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In this study, we evaluated the antimicrobial activity of bacteria isolated from the marine sponges Hymeniacidon perlevis and Halichondria panicea against seven Acinetobacter baumannii strains, the majority of which were clinically relevant carbapenem-resistant A. baumannii strains. We observed the inhibitory activity of 18 (out of 114) sponge-isolated bacterial strains against all A. baumannii strains using medium-throughput solid agar overlay assays. These inhibitory strains belonged to the genera Lactococcus, Pseudomonas, and Vagococcus. In addition, this antimicrobial activity was validated through a liquid co-cultivation challenge using an inhibitory strain of each genus and a green fluorescent protein-tagged A. baumannii strain. Fluorescence measurements indicated that the growth of A. baumannii was inhibited by the sponge isolates. In addition, the inability of A. baumannii to grow after spreading the co-cultures on solid medium allowed us to characterize the activity of the sponge isolates as bactericidal. In conclusion, this study demonstrates that marine sponges are a reservoir of bacteria that deserves to be tapped for antibiotic discovery against A. baumannii., info:eu-repo/semantics/published

Saturation diving is a standard method of intervention for commercial diving during offshore operations. Current saturation procedures achieve a high level of safety with regards to decompression sickness but still put the divers under multiple stressors: 1) Environmental stress (long confinement, heat/cold, dense gases, high oxygen levels), 2) Work stress (muscular fatigue, psychological pressure, breathing equipment, etc.), 3) venous gas emboli associated with decompression, 4) Inflammation related to oxidative stress and microparticles. We present the results of a saturation divers monitoring campaign performed in the North Sea Danish sector, on the Tyra field, during 2022. The study was supported by TotalEnergies, the field operator, and performed by Boskalis Subsea Services, the diving contractor, onboard the diving support vessel Boka Atlantis. The objective was twofold: document the level of diving stress during saturation operations in the Danish sector, and compare the performances of two saturation procedures, the Boskalis and the NORSOK procedures., SCOPUS: ar.j, info:eu-repo/semantics/published

Sphaeropsidins are iso -pimarane diterpenes produced by phytopathogenic fungi that display promising anticancer activities. Sphaeropsidin A, in particular, has been shown to counteract regulatory volume increase, a process used by cancer cells to avoid apoptosis. This study reports the hemi-synthesis of new lipophilic derivatives obtained by modifications of the C15,C16-alkene moiety. Several of these compounds triggered severe ER swelling associated with strong proteasomal inhibition and consequently cell death, a feature that was not observed with respect to mode of action of the natural product. Significantly, an analysis from the National Cancer Institute sixty cell line testing did not reveal any correlations between the most potent derivative and any other compound in the database, except at high concentrations (LC 50 ). This study led to the discovery of a new set of sphaeropsidin derivatives that may be exploited as potential anti-cancer agents, notably due to their maintained activity towards multidrug resistant models., SCOPUS: ar.j, info:eu-repo/semantics/published

The EFSA Panel on Plant Health performed a pest categorisation of Matsucoccus matsumurae (Hemiptera: Matsucoccidae), the Massonian pine bast scale, for the EU territory. This pest categorisation was initiated following the commodity risk assessment of artificially dwarfed plants from China consisting of Pinus parviflora (Japanese white pine) grafted on P. thunbergii (Japanese black pine) performed by EFSA, in which M. matsumurae was identified as a pest of possible concern. However, its identity is not firmly established due to uncertainty regarding its taxonomic relationship with Matsucoccus pini (Green), a species widespread in Europe. M. matsumurae occurs in western China and has been reported as a pest of P. massoniana (Chinese red pine) and P. thunbergii. These hosts occur in the EU as ornamental/amenity trees. Other scales in the Matsucoccus genus feed on a variety of Pinus species and the host range of M. matsumurae could be wider than is currently recorded. The scale has one or two generations per year. All stages occur on the branches and stems of hosts with developing nymphs and adult females feeding through the bark on host phloem vessels. Symptoms include the yellowing/browning of host needles, early needle drop, desiccation of shoots and bark necrosis. The most serious infestations occur in hosts that are 8–25 years old and there can be some host mortality. In principle, host plants for planting and plant products such as cut branches and wood with bark could provide entry pathways into the EU. However, prohibitions on the import of Pinus from non‐European third countries regulate these pathways. In China, M. matsumurae occurs in regions with temperate humid conditions and hot summers. These conditions are also found in parts of southern EU. Were M. matsumurae to establish in the EU, it is conceivable that it could expand its host range; however, this remains uncertain. Some uncertainty exists over the magnitude of potential impacts. M. matsumu, info:eu-repo/semantics/published

The transduction of mechanical stimuli produced by blood flow is an important regulator of vascular development. The vitelline and umbilico-placental circulations are extraembryonic vascular systems that are required for proper embryonic development in mammalian embryos. The morphogenesis of the extraembryonic vasculature and the cardiovascular system of the embryo are hemodynamically and molecularly connected. Here we provide an overview of the establishment of the murine and human vitelline and umbilico-placental vascular systems and how blood flow influences various steps in their development. A deeper comprehension of extraembryonic vessel development may aid the establishment of stem-cell based embryo models and provide novel insights to understanding pregnancy complications related to the umbilical cord and placenta., SCOPUS: re.j, info:eu-repo/semantics/published

