Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis.

Histone H3.3 glycine 34 to arginine/valine (G34R/V) mutations drive deadly gliomas and show exquisite regional and temporal specificity, suggesting a developmental context permissive to their effects. Here we show that 50% of G34R/V tumors (n = 95) bear activating PDGFRA mutations that display strong selection pressure at recurrence.

A modified IRS-III chemotherapy regimen leads to prolonged survival in children with embryonal tumor with multilayer rosettes.

Background: Embryonal tumor with multilayer rosettes (ETMR) is a rare CNS malignancy affecting young children that carries a very poor prognosis. Treatment with intensive surgical resection, radiotherapy, and high-dose chemotherapy is insufficient treatment in the vast majority of cases. Effective, biologically based therapies for this tumor are therefore desperately needed.

Interaction between magnesium and methylglyoxal in diabetic polyneuropathy and neuronal models.

Objective: The lack of effective treatments against diabetic sensorimotor polyneuropathy demands the search for new strategies to combat or prevent the condition. Because reduced magnesium and increased methylglyoxal levels have been implicated in the development of both type 2 diabetes and neuropathic pain, we aimed to assess the putative interplay of both molecules with diabetic sensorimotor polyneuropathy.

Methods: In a cross-sectional study, serum magnesium and plasma methylglyoxal levels were measured in recently diagnosed type 2 diabetes patients with (n = 51) and without (n = 184) diabetic sensorimotor polyneuropathy from the German Diabetes Study baseline cohort.

Recurrent fusions in pediatric sarcoma and brain tumors.

The identification of rearrangements driving expression of neurotrophic receptor tyrosine kinase () family kinases in tumors has become critically important because of the availability of effective, specific inhibitor drugs. Whole-genome sequencing (WGS) combined with RNA sequencing (RNA-seq) can identify novel and recurrent expressed fusions. Here we describe three fusions identified in two pediatric central nervous system cancers and an extracranial solid tumor using WGS and RNA-seq.

Association of cardiac autonomic dysfunction with higher levels of plasma lipid metabolites in recent-onset type 2 diabetes.

Aims/hypothesis: Emerging evidence suggests that in addition to hyperglycaemia, dyslipidaemia could represent a contributing pathogenetic factor to diabetic neuropathy, while obesity and insulin resistance play a role in the development of diabetic cardiac autonomic neuropathy (CAN) characterised by reduced heart rate variability (HRV), particularly in type 2 diabetes. We hypothesised that distinct lipid metabolites are associated with diminished HRV in recent-onset type 2 diabetes rather than type 1 diabetes.

Methods: We analysed 127 plasma lipid metabolites (11 acylcarnitines, 39 NEFA, 12 sphingomyelins (SMs), 56 phosphatidylcholines and nine lysophosphatidylcholines) using MS in participants from the German Diabetes Study baseline cohort recently diagnosed with type 1 (n = 100) and type 2 diabetes (n = 206).

Rate of true recurrent implantation failure is low: results of three successive frozen euploid single embryo transfers.

Objective: To study the true prevalence of recurrent implantation failure.

Design: Retrospective cohort study.

Setting: A private assisted reproductive technology center.

Focus on the Breath: Brain Decoding Reveals Internal States of Attention During Meditation.

Meditation practices are often used to cultivate interoception or internally-oriented attention to bodily sensations, which may improve health cognitive and emotional regulation of bodily signals. However, it remains unclear how meditation impacts internal attention (IA) states due to lack of measurement tools that can objectively assess mental states during meditation practice itself, and produce time estimates of internal focus at individual or group levels. To address these measurement gaps, we tested the feasibility of applying multi-voxel pattern analysis (MVPA) to single-subject fMRI data to: (1) learn and recognize internal attentional states relevant for meditation during a directed IA task; and (2) decode or estimate the presence of those IA states during an independent meditation session.

Is there a link between plasma progesterone 1-2 days before frozen embryo transfers (FET) and ART outcomes in frozen blastocyst transfers?

Objective: To study the efficacy of combined administration of subcutaneous and vaginal progesterone for priming frozen blastocysts transfers, looking at progesterone levels and ART outcome.

Design: Retrospective study.

Setting Patients: Three hundred and twenty frozen blastocyst transfer cycles conducted in 213 women aged up to 42 years, BMI between 18 and 30 kg/m, with anatomically normal uterus who underwent frozen embryo transfers (FETs) from February 2019 to December 2019 with a combined luteal-phase support (LPS) associating subcutaneous and vaginal progesterone.

