TREAT: systematic and inclusive selection process of genes for genomic newborn screening as part of the Screen4Care project.

Background: Genomic newborn screening (gNBS) offers the potential to detect genetic conditions early, enhancing outcomes through timely treatment. It can serve as an additional tool to identify conditions that are not detectable via metabolic screening. The Screen4Care project seeks to develop a systematic approach for selecting treatable rare diseases (RDs) for inclusion in gNBS through the creation of the TREAT-panel.

Exploiting Integrin-αVβ3 to Enhance Radiotherapy Efficacy in Medulloblastoma via Ferroptosis.

Medulloblastoma, a malignant pediatric brain tumor, has a poor prognosis upon relapse, highlighting a critical clinical need. Our previous research linked medulloblastoma cell radioresistance to integrin-αvβ3 expression. β3-depleted (β3_KO) medulloblastoma cells exhibit lipid hydroxyperoxide accumulation after radiotherapy, indicating ferroptosis, a regulated cell death induced by ROS and inhibited by antioxidants such as cysteine, glutathione (GSH), and glutathione peroxidase 4 (GPx4).

Patient preferences in genetic newborn screening for rare diseases: study protocol.

Introduction: Rare diseases (RDs) collectively impact over 30 million people in Europe. Most individual conditions have a low prevalence which has resulted in a lack of research and expertise in this field, especially regarding genetic newborn screening (gNBS). There is increasing recognition of the importance of incorporating patients' needs and general public perspectives into the shared decision-making process regarding gNBS.

Development of a Conceptual Model for the Patient Experience of Immunoglobulin A Nephropathy (IgAN): A Qualitative Literature Review.

Introduction: Immunoglobulin A nephropathy (IgAN) is a kidney disorder that can lead to progressive kidney disease. Currently, there lacks a comprehensive overview of the symptoms and impacts experienced by those living with IgAN that would help inform the selection or development of fit-for-purpose clinical outcome assessments (COA) to be used in clinical trials. The aim of this study was to develop a conceptual model of the adult and pediatric patient experience of IgAN, including disease signs and symptoms, treatment side effects, and impact on functioning and well-being.

Integrin-αvβ3 is a Therapeutically Targetable Fundamental Factor in Medulloblastoma Tumorigenicity and Radioresistance.

Unlabelled: Medulloblastoma is one of the most prevalent solid tumors found in children, occurring in the brain's posterior fossa. The standard treatment protocol involves maximal resection surgery followed by craniospinal irradiation and chemotherapy. Despite a long-term survival rate of 70%, wide disparities among patients have been observed.

Genetic newborn screening and digital technologies: A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations.

Development of a Conceptual Model for the Patient Experience of Focal Segmental Glomerulosclerosis (FSGS): A Qualitative Targeted Literature Review.

Introduction: Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease and can progress to end stage kidney disease (ESKD). An overview of symptoms and impacts of the disease experienced will help inform the selection or development of fit-for-purpose clinical outcome assessments (COA) to be used in FSGS clinical trials. This study aimed to develop a conceptual model (CM) of the adult and pediatric patient experience of FSGS including disease signs/symptoms, treatment side-effects, and impact on functioning and wellbeing.

Rare diseases' genetic newborn screening as the gateway to future genomic medicine: the Screen4Care EU-IMI project.

Following the reverse genetics strategy developed in the 1980s to pioneer the identification of disease genes, genome(s) sequencing has opened the era of genomics medicine. The human genome project has led to an innumerable series of applications of omics sciences on global health, from which rare diseases (RDs) have greatly benefited. This has propelled the scientific community towards major breakthroughs in disease genes discovery, in technical innovations in bioinformatics, and in the development of patients' data registries and omics repositories where sequencing data are stored.

Quantitative analysis of Tc-pertechnetate thyroid uptake with a large-field CZT gamma camera: feasibility and comparison between SPECT/CT and planar acquisitions.

Purpose: The main objective of this study was to evaluate the ability of a large field Cadmium Zinc Telluride (CZT) camera to estimate thyroid uptake (TU) on single photon emission computed tomography (SPECT) images with and without attenuation correction (Tomo-AC and Tomo-NoAC) compared with Planar acquisition in a series of 23 consecutive patients. The secondary objective was to determine radiation doses for the tracer administration and for the additional Computed Tomography (CT) scan.