Adipose tissue homeostasis relies on the interplay between several regulatory lineages, such as type 2 innate lymphoid cells (ILC2s), T helper 2 (Th2) cells, regulatory T cells, eosinophils, and type 2 macrophages. Among them, ILC2s are numerically the dominant source of type 2 cytokines and are considered as major regulators of adiposity. Despite the overlap in immune effector molecules and sensitivity to alarmins (thymic stromal lymphopoietin and interleukin-33) between ILC2s and resident memory Th2 lymphocytes, the role of the adaptive axis of type 2 immunity remains unclear. We show that mice deficient in CD27, a member of the tumor necrosis factor receptor superfamily, are more resistant to obesity and associated disorders. A comparative analysis of the CD4 compartment of both strains revealed higher numbers of fat-resident memory Th2 cells in the adipose tissue of CD27 knockout mice, which correlated with decreased programmed cell death protein 1-induced apoptosis. Our data point to a non-redundant role for Th2 lymphocytes in obesogenic conditions., SCOPUS: ar.j, info:eu-repo/semantics/published

There are currently no established biomarkers for predicting the therapeutic effectiveness of Vagus Nerve Stimulation (VNS). Given that neural desynchronization is a pivotal mechanism underlying VNS action, EEG synchronization measures could potentially serve as predictive biomarkers of VNS response. Notably, an increased brain synchronization in delta band has been observed during sleep–potentially due to an activation of thalamocortical circuitry, and interictal epileptiform discharges are more frequently observed during sleep. Therefore, investigation of EEG synchronization metrics during sleep could provide a valuable insight into the excitatory-inhibitory balance in a pro-epileptogenic state, that could be pathological in patients exhibiting a poor response to VNS. A 19-channel-standard EEG system was used to collect data from 38 individuals with Drug-Resistant Epilepsy (DRE) who were candidates for VNS implantation. An EEG synchronization metric–the Weighted Phase Lag Index (wPLI)—was extracted before VNS implantation and compared between sleep and wakefulness, and between responders (R) and non-responders (NR). In the delta band, a higher wPLI was found during wakefulness compared to sleep in NR only. However, in this band, no synchronization difference in any state was found between R and NR. During sleep and within the alpha band, a negative correlation was found between wPLI and the percentage of seizure reduction after VNS implantation. Overall, our results suggest that patients exhibiting a poor VNS efficacy may present a more pathological thalamocortical circuitry before VNS implantation. EEG synchronization measures could provide interesting insights into the prerequisites for responding to VNS, in order to avoid unnecessary implantations in patients showing a poor therapeutic efficacy., SCOPUS: ar.j, info:eu-repo/semantics/published

Subclonal reconstruction algorithms use bulk DNA sequencing data to quantify parameters of tumor evolution, allowing an assessment of how cancers initiate, progress and respond to selective pressures. We launched the ICGC-TCGA (International Cancer Genome Consortium-The Cancer Genome Atlas) DREAM Somatic Mutation Calling Tumor Heterogeneity and Evolution Challenge to benchmark existing subclonal reconstruction algorithms. This 7-year community effort used cloud computing to benchmark 31 subclonal reconstruction algorithms on 51 simulated tumors. Algorithms were scored on seven independent tasks, leading to 12,061 total runs. Algorithm choice influenced performance substantially more than tumor features but purity-adjusted read depth, copy-number state and read mappability were associated with the performance of most algorithms on most tasks. No single algorithm was a top performer for all seven tasks and existing ensemble strategies were unable to outperform the best individual methods, highlighting a key research need. All containerized methods, evaluation code and datasets are available to support further assessment of the determinants of subclonal reconstruction accuracy and development of improved methods to understand tumor evolution., info:eu-repo/semantics/published

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This study examined functional trajectories of subjects during the transition phase between ambulatory and non-ambulatory Duchenne muscular dystrophy (DMD) to inform clinical trial designs for new therapeutics. Ambulatory, pulmonary, and upper limb function leading up to loss of ambulation (LoA) and non-ambulatory measures following LoA were quantified; time ordering of pulmonary and upper limb milestones relative to LoA were determined; and the 10-second time threshold for 10-meter walk/run (10MWR) as a marker of approaching LOA was explored. Included in this analysis were 51 subjects aged between 7 and 18 years who experienced LoA during follow-up in the PRO-DMD-01 natural history study. Mean age at LoA was 12.7 (7.1–18.6) years. Mean annual rates of decline in forced vital capacity (FVC) <80%-predicted and performance of upper limb (PUL) 1.2 total score were smaller before than after LoA, but not significantly (FVC %-predicted: 5.6% vs. 10.1%, p = 0.21; PUL 1.2 total score: 2.3 vs. 3.8 units, p = 0.20). More than half of patients experienced clinically significant deficits in FVC %-predicted and PUL 1.2 before experiencing LoA. Among subjects with baseline 10MWR >10 s, those with <1 year to LoA had similar mean ages but significantly worse mean ambulatory function at baseline compared to those with 1 year to LoA. Enriching DMD clinical trials for patients with declining pulmonary or upper limb function is achievable without restricting enrollment to non-ambulatory patients. The sequencing of LoA and initial deficits in pulmonary and upper limb function varied across patients and highlights the potential for composite outcomes or multi-outcome trial designs to assess disease-modifying therapies more comprehensively., SCOPUS: ar.j, info:eu-repo/semantics/published