Gastrointestinal Hemorrhage: A Manifestation of the Telomere Biology Disorders.

Objective: To describe the clinical features, therapeutic interventions, and patient outcomes of gastrointestinal (GI) hemorrhage in individuals with a telomere biology disorder, including dyskeratosis congenita, Hoyeraal-Hreidarsson syndrome, Revesz syndrome, and Coats plus.

Study Design: Clinical Care Consortium for Telomere Associated Ailments members were invited to contribute data on individuals with telomere biology disorders at their institutions who experienced GI bleeding. Patient demographic, laboratory, imaging, procedural, and treatment information and outcomes were extracted from the medical record.

Current concepts in the management of diabetic polyneuropathy.

Diabetic sensorimotor polyneuropathy (DSPN) is encountered in approximately one-third of people with diabetes. This, in turn, might markedly impoverish their quality of life, mainly owing to neuropathic pain and foot ulcerations. Painful DSPN might be as frequent as 25% in diabetes patients.

Germline-driven replication repair-deficient high-grade gliomas exhibit unique hypomethylation patterns.

Replication repair deficiency (RRD) leading to hypermutation is an important driving mechanism of high-grade glioma (HGG) occurring predominantly in the context of germline mutations in RRD-associated genes. Although HGG presents specific patterns of DNA methylation corresponding to oncogenic mutations, this has not been well studied in replication repair-deficient tumors. We analyzed 51 HGG arising in the background of gene mutations in RRD utilizing either 450 k or 850 k methylation arrays.

Evaluation of molecular inversion probe versus TruSeq® custom methods for targeted next-generation sequencing.

Resolving the genetic architecture of painful neuropathy will lead to better disease management strategies. We aimed to develop a reliable method to re-sequence multiple genes in a large cohort of painful neuropathy patients at low cost. In this study, we compared sensitivity, specificity, targeting efficiency, performance and cost effectiveness of Molecular Inversion Probes-Next generation sequencing (MIPs-NGS) and TruSeq® Custom Amplicon-Next generation sequencing (TSCA-NGS).

The Association Between Early Postoperative Leg Pain Intensity and Disability at 1-Year and 2-Year Follow-Up After First-Time Lumbar Discectomy.

Study Design: Longitudinal cohort study.

Objectives: To investigate whether a cutoff point in leg pain intensity measured preoperatively or at early follow-up could identify patients at risk of poor outcomes in terms of disability at 1-year and 2-year follow-up after first-time lumbar discectomy, and to identify the characteristics associated with early postoperative leg pain intensity.

Methods: From 2010 to 2013, 556 patients underwent lumbar discectomy.

Double-blind, randomized, placebo-controlled crossover trial of alpha-lipoic acid for the treatment of fibromyalgia pain: the IMPALA trial.

Fibromyalgia is a common and challenging chronic pain disorder with few, if any, highly effective and well-tolerated treatments. Alpha-lipoic acid (ALA) is a nonsedating antioxidant with evidence of efficacy in the treatment of symptomatic diabetic neuropathy that has not been evaluated in the setting of fibromyalgia treatment. Thus, we conducted a single-centre, proof-of-concept, randomized, placebo-controlled, crossover trial of ALA for the treatment of fibromyalgia.

Managing an obstetrics and gynaecology department in time of COVID pandemic: safety and efficacy first at Foch hospital.

Obstetrics and Gynecology department in France were not ready for the outbreak of the COVID pandemic, but ingenuity and dedication of personnel allowed to perform safely and avoid nocomial transmission of COVID.

β-amyloid and tau drive early Alzheimer's disease decline while glucose hypometabolism drives late decline.

Clinical trials focusing on therapeutic candidates that modify β-amyloid (Aβ) have repeatedly failed to treat Alzheimer's disease (AD), suggesting that Aβ may not be the optimal target for treating AD. The evaluation of Aβ, tau, and neurodegenerative (A/T/N) biomarkers has been proposed for classifying AD. However, it remains unclear whether disturbances in each arm of the A/T/N framework contribute equally throughout the progression of AD.

Uterus Transplantation with Live Donors: Screening Candidates in One French Center.

We report our experience regarding the profile and screening process of potential recipients (R) and their live donors (D) in our Uterus transplantation (UTx) trial from 2014 to 2020. The initial screening was performed using medical questionnaires and consultations. The second step of the screening consisted of two individual interviews with an independent multidisciplinary committee.