) compared to the PPB group (279.38 ± 183.38 ml). Subgroup analysis demonstrated that PPB significantly reduced postoperative wound fluid in patients with BMI > 30 kg/m² (p* = 0.0284), without prior neoadjuvant chemotherapy (p** = 0.0041), and among non-smokers (p = 0.0046). Furthermore, postoperative pain was significantly (p**** < 0.0001) lower in the PPB cohort. This study confirms the non-inferiority of the PEAK PlasmaBlade to conventional electrocautery for abdominal flap harvesting. The PPB demonstrated advantages, notably reduced drainage volume and lower postoperative pain levels. Recognizing patient subsets that benefit more from the PPB highlights the importance of personalized device selection based on patient characteristics.

In addition to absorbing nitrogen from the soil, legumes have the ability to use atmospheric N2 through symbiotic nitrogen fixation. Therefore, legumes have developed mechanisms regulating nodulation in response to the amount of nitrate in the soil; in the presence of high nitrate concentrations, nodulation is inhibited while low nitrate concentrations stimulate nodulation and nitrogen fixation. This allows the legumes to switch from soil nitrogen acquisition to symbiotic nitrogen fixation. Recently, a particular interest has been given to the nitrate transporters, such as NPF or NRT2, having a role in the functioning of nodules. Nitrate transporters of the two model plants, Lotus japonicus and Medicago truncatula, shown to have a positive and/or a negative role in nodule functioning, depending on nitrate concentration, are presented in this review. Also, by exploiting available genomic and transcriptomic data in the literature we have identified the complete PsNPF family in Pisum sativum (69 sequences previously described and 21 new that we have annotated) and putative nitrate transporters candidate for playing a role in nodule functioning in P. sativum.