To Develop and Implement a Preclinical Operative Dentistry Module to Enhance Class-II Cavity Preparation Training.

Background: A competent dental undergraduate at the preclinical level will ensure a confident transition into clinics and quality treatment for patients. Cavity preparation of a tooth is one of the key competencies in dentistry. A preclinical training module was introduced to enhance the skill training and improve students' learning.

Expanding the clinical spectrum of biglycan-related Meester-Loeys syndrome.

Pathogenic loss-of-function variants in BGN, an X-linked gene encoding biglycan, are associated with Meester-Loeys syndrome (MRLS), a thoracic aortic aneurysm/dissection syndrome. Since the initial publication of five probands in 2017, we have considerably expanded our MRLS cohort to a total of 18 probands (16 males and 2 females). Segregation analyses identified 36 additional BGN variant-harboring family members (9 males and 27 females).

Monte Carlo based continuous aperture optimization for VMAT on conventional and MR-linacs: A proof of concept.

Background: Currently, the commercial treatment planning systems for magnetic-resonance guided linear accelerators (MR-linacs) only support step-and-shoot intensity-modulated radiation therapy (IMRT). However, recent studies have shown the feasibility of delivering arc therapy on MR-linacs, which is expected to improve dose distributions and delivery speed. By accurately accounting for the electron return effect in the presence of a magnetic field, a Monte Carlo (MC) algorithm is ideally suited for the inverse treatment planning of this technique.

A complex case of delayed diagnosis of ornithine transcarbamylase deficiency in an adult patient with multiple comorbidities.

We report the case of a medically complex African American adult female with ornithine transcarbamylase (OTC) deficiency diagnosed after lifelong protein aversion and new onset of chronic vomiting and abdominal pain with intermittent lethargy and confusion. Symptomatology was crucial to diagnosis as genetic testing did not identify any pathogenic variants in ; however, the patient's diagnosis was delayed despite her having longstanding symptoms of a urea cycle disorder (UCD). Her symptoms improved after treatment with a modified protein-restricted diet, long-term nitrogen-scavenger therapy, and supplemental L-citrulline.

Molecular Modeling and Phenotypic Description of a Patient with a Novel Exonic Deletion of with Resultant Morquio Syndrome with Two Successful Pregnancies.

In this report, we describe phenotypic features of a patient with mucopolysaccharidosis type IVA (Morquio syndrome) harboring a novel exon 1 deletion in with enzymatic confirmation consistent with Morquio syndrome. To our knowledge, this is the first reported case of this variant. Additionally, we protein modelled wild-type GALNS and the pathogenic variant with an exon 1 deletion for comparative analysis using statistical mechanics methods described herein.

Sex differences in comorbidities associated with Sjögren's disease.

Background: Little is known about the association of comorbidities with sex and age at diagnosis in Sjögren's disease. We tested the hypothesis that sex differences occur in comorbidities in patients with Sjögren's disease.

Methods: Patients with Sjögren's disease were identified from 11/1974 to 7/2018 in the Mayo Clinic electronic medical record and assessed for 22 comorbidities according to sex and age at diagnosis.

A patient with a novel pathogenic variant in COL5A1 exhibiting prominent vascular and cardiac features.

The Ehlers-Danlos Syndromes (EDS) are a group of inherited connective tissue disorders with a worldwide prevalence of 1 in 2500 to 1 in 5000 births irrespective of sex or ethnicity. Fourteen subtypes of Ehlers-Danlos Syndrome (EDS) have been described, each with characteristic phenotypes and associated genes. Pathogenic variants in COL5A1 and COL5A2 cause the classical EDS subtypes.

A bibliometric analysis of the top 50 most cited articles published in the .

Background: Bibliometric analysis is the quantitative analysis of measurable citation information of a journal. It unveils research topics, publishing trends, assess research impact, and productivity.

Aims: The purpose of this study was to conduct a bibliometric analysis to identify and analyze the top 50 most cited articles published in the (JCD).

A new DOSXYZnrc method for Monte Carlo simulations of 4D dose distributions.

The purpose of this study is to present a novel method for generating Monte Carlo 4D dose distributions in a single DOSXYZnrc simulation. During a standard simulation, individual energy deposition events are summed up to generate a 3D dose distribution and their associated temporal information is discarded. This means that in order to determine dose distributions as a function of time, separate simulations would have to be run for each interval of interest.

Importance of Family History in the Era of Exome Analysis: A Report of a Family with Multiple Concurrent Genetic Diseases.

Multiple familial diseases in a single patient often present with overlapping symptomatology that confers difficulty in delineating a clinical diagnosis. Pedigree analysis has been a long-standing practice in the field of medical genetics to discover familial diseases. In recent years, whole exome sequencing (WES) has proven to be a useful tool for aiding physicians in diagnosing and understanding disease etiology.

Physician-directed genetic screening to evaluate personal risk for medically actionable disorders: a large multi-center cohort study.

