A Rare Case of Extranodal Natural Killer/T-cell Lymphoma, Nasal Type Associated With Hemophagocytic Lymphohistiocytosis in a Patient With Recurrent Sinusitis.

We present a rare case of hemophagocytic lymphohistiocytosis (HLH) secondary to nasal-type extranodal natural killer/T-cell lymphoma (ENKL). Nasal-type ENKL is a rare subtype of non-Hodgkin's lymphoma usually associated with Epstein-Barr virus (EBV). The patient was a 19-year-old woman who presented with facial numbness, diminished hearing, and dysgeusia.

HerediGene Population Study IT infrastructure: A model to support genomic research recruitment and precision public health.

The HerediGene Population Study is a large research study focused on identifying new genetic biomarkers for disease prevention, diagnosis, prognosis, and development of new therapeutics. A substantial IT infrastructure evolved to reach enrollment targets and return results to participants. More than 170,000 participants have been enrolled in the study to date, with 5.

Paving a pathway for large-scale utilization of genomics in precision medicine and population health.

Having worked with two large population sequencing initiatives, the separation between the potential for genomics in precision medicine and the current reality have become clear. To realize this potential requires workflows, policies, and technical architectures that are foreign to most healthcare systems. Many historical processes and regulatory barriers currently impede our progress.

The Development of an Infrastructure to Facilitate the Use of Whole Genome Sequencing for Population Health.

The clinical use of genomic analysis has expanded rapidly resulting in an increased availability and utility of genomic information in clinical care. We have developed an infrastructure utilizing informatics tools and clinical processes to facilitate the use of whole genome sequencing data for population health management across the healthcare system. Our resulting framework scaled well to multiple clinical domains in both pediatric and adult care, although there were domain specific challenges that arose.

Diagnostic Accuracy of Ultrasound in Predicting Extrathyroidal Extension and Its Relation to Body Mass Index in a North American Population.

Detection of extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC) influences treatment plan and surgical aggressiveness. Ultrasound (US) is the long-standing preoperative imaging method of choice. Recent literature from Asia suggests US accuracy to be influenced by patient characteristics, such as body mass index (BMI).

Machine learning algorithms to estimate 10-Year survival in patients with bone metastases due to prostate cancer: toward a disease-specific survival estimation tool.

Background: Prognostic indicators, treatments, and survival estimates vary by cancer type. Therefore, disease-specific models are needed to estimate patient survival. Our primary aim was to develop models to estimate survival duration after treatment for skeletal-related events (SREs) (symptomatic bone metastasis, including impending or actual pathologic fractures) in men with metastatic bone disease due to prostate cancer.

Neuroendocrine Carcinoma as a Cause of Humoral Hypercalcemia of Malignancy: A Case of a Patient With Elevated Parathyroid Hormone-Related Protein.

Humoral hypercalcemia of malignancy (HHM) is a paraneoplastic syndrome caused by elevations in parathyroid hormone-related protein (PTH-rP). HHM often presents in patients with squamous cell carcinomas of the lung, head, and neck, as well as breast, ovarian, renal, and bladder carcinomas. HHM associated with neuroendocrine carcinoma (NEC) is rarely observed.

Evaluating the applicability of the ratio of PM and carbon monoxide as source signatures.

Air pollution is among the top risk faced by people around the world, and therefore combating it is among the top priorities. It begins with identifying the sources that contribute the most to local air pollution to prioritize their control. There are advanced methods for source identification and apportionment, but such methods are not available in many low-income countries and not everywhere in all high-income countries.

Update on First-Line Combination Treatment Approaches in Metastatic Clear-Cell Renal Cell Carcinoma.

The treatment for metastatic renal cell carcinoma (mRCC) has significantly evolved in recent years with a deeper understanding of the molecular make-up of the disease and the clinical development of therapies with novel mechanisms of action. While some patients with more indolent disease may benefit from local therapy such as metastasectomy or cytoreductive nephrectomy, others may safely embark on an active surveillance program or be offered targeted therapy. Yet, a combination regimen including an ICI is the most effective regimen and should be considered in most mRCC cases.

A comparison of match outcomes between traditional medical degree and dual-degree applicants.

Background: Dual degrees combining and MD with another professional degree (MPH, MBA, or PhD) are becoming more common in an attempt to increase an applicant's competitivity for a residency.

Objective: This study was designed to assess differences in MD-only and dual degree MD applicants with respect to applicant characteristics and match outcomes.

Methods: Utilizing the voluntarily-reported publicly available 2017-2019 Texas STAR database, we assessed applicants from 115 medical schools.

Discovery of TITIN Gene Truncating Variant Mutations and 5-Year Outcomes in Patients With Nonischemic Dilated Cardiomyopathy.

