Paris Diderot University

Close relationships have been reported between sleep alterations and suicidal behaviors, nevertheless few studies used objective measures of sleep. Such objective markers would be interesting in clinical practice to better screen and prevent suicide. We conducted a systematic review and meta-analysis of published studies examining the relationship between sleep markers and suicidal behaviors using PubMed, Cochrane Library, and Web of Science databases. Actigraphy, polysomnography, and nocturnal EEG were considered. The qualitative analysis retained 15 original studies, including 1179 participants (939 with a psychiatric disorder), and 11 studies were included for the meta-analysis. Current suicidal behaviors were associated with a decreased total sleep time (TST) (SMD = -0.35, [95% CI: -0.66 to -0.04], p = 0.026, I2 = 39.8%). The evaluation of possible moderators shows that age, gender, and depression scores had no effects on the random effect model. No significant differences were observed regarding sleep efficiency, REM latency, or percentage of REM sleep. In conclusion, among candidate objective markers, decreased total sleep time seems associated with suicidal behaviors and could be easily used to assess suicide risk. Alterations of regular sleep duration should invite healthcare professionals to screen the cause and propose sleep interventions to prevent suicide.

Transport in complex networks can describe a variety of natural and human-engineered processes including biological, societal and technological ones. However, how the properties of the source and drain nodes can affect transport subject to random failures, attacks or maintenance optimization in the network remain unknown. In this article, the effects of both the distance between the source and drain nodes and the degree of the source node on the time of transport collapse are studied in scale-free and lattice-based transport networks. These effects are numerically evaluated for two strategies, which employ either transport-based or random link removal. Scale-free networks with small distances are found to result in larger times of collapse. In lattice-based networks, both the dimension and boundary conditions are shown to have a major effect on the time of collapse. We also show that adding a direct link between the source and the drain increases the robustness of scale-free networks when subject to random link removals. Interestingly, the distribution of the times of collapse is then similar to the one of lattice-based networks.

Aim To investigate a pre-therapeutic radiomics nomogram to accurately predict hepatocellular carcinoma (HCC) lesion responses to transcatheter arterial chemoembolization (TACE). Methods This retrospective study from January 2012 to 2022 included 92 TACE-treated patients who underwent liver contrast-enhanced CT scan 7 days before treatment, having complete clinical information. We extracted quantitative texture parameters and clinical factors for the largest tumors on the baseline arterial and portal venous phase CT images. An adaptive least absolute shrinkage and selection operator (LASSO)-penalized logistic regression identified independent predictors of tumor activity after TACE. Results We fitted an adaptive LASSO regression model to narrow down the texture features and clinical risk factors of the tumor activity status. The selected texture features were used to construct radiomic scores (RadScore), which demonstrated superior performance in predicting tumor activity on both the training (area under the curve (AUC): 0.881, 95% CI: 0.799–0.963) and testing sets (AUC: 0.88, 95% CI: 0.726–1). A logistic regression-based nomogram was developed using RadScore and four selected clinical features. In the testing set, nomogram total points were significant predictors (P = 0.034), and the training set showed no departure from perfect fit (P = 0.833). Internal validation of the nomogram was obtained for the training (AUC: 0.91, 95% CI: 0.837–0.984) and testing (AUC: 0.889, 95% CI: 0.746–1) sets. Conclusion We propose a nomogram to predict the early response of HCC lesions to TACE treatment with high accuracy, which may serve as an additional criterion in multidisciplinary decision-making treatment. Graphical Abstract

Kidney transplantation is the preferred treatment for end-stage renal failure in children but remains a rare procedure with only 100 to 120 pediatric kidney transplants per year in France. Although the main principles of kidney transplantation are the same in children and adults, some specificities regarding underlying kidney diseases, surgical technique, immunosuppressive drugs metabolism and the risk of infectious complications require a specific expertise to care for these patients. Similarly, the major morbidity of dialysis in children and the need for repeated transplants during the patient's life justify pediatric specificities in the choice of donors and the allocation of grafts in most kidney allocation systems worldwide. The objectives of this review are to present the history and specificities of pediatric kidney transplantation, to describe the current activity in France and to discuss future developments while emphasizing the need for basic and clinical research focused on the pediatric population.

