Dynamic proportional loss of functional connectivity revealed change of left superior frontal gyrus in subjective cognitive decline: an explanatory study based on Chinese and Western cohorts.

Brain network dynamics have been extensively explored in patients with subjective cognitive decline (SCD). However, these studies are susceptible to individual differences, scanning parameters, and other confounding factors. Therefore, how to reveal subtle SCD-related subtle changes remains unclear.

Impact of calreticulin mutations on treatment and survival outcomes in myelofibrosis during ruxolitinib therapy.

Calreticulin (CALR) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless of driver mutations, patients with splenomegaly and symptoms are generally treated with JAK2-inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the CALR mutant clone have entered clinical investigation.

Carbohydrate Ingestion Eliminates Hypoglycemia & Improves Endurance Exercise Performance in Triathletes Adapted to Very Low & High Carbohydrate Isocaloric Diets.

Very-low-carbohydrate diets (LCHF; <50g/day) have been debated for their potential to lower pre-exercise muscle and liver glycogen stores and metabolic efficiency, risking premature fatigue. It is also hypothesized that carbohydrate ingestion during prolonged exercise delays fatigue by increasing carbohydrate oxidation, thereby sparing muscle glycogen. Leveraging a randomized crossover design, we evaluated performance during strenuous time-to-exhaustion (70%⩒O) tests in trained triathletes following 6-week high-carbohydrate (HCLF, 380g/day) or very-low-carbohydrate (LCHF, 40g/day) diets to determine (i) if adoption of the LCHF diet impairs time-to-exhaustion performance, (ii) whether carbohydrate ingestion (10g/hour) 6-12x lower than current CHO fuelling recommendations during low glycogen availability (>15-hour pre-exercise overnight fast and/or LCHF diet) improves time-to-exhaustion by preventing exercise-induced hypoglycemia (EIH; <3.

Long-Term Effectiveness and Safety of Ustekinumab in Crohn's Disease: Results from a Large Real-Life Cohort Study.

Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist approved for the treatment of Crohn's disease (CD). Only limited real-life data on the long-term outcomes of CD patients treated with UST are available. This study assessed UST's long-term effectiveness and safety in a large population-based cohort of moderate to severe CD patients.

Green Cu particles for functional and biodegradable food packaging solutions.

This study demonstrates a simple approach to synthesize green Cu particles stabilized by poly(n-vinyl)pyrrolidone (PVP): the latter acts as stabilizer and dispersant, and its presence in solution eliminates the need for an inert atmosphere. Synthetic parameters were tuned to obtain particles with diameters >200 nm, to be human-safe and prevent nano-cytotoxicity. PVP and reductant concentrations, with reaction times, were varied to investigate their effect on colloidal stability, kinetics, and particles size.

Neuroregeneration Improved by Sodium-D,L-Beta-Hydroxybutyrate in Primary Neuronal Cultures.

Ketone bodies are considered alternative fuels for the brain when glucose availability is limited. To determine the neuroregenerative potential of D,L-sodium-beta-hydroxybutyrate (D/L-BHB), Sprague Dawley rat primary cortical neurons were exposed to simulated central nervous system injury using a scratch assay. The neuronal cell migration, cell density and degree of regeneration in the damaged areas (gaps) in the absence (control) and presence of BHB (2 mM) were documented with automated live-cell imaging by the CytoSMART system over 24 h, which was followed by immunocytochemistry, labeling synapsin-I and β3-tubulin.

Putative Role of Adenosine A1 Receptors in Exogenous Ketone Supplements-Evoked Anti-Epileptic Effect.

Approximately 30% of patients with epilepsy are drug-refractory. There is an urgent need to elucidate the exact pathophysiology of different types of epilepsies and the mechanisms of action of both antiseizure medication and metabolic therapies to treat patients more effectively and safely. For example, it has been demonstrated that exogenous ketone supplement (EKS)-generated therapeutic ketosis, as a metabolic therapy, may decrease epileptic activity in both animal models and humans, but its exact mechanism of action is unknown.

Disparities in clinical studies of AI enabled applications from a global perspective.

Artificial intelligence (AI) has been extensively researched in medicine, but its practical application remains limited. Meanwhile, there are various disparities in existing AI-enabled clinical studies, which pose a challenge to global health equity. In this study, we conducted an in-depth analysis of the geo-economic distribution of 159 AI-enabled clinical studies, as well as the gender disparities among these studies.

Genotype-Phenotype Correlation in Neurofibromatosis Type 1: Evidence for a Mild Phenotype Associated with Splicing Variants Leading to In-Frame Skipping of Exon 24 [19a].

