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Abstract Sperm whales (Physeter macrocephalus) have been studied for decades, but the development of their clicks during the animal growth is not yet well known. The click they emit during socialization and echolocation contains information about the length of their acoustic organs and, therefore the length of the body through the interpulse interval (IPI). This paper provides the first IPI/age relationship for juvenile male and female sperm whales (Physeter macrocephalus) based on field recordings of individuals whose age is largely known. Across 9 years, audiovisual recordings of a Mauritian sperm whale social unit were carried out. Adult female and juvenile sperm whales were identified and aged. The dataset made from those recordings is publicly available. The interpulse interval was measured for individuals whose ages ranged from 7 days to around 38 years. The growth of the acoustic organ of juveniles showed an early inter-individual variability as well as sexual dimorphism. Usual growth models were also fitted, predicting a mean $$IPI_\infty$$ I P I ∞ of 3.5 ms for adults and a physical maturity reached at around 30 years old. The use of passive acoustic monitoring (PAM) is one of the main tools used to study sperm whales. This IPI-age relationship may aid demographic studies on sperm whales by enabling PAM to assess the ages of recorded sperm whales.

Abstract $$^{177}{\hbox {Lu}}$$ 177 Lu radiopharmaceutical therapy is a standardized systemic treatment, with a typical dose of 7.4 GBq per injection, but its response varies from patient to patient. Dosimetry provides the opportunity to personalize treatment, but it requires multiple post-injection images to monitor the radiopharmaceutical’s biodistribution over time. This imposes an additional imaging burden on centers with limited resources. This review explores methods to lessen this burden by optimizing acquisition types and minimizing the number and duration of imaging sessions. After summarizing the different steps of dosimetry and providing examples of dosimetric workflows for $$^{177}{\hbox {Lu}}$$ 177 Lu -DOTATATE and $$^{177}{\hbox {Lu}}$$ 177 Lu -PSMA, we examine dosimetric workflows based on a reduced number of acquisitions, or even just one. We provide a non-exhaustive description of simplified methods and their assumptions, as well as their limitations. Next, we detail the specificities of each normal tissue and tumors, before reviewing dose-response relationships in the literature. In conclusion, we will discuss the current limitations of dosimetric workflows and propose avenues for improvement.

Abstract Background Despite advancements in managing metastatic clear cell renal carcinoma (mccRCC) through antiangiogenic tyrosine kinase inhibitors and immunotherapy, there remains a demand for novel treatments for patients experiencing progression despite the use of these medications. There is currently no established standard treatment for patients receiving third therapy line. Prostate Specific Membrane Antigen (PSMA) whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma is also highly expressed in neovessels of various solid tumors including renal cell carcinoma (RCC): 86% of clear cell RCC, 61% of chromophobe RCC, and 28% of papillary RCC. Therefore, PSMA may be a target expressed in metastatic ccRCC for radionuclide therapy using PSMA ligands radiolabeled with Lutetium-177 (PRLT). 177Lu-PSMA delivers ß-particle radiation to PSMA-expressing cells and the surrounding microenvironment with demonstrated efficacy in metastatic prostate cancer. Methods This is a multicenter phase I/II study designed to assess the tolerability and effectiveness of 177Lu-PSMA-1 in individuals with PSMA-positive metastatic clear cell renal cell carcinoma (ccRCC), identified through 68Ga-PSMA PET, conducted in France (PRadR). 48 patients will be treated with 4 cycles of 7.4 GBq of 177Lu-PSMA-1 every 6 weeks. The primary objective is to evaluate the safety of 177Lu-PSMA-1 (phase I) and the efficacy of 177Lu-PSMA-1 in mccRCC patients (phase II). Primary endpoints are incidence of Severe Toxicities (ST) occurring during the first cycle (i.e. 6 first weeks) and disease Control Rate after 24 weeks of treatment (DCR24w) as per RECIST V1.1. Secondary objective is to further document the clinical activity of 177Lu-PSMA-1 in mccRCC patients (duration of response (DoR), best overall response rate (BORR), progression fee survival (PFS) and overall survival (OS). Discussion Our prospective study may lead to new potential indications for the use of 177Lu-PSMA-1 in mccRCC patients and should confirm the efficacy and safety of this radionuclide therapy with limited adverse events. The use of 177Lu-PSMA-1may lead to increase disease control, objective response rate and the quality of life in mccRCC patients. Trial registration ClinicalTrials.gov: NCT06059014.

