Long-term safety and effectiveness of fenfluramine in children and adults with Dravet syndrome.

Objective: We analyzed the long-term safety and effectiveness of fenfluramine (FFA) in patients with Dravet syndrome (DS) in an open-label extension (OLE) study after participating in randomized controlled trials (RCTs) or commencing FFA de novo as adults.

Methods: Patients with DS who participated in one of three RCTs or were 19 to 35 years of age and started FFA de novo were included. Key endpoints were: incidence of treatment-emergent adverse events (TEAEs) in the safety population, and median percentage change in monthly convulsive seizure frequency (MCSF) from the RCT baseline to end of study (EOS) in the modified intent-to-treat (mITT) population.

Inflammatory Signatures in VEXAS Syndrome, Myelodysplasia Cutis, and Sweet Syndrome.

Importance: VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a monogenic disease caused by UBA1 somatic variants in hematopoietic progenitor cells, mostly involving adult men. It is associated with inflammatory-related symptoms, frequently involving the skin and hematological disorders. Recently described myelodysplasia cutis (MDS-cutis) is a cutaneous manifestation of myelodysplasia in which clonal myelodysplastic cells infiltrate the skin.

Association of Diet and Waist-to-Hip Ratio With Brain Connectivity and Memory in Aging.

Importance: Epidemiological studies suggest that lifestyle factors are associated with risk of dementia. However, few studies have examined the association of diet and waist to hip ratio (WHR) with hippocampus connectivity and cognitive health.

Objective: To ascertain how longitudinal changes in diet quality and WHR during midlife are associated with hippocampal connectivity and cognitive function in later life.

Retinal Microvascular Biomarker Assessment With Automated Algorithm and Semiautomated Software in the Montrachet Dataset.

Purpose: To compare automated and semiautomated methods for the measurement of retinal microvascular biomarkers: the automated retinal vascular morphology (AutoMorph) algorithm and the Singapore "I" Vessel Assessment (SIVA) software.

Methods: Analysis of retinal fundus photographs centered on optic discs from the population-based Montrachet Study of adults aged 75 years and older. Comparison and agreement evaluation with intraclass correlation coefficients (ICCs) between SIVA and AutoMorph measures of the central retinal venular and arteriolar equivalent, arteriolar-venular ratio, and fractal dimension.

Multinuclear Silver(I)-Selenium Clusters Formation in Selenopeptides.

The reactions of ionic silver (Ag) with arginine vasopressin (AVP), a nonapeptide hormone cyclized by two cysteine residues, and its diselenium analogue was explored by an integrated LC-MS, UV-vis, and DFT approach. The replacement of Cys by SeCys in AVP increased the reactivity of the peptide toward Ag ions under mildly reducing conditions, with the formation of a SeAg cluster provided by Ag(I)-mediated dimerization of diselenide AVP. Specific electronic absorption bands confirmed the formation of the Agpeptide complex, supported by DFT calculations.

Leukemogenic Kras mutation reprograms multipotent progenitors to facilitate its spread through the hematopoietic system.

Leukemia-driving mutations are thought to arise in hematopoietic stem cells (HSC), yet the natural history of their spread is poorly understood. We genetically induced mutations within endogenous murine HSC and traced them in unmanipulated animals. In contrast to mutations associated with clonal hematopoiesis (such as Tet2 deletion), the leukemogenic KrasG12D mutation dramatically accelerated HSC contribution to all hematopoietic lineages.

Update on Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome.

Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition condition characterized by a high lifetime risk for a wide spectrum of malignancies associated with germline pathogenic/likely pathogenic (P/LP) variants in the TP53 tumor suppressor gene. Secondary malignant neoplasms are particularly common. Early cancer detection through surveillance enables early intervention and leads to improved clinical outcomes with reduced tumor-related mortality and treatment-related morbidity.

Tuning higher order structure in colloidal fluids.

Colloidal particles self assemble into a wide range of structures under external AC electric fields due to induced dipolar interactions [Yethiraj and Van Blaaderen, , 2003, , 513]. As a result of these dipolar interactions, at low volume fraction the system is modulated between a hard-sphere like state (in the case of zero applied field) and a "string fluid" upon application of the field. Using both particle-resolved experiments and computer simulations, we investigate the emergence of the string fluid with a variety of structural measures including two-body and higher-order correlations.

Announcements of Death During the COVID-19 Pandemic: A Qualitative Study of Family Experiences.

Introduction: Health restrictions resulting from COVID-19 made it more difficult for families to mourn. The death announcement is a significant moment for families. The aim of this study was to explore the experiences, perceptions and expectations of families who were informed of the death of a close relative in the hospital, at home or in a care home for dependent elderly people (EHPAD) during the COVID-19 pandemic.

Sustainable 4D Printed Meta Biocomposite Materials for Programmable Structural Shape Changing.

Biological structures provide inspiration for developing advanced materials from sustainable resources, enabling passive structural morphing. Despite an increasing interest for parsimony-oriented innovation, sustainable shape-changing materials based on renewable resources remain underexplored. In this work, the architecture of a single plant fiber cell wall (S, for instance) is simplified to design novel concepts of 4D printed tubular moisture-driven structural actuators, using the hygromorphic properties of continuous flax fiber (cFF) reinforced materials.

Conjugation Effects in the Generation of Dynamic Covalent Libraries of Bis-Imines from Substituted Aromatic Aldehyde and Amine Components.

The conjugation-driven stability and reactivity of bis-imine formation from the reaction of substituted aromatic aldehydes and amines bearing electron donor and acceptor groups were studied in two approaches involving aldehydes and amines with the substituents either conjugated (para position) or non-conjugated (meta position) to the reacting functional groups. The bis-imine from the reaction of a bis-amine (B) with different types of aldehydes (A) constituted an ABA module, whereas the reaction of bis-aldehydes with different amines resulted in a BAB module. The competitive reactions were also studied for a specified bis-amine (B1 or B2) in similar conditions with a mixture of different aldehydes, and the time-dependent generations of dynamic covalent libraries were followed.