Toxic small alarmone synthetase (toxSAS) enzymes constitute a family of bacterial effectors present in toxin-antitoxin and secretion systems. toxSASs act through either translation inhibition mediated by pyrophosphorylation of transfer RNA (tRNA) CCA ends or synthesis of the toxic alarmone adenosine pentaphosphate ((pp)pApp) and adenosine triphosphate (ATP) depletion, exemplified by FaRel2 and FaRel, respectively. However, structural bases of toxSAS neutralization are missing. Here we show that the pseudo-Zn2+ finger domain (pZFD) of the ATfaRel2 antitoxin precludes access of ATP to the pyrophosphate donor site of the FaRel2 toxin, without affecting recruitment of the tRNA pyrophosphate acceptor. By contrast, (pp)pApp-producing toxSASs are inhibited by Tis1 antitoxin domains though occlusion of the pyrophosphate acceptor-binding site. Consequently, the auxiliary pZFD of AT2faRel is dispensable for FaRel neutralization. Collectively, our study establishes the general principles of toxSAS inhibition by structured antitoxin domains, with the control strategy directly coupled to toxSAS substrate specificity., SCOPUS: ar.j, info:eu-repo/semantics/published

Liver macrophages fulfill various homeostatic functions and represent an essential line of defense against pathogenic insults. However, it remains unclear whether a history of infectious disease in the liver instructs long-term alterations to the liver macrophage compartment., info:eu-repo/semantics/published

The EFSA Panel on Plant Health performed a pest categorisation of Cenopalpus irani (Trombidiformes: Tenuipalpidae), known as the Iranian false spider mite, following the commodity risk assessment of Malus domestica plants from Türkiye, in which C. irani was identified as a pest of possible concern for the territory of the European Union (EU). The pest is only known to be present in Iran and Türkiye and has not been reported from the EU. The mite primarily feeds on Rosaceae plants but is considered polyphagous. Important crops of the EU that are hosts of C. irani include apples (Malus domestica), pears (Pyrus communis) and figs (Ficus carica). Plants for planting and fruits provide potential pathways for entry into the EU. Host availability and climate suitability in southern EU countries would most probably allow this species to successfully establish and spread. This mite is not listed in Annex II of Commission Implementing Regulation (EU) 2019/2072. Phytosanitary measures are available to reduce the likelihood of entry and spread of this species into the EU. The mite C. irani satisfies the criteria that are within the remit of EFSA to assess for it to be regarded as a potential Union quarantine pest, although there is a key uncertainty over the likelihood and magnitude of impact., info:eu-repo/semantics/published

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This study investigated the efficacy of various traps differing in colour (green or yellow), presence or absence of decoys (dead Agrilus planipennis ) or design (commercial MULTz or multifunnel traps, and homemade bottle- or fan-traps ) for monitoring European Buprestidae in deciduous forests and pear orchards. Over two years, we collected 2220 samples on a two-week basis from 382 traps across 46 sites in Belgium and France. None of the traps proved effective for monitoring Agrilus sinuatus in infested pear orchards (17 specimens captured in 2021, 0 in 2022). The decoys did not affect the catch rates whatever the trap model, colour, buprestid species or sex. The fluorescent yellow traps (MULTz and yellow fan-traps ) tended to be more attractive than the green traps (green fan-traps and, to a lower extent, multifunnel green traps). Most Agrilus species showed similar patterns in mean trap catches, with the exception of Agrilus biguttatus ,which had the largest catches in the green multifunnel traps. Finally, we observed a high variation in catch rates between localities: the site explained 64% of the catches variance, while the tree within the site and the type of trap explained only 6–8.5% each. In many sites, we captured very few specimens, despite the abundance of dying mature trees favourable to the development of Buprestidae. For the early detection of non-native Buprestidae, it therefore seems essential to maximise the number of monitoring sites. Due to their cost-effectiveness, lightweight design, and modularity, fan-traps emerged as promising tools for buprestid monitoring. The study’s findings extend beyond European fauna, as a preliminary trial in Canada suggested that yellow fan-traps could also improve captures of non-European buprestid species and catch species of interest such as Agrilus bilineatus (a species on the EPPO A2 list of pests/pathogens recommended for regulation in the EU)., SCOPUS: ar.j, info:eu-repo/semantics/published

