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Abstract The recent emergence of chronic wasting disease (CWD) in Europe has become a new public health risk for monitoring of wild and farmed cervids. This disease, due to prions, has proliferated in North America in a contagious manner. In several mammalian species, polymorphisms in the prion protein gene (PRNP) play a crucial role in the susceptibility to prions and their spread. To obtain a reliable picture of the distribution of PRNP polymorphisms in the two most common cervid species in France, we sequenced the open reading frame (ORF) of this gene in 2114 animals, 1116 roe deer (Capreolus capreolus) and 998 red deer (Cervus elaphus). Selection criteria such as historical origin, spatial distribution and sex ratio have been integrated to establish this sample collection. Except for one heterozygous animal with a non-synonymous mutation at codon 37 (G37A), all the 1116 French roe deer were monomorphic. Red deer showed greater variation with two non-synonymous substitutions (T98A; Q226E), three synonymous substitutions (codons 21, 78 and 136) and a new 24pb deletion (Δ69-77). We found significant regional variations between French regions in the frequency of the identified substitutions. After cloning of the PRNP ORF from animals presenting multiple non-synonymous polymorphisms, we identified six haplotypes and obtained a total of twelve genotypes. As in other European countries, we highlighted the apparent homogeneity of PRNP in the French roe deer and the existence of a greater diversity in the red deer. These results were in line with European phylogeographic studies on these two species.

Abstract Background CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) disease is ultra-rare (

Abstract Background Adaptation to a stressor can lead to costs on other traits. These costs play an unavoidable role on fitness and influence the evolutionary trajectory of a population. Host defense seems highly subject to these costs, possibly because its maintenance is energetically costly but essential to the survival. When assessing the ecological risk related to pollution, it is therefore relevant to consider these costs to evaluate the evolutionary consequences of stressors on populations. However, to the best of our knowledge, the effects of evolution in irradiate environment on host defense have never been studied. Using an experimental evolution approach, we analyzed fitness across 20 transfers (about 20 generations) in Caenorhabditis elegans populations exposed to 0, 1.4, and 50.0 mGy.h− 1 of 137Cs gamma radiation. Then, populations from transfer 17 were placed in the same environmental conditions without irradiation (i.e., common garden) for about 10 generations before being exposed to the bacterial parasite Serratia marcescens and their survival was estimated to study host defense. Finally, we studied the presence of an evolutionary trade-off between fitness of irradiated populations and host defense. Results We found a lower fitness in both irradiated treatments compared to the control ones, but fitness increased over time in the 50.0 mGy.h− 1, suggesting a local adaptation of the populations. Then, the survival rate of C. elegans to S. marcescens was lower for common garden populations that had previously evolved under both irradiation treatments, indicating that evolution in gamma-irradiated environment had a cost on host defense of C. elegans. Furthermore, we showed a trade-off between standardized fitness at the end of the multigenerational experiment and survival of C. elegans to S. marcescens in the control treatment, but a positive correlation between the two traits for the two irradiated treatments. These results indicate that among irradiated populations, those most sensitive to ionizing radiation are also the most susceptible to the pathogen. On the other hand, other irradiated populations appear to have evolved cross-resistance to both stress factors. Conclusions Our study shows that adaptation to an environmental stressor can be associated with an evolutionary cost when a new stressor appears, even several generations after the end of the first stressor. Among irradiated populations, we observed an evolution of resistance to ionizing radiation, which also appeared to provide an advantage against the pathogen. On the other hand, some of the irradiated populations seemed to accumulate sensitivities to stressors. This work provides a new argument to show the importance of considering evolutionary changes in ecotoxicology and for ecological risk assessment.

Abstract Building stimuli-responsive supramolecular systems is a way for chemists to achieve spatio-temporal control over complex systems as well as a promising strategy for applications ranging from sensing to drug-delivery. For its large spectrum of biological and biomedical implications, adenosine 5’-triphosphate (ATP) is a particularly interesting target for such a purpose but photoresponsive ATP-based systems have mainly been relying on covalent modification of ATP. Here, we show that simply mixing ATP with AzoDiGua, an azobenzene-guanidium compound with photodependent nucleotide binding affinity, results in the spontaneous self-assembly of the two non-fluorescent compounds into photoreversible, micrometer-sized and fluorescent aggregates. Obtained in water at room temperature and physiological pH, these supramolecular structures are dynamic and respond to several chemical, physical and biological stimuli. The presence of azobenzene allows a fast and photoreversible control of their assembly. ATP chelating properties to metal dications enable ion-triggered disassembly and fluorescence control with valence-selectivity. Finally, the supramolecular aggregates are disassembled by alkaline phosphatase in a few minutes at room temperature, resulting in enzymatic control of fluorescence. These results highlight the interest of using a photoswitchable nucleotide binding partner as a self-assembly brick to build highly responsive supramolecular entities involving biological targets without the need to covalently modify them.

Abstract The first case of CWD in a Norwegian red deer was detected by a routine ELISA test and confirmed by western blotting and immunohistochemistry in the brain stem of the animal. Two different western blotting tests were conducted independently in two different laboratories, showing that the red deer glycoprofile was different from the Norwegian CWD reindeer and CWD moose and from North American CWD. The isolate showed nevertheless features similar to the classical BSE (BSE-C) strain. Furthermore, BSE-C could not be excluded based on the PrPSc immunohistochemistry staining in the brainstem and the absence of detectable PrPSc in the lymphoid tissues. Because of the known ability of BSE-C to cross species barriers as well as its zoonotic potential, the CWD red deer isolate was submitted to the EURL Strain Typing Expert Group (STEG) as a BSE-C suspect for further investigation. In addition, different strain typing in vivo and in vitro strategies aiming at identifying the BSE-C strain in the red deer isolate were performed independently in three research groups and BSE-C was not found in it. These results suggest that the Norwegian CWD red deer case was infected with a previously unknown CWD type and further investigation is needed to determine the characteristics of this potential new CWD strain.

A lake monitoring regime optimised to detect natural and anthropogenic variations in water quality is critical for supporting and understanding the impact of lake restoration actions. It can support efficient investment in monitoring by minimising the time required for change detection of lake water quality attributes. The objective of this study was to develop tools and resources to support the development of optimised lake monitoring programs tailored for individual monitored and unmonitored lakes in New Zealand, targeted to detecting change in key water quality attributes in response to restoration actions. We used monitoring data collected routinely from 148 lakes and modelled variability of chlorophyll-a (chl-a), total nitrogen (TN), total phosphorus (TP), and Secchi disk depth (SDD). Using a gradient boosted regression tree (BRT) procedure, we estimated the number of samples per year required over a 5-year and 20-year period to detect improvement in water quality equivalent to meeting thresholds for minimum acceptable water quality states in national policy. At monitored sites, chl-a monitoring to detect improvements within five years was estimated to increase current costs by over 16 times and over 3 times to detect improvements within 20 years. Monitoring to document the effects of restoration actions is important for justifying investments in restoration. Our assessment indicates the importance of monitoring frequency for the level of investment and duration with what is possible to detect the resulting changes in water quality.

