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The rural-urban learning achievements gap is a persistent issue to be addressed from a different approach. This study employed re-centered influence function decomposition with Young Lives data to estimate the rural-urban education production function and decompose the rural-urban learning achievements gap in Ethiopia. Results revealed that the rural-urban education production function is different across achievements distributions. Moreover, most of the rural-urban learning achievements gap is explained by student background characteristics. Unmeasured characteristics explain much of the proportion of the gap but the importance of that proportion varies across the distribution. Policy implications of the findings were discussed.

The oncolytic virus represents a promising therapeutic strategy involving the targeted replication of viruses to eliminate cancer cells, while preserving healthy ones. Despite ongoing clinical trials, this approach encounters significant challenges. This study delves into the interaction between an oncolytic virus and extracellular matrix mimics (ECM mimics). A three-dimensional colorectal cancer model, enriched with ECM mimics through bioprinting, was subjected to infection by an oncolytic virus derived from the vaccinia virus (oVV). The investigation revealed prolonged expression and sustained oVV production. However, the absence of a significant antitumor effect suggested that the virus’s progression toward non-infected tumoral clusters was hindered by the ECM mimics. Effective elimination of tumoral cells was achieved by introducing an oVV expressing FCU1 (an enzyme converting the prodrug 5-FC into the chemotherapeutic compound 5-FU) alongside 5-FC. Notably, this efficacy was absent when using a non-replicative vaccinia virus expressing FCU1. Our findings underscore then the crucial role of oVV proliferation in a complex ECM mimics. Its proliferation facilitates payload expression and generates a bystander effect to eradicate tumors. Additionally, this study emphasizes the utility of 3D bioprinting for assessing ECM mimics impact on oVV and demonstrates how enhancing oVV capabilities allows overcoming these barriers. This showcases the potential of 3D bioprinting technology in designing purpose-fit models for such investigations.

Abstract The article introduces an optical microscopy technique capable of simultaneously acquiring quantitative fluorescence and phase (or equivalently wavefront) images with a single camera sensor, avoiding any delay between both images, or registration of images acquired separately. The method is based on the use of a 2-dimensional diffraction grating (aka cross-grating) positioned at a millimeter distance from a 2-color camera. Fluorescence and wavefront images are extracted from the two color channels of the camera, and retrieved by image demodulation. The applicability of the method is illustrated on various samples, namely fluorescent micro-beads, bacteria and mammalian cells.

Treponematoses encompass a group of chronic and debilitating bacterial diseases transmitted sexually or by direct contact and attributed to Treponema pallidum. Despite being documented since as far back as 1963, the epidemiology of treponematoses in wild primates has remained an uninvestigated territory due to the inherent challenges associated with conducting examinations and obtaining invasive biological samples from wild animals. The primary aim of this study was to investigate the presence of treponemal infections in the critically endangered Western chimpanzees in Senegal, utilizing an innovative non-invasive stool serology method. We provide compelling evidence of the existence of anti-Treponema-specific antibodies in 13 out of 29 individual chimpanzees. Our study also underscores the significant potential of stool serology as a valuable non-invasive tool for monitoring and surveilling crucial emerging diseases in wild animals. We recognize two major implications: (1) the imperative need to assess the risks of treponematosis in Western chimpanzee populations and (2) the necessity to monitor and manage this disease following a holistic One Health approach.

Evidence is widespread that many species of Bombus are in population and biogeographical decline in response to adverse effects of global climate warming. The complex interactions of the mechanisms at the root of the declines are poorly understood. Among the numerous factors, we posit that heat stress in the nests could play a key role in the decline of bumblebee species. The similarity of the optimum temperature range in incubating nests is remarkable, about 28–32 °C regardless of species from the cold High Arctic to tropical environments indicates that the optimal temperature for rearing of brood in Bombus spp. is a characteristic common to bumblebees (perhaps a synapomorphy) and with limited evolutionary plasticity. We do note that higher brood rearing temperature for the boreal and Arctic species that have been tested is stressfully high when compared with that for B. terrestris. The Thermal Neutral Zone (TNZ), temperatures over which metabolic expenditure is minimal to maintain uniform nest temperatures, has not been studied in Bombus and may differ between species and biogeographic conditions. That heat stress is more serious than chilling is illustrated by the Thermal Performance Curve Relationship (TPC) (also sometimes considered as a Thermal Tolerance Relationship). The TPC indicates that development and activity increase more slowly as conditions become warmer until reaching a plateau of the range of temperatures over which rates of activity do not change markedly. After that, activity rates decline rapidly, and death ensues. The TPC has not been studied in eusocial bees except Apis dorsata but may differ between species and biogeographic conditions. The importance of the TPC and the TNZ indicates that environmental temperatures in and around bumblebee nests (which have been rarely studied especially in the contexts of nest architecture and substrate thermal characteristics) are factors central to understanding the adverse effects of heat stress and climatic warming on bumblebee populations, health, and biogeographical decline.