IntroductionPatients with high-grade gliomas are at risk of developing increased intracranial hypertension (ICHT) in relation to the increase in volume of their tumor. ICP change cannot be measured by invasive method but can be estimated by using routine clinical signs, in combination with a standard imaging method, magnetic resonance imaging (MRI). A non-invasive monitoring of ICP could be of interest in high-grade glioma, in particular after radiotherapy treatment with as major side effect a cerebral oedema.Patients and MethodsThis prospective clinical study aimed to compare the ICP changes (estimated by a non-invasive method based upon distortion product otoacoustic emissions (DPOAE) monitoring) with volume changes observed on MRI in patients with high-grade gliomas treated with radiotherapy. DPOAE measurements were performed one month after the end of radiotherapy and then every 3 months for one year. At each visit, the patient also underwent MRI as well as an evaluation of clinical signs.ResultsThe variation in the estimate of intracranial pressure readout measured at each follow-up visit (in absolute value with respect to the baseline measurements) was significantly associated with the variation of T2/FLAIR volume (n=125; p

As older adults tend to reduce their intake of animal-source proteins, plant-source proteins may offer valuable resources for better protein intake. The aim of this study was to assess whether the pea proteins can be used to achieve blood amino acid levels that stimulate muscle protein synthesis. We measured variations in plasma amino acid concentrations in young and older adults given pea (NUTRALYS® S85 Plus) or whey proteins either alone or in a standardized meal. The effect of amino acid concentrations on protein synthesis in C2C12 myotubes was determined. In terms of results, plasma amino acid concentrations reflected the difference between the amino acid contents of whey and pea proteins. Blood leucine showed a greater increase of 91 to 130% with whey protein compared to pea protein, while the opposite was observed for arginine (A greater increase of 147 to 210% with pea compared to whey). Culture media prepared with plasmas from the human study induced age-dependent but not protein-type-dependent changes in myotube protein synthesis. In conclusion, pea and whey proteins have the same qualities in terms of their properties to maintain muscle protein synthesis. Pea proteins can be recommended for older people who do not consume enough animal-source proteins.

Hearing impairment (HI) is a prevalent neurosensory condition globally, impacting 5% of the population, with over 50% of congenital cases attributed to genetic etiologies. In Tunisia, HI underdiagnosis prevails, primarily due to limited access to comprehensive clinical tools, particularly for syndromic deafness (SD), characterized by clinical and genetic heterogeneity. This study aimed to uncover the SD spectrum through a 14-year investigation of a Tunisian cohort encompassing over 700 patients from four referral centers (2007–2021). Employing Sanger sequencing, Targeted Panel Gene Sequencing, and Whole Exome Sequencing, genetic analysis in 30 SD patients identified diagnoses such as Usher syndrome, Waardenburg syndrome, cranio-facial-hand-deafness syndrome, and H syndrome. This latter is a rare genodermatosis characterized by HI, hyperpigmentation, hypertrichosis, and systemic manifestations. A meta-analysis integrating our findings with existing data revealed that nearly 50% of Tunisian SD cases corresponded to rare inherited metabolic disorders. Distinguishing between non-syndromic and syndromic HI poses a challenge, where the age of onset and progression of features significantly impact accurate diagnoses. Despite advancements in local genetic characterization capabilities, certain ultra-rare forms of SD remain underdiagnosed. This research contributes critical insights to inform molecular diagnosis approaches for SD in Tunisia and the broader North-African region, thereby facilitating informed decision-making in clinical practice.

Non-mutated FVIII-specific CD4 T cell epitopes have been recently found to contribute to the development of inhibitors in patients with hemophilia A (HA), while auto-reactive CD4 T cells specific to FVIII circulate in the blood of healthy individuals at a frequency close to the foreign protein ovalbumin. Thus, although FVIII is a self-protein, the central tolerance raised against FVIII appears to be low. In this study, we conducted a comprehensive analysis of the FVIII CD4 T cell repertoire in 29 healthy donors. Sequencing of the CDR3β TCR region from isolated FVIII-specific CD4 T cells revealed a limited usage and pairing of TRBV and TRBJ genes as well as a mostly hydrophobic composition of the CDR3β region according to their auto-reactivity. The FVIII repertoire is dominated by a few clonotypes, with only 13 clonotypes accounting for half of the FVIII response. Through a large-scale epitope mapping of the full-length FVIII sequence, we identified 18 immunodominant epitopes located in the A1, A3, C1, and C2 domains and covering half of the T cell response. These epitopes exhibited a broad specificity for HLA-DR or DP molecules or both. T cell priming with this reduced set of peptides revealed that highly expanded clonotypes specific to these epitopes were responsible individually for up to 32% of the total FVIII repertoire. These FVIII T cell epitopes and clonotypes were shared among HLA-unrelated donors tested and previously reported HA patients. Our study highlights the role of the auto-reactive T cell response against FVIII in HA and its similarity to the response observed in healthy individuals. Thus, it provides valuable insights for the development of new tolerance induction and deimmunization strategies.

