New Insights on In Vitro Maturation of Oocytes for Fertility Preservation.

In the last decade, the evolution of oncofertility has sparked a resurgence of interest in in vitro maturation (IVM) due to its suitability in certain oncological scenarios where controlled ovarian hyperstimulation may not be feasible. The retrieval of immature cumulus-oocyte complexes from small antral follicles, regardless of the menstrual cycle phase, presents a swift opportunity to vitrify mature oocytes or embryos post-IVM in urgent situations or when stimulation is not advisable. Harvesting immature cumulus-oocyte complexes and immature oocytes can be achieved transvaginally or directly in the laboratory from extracorporeal ovarian tissue.

Diffusion mechanisms for spinel ferrite NiFe2O4 by using kinetic activation-relaxation technique.

Mass transport in bulk spinel ferrites NiFe2O4 is studied computationally using the kinetic activation-relaxation technique (k-ART), an off-lattice kinetic Monte Carlo algorithm. Diffusion mechanisms-difficult to observe with molecular dynamics-are described by k-ART. Point defects are assumed to be responsible for ionic diffusion; thus, both cation and anion defects are investigated.

Incorporation of Intracellular NanoSIMS Tracers to Oligonucleotide Conjugates via Strain Promoted Sydnone-Alkyne Cycloaddition.

Extensive efforts have been dedicated to developing cell-specific targeting ligands that can be conjugated to therapeutic cargo, offering a promising yet still challenging strategy to deliver oligonucleotide therapeutics beyond the liver. Indeed, while the cargo and the ligand are crucial, the third component, the linker, is integral but is often overlooked. Here, we present strain-promoted sydnone-alkyne cycloaddition as a versatile linker chemistry for oligonucleotide synthesis, expanding the choices for bioconjugation of therapeutics while enabling subcellular detection of the linker and payload using nanoscale secondary ion mass spectrometry (NanoSIMS) imaging.

Real-life use of apremilast for the treatment of psoriasis in patients with oncological comorbidities: a retrospective descriptive multicentre study in France.

Background: Systemic treatment options for psoriasis are limited for patients with recent neoplasia.

Objectives: We report the real-life use of apremilast (APR) in patients with psoriasis and recent cancer.

Materials & Methods: We conducted a retrospective, multicentre study in five hospitals and among 120 private dermatologists in the north of France from January 2015 to May 2021.

Elevated Adipocyte Membrane Phospholipid Saturation Does Not Compromise Insulin Signaling.

Increased saturated fatty acid (SFA) levels in membrane phospholipids have been implicated in the development of metabolic disease. Here, we tested the hypothesis that increased SFA content in cell membranes negatively impacts adipocyte insulin signaling. Preadipocyte cell models with elevated SFA levels in phospholipids were generated by disrupting the ADIPOR2 locus, which resulted in a striking twofold increase in SFA-containing phosphatidylcholines and phosphatidylethanolamines, which persisted in differentiated adipocytes.

Intracellular Absolute Quantification of Oligonucleotide Therapeutics by NanoSIMS.

Antisense oligonucleotide (ASO)-based therapeutics hold great potential for the treatment of a variety of diseases. Therefore, a better understanding of cellular delivery, uptake, and trafficking mechanisms of ASOs is highly important for early-stage drug discovery. In particular, understanding the biodistribution and quantifying the abundance of ASOs at the subcellular level are needed to fully characterize their activity.

NanoSIMS Imaging Reveals the Impact of Ligand-ASO Conjugate Stability on ASO Subcellular Distribution.

The delivery of antisense oligonucleotides (ASOs) to specific cell types via targeted endocytosis is challenging due to the low cell surface expression of target receptors and inefficient escape of ASOs from the endosomal pathway. Conjugating ASOs to glucagon-like peptide 1 (GLP1) leads to efficient target knockdown, specifically in pancreatic β-cells. It is presumed that ASOs dissociate from GLP1 intracellularly to enable an ASO interaction with its target RNA.

Investigating the kinetics of the formation of a C Cottrell atmosphere around a screw dislocation in bcc iron: a mixed-lattice atomistic kinetic Monte-Carlo analysis.

We present a mixed-lattice atomistic kinetic Monte-Carlo algorithm (MLKMC) that integrates a rigid-lattice AKMC approach with the kinetic activation-relaxation technique (k-ART), an off-lattice/self-learning AKMC. This approach opens the door to study large and complex systems adapting the cost of identification and evaluation of transition states to the local environment. To demonstrate its capacity, MLKMC is applied to the problem of the formation of a C Cottrell atmosphere decorating a screw dislocation in α-Fe.

Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR.

Innate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-like receptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatory signals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect the immune response is unknown.

A single typical trichoscopic feature is predictive of tinea capitis: a prospective multicentre study.

Background: Specific trichoscopic signs of tinea capitis (TC) were first described in 2008. The accuracy of this diagnostic tool has not been evaluated.