Pleural empyema is a serious complication of pneumonia in children. Negative bacterial cultures commonly impede optimal antibiotic therapy. To improve bacterial identification, we developed a molecular assay and evaluated its performance compared with bacterial culture. Our multiplex-quantitative PCR to detect Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophilus influenzae was assessed using bacterial genomic DNA and laboratory-prepared samples (n = 267). To evaluate clinical performance, we conducted the Molecular Assessment of Thoracic Empyema (MATE) observational study, enrolling children hospitalised with empyema. Pleural fluids were tested by bacterial culture and multiplex-qPCR, and performance determined using a study gold standard. We determined clinical sensitivity and time-to-organism-identification to assess the potential of the multiplex-qPCR to reduce the duration of empiric untargeted antibiotic therapy. Using spiked samples, the multiplex-qPCR demonstrated 213/215 (99.1%) sensitivity and 52/52 (100%) specificity for all organisms. During May 2019–March 2023, 100 children were enrolled in the MATE study; median age was 3.9 years (IQR 2–5.6). A bacterial pathogen was identified in 90/100 (90%) specimens by multiplex-qPCR, and 24/ 100 (24%) by bacterial culture (P <0.001). Multiplex-qPCR identified a bacterial cause in 68/ 76 (90%) culture-negative specimens. S. pneumoniae was the most common pathogen, identified in 67/100 (67%) specimens. We estimate our multiplex-qPCR would have reduced the duration of untargeted antibiotic therapy in 61% of cases by a median 20 days (IQR 17.5–23, range 1–55). Multiplex-qPCR significantly increased pathogen detection compared with culture and may allow for reducing the duration of untargeted antibiotic therapy., SCOPUS: ar.j, info:eu-repo/semantics/published

The Objective of this study was to examine change over time of prevalence of chronic diseases medications (CDM) prescriptions among People living with HIV (PLWH) in Belgium, using Pharmanet database from 2018 to 2021. We identified 13,570, 14,175, 14,588 and 14,813 PLWH in 2018, 2019, 2020 and 2021, respectively. Prescriptions of cardiovascular diseases (CVD) medications (31.7-37.2%) and antidiabetics (7.4-9.0%), increased significantly (p for trend < 0.001 for all), while the prescription of neurological and mental disorders medications (18.0-19.3%) remained stable (p for trend = 0.11) and the prescription of chronic respiratory diseases (CRD) medications decreased from 12.2 to 10.6% (p for trend < 0.001), between 2018 and 2021. It is imperative to ensure that these medications are used appropriately., info:eu-repo/semantics/published

Tumors frequently display high chromosomal instability and contain multiple copies of genomic regions. Here, we describe GRITIC, a generic method for timing genomic gains leading to complex copy number states, using single-sample bulk whole-genome sequencing data. By applying GRITIC to 6,091 tumors, we found that non-parsimonious evolution is frequent in the formation of complex copy number states in genome-doubled tumors. We measured chromosomal instability before and after genome duplication in human tumors and found that late genome doubling was followed by an increase in the rate of copy number gain. Copy number gains often accumulate as punctuated bursts, commonly after genome doubling. We infer that genome duplications typically affect the landscape of copy number losses, while only minimally impacting copy number gains. In summary, GRITIC is a novel copy number gain timing framework that permits the analysis of copy number evolution in chromosomally unstable tumors., info:eu-repo/semantics/published

The EFSA Panel on Plant Health performed a pest categorisation of Monema flavescens (Lepidoptera, Limacodidae), following the commodity risk assessment of Acer palmatum plants grafted on A. davidii from China, in which M. flavescens was identified as a pest of possible concern to the European Union. This species can be identified by morphological taxonomic keys and by barcoding. The adults of the overwintering generation emerge from late June to late August. The eggs are laid in groups on the underside of the host‐plant leaves, on which the larvae feed throughout their six to eight larval instars. Pupation occurs in ovoid cocoons at the junction between twigs and branches, or on the trunk. Overwintering occurs as fully grown larvae or prepupae in their cocoon. There are one or two generations per year. M. flavescens is polyphagous and feeds on broadleaves; it has been reported on 51 plant species belonging to 24 families. It mainly occurs in Asia (Bhutan, China, the Democratic People's Republic of Korea, Japan, Nepal, the Republic of Korea), Russia (Eastern Siberia) and Taiwan. It is also present in the USA (Massachusetts). The pest's flight capacities are unknown. The main pathway for entry and spread is plants for planting with cocoons attached. This is partially closed by prohibition of some hosts. In several EU member states climatic conditions are conducive for establishment and many host plants are widespread. Introduction of M. flavescens may result in defoliations influencing tree health and forest diversity. The caterpillars also have urticating spines affecting human health. Phytosanitary measures are available to reduce the likelihood of entry, establishment and spread, and there is a definite potential for classical biological control. Recognising that natural enemies prevent M. flavescens being regarded as a pest in Asia, there is uncertainty regarding the magnitude of potential impact in EU depending on the influence of natural enemies. All cr, info:eu-repo/semantics/published

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The European Commission requested the EFSA Panel on Plant Health to conduct a pest categorisation of Ceroplastes rubens Maskell (Hemiptera: Coccidae), following the commodity risk assessments of Acer palmatum plants grafted on A. davidii and Pinus parviflora bonsai plants grafted on P. thunbergii from China, in which C. rubens was identified as a pest of possible concern to the European Union (EU). The pest, which is commonly known as the pink, red or ruby wax scale, originates in Africa and is highly polyphagous attacking plants from more than 193 genera in 84 families. It has been present in Germany since 2010 in a single tropical glasshouse. It is known to attack primarily tropical and subtropical plants, but also other host plants commonly found in the EU, such as Malus sylvestris, Prunus spp. Pyrus spp. and ornamentals. It is considered an important pest of Citrus spp. The pink wax scale reproduces mainly parthenogenetically, and it has one or two generations per year. Fecundity ranges from 5 to 1178 eggs. Crawlers settle usually on young twigs and later stages are sessile. All life stages of C. rubens egest honeydew on which sooty mould grows. Host availability and climate suitability suggest that parts of the EU would be suitable for establishment. Plants for planting and cut branches provide the main pathways for entry. Crawlers could spread over short distances naturally through wind, animals, humans or machinery. C. rubens could be dispersed more rapidly and over long distances via infested plants for planting for trade. The introduction of C. rubens into the EU could lead to outbreaks causing damage to orchards, amenity ornamental trees and shrubs. Phytosanitary measures are available to inhibit the entry and spread of this species. C. rubens satisfies the criteria that are within the remit of EFSA to assess for it to be regarded as a potential Union quarantine pest., info:eu-repo/semantics/published