Preserving the Biologically Coherent Generic Concept of , 'Plant Destroyer'.

is a long-established, well known and globally important genus of plant pathogens. Phylogenetic evidence has shown that the biologically distinct, obligate biotrophic downy mildews evolved from at least twice. Since, cladistically, this renders 'paraphyletic', it has been proposed that evolutionary clades be split into multiple genera (Runge et al.

Sponge Morphology of Osteosarcoma Finds Origin in Synergy Between Bone Synthesis and Tumor Growth.

Osteosarcoma is medically defined as a bone-forming tumor with associated bone-degrading activity. There is a lack of knowledge about the network that generates the overproduction of bone. We studied the early stage of osteosarcoma development with mice enduring a periosteum injection of osteosarcoma cells at the proximal third of the tibia.

Spheroids Composed of Reaggregated Neonatal Porcine Islets and Human Endothelial Cells Accelerate Development of Normoglycemia in Diabetic Mice.

The engraftment of transplanted islets depends on the rapid establishment of a novel vascular network. The present study evaluated the effects of cord blood-derived blood outgrowth endothelial cells (BOECs) on the viability of neonatal porcine islets (NPIs) and the post-transplant outcome of grafted NPIs. Dispersed NPIs and human BOECs were reaggregated on microwell cell culture plates and tested for their anti-apoptotic and pro-angiogenic capacity by qRT-PCR and immunohistochemistry.

In-device Battery Failure Analysis.

Lithium-ion batteries are indispensable power sources for a wide range of modern electronic devices. However, battery lifespan remains a critical limitation, directly affecting the sustainability and user experience. Conventional battery failure analysis in controlled lab settings may not capture the complex interactions and environmental factors encountered in real-world, in-device operating conditions.

RNA anchoring of Upf1 facilitates recruitment of Dcp2 in the NMD decapping complex.

Upf1 RNA helicase is a pivotal factor in the conserved nonsense-mediated mRNA decay (NMD) process. Upf1 is responsible for coordinating the recognition of premature termination codons (PTCs) in a translation-dependent manner and subsequently triggering mRNA degradation. Multiple factors assist Upf1 during these two consecutive steps.

Perioperative Management During Liver Transplantation: A National Survey From the French Special Interest Group in "Liver Anesthesiology and Intensive Care".

Background: Perioperative management practices in liver transplantation (LT) evolve very quickly. There are few specific recommendations, often based on a low level of evidence, resulting in wide heterogeneity of practices.

Methods: We performed a survey in all 16 French centers in 2021 by focusing on center organization, preoperative cardiovascular assessment, antimicrobial prophylaxis, hemostasis management, intraoperative use of hemodynamic monitoring and renal replacement therapy, immunosuppression, and postoperative prevention of arterial complications and compared it with current recommendations.

Vaccine Effectiveness Dynamics against Influenza and SARS-CoV-2 in Community-tested Patients in France 2023-2024.

Background: The epidemiology of respiratory viruses and vaccine effectiveness (VE) in the community is not well described. This study assessed VE against a positive test of influenza (VEf) and SARS-CoV-2 (VECov).

Methods: Data from two large networks of community-based laboratories in France were collected during standard of care in the 2023-2024 epidemic season (n = 511,083 RT-PCR tests).

Impact of tacrolimus on interferon gamma ELISpot assay results for the assessment of T-cell immunity: Proof-of-concept.

SOT patients require immunosuppressors to avoid graft rejection. Therapeutic drug monitoring is insufficient to find the optimal balance with immunosuppression. The evaluation of cell-mediated immunity by enzyme-linked immunospot (ELISpot) assay enumerating interferon-gamma (IFN-γ) is increasingly use.

IL-23p19 Antagonists vs. Ustekinumab for Treatment of Crohn's Disease: A Meta-analysis of Randomized Controlled Trials.

Background And Aims: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing interleukin (IL)-23p19 antagonists with ustekinumab, stratified by prior biologic exposure, in patients with moderate-to-severe Crohn's disease (CD).

Methods: Through a systematic review through August 17, 2024, we identified phase 2 and 3 RCTs comparing IL-23p19 antagonists vs. ustekinumab in adults with moderate-to-severe CD.

Extent of surgical repair and outcomes after surgery for type A aortic dissection.

Background: Acute Stanford type A aortic dissection is a severe emergency condition that, if left untreated, is associated with a high mortality rate. The extent of surgical repair may impact the outcomes of these patients.

Method: Patients operated for acute type A aortic dissection from a multicentre European registry were included.

Performance of an Automated Insulin Delivery System in People Living With Type 2 Diabetes and Insulin Resistance: First Real-World Evidence in 26 427 Users.

Background: Type 2 diabetes (T2D) is a phenotypically heterogeneous disease. The use of insulin is required in a significant portion of people with T2D, despite recent developments in antidiabetic medications. This study analyzes glycemic outcomes in automated insulin delivery (AID) users with T2D with different insulin requirements.

Platinum-based nanoalloys for the oxygen reduction reaction: exposing the true active phase techniques.

Platinum-based nanoalloys are efficient electrocatalysts for the oxygen reduction reaction (ORR). measurements have revealed that key properties including induced strain, chemical composition, coordination environment, evolve significantly during operation, which can hampertheir effective implementation in fuel cells. In fact, recent studies indicate that the impact of the early surface activation steps of Pt-based nanoalloys has been hitherto underestimated and is an important factor contributing to loss of their initial electroactivity.