Once-daily extended-release tacrolimus (LCPT) exhibits increased bioavailability versus immediate-release (IR-TAC) and prolonged release (PR-TAC) tacrolimus. Improvements in tremor were previously reported in a limited number of kidney transplant patients who switched to LCPT. We conducted a non-interventional, non-randomized, uncontrolled, longitudinal, prospective, multicenter study to assess the impact of switching to LCPT on tremor and quality of life (QoL) in a larger population of stable kidney transplant patients. The primary endpoint was change in The Essential Tremor Rating Assessment Scale (TETRAS) score; secondary endpoints included 12-item Short Form Survey (SF-12) scores, tacrolimus trough concentrations, neurologic symptoms, and safety assessments. Subgroup analyses were conducted to assess change in TETRAS score and tacrolimus trough concentration/dose (C0/D) ratio by prior tacrolimus formulation and tacrolimus metabolizer status. Among 221 patients, the mean decrease of TETRAS score after switch to LCPT was statistically significant (p < 0.0001 vs. baseline). There was no statistically significant difference in change in TETRAS score after switch to LCPT between patients who had received IR-TAC and those who had received PR-TAC before switch, or between fast and slow metabolizers of tacrolimus. The overall increase of C0/D ratio post-switch to LCPT was statistically significant (p < 0.0001) and from baseline to either M1 or M3 (both p < 0.0001) in the mITT population and in all subgroups. In the fast metabolizers group, the C0/D ratio crossed over the threshold of 1.05 ng/mL/mg after the switch to LCPT. Other neurologic symptoms tended to improve, and the SF-12 mental component summary score improved significantly. No new safety concerns were evident. In this observational study, all patients had a significant improvement of tremor, QoL and C0/D ratio post-switch to LCPT irrespective of the previous tacrolimus formulation administered (IR-TAC or PR-TAC) and irrespective from their metabolism status (fast or slow metabolizers).

Carbohydrate sequencing is a formidable task identified as a strategic goal in modern biochemistry. It relies on identifying a large number of isomers and their connectivity with high accuracy. Recently, gas phase vibrational laser spectroscopy combined with mass spectrometry tools have been proposed as a very promising sequencing approach. However, its use as a generic analytical tool relies on the development of recognition techniques that can analyse complex vibrational fingerprints for a large number of monomers. In this study, we used a Bayesian deep neural network model to automatically identify and classify vibrational fingerprints of several monosaccharides. We report high performances of the obtained trained algorithm (GlAIcomics), that can be used to discriminate contamination and identify a molecule with a high degree of confidence. It opens the possibility to use artificial intelligence in combination with spectroscopy-augmented mass spectrometry for carbohydrates sequencing and glycomics applications.

Abstract In this study, we investigate how the terrestrial-aquatic transition influenced patterns of axial integration and modularity in response to the secondary adaptation to a marine lifestyle. We use 3D geometric morphometrics to quantify shape covariation among presacral vertebrae in pinnipeds (Carnivora; Pinnipedia) and to compare with patterns of axial integration and modularity in their close terrestrial relatives. Our results indicate that the vertebral column of pinnipeds has experienced a decrease in the strength of integration among all presacral vertebrae when compared to terrestrial carnivores (=fissipeds). However, separate integration analyses among the speciose Otariidae (i.e., sea lions and fur seals) and Phocidae (i.e., true seals) also suggests the presence of different axial organizations in these two groups of crown pinnipeds. While phocids present a set of integrated “thoracic” vertebrae, the presacral vertebrae of otariids are characterized by the absence of any set of vertebrae with high integration. We hypothesize that these differences could be linked to their specific modes of aquatic locomotion –i.e., pelvic vs pectoral oscillation. Our results provide evidence that the vertebral column of pinnipeds has been reorganized from the pattern observed in fissipeds but is more complex than a simple “homogenization” of the modular pattern of their close terrestrial relatives.

