The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the Clinical Validity of 111 Gene-Disease Relationships.

Purpose: The Clinical Genome Resource (ClinGen) Gene Curation Expert Panels (GCEPs) have historically focused on specific organ systems or phenotypes; thus, the ClinGen Syndromic Disorders GCEP (SD-GCEP) was formed to address an unmet need.

Methods: The SD-GCEP applied ClinGen's framework to evaluate the clinical validity of genes associated with rare syndromic disorders. 111 Gene-Disease Relationships (GDRs) associated with 100 genes spanning the clinical spectrum of syndromic disorders were curated.

Expert panel curation of 31 genes in relation to limb girdle muscular dystrophy.

Objective: Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD.

Temporal Optimization in the Synthesis of Multifunctional Nano Agents for Enhanced MRI Contrast, Hyperthermia Therapy, and ROS Generation.

Advanced methodologies, such as hyperthermia and modulation of reactive oxygen species (ROS), exhibit considerable promise in the therapeutic landscape of cancer. These strategies offer a targeted paradigm for combating malignant cells while mitigating damage to healthy tissue. Noteworthy among these approaches is the utilization of superparamagnetic iron oxide nanoparticles, which are renowned for their ability to enhance both hyperthermia and ROS generation specifically within tumor microenvironments.

Automatic removal of large blood vasculature for objective assessment of brain tumors using quantitative dynamic contrast-enhanced magnetic resonance imaging.

The presence of a normal large blood vessel (LBV) in a tumor region can impact the evaluation of quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters and tumor classification. Hence, there is a need for automatic removal of LBVs from brain tissues including intratumoral regions for achieving an objective assessment of tumors. This retrospective study included 103 histopathologically confirmed brain tumor patients who underwent MRI, including DCE-MRI data acquisition.

Salivary gland tumors: an audit from a tertiary care centre in Northern India.

Salivary gland tumors are relatively rare and can exhibit various clinical behaviors. The study aims to understand the natural history, pathology, diagnostic workup, and treatment strategies for these tumors to improve patient outcomes. The audit included patients with salivary gland tumors detected through radiology or cytology.

Expert Panel Curation of 31 Genes in Relation to Limb Girdle Muscular Dystrophy.

Introduction: Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD.

Incidence and prevalence of hypertension in 18-40-year-old patients referred for palpitations with normal cardiac monitor findings.

Sixteen percent of patients referred for cardiology evaluation are found to have no cause for palpitations. Studies show that hypertension intricately influences "heart rate" and "contractility,?" the key components of "palpitation." While the prevalence of hypertension is 22.

A framework for the evaluation and reporting of incidental findings in clinical genomic testing.

Currently, there are no widely accepted recommendations in the genomics field guiding the return of incidental findings (IFs), defined here as unexpected results that are unrelated to the indication for testing. Consequently, reporting policies for IFs among laboratories offering genomic testing are variable and may lack transparency. Herein we describe a framework developed to guide the evaluation and return of IFs encountered in probands undergoing clinical genome sequencing (cGS).

A protein-proximity screen reveals Ebola virus co-opts the mRNA decapping complex through the scaffold protein EDC4.

The interaction of host and Ebola virus (EBOV) proteins is required for establishing infection of the cell. To identify protein binding partners, a proximity-dependent protein interaction screen was performed for six EBOV proteins. Hits were computationally mapped onto a human protein-protein interactome and then annotated with viral proteins to reveal known and previously undescribed EBOV-host protein interactions and processes.

Genome sequencing detects a balanced pericentric inversion with breakpoints that impact the DMD and upstream region of POU3F4 genes.

We describe a family with two maternal half-brothers both of whom presented with muscular dystrophy, autism spectrum disorder, developmental delay, and sensorineural hearing loss. The elder brother had onset of features at ~3 months of age, followed by clinical confirmation of muscular dystrophy at 3 years. Skeletal biopsy staining at 4.

An Evaluation of the Effectiveness of Various Luting Cements on the Retention of Implant-Supported Metal Crowns.

Background and objective Cement-retained prostheses have replaced screw-retained prostheses as the preferred restoration in recent years in order to overcome the latter's limitations. In this study, four different luting cements were compared to evaluate their efficacy on the retention of cement-based metal crowns to implant abutments. Materials and methods In the right and left first molar regions, four implant analogs (Internal Hex, Adin Dental Implant Systems Ltd.