Methods: Cross-calibration factors were determined using a thyroid phantom, for Planar, Tomo-AC and Tomo-NoAC images.

Radiosurgery for classical trigeminal neuralgia: impact of the shot size on clinical outcome.

Background: This study compares the outcome of patients suffering from medically refractory classical trigeminal neuralgia (TN) after treatment with radiosurgery using two different shot sizes (5- and 6-mm).

Methods: All patients included in this open, prospective, non-controlled study were treated in a single institution for TN (95 cases in 93 patients) with LINear ACcelerators (LINAC) single-dose radiosurgery using a 5-mm shot (43 cases) or 6-mm shot (52 cases). The target was positioned on the intracisternal part of the trigeminal nerve.

Newborn Screening by Genomic Sequencing: Opportunities and Challenges.

Newborn screening for treatable disorders is one of the great public health success stories of the twentieth century worldwide. This commentary examines the potential use of a new technology, next generation sequencing, in newborn screening through the lens of the Wilson and Jungner criteria. Each of the ten criteria are examined to show how they might be applied by programmes using genomic sequencing as a screening tool.

Identification of new ETV6 modulators through a high-throughput functional screening.

transcriptional activity is critical for proper blood cell development in the bone marrow. Despite the accumulating body of evidence linking malfunction to hematological malignancies, its regulatory network remains unclear. To uncover genes that modulate repressive transcriptional activity, we performed a specifically designed, unbiased genome-wide shRNA screen in pre-B acute lymphoblastic leukemia cells.

Quantifying Non-Stationarity with Information Theory.

We introduce an index based on information theory to quantify the stationarity of a stochastic process. The index compares on the one hand the information contained in the increment at the time scale τ of the process at time with, on the other hand, the extra information in the variable at time that is not present at time t-τ. By varying the scale τ, the index can explore a full range of scales.

Distance to Healthy Metabolic and Cardiovascular Dynamics From Fetal Heart Rate Scale-Dependent Features in Pregnant Sheep Model of Human Labor Predicts the Evolution of Acidemia and Cardiovascular Decompensation.

The overarching goal of the present work is to contribute to the understanding of the relations between fetal heart rate (FHR) temporal dynamics and the well-being of the fetus, notably in terms of predicting the evolution of lactate, pH and cardiovascular decompensation (CVD). It makes uses of an established animal model of human labor, where 14 near-term ovine fetuses subjected to umbilical cord occlusions (UCO) were instrumented to permit regular intermittent measurements of metabolites lactate and base excess, pH, and continuous recording of electrocardiogram (ECG) and systemic arterial blood pressure (to identify CVD) during UCO. ECG-derived FHR was digitized at the sampling rate of 1,000 Hz and resampled to 4 Hz, as used in clinical routine.

Spatial and temporal regularization to estimate COVID-19 reproduction number R(t): Promoting piecewise smoothness via convex optimization.

Among the different indicators that quantify the spread of an epidemic such as the on-going COVID-19, stands first the reproduction number which measures how many people can be contaminated by an infected person. In order to permit the monitoring of the evolution of this number, a new estimation procedure is proposed here, assuming a well-accepted model for current incidence data, based on past observations. The novelty of the proposed approach is twofold: 1) the estimation of the reproduction number is achieved by convex optimization within a proximal-based inverse problem formulation, with constraints aimed at promoting piecewise smoothness; 2) the approach is developed in a multivariate setting, allowing for the simultaneous handling of multiple time series attached to different geographical regions, together with a spatial (graph-based) regularization of their evolutions in time.

Extracellular vesicles isolated from patients undergoing remote ischemic preconditioning decrease hypoxia-evoked apoptosis of cardiomyoblasts after isoflurane but not propofol exposure.