COMPA-Trono is one of the most emblematic cultural initiatives in Bolivia, both as a theater company, cultural center and pedagogical project, but also as an actor mobilized in the name of «art for social transformation». Between artistic, educational and political challenges, its members contribute to rescue and reinvent various local and regional «identity figures». In a sociological perspective, let us see how these actors, through the action of the group, appropriate and reconstruct them in different social arenas both local and global.

Abstract Coastal habitats are amongst the most dynamic on Earth, due to their simultaneous exposure to terrestrial, oceanic and atmospheric processes. Coastal taxa are therefore often ecologically specialised and adapted to withstand frequent shifts in sea level, wave exposure, temperature or salinity. This specialisation often resulting in significant cryptic diversity. Previous molecular studies have suggested that genetic differentiation in non-marine coastal organisms may be influenced by oceanic currents and fronts, but the extent to which such processes affect dispersal and evolution of such taxa remains unclear. Here we explore whether population genetic structure in two supralittoral rockpool beetle species (genus Ochthebius) can be predicted from the general circulation pattern of the marine currents and associated oceanic fronts. We simulated dispersal using a Lagrangian particle tracking model and compared this with population genetic structure inferred from COI (mitochondrial) and wingless (nuclear) genes applying linear models and Mantel tests. We show that a biophysical model based on oceanic currents and fronts in the western Mediterranean Sea is a much better predictor of observed population genetic structure than isolation by distance in both species. Our results show that oceanic processes, besides shaping contemporary population connectivity in fully marine organisms, also exert a meaningful influence on terrestrially-derived coastal taxa such as supralittoral rockpool beetles — the first time this mode of dispersal has been demonstrated in an insect.

Abstract Background The corpus callosum (CC) is a key brain structure. In children with neurodevelopmental delay, we compared standard qualitative radiological assessments with an automatic quantitative tool. Methods We prospectively enrolled 73 children (46 males, 63.0%) with neurodevelopmental delay at single university hospital between September 2020 and September 2022. All of them underwent 1.5-T brain magnetic resonance imaging (MRI) including a magnetization-prepared 2 rapid acquisition gradient echoes − MP2RAGE sequence. Two radiologists blindly reviewed the images to classify qualitatively the CC into normal, hypoplasic, hyperplasic, and/or dysgenetic classes. An automatic tool (QuantiFIRE) was used to provide brain volumetry and T1 relaxometry automatically as well as deviations of those parameters compared with a healthy age-matched cohort. The MRI reference standard for CC volumetry was based on the Garel et al. study. Cohen κ statistics was used for interrater agreement. The radiologists and QuantiFIRE’s diagnostic accuracy were compared with the reference standard using the Delong test. Results The CC was normal in 42 cases (57.5%), hypoplastic in 20 cases (27.4%), and hypertrophic in 11 cases (15.1%). T1 relaxometry values were abnormal in 26 children (35.6%); either abnormally high (18 cases, 24.6%) or low (8 cases, 11.0%). The interrater Cohen κ coefficient was 0.91. The diagnostic accuracy of the QuantiFIRE prototype was higher than that of the radiologists for hypoplastic and normal CC (p = 0.003 for both subgroups, Delong test). Conclusions An automated volumetric and relaxometric assessment can assist the evaluation of brain structure such as the CC, particularly in the case of subtle abnormalities. Relevance statement Automated brain MRI segmentation combined with statistical comparison to normal volume and T1 relaxometry values can be a useful diagnostic support tool for radiologists. Key points • Corpus callosum abnormality detection is challenging but clinically relevant. • Automated quantitative volumetric analysis had a higher diagnostic accuracy than that of visual appreciation of radiologists. • Quantitative T1 relaxometric analysis might help characterizing corpus callosum better. Graphical Abstract

