RetroFun-RVS: A Retrospective Family-Based Framework for Rare Variant Analysis Incorporating Functional Annotations.

A large proportion of genetic variations involved in complex diseases are rare and located within noncoding regions, making the interpretation of underlying biological mechanisms a daunting task. Although technical and methodological progress has been made to annotate the genome, current disease-rare-variant association tests incorporating such annotations suffer from two major limitations. First, they are generally restricted to case-control designs of unrelated individuals, which often require tens or hundreds of thousands of individuals to achieve sufficient power.

Influence of Anticoagulants on Platelet Counts: A Study and Recommendations From the French Speaking Cellular Hematology Group (GFHC).

Introduction: For complete blood count, ethylenediaminetetraacetic acid (EDTA) is universally used and has been recognized as the most robust anticoagulant. However, it may lead to pseudothrombocytopenia (PTCT), due to the formation of platelet clumps, which is currently followed by resampling on sodium citrate. Other possible anticoagulants are citrate theophylline adenosine dipyridamole (CTAD) and MgSO.

Evaluation of the In Vivo Efficacy of the JAK Inhibitor AZD1480 in Uterine Leiomyomas Using a Patient-derived Xenograft Murine Model.

Uterine leiomyomas are common noncancerous hormonally-dependent neoplasms comprised of uterine smooth-muscle cells and fibroblasts. Despite their significant impact on morbidity, effective non-hormonal medical treatments are lacking. In vitro studies have identified the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway as a promising target in leiomyoma cells.

A transcriptomic comparison of in vitro models of the human placenta.

Introduction: Selecting an in vitro culture model of the human placenta is challenging due to representation of different trophoblast cell types with distinct biological roles and limited comparative studies that define key characteristics of these models. The aim of this research was to compare the transcriptomes of common in vitro models of the human placenta compared to bulk human placental tissue.

Methods: We performed differential gene expression analysis on publicly available transcriptomic data from 7 in vitro models of the human placenta (HTR-8/SVneo, BeWo, JEG-3, JAR, Primary Trophoblasts, Villous Explants, and Trophoblast Stem Cells) and compared to bulk placental tissue from 2 cohort studies (CANDLE and GAPPS) or individual trophoblast cell types derived from bulk placental tissue.

Learning extreme expected shortfall and conditional tail moments with neural networks. Application to cryptocurrency data.

We propose a neural networks method to estimate extreme Expected Shortfall, and even more generally, extreme conditional tail moments as functions of confidence levels, in heavy-tailed settings. The convergence rate of the uniform error between the log-conditional tail moment and its neural network approximation is established leveraging extreme-value theory (in particular the high-order condition on the distribution tails) and using critically two activation functions (eLU and ReLU) for neural networks. The finite sample performance of the neural network estimator is compared to bias-reduced extreme-value competitors using synthetic heavy-tailed data.

Fine-scale genetic structure and rare variant frequencies.

In response to the current challenge in genetic studies to make new associations, we advocate for a shift toward leveraging population fine-scale structure. Our exploration brings to light distinct fine-structure within populations having undergone a founder effect such as the Ashkenazi Jews and the population of the Quebec' province. We leverage the fine-scale population structure to explore its impact on the frequency of rare variants.

Circulating Immune Cells from Early- and Late-onset Pre-eclampsia Displays Distinct Profiles with Differential Impact on Endothelial Activation.

Pre-eclampsia (PE) affects 5-8% of pregnancies and has detrimental effects on maternal-fetal health. PE is characterized by de novo hypertension after 20 wk of gestation and end-organ damage. Systemic inflammatory imbalance has been associated with PE, but its contribution to the pathology is poorly understood.

Photobleaching Effect on the Sensitivity Calibration at 638 nm of a Phosphorus-Doped Single-Mode Optical Fiber Dosimeter.

We investigated the influence of the photobleaching (PB) effect on the dosimetry performances of a phosphosilicate single-mode optical fiber (core diameter of 6.6 µm) operated at 638 nm, within the framework of the LUMINA project. Different irradiation tests were performed under ~40 keV mean energy fluence X-rays at a 530 µ Gy(SiO)/s dose rate to measure in situ the radiation-induced attenuation (RIA) growth and decay kinetics while injecting a 638 nm laser diode source with powers varying from 500 nW to 1 mW.

Maternal Innate Immune Reprogramming After Complicated Pregnancy.

Problem: Preeclampsia (PE) and fetal growth restriction (FGR) are often associated with maternal inflammation and an increased risk of cardiovascular and metabolic disease in the affected mothers. The mechanism responsible for this increased risk of subsequent disease may involve reprogramming of innate immune cells, characterized by epigenetic modifications.

Method Of Study: Circulating monocytes from women with PE, FGR, or uncomplicated pregnancies (control) were isolated before labor.

Identification of divergent placental profiles in clinically distinct pregnancy complications revealed by the transcriptome.

Introduction: Pregnancy complications, including preeclampsia (PE), preterm birth (PTB), and intra-uterine growth restriction (IUGR) have individually been associated with inflammation but the combined comparative analysis of their placental profiles at the transcriptomic and histological levels is lacking.

Methods: Bulk RNA-sequencing of human placental biopsies from uncomplicated term pregnancies (CTL) and pregnancies complicated with early-onset (EO), and late-onset (LO) PE, as well as PTB and term IUGR were used to characterize individual molecular profiles. We also applied immune-cell-specific cellular deconvolution to address local immune cell compositions and analyzed placental lesions by histology to further characterize these complications.