Boron carbide (B4C)-reinforced metal matrix composites (MMCs) are materials of choice for the manufacturing of radioactive material containers due to their neutron absorption properties. The neutron absorption capacity of this material depends mainly on the density of B4C particles in the aluminum matrix. The reinforced MMC sheets used to manufacture these containers are produced by a lamination process. The raw sheets coming out of the rolling mill show uneven distribution of B4C particles between the extremities of the sheets, constituted solely of aluminum (rejection zone), and the interior of the laminated sheet, with the right aluminum / B4C ratio (useful zone). Detecting the boundary between the useful zone and the rejection zone is a crucial step in the process, as it defines which part of the sheet should be used to manufacture the containers. Determination of this boundary is currently carried out by chemical digestion, which is costly, time-consuming, and provides only localized information. The aim of this work was to develop a non-destructive technique able to detect the boundary between the rejection zone and the useful zone. The approach is based on the difference in acoustic attenuation between rejection and useful zones. More precisely, the ultrasonic parameter used was the amplitude ratio between the backwall and the front wall echo of the sheet when performing a pulse-echo inspection at 20 MHz. The amplitude ratio in aluminum is smaller than in the useful zone containing B4C, which is more attenuating for the ultrasounds. Two types of scans were performed: 1D linear scan and 2D scan. The linear scan was performed using a conventional probe coupled to the part via a conformable wedge. The boundary between both zones was detected by segmenting the amplitude ratio profile into different sections with constant statistical parameters. The 2D scan was performed with an automated 5-axis inspection system in a water tank using a conventional probe. A map of amplitude ratios was generated, and the useful zone was detected using an agglomerative clustering segmentation. Validation was carried out by comparing the amplitude ratio profile with chemical digestion data from samples taken from these sheets. Experimental validation, performed on sheets with different B4C densities and thicknesses, showed that amplitude ratio enables a good detection of the boundary and therefore the useful zone.

High-velocity oxygen Fuel (HVOF) is a coating process that produces a dense, tightly bonded layer that significantly enhances wear resistance on the coated component. Our partner, the National Research Council of Canada (NRC), develops innovative HVOF coating methods for cylindrical parts' internal surfaces used in critical applications such as landing gear components. However, to be adopted by the aerospace industry, it is necessary to demonstrate that these HVOF-coated parts can be reliably inspected using non-destructive testing (NDT) techniques. Although inspections using conventional ultrasonic of HVOF-coated parts are already well established, phased array ultrasonics (PAUT) have the potential to increase inspection productivity, defect detectability and traceability. Therefore, this study focused on the evaluation of PAUT methods performance for assessing internally coated cylindrical components in terms of defect type, size and orientation.

be challenging. The manual inspection techniques usually used in this context are time-consuming and can lead to inconsistent results. L3Harris and the Centre Technologique en Aérospatiale (CTA) have developed a novel robotized solution to conduct efficient ultrasonic inspection of sandwich-structured components. The system is based on collaborative robots to enhance safety for both components and operators and uses custom-made probe-holders designed to achieve smooth scanning movements and proper coupling conditions. This paper focuses on the ultrasonic aspects of the solution: customized phased-array probes, specific firing sequences and novel data analysis techniques. The objectives were to reduce the inspection time, lower the number of different probes and passes required to cover the full components, obtain complete ultrasonic images of the components ensuring data traceability over time, and provide guidance for the diagnostic. The solution uses a pair of custom 1.5D linear phased-array probes mounted on conformable wedges. The firing technique varies the active aperture during the scan. This allows for simultaneous acquisition of pulse-echo (PE) data in the lower and upper skins, and through-transmission (TT) data through the sandwich, during a single pass. A novel analysis algorithm was developed to automatically compare the collected A-scan signals in each of the three available channels (PE top, PE bottom and TT) to reference signals. Depending on the similitude of the signal triplets with the references, each inspected pixel can be classified in one situation (pristine or defective) and color-coded accordingly. A diagnostic map is then generated and can be used by the inspector in correlation with more classical data (A-scans, B-scans, and C-scans) to make an informed decision.

Abstract The European Commission requested an estimation of the BSE risk (C‐, L‐ and H‐BSE) from gelatine and collagen derived from ovine, caprine or bovine bones, and produced in accordance with Regulation (EC) No 853/2004, or Regulation (EC) No 1069/2009 and its implementing Regulation (EU) No 142/2011. A quantitative risk assessment was developed to estimate the BSE infectivity, measured in cattle oral infectious dose 50 (CoID50), in a small size batch of gelatine including one BSE‐infected bovine or ovine animal at the clinical stage. The model was built on a scenario where all ruminant bones could be used for the production of gelatine and high‐infectivity tissues remained attached to the skull (brain) and vertebral column (spinal cord). The risk and exposure pathways defined for humans and animals, respectively, were identified. Exposure routes other than oral via food and feed were considered and discussed but not assessed quantitatively. Other aspects were also considered as integrating evidence, like the epidemiological situation of the disease, the species barrier, the susceptibility of species to BSE and the assumption of an exponential dose–response relationship to determine the probability of BSE infection in ruminants. Exposure to infectivity in humans cannot be directly translated to risk of disease because the transmission barrier has not yet been quantified, although it is considered to be substantial, i.e. much greater amounts of infectivity would be needed to successfully infect a human and greater in the oral than in the parenteral route of exposure. The probability that no new case of BSE in the cattle or small ruminant population would be generated through oral exposure to gelatine made of ruminant bones is 99%–100% (almost certain) This conclusion is based on the current state of knowledge, the epidemiological situation of the disease and the current practices, and is also valid for collagen.

Recently, interest in transcriptomic assessment of kidney biopsies has been growing. This study investigates the use of NGS to identify gene expression changes and analyse the pathways involved in rejection. An Illumina bulk RNA sequencing on the polyadenylated RNA of 770 kidney biopsies was conducted. Differentially-expressed genes (DEGs) were determined for AMR and TCMR using DESeq2. Genes were segregated according to their previous descriptions in known panels (microarray or the Banff Human Organ Transplant (B-HOT) panel) to obtain NGS-specific genes. Pathway enrichment analysis was performed using the Reactome and Kyoto Encyclopaedia of Genes and Genomes (KEGG) public repositories. The differential gene expression using NGS analysis identified 6,141 and 8,478 transcripts associated with AMR and TCMR. While most of the genes identified were included in the microarray and the B-HOT panels, NGS analysis identified 603 (9.8%) and 1,186 (14%) new specific genes. Pathways analysis showed that the B-HOT panel was associated with the main immunological processes involved during AMR and TCMR. The microarrays specifically integrated metabolic functions and cell cycle progression processes. Novel NGS-specific based transcripts associated with AMR and TCMR were discovered, which might represent a novel source of targets for drug designing and repurposing.