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Background: Maternal pertussis vaccination with Tdap vaccine is recommended to protect newborns from severe postnatal infection. HIV-exposed uninfected (HEU) infants have a higher incidence of pertussis infection and may particularly benefit from maternal immunization. The impact of HIV infection on the quality of IgG and memory B cell (MBC) responses to Tdap vaccination in pregnant women (PW) living with HIV (PWH) is unknown. Methods: In this observational study, humoral immune responses to Tdap vaccination, including IgG levels, Fc-dependent effector functions, and MBC frequencies, were measured before and after vaccination in 40 PWH and 42 HIV-uninfected PW. Placental transfer of IgG and avidity were assessed in cord blood (CB). Soluble and cellular immune activation markers were quantified at baseline. Findings: One month after vaccination, PWH had lower frequencies of MBC compared with HIV-uninfected PW. At delivery, PWH had attenuated pertussis-specific IgG levels and Fc-dependent effector functions. Reduced levels of maternal vaccine polyfunctional IgG and IgG avidity were transferred to HEU as compared to HIV-unexposed newborns. After adjustment with ethnicity, maternal antibody levels and gestational age at vaccination, HIV infection was independently associated with decreased levels of PT specific-IgG in CB. Both maternal and neonatal pertussis-specific IgG responses as well as PT-specific IgG avidity were inversely correlated with maternal sCD14 levels before vaccination among PWH. Interpretation: Maternal HIV infection is associated with attenuated humoral immune responses to Tdap vaccination that correlate with sCD14. Suboptimal transfer of maternal immunity may further increase the risk of severe pertussis infection in HEU infants. Funding: This work was supported by IRIS Fund managed by the Foundation Roi Baudouin [ 2017J1820690206902], Association Vésale pour la Recherche Médicale and the Medical Council of CHU Saint-Pierre and has been funded in par, SCOPUS: ar.j, info:eu-repo/semantics/published

Starvation causes the accumulation of lipid droplets in the liver, a somewhat counterintuitive phenomenon that is nevertheless conserved from flies to humans. Much like fatty liver resulting from overfeeding, hepatic lipid accumulation (steatosis) during undernourishment can lead to lipotoxicity and atrophy of the liver. Here, we found that although surface populations of Astyanax mexicanus undergo this evolutionarily conserved response to starvation, the starvation-resistant cavefish larvae of the same species do not display an accumulation of lipid droplets upon starvation. Moreover, cavefish are resistant to liver atrophy during starvation, providing a unique system to explore strategies for liver protection. Using comparative transcriptomics between zebrafish, surface fish, and cavefish, we identified the fatty acid transporter slc27a2a/fatp2 to be correlated with the development of fatty liver. Pharmacological inhibition of slc27a2a in zebrafish rescues steatosis and atrophy of the liver upon starvation. Furthermore, down-regulation of FATP2 in Drosophila larvae inhibits the development of starvation-induced steatosis, suggesting the evolutionarily conserved importance of the gene in regulating fatty liver upon nutrition deprivation. Overall, our study identifies a conserved, druggable target to protect the liver from atrophy during starvation., SCOPUS: ar.j, info:eu-repo/semantics/published

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We recently discovered that sphaeropsidin A (SphA), a fungal metabolite from Diplodia cupressi, overcomes apoptosis resistance in cancer cells by inducing cellular shrinkage by impairing regulatory volume increase. Previously, we prepared a pyrene‐conjugated derivative of SphA by a cross‐metathesis reaction involving the phytotoxin’s C15,C16‐alkene. This derivative’s evaluation in a cancer cell panel revealed a significant increase in potency, with the IC50 values 5–10× lower than those displayed by the original natural product. Herein, we describe the preparation and anticancer evaluation of fifteen novel C15,C16‐alkene cross‐metathesis analogues in which the pyrene moiety was replaced with other aromatic or non‐aromatic hydrophobic groups. The idea for this replacement was to prepare a family of compounds that would not be predicted to be mutagenic compared with the original pyrene analogue. We predict several of our new compounds to be non‐mutagenic, while retaining the high potency of the original pyrene‐containing analogues. Examples of these potential lead compounds included those containing pentamethylphenyl and triphenylethylene pendant groups. As an additional feature of the current investigation, we prepared several deuterated pyrene‐containing compounds to overcome intellectual property issues associated with non‐patentability of the original pyrene derivative., info:eu-repo/semantics/published