Assessment of Aminoglycoside-Induced Hearing Loss Risk in the Perinatal Period.

Objective:  This study aimed to determine the prevalence and heteroplasmy level(s) of variants m.1555A > G and m.1494C > T, which are associated with aminoglycoside-induced hearing loss, in a general perinatal population.

Transcriptomic comparison of in vitro models of the human placenta.

Studying the human placenta through in vitro cell culture methods is necessary due to limited access and amenability of human placental tissue to certain experimental methods as well as distinct anatomical and physiological differences between animal and human placentas. Selecting an in vitro culture model of the human placenta is challenging due to representation of different trophoblast cell types with distinct biological roles and limited comparative studies that define key characteristics of these models. Therefore, the aim of this research was to create a comprehensive transcriptomic comparison of common in vitro models of the human placenta compared to bulk placental tissue from the CANDLE and GAPPS cohorts (N=1083).

Preventing Preterm Birth: Exploring Innovative Solutions.

This review examines the complexities of preterm birth (PTB), emphasizes the pivotal role of inflammation in the pathogenesis of preterm labor, and assesses current available interventions. Antibiotics, progesterone analogs, mechanical approaches, nonsteroidal anti-inflammatory drugs, and nutritional supplementation demonstrate a limited efficacy. Tocolytic agents, targeting uterine activity and contractility, inadequately prevent PTB by neglecting to act on uteroplacental inflammation.

Involving community pharmacists in interprofessional collaboration in primary care: a systematic review.

Background: The World Health Organization supports interprofessional collaboration in primary care. On over the past 20 years, community pharmacists had been taking a growing number of new responsibilities and they are recognized as a core member of collaborative care teams as patient-centered care providers. This systematic review aimed to describe interprofessional collaboration in primary care involving a pharmacist, and its effect on patient related outcomes.

mutations provide genetic vulnerability to copper ionophores in human acute myeloid leukemia.

In a phenotypical screen of 56 acute myeloid leukemia (AML) patient samples and using a library of 10,000 compounds, we identified a hit with increased sensitivity toward -mutated and adverse risk AMLs. Through structure-activity relationship studies, this hit was optimized into a potent, specific, and nongenotoxic molecule called UM4118. We demonstrated that UM4118 acts as a copper ionophore that initiates a mitochondrial-based noncanonical form of cell death known as cuproptosis.

Pregnant individuals with uncomplicated pregnancies display pro-inflammatory immune changes when exposed to the COVID-19 pandemic.

Problem: The COVID-19 pandemic has been shown to have a detrimental impact on the mental health of pregnant individuals, and chronic stress can alter the immune profile. However, the effects of the COVID-19 pandemic on the immune system in pregnancy are still poorly understood. We aimed to evaluate the impact of pandemic exposure on the maternal immune profile in uncomplicated pregnancies.

[Suspicion of constitutional abnormality at diagnosis of childhood leukemia: Update of the leukemia committee of the French Society of Childhood Cancers].

The spectrum of childhood leukemia predisposition syndromes has grown significantly over last decades. These predisposition syndromes mainly involve CEBPA, ETV6, GATA2, IKZF1, PAX5, RUNX1, SAMD9/SAMD9L, TP53, RAS-MAPK pathway, DNA mismatch repair system genes, genes associated with Fanconi anemia, and trisomy 21. The clinico-biological features leading to the suspicion of a leukemia predisposition are highly heterogeneous and require varied exploration strategies.

Circulating levels of inflammatory mediators in pregnant people living with HIV according to antiretroviral therapy regimen.

Introduction: The use of antiretroviral therapy (ART) during pregnancy, particularly protease-inhibitor-based regimens (PI), has been linked to adverse outcomes including preterm delivery. As this outcome may be related to systemic inflammation, we sought to characterize inflammatory profiles of pregnant people living with HIV (PLWH) by comparing their levels of inflammatory mediators at two timepoints during pregnancy according to ART regimen, and to HIV-negative controls.

Methods: Second and third trimester samples from 144 pregnant PLWH treated with ART and 24 HIV-uninfected controls were retrieved from the CARMA-PREG cohort.

KBTBD4-mediated reduction of MYC is critical for hematopoietic stem cell expansion upon UM171 treatment.

Ex vivo expansion of hematopoietic stem cells (HSCs) is gaining importance for cell and gene therapy, and requires a shift from dormancy state to activation and cycling. However, abnormal or excessive HSC activation results in reduced self-renewal ability and increased propensity for myeloid-biased differentiation. We now report that activation of the E3 ligase complex CRL3KBTBD4 by UM171 not only induces epigenetic changes through CoREST1 degradation but also controls chromatin-bound master regulator of cell cycle entry and proliferative metabolism (MYC) levels to prevent excessive activation and maintain lympho-myeloid potential of expanded populations.

Spatial proteomics reveals phenotypic and functional differences in T cell and macrophage subsets during villitis of unknown etiology.

Villitis of unknown etiology (VUE) is a prevalent inflammatory pathology of the placenta characterized by infiltration of maternal T cells and accumulation of fetal macrophages into chorionic villi. VUE is associated with a variety of adverse clinical outcomes, including fetal growth restriction and fetal demise. Evaluation of the phenotypic and functional differences between two immune cell types associated with this pathology, namely T cells and macrophages, was completed to gain a deeper understanding of the immuno-pathogenesis of VUE.