This study aimed to estimate the prevalence of poultry aspergillosis and evaluate the accuracy of histopathology (test under evaluation) and mycological culture (an imperfect reference test). Farms raising layer and breeder or broiler birds, with suspected aspergillosis cases, clinical or subclinical, were eligible and visited for sampling. After necropsy, histopathology and mycological culture examinations were conducted by two evaluators. A Bayesian latent class model was used to estimate the accuracy of histopathology when compared to the imperfect reference test, mycological culture. A total of 142 chicken farms, 96 laying and breeding hen farms, and 46 broiler farms were used for the study. True aspergillosis median prevalence was estimated at 63.7% (95% credibility intervals, CrI: 53.8%, 73.0%) in layers and breeders and at 65.2% (95% CrI: 50.2%, 78.3%) in the broiler farms’ population. The median diagnostic sensitivity of histopathology and culture were estimated at, respectively, 98.8% (95% CrI: 94.6%, 100.0%) and 90.4% (95% CrI: 83.6%, 95.3%). Tests’ diagnostic specificity was estimated at, respectively, 97.3% (95% CrI: 87.7%, 99.9%) and 95.7% (95% CrI: 91.8%, 98.2%). Both tests had very high and comparable positive predictive values, but, in a population where disease prevalence was 25%, histopathology had a higher negative predictive value than culture.

Abstract Background Although moderate physical activity (PA) during cancer treatment has been associated with improved quality of life, reduced side effects, and even lower mortality, many barriers to successful implementation remain. Digital technology has been perceived as an effective lever for overcoming access and motivational issues but few studies have been performed to confirm this assumption. The “VISIO-AJUST” study explored the factors affecting the conditions of adherence to video-conference-based PA programs in patients undergoing cancer treatment. Methods The VISIO-AJUST study was based on a qualitative successive case approach, guided by the principles of the realist evaluation, and applied to two French programs of PA, following three main steps: (1) Identification of factors likely to influence conditions of patients’ adherence; (2) Elaboration and testing of explanatory “Context-Mechanism-Outcome (CMO)” configurations; (3) Refinement of CMO configurations, in order to understand what, how, for whom, and under what circumstances video-conference-based PA programs work. Results Five main CMO configurations were found to be associated with adherence to video-conferencing-based PA programs, promoting (i) accessibility and a supportive environment for adapted physical activity, (ii) a setting conducive to sociability despite distance, (iii) Confidence and security of practice, (iv) a combination of several motivational levers in favor of continuity of effort and progress, (v) regularity of the sessions, progressiveness in the effort and evaluation of progress as a basis for the adoption of a regular physical practice. Conclusion This study provides original insights into the use of videoconferencing to enable patients to improve their PA during cancer treatment. Future research with long-term follow-up would allow for a better understanding of the key conditions promoting sustainable behavior change.

Background and Aim: Ostrich (Struthio camelus) farming in the United Arab Emirates (UAE) is a relatively new field of farming. Farmed ostriches are susceptible to ectoparasite infestation, which affects their production. This study was conducted to estimate the prevalence of ectoparasites on ostriches raised on a farm in Abu Dhabi Emirate. Materials and Methods: The feathers of 42 ostriches (26 females and 16 males) were collected and morphologically examined for ectoparasites. In total, 283 lice (89 males and 194 females) were collected from birds. However, there were no ticks or other ectoparasites. Lice were preserved in 1.5 mL tubes containing 70% ethanol and were later identified using taxonomic keys. The prevalence, mean intensity of infection, and mean abundance were estimated. Results: One louse species, Struthiolipeurus struthionis was identified. To the best of our knowledge, this is the first report of S. struthionis in ostriches raised in the UAE with an overall prevalence of 88%. The prevalence of lice was significantly higher in July (100%) than that in May (66.7%). Likewise, the mean intensity and abundance of lice were significantly higher in June (10.6 and 9.94, respectively) than in May (3.25 and 2.2, respectively). Conclusion: The high prevalence of lice poses a serious risk to ostrich farming by negatively affecting the health and productivity of ostriches.

Abstract In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate between donor-inherited lesions and those acquired post-transplantation. However, many centers do not perform such biopsies since they are invasive, costly and may delay the transplant procedure. We aim to generate a non-invasive virtual biopsy system using routinely collected donor parameters. Using 14,032 day-zero kidney biopsies from 17 international centers, we develop a virtual biopsy system. 11 basic donor parameters are used to predict four Banff kidney lesions: arteriosclerosis, arteriolar hyalinosis, interstitial fibrosis and tubular atrophy, and the percentage of renal sclerotic glomeruli. Six machine learning models are aggregated into an ensemble model. The virtual biopsy system shows good performance in the internal and external validation sets. We confirm the generalizability of the system in various scenarios. This system could assist physicians in assessing organ quality, optimizing allograft allocation together with discriminating between donor derived and acquired lesions post-transplantation.

Abstract Many genes that drive normal cellular development also contribute to oncogenesis. Medulloblastoma (MB) tumors likely arise from neuronal progenitors in the cerebellum, and we hypothesized that the heterogeneity observed in MBs with sonic hedgehog (SHH) activation could be due to differences in developmental pathways. To investigate this question, here we perform single-nucleus RNA sequencing on highly differentiated SHH MBs with extensively nodular histology and observed malignant cells resembling each stage of canonical granule neuron development. Through innovative computational approaches, we connect these results to published datasets and find that some established molecular subtypes of SHH MB appear arrested at different developmental stages. Additionally, using multiplexed proteomic imaging and MALDI imaging mass spectrometry, we identify distinct histological and metabolic profiles for highly differentiated tumors. Our approaches are applicable to understanding the interplay between heterogeneity and differentiation in other cancers and can provide important insights for the design of targeted therapies.

BackgroundAbout 10–20% of pancreas allografts are still lost in the early postoperative period despite the identification of numerous detrimental risk factors that correlate with graft thrombosis.MethodsWe conducted a multicenter study including 899 pancreas transplant recipients between 2000 and 2018. Early pancreas failure due to complete thrombosis, long-term pancreas, kidney and patient survivals were analyzed and adjusted to donor, recipient and perioperative variables using a multivariate cause-specific Cox model stratified to transplant centers.ResultsPancreas from donors with history of hypertension (6.7%), as well as with high body mass index (BMI), were independently associated with an increased risk of pancreas failure within the first 30 post-operative days (respectively, HR= 2.57, 95% CI from 1.35 to 4.89 and HR= 1.11, 95% CI from 1.04 to 1.19). Interaction term between hypertension and BMI was negative. Donor hypertension also impacted long-term pancreas survival (HR= 1.88, 95% CI from 1.13 to 3.12). However, when pancreas survival was calculated after the postoperative day 30, donor hypertension was no longer a significant risk factor (HR= 1.22, 95% CI from 0.47 to 3.15). A lower pancreas survival was observed in patients receiving a pancreas from a hypertensive donor without RAAS (Renin Angiotensin Aldosterone System) blockers compared to others (50% vs 14%, p < 0.001). Pancreas survival was similar among non-hypertensive donors and hypertensive ones under RAAS blockers.ConclusionDonor hypertension was a significant and independent risk factor of pancreas failure. The well-known pathogenic role of renin-angiotensin-aldosterone system seems to be involved in the genesis of this immediate graft failure.

