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Le génie végétal est une technique qui se base sur l’utilisation de végétaux vivants et de leurs propriétés mécaniques ou biologiques pour assurer certaines fonctionnalités. En ville, il peut être utilisé comme une alternative au génie civil pour la stabilisation des berges, la protection contre les inondations et le contrôle de l'érosion. Bien que fournissant de nombreux bénéfices écologiques et sociaux, son utilisation reste encore marginale dans l’aménagement des berges, de surcroît en zone urbaine. Dans cet article, nous questionnons les freins et les leviers pour une utilisation plus large du génie végétal en ville, en nous focalisant sur les perceptions qu’en ont les praticiens (recueillies à travers des entretiens semi-directifs), et les usagers (recueillies à travers une enquête par photo-questionnaire), en relation avec les services écosystémiques rendus par le génie végétal. Nos résultats montrent que selon les praticiens, plus qu’un changement technique, le recours au génie végétal nécessite un changement de paradigme de gestion, à travers une redéfinition de la performance, une meilleure acceptation et partage du risque et un changement de posture professionnelle. Les usagers, quant à eux, accueillent plutôt positivement ces techniques, notamment du fait de leur valeur esthétique, mais expriment tout de même certaines réticences liées à la valeur récréative des berges et au sentiment de vulnérabilité en cas de crue. Le premier type de réticence peut être en partie levé en ménageant, au moment de l’installation des ouvrages, des accès physiques et visuels au cours d’eau ainsi qu’en instaurant un entretien régulier de la végétation. Le second suppose de poursuivre les travaux sur les risques liés à la déstabilisation de ces ouvrages, tant sur le plan physique que sur le plan de son acceptation sociale.

Abstract Corticotroph macroadenomas are rare but difficult to manage intracranial neoplasms. Mutations in the two Cushing’s disease mutational hotspots USP8 and USP48 are less frequent in corticotroph macroadenomas and invasive tumors. There is evidence that TP53 mutations are not as rare as previously thought in these tumors. The aim of this study was to determine the prevalence of TP53 mutations in corticotroph tumors, with emphasis on macroadenomas, and their possible association with clinical and tumor characteristics. To this end, the entire TP53 coding region was sequenced in 86 functional corticotroph tumors (61 USP8 wild type; 66 macroadenomas) and the clinical characteristics of patients with TP53 mutant tumors were compared with TP53/USP8 wild type and USP8 mutant tumors. We found pathogenic TP53 variants in 9 corticotroph tumors (all macroadenomas and USP8 wild type). TP53 mutant tumors represented 14% of all functional corticotroph macroadenomas and 24% of all invasive tumors, were significantly larger and invasive, and had higher Ki67 indices and Knosp grades compared to wild type tumors. Patients with TP53 mutant tumors had undergone more therapeutic interventions, including radiation and bilateral adrenalectomy. In conclusion, pathogenic TP53 variants are more frequent than expected, representing a relevant amount of functional corticotroph macroadenomas and invasive tumors. TP53 mutations associated with more aggressive tumor features and difficult to manage disease.

Abstract The in vitro modeling of human brain connectomes is key to exploring the structure-function relationship of the central nervous system. Elucidating this intricate relationship will allow better studying of the pathological mechanisms of neurodegeneration and hence result in improved drug screenings for complex neurological disorders, such as Alzheimer’s and Parkinson diseases. However, currently used in vitro modeling technologies lack the potential to mimic physiologically relevant neural structures. Herein, we present an innovative microfluidic design that overcomes one of the current limitations of in vitro brain models: their inability to recapitulate the heterogeneity of brain regions in terms of cellular density and number. This device allows the controlled and uniform deposition of any cellular population within unique plating chambers of variable size and shape. Through the fine tuning of the hydrodynamic resistance and cell deposition rate, the number of neurons seeded in each plating chamber can be tailored from a thousand up to a million. By applying our design to so-called neurofluidic devices, we offer novel neuro-engineered microfluidic platforms that can be strategically used as organ-on-a-chip platforms for neuroscience research. These advances provide essential enhancements to in vitro platforms in the quest to provide structural architectures that support models for investigating human neurodegenerative diseases.