The smallest likely pathogenic duplication of a SOX9 enhancer identified to date in a family with 46,XX testicular differences of sex development.

Copy number variants that duplicate distal upstream enhancer elements of the SOX9 gene cause 46,XX testicular differences of sex development (DSD) which is characterized by a 46,XX karyotype in an individual presenting with either ambiguous genitalia or genitalia with varying degrees of virilization, including those resembling typical male genitalia. Reported duplications in this region range in size from 24 to 780 kilobases (kb). Here we report a family with two affected individuals, the proband and his maternal uncle, harboring a 3.

Wide range of phenotypic severity in individuals with late truncations unique to the predominant CDKL5 transcript in the brain.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is caused by heterozygous or hemizygous variants in CDKL5 and is characterized by refractory epilepsy, cognitive and motor impairments, and cerebral visual impairment. CDKL5 has multiple transcripts, of which the longest transcripts, NM_003159 and NM_001037343, have been used historically in clinical laboratory testing. However, the transcript NM_001323289 is the most highly expressed in brain and contains 170 nucleotides at the 3' end of its last exon that are noncoding in other transcripts.

A Novel Proximity Biotinylation Assay Based on the Self-Associating Split GFP1-10/11.

Proximity biotinylation was developed to detect physiologically relevant protein-protein interactions in living cells. In this method, the protein of interest is tagged with a promiscuous biotin ligase, such as BioID or BioID2, which produces activated biotin that reacts with nearby proteins; these proteins can subsequently be purified and identified by mass spectrometry. Here we report a novel modification of this technique by combining it with a self-associating split-GFP system in which we exploit the high-affinity interaction between GFP1-10 and GFP11 to recruit BioID2 to the protein of interest.

Zika virus NS5 localizes at centrosomes during cell division.

Zika virus (ZIKV) nonstructural protein 5 (NS5) plays a critical role in viral RNA replication and mediates key virus-host cell interactions. As with other flavivirus NS5 proteins, ZIKV NS5 is primarily found in the nucleus. We previously reported that the NS5 protein of dengue virus, another flavivirus, localized to centrosomes during cell division.

Role of heparan sulfate in entry and exit of Ross River virus glycoprotein-pseudotyped retroviral vectors.

Variants of Ross River virus (RRV) that bind to heparan sulfate (HS) were previously selected by serial passaging in cell culture. To explore the effects of mutations that convey HS utilization, we pseudotyped Moloney murine leukemia virus (MoMLV), with the RRV envelope. We substituted amino-acid residues 216 and 218 on RRV-E2-envelope glycoprotein with basic amino-acid residues, because these mutations confer affinity for HS upon RRV.

Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients.

Objective: Limb-girdle muscular dystrophies (LGMDs), one of the most heterogeneous neuromuscular disorders (NMDs), involves predominantly proximal-muscle weakness with >30 genes associated with different subtypes. The clinical-genetic overlap among subtypes and with other NMDs complicate disease-subtype identification lengthening diagnostic process, increases overall costs hindering treatment/clinical-trial recruitment. Currently seven LGMD clinical trials are active but still no gene-therapy-related treatment is available.

Osteopontin is linked with AKT, FoxO1, and myostatin in skeletal muscle cells.

Introduction: Osteopontin (OPN) polymorphisms are associated with muscle size and modify disease progression in Duchenne muscular dystrophy (DMD). We hypothesized that OPN may share a molecular network with myostatin (MSTN).

Methods: Studies were conducted in the golden retriever (GRMD) and mdx mouse models of DMD.

Idiopathic Sialolithiasis: Scalpel Versus Current Trends in Management.

Idiopathic sialolithiasis is one of the most common affliction of the salivary glands with the submandibular gland most frequently involved. The article discusses the occurrence and incidence of this condition with a review of different diagnostic and treatment modalities. In light of several advances to diagnose and treat sialolithiasis, a simple sialolithotomy for idiopathic submandibular gland sialolithiasis may prove to be a preferred treatment for selected patients as it remains a cost-effective and simple out-patient department procedure with minimal/no complications and a highly satisfactory outcome.