Abstract Atypical teratoid rhabdoid tumors (ATRT) are divided into MYC, TYR and SHH subgroups, suggesting diverse lineages of origin. Here, we investigate the imaging of human ATRT at diagnosis and the precise anatomic origin of brain tumors in the Rosa26-CreERT2::Smarcb1flox/flox model. This cross-species analysis points to an extra-cerebral origin for MYC tumors. Additionally, we clearly distinguish SHH ATRT emerging from the cerebellar anterior lobe (CAL) from those emerging from the basal ganglia (BG) and intra-ventricular (IV) regions. Molecular characteristics point to the midbrain-hindbrain boundary as the origin of CAL SHH ATRT, and to the ganglionic eminence as the origin of BG/IV SHH ATRT. Single-cell RNA sequencing on SHH ATRT supports these hypotheses. Trajectory analyses suggest that SMARCB1 loss induces a de-differentiation process mediated by repressors of the neuronal program such as REST, ID and the NOTCH pathway.

Abstract Transcriptional cofactors of the ETO family are recurrent fusion partners in acute leukemia. We characterized the ETO2 regulome by integrating transcriptomic and chromatin binding analyses in human erythroleukemia xenografts and controlled ETO2 depletion models. We demonstrate that beyond its well‐established repressive activity, ETO2 directly activates transcription of MYB, among other genes. The ETO2‐activated signature is associated with a poorer prognosis in erythroleukemia but also in other acute myeloid and lymphoid leukemia subtypes. Mechanistically, ETO2 colocalizes with EP300 and MYB at enhancers supporting the existence of an ETO2/MYB feedforward transcription activation loop (e.g., on MYB itself). Both small‐molecule and PROTAC‐mediated inhibition of EP300 acetyltransferases strongly reduced ETO2 protein, chromatin binding, and ETO2‐activated transcripts. Taken together, our data show that ETO2 positively enforces a leukemia maintenance program that is mediated in part by the MYB transcription factor and that relies on acetyltransferase cofactors to stabilize ETO2 scaffolding activity.

The living conditions imposed on horses mean that they are inevitably confronted with situations that can induce stress. Music is a promising tool for managing such situations, but its benefits could be attenuated by repeated exposure. In this study, we aim to determine whether music can mitigate horses' reactions to unexpected stimuli and if playing the same music daily leads to a loss of its efficiency. We compared three groups of 12 horses that were led on a route punctuated by potentially stressful stimuli for 10 consecutive days. Each group of individuals wore headphones and was consistently subjected to one of the three experimental conditions: a "music" test condition during which the same music track was played, a "noise" condition during which pink noise was played, and a "no-music" control condition. We found that music has a relaxing effect on horse behavior and heart rate. Interestingly, parameters with the pink noise were intermediate between the music and no-music conditions. Regarding the music's loss of efficiency through repeated playing, our results show that this tool continues to effectively mitigate the behavioral expression of stress after seven consecutive exposures, but this effect was not found every day. Music can therefore help make human-horse interactions safer by limiting the stress of horses faced with unexpected events, but further investigation is needed to understand the underlying mechanisms and ensure a safe and consistently efficient use in the field.

Summary: The role of T cell receptor (TCR) diversity in infectious disease susceptibility is not well understood. We use a systems immunology approach on three cohorts of herpes zoster (HZ) patients and controls to investigate whether TCR diversity against varicella-zoster virus (VZV) influences the risk of HZ. We show that CD4+ T cell TCR diversity against VZV glycoprotein E (gE) and immediate early 63 protein (IE63) after 1-week culture is more restricted in HZ patients. Single-cell RNA and TCR sequencing of VZV-specific T cells shows that T cell activation pathways are significantly decreased after stimulation with VZV peptides in convalescent HZ patients. TCR clustering indicates that TCRs from HZ patients co-cluster more often together than TCRs from controls. Collectively, our results suggest that not only lower VZV-specific TCR diversity but also reduced functional TCR affinity for VZV-specific proteins in HZ patients leads to lower T cell activation and consequently affects the susceptibility for viral reactivation.

Summary: In the ciliate Paramecium, precise excision of numerous internal eliminated sequences (IESs) from the somatic genome is essential at each sexual cycle. DNA double-strands breaks (DSBs) introduced by the PiggyMac endonuclease are repaired in a highly concerted manner by the non-homologous end joining (NHEJ) pathway, illustrated by complete inhibition of DNA cleavage when Ku70/80 proteins are missing. We show that expression of a DNA-binding-deficient Ku70 mutant (Ku70-6E) permits DNA cleavage but leads to the accumulation of unrepaired DSBs. We uncoupled DNA cleavage and repair by co-expressing wild-type and mutant Ku70. High-throughput sequencing of the developing macronucleus genome in these conditions identifies the presence of extremities healed by de novo telomere addition and numerous translocations between IES-flanking sequences. Coupling the two steps of IES excision ensures that both extremities are held together throughout the process, suggesting that DSB repair proteins are essential for assembly of a synaptic precleavage complex.

Abstract We report on an ultrafast infrared optical parametric chirped-pulse amplifier (OPCPA), pumped by a 200-W thin-disk Yb-based regenerative amplifier at a repetition rate of 100 kHz. The OPCPA is tunable in the spectral range 1.4–3.9 $$\upmu $$ μ m, generating up to 23 W of < 100-fs signal and 13 W of < 200-fs idler pulses for infrared spectroscopy, with additional spectral filtering capabilities for Raman spectroscopy. The OPCPA can also yield 19 W of 49-fs 1.75- $$\upmu $$ μ m signal or 5 W of 62-fs 2.8- $$\upmu $$ μ m idler pulses with active carrier-to-envelope-phase (CEP) stabilisation for high-harmonic generation (HHG). We illustrate the versatility of the laser design, catering to various experimental requirements for probing ultrafast science.

Abstract Investigations of the in-plane positioning capabilities of microscopes using machine-readable encoded patterned scales are presented. The scales have patterns that contain absolute position information, and adequate software accurately determines the in-plane position from the scale images captured by the microscope camera. This makes in-plane positioning experiments simple and fast. The scales and software used in this study are commercially available. We investigated different microscopy systems and found that positioning performance is a system issue that is not determined solely by stage performance. In some cases, our experiments revealed software or hardware glitches that limited the positioning performance, which we easily fixed. We have also shown that it is possible to investigate vibrations using this approach and quantify their impact on image blurring. This is, for example, useful for experimentally determining the settling time after a stage movement.

