Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b SMART Study.

Background And Objectives: Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing <8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.

Systematic evaluation of machine learning models for postoperative surgical site infection prediction.

Background: Surgical site infections (SSIs) lead to increased mortality and morbidity, as well as increased healthcare costs. Multiple models for the prediction of this serious surgical complication have been developed, with an increasing use of machine learning (ML) tools.

Objective: The aim of this systematic review was to assess the performance as well as the methodological quality of validated ML models for the prediction of SSIs.

ETFDH mutation involves excessive apoptosis and neurite outgrowth defect via Bcl2 pathway.

The most common mutation in southern Chinese individuals with late-onset multiple acyl-coenzyme A dehydrogenase deficiency (MADD; a fatty acid metabolism disorder) is c.250G > A (p.Ala84Thr) in the electron transfer flavoprotein dehydrogenase gene (ETFDH).

Erratum to 'Performance of Risk Scores in Predicting Major Bleeding in Left Ventricular Assist Device (LVAD) Recipients: a Comparative External Validation. '[Res Pract Thromb Haemost. 2024;8:e102437].

[This corrects the article DOI: 10.1016/j.rpth.

Impact of Extreme Prematurity, Chorioamnionitis, and Sepsis on Neonatal Monocyte Characteristics and Functions.

Introduction: The innate branch of the immune system is important in early life, in particular for infants born preterm.

Methods: We performed a longitudinal analysis of the peripheral monocyte compartment in extremely preterm children from a randomized, placebo-controlled study of probiotic supplementation. PBMCs and fecal samples were collected at several timepoints during the first months of life.

Mice Engrafted with Human Liver Cells.

Rodents are commonly employed to model human liver conditions, although species differences can restrict their translational relevance. To overcome some of these limitations, researchers have long pursued human hepatocyte transplantation into rodents. More than 20 years ago, the first primary human hepatocyte transplantations into immunodeficient mice with liver injury were able to support hepatitis B and C virus infections, as these viruses cannot replicate in murine hepatocytes.

Do help-seeking adolescents report more psychotic-like experiences than young adults on the 16-item version of the prodromal questionnaire (PQ-16)?

Aim: To compare psychotic-like experiences (PLEs) in adolescents and young adults referred to the Mental Health Services (MHSs).

Methods: Participants scored the 16-item Prodromal Questionnaire (PQ-16) as part of the intake procedure. Data on the Diagnostic and Statistical Manual of Mental Disorders (DSM) classification and demographic data were collected.

Performance of risk scores in predicting major bleeding in left ventricular assist device recipients: a comparative external validation.

Background: Implantation of a left ventricular assist device (LVAD) is a crucial therapeutic option for selected end-stage heart failure patients. However, major bleeding (MB) complications postimplantation are a significant concern.

Objectives: We evaluated current risk scores' predictive accuracy for MB in LVAD recipients.

Innate Immune Sensing of Adeno-Associated Virus Vectors.

Adeno-associated virus (AAV) based viral vectors are widely used in human gene therapy and form the basis of approved treatments for several genetic diseases. Immune responses to vector and transgene products, however, substantially complicate these applications in clinical practice. The role of innate immune recognition of AAV vectors was initially unclear, given that inflammatory responses early after vector administration were typically mild in animal models.

Optimizing liver health before and after gene therapy for hemophilia A.

Gene therapy for severe hemophilia A uses an adeno-associated virus (AAV) vector and liver-specific promoters that depend on healthy hepatocyte function to achieve safe and long-lasting increases in factor VIII (FVIII) activity. Thus, hepatocyte health is an essential aspect of safe and successful gene therapy. Many people living with hemophilia A have current or past chronic hepatitis C virus infection, metabolic dysfunction-associated steatosis or steatohepatitis, or other conditions that may compromise the efficacy and safety of AAV-mediated gene therapy.

Creatine and L-carnitine attenuate muscular laminopathy in the LMNA mutation transgenic zebrafish.

Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants.

First-principles study of molecular hydrogen binding to heme in competition with O, NO and CO.