Abstract Background The aim of this study was to investigate the quantification performance of a 360° CZT camera for 177Lu-based treatment monitoring. Methods Three phantoms with known 177Lu activity concentrations were acquired: (1) a uniform cylindrical phantom for calibration, (2) a NEMA IEC body phantom for analysis of different-sized spheres to optimise quantification parameters and (3) a phantom containing two large vials simulating organs at risk for tests. Four sets of reconstruction parameters were tested: (1) Scatter, (2) Scatter and Point Spread Function Recovery (PSFR), (3) PSFR only and (4) Penalised likelihood option and Scatter, varying the number of updates (iterations × subsets) with CT-based attenuation correction only. For each, activity concentration (ARC) and contrast recovery coefficients (CRC) were estimated as well as root mean square. Visualisation and quantification parameters were applied to reconstructed patient image data. Results Optimised quantification parameters were determined to be: CT-based attenuation correction, scatter correction, 12 iterations, 8 subsets and no filter. ARC, CRC and RMS results were dependant on the methodology used for calculations. Two different reconstruction parameters were recommended for visualisation and for quantification. 3D whole-body SPECT images were acquired and reconstructed for 177Lu-PSMA patients in 2–3 times faster than the time taken for a conventional gamma camera. Conclusion Quantification of whole-body 3D images of patients treated with 177Lu-PSMA is feasible and an optimised set of parameters has been determined. This camera greatly reduces procedure time for whole-body SPECT.

Understanding speech in noise is particularly difficult for individuals occupationally exposed to noise due to a mix of noise-induced auditory lesions and the energetic masking of speech signals. For years, the monitoring of conventional audiometric thresholds has been the usual method to check and preserve auditory function. Recently, suprathreshold deficits, notably, difficulties in understanding speech in noise, has pointed out the need for new monitoring tools. The present study aims to identify the most important variables that predict speech in noise understanding in order to suggest a new method of hearing status monitoring. Physiological (distortion products of otoacoustic emissions, electrocochleography) and behavioral (amplitude and frequency modulation detection thresholds, conventional and extended high-frequency audiometric thresholds) variables were collected in a population of individuals presenting a relatively homogeneous occupational noise exposure. Those variables were used as predictors in a statistical model (random forest) to predict the scores of three different speech-in-noise tests and a self-report of speech-in-noise ability. The extended high-frequency threshold appears to be the best predictor and therefore an interesting candidate for a new way of monitoring noise-exposed professionals.

Abstract Glanzmann thrombasthenia (GT) is a genetic bleeding disorder characterised by severely reduced/absent platelet aggregation in response to multiple physiological agonists. The severity of bleeding in GT varies markedly, as does the emergency situations and complications encountered in patients. A number of emergency situations may occur in the context of GT, including spontaneous or provoked bleeding, such as surgery or childbirth. While general management principles apply in each of these settings, specific considerations are essential for the management of GT to avoid escalating minor bleeding events. These recommendations have been developed from a literature review and consensus from experts of the French Network for Inherited Platelet Disorders, the French Society of Emergency Medicine, representatives of patients’ associations, and Orphanet to aid decision making and optimise clinical care by non-GT expert health professionals who encounter emergency situations in patients with GT.

ObjectivesTo determine factors associated with COVID-19-related death in people with rheumatic diseases.MethodsPhysician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category.ResultsOf 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death.ConclusionAmong people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Abstract The understanding of transport and mixing in fluids in the presence and in the absence of external fields and reactions represents a challenging topic of strategic relevance for space exploration. Indeed, mixing and transport of components in a fluid are especially important during long-term space missions where fuels, food and other materials, needed for the sustainability of long space travels, must be processed under microgravity conditions. So far, the processes of transport and mixing have been investigated mainly at the macroscopic and microscopic scale. Their investigation at the mesoscopic scale is becoming increasingly important for the understanding of mass transfer in confined systems, such as porous media, biological systems and microfluidic systems. Microgravity conditions will provide the opportunity to analyze the effect of external fields and reactions on optimizing mixing and transport in the absence of the convective flows induced by buoyancy on Earth. This would be of great practical applicative relevance to handle complex fluids under microgravity conditions for the processing of materials in space.

