Serum metabolome indicators of early childhood development in the Brazilian National Survey on Child Nutrition (ENANI-2019).

The role of circulating metabolites on child development is understudied. We investigated associations between children's serum metabolome and early childhood development (ECD). Untargeted metabolomics was performed on serum samples of 5,004 children aged 6-59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019).

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Rapidly spreading with OXA-48-like carbapenemases.

(mostly , ) with OXA-48-like carbapenemases (e.g., OXA-48, -181, -232, -244) are undermining the global efficiency of carbapenem therapy.

Wake up!: a novel, cadaver-based approach to training emergency physicians in awake intubation.

Despite awake tracheal intubation being considered the safest method of intubation for patients with predicted difficult airways, there is limited evidence and poor availability of training interventions to assist emergency medicine physicians achieve competency in this technique. Here, we describe a novel, cadaver-based course for emergency medicine physicians to acquire skills in awake tracheal intubation. A convenience sample of 15 emergency medicine physicians from across Canada participated in the pilot course.

Novel thermosensitive small multilamellar lipid nanoparticles with promising release characteristics made by dual centrifugation.

Thermosensitive liposomes (TSLs) have great potential for the selective delivery of cytostatic drugs to the tumor site with greatly reduced side effects. Here we report the discovery and characterization of new thermosensitive small multilamellar lipid nanoparticles (tSMLPs) with unusually high temperature selectivity. Furthermore, the temperature-dependent release of the fluorescent marker calcein from tSMLPs is enhanced by human serum albumin.

Impact of Bifurcation Lesions on Outcomes After FFR-Guided PCI or CABG.

Background: In the era of first-generation drug-eluting stents and angiography-guided percutaneous coronary intervention (PCI), the presence of a bifurcation lesion was associated with adverse outcomes after PCI. In contrast, the presence of a bifurcation lesion had no impact on outcomes following coronary artery bypass grafting (CABG). Therefore, the presence of a coronary bifurcation lesion requires special attention when choosing between CABG and PCI.

Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma.

Background: Daratumumab, an anti-CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma. Data are needed regarding the use of daratumumab for high-risk smoldering multiple myeloma, a precursor disease of active multiple myeloma for which no treatments have been approved.

Methods: In this phase 3 trial, we randomly assigned patients with high-risk smoldering multiple myeloma to receive either subcutaneous daratumumab monotherapy or active monitoring.

Body dysmorphic disorder.

Body dysmorphic disorder (BDD) is an obsessive-compulsive disorder-related psychiatric condition characterized by an intense preoccupation with perceived physical flaws that are not observable by others. BDD affects ~2% of the adult population but is underdiagnosed, partly owing to limited clinician awareness, and undertreated, partly due to limited access to treatment. Research on the aetiology of BDD is scarce but likely involves an interplay between genetic and environmental factors.

Interlaboratory comparison of standardised metabolomics and lipidomics analyses in human and rodent blood using the MxP Quant 500 kit.

Metabolomics and lipidomics are pivotal in understanding phenotypic variations beyond genomics. However, quantification and comparability of mass spectrometry (MS)-derived data are challenging. Standardised assays can enhance data comparability, enabling applications in multi-center epidemiological and clinical studies.

Sex-dependent additive effects of dorzagliatin and incretin on insulin secretion in a novel mouse model of -MODY.

Glucokinase (GK) catalyses the key regulatory step in glucose-stimulated insulin secretion. Correspondingly, hetero- and homozygous mutations in human cause maturity-onset diabetes of the young (GCK-MODY) and permanent neonatal diabetes (PNDM), respectively. To explore the possible utility of glucokinase activators (GKA) and of glucagon-like receptor-1 (GLP-1) agonists in these diseases, we have developed a novel hypomorphic allele in mice encoding an aberrantly spliced mRNA deleted for exons 2 and 3.

Head-to-head comparison of tau PET tracers [F]PI-2620 and [F]RO948 in non-demented individuals with brain amyloid deposition: the TAU-PET FACEHBI cohort.

Background: Second-generation tau tracers for positron emission tomography (PET) show high affinity for paired helical filaments tau deposits characteristic of Alzheimer´s disease and low off-target binding. Differences in their chemical structure though may lead to variations in their regional tau uptake and off-target signal. In this work, we aimed to compare the in-vivo uptake of tau tracers [F]PI-2620 and [F]RO948 in the early stages of the AD continuum.

Hereditary Transthyretin Amyloidosis in Patients Referred to a Genetic Testing Program.