Remote ischemic preconditioning (RIPC) can evoke cardioprotection following ischemia/reperfusion and this may depend on the anesthetic used. We tested whether 1) extracellular vesicles (EVs) isolated from humans undergoing RIPC protect cardiomyoblasts against hypoxia-induced apoptosis and 2) this effect is altered by cardiomyoblast exposure to isoflurane or propofol. EVs were isolated before and 60 min after RIPC or Sham from ten patients undergoing coronary artery bypass graft surgery with isoflurane anesthesia and quantified by Nanoparticle Tracking Analysis.

Categorizing factors of adherence to parenteral treatment in growth hormone deficiencies and hemophilia: What should be the targets for future research?

Adherence to treatment regimens in growth hormone dysregulations and hemophilia is related to better outcome and fewer complications over time. Subcutaneous growth hormone injection and intravenous blood factor replacement therapies are parenteral treatments with a comparable regimen calling for similar behavioral processes. Although we have lists of possible factors influencing adherence in these conditions, the evidence is scattered.

Detectors assessment for stereotactic radiosurgery with cones.

The purpose of this work is to assess eight detectors performance for output factor (OF), percent depth dose (PDD), and beam profiles in a 6-MV Clinac stereotactic radiosurgery mode for cone irradiation using Monte Carlo simulation as reference. Cones with diameters comprised between 30 and 4 mm have been studied. The evaluated detectors were ionization chambers: pinpoint and pinpoint 3D, diodes: SRS, P and E, Edge, MicroDiamond and EBT3 radiochromic films.

Kullback-Leibler divergence measure of intermittency: Application to turbulence.

For generic systems exhibiting power law behaviors, and hence multiscale dependencies, we propose a simple tool to analyze multifractality and intermittency, after noticing that these concepts are directly related to the deformation of a probability density function from Gaussian at large scales to non-Gaussian at smaller scales. Our framework is based on information theory and uses Shannon entropy and Kullback-Leibler divergence. We provide an extensive application to three-dimensional fully developed turbulence, seen here as a paradigmatic complex system where intermittency was historically defined and the concepts of scale invariance and multifractality were extensively studied and benchmarked.

Mutual information for intrapartum fetal heart rate analysis.

The analysis of the temporal dynamics in intrapartum fetal heart rate (FHR), aiming at early detection of fetal acidosis, constitutes an intricate signal processing task, that continuously receives significant research efforts. Entropy and entropy rates, envisaged as measures of complexity, often computed via popular implementations referred to as Approximate Entropy (ApEn) or Sample Entropy (SampEn), have regularly been reported as significant features for intrapartum FHR analysis. The present contribution aims to show how mutual information enhances characterization of FHR temporal dynamics and improves fetal acidosis detection performance.

Potential of big data analytics in the French in vitro diagnostics market.

The new paradigm of the big data raises many expectations, particularly in the field of health. Curiously, even though medical biology laboratories generate a great amount of data, the opportunities offered by this new field are poorly documented. For better understanding the clinical context of chronical disease follow-up, for leveraging preventive and/or personalized medicine, the contribution of big data analytics seems very promising.

Added Value of a Single Fast 20-second Deep-Inspiration Breath-hold Acquisition in FDG PET/CT in the Assessment of Lung Nodules.

Purpose To compare the accuracy of a single 20-second deep-inspiration breath hold (DIBH) in fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) to that with conventional free-breathing (FB) whole-body PET/CT for the assessment, characterization, and quantification of lung lesions in terms of the blurring effect of respiratory motion. Materials and Methods Institutional review board approval was obtained, and the requirement to obtain informed consent was waived. A preclinical study was performed in a test population of 19 patients to evaluate the feasibility and consistency of DIBH techniques compared with phase-based respiratory gating (PBRG).

Continuous and discontinuous transitions to synchronization.

We describe how the transition to synchronization in a system of globally coupled Stuart-Landau oscillators changes from continuous to discontinuous when the nature of the coupling is moved from diffusive to reactive. We explain this drastic qualitative change as resulting from the co-existence of a particular synchronized macrostate together with the trivial incoherent macrostate, in a range of parameter values for which the latter is linearly stable. In contrast to the paradigmatic Kuramoto model, this particular state observed at the synchronization transition contains a finite, non-vanishing number of synchronized oscillators, which results in a discontinuous transition.