A Phase 2b, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of intravenous prasinezumab in early-stage Parkinson's disease (PADOVA): Rationale, design, and baseline data.

Introduction: Prasinezumab was shown to potentially delay motor progression in individuals with early-stage Parkinson's disease (PD) who were either treatment-naïve or on monoamine oxidase type B inhibitor (MAO-Bi) therapy in the PASADENA study. We report the rationale, design, and baseline patient characteristics of the PADOVA study, designed to evaluate prasinezumab in an early-stage PD population receiving standard-of-care (SOC) symptomatic medications.

Methods: PADOVA (NCT04777331) is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, in which individuals with early-stage PD on SOC stable symptomatic monotherapy (levodopa or MAO-Bi) receive intravenous prasinezumab 1500 mg every 4 weeks.

Sustained effect of prasinezumab on Parkinson's disease motor progression in the open-label extension of the PASADENA trial.

The Phase II trial of Anti-alpha-Synuclein Antibody in Early Parkinson's Disease (PASADENA) is an ongoing double-blind, placebo-controlled trial evaluating the safety and efficacy of prasinezumab in early-stage Parkinson's disease (PD). During the double-blind period, prasinezumab-treated individuals showed less progression of motor signs (Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III) than placebo-treated individuals. We evaluated whether the effect of prasinezumab on motor progression, assessed as a change in MDS-UPDRS Part III score in the OFF and ON states, and MDS-UPDRS Part II score, was sustained for 4 years from the start of the trial.

Modeling of Parkinson's Disease Progression and Implications for Detection of Disease Modification in Treatment Trials.

Background: Objectively measuring Parkinson's disease (PD) signs and symptoms over time is critical for the successful development of treatments aimed at halting the disease progression of people with PD.

Objective: To create a clinical trial simulation tool that characterizes the natural history of PD progression and enables a data-driven design of randomized controlled studies testing potential disease-modifying treatments (DMT) in early-stage PD.

Methods: Data from the Parkinson's Progression Markers Initiative (PPMI) were analyzed with nonlinear mixed-effect modeling techniques to characterize the progression of MDS-UPDRS part I (non-motor aspects of experiences of daily living), part II (motor aspects of experiences of daily living), and part III (motor signs).

DCE-MRI to distinguish all monoclonal plasma cell disease stages and correlation with diffusion-weighted MRI/PET-based biomarkers in a hybrid simultaneous whole body-2-[18F]FDG-PET/MRI imaging approach.

Background: Dynamic contrast-enhanced-MRI (DCE-MRI) is able to study bone marrow angiogenesis in patients with multiple myeloma (MM) and asymptomatic precursor diseases but its role in the management of MM has not yet been established. The aims of this prospective study was to compare DCE-MRI-based parameters between all monoclonal plasma cell disease stages in order to find out discriminatory parameters and to seek correlations with other diffusion-weighted MRI and positron emission tomography (PET)-based biomarkers in a hybrid simultaneous whole-body-2-[18F]fluorodeoxyglucose (FDG)-PET/MRI (WB-2-[18F]FDG-PET/MRI) imaging approach.

Methods: Patients with newly diagnosed Monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) or symptomatic MM according to international myeloma working group and underwent WB-2-[18F]FDG-PET/MRI imaging including bone marrow DCE sequences at the Nantes University Hospital were prospectively enrolled in this study before receiving treatment.

Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson's disease.

Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson's disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). We report here an exploratory analysis assessing whether prasinezumab showed greater benefits on motor signs progression in prespecified subgroups with faster motor progression.

Hybrid simultaneous whole-body 2-[F]FDG-PET/MRI imaging in newly diagnosed multiple myeloma: first diagnostic performance and clinical added value results.

Objectives: Mixing diagnostic and prognostic data provided by whole-body MRI (WB-MRI) and 2-F-fluorodeoxyglucose (2-[F]FDG) positron emission tomography (2-[F]FDG-PET) from a single simultaneous imaging technique for newly diagnosed multiple myeloma (NDMM) initial workup seems attractive. However, to date, the published data are scarce and this possibility has not been fully explored. In this prospective study, we aimed to explore the diagnostic performance and added clinical value of WB-2-[F]FDG-PET/MRI imaging in NDMM.

Trial of Prasinezumab in Early-Stage Parkinson's Disease.

Background: Aggregated α-synuclein plays an important role in the pathogenesis of Parkinson's disease. The monoclonal antibody prasinezumab, directed at aggregated α-synuclein, is being studied for its effect on Parkinson's disease.