Background: The use of proactive genetic screening for disease prevention and early detection is not yet widespread. Professional practice guidelines from the American College of Medical Genetics and Genomics (ACMG) have encouraged reporting pathogenic variants that confer personal risk for actionable monogenic hereditary disorders, but only as secondary findings from exome or genome sequencing. The Centers for Disease Control and Prevention (CDC) recognizes the potential public health impact of three Tier 1 actionable disorders.

Lung cancer epidermal growth factor receptor mutations and radiotherapy response: A multicentre clinical study.

Purpose: To examine the impact of epidermal growth factor receptor (EGFR) mutations on objective response to palliative lung radiotherapy in patients with metastatic non-small cell lung cancer (NSCLC).

Materials And Methods: A multicentre retrospective study was conducted of patients with metastatic NSCLC diagnosed between March 2010 and June 2012 who received palliative radiotherapy to the chest. Patients included for study had baseline imaging and follow-up imaging 1-3 months after radiotherapy.

RT001 in Progressive Supranuclear Palsy-Clinical and In-Vitro Observations.

Background: Progressive supranuclear palsy (PSP) is a progressive movement disorder associated with lipid peroxidation and intracerebral accumulation of tau. RT001 is a deuterium reinforced isotopologue of linoleic acid that prevents lipid peroxidation (LPO) through the kinetic isotope effect.

Methods: The effects of RT001 pre-treatment on various oxidative and bioenergetic parameters were evaluated in mesenchymal stem cells (MSC) derived from patients with PSP compared to controls.

Application of the community dialogues method to identify ethical values and priorities related to pharmacogenomics.

Given the expansion of genetics in medicine, there is a growing need to develop approaches to engage patients in understanding how genetics affects their health. Various qualitative methods have been applied to gain a deeper understanding of patient perspectives in topics related to genetics. Community dialogues (CD) are a bi-directional research method that invites community members to discuss a pertinent, challenging topic over the course of a multi-week period and the community members openly discuss their positions on the topic.

Sex Differences, Genetic and Environmental Influences on Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is characterized by dilatation of the left ventricle and impaired systolic function and is the second most common cause of heart failure after coronary heart disease. The etiology of DCM is diverse including genetic pathogenic variants, infection, inflammation, autoimmune diseases, exposure to chemicals/toxins as well as endocrine and neuromuscular causes. DCM is inherited in 20-50% of cases where more than 30 genes have been implicated in the development of DCM with pathogenic variants in (Titin) most frequently associated with disease.

Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders.

Background: With the increasing number of genomic sequencing studies, hundreds of genes have been implicated in neurodevelopmental disorders (NDDs). The rate of gene discovery far outpaces our understanding of genotype-phenotype correlations, with clinical characterization remaining a bottleneck for understanding NDDs. Most disease-associated Mendelian genes are members of gene families, and we hypothesize that those with related molecular function share clinical presentations.

Clinical description & molecular modeling of novel MAX pathogenic variant causing pheochromocytoma in family, supports paternal parent-of-origin effect.

The titular member of the MAX network of proteins, MYC-associated factor X (MAX), serves an important regulatory function in transcription of E-box genes associated with cell proliferation, differentiation, and apoptosis. Wild type MAX dimerizes with both MYC and MAD, both of which are members of the MAX network, and can promote or repress cell functions as needed. However, pathogenic variants in MAX are known to upset this balance, leading to uncontrolled oncogenic activity and disease phenotypes such as paragangliomas and pheochromocytomas.

Poirier-Bienvenu neurodevelopmental syndrome: A report of a patient with a pathogenic variant in CSNK2B with abnormal linear growth.

Casein kinase 2-related disorders have been linked to pathogenic variants in CSNK2A1 and CSNK2B. CSNK2B-related disease is predominantly associated with neurodevelopmental abnormalities affecting cognition; however, the extent of the phenotype associated with CSNK2B pathogenic variants is yet to be fully explored. Here, we describe a patient with features suggestive of Poirier-Bienvenu neurodevelopmental syndrome, harboring a novel CSNK2B pathogenic variant.

Impact of integrated translational research on clinical exome sequencing.

Purpose: Exome sequencing often identifies pathogenic genetic variants in patients with undiagnosed diseases. Nevertheless, frequent findings of variants of uncertain significance necessitate additional efforts to establish causality before reaching a conclusive diagnosis. To provide comprehensive genomic testing to patients with undiagnosed disease, we established an Individualized Medicine Clinic, which offered clinical exome testing and included a Translational Omics Program (TOP) that provided variant curation, research activities, or research exome sequencing.

Chimerism involving a RB1 pathogenic variant in monochorionic dizygotic twins with twin-twin transfusion syndrome.

We report the first case of blood chimerism involving a pathogenic RB1 variant in naturally conceived monochorionic-dizygotic twins (MC/DZ) with the twin-twin-transfusion syndrome (TTTS), presumably caused by the exchange of stem-cells. Twin A developed bilateral retinoblastoma at 7 months of age. Initial genetic testing identified a de novo RB1 pathogenic variant, with a 20% allelic ratio in both twins' blood.