SPA14 liposomes combining saponin with fully synthetic TLR4 agonist provide adjuvanticity to hCMV vaccine candidate.

In the aim of designing and developing a novel saponin-based adjuvant system, we combined the QS21 saponin with low microgram amounts of the fully synthetic TLR4 agonist, E6020, in cholesterol-containing liposomes. The resulting adjuvant system, termed SPA14, appeared as a long-term stable and homogeneous suspension of mostly unilamellar and a few multilamellar vesicles, with an average hydrodynamic diameter of 93 nm, when formulated in citrate buffer at pH 6.0-6.

Exome and Genome Sequencing to Diagnose the Genetic Basis of Neonatal Hypotonia: An International Consortium Study.

Background And Objectives: Hypotonia is a relatively common finding among infants in the neonatal intensive care unit (NICU). Consideration of genetic testing is recommended early in the care of infants with unexplained hypotonia. We aimed to assess the diagnostic yield and overall impact of exome and genome sequencing (ES and GS).

SOX17-Associated Pulmonary Hypertension in Children: A Distinct Developmental and Clinical Syndrome.

Objective: To characterize clinical, hemodynamic, imaging, and pathologic findings in children with pulmonary arterial hypertension (PAH) and variants in SRY-box transcription factor 17 (SOX17), a novel risk gene linked to heritable and congenital heart disease-associated PAH.

Study Design: We assembled a multi-institutional cohort of children with PAH and SOX17 variants enrolled in the Pediatric Pulmonary Hypertension Network (PPHNet) and other registries. Subjects were identified through exome and PAH gene panel sequencing.

Implementation of multi-omics in diagnosis of pediatric rare diseases.

The rapid and accurate diagnosis of rare diseases is paramount in directing clinical management. In recent years, the integration of multi-omics approaches has emerged as a potential strategy to overcome diagnostic hurdles. This review examines the application of multi-omics technologies, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, in relation to the diagnostic journey of rare diseases.

Recycling of Acrylonitrile Butadiene Styrene from Electronic Waste for the Production of Eco-Friendly Filaments for 3D Printing.

In this work, acrylonitrile butadiene styrene (ABS) copolymer from electronic waste (e-waste) was used to produce filaments for application in 3D printing. Recycled ABS (rABS) from e-waste was blended with virgin ABS (vABS) in different concentrations. By differential scanning calorimetry, it was observed that the values of the glass transition temperatures for vABS/rABS blends ranged between the values of vABS and rABS.

HBS1L deficiency causes retinal dystrophy in a child and in a mouse model associated with defective development of photoreceptor cells.

Inherited retinal diseases encompass a genetically diverse group of conditions caused by variants in genes critical to retinal function, including handful of ribosome-associated genes. This study focuses on the HBS1L gene, which encodes for the HBS1-like translational GTPase that is crucial for ribosomal rescue. We have reported a female child carrying biallelic HBS1L variants, manifesting with poor growth and neurodevelopmental delay.

Fetoscopic Tracheal Occlusion for Isolated Severe Left Diaphragmatic Hernia: A Systematic Review and Meta-Analysis.

We aimed to conduct a systematic review and meta-analysis to evaluate the fetoscopic tracheal occlusion in patients with isolated severe and left-sided diaphragmatic hernia. Cochrane Library, Embase, and PubMed (Medline) databases were searched from inception to February 2024 with no filters or language restrictions. We included studies evaluating the outcomes of fetoscopic intervention compared to expectant management among patients with severe congenital diaphragmatic hernia exclusively on the left side.

"It's hard to wait": Provider perspectives on current genomic care in safety-net NICUs.

Purpose: Critically ill infants from marginalized populations disproportionately receive care in neonatal intensive care units (NICUs) that lack access to state-of-the-art genomic care, leading to inequitable outcomes. We sought provider perspectives to inform our implementation study (VIGOR) providing rapid genomic sequencing within these settings.

Methods: We conducted semistructured focus groups with neonatal and genetics providers at 6 NICUs at safety-net hospitals, informed by the Promoting Action on Research Implementation in Health Services framework, which incorporates evidence, context, and facilitation domains.

The solute carrier family 26 member 9 modifies rapidly progressing cystic fibrosis associated with homozygous F508del CFTR mutation.

Background And Aims: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations to the CF transmembrane conductance regulator (CFTR). Symptoms and severity of the disease can be quite variable suggesting modifier genes play an important role.