Abstract The emergence of bovine spongiform encephalopathy (BSE) prions from atypical scrapie has been recently observed upon experimental transmission to rodent and swine models. This study aimed to assess whether the inoculation of atypical scrapie could induce BSE-like disease in cattle. Four calves were intracerebrally challenged with atypical scrapie. Animals were euthanized without clinical signs of prion disease and tested negative for PrPSc accumulation by immunohistochemistry and western blotting. However, an emergence of BSE-like prion seeding activity was detected during in vitro propagation of brain samples from the inoculated animals. These findings suggest that atypical scrapie may represent a potential source of BSE infection in cattle.

After the detection of bovine spongiform encephalopathy (BSE), and a zoonotic transmissible spongiform encephalopathy (TSE) caused by the pathological prion protein (PrPSc) in two goats, the investigation of goat prions became of greater interest. Therefore, a broad collection of European goat TSE isolates, including atypical scrapie, CH1641 and goat BSE as reference prion strains were biochemically characterised and subsequently inoculated into seven rodent models for further analysis (already published results of this comprehensive study are reviewed here for comparative reasons). We report here the histopathological and immunohistochemical data of this goat TSE panel, obtained after the first passage in Tgshp IX (tg-shARQ) mice, which overexpress the ovine prion protein. In addition to the clear-cut discrimination of all reference prion strains from the classical scrapie (CS) isolates, we were further able to determine three categories of CS strains. The investigation further indicates the occurrence of sub-strains that slightly resemble distant TSE strains, such as BSE or CH1641, reinforcing the theory that CS is not a single strain but a mixture of sub-strains, existing at varying extents in one isolate. This study further proved that Tgshp IX is a potent and reliable tool for the in-depth characterisation of prion strains.

The unprecedented medium-resolution ( R _λ ∼ 1500–3500) near- and mid-infrared (1–18 μ m) spectrum provided by JWST for the young (140 ± 20 Myr) low-mass (12–20 M _Jup ) L–T transition (L7) companion VHS 1256 b gives access to a catalog of molecular absorptions. In this study, we present a comprehensive analysis of this data set utilizing a forward-modeling approach applying our Bayesian framework, ForMoSA . We explore five distinct atmospheric models to assess their performance in estimating key atmospheric parameters: T _eff , log( g ), [M/H], C/O, γ , f _sed , and R . Our findings reveal that each parameter’s estimate is significantly influenced by factors such as the wavelength range considered and the model chosen for the fit. This is attributed to systematic errors in the models and their challenges in accurately replicating the complex atmospheric structure of VHS 1256 b, notably the complexity of its clouds and dust distribution. To propagate the impact of these systematic uncertainties on our atmospheric property estimates, we introduce innovative fitting methodologies based on independent fits performed on different spectral windows. We finally derived a T _eff consistent with the spectral type of the target, considering its young age, which is confirmed by our estimate of log( g ). Despite the exceptional data quality, attaining robust estimates for chemical abundances [M/H] and C/O, often employed as indicators of formation history, remains challenging. Nevertheless, the pioneering case of JWST’s data for VHS 1256 b has paved the way for future acquisitions of substellar spectra that will be systematically analyzed to directly compare the properties of these objects and correct the systematics in the models.

We present a performance analysis for the aperture masking interferometry (AMI) mode on board the James Webb Space Telescope Near Infrared Imager and Slitless Spectrograph (JWST/NIRISS). Thanks to self-calibrating observables, AMI accesses inner working angles down to and even within the classical diffraction limit. The scientific potential of this mode has recently been demonstrated by the Early Release Science (ERS) 1386 program with a deep search for close-in companions in the HIP 65426 exoplanetary system. As part of ERS 1386, we use the same data set to explore the random, static, and calibration errors of NIRISS AMI observables. We compare the observed noise properties and achievable contrast to theoretical predictions. We explore possible sources of calibration errors and show that differences in charge migration between the observations of HIP 65426 and point-spread function calibration stars can account for the achieved contrast curves. Lastly, we use self-calibration tests to demonstrate that with adequate calibration NIRISS F380M AMI can reach contrast levels of ∼9–10 mag at ≳ λ / D . These tests lead us to observation planning recommendations and strongly motivate future studies aimed at producing sophisticated calibration strategies taking these systematic effects into account. This will unlock the unprecedented capabilities of JWST/NIRISS AMI, with sensitivity to significantly colder, lower-mass exoplanets than lower-contrast ground-based AMI setups, at orbital separations inaccessible to JWST coronagraphy.

Abstract Background Several cancer immunotherapies that target the PD-L1/PD-1 pathway show promising clinical activity in patients with hepatocellular carcinoma (HCC). However, the standard of care in first-line treatment with atezolizumab (anti-PD-L1 therapy) in combination with bevacizumab is associated with a limited objective response rate. Telomerase reverse transcriptase (TERT) activation meets the criteria of oncogenic addiction in HCC and could be actionable therapeutic target and a relevant tumor antigen. Therefore we hypothesized that combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine might be an attractive therapy in HCC. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (human TERT). UCPVax has been evaluated in a multicenter phase I/II study in non–small cell lung cancers and has demonstrated to be safe and immunogenic, and is under evaluation in combination with atezolizumab in a phase II clinical trial in tumors where telomerase reactivation contributes to an oncogene addiction (HPV+ cancers). The aim of the TERTIO study is to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer anti-telomerase vaccine (UCPVax) with atezolizumab and bevacizumab in unresectable HCC in a multicenter randomized phase II study. Methods Patients with locally advanced, metastatic or unresectable HCC who have not previously received systemic anti-cancer treatment are eligible. The primary end point is the objective response rate at 6 months. Patients will be allocated to a treatment arm with a randomization 2:1. In both arms, patients will receive atezolizumab at fixed dose of 1200 mg IV infusion and bevacizumab at fixed dose of 15 mg/kg IV infusion, every 3 weeks, according to the standard of care. In the experimental arm, these treatments will be combined with the UCPVax vaccine at 0.5 mg subcutaneously. Discussion Combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine gains serious consideration in HCC, in order to extend the clinical efficacy of anti-PD-1/PD-L1. Indeed, anti-cancer vaccines can induce tumor-specific T cell expansion and activation and therefore restore the cancer-immunity cycle in patients lacking pre-existing anti-tumor responses. Thus, there is a strong rational to combine immune checkpoint blockade therapy and anticancer vaccine (UCPVax) in order to activate antitumor T cell immunity and bypass the immunosuppression in the tumor microenvironment in HCC. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a CD4 Th1-inducer cancer vaccine derived from telomerase (UCPVax) and atezolizumab plus bevacizumab in unresectable HCC, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials. Trial registration NCT05528952.