Prenatal therapy for LUTO (Lower Urinary Tract Obstruction) is debated due to mixed results regarding postnatal renal function following fetal cystoscopy or vesicoamniotic shunting. Current literature is, however, limited by the inability to determine the cause of the obstruction using plain sonography and the lack of selection criteria for fetuses who may benefit from prenatal therapy. Fetal cystoscopy may serve as a diagnostic tool and would offer a more "physiologic" treatment for bladder outlet obstruction. However, it carries additional technical issues due to inappropriate instrumentation.

Genetic studies of hereditary steroid resistant nephrotic syndrome (SRNS) have identified more than 60 genes involved in the development of single-gene, isolated or syndromic forms of hereditary podocytoapthies. Sometimes, syndromic SRNS is associated with neurological disorders. Over the past decades, various studies have established links between the podocyte, an epithelial glomerular cell involved in the renal filtration barrier, and neuronal cells, both morphologically (slit diaphragm and synapse) and functionally (signaling platforms). Variants of genes encoding proteins expressed in different compartments of the podocyte and neurons are responsible for phenotypes associating renal lesions with proteinuria to central and/or peripheral neurological disorders. In this review, we aim to focus on genetic syndromes associating proteinuria and neurological disease and to present the latest advances in the description of these neuro-renal disorders.

The rise of genetics in the last decades has allowed major advances in the understanding of the mechanisms leading to inherited kidney diseases. From the first positional cloning studies to the advent of high-throughput sequencing (NGS), genome analysis technologies have become increasingly efficient, with an extraordinary level of resolution. Moreover, sequencing prices have decreased from one million dollars for the sequencing of James Watson's genome in 2008, to a few hundred dollars for the sequencing of a genome today. Thus, molecular diagnosis has a central place in the diagnosis of these patients and influences the therapeutic management in many situations. However, although NGS is a powerful tool for the identification of variants involved in diseases, it also exposes to the risk of over-interpretation of certain variants, leading to erroneous diagnoses, requiring the use of specialists. In this review, we first propose a brief retrospective of the essential steps that led to the current knowledge and the development of NGS for the study of hereditary nephropathies in children. This review is then an opportunity to present the main hereditary nephropathies and the underlying molecular mechanisms. Among them, we emphasize ciliopathies, congenital anomalies of the kidney and urinary tract, podocytopathies and tubulopathies.

In the direct searches for Weakly Interacting Massive Particles (WIMPs) as Dark Matter candidates, the sensitivity of the detector to the incom- ing particle direction could provide a smoking gun signature for an interesting event. The SCENE collaboration firstly suggested the possible directional de- pendence of a dual-phase argon Time Projection Chamber through the columnar recombination effect. The Recoil Directionality project (ReD) within the Global Argon Dark Matter Collaboration aims to characterize the light and charge re- sponse of a liquid Argon dual-phase TPC to neutron-induced nuclear recoils to probe for the hint by SCENE. In this work, the directional sensitivity of the de- tector in the energy range of interest for WIMPs (20-100 keV) is investigated with a data-driven analysis involving a Machine Learning algorithm.

We report progress on the ongoing recalibration of the Wolf sunspot number ( $S_{\mathrm{N}}$ S N ) and group-sunspot number ( $G_{\mathrm{N}}$ G N ) following the release of version 2.0 of $S_{\mathrm{N}}$ S N in 2015. This report constitutes both an update of the efforts reported in the 2016 Topical Issue of Solar Physics and a summary of work by the International Space Science Institute (ISSI) International Team formed in 2017 to develop optimal $S_{\mathrm{N}}$ S N and $G_{\mathrm{N}}$ G N reconstruction methods while continuing to expand the historical sunspot-number database. Significant progress has been made on the database side while more work is needed to bring the various proposed $S_{\mathrm{N}}$ S N and (primarily) $G_{\mathrm{N}}$ G N reconstruction methods closer to maturity, after which the new reconstructions (or combinations thereof) can be compared with (a) “benchmark” expectations for any normalization scheme (e.g., a general increase in observer normalization factors going back in time), and (b) independent proxy data series such as F10.7 and the daily range of variations of Earth’s undisturbed magnetic field. New versions of the underlying databases for $S_{\mathrm{N}}$ S N and $G_{\mathrm{N}}$ G N will shortly become available for years through 2022 and we anticipate the release of the next versions of these two time series in 2024.