Abstract Background Chronic kidney disease (CKD) induces muscle wasting and a reduction in the maximum voluntary force (MVF). Little is known about the neuromuscular fatigability in CKD patients, defined as the reduction of muscle force capacities during exercise. Neuromuscular fatigability is a crucial physical parameter of the daily living. The quantification of explosive force has been shown to be a sensitive means to assess neuromuscular fatigability. Thus, our study used explosive force estimates to assess neuromuscular fatigability in elderly CKD patients. Methods Inclusion criteria for CKD patients were age ≥ 60 years old and glomerular filtration rate (GFR) 60 mL/min/1.73 m2, age and diabetes matched. The fatigability protocol focused on a handgrip task coupled with surface electromyography (sEMG). Scalars were extracted from the rate of force development (RFD): absolute and normalized time periods (50, 75, 100, 150 and 200 ms, RFD50, RFD75, RFD100, RFD150 and RFD200, respectively), peak RFD (RFDpeak in absolute; NRFDpeak normalized), time‐to‐peak RFD (t‐RFDpeak) and the relative force at RFDpeak (MVF‐RFDpeak). A statistical parametric mapping approach was performed on the force, impulse and RFD–time curves. The integrated sEMG with time at 0–30, 0–50, 0–100 and 0–200 ms time intervals relative to onset of sEMG activity was extracted and groups were compared separately for each sex. Results The cohort of 159 individuals had a median age of 69 (9IQR) years and body mass index was 27.6 (6.2IQR) kg/m2. Propensity‐score‐matched groups balanced CKD patients and controls by gender with 66 males and 34 females. In scalar analysis, CKD patients manifested a higher decrement than controls in the early phase of contraction, regarding the NRFDpeak (P = 0.009; η2p = 0.034) and RFD75 and RFD100 (for both P

This work presents a novel approach to enhancing iris recognition systems through a two-module approach focusing on low-level image preprocessing techniques and advanced feature extraction. The primary contributions of this paper include: (i) the development of a robust preprocessing module utilizing the Canny algorithm for edge detection and the circle-based Hough transform for precise iris extraction, and (ii) the implementation of Binary Statistical Image Features (BSIF) with domain-specific filters trained on iris-specific data for improved biometric identification. By combining these advanced image preprocessing techniques, the proposed method addresses key challenges in iris recognition, such as occlusions, varying pigmentation, and textural diversity. Experimental results on the Human-inspired Domain-specific Binarized Image Features (HDBIF) Dataset, consisting of 1892 iris images, confirm the significant enhancements achieved. Moreover, this paper offers a comprehensive and reproducible research framework by providing source codes and access to the testing database through the Notre Dame University dataset website, thereby facilitating further application and study. Future research will focus on exploring adaptive algorithms and integrating machine learning techniques to improve performance across diverse and unpredictable real-world scenarios.

Background and aimsRight phrenic nerve palsy is the most frequent complication of cryoballoon procedures. The SMARTFREEZE™ console (Boston Scientific, St. Paul, MN, USA) has integrated a new tool for diaphragm monitoring—the Diaphragm Movement Sensor; however, it has not been evaluated in clinical practice. We aimed to assess the diagnostic performance of the Diaphragm Movement Sensor based on compound motor action potential data recorded simultaneously.MethodsThirty consecutive patients (mean age 63.2 ± 10.2 years) were included. We simultaneously recorded the compound motor action potential and the Diaphragm Movement Sensor during cryoapplications in the right pulmonary veins. The right phrenic nerve was paced at 60 per minute, 12 V and 2.9 ms. Compound motor action potential monitoring with a 30% decrease cutoff for the diagnosis of phrenic nerve threatening was considered the gold standard. The Diaphragm Movement Sensor decrease threshold was also set at 30%.ResultsConsidering compound motor action potential monitoring, phrenic nerve threatening occurred 11 times (in seven patients) among 84 cryoapplications (13.1%) at the right pulmonary veins. The sensitivity and specificity of the Diaphragm Movement Sensor were, respectively, 33% (95% CI: 7%–70%) and 49% (95% CI: 38%–61%; P