Vitamin D has an impact on mitochondrial biogenesis and oxidative activity in skeletal muscle both in vitro and in vivo, and vitamin D supplementation in older people may improve muscle mass and strength.

Reducing greenhouse gas emissions in residential buildings relies on three channels that are rarely assessed together—insulating homes, switching to low-carbon heating systems and decarbonizing heating fuels. Their combination results from an interplay between top-down planning of the energy system and decentralized policies for the residential sector—insulation subsidies in particular. In this paper, we examine how the design of insulation subsidies influences the allocation of efforts between these three channels. To do so, we use an innovative framework coupling a highly detailed model of residential energy demand with a highly detailed model of the energy system, both focused on France. We find that the most cost-effective effort allocation to reach carbon neutrality implies 19% emission reductions from home insulation, 36% from fuel switch and 45% from fuel decarbonization. This however requires perfectly targeted subsidies. In three alternative, arguably more realistic subsidy scenarios, we find that total system cost is increased by 11%–16%. Our results highlight the key role played by subsidy specifications in determining the trade-off between insulation and fuel switch, e.g. insulation investments doubles, and heat pump adoption is 19% lower, when subsidies are restricted to the most comprehensive measures. Finally, alternative assumptions regarding the availability of renewable energy sources—biogas in particular—imply stronger energy efficiency efforts.

Abstract Launched in 2019, the French Citizens’ Convention for Climate (CCC) tasked 150 randomly chosen citizens with proposing fair and effective measures to fight climate change. This was to be fulfilled through an “innovative co-construction procedure”, involving some unspecified external input alongside that from the citizens. Did inputs from the steering bodies undermine the citizens’ accountability for the output? Did co-construction help the output resonate with the general public, as is expected from a citizens’ assembly? To answer these questions, we build on our unique experience in observing the CCC proceedings and documenting them with qualitative and quantitative data. We find that the steering bodies’ input, albeit significant, did not impair the citizens’ agency, creativity, and freedom of choice. While succeeding in creating consensus among the citizens who were involved, this co-constructive approach, however, failed to generate significant support among the broader public. These results call for a strengthening of the commitment structure that determines how follow-up on the proposals from a citizens’ assembly should be conducted.

Abstract Background The number of SPECT/CT time-points is important for accurate patient dose estimation in peptide receptor radionuclide therapy. However, it may be limited by the patient’s health and logistical reasons. Here, an image-based dosimetric workflow adapted to the number of SPECT/CT acquisitions available throughout the treatment cycles was proposed, taking into account patient-specific pharmacokinetics and usable in clinic for all organs at risk. Methods Thirteen patients with neuroendocrine tumors were treated with four injections of 7.4 GBq of $$^{177}$$ 177 Lu-DOTATATE. Three SPECT/CT images were acquired during the first cycle (1H, 24H and 96H or 144H post-injection) and a single acquisition (24H) for following cycles. Absorbed doses were estimated for kidneys (LK and RK), liver (L), spleen (S), and three surrogates of bone marrow (L2 to L4, L1 to L5 and T9 to L5) that were compared. 3D dose rate distributions were computed with Monte Carlo simulations. Voxel dose rates were averaged at the organ level. The obtained Time Dose-Rate Curves (TDRC) were fitted with a tri-exponential model and time-integrated. This method modeled patient-specific uptake and clearance phases observed at cycle 1. Obtained fitting parameters were reused for the following cycles, scaled to the measure organ dose rate at 24H. An alternative methodology was proposed when some acquisitions were missing based on population average TDRC (named STP-Inter). Seven other patients with three SPECT/CT acquisitions at cycles 1 and 4 were included to estimate the uncertainty of the proposed methods. Results Absorbed doses (in Gy) per cycle available were: 3.1 ± 1.1 (LK), 3.4 ± 1.5 (RK), 4.5 ± 2.8 (L), 4.6 ± 1.8 (S), 0.3 ± 0.2 (bone marrow). There was a significant difference between bone marrow surrogates (L2 to L4 and L1 to L5, Wilcoxon’s test: p value < 0.05), and while depicting very doses, all three surrogates were significantly different than dose in background (p value < 0.01). At cycle 1, if the acquisition at 24H is missing and approximated, medians of percentages of dose difference (PDD) compared to the initial tri-exponential function were inferior to 3.3% for all organs. For cycles with one acquisition, the median errors were smaller with a late time-point. For STP-Inter, medians of PDD were inferior to 7.7% for all volumes, but it was shown to depend on the homogeneity of TDRC. Conclusion The proposed workflow allows the estimation of organ doses, including bone marrow, from a variable number of time-points acquisitions for patients treated with $$^{177}$$ 177 Lu-DOTATATE.