Background Moyamoya angiopathy (MMA) is a rare cerebrovascular condition leading to stroke. Mutations in 15 genes have been identified in Mendelian forms of MMA, but they explain only a very small proportion of cases. Our aim was to investigate the genetic basis of MMA in consanguineous patients having unaffected parents in order to identify genes involved in autosomal recessive MMA. Methods Exome sequencing (ES) was performed in 6 consecutive consanguineous probands having MMA of unknown etiology. Functional consequences of variants were assessed using western blot and protein 3D structure analyses. Results Causative homozygous variants of NOS3, the gene encoding the endothelial nitric oxide synthase (eNOS), and GUCY1A3, the gene encoding the alpha1 subunit of the soluble guanylate cyclase (sGC) which is the major nitric oxide (NO) receptor in the vascular wall, were identified in 3 of the 6 probands. One NOS3 variant (c.1502 + 1G > C) involves a splice donor site causing a premature termination codon and leads to a total lack of eNOS in endothelial progenitor cells of the affected proband. The other NOS3 variant (c.1942 T > C) is a missense variant located into the flavodoxine reductase domain; it is predicted to be destabilizing and shown to be associated with a reduction of eNOS expression. The GUCY1A3 missense variant (c.1778G > A), located in the catalytic domain of the sGC, is predicted to disrupt the tridimensional structure of this domain and to lead to a loss of function of the enzyme. Both NOS3 mutated probands suffered from an infant-onset and severe MMA associated with posterior cerebral artery steno-occlusive lesions. The GUCY1A3 mutated proband presented an adult-onset MMA associated with an early-onset arterial hypertension and a stenosis of the superior mesenteric artery. None of the 3 probands had achalasia. Conclusions We show for the first time that biallelic loss of function variants in NOS3 is responsible for MMA and that mutations in NOS3 and GUCY1A3 are causing fifty per cent of MMA in consanguineous patients. These data pinpoint the essential role of the NO pathway in MMA pathophysiology.

Cajal-Retzius cells (CRs) are transient neurons, disappearing almost completely in the postnatal neocortex by programmed cell death (PCD), with a percentage surviving up to adulthood in the hippocampus. Here, we evaluate CR’s role in the establishment of adult neuronal and cognitive function using a mouse model preventing Bax-dependent PCD. CRs abnormal survival resulted in impairment of hippocampus-dependent memory, associated in vivo with attenuated theta oscillations and enhanced gamma activity in the dorsal CA1. At the cellular level, we observed transient changes in the number of NPY⁺ cells and altered CA1 pyramidal cell spine density. At the synaptic level, these changes translated into enhanced inhibitory currents in hippocampal pyramidal cells. Finally, adult mutants displayed an increased susceptibility to lethal tonic-clonic seizures in a kainate model of epilepsy. Our data reveal that aberrant survival of a small proportion of postnatal hippocampal CRs results in cognitive deficits and epilepsy-prone phenotypes in adulthood.

The present research examines the stereotypes held about North Africans in French society today. Extending past works, we included gender and separately studied the stereotypes of North African men and women. Using three techniques, namely, spontaneous generation, attribute rating, and pathfinder analysis, our results revealed distinct stereotypes of North African men and women in French society. North African men are ascribed more antisocial traits. Traits associated with North African women are related to submissiveness and domestic chores. This suggests that stereotypes revealed in past studies concerned mainly the men of the group. The results underscore the need to consider gender when studying stereotypes of ethnic and minority groups.

Monoclonal antibodies (mAbs) have established themselves as the leading biopharmaceutical therapeutic modality. Once the developability of a mAb drug candidate has been assessed, an important step is to check its in vivo stability through pharmacokinetics (PK) studies. The gold standard is ligand-binding assay (LBA) and LC–MS (Liquid Chromatography- Mass Spectrometry) performed at the peptide level (bottom-up approach). However, these analytical techniques do not allow to address the different mAb proteoforms that can arise from biotransformation. In recent years, top-down and middle-down mass spectrometry approaches have gained popularity to characterize proteins at the proteoform level but are not yet widely used for PK studies. We propose here a workflow based on an automated immunocapture followed by top-down and middle-down LC-MS/MS approaches to characterize mAb proteoforms spiked in mouse plasma. We demonstrate the applicability of our workflow on a large concentration range using pembrolizumab as a model. We also compare the performance of two state-of-the-art Orbitrap platforms (Tribrid Eclipse and Exploris 480) for these studies. The added value of our workflow for an accurate and sensitive characterization of mAb proteoforms in mouse plasma is highlighted.