Engineered T cell-based adoptive immunotherapies met promising success for the treatment of hematological malignancies. Nevertheless, major hurdles remain to be overcome regarding the management of relapses and the translation to solid tumor settings. Properties of T cell-based final product should be appropriately controlled to fine-tune the analysis of clinical trial results, to draw relevant conclusions, and finally to improve the efficacy of these immunotherapies. For this purpose, we addressed the existence of atypical T cell subsets and deciphered their phenotypic and functional features in an HPV16-E7 specific and MHC II-restricted transgenic-TCR-engineered T cell setting. To note, atypical T cell subsets include mismatched MHC/co-receptor CD8 or CD4 and miscommitted CD8+ or CD4+ T cells. We generated both mismatched and appropriately matched MHC II-restricted transgenic TCR on CD8 and CD4-expressing T cells, respectively. We established that CD4+ cultured T cells exhibited miscommitted phenotypic cytotoxic pattern and that both interleukin (IL)-2 or IL-7/IL-15 supplementation allowed for the development of this cytotoxic phenotype. Both CD4+ and CD8+ T cell subsets, transduced with HPV16-E7 specific transgenic TCR, demonstrated cytotoxic features after exposure to HPV-16 E7-derived antigen. Ultimately, the presence of such atypical T cells, either mismatched MHC II-restricted TCR/CD8+ T cells or cytotoxic CD4+ T cells, is likely to influence the fate of patient-infused T cell product and would need further investigation.

University laboratories and research institutes are progressively engaging in reducing greenhouse gas (GHG) emissions from their operations. It can be difficult to target all sources of GHG emissions at once, given the diversity of problems posed by each source individually. However, targeting only one or a subset of emissions sources can lead to reallocation of expenditures and thus transfers between emissions items when the financial budget is constant. A simple toy model with 2 or 3 expenditure items and 2 classes of laboratory personnel allows us to explore the communicating vessels effects associated with the partial decarbonization of research entities in different scenarios. More generally, the model highlights the trade-offs between CO2 emissions, expenditures, and output/research production. Decarbonization measures must be carefully planned based on thorough identification and quantification of direct emissions sources inside and outside the laboratory. Examples pertaining to air travel and use of labware are discussed in detail. Redefining expectations in terms of research production could allow for a greater emphasis on environmental constraints but this requires institutional as well as ethical transformations.

Not available.

Summary: Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral or non-viral etiologies including steatotic liver diseases (SLDs). Expansion of immunosuppressive myeloid cells is a hallmark of inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance. Here, we present a high-resolution atlas of innate immune cells from patients with HCC that unravels an SLD-associated contexture characterized by influx of inflammatory and immunosuppressive myeloid cells, including a discrete population of THBS1+ regulatory myeloid (Mreg) cells expressing monocyte- and neutrophil-affiliated genes. THBS1+ Mreg cells expand in SLD-associated HCC, populate fibrotic lesions, and are associated with poor prognosis. THBS1+ Mreg cells are CD163+ but distinguished from macrophages by high expression of triggering receptor expressed on myeloid cells 1 (TREM1), which contributes to their immunosuppressive activity and promotes HCC tumor growth in vivo. Our data support myeloid subset-targeted immunotherapies to treat HCC.

Vocal communication is widespread in animals, with vocal repertoires of varying complexity. The social complexity hypothesis predicts that species may need high vocal complexity to deal with complex social organization (e.g. have a variety of different interindividual relations). We quantified the vocal complexity of two geographically distant captive colonies of rooks, a corvid species with complex social organization and cognitive performances, but understudied vocal abilities. We quantified the diversity and gradation of their repertoire, as well as the inter-individual similarity at the vocal unit level. We found that males produced call units with lower diversity and gradation than females, while song units did not differ between sexes. Surprisingly, while females produced highly similar call repertoires, even between colonies, each individual male produced almost completely different call repertoires from any other individual. These findings question the way male rooks communicate with their social partners. We suggest that each male may actively seek to remain vocally distinct, which could be an asset in their frequently changing social environment. We conclude that inter-individual similarity, an understudied aspect of vocal repertoires, should also be considered as a measure of vocal complexity.

Abstract Background Individual functional modifications shape the ability of wildlife populations to cope with anthropogenic environmental changes. But instead of adaptive response, human-altered environments can generate a succession of deleterious functional changes leading to the extinction of the population. To study how persistent anthropogenic changes impacted local species’ population status, we characterised population structure, genetic diversity and individual response of gene expression in the tree frog Hyla orientalis along a gradient of radioactive contamination around the Chernobyl nuclear power plant. Results We detected lower effective population size in populations most exposed to ionizing radiation in the Chernobyl Exclusion Zone that is not compensated by migrations from surrounding areas. We also highlighted a decreased body condition of frogs living in the most contaminated area, a distinctive transcriptomics signature and stop-gained mutations in genes involved in energy metabolism. While the association with dose will remain correlational until further experiments, a body of evidence suggests the direct or indirect involvement of radiation exposure in these changes. Conclusions Despite ongoing migration and lower total dose rates absorbed than at the time of the accident, our results demonstrate that Hyla orientalis specimens living in the Chernobyl Exclusion Zone are still undergoing deleterious changes, emphasizing the long-term impacts of the nuclear disaster.

Abstract Background Non-small cell lung cancer is a very poor prognosis disease. Molecular analyses have highlighted several genetic alterations which may be targeted by specific therapies. In clinical practice, progression-free survival on EGFR TKI treatment is between 12 and 14 months. However, some patients progress rapidly in less than 6 months, while others remain free of progression for 16 months or even longer during EGFR TKI treatment. Methods We sequenced tumor exomes from 135 lung cancer patients (79 with EGFR-wildtype (WT), 56 with EGFR-mutant tumors) enrolled in the ALCAPONE trial (genomic analysis of lung cancers by next generation sequencing for personalized treatment). Results Some germline polymorphisms were enriched in the EGFR-mutant subset compared to EGFR-WT tumors or to a reference population. However, the most interesting observation was the negative impact of some germline SNPs in immunity-related genes on survival on EGFR TKI treatment. Indeed, the presence of one of three particular SNPs in the HLA-DRB5 gene was associated with a decreased PFS on EGFR TKI. Moreover, some SNPs in the KIR3DL1 and KIR3DL2 genes were linked to a decrease in both progression-free and overall survival of patients with EGFR-mutant tumors. Conclusion Our data suggest that SNPs in genes expressed by immune cells may influence the response to targeted treatments, such as EGFR TKIs. This indicates that the impact of these cells may not be limited to modulating the response to immunotherapies. Further studies are needed to determine the exact mechanisms underlying this influence and to identify the associated predictive and prognostic markers that would allow to refine treatments and so improve lung cancer patient outcomes. Trial registration NCT02281214: NGS Genome Analysis in Personalization of Lung Cancer Treatment (ALCAPONE).