Abstract Gene-editing holds promise as a new technique for growth promotion in livestock, especially in the face of increased opposition to traditional methods of growth promotion like feed additives. However, to date, there has been only limited progress toward models of growth promotion through gene-editing. The vast majority of gene-editing projects have focused on a single gene, myostatin (MSTN), with several reports of successful editing events. These attempts have been limited by the low efficiency of successful edits and issues of viability. The use of both microinjection and somatic cell nuclear transfer appear to be susceptible to these viability issues. Herein, we report a successful editing of myostatin in pigs using a zinc-finger nuclease targeted at exon 3 of myostatin. Overall, the successful editing rate was 1% (37 edited cell lines/3616 screened cell lines). Edits included a variety of small indels and larger deletions. One male and one female cell line with a deletion of one thymidine residue (− 1 T) were selected for somatic cell nuclear transfer. Of the ~ 900 embryos transferred, there were 12 live births (1 male, 11 females) but only 5 female pigs survived to sexual maturity. These animals were bred to commercial sires to expand the population and determine potential interactive effects between myostatin mutations and the naturally-occurring g.3072G > A mutation in insulin-like growth factor 2. Even in subsequent generations (F0xWT, F1xF0, F1xF1), viability of piglets continued to be poor and was associated with the progeny’s proportion of the original clone genome, even in pigs lacking MSTN loss-of-function (LOF) mutations. However, viability of pigs with myostatin LOF (MSTN −/−) was especially poor as none of the 37 animals born were viable. Sequencing of cloned pigs indicated that off-target effects did not explain this poor viability. Reducing the percentage of the cloned genome by outcrossing successfully improved viability of MSTN +/+ and MSTN ± pigs, but not of MSTN −/− pigs. Characterization of MSTN ± pigs did reveal an increase in muscle growth and body weight compared with MSTN +/+ pigs. Therefore, in order for the promise of gene-editing of myostatin for growth promotion in livestock to be fulfilled, issues of viability of offspring and efficacy of editing have yet to be overcome. Additionally, gene-editing targets other than myostatin must be explored.

Objective: Epilepsy is considered as a network disorder of interacting brain regions. The propagation of local epileptic activity from the seizure onset zone (SOZ) along neuronal networks determines the semiology of seizures. However, in highly interconnected brain regions such as the insula, the association between the SOZ and semiology is blurred necessitating invasive stereoelectroencephalography (SEEG). Normative connectomes on MRI data enable to link different symptoms and lesion locations to a common functional network. The present study applied connectomics to disentangle epilepsy networks from insular SEEG recordings and to describe their relationship to seizure semiology. Methods: We retrospectively extracted functional networks by normative connectome analysis from 118 insular contacts depicting epileptic discharges during SEEG in 20 epilepsy patients. The resulting epilepsy networks were correlated to the corresponding semiology by voxel-wise regression and multivariate analyses of variances. Results: Epileptic foci were found in the posterior insula for somatosensory, other sensory and motor seizures, while cognitive and autonomic symptoms were related to the anterior insula. We identified insular connections to the superior temporal gyrus and heschl gyrus in sensory seizures and projections to the somatosensory cortex in somatosensory seizures. Insula-basal ganglia pathways were found in cognitive seizure manifestations, while insular connectivity to fronto-basal regions were strongest in patients with autonomic seizures. Conclusion: The semiology of seizures is mirrored in the functional connectivity of insular epileptic discharges. Combining SEEG and connectomics could provide additional information about seizure propagation within the epilepsy network and might enable new treatment options in the future like deep brain stimulation. [ABSTRACT FROM AUTHOR]