Background: Diagnosis of hereditary amyloid transthyretin (hATTR) amyloidosis with cardiomyopathy is frequently delayed, in large part because of symptom overlap with other cardiovascular diseases and limited provider knowledge of this disease. The sponsored and provider referred hATTR Compass Genetic Testing Program (Ionis, Carlsbad, CA; Ambry Genetics, Aliso Viejo, CA) provided no-cost genetic testing to adults with a family history or clinical suspicion of hATTR amyloidosis. This study aims to characterize patients with hATTR amyloidosis and increase awareness of genetic testing for hATTR.

The emerging field of non-invasive brain stimulation in Alzheimer's disease.

Treating cognitive impairment is a holy grail of modern clinical neuroscience. In the past few years, non-invasive brain stimulation is increasingly emerging as a therapeutic approach to ameliorate performance in patients with cognitive impairment and as an augmentation approach in persons whose cognitive performance is within normal limits. In patients with Alzheimer's disease, better understanding of brain connectivity and function has allowed for the development of different non-invasive brain stimulation protocols.

The Role of Active Brown Adipose Tissue in Patients With Pheochromocytoma or Paraganglioma.

Objectives: Metabolically-active brown adipose tissue (aBAT) is a common finding on fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in patients with pheochromocytoma or paraganglioma (PPGL). In addition to its clinical significance, we aimed to explore the prevalence of this finding on FDG-PET imaging in patients with PPGL.

Methods: We conducted a systematic review and meta-analysis of prospective and retrospective studies.

PCSK9 in metabolism and diseases.

PCSK9 is a serine protease that regulates plasma levels of low-density lipoprotein (LDL) and cholesterol by mediating the endolysosomal degradation of LDL receptor (LDLR) in the liver. When PCSK9 functions unchecked, it leads to increased degradation of LDLR, resulting in elevated circulatory levels of LDL and cholesterol. This dysregulation contributes to lipid and cholesterol metabolism abnormalities, foam cell formation, and the development of various diseases, including cardiovascular disease (CVD), viral infections, cancer, and sepsis.

Bexotegrast in people with idiopathic pulmonary fibrosis (IPF): a plain language summary of publication of the INTEGRIS-IPF study.

This plain language summary shares results from a clinical study called INTEGRIS-IPF that was published in the in 2024. This study looked at a medicine called (beck-so-teh-grast) as a possible treatment for (i-dee-uh-pa-thick pul-muh-ner-ee fie-bro-sis; IPF). is an investigational medicine, which means that it is being studied and has not yet been approved by the US Food and Drug Administration (FDA), for people with IPF to take as a treatment.

Advances in myocardial energy metabolism: metabolic remodelling in heart failure and beyond.

The very high energy demand of the heart is primarily met by adenosine triphosphate (ATP) production from mitochondrial oxidative phosphorylation, with glycolysis providing a smaller amount of ATP production. This ATP production is markedly altered in heart failure, primarily due to a decrease in mitochondrial oxidative metabolism. Although an increase in glycolytic ATP production partly compensates for the decrease in mitochondrial ATP production, the failing heart faces an energy deficit that contributes to the severity of contractile dysfunction.

Randomised controlled trial comparing different intersession intervals of intermittent theta burst delivered to the dorsal medial prefrontal cortex.

Background: Intermittent theta burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation (rTMS) that can be administered in a fraction of the time of standard rTMS. Applying multiple daily iTBS sessions (ie, accelerated iTBS) may enable patients to achieve remission more rapidly. However, questions remain regarding the optimal time interval between treatment sessions.

Disease Activity in Pregnant and Postpartum Women With Multiple Sclerosis Receiving Ocrelizumab or Other Disease-Modifying Therapies.

Background And Objectives: Women with multiple sclerosis (MS) are at risk of disease reactivation in the early postpartum period. Ocrelizumab (OCR) is an anti-CD20 therapy highly effective at reducing MS disease activity. Data remain limited regarding use of disease-modifying therapies (DMTs), including OCR, and disease activity during peripregnancy periods.

Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2b trial.

Background: Denifanstat, an oral fatty acid synthase (FASN) inhibitor, blocks de-novo lipogenesis, a key pathway driving progressive lipotoxicity, inflammation, and fibrosis in metabolic dysfunction-associated steatohepatitis (MASH). This study aimed to examine the safety and efficacy of denifanstat for improving liver histology in individuals with MASH and moderate to advanced fibrosis.

Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2b trial was conducted at 100 clinical sites in the USA, Canada, and Poland.