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The EFSA Panel on Plant Health performed a pest categorisation of Popillia quadriguttata (Coleoptera: Scarabaeidae), following a commodity risk assessment of bonsai Pinus parviflora grafted onto P. thunbergii from China, in which P. quadriguttata was identified as a pest of possible concern for the territory of the European Union. This is a univoltine polyphagous pest that occurs in eastern Asia from Vietnam northwards through eastern China and Taiwan, South Korea and into Far East Russia. Hosts include species of fruit trees within the genera Malus and Prunus, trees of forestry and environmental importance such as Quercus and Ulmus, shrubs such as Wisteria, soft fruit such as Rubus, grasses, including amenity turf and field crops such as potatoes, maize and soybean. Adults feed on host leaves, tender stems, flower buds, flowers and fruits; larvae feed on host roots. In northern China P. quadriguttata is a major pest of soybean; in South Korea, P. quadriguttata is one of the most serious insect pests of golf course turf. P. quadriguttata could enter the EU on various pathways including infested soil and growing media accompanying host plants for planning. Biotic factors (host availability) and abiotic factors (climate suitability) suggest that large parts of the EU would be suitable for establishment. Local spread would be mainly via natural dispersal of adults. Long distance spread would be facilitated by the movement of eggs, larvae and pupae infesting soil especially with plants for planting; adults could spread on plants for planting without soil. Economic and or environmental impacts would be expected on a range of plants if P. quadriguttata were to establish in the EU. Phytosanitary measures are available to reduce the likelihood of its introduction. P. quadriguttata satisfies all of the criteria that are within the remit of EFSA to assess for it to be regarded as a potential Union quarantine pest., info:eu-repo/semantics/published

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Cerebrovascular Reactivity (CVR) refers to the ability of cerebral blood vessels to dilate or constrict under the effect of vasoactive substances and can be estimated using functional Magnetic Resonance Imaging (fMRI). Computation of CVR maps is relevant in various brain diseases and requires specialized data processing. We introduce CVRmap, an opensource software that automates the computation of CVR map. The toolbox complies with the Brain Imaging Data Structure (BIDS) standards., SCOPUS: ar.j, info:eu-repo/semantics/published

Lymphangiogenesis, the formation of lymphatic vessels, is tightly linked to the development of the venous vasculature, both at the cellular and molecular levels. Here, we identify a novel role for Sorbs1, the founding member of the SoHo family of cytoskeleton adaptor proteins, in vascular and lymphatic development in the zebrafish., SCOPUS: ar.j, info:eu-repo/semantics/published

To investigate cortical oscillations during a sentence completion task (SC) using magnetoencephalography (MEG), focusing on the semantic control network (SCN), its leftward asymmetry, and the effects of semantic control load., SCOPUS: ar.j, info:eu-repo/semantics/published

Anemia is common among hospitalized critically ill and surgical oncological patients. The rising incidence of cancer and aggressive treatments has increased the demand for blood products, further strained by a dwindling donor pool. The normobaric oxygen paradox (NOP) has emerged as a potential avenue to increase EPO levels. While some studies support its efficacy, research remains limited in clinical settings. This study aims to assess the effectiveness of a NOP protocol in stimulating erythropoiesis, as measured by changes in reticulocyte counts, in cancer patients undergoing abdominal surgeries., SCOPUS: ar.j, info:eu-repo/semantics/published

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Background and Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Though MASH is closely tied to metabolic risk factors, the underlying pathogenic mechanisms remain scarcely understood. Recent research underscores the importance of the gut-liver axis in its pathogenesis, an aspect less explored in human studies. Here, we investigated whether the duodenal epithelium of MASH patients, could exhibit intrinsic dysfunctions.Methods: Duodenal epithelial organoids were generated from 16 MASH patients and 14 healthy controls. Biopsies and patient-derived organoid transcriptomes were then analyzed to evaluate if specific intestinal pathways were differentially modulated in MASH subjects. Functional assays were performed to assess the duodenal epithelial digestive potential and barrier functionality.Results: Organoid formation efficiency was similar between control-derived epithelial organoids (CDEOs) and MASH-derived epithelial organoids (MDEOs) (71% and 69%, respectively). Despite global heterogeneity in growth patterns, MDEOs frequently exhibited cystic spheroid morphology. MDEOs displayed altered digestive homeostasis associated with reduced mature absorptive cell fate, but they retained their lipid metabolic capacity, possibly mediated by lipid oxidation in stem/progenitor cells. Additionally, MDEOs misexpressed components of tight and adherens junctions and desmosomes compared to controls. However, MDEOs maintained pore and leak pathway integrity, indicating that the duodenal epithelial barrier remained functionally preserved under tested conditions.Conclusions: This study provides evidence that the duodenal epithelium of MASH patients exhibits significant alterations in its digestive and barrier functions. This study sheds light on the intricate dynamics of duodenal epithelial alterations in MASH, highlighting potential therapeutic avenues for restoring intesti, info:eu-repo/semantics/published