Background/Objectives: Periprosthetic joint infections (PJI) are difficult to treat due to biofilm formation on implant surfaces and the surrounding tissue, often requiring removal or exchange of prostheses along with long-lasting antibiotic treatment. Antiseptic irrigation during revision surgery might decrease bacterial biofilm load and thereby improve treatment success. This in vitro study investigated and compared the effect of five advanced wound irrigation solutions to reduce bacterial burden in the PJI microenvironment. Methods: We treated in vitro biofilms grown on titanium alloy implant discs with clinical bacterial strains isolated from patients with PJIs, as well as abscess communities in a plasma-supplemented collagen matrix. The biofilms were exposed for 1 min to the following wound irrigation solutions: Preventia®, Prontosan®, Granudacyn®, ActiMaris® forte ('Actimaris'), and Octenilin®. We measured the bacterial reduction of these irrigation solutions compared to Ringer–Lactate and to the strong bactericidal but not approved Betaseptic solution. Additionally, ex vivo free-floating bacteria isolated directly from clinical sonication fluids were treated in the same way, and regrowth or lack of regrowth was recorded as the outcome. Results: Irrigation solutions demonstrated variable efficacy. The mean CFU log10 reduction was as follows: Octenilin, 3.07, Preventia, 1.17, Actimaris, 1.11, Prontosan, 1.03, and Granudacyn, 0.61. For SACs, the reduction was: Actimaris, 8.27, Octenilin, 0.58, Prontosan, 0.56, Preventia, 0.35, and Granudacyn, 0.24. Conclusions: All solutions achieved complete bacterial eradication in all tested ex vivo sonication fluids, except Granudacyn, which was ineffective in 33% of the samples (2 out of 6). Advanced wound irrigation solutions have the potential to reduce bacterial burden in the PJI microenvironment during revision surgery. However, their efficacy varies depending on bacterial species, growth state, and the composition of the irrigation solution. This underscores the importance of considering these factors when developing future PJI-specific irrigation solutions. [ABSTRACT FROM AUTHOR]

Attention to carbon dioxide removal (CDR) in climate policy is growing, and many CDR methods such as direct air carbon capture and storage (DACCS) are controversial. As such, broadening knowledge creation to include stakeholder perspectives upstream of policy is important. This exploratory study provides insights into the stakeholder engagement process of a transdisciplinary research project and its findings regarding co-creative CDR policy design and evaluation. It analyzes the views of participants in a stakeholder engagement workshop on CDR and an online survey. In all instances, experts highlighted the importance of the context in which these technologies are deployed. Workshop participants' views of DACCS, including its risks and opportunities, evolved throughout the process, indicating that learning took place. We also present stakeholders' reflections on their own role in knowledge creation and policy design. The qualitative experience and joint exploration of topics reaffirm the relevance of proper engagement on controversial, wicked problems such as the scaling of CDR as exemplified for DACCS. A nuanced discussion of the deployment context matters for stakeholders' perception of DACCS. Our results underscore the importance of deliberative and adaptable policymaking in the current formative phase of CDR policy in Europe. Additionally, they highlight the need for policies to proactively address tradeoffs between climate mitigation efficiency and other goals. They advocate for government-backed CDR research and development (R&D) as a basis for future deployment alongside a fossil fuel phaseout to maintain a clear carbon budget and avert mitigation deterrence. [ABSTRACT FROM AUTHOR]

Grazia Honegger Fresco gives us direct observations of her daughter from birth to eight months, grouping her observations by age even further into birth to fourth month, fifth and sixth months, and seventh and eighth months. Within each age range, she focuses on Sara's sensory life and her relationships. Her observations are detailed and gentle as she strives to be free of preconceived judgements. She offers a lovely example of what it means to use observation as a tool to learn the inner life of the child. [Reprinted from "The NAMTA Journal" 15.3 (1990): 50-57.]

ObjectiveTo evaluate diagnostic accuracy of the corticotropin-releasing hormone (CRH) stimulation test and the overnight 8 mg dexamethasone suppression test (DST) for the differentiation of Cushing’s disease (CD) and ectopic Cushing’s syndrome (ECS).MethodsRetrospective study in 6 European centers. Inclusion criteria: patients with a) overt adrenocorticotropin (ACTH)-dependent Cushing’s syndrome at the time of dynamic testing, b) histopathological confirmed tumors and/or c) postoperative biochemical remission and/or adrenal insufficiency. Optimal cut-offs were calculated via receiver operating characteristic (ROC) analysis using CD as reference.Results469 patients were analyzed [78% females; median age 43 years (IQR 19)]. CRH test and overnight 8 mg DST were performed in 420 [CD, n=394 (94%); ECS, n=26 (6%)] and 237 patients [228 CD (96%), 9 ECS (4%)]. Both tests were performed in 205 patients (44%). The post-CRH %-increase at 30 minutes of both ACTH (cut-off ≥31%, sensitivity 83%, specificity 85%, AUC 0.81) and cortisol (cut-off ≥12%, sensitivity 82%, specificity 89%, AUC 0.86) discriminated best between CD and ECS. A test duration of >60 minutes did not improve diagnostic performance of the CRH test. The optimal cortisol cut-off for the %-suppression during the 8 mg DST was ≥55% (sensitivity 80%, specificity 78%, AUC 0.75).ConclusionThe CRH test has equivalent sensitivity but higher specificity than the 8 mg DST and is therefore the test of first choice. The diagnostic outcome of ACTH and cortisol is well comparable, however, sampling beyond 60 minutes post-CRH does not provide diagnostic benefits.