Hilary Bowman-Smart et al. (2023) have rightly pointed out that one of the recurring criticisms of the use of noninvasive prenatal testing (NIPT) for nonmedical trait prediction is the probabilistic nature of polygenic scores. Those estimates do not establish a direct causal relationship, but rather a probabilistic association between having some genetic variants and the development of particular traits. The authors then suggest that differences in the predictive value of polygenic scores may pose a practical problem that increases the information overload of the reproductive decisions after NIPT. In this commentary, we offer a reframing of this issue in three steps. First, drawing on various empirical articles from the genomic medicine literature, we indicate how the appraisal of uncertainty may entail a different psychological cost between individuals when considering genetic information. Second, we analyze the specific limitation of having probabilistic information on non-medical traits with genetic contribution and compare the burden placed on reproductive decisions by the use of polygenic scores in gestational periods after NIPT with the case of embryo selection. Third, following the authors’ claim that “understanding causality is important,” we briefly address the problem of causation in the debate on polygenic scores.

Background Mechanisms underlying the associations between changes in the urban environment and changes in health-related outcomes are complex and their study requires specific approaches. We describe the protocol of the interdisciplinary UrbASanté study, which aims to explore how urban interventions can modify environmental exposures (built, social, and food environments; air quality; noise), health-related behaviors, and self-reported health using a natural experiment approach. Methods The study is based on a natural experiment design using a before/after protocol with a control group to assess changes in environmental exposures, health-risk behaviors, and self-reported health outcomes of a resident adult population before and after the implementation of a time series of urban interventions in four contiguous neighborhoods in Paris (France). The changes in environmental exposures, health-related behaviors, and self-reported health outcomes of a resident adult population will be concurrently monitored in both intervention and control areas. We will develop a mixed-method framework combining substantial fieldwork with quantitative and qualitative analytical approaches. This study will make use of (i) data relating to exposures and health-related outcomes among all participants and in subsamples and (ii) interviews with residents regarding their perceptions of their neighborhoods and with key stakeholders regarding the urban change processing, and (iii) existing geodatabases and field observations to characterize the built, social, and food environments. The data collected will be analyzed with a focus on interrelationships between environmental exposures and health-related outcomes using appropriate approaches (e.g., interrupted time series, difference–in-differences method). Discussion Relying on a natural experiment approach, the research will provide new insights regarding issues such as close collaboration with urban/local stakeholders, recruitment and follow-up of participants, identification of control and intervention areas, timing of the planned urban interventions, and comparison of subjective and objective measurements. Through the collaborative work of a consortium ensuring complementarity between researchers from different disciplines and stakeholders, the UrbASanté study will provide evidence-based guidance for designing future urban planning and public health policies. Trial registration This research was registered at the ClinicalTrial.gov (NCT05743257).

Objective The interdependence of hospitals is underappreciated in patient outcomes studies. We used a network science approach to foreground this interdependence. Specifically, within two large state-based interhospital networks, we examined the relationship of a hospital’s network position with in-hospital mortality and length of stay. Methods We constructed interhospital network graphs using data from the Healthcare Cost and Utilization Project and the American Hospital Association Annual Survey for Florida (2014) and California (2011). The exposure of interest was hospital centrality, defined as weighted degree (sum of all ties to a given hospital from other hospitals). The outcomes were in-hospital mortality and length of stay with sub-analyses for four acute medical conditions: pneumonia, heart failure, ischemic stroke, myocardial infarction. We compared outcomes for each quartile of hospital centrality relative to the most central quartile (Q4), independent of patient- and hospital-level characteristics, in this retrospective cross-sectional study. Results The inpatient cohorts had 1,246,169 patients in Florida and 1,415,728 in California. Compared to Florida’s central hospitals which had an overall mortality 1.60%, peripheral hospitals had higher in-hospital mortality (1.97%, adjusted OR (95%CI): Q1 1.61 (1.37, 1.89), p