Optical coherence tomography-angiography is a technique that allows us to non-invasively study in vivo the different retinal vascular networks. This allows a deeper understanding of retinal capillary anatomy and function, in addition to the pathophysiologic changes encountered in diverse diseases. The four retinal capillary layers have different anatomies and functions, implying distinct adaptation and roles in the course of the diseases. Diabetic retinopathy is the leading cause of blindness in working-age adults. Several studies have evaluated how each retinal capillary layer is specifically affected according to the stage of the disease. Unfortunately, too few studies have considered the intermediate capillary plexus as a separate layer, as it has often been incorporated in another layer. In this review, we shed light on the potential role the intermediate capillary plexus plays in the physiopathology of diabetic retinal disease as well as its potential use in grading diabetic retinopathy and its clinical added value in estimating the disease prognosis., SCOPUS: re.j, info:eu-repo/semantics/published

Conventional magnetoencephalography (MEG) requires cryogenic cooling of magnetic field sensors, which are positioned in a one-size-fits-all rigid helmet to maintain a thermal insulation space with the scalp. Optically pumped magnetometers (OPMs) are new sensors that do not require cryogenic cooling. Their placement directly on the scalp allows to perform on-scalp MEG recordings which benefit from a higher signal-to-noise ratio thanks to the reduced brain-tosensor distance. The advantages of on-scalp MEG based on OPMs make it a future promising diagnostic tool for the investigation of numerous neurological pathologies, such as epilepsy or Alzheimer's disease. On-scalp MEG also opens the way to a better understanding of the pathophysiological processes underlying these neurological diseases. This review reports the current knowledge acquired thanks to both cryogenic and on-scalp MEG in these two neurological pathologies and the perspectives raised by the advent of on-scalp MEG., SCOPUS: ar.j, info:eu-repo/semantics/published

To compare sustainability, financial implications and surgical efficiency of two phacoemulsification cassette systems for cataract surgery: a machine with single-use cassettes and another with daily, reusable ones., SCOPUS: ar.j, info:eu-repo/semantics/published

We explored the potential for differential efficacy of vedolizumab between early and late ulcerative colitis [UC] with evaluation of clinical, endoscopic, and histological endpoints., info:eu-repo/semantics/published

Rigorous donor preselection on microbiota level, strict anaerobic processing, and repeated fecal microbiota transplantation (FMT) administration were hypothesized to improve FMT induction of remission in ulcerative colitis (UC)., info:eu-repo/semantics/published

Antibodies play a central role in the adaptive immune response of vertebrates through the specific recognition of exogenous or endogenous antigens. The rational design of antibodies has a wide range of biotechnological and medical applications, such as in disease diagnosis and treatment. However, there are currently no reliable methods for predicting the antibodies that recognize a specific antigen region (or epitope) and, conversely, epitopes that recognize the binding region of a given antibody (or paratope). To fill this gap, we developed ImaPEp, a machine learning-based tool for predicting the binding probability of paratope–epitope pairs, where the epitope and paratope patches were simplified into interacting two-dimensional patches, which were colored according to the values of selected features, and pixelated. The specific recognition of an epitope image by a paratope image was achieved by using a convolutional neural network-based model, which was trained on a set of two-dimensional paratope–epitope images derived from experimental structures of antibody–antigen complexes. Our method achieves good performances in terms of cross-validation with a balanced accuracy of 0.8. Finally, we showcase examples of application of ImaPep, including extensive screening of large libraries to identify paratope candidates that bind to a selected epitope, and rescoring and refining antibody–antigen docking poses., SCOPUS: ar.j, info:eu-repo/semantics/published

info:eu-repo/semantics/published

The genus Niphargus is the most diverse subterranean amphipod genus in the western Palearctic region but, owing to the presence of cryptic species and homoplasy, its taxonomy and biogeographic scenarios are complex, making molecular methods essential to understand its evolution. We conducted a study combining dna -based taxonomy with traditional morphotaxonomy to investigate Niphargus bihorensis Schellenberg, 1940, known from the Western Alps and Carpathians. We redescribed the type material of N. bihorensis from Bihor County, Romania, and revealed the presence of a cryptic species, N. absconditus n. sp. in the same karstic area (Pădurea Craiului Mountains). Additionally, the Alpine populations previously attributed to N. bihorensis turned out to belong to a new, not so closely related species, N. tizianoi n. sp. Phylogenetic analyses based on a concatenated dataset of one mitochondrial and two nuclear markers suggest that the N. bihorensis species complex belongs to a strongly supported clade, together with several species distributed from Switzerland to Iran., SCOPUS: ar.j, info:eu-repo/semantics/published

Si le traitement du cancer du sein a fait des progrès remarquables au cours des dernières années, les options thérapeutiques en cas d’atteinte métastatique au niveau hépatique restent limitées, et associées à un pronostic sombre. Dans certains cas, la chirurgie ciblée des métastases hépatiques du cancer du sein peut être associée à des survies prolongées. A l’heure actuelle, il n’existe cependant pas de critères permettant de sélectionner ces patientes. L’identification de nouveaux biomarqueurs du comportement métastatique dans ces conditions représenterait donc une avancée importante. Dans cette thèse, nous nous sommes intéressés à la caractérisation clinique, histologique et biologique des métastases hépatiques chez les patientes atteintes d’un cancer du sein, et plus particulièrement aux profils de croissance histopathologiques des métastases hépatiques.Nous avons d’abord identifié deux profils de croissance histopathologiques :le profil de croissance de remplacement et desmoplastique. Nous avons rapporté des différences morphologiques, comme le contact direct entre les cellules cancéreuses et les hépatocytes dans le cas d’un profil de remplacement, ou une marge fibreuse isolant les cellules cancéreuses dans le cas d’un profil desmoplastique. Nous avons analysé les profils de croissance dans deux cohortes, une série rétrospective de patientes opérées pour métastases hépatiques et une série d’autopsie. Par rapport à la série chirurgicale, nous avons observé une augmentation de la prévalence du profil de remplacement dans les métastases hépatiques prélevées lors d’autopsies, suggérant que ce profil pouvait être associé à une maladie plus agressive. De façon cohérente avec cette observation, nous avons également montré la valeur pronostique de ces profils de croissance, le profil de remplacement étant significativement associé à une moins bonne survie globale et survie sans récidive que le profil desmoplastique. Parallèlement, nous avons mis en évidence une associat, Doctorat en Sciences biomédicales et pharmaceutiques (Médecine), info:eu-repo/semantics/nonPublished