Bacterial infections represent a key public health issue due to the occurrence of multidrug-resistant bacteria. Recently, the amount of data supporting the dynamic control of epigenetic pathways by environmental cues has triggered research efforts toward the clarification of their role in microbial infections. Among protein post-translational modifications, reversible acetylation is the most implicated in the feedback to environmental stimuli and in cellular homeostasis. Accordingly, the latest studies identified the histone deacetylase 6 (HDAC6) enzyme as a crucial player in the complex molecular machinery underlying bacterial clearance or killing. A very important milestone for the elucidation of the consequence of HDAC6 activity in bacterial infections is herein described, unveiling for the first time the role of a potent HDAC6 inhibitor in interfering with biofilm formation and modulating virulence factors of P. aeruginosa. We demonstrated that compound F2F-2020202 affected the production of some important virulence factors in P. aeruginosa, namely pyocyanin and rhamnolipids, clearly impairing its ability to form biofilm. Furthermore, evidence of possible QS involvement is supported by differential regulation of specific genes, namely RhlI, phAz1, and qsrO. The data herein obtained also complement and in part explain our previous results with selective HDAC6 inhibitors able to reduce inflammation and bacterial load in chronic infection models recapitulating the cystic fibrosis (CF) phenotype. This study fosters future in-depth investigation to allow the complete elucidation of the molecular mechanisms underlying HDAC6’s role in bacterial infections.

BackgroundRepeated sub-concussive head impacts are a growing brain health concern, but their possible biomarkers remain elusive. One impediment is the lack of a randomised controlled human experimental model to study their effects on the human brain.ObjectivesThis work had two objectives. The first one was to provide a randomised controlled human experimental model to study the acute effects of head impacts on brain functions. To achieve this, this work's second objective was to investigate if head impacts from heading footballs acutely alter brain excitability by increasing corticospinal inhibition as compared to a control group.MethodsIn practised and unpractised young healthy adults, transcranial magnetic stimulation was used to assess corticospinal silent period (CSP) duration and corticospinal excitability (CSE) before and immediately after performing headings by returning 20 hand-thrown balls directed to the head (Headings; n = 30) or the dominant foot (Control; n = 30). Moreover, the Rivermead Post-Concussion Questionnaire (RPQ) was used to assess the symptoms of head impacts. Head acceleration was also assessed in subgroups of participants.ResultsThe intervention lengthened CSP duration in both the Headings (6.4 ± 7.5%) and Control groups (4.6 ± 2.6%), with no difference in lengthening between the two groups. Moreover, CSE was not altered by the intervention and did not differ between groups. However, performing headings increased headaches and dizziness symptoms and resulted in greater head acceleration upon each football throw (12.5 ± 1.9g) as compared to the control intervention (5.5 ± 1.3g).ConclusionsThe results suggest that head impacts from football headings do not acutely alter brain excitability as compared to a control intervention. However, the results also suggest that the present protocol can be used as an experimental model to investigate the acute effects of head impacts on the human brain.

African elephants have a wide range of abilities using their trunk. As a muscular hydrostat, and thanks to the two finger-like processes at its tip, this proboscis can both precisely grasp and exert considerable force by wrapping. Yet few studies have attempted to quantify its distal grasping force. Thus, using a device equipped with force sensors and an automatic reward system, the trunk tip pinch force has been quantified in five captive female African savanna elephants. Results showed that the maximum pinch force of the trunk was 86.4 N, which may suggest that this part of the trunk is mainly dedicated to precision grasping. We also highlighted for the first time a difference in force between the two fingers of the trunk, with the dorsal finger predominantly stronger than the ventral finger. Finally, we showed that the position of the trunk, particularly the torsion, influences its force and distribution between the two trunk fingers. All these results are discussed in the light of the trunk's anatomy, and open up new avenues for evolutionary reflection and soft robot grippers.

Okapi (Okapia johnstoni) belong to the Giraffidae family and is the only representative of the Okapia genus. The species has been declared as endangered and due to its very elusive nature, little is known about its reproductive behavior. The wild population has continued to decrease over the last decades despite the different conservation programs developed worldwide. Captive breeding is difficult and the European population is not self-sustaining. An alternative tool to prevent the extinction of this charismatic species is the use of assisted reproductive technologies (ART). Specifically, we introduce a novel protocol for the in vitro maturation (IVM) and cryopreservation of matured oocytes obtained post-mortem. Out of sixteen cumulus-oocytes complexes isolated from one deceased individual, four matured metaphase II (MII) oocytes were successfully obtained following IVM. Furthermore, these matured oocytes demonstrated resilience during the vitrification/warming process and underwent sperm injection. Although no embryos were obtained, this study represents the first step towards the application of ART in okapi, providing a foundation for future reproductive interventions aimed at preserving self-sustaining captive populations.