Molecular hydrogen shows antioxidant activity and distinct efficacy towards vascular diseases, but the understanding of this is not yet satisfactory at the atomic level. In this work, we study the binding properties of H to the heme group in relation with other diatomic molecules (DMs), including O, NO and CO, and their displacement reactions, using first-principles calculations. We carry out molecular modeling of the heme group, using iron-porphyrin with the imidazole ligand, , FePIm, and smaller models of Fe(CHN)NH with = 3 and 1, and of molecular complexes of heme-DM and -H.

The bii4africa dataset of faunal and floral population intactness estimates across Africa's major land uses.

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species' population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate 'intactness scores': the remaining proportion of an 'intact' reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region's major land uses (urban, cropland, rangeland, plantation, protected, etc.

Microbiota signatures associated with invasive infection in the gastrointestinal tract of immunodeficient mice.

is a commensal microorganism in the human gut but occasionally causes invasive infection (ICA), especially in immunocompromised individuals. Early initiation of antifungal therapy is associated with reduced mortality of ICA, but rapid diagnosis remains a challenge. The ICA-associated changes in the gut microbiota can be used as diagnostic and therapeutic targets but have been poorly investigated.

TLR9-independent CD8 T cell responses in hepatic AAV gene transfer through IL-1R1-MyD88 signaling.

Upon viral infection of the liver, CD8 T cell responses may be triggered despite the immune suppressive properties that manifest in this organ. We sought to identify pathways that activate responses to a neoantigen expressed in hepatocytes, using adeno-associated viral (AAV) gene transfer. It was previously established that cooperation between plasmacytoid dendritic cells (pDCs), which sense AAV genomes by Toll-like receptor 9 (TLR9), and conventional DCs promotes cross-priming of capsid-specific CD8 T cells.

Possibility of decryption speed-up by parallel processing in CCA secure hashed ElGamal.

In order to prove the ElGamal CCA(Chosen Ciphertext Attack) security in the random oracle model, it is necessary to use the group where ICDH(Interactive Computational Diffie Hellman) assumption holds. Until now, only bilinear group with complex algebraic structure has been known as the ICDH group. In this paper, we introduce the ICDH group with simple algebraic structure.

Predictive analytics for cardio-thoracic surgery duration as a stepstone towards data-driven capacity management.

Effective capacity management of operation rooms is key to avoid surgery cancellations and prevent long waiting lists that negatively affect clinical and financial outcomes as well as patient and staff satisfaction. This requires optimal surgery scheduling, leveraging essential parameters like surgery duration, post-operative bed type and hospital length-of-stay. Common clinical practice is to use the surgeon's average procedure time of the last N patients as a planned surgery duration for the next patient.

Drivers of habitat availability for terrestrial mammals: Unravelling the role of livestock, land conversion and intrinsic traits in the past 50 years.

The global decline of terrestrial species is largely due to the degradation, loss and fragmentation of their habitats. The conversion of natural ecosystems for cropland, rangeland, forest products and human infrastructure are the primary causes of habitat deterioration. Due to the paucity of data on the past distribution of species and the scarcity of fine-scale habitat conversion maps, however, accurate assessment of the recent effects of habitat degradation, loss and fragmentation on the range of mammals has been near impossible.

Correlation of gene expression with magnetic resonance imaging features of retinoblastoma: a multi-center radiogenomics validation study.

Objectives: To validate associations between MRI features and gene expression profiles in retinoblastoma, thereby evaluating the repeatability of radiogenomics in retinoblastoma.

Methods: In this retrospective multicenter cohort study, retinoblastoma patients with gene expression data and MRI were included. MRI features (scored blinded for clinical data) and matched genome-wide gene expression data were used to perform radiogenomic analysis.

WNTinib is a multi-kinase inhibitor with specificity against β-catenin mutant hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. β-Catenin (CTNNB1)-mutated HCC represents 30% of cases of the disease with no precision therapeutics available. Using chemical libraries derived from clinical multi-kinase inhibitor (KI) scaffolds, we screened HCC organoids to identify WNTinib, a KI with exquisite selectivity in CTNNB1-mutated human and murine models, including patient samples.