Abstract Targeted radionuclide therapy is a revolutionary tool for the treatment of highly spread metastatic cancers. Most current approaches rely on the use of vectors to deliver radionuclides to tumor cells, targeting membrane‐bound cancer‐specific moieties. Here, we report the embryonic navigation cue netrin‐1 as an unanticipated target for vectorized radiotherapy. While netrin‐1, known to be re‐expressed in tumoral cells to promote cancer progression, is usually characterized as a diffusible ligand, we demonstrate here that netrin‐1 is actually poorly diffusible and bound to the extracellular matrix. A therapeutic anti‐netrin‐1 monoclonal antibody (NP137) has been preclinically developed and was tested in various clinical trials showing an excellent safety profile. In order to provide a companion test detecting netrin‐1 in solid tumors and allowing the selection of therapy‐eligible patients, we used the clinical‐grade NP137 agent and developed an indium‐111‐NODAGA‐NP137 single photon emission computed tomography (SPECT) contrast agent. NP137‐111In provided specific detection of netrin‐1‐positive tumors with an excellent signal‐to‐noise ratio using SPECT/CT imaging in different mouse models. The high specificity and strong affinity of NP137 paved the way for the generation of lutetium‐177‐DOTA‐NP137, a novel vectorized radiotherapy, which specifically accumulated in netrin‐1‐positive tumors. We demonstrate here, using tumor cell‐engrafted mouse models and a genetically engineered mouse model, that a single systemic injection of NP137‐177Lu provides important antitumor effects and prolonged mouse survival. Together, these data support the view that NP137‐111In and NP137‐177Lu may represent original and unexplored imaging and therapeutic tools against advanced solid cancers.

Hydrotherapy has been utilized in horse rehabilitation programs for over four decades. However, a comprehensive description of the swimming cycle of horses is still lacking. One of the challenges in studying this motion is 3D underwater motion capture, which holds potential not only for understanding equine locomotion but also for enhancing human swimming performance. In this study, a marker-based system that combines underwater cameras and markers drawn on horses is developed. This system enables the reconstruction of the 3D motion of the front and hind limbs of six horses throughout an entire swimming cycle, with a total of twelve recordings. The procedures for pre- and post-processing the videos are described in detail, along with an assessment of the estimated error. This study estimates the reconstruction error on a checkerboard and computes an estimated error of less than 10 mm for segments of tens of centimeters and less than 1 degree for angles of tens of degrees. This study computes the 3D joint angles of the front limbs (shoulder, elbow, carpus, and front fetlock) and hind limbs (hip, stifle, tarsus, and hind fetlock) during a complete swimming cycle for the six horses. The ranges of motion observed are as follows: shoulder: 17 ± 3°; elbow: 76 ± 11°; carpus: 99 ± 10°; front fetlock: 68 ± 12°; hip: 39 ± 3°; stifle: 68 ± 7°; tarsus: 99 ± 6°; hind fetlock: 94 ± 8°. By comparing the joint angles during a swimming cycle to those observed during classical gaits, this study reveals a greater range of motion (ROM) for most joints during swimming, except for the front and hind fetlocks. This larger ROM is usually achieved through a larger maximal flexion angle (smaller minimal angle of the joints). Finally, the versatility of the system allows us to imagine applications outside the scope of horses, including other large animals and even humans.

Aging is associated with a decline in muscle mass and function, leading to increased risk for mobility limitations and frailty. Dietary interventions incorporating specific nutrients, such as pea proteins or inulin, have shown promise in attenuating age-related muscle loss. This study aimed to investigate the effect of pea proteins given with inulin on skeletal muscle in old rats. Old male rats (20 months old) were randomly assigned to one of two diet groups for 16 weeks: a ‘PEA’ group receiving a pea-protein-based diet, or a ‘PEA + INU’ group receiving the same pea protein-based diet supplemented with inulin. Both groups showed significant postprandial stimulation of muscle p70 S6 kinase phosphorylation rate after consumption of pea proteins. However, the PEA + INU rats showed significant preservation of muscle mass with time together with decreased MuRF1 transcript levels. In addition, inulin specifically increased PGC1-α expression and key mitochondrial enzyme activities in the plantaris muscle of the old rats. These findings suggest that dietary supplementation with pea proteins in combination with inulin has the potential to attenuate age-related muscle loss. Further research is warranted to explore the underlying mechanisms and determine the optimal dosage and duration of intervention for potential translation to human studies.