Flowgy is a semi-automated tool designed to simulate airflow across the nasal passage and detect airflow alterations in humans. In this study, we tested the use and accuracy of Flowgy in non-human vertebrates, using large felids as the study group. Understanding the dynamics of nasal airflow in large felids such as lions (Panthera leo) is crucial for their health and conservation. Therefore, we simulated airflow during inspiration through the nasal passage in three lions (Panthera leo), two of which were siblings (specimens ZPB_PL_002 and ZPB_PL_003), without breathing obstructions. However, one of the specimens (ZPB_PL_001) exhibited a slight obstruction in the nasal vestibule, which precluded the specimen from breathing efficiently. Computed tomography (CT) scans of each specimen were obtained to create detailed three-dimensional models of the nasal passage. These models were then imported into Flowgy to simulate the airflow dynamics. Virtual surgery was performed on ZPB_PL_001 to remove the obstruction and re-simulate the airflow. In parallel, we simulated the respiration of the two sibling specimens and performed an obstructive operation followed by an operation to remove the obstruction at the same level and under the same conditions as the original specimen (ZPB_PL_001). Thus, we obtained a pattern of precision for the operation by having two comparable replicas with the obstructed and operated specimens. The simulations revealed consistent airflow patterns in the healthy specimens, demonstrating the accuracy of Flowgy. The originally obstructed specimen and two artificially obstructed specimens showed a significant reduction in airflow through the right nostril, which was restored after virtual surgery. Postoperative simulation indicated an improvement of >100% in respiratory function. Additionally, the temperature and humidity profiles within the nostrils showed marked improvements after surgery. These findings underscore the potential of Flowgy in simulating nasal airflow and predicting the outcomes of surgical interventions in large felids. This could aid in the early detection of respiratory diseases and inform clinical decision-making, contributing to improved veterinary care and conservation efforts. However, further research is needed to validate these findings in other species and explore the potential of integrating Flowgy with other diagnostic and treatment tools in veterinary medicine.

TG6002 is an oncolytic vaccinia virus expressing FCU1 protein, which converts 5-fluorocytosine into 5-fluorouracil. The study objectives were to assess tolerance, viral replication, 5-fluorouracil synthesis, and tumor microenvironment modifications to treatment in dogs with spontaneous malignant tumors. Thirteen dogs received one to three weekly intratumoral injections of TG6002 and 5-fluorocytosine. The viral genome was assessed in blood and tumor biopsies by qPCR. 5-Fluorouracil concentrations were measured in serum and tumor biopsies by liquid chromatography or high-resolution mass spectrometry. Histological and immunohistochemical analyses were performed. The viral genome was detected in blood (7/13) and tumor biopsies (4/11). Viral replication was suspected in 6/13 dogs. The median intratumoral concentration of 5-fluorouracil was 314 pg/mg. 5-Fluorouracil was not detected in the blood. An increase in necrosis (6/9) and a downregulation of intratumoral regulatory T lymphocytes (6/6) were observed. Viral replication, 5-fluorouracil synthesis, and tumor microenvironment changes were more frequently observed with higher TG6002 doses. This study confirmed the replicative properties, targeted chemotherapy synthesis, and reversion of the immunosuppressive tumor microenvironment in dogs with spontaneous malignant tumors treated with TG6002 and 5-fluorocytosine.

