Safety and Immunogenicity of Respiratory Syncytial Virus Prefusion F Protein Vaccine when Co-administered with Adjuvanted Seasonal Quadrivalent Influenza Vaccine in Older Adults: A Phase 3 Randomized Trial.

Background: We evaluated co-administration of adjuvanted seasonal quadrivalent influenza vaccine (FLU-aQIV) and respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) in ≥65-year-olds.

Methods: This phase 3, open-label trial randomized ≥65-year-olds to receive FLU-aQIV and RSVPreF3 OA concomitantly (Co-Ad) or sequentially, 1 month apart (Control). Primary objectives were to demonstrate the non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration in terms of hemagglutination inhibition (HI) titers for each FLU-aQIV strain and RSV-A and RSV-B neutralization titers, 1 month post-vaccination.

Soil microbial community response to corrinoids is shaped by a natural reservoir of vitamin B12.

Soil microbial communities perform critical ecosystem services through the collective metabolic activities of numerous individual organisms. Most microbes use corrinoids, a structurally diverse family of cofactors related to vitamin B12. Corrinoid structure influences the growth of individual microbes, yet how these growth responses scale to the community level remains unknown.

Molecular and Phenotypic Characterization of the -Related Disorder.

Background And Objectives: Heterozygous variants in RAR-related orphan receptor B () have recently been associated with susceptibility to idiopathic generalized epilepsy. However, few reports have been published so far describing pathogenic variants of this gene in patients with epilepsy and intellectual disability (ID). In this study, we aimed to delineate the epilepsy phenotype associated with pathogenic variants and to provide arguments in favor of the pathogenicity of variants.

A subset of viruses thrives following microbial resuscitation during rewetting of a seasonally dry California grassland soil.

Viruses are abundant, ubiquitous members of soil communities that kill microbial cells, but how they respond to perturbation of soil ecosystems is essentially unknown. Here, we investigate lineage-specific virus-host dynamics in grassland soil following "wet-up", when resident microbes are both resuscitated and lysed after a prolonged dry period. Quantitative isotope tracing, time-resolved metagenomics and viromic analyses indicate that dry soil holds a diverse but low biomass reservoir of virions, of which only a subset thrives following wet-up.

Deciphering Differential Behavior of Immune Responses as the Foundation for Precision Dosing in Allergen Immunotherapy.

Like in many fields of medicine, the concept of precision dosing has re-emerged in routine practice in allergology. Only one retrospective study on French physicians' practice has addressed this topic so far and generated preliminary data supporting dose adaptation, mainly based on experience, patient profile understanding and response to treatment. Both intrinsic and extrinsic factors shape the individual immune system response to allergen immunotherapy (AIT).

Drug characteristics derived from kinetic modeling: combined C-UCB-J human PET imaging with levetiracetam and brivaracetam occupancy of SV2A.

Background: Antiepileptic drugs, levetiracetam (LEV) and brivaracetam (BRV), bind to synaptic vesicle glycoprotein 2A (SV2A). In their anti-seizure activity, speed of brain entry may be an important factor. BRV showed faster entry into the human and non-human primate brain, based on more rapid displacement of SV2A tracer C-UCB-J.

CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition.

Amplification of the CCNE1 locus on chromosome 19q12 is prevalent in multiple tumour types, particularly in high-grade serous ovarian cancer, uterine tumours and gastro-oesophageal cancers, where high cyclin E levels are associated with genome instability, whole-genome doubling and resistance to cytotoxic and targeted therapies. To uncover therapeutic targets for tumours with CCNE1 amplification, we undertook genome-scale CRISPR-Cas9-based synthetic lethality screens in cellular models of CCNE1 amplification. Here we report that increasing CCNE1 dosage engenders a vulnerability to the inhibition of the PKMYT1 kinase, a negative regulator of CDK1.

Owner-Perception of the Effects of Two Long-Lasting Dog-Appeasing Pheromone Analog Devices on Situational Stress in Dogs.

Devices that release a synthetic analog of the canine-appeasing pheromone can help to relax dogs during stressful situations, but they usually last for only one month. Two new devices with this analog were tested by owners of dogs showing signs of stress in a range of everyday situations: Zenidog™ collar, lasting three months, and Zenidog™ diffusing gel, lasting two months (Virbac, Carros, France). They were compared against reference products that last for one month.

Longitudinal Changes of Mineral Concentrations in Preterm and Term Human Milk from Lactating Swiss Women.

An adequate mineral supply to preterm infants is essential for normal growth and development. This study aimed to compare the mineral contents of human milk (HM) from healthy mothers of preterm (28-32 weeks) and full term (>37 weeks) infants. Samples were collected weekly for eight weeks for the term group ( = 34) and, biweekly up to 16 weeks for the preterm group ( = 27).

A single-center, open-label positron emission tomography study to evaluate brivaracetam and levetiracetam synaptic vesicle glycoprotein 2A binding in healthy volunteers.

Objective: Brivaracetam (BRV) and levetiracetam (LEV) are antiepileptic drugs that bind synaptic vesicle glycoprotein 2A (SV2A). In vitro and in vivo animal studies suggest faster brain penetration and SV2A occupancy (SO) after dosing with BRV than LEV. We evaluated human brain penetration and SO time course of BRV and LEV at therapeutically relevant doses using the SV2A positron emission tomography (PET) tracer C-UCB-J (EP0074; NCT02602860).

ABCA7 rare variants and Alzheimer disease risk.

Objective: To study the association between ABCA7 rare coding variants and Alzheimer disease (AD) in a case-control setting.

Methods: We conducted a whole exome analysis among 484 French patients with early-onset AD and 590 ethnically matched controls.

Results: After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of ABCA7 loss of function (LOF) and predicted damaging missense variants in cases (odds ratio [OR] 3.