Many mobile robotics applications require robots to navigate around humans who may interpret the robot’s motion in terms of social attitudes and intentions. It is essential to understand which aspects of the robot’s motion are related to such perceptions so that we may design appropriate navigation algorithms. Current works in social navigation tend to strive towards a single ideal style of motion defined with respect to concepts such as comfort, naturalness, or legibility. These algorithms cannot be configured to alter trajectory features to control the social interpretations made by humans. In this work, we firstly present logistic regression models based on perception experiments linking human perceptions to a corpus of linear velocity profiles, establishing that various trajectory features impact human social perception of the robot. Secondly, we formulate a trajectory planning problem in the form of a constrained optimization, using novel constraints that can be selectively applied to shape the trajectory such that it generates the desired social perception. We demonstrate the ability of the proposed algorithm to accurately change each of the features of the generated trajectories based on the selected constraints, enabling subtle variations in the robot’s motion to be consistently applied. By controlling the trajectories to induce different social perceptions, we provide a tool to better tailor the robot’s actions to its role and deployment context to enhance acceptability.

Abstract Background Vector-/tick-borne pathogens (V/TBPs) pose a potential threat to human and animal health globally. Information regarding canine V/TBPs is scarce and no specific study has been conducted so far to explore the microbial diversity within ticks infesting dogs from Pakistan. Herein, this knowledge gap is addressed by assessing the genetic diversity and prevalence pattern of V/TBPs in ixodid ticks with special implications for public and canine health. Methods A total of 1150 hard ticks were collected from 300 dogs across central Khyber Pakhtunkhwa (KP), Pakistan. After morpho-molecular identification, 120 tick samples were screened for the presence of V/TBPs by amplifying 16S rRNA/gltA (Rickettsia/Ehrlichia and Wolbachia sp.), 18S rRNA (Theileria sp.) and cox1 (Dirofilaria sp.) genes through PCR followed by sequencing and phylogenetic study. Results In toto, 50 ixodid ticks (50/120, 41.7%) were found positive for V/TBPs DNA. The detected V/TBPs were categorized into five genera and eight species, viz. Ehrlichia (E. canis and Ehrlichia sp.), Rickettsia (R. massiliae, R. raoultii and Rickettsia sp.), Theileria (T. annulata), Dirofilaria (D. immitis) and Wolbachia (Wolbachia sp.). The pathogen prevalence patterns showed that R. massiliae was the most prevalent zoonotic V/TBP (19.5%), followed by E. canis (10.8%), Rickettsia sp. (7.5%), R. raoultii (6.7%), T. annulata (5.8%), D. immitis (5.8%), Wolbachia sp. (4.2%) and Ehrlichia sp. (3.3%), respectively. Among the screened tick species, most Rhipicephalus sanguineus sensu lato samples were found positive for V/TBP DNA (20/20,100%) followed by Rh. turanicus sensu stricto (13/20, 65%), Hyalomma dromedarii (8/20, 40%), Rh. haemaphysaloides (6/20, 30%), Hy. excavatum (2/20, 10%) and Rh. microplus (1/20, 5%). Co-occurrence of V/TBP was also detected in tick specimens (single V/TBP infection: 32 ticks; double and triple: 13 and 5 tick samples). The detected pathogens shared a phylogenetic relationship with similar isolates published in NCBI GenBank from Old and New World countries. Conclusion Ixodid ticks infesting dogs harbor a diverse array of V/TBPs including zoonotic agents from Pakistan. Furthermore, the presence of D. immitis in ticks that infest dogs raises the possibility that this parasite has either attained its dead-end host (i.e. the tick) while feeding on dogs or has expanded its range of intermediate/paratenic hosts. Further research work is needed to investigate the epidemiology and confirm the vector competence of screened tick species for these pathogens from Pakistan. Graphical Abstract

Under standard care, psychotic disorders can have limited response to treatments, high rates of chronicity and disability, negative impacts on families, and wider social and economic costs. In an effort to improve early detection and care of individuals developing a psychotic illness, early intervention in psychosis services and early detection services have been set up in various countries since the 1980s. In April 2016, NHS England implemented a new ‘access and waiting times’ standard for early intervention in psychosis to extend the prevention of psychosis across England. Unfortunately, early intervention and early detection services are still not uniformly distributed in the UK, leaving gaps in service provision. The aim of this paper is to provide a business case model that can guide clinicians and services looking to set up or expand early detection services in their area. The paper also focuses on some existing models of care within the Pan-London Network for Psychosis Prevention teams.

In mammals, lactation is the universal behavior of feeding offspring and has a fundamental nutritional and social value with offspring staying near their mothers. In order to obtain milk, terrestrial mammal offspring squeeze the breast of lactating females and suckle the nipples with their tongues. In the specific case of cetacean species, it was reported that lactating females intentionally eject milk from their mammary slit into the calves’ mouths. Nursing behavior in sperm whales has already been broadly described, but the results of our current study, based on 127 underwater videos, recording over 7 years and displaying explicit nursing behavior, bring a higher level of understanding. We first showed that sperm whale calves are proactive in getting milk. We were then able to illustrate and describe with a high level of precision their suckling behavior: firstly, the calf bumps its head onto the female’s genital area to signal the mother its willingness to suckle; secondly, the calf introduces its lower jawbone into the genital slit, this action makes the nipple pop up from its slit; thirdly, the calf squeezes the nipple with its tongue against the hard palate and suckles; fourthly, the calf removes its jawbone from the female and swims off. Moreover, our underwater visual observations provided the first direct evidence for allosuckling in sperm whales, a situation during which a calf obtains milk from an adult female who is not its mother.

Objective Vaccinated patients with cancer in follow-up studies showed a high seropositivity rate but impaired antibody titres and T cell responses following mRNA vaccine against COVID-19. Besides clinical characteristics and the type of anticancer treatment before vaccination, the identification of patients susceptible to non-response following vaccination using immunological markers is worth to be investigated.Methods and analysis All patients (n=138, solid cancers) were included in the CACOV-VAC Study comprising three cohorts ((neo)-adjuvant, metastatic and surveillance). Immune responses were assessed using, respectively, anti-receptor-binding domain (RBD) SARS-CoV-S-IgG assay and interferon-γ ELISpot assay 3 months following the prime vaccination dose. Immunophenotyping of T cells and immunosuppressive cells from peripheral blood was performed before the prime dose. The serological threshold 3563 AU/mL was used to discriminate non-responders or suboptimal responders versus responders.Results Most patients achieved seroconversion after receiving the two doses of vaccine (97.6%). The median serological level of anti-RBD SARS-CoV-S-IgG was equal to 3029 for patients at the metastatic stage. The patient’s age was the main demographic characteristic that influenced vaccine efficacy. Among the immunological parameters measured at baseline, lower TIGIT (T cell immunoreceptor with Ig and ITIM domains) expression on CD8 T cells was associated with a better vaccine immunogenicity both in terms of humoral and cellular immune responses.Conclusion Despite a high seroconversion rate, median serological levels of patients with cancer, particularly elderly patients, were below the threshold equal to 3563 AU/mL considered as a humoral correlate of protection against SARS-CoV-2. Our findings suggest that the inhibitory receptor TIGIT might be an interesting predictive biomarker of COVID-19 vaccine immunogenicity and beyond in an anticancer vaccine context.Trial registration number ClinicalTrials.gov Registry (NCT04836793).