Materials And Methods: Exome sequencing was performed on six individuals carrying homozygous deltaF508 for CFTR genotype but present with rapidly progressing CF (RPCF).

Integrated multi-omics approach reveals the role of striated muscle preferentially expressed protein kinase in skeletal muscle including its relationship with myospryn complex.

Background: Autosomal-recessive mutations in SPEG (striated muscle preferentially expressed protein kinase) have been linked to centronuclear myopathy with or without dilated cardiomyopathy (CNM5). Loss of SPEG is associated with defective triad formation, abnormal excitation-contraction coupling, calcium mishandling and disruption of the focal adhesion complex in skeletal muscles. To elucidate the underlying molecular pathways, we have utilized multi-omics tools and analysis to obtain a comprehensive view of the complex biological processes and molecular functions.

WNT2B Deficiency Causes Enhanced Susceptibility to Colitis Due to Increased Inflammatory Cytokine Production.

Background & Aims: Humans with WNT2B deficiency have severe intestinal disease, including significant inflammatory injury, highlighting a critical role for WNT2B. We sought to understand how WNT2B contributes to intestinal homeostasis.

Methods: We investigated the intestinal health of Wnt2b knock out (KO) mice.

Comparative Evaluation of Cutting Efficiency of Three File Systems-Kedo-SH Manual, Pedoflex Rotary, and Manual K File: An Study.

Aims: The purpose of this study was to comparatively evaluate the cutting efficiency of Pedoflex rotary, Kedo SH manual file, and manual K file systems used in root canal instrumentation while performing pulp therapy of deciduous teeth with a stereomicroscope.

Materials And Methods: Forty-five extracted primary human root canals were chosen, and following the removal of pulp tissue, the canals were dyed with Indian ink and left to dry for 2 h. The samples were randomly divided into three groups, Group A: Kedo SH manual file system ( = 15), Group B: Pedoflex rotary file system ( = 15), and Group C: Manual K files ( = 15).

Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease.

Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and, with new innovative methods, can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing collected at the Broad Institute Center for Mendelian Genomics of the Genomics Research to Elucidate the Genetics of Rare Diseases consortium and analyzed using the seqr platform.

Artificial intelligence in oral health surveillance among under-served communities.

A sizable percentage of the population in India still does not have easy access to dental facilities. Therefore, it is of interest to document the role of artificial intelligence (AI) in oral surveillance of underserved communities. Available data shows that AI makes it possible to screen, diagnose, track, prioritize, and monitor dental patients remotely via smart devices.

Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis.

Background: Causal variants underlying rare disorders may remain elusive even after expansive gene panels or exome sequencing (ES). Clinicians and researchers may then turn to genome sequencing (GS), though the added value of this technique and its optimal use remain poorly defined. We therefore investigated the advantages of GS within a phenotypically diverse cohort.

A Predictive Model of Vaccine Reactogenicity Using Data from an In Vitro Human Innate Immunity Assay System.

A primary concern in vaccine development is safety, particularly avoiding an excessive immune reaction in an otherwise healthy individual. An accurate prediction of vaccine reactogenicity using in vitro assays and computational models would facilitate screening and prioritization of novel candidates early in the vaccine development process. Using the modular in vitro immune construct model of human innate immunity, PBMCs from 40 healthy donors were treated with 10 different vaccines of varying reactogenicity profiles and then cell culture supernatants were analyzed via flow cytometry and a multichemokine/cytokine assay.

High number of candidate gene variants are identified as disease-causing in a period of 4 years.

Advances in bioinformatic tools paired with the ongoing accumulation of genetic knowledge and periodic reanalysis of genomic sequencing data have led to an improvement in genetic diagnostic rates. Candidate gene variants (CGVs) identified during sequencing or on reanalysis but not yet implicated in human disease or associated with a phenotypically distinct condition are often not revisited, leading to missed diagnostic opportunities. Here, we revisited 33 such CGVs from our previously published study and determined that 16 of them are indeed disease-causing (novel or phenotype expansion) since their identification.

Striated preferentially expressed gene deficiency leads to mitochondrial dysfunction in developing cardiomyocytes.

A deficiency of striated preferentially expressed gene (Speg), a member of the myosin light chain kinase family, results in abnormal myofibril structure and function of immature cardiomyocytes (CMs), corresponding with a dilated cardiomyopathy, heart failure and perinatal death. Mitochondrial development plays a role in cardiomyocyte maturation. Therefore, this study investigated whether Speg deficiency ( - / - ) in CMs would result in mitochondrial abnormalities.