Abstract Background Hypertension is the most frequent chronic pathology in France and in the world. It is one of the main modifiable cardiovascular risk factors. In France, 50% of treated hypertensives are uncontrolled and only 30% of treated patients are fully adherent to their antihypertensive treatment. Poor adherence to drug treatments is considered as one of the main causes of non-control of hypertension. Since 2018, a new profession has entered the French healthcare system: advanced practice nurses (APN). They have many broad-based skills, at the interface of nursing and medical exercises. The purpose of this study is to assess the impact of an APN intervention versus usual care on hypertension control. Methods The study will take place at the Hôtel-Dieu University Hospital, Paris, France, as prospective, open-label, controlled, randomized 1-to-1, monocentric, and superiority trial. The participants will be recruited during day hospitalization for cardiovascular assessment in the context of their hypertension management. Patients will be divided into two groups: a “usual care” group which will continue traditional follow-up (day hospitalization followed by consultation with a medical doctor (MD) within approximately 2–12 months) and an “intervention” group which will meet an APN between the day hospitalization and the MD consultation. Participants will be monitored until 12 months after the day hospitalization, depending on their last follow-up study appointment (MD consultation). The primary outcome is the rate of controlled BP (BP < 140/90 mmHg in office BP measurement) in each group. The hypothesis formulated is that an individual APN intervention, included in usual hypertension management, improves hypertension control. Discussion This innovative study will be the first in France where APNs are beginning to be established in the healthcare system. It will provide an objective look at this new profession and the impact it can have in the framework of global management of hypertension. Trial registration ClinicalTrials.gov NCT0448249. Registered on June 24, 2020.

The venous anatomy of the two-toed sloth (Choloepus didactylus) remains poorly understood, particularly in living specimens due to the limitations of traditional cadaveric studies. This study aims to describe the unique venous structures of Choloepus didactylus using computed tomography, enhancing our understanding of this species in a live setting. Three living Choloepus didactylus underwent CT scans as part of routine clinical assessments. The images were reconstructed using 3D Slicer software (version 5.6.2), focusing on the caudal vena cava anatomy. The reconstructions confirmed the presence of a significant intravertebral vein, showing complex venous connections through the ventral sacral foramen and vertebral foramina. These findings highlight notable anatomical variations and challenge existing literature on the species’ venous architecture. By employing modern imaging technologies, this research provides new insights into the venous anatomy of Choloepus didactylus, demonstrating the value of non-invasive techniques in studying the anatomical features of live animals, thereby offering a foundation for further comparative and evolutionary studies.

Objectives: To assess the ability of the aortic aneurysm volume (AAV), aneurysmal lumen volume (ALV), and aneurysmal thrombus volume (ATV) to predict the need for aortic reintervention when using the maximal aortic diameter as a reference. Methods: This monocentric retrospective study included 31 consecutive patients who underwent successful thoracic endovascular aortic repair (TEVAR) to treat an atheromatous thoracic aortic aneurysm. All patients underwent clinical and computed tomography angiography (CTA) for 3 years after TEVAR. The patients were categorized into group 0 if no aortic reintervention was required during the follow-up period and categorized into group 1 if they experienced a type I or III endoleak or aneurysm diameter increase requiring intervention. The maximum aneurysm sac diameter and the AAV, ALV, and ATV were calculated using CTA images obtained preoperatively (T0) and at 6–12 months (T1), 24 months (T2), and 36 months (T3) postoperatively, and their changes over time were analyzed. Correlations between diameter and changes in AAV, ALV, and ATV were assessed, and the association between diameter and volume changes and reintervetion was examined. The cutoff values for predicting the need for reintervention was determined using a receiver operating characteristic (ROC) curve. The accuracy of volume change versus diameter change for predicting the need for reintervention was analyzed. Results: There were no significant differences in terms of the mean aneurysm diameter or AAV, ALV or ATV between the groups at preoperative CTA or after one year of follow-up imaging. The mean ATV was higher in group 1 than in group 0 at 2 years (187.6 ± 86.3 mL vs. 114.7 ± 64.7 mL; p = 0.057) and after 3 years (195.0 ± 86.7 mL vs. 82.1 ± 39.9 mL; p = 0.013). The maximal diameter was greater in group 1 than in group 0 at 3 years (67.3 ± 9.5 mm vs. 55.3 ± 12.6 mm; p = 0.044). The rate of AAV change between T0 and T1 was significantly higher in group 1 (7 ± 4.5%) than in group 0 (−6 ± 6.8%; p < 0.001). The rate of ATV change between T1-T3 was significantly higher in group 1 than in group 0 (34 ± 40.9% vs. −13 ± 14.4% (p = 0.041)); similar results were observed for the rate of ATV change between T2 and T3 (27 ± 50.1% for group 1 vs. −8 ± 49.5% in group 0 (p < 0.001)). According to our multivariate analysis, the annual growth rate for AAV between T0 and T1 was the only independent factor that was significantly associated with aortic reintervention (area under the curve (AUC) = 0.84, OR = 1.57, p = 0.025; optimal cutoff +0.4%). An increase in the annual growth rate of the ATV between T0 and T3 was independently associated with the need for aortic reintervention (area under the curve (AUC) = 0.90, OR = 1.11, p = 0.0347; optimal cutoff +10.1%). Conclusions: Aortic volume analysis can predict the need for aortic reintervention more accurately and earlier than maximal aortic diameter.

Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

ABSTRACTToll-like receptor 3 (TLR3) agonists such as polyinosinic:polycytidylic acid (poly(I:C)) have immunostimulatory effects that can be taken advantage of to induce anticancer immune responses in preclinical models. In addition, poly(I:C) has been introduced into clinical trials to demonstrate its efficacy as an adjuvant and to enhance the immunogenicity of locally injected tumors, thus reverting resistance to PD-L1 blockade in melanoma patients. Here, we report the pharmacokinetic, pharmacodynamic, mechanistic and toxicological profile of a novel TLR3 agonist, TL-532, a chemically synthesized double-stranded RNA that is composed by blocks of poly(I:C) and poly(A:U) (polyadenylic – polyuridylic acid). In preclinical models, we show that TL-532 is bioavailable after parenteral injection, has an acceptable toxicological profile, and stimulates the production of multiple chemokines and interleukins that constitute pharmacodynamic markers of its immunostimulatory action. When given at a high dose, TL-532 monotherapy reduced the growth of bladder cancers growing on mice. In addition, in immunodeficient mice lacking formylpeptide receptor-1 (FPR1), TL-532 was able to restore the response of orthotopic subcutaneous fibrosarcoma to immunogenic chemotherapy. Altogether, these findings may encourage further development of TL-532 as an immunotherapeutic anticancer agent.

In the coming years, climate change is likely to increase the frequency and intensity of heatwaves. In many organisms, heat stress provokes physiological perturbations and can lead to decreased male fertility. Bumblebees are endo-heterothermic but display interspecific differences in thermotolerance that could have conservation implications. For the species of concern Bombus magnus, exposure to high temperatures can severely reduce sperm quality and, consequently, reproductive success. Such is not the case for B. terrestris, a ubiquitous species. To decipher the mechanisms at play, we characterized the seminal fluid proteomes of the two species. We quantified 1121 proteins, of which 522 were differentially expressed between B. terrestris and B. magnus. Several proteins with protective functions, such as proteases, antioxidant proteins and various heat-shock proteins, were present at higher levels in B. terrestris than in B. magnus under both control and heat-stress conditions. The same was true for proteins involved in cellular homeostasis, immunity, lipid/sugar metabolism and thermotolerance. Furthermore, proteins involved in the capture and elimination of reactive oxygen species also occurred at much high levels in B. terrestris. Overall, these results clearly indicate differences in the seminal proteome of the more thermotolerant B. terrestris versus B. magnus. The differences may contribute to explaining interspecific differences in sperm survival.

The gut microbiota plays a crucial role in animal health and homeostasis, particularly in endangered species conservation. This study investigated the fecal microbiota composition of European captive-bred African savanna elephants (Loxodonta africana) housed in French zoos, and compared it with wild African savanna elephants. Fecal samples were collected and processed for DNA extraction and amplicon sequencing of the 16S rRNA gene. The analysis of α and β diversity revealed significant effects of factors such as diet, daily activity, and institution on microbiota composition. Specifically, provision of branches as part of the diet positively impacted microbiota diversity. Comparative analyses demonstrated distinct differences between captive and wild elephant microbiomes, characterized by lower bacterial diversity and altered co-occurrence patterns in the captive population. Notably, specific taxa were differentially abundant in captive and wild elephants, suggesting the influence of the environment on microbiota composition. Furthermore, the study identified a core association network shared by both captive and wild elephants, emphasizing the importance of certain taxa in maintaining microbial interactions. These findings underscore the impact of environment and husbandry factors on elephant gut microbiota, highlighting the benefits of dietary enrichment strategies in zoos to promote microbiome diversity and health. The study contributes to the broader understanding of host-microbiota interactions and provides insights applicable to conservation medicine and captive animal management.