Methods: In this phase 2 trial, we randomly assigned participants with early-stage Parkinson's disease in a 1:1:1 ratio to receive intravenous placebo or prasinezumab at a dose of 1500 mg or 4500 mg every 4 weeks for 52 weeks.

Chest PET/MRI in Solid Cancers: Comparing the Diagnostic Performance of a Free-Breathing 3D-T1-GRE Stack-of-Stars Volume Interpolated Breath-Hold Examination (StarVIBE) Acquisition With That of a 3D-T1-GRE Volume Interpolated Breath-Hold Examination (VIBE) for Chest Staging During Whole-Body PET/MRI.

Background: Whole-body positron emission tomography/magnetic resonance imaging (WB-PET/MRI) is increasingly used in oncology. However, chest staging remains challenging.

Purpose: To compare the diagnostic performance of a free-breathing 3D-T1-GRE stack-of-stars volume interpolated breath-hold examination (StarVIBE) with that of a 3D-T1-GRE volume interpolated breath-hold examination (VIBE) during WB-PET/MRI for chest staging.

Effect of the order of incorporation of cake ingredients on the formation of batter and the final properties: contribution of the addition of pea flour.

The investigation dealt with the effect of the replacement of a part of wheat flour by pea flour on the properties of batters and cakes. As the protein composition of pea flour differs from that of wheat, the effect of its incorporation on batter formation and cake properties was monitored throughout the different steps of cake processing. The incorporation of air, which influences the cell structure and density of the cake, was the subject of particular attention.

Impact of the F-FDG-PET/MRI on Metastatic Staging in Patients with Hepatocellular Carcinoma: Initial Results from 104 Patients.

Optimal HCC therapeutic management relies on accurate tumor staging. Our aim was to assess the impact of F-FDG-WB-PET/MRI on HCC metastatic staging, compared with the standard of care CT-CAP/liver MRI combination, in patients with HCC referred on a curative intent or before transarterial radioembolization. One hundred and four consecutive patients followed for HCC were retrospectively included.

Replacement of animal proteins in food: How to take advantage of nutritional and gelling properties of alternative protein sources.

Given the growing world population, there is a need to balance animal and vegetable sources of dietary protein and to limit overall protein resources, and food formulation has to consider alternative protein sources as a way to meet human requirements. The protein concentration, essential amino acids (EAA) of all protein sources were analyzed with respect to human needs along with additional macronutrients of nutritional and energy interest ( carbohydrates and lipids). New indexes are proposed to classify the alternative protein sources considering their EAA balance and how it may change during food processing.

WOODIV, a database of occurrences, functional traits, and phylogenetic data for all Euro-Mediterranean trees.

Trees play a key role in the structure and function of many ecosystems worldwide. In the Mediterranean Basin, forests cover approximately 22% of the total land area hosting a large number of endemics (46 species). Despite its particularities and vulnerability, the biodiversity of Mediterranean trees is not well known at the taxonomic, spatial, functional, and genetic levels required for conservation applications.

Murine double minute 2 inhibition alone or with cytarabine in acute myeloid leukemia: Results from an idasanutlin phase 1/1b study⋆.

The prognosis remains poor for patients with relapsed or refractory (r/r) acute myeloid leukemia; thus, novel therapies are needed. We evaluated idasanutlin-a new, potent murine double minute 2 antagonist-alone or with cytarabine in patients with r/r acute myeloid leukemia, de novo untreated acute myeloid leukemia unsuitable for standard treatment or with adverse features, or secondary acute myeloid leukemia in a multicenter, open-label, phase 1/1b trial. Primary objectives were to determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) and characterize the safety profile of idasanutlin monotherapy and combination therapy.

MIRROS: a randomized, placebo-controlled, Phase III trial of cytarabine ± idasanutlin in relapsed or refractory acute myeloid leukemia.

Patients with refractory or relapsed acute myeloid leukemia (R/R AML) have a poor prognosis, with a high unmet medical need. Idasanutlin is a small-molecule inhibitor of MDM2, a negative regulator of tumor suppressor p53. By preventing the p53-MDM2 interaction, idasanutlin allows for p53 activation, particularly in patients with wild-type (WT) status.

F-sodium fluoride PET/MRI myocardial imaging in patients with suspected cardiac amyloidosis.

Background: We evaluated the diagnostic performance of F-NaF PET/MRI in patients with suspected cardiac amyloidosis (CA).