Background The success rate of non-operative treatment (NOT) of acute uncomplicated appendicitis (AUA) in children varies from 65% to 95%. There are no recommendations on the appropriate antibiotic therapy.Objective To determine the clinical efficacy of amoxicillin-clavulanic acid for NOT of AUA in children.Methods Design: Cross-sectional study in a single medical centre. Settings: Emergency department and Paediatric Visceral Surgery department of the Children Hospital in Toulouse, France. Patients: Patients 5–15 years old who were diagnosed with appendicitis, (1) With abdominal pain and a first episode of acute appendicitis, (2) With no radiological or ultrasound evidence of appendicolith, appendiceal perforation, pelvic abscess nor peritonitis, and (3) With non-septic general aspect, were included. Interventions: NOT consisted of hospital admission. The antibiotic treatment was a combination of amoxicillin and clavulanic acid (80 mg/kg/day of amoxicillin): intravenous regimen during 48 hours followed by oral route during 7 days. Main outcome measure: Success rate of amoxicillin-clavulanic acid NOT in children with AUA at 2 years.Results The initial success rate of amoxicillin-clavulanic acid NOT in children with AUA was 100% (104/104 patients). The success rate at 2 years was 85.6% (89/104) at discharge. None of the 15 patients who underwent surgery after recurrence of appendicitis presented with peritonitis, appendiceal perforation nor pelvic abscess.Conclusion Narrowed antibiotic therapy with amoxicillin and clavulanic acid seems to be an alternative to surgery in children with AUA. It is necessary to wait for the results of ongoing studies to confirm these results.

Abstract The large‐scale proliferation of pelagic Sargassum in the Tropical Atlantic from 2011 has been the subject of increasing attention because of its negative consequences on the environment, fishing, and socioeconomic activities when stranding on coastal areas. This recurrent phenomenon presents strong seasonal and year to year variations. Anticipating the abundances and stranding on seasonal scale poses important challenges in terms of observations and modeling. We show that skillful seasonal forecast of Sargassum distribution can be achieved with up to 7 months in advance over the Tropical Atlantic, by integrating both transport and current knowledge on physiology of Sargassum. This forecast is designed to help marine stakeholders to develop mitigation and resilience strategies through anticipatory decision‐making.

Carbon capture and storage using chemical absorption is a viable method for reducing CO2 emissions from the industrial sector. Thermodynamic analysis of MDEA-PZ aqueous alkanolamine solution is of paramount importance to better simulate and improve the efficiency of CO2 capture processes. In this study, we use the Aspen Plus simulator (V12.1) to compare the theoretical differences and the regression results of the two-liquid activity coefficient models ELECNRTL and ENRTL-RK in terms of CO2 solubility. The quaternary system CO2-MDEA-PZ-H2O vapor-liquid equilibrium (VLE) data found in the open literature are first collected. After excluding anomalous points according to some criteria, 521 confirmed data ranging from 40 °C to 120 °C are then used to regress the binary interaction parameters of molecule-molecule and molecule-electrolyte pairs for both models using the maximum likelihood method. The fitting results show an accuracy enhancement of 34 % for ELECNRTL and 68 % for ENRTL-RK compared to the Aspen default models. The regressed models can be used to improve the accuracy of absorber and stripper simulations in CO2 capture processes.

Antibiotics resistance is a clear threat to the future of current tuberculosis treatments like rifampicin, prompting the need for new treatment options in this field. While plants can offer a plethora of chemical diversity in their constitutive natural products to tackle this issue, finding potentially bioactive compounds in them has not always proven to be that simple. Classical bioactivity-guided fractionation approaches are still trendy, but they bear significant shortfalls, like their time-consuming nature as well as the ever-increasing risk of isolating known bioactive compounds. In this regard, we have developed an alternative method to the latter approach that allows for natural derivatives of a known bioactive scaffold to be efficiently targeted and isolated within a large library of plant extracts. Hence our approach allows for the anticipation of bioactive structure independently of preliminary bioassays. By relying on the chemical diversity of a set of 1,600 plant extracts analyzed by HRMS/MS, we were able to isolate and characterize several minor derivatives of a previously reported bioactive aza-anthraquinone compound from Cananga brandisiana, selected within the plant set. Assessment of bioactivity on these derivatives (especially onychine, with an IC50 value of 39 µM in infection) confirmed their expected activity on Mycobacterium marinum in our anti-infective assay. This proof-of-concept study has established an original path towards bioactive compounds isolation, with the advantage of potentially highlighting minor bioactive compounds, whose activity may not even be detectable at the extract level.

IntroductionSeveral studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.MethodsWe conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.ResultsIn total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p

Background: This study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa. Methods: Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars ($). Results: High FiO2 may be cost-effective (cheaper and effective). In Nigeria, the average cost for high FiO2 was $216 compared with $222 for low FiO2 leading to a −$6 (95% confidence interval [CI]: −$13 to −$1) difference in costs. In India, the average cost for high FiO2 was $184 compared with $195 for low FiO2 leading to a −$11 (95% CI: −$15 to −$6) difference in costs. In South Africa, the average cost for high FiO2 was $1164 compared with $1257 for low FiO2 leading to a −$93 (95% CI: −$132 to −$65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs. Conclusion: High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this.

L’utilisation des méthodes de contrôle nondestructif (CND) est essentielle pour assurer l’intégrité des structures aéronautiques, et les systèmes de contrôle santé intégré des structures (SHM) offrent la possibilité de surveiller en temps réel l’état des structures ou de contrôler des pièces difficiles d’accès. Les matériaux composites, de plus en plus utilisés pour la fabrication des aéronefs, permettent d’intégrer des systèmes SHM directement à coeur du matériau. L’étude se concentre sur l’intégration d’un transducteur piézoélectrique (PZT) à coeur du composite stratifié. L’intégrité du PZT intégré est vérifiée par radiographie X, et sa capacité d’émission et de réception des ondes ultrasonores guidées est vérifiée avec un banc de vibrométrie laser et des essais pitch-catch. Les résultats montrent que l'intégration du PZT à coeur du composite est réussie, et que le système SHM intégré est capable de générer et détecter des ondes ultrasonores guidées. Les paramètres optimaux pour réaliser un essai de détection de défauts sont ensuite déterminés. L’amplitude des ondes de flexion est favorisée par un positionnement du PZT intégré près de la surface du composite. De plus, la fréquence d'excitation optimale du PZT est déterminée pour permettre une détection efficace des défauts. Les résultats ouvrent la voie à l'utilisation de cette méthode pour assurer la surveillance et la maintenance des structures aéronautiques de manière fiable et plus efficace. 1.