Personal wellbeing is greatly influenced by our childhood and adolescence, and the relationships formed during those phases of our development. The human-dog bond represents a significant relationship that started thousands of years ago. There is a higher prevalence of dog ownership around the world, especially in households including children. This has resulted in a growing number of researchers studying our interactions with dogs and an expanding evidence base from the exploration of child-dog interactions. We review the potential effects of child-dog interactions on the physical, mental, and social wellbeing of both species. A search of the SCOPUS database identified documents published between January 1980 and April 2022. Filtering for key inclusion criteria, duplicate removals, and inspecting the references of these documents for additional sources, we reviewed a total of 393 documents, 88% of which were scientific articles. We were able to define the numerous ways in which children and dogs interact, be it neutral (e.g., sharing a common area), positive (e.g., petting), or negative (e.g., biting). Then, we found evidence for an association between childhood interaction with dogs and an array of benefits such as increased physical activities, a reduction of stress, and the development of empathy. Nonetheless, several detrimental outcomes have also been identified for both humans and dogs. Children are the most at-risk population regarding dog bites and dog-borne zoonoses, which may lead to injuries/illness, a subsequent fear of dogs, or even death. Moreover, pet bereavement is generally inevitable when living with a canine companion and should not be trivialized. With a canine focus, children sometimes take part in caretaking behaviors toward them, such as feeding or going for walks. These represent opportunities for dogs to relieve themselves outside, but also to exercise and socialize. By contrast, a lack of physical activity can lead to the onset of obesity in both dogs and children. Dogs may present greater levels of stress when in the presence of children. Finally, the welfare of assistance, therapy, and free-roaming dogs who may interact with children remains underexplored. Overall, it appears that the benefits of child-dog interactions outweigh the risks for children but not for dogs; determination of the effects on both species, positive as well as negative, still requires further development. We call for longitudinal studies and cross-cultural research in the future to better understand the impact of child-dog interactions. Our review is important for people in and outside of the scientific community, to pediatricians, veterinarians, and current or future dog owners seeking to extend their knowledge, and to inform future research of scientists studying dogs and human-animal interactions.

Prostate-specific membrane antigen (PSMA), whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma, is also highly expressed in the neovessels of various solid tumors, including clear cell renal cell carcinoma (ccRCC). In the VISION phase III clinical trial, PSMA-targeted radioligand therapy (PRLT) with lutetium 177 demonstrated a 4-month overall survival OS benefit compared to the best standard of care in heavily pretreated metastatic prostate cancer. Despite the improvement in the management of metastatic clear cell renal cell carcinoma (mccRCC) with antiangiogenic tyrosine kinase inhibitor (TKI) and immunotherapy, there is still a need for new treatments for patients who progress despite these drugs. In this study, we discuss the rationale of PRLT applied to the treavtment of mccRCC.

This study assessed the environmental footprint of emerging micropollutants in Cambodia and France. The aim was to develop and apply an analytical method to detect micropollutants in diverse water sources and climatic regions. Consequently, an analytical method, using online solid-phase extraction coupled with an ultra-performance liquid chromatography-tandem mass spectrometer (online-SPE-UPLC-MS/MS), was successfully developed and validated. This method permits the accurate and rapid multi-residual determination of 15 emerging micropollutants in water at low detection and quantification limits, around 10 ng.L−1 and 30 ng.L−1, respectively, within a total analytical run of seven minutes, including the equilibrium step. The findings revealed that no water body was free of micropollutants in any case of its sources (effluent wastewater, surface water, and even tap water). In surface water, 13 and 11 of the 15 target micropollutants were detected at least once in the Couesnon River (France) and Upper Mekong River (Cambodia), respectively. The concentration of micropollutant detected in Couesnon River ranged from 6–975.5 ng.L−1, with tramadol having the highest concentration. In the Upper Mekong River, the concentration detected ranged from 5–240 ng.L−1, with ketoprofen having the highest concentration. Caffeine was found in the highest concentration in the treated effluent of a Cambodian wastewater treatment plant (WWTP).