Background: Inflammatory bowel disease [IBD] is associated with an increased risk of developing lymphoma. Although recent data have clarified the epidemiology of lymphoma in IBD patients, the clinical and pathological characteristics of lymphoma in IBD remain poorly known. Methods: Patients with IBD and lymphoma were retrospectively identified in the framework of a national collaborative study including the Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif [GETAID] and the Lymphoma Study Association [LYSA]. We characterized clinical and prognostic features for the three most frequent lymphoma subtypes occurring in IBD. We performed a multicentre case-control study. Controls [lymphoma de novo] were matched [5:1] to cases on gender, age at diagnosis, lymphoma subtype, year of diagnosis, and IPI/FLIPI indexes. Overall survival and progression-free survival were compared between cases and controls. Results: In total, 133 IBD patients with lymphoma were included [males = 62.4%, median age at lymphoma diagnosis = 49 years in males; 42 years in females]. Most had Crohn’s disease [73.7%] and were exposed to thiopurines [59.4%]. The most frequent lymphoma subtypes were diffuse large B cell lymphoma [DLBCL, 45.1%], Hodgkin lymphoma [HL, 18.8%], and follicular lymphoma [FL, 10.5%]. When matched with 365 controls, prognosis was improved in IBD patients with DLBCL compared to controls [p = 0.0064, hazard ratio = 0.36] or similar [HL and FL]. Conclusions: Lymphomas occurring in IBD patients do not seem to have a worse outcome than in patients without IBD. Due to the rarity of this situation, such patients should be managed in expert centres., SCOPUS: ar.j, info:eu-repo/semantics/published

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are critical neurological conditions that necessitate specialized care in the Intensive Care Unit (ICU). Managing cerebral perfusion pressure (CPP) and mean arterial pressure (MAP) is of primary importance in these patients. To maintain targeted MAP and CPP, vasopressors and/or inotropes are commonly used. However, their effects on cerebral oxygenation are not fully understood. The aim of this review is to provide an up-to date review regarding the current uses and pathophysiological issues related to the use of vasopressors and inotropes in TBI and SAH patients. According to our findings, despite achieving similar hemodynamic parameters and CPP, the effects of various vasopressors and inotropes on cerebral oxygenation, local CBF and metabolism are heterogeneous. Therefore, a more accurate understanding of the cerebral activity of these medications is crucial for optimizing patient management in the ICU setting., SCOPUS: re.j, info:eu-repo/semantics/published

Maintaining blood glucose levels within a safe range is critical for diabetic management. In recent decades, microneedles (MNs) have emerged as a potential method for delivering drugs to treat diabetes. However, insufficient drug loading and the complexity of achieving long-acting release have presented challenges that research has not addressed well. In this study, the hollow-adjustable biocompatible polymer MNs with varying cavity volumes were developed by cyclic freeze-thawing technique. The structure of shell-layer of hollow MNs was optimized with a sequential casting approach for regulating drug release kinetics. This design can ensure the sufficient mechanical strength of MNs and help to improve the drug-loading capacity, thereby solving the problem of low drug-loading capacity and short pharmacodynamic action time of traditional polymer MNs. In vivo experiments performed on diabetic rat models revealed the potential of the as-fabricated MNs to effectively pierce into the skin, leading to a notable hypoglycemic effect lasting up to 14 h without inducing the risk of hypoglycemia. These results indicate that the fabricated hollow-adjustable polymer MNs is a potential candidate for transdermal delivery of high-dose drugs., SCOPUS: ar.j, info:eu-repo/semantics/published

The increased demand for improved strategies for wound healing has, in recent years, motivated the development of multifunctional hydrogels with favorable bio-compatibility and antibacterial properties. To this regard, the current study presented the design of a novel self-healing composite hydrogel that could perform as wound dressing for the promotion of wound healing. The composite hydrogels were composed of polyvinyl alcohol (PVA), borax and chitosan functionalized with sialic acid (SA-CS) and curcumin loaded pluronic F127 micelles. The hydrogels were formed through the boronic ester bond formation between PVA, SA-CS and borax under physiological conditions and demonstrated adjustable mechanical properties, gelation kinetics and antibacterial properties. When incubating with NIH3T3 cells, the hydrogels also demonstrated good biocompatibility. These aspects offer a promising foundation for their prospective applications in developing clinical materials for wound healing., SCOPUS: ar.j, info:eu-repo/semantics/published