Methods: Twenty-seven consecutive patients underwent myocardial PET 1 hour after injection of 4 MBq/kg F-NaF with simultaneous MRI including cine-MRI, T1 and T2 mapping, first-pass and late gadolinium enhancement (LGE). F-NaF uptake was measured visually and semi-quantitatively by calculating myocardium-to-blood pool (M/B) ratios.

Compressed sensing real-time cine imaging for assessment of ventricular function, volumes and mass in clinical practice.

Objectives: This study was conducted in order to evaluate the accuracy of a compressed sensing (CS) real-time single-breath-hold cine sequence for the assessment of left and right ventricular functional parameters in daily practice.

Methods: Cardiac magnetic resonance (CMR) cine images were acquired from 100 consecutive patients using both the reference segmented multi-breath-hold steady-state free precession (SSFP) acquisition and a prototype single-breath-hold real-time CS sequence, providing the same slice number, position, and thickness. For both sequences, the left (LV) and right ventricular (RV) ejection fractions (EF) and end-diastolic volumes (EDV) were assessed as well as LV mass (LVM).

Validation of the Strain Assessment of a Phantom of Abdominal Aortic Aneurysm: Comparison of Results Obtained From Magnetic Resonance Imaging and Stereovision Measurements.

Predicting aortic aneurysm ruptures is a complex problem that has been investigated by many research teams over several decades. Work on this issue is notably complex and involves both the mechanical behavior of the artery and the blood flow. Magnetic resonance imaging (MRI) can provide measurements concerning the shape of an organ and the blood that flows through it.

Habitat suitability and demography, a time-dependent relationship.

The habitat suitability index, which reflects spatial variability in species occurrence probability, has been shown to exhibit various contrasting relationships with local demographic performances (survival, productivity) in several species. One proposed explanation for these discrepancies is that the link between the habitat suitability index and demography is influenced by density-dependent, temporally variable processes. Based on the survival rates of more than 3,000 nests monitored over 12 years in the North African Houbara Bustard, we investigated whether the habitat suitability index computed over the species breeding range is related to nest survival throughout the breeding season, accounting for variation in meteorological conditions.

Fixism and conservation science.

The field of biodiversity conservation has recently been criticized as relying on a fixist view of the living world in which existing species constitute at the same time targets of conservation efforts and static states of reference, which is in apparent disagreement with evolutionary dynamics. We reviewed the prominent role of species as conservation units and the common benchmark approach to conservation that aims to use past biodiversity as a reference to conserve current biodiversity. We found that the species approach is justified by the discrepancy between the time scales of macroevolution and human influence and that biodiversity benchmarks are based on reference processes rather than fixed reference states.

Late Quaternary climate stability and the origins and future of global grass endemism.

Background And Aims: Earth's climate is dynamic, with strong glacial-interglacial cycles through the Late Quaternary. These climate changes have had major consequences for the distributions of species through time, and may have produced historical legacies in modern ecological patterns. Unstable regions are expected to contain few endemic species, many species with strong dispersal abilities, and to be susceptible to the establishment of exotic species from relatively stable regions.

Kinetics of bread crumb hydration as related to porous microstructure.

During oral processing and throughout the digestion process, hydration mechanisms have a key influence on the functional properties of food. This is the case with bread, for which hydration may affect the kinetics of starch hydrolysis as well as taste, aroma and texture perceptions. In this context, the aim of the present study is to understand how crumb porous micro-architecture impacts hydration kinetics.

Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study.

Purpose: Crizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC), but progression invariably occurs. We investigated the efficacy and safety of alectinib, a potent and selective ALK inhibitor with excellent CNS penetration, in patients with crizotinib-refractory ALK-positive NSCLC.

Patients And Methods: Alectinib 600 mg was administered orally twice daily.

Beyond ectomycorrhizal bipartite networks: projected networks demonstrate contrasted patterns between early- and late-successional plants in Corsica.

The ectomycorrhizal (ECM) symbiosis connects mutualistic plants and fungal species into bipartite networks. While links between one focal ECM plant and its fungal symbionts have been widely documented, systemic views of ECM networks are lacking, in particular, concerning the ability of fungal species to mediate indirect ecological interactions between ECM plant species (projected-ECM networks). We assembled a large dataset of plant-fungi associations at the species level and at the scale of Corsica using molecular data and unambiguously host-assigned records to: (i) examine the correlation between the number of fungal symbionts of a plant species and the average specialization of these fungal species, (ii) explore the structure of the plant-plant projected network and (iii) compare plant association patterns in regard to their position along the ecological succession.