Objectives: To assess the diagnostic accuracy of trichoscopy.

A model of defect cluster creation in fragmented cascades in metals based on morphological analysis.

The impacts of ions and neutrons in metals cause cascades of atomic collisions that expand and shrink, leaving microstructure defect debris, i.e. interstitial or vacancy clusters or loops of different sizes.

Keratinocyte Expression of A20/TNFAIP3 Controls Skin Inflammation Associated with Atopic Dermatitis and Psoriasis.

Keratinocytes are key players in chronic inflammatory skin diseases. A20 regulates NF-κB-dependent expression of proinflammatory genes and cell death, but the impact of its expression in keratinocytes on systemic inflammation and skin disorders has not been determined. Comparative transcriptomic analysis of microdissected epidermis showed that A20 is down-regulated in involved epidermis, but not in dermis, of psoriasis and atopic dermatitis patients, suggesting that loss of A20 expression in keratinocytes increases the vulnerability for psoriasis/atopic dermatitis induction.

Building of neomycin-nucleobase-amino acid conjugates for the inhibition of oncogenic miRNAs biogenesis.

MicroRNAs (miRNAs) are a recently discovered category of small RNA molecules that regulate gene expression at the post-transcriptional level. Accumulating evidence indicates that miRNAs are aberrantly expressed in a variety of human cancers, thus being oncogenic. The inhibition of oncogenic miRNAs (defined as the blocking of miRNAs' production or function) would find application in the therapy of different types of cancer in which these miRNAs are implicated.

Interaction between interstitial carbon atoms and a ½ 〈1 1 1〉 self-interstitial atoms loop in an iron matrix: a combined DFT, off lattice KMC and MD study.

A static and kinetic study of the interaction between a 19 ½ 〈1 1 1〉 self-interstitial atoms loop and C atoms in body-centred cubic iron is presented in this work. An empirical potential matching the density functional theory calculations is used to study the static properties of the system. The usual kinetic Monte-Carlo (KMC) on-lattice restriction is not valid when the material is highly distorted, especially in the presence of a dislocation loop.

An empirical potential for simulating vacancy clusters in tungsten.

We present an empirical interatomic potential for tungsten, particularly well suited for simulations of vacancy-type defects. We compare energies and structures of vacancy clusters generated with the empirical potential with an extensive new database of values computed using density functional theory, and show that the new potential predicts low-energy defect structures and formation energies with high accuracy. A significant difference to other popular embedded-atom empirical potentials for tungsten is the correct prediction of surface energies.

Hemophagocytic lymphohistiocytosis in patients with metastatic malignant melanoma.

Hemophagocytic lymphohistiocytosis (HLH) is an autoinflammatory disease that classically occurs because of infections, autoinflammatory, or autoimmune diseases, hematologic cancers, and rarely because of solid tumor. We report a rare case of HLH attributed to metastatic malignant melanoma treated without corticosteroid and with a nonfatal outcome thanks to specific therapies: etoposide for HLH and a selective inhibitor of mutated forms of BRAF kinase associated with a MEK inhibitor for melanoma.

Extensive levamisole-induced vasculitis.

Levamisole (an increasingly frequent contaminant of cocaine) can cause antineutrophil cytoplasmic antibody-associated vasculitis. Dermatologists should consider a diagnosis of cocaine/levamisole-associated cutaneous vasculopathy syndrome in cases of purpura of the ears and/or extensive retiform purpura in drug users. We report a case of particularly severe levamisole-induced necrotic purpura and immunological abnormalities in a 40-year-old woman.

[Bacillus cereus endocarditis and a probable cutaneous gateway].

Background: Bacillus cereus is a ubiquitous telluric organism. B. cereus endocarditis is a rare condition seen mostly in prosthetic heart valves and among intravenous drug users.

Extensive Necrotic Purpura in Levamisole-Adulterated Cocaine Abuse - A Case Report.

Levamisole, which is used as an adulterated compound of cocaine, is currently being seen year after year in cocaine intoxication. For a few cases in the last decade, necrotic purpura and neutropenia after levamisole/cocaine intoxication have been described in the medical community. Herein, we present an original case of levamisole intoxication of a 40-year-old woman who smoked heroin and cocaine few during a month.

Influence of surface vacancy defects on the carburisation of Fe 110 surface by carbon monoxide.

Adsorption and dissociation of gaseous carbon monoxide (CO) on metal surfaces is one of the most frequently occurring processes of carburisation, known as primary initiator of metal dusting corrosion. Among the various factors that can significantly influence the carburisation process are the intrinsic surface defects such as single surface vacancies occurring at high concentrations due to their low formation energy. Intuitively, adsorption and dissociation barriers of CO are expected to be lowered in the vicinity of a surface vacancy, due to the strong attractive interaction between the vacancy and the C atom.