BackgroundWalking among crowds avoiding colliding with people is described by patients with vestibular disorders as vertigo-inducing. Accurate body motion while circumventing an impeding obstacle in the gait pathway is dependent on an integration of multimodal sensory cues. However, a direct role of vestibular signals in spatial perception of distance or orientation during obstacle circumvention has not been investigated to date.Materials and methodsWe examined trunk yaw motion during circumvention in patients with acute unilateral vestibular loss (aUVL) and compared their results with age-matched healthy controls (HCs). Subjects performed five gait tasks with eyes open two times: walk 6 m in total, but after 3 m, circumvent to the left or right, as closely as possible, a cylindrical obstacle representing a person, and then veer back to the original path; walk 6 m, but after left and right circumvention at 3 m, veer, respectively, to the right, and left 45 deg; and walk 6 m without circumvention. Trunk yaw angular velocities (YAVs) were measured using a gyroscope system.ResultsYaw angular velocity peak amplitudes approaching to, and departing from, the circumvented object were always greater for patients with aUVL compared to HCs, regardless of whether passing was to the aUVLs’ deficit or normal side. The departing peak YAV was always greater, circa 52 and 87%, than the approaching YAV for HCs when going straight and veering 45 deg (p ≤ 0.0006), respectively. For patients with aUVL, departing velocities were marginally greater (12%) than approaching YAVs when going straight (p < 0.05) and were only 40% greater when veering 45 deg (p = 0.05). The differences in departing YAVs resulted in significantly lower trajectory-end yaw angles for veering trials to the deficit side in patients with aUVL (34 vs. 43 degs in HCs).ConclusionThe results demonstrate the effects of vestibular loss on yaw velocity control during the three phases of circumvention. First, approaching an obstacle, a greater YAV is found in patients with aUVL. Second, the departing YAV is found to be less than in HCs with respect to the approaching velocity, resulting in larger deficit side passing yaw angles. Third, patients with UVLs show yaw errors returning to the desired trajectory. These results could provide a basis for rehabilitation protocols helping to avoid collisions while walking in crowded spaces.

HER2 acts an oncogenic driver in numerous cancers. Here, the authors design an anti-HER2 biparatopic and tetravalent IgG fusion with inhibitory effects in a xenograft model.

Adequate use of multimodal stimuli plays a crucial role in help forming the sense of presence within a virtual environment. While most of the presence research attempts to engage more sensory modalities to induce a higher sense of presence, this paper investigates the relevance of each sensory modality and different combinations on the subjective sense of presence using a specifically designed scenario of a passive experience. We chose a neutral test scenario of “waiting at a train station while a train is passing by” to avoid the potential influence of story narrative on mental presence and replicated realistic multimodal stimuli that are highly relevant to our test setting. All four stimuli - visual, auditory, vibration, and draught - with 16 possibilities of combinations were systematically evaluated with 24 participants. The evaluation was performed on one crucial aspect of presence – “realness” to reflect user presence in general. The perceived realism value was assessed using a scalometer. The findings of main effects indicate that the auditory stimuli had the most significant contribution in creating the sense of presence. The results of interaction effects suggest the impact of draught stimuli is significant in relation to other stimuli - visual and auditory. Also, the gender effects revealed that the sense of presence reported by female participants is influenced by more factors than merely adding more sensory modalities.