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder caused by loss-of-function variants in the gene. As of 20 November 2023, over 5000 distinct pathogenic or likely pathogenic variants have been reported in public databases. However, only a few genotype-phenotype correlations have been established so far.

Lack of differences in outcomes between 3 immunosuppression protocols in the first year after pediatric liver transplantation: A multicenter study.

Advances in immunosuppression have extended patient and graft survival rates after solid organ transplantation; however, this is not free of side effects. Balancing safety and efficacy is of paramount importance, particularly in the pediatric setting. Current literature comparing different protocols is scarce, and decisions are mostly guided by physician preference.

International society of sports nutrition position stand: ketogenic diets.

Position Statement: The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the use of a ketogenic diet in healthy exercising adults, with a focus on exercise performance and body composition. However, this review does not address the use of exogenous ketone supplements. The following points summarize the position of the ISSN.

The Metabolic and Endocrine Effects of a 12-Week Allulose-Rich Diet.

The global rise in type 2 diabetes (T2D) and obesity necessitates innovative dietary interventions. This study investigates the effects of allulose, a rare sugar shown to reduce blood glucose, in a rat model of diet-induced obesity and T2D. Over 12 weeks, we hypothesized that allulose supplementation would improve body weight, insulin sensitivity, and glycemic control.

Multicenter expanded access program for access to investigational products for amyotrophic lateral sclerosis.

Introduction/aims: Expanded access (EA) is a Food and Drug Administration-regulated pathway to provide access to investigational products (IPs) to individuals with serious diseases who are ineligible for clinical trials. The aim of this report is to share the design and operations of a multicenter, multidrug EA program for amyotrophic lateral sclerosis (ALS) across nine US centers.

Methods: A central coordination center was established to design and conduct the program.

Learning active subspaces and discovering important features with Gaussian radial basis functions neural networks.

Providing a model that achieves a strong predictive performance and is simultaneously interpretable by humans is one of the most difficult challenges in machine learning research due to the conflicting nature of these two objectives. To address this challenge, we propose a modification of the radial basis function neural network model by equipping its Gaussian kernel with a learnable precision matrix. We show that precious information is contained in the spectrum of the precision matrix that can be extracted once the training of the model is completed.

Ketone ester supplementation of Atkins-type diet prolongs survival in an orthotopic xenograft model of glioblastoma.

Heavy reliance on glucose metabolism and a reduced capacity to use ketone bodies makes glioblastoma (GBM) a promising candidate for ketone-based therapies. Ketogenic diet (KD) is well-known for its promising effects in controlling tumor growth in GBM. Moreover, synthetic ketone ester (KE) has demonstrated to increase blood ketone levels and enhance animal survival in a metastatic VM-M3 murine tumor model.

InCliniGene enables high-throughput and comprehensive in vivo clonal tracking toward clinical genomics data integration.

High-throughput clonal tracking in patients under hematopoietic stem cell gene therapy with integrating vector is instrumental in assessing bio-safety and efficacy. Monitoring the fate of millions of transplanted clones and their progeny across differentiation and proliferation over time leverages the identification of the vector integration sites, used as surrogates of clonal identity. Although γ-tracking retroviral insertion sites (γ-TRIS) is the state-of-the-art algorithm for clonal identification, the computational drawbacks in the tracking algorithm, based on a combinatorial all-versus-all strategy, limit its use in clinical studies with several thousands of samples per patient.

Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease: A Novel Analysis of the VITAL Trial Using Win Ratio and Hierarchical Composite Outcomes.

This study aimed to investigate whether n-3 fatty acid supplementation reduced cardiovascular disease (CVD) events in a novel analysis using hierarchical composite CVD outcomes based on win ratio in the VITamin D and OmegA-3 TriaL (VITAL). This was a secondary analysis of our VITAL randomized trial, which assessed the effects of marine n-3 fatty acids (1 g/day) and vitamin D3 on incident CVD and cancer among healthy older adults ( = 25,871). The primary analysis estimated win ratios of a composite of major CVD outcomes prioritized as fatal coronary heart disease, other fatal CVD including stroke, non-fatal myocardial infarction (MI), and non-fatal stroke, comparing n-3 fatty acids to placebo.

On the Origins of Phenotypic Parallelism in Benthic and Limnetic Stickleback.

Rapid evolution of similar phenotypes in similar environments, giving rise to in situ parallel adaptation, is an important hallmark of ecological speciation. However, what appears to be in situ adaptation can also arise by dispersal of divergent lineages from elsewhere. We test whether two contrasting phenotypes repeatedly evolved in parallel, or have a single origin, in an archetypal example of ecological adaptive radiation: benthic-limnetic three-spined stickleback (Gasterosteus aculeatus) across species pair and solitary lakes in British Columbia.