Genetic factors play an important role in nonischemic dilated cardiomyopathy (NIDC). However, prime opportunities remain for genetic discovery and prognostic understanding. TITIN gene truncating variant mutations (TTNtv) are of interest because of their frequent appearance in NIDC series.

Low-cost sensors as an alternative for long-term air quality monitoring.

Low-cost air quality sensors are increasingly being used in many applications; however, many of their performance characteristics have not been adequately investigated. This study was conducted over a period of 13 months using low-cost air quality monitors, each comprising two low-cost sensors, which were subjected to a wide range of pollution sources and concentrations, relative humidity and temperature at four locations in Australia and China. The aim of the study was to establish the performance characteristics of the two low-cost sensors (a Plantower PMS1003 for PM and an Alphasense CO-B4 for carbon monoxide, CO) and the KOALA monitor as a whole under various conditions.

TP53 Gain-of-Function Mutations in Circulating Tumor DNA in Men With Metastatic Castration-Resistant Prostate Cancer.

Background: Circulating tumor DNA (ctDNA), which can be assessed by liquid biopsy, can provide valuable genomic information that may affect treatment response in prostate cancer. The aim of this study was to characterize TP53 mutations and treatment history in prostate cancer.

Patients And Methods: This study included 143 patients with metastatic castration-resistant prostate cancer who had undergone ctDNA sequencing via Guardant360 testing.

Using virtual reality to estimate aesthetic values of coral reefs.

Aesthetic value, or beauty, is important to the relationship between humans and natural environments and is, therefore, a fundamental socio-economic attribute of conservation alongside other ecosystem services. However, beauty is difficult to quantify and is not estimated well using traditional approaches to monitoring coral-reef aesthetics. To improve the estimation of ecosystem aesthetic values, we developed and implemented a novel framework used to quantify features of coral-reef aesthetics based on people's perceptions of beauty.

Applications of low-cost sensing technologies for air quality monitoring and exposure assessment: How far have they gone?

Over the past decade, a range of sensor technologies became available on the market, enabling a revolutionary shift in air pollution monitoring and assessment. With their cost of up to three orders of magnitude lower than standard/reference instruments, many avenues for applications have opened up. In particular, broader participation in air quality discussion and utilisation of information on air pollution by communities has become possible.

Concepts and relevance of genome-wide association studies.

Genome-wide association study (GWAS) technology has been a primary method for identifying the genes responsible for diseases and other traits for the past 10 years. Over 2,000 human GWAS reports now appear in the scientific journals. The technology is continuing to improve, and has recently become accessible to researchers studying a wide variety of animals, plants and model organisms.

Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms.

Objective: We sought to use an innovative tool that is based on common biologic pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB) to enhance investigators' ability to identify and to highlight common mechanisms and underlying genetic factors that are responsible for SPTB.

Study Design: We performed a secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.

Identification of rare recurrent copy number variants in high-risk autism families and their prevalence in a large ASD population.

Structural variation is thought to play a major etiological role in the development of autism spectrum disorders (ASDs), and numerous studies documenting the relevance of copy number variants (CNVs) in ASD have been published since 2006. To determine if large ASD families harbor high-impact CNVs that may have broader impact in the general ASD population, we used the Affymetrix genome-wide human SNP array 6.0 to identify 153 putative autism-specific CNVs present in 55 individuals with ASD from 9 multiplex ASD pedigrees.

Search for compound heterozygous effects in exome sequence of unrelated subjects.

To enable the assessment of compound heterozygosity, we propose a simple approach for incorporating genotype phase in a rare variant collapsing procedure for the analysis of DNA sequence data. When multiple variants are identified within a gene, knowing the phase of each variant may provide additional statistical power to detect associations with phenotypes that follow a recessive or additive inheritance pattern. We begin by phasing all marker data; then, we collapse nonsynonymous single-nucleotide polymorphisms within genes on each phased haplotype, resulting in a single diploid genotype for each gene, which represents whether one or both haplotypes carry a nonsynonymous variant allele.

Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics using novel sumLINK and sumLOD analyses.

Background: Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity.

Methods: We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD.

Replication of the 10q11 and Xp11 prostate cancer risk variants: results from a Utah pedigree-based study.

A recent genome-wide association study suggested seven new loci as associated with prostate cancer susceptibility. The strongest associated single nucleotide polymorphism (SNP) in each region was identified (rs2660753, rs9364554, rs6465657, rs10993994, rs7931342, rs2735839, rs5945619). We studied these seven SNPs in a replication study consisting of 169 familial prostate cancer cases selected from Utah high-risk prostate cancer pedigrees and 805 controls.

Extracting disease risk profiles from expression data for linkage analysis: application to prostate cancer.

The genetic factors underlying many complex traits are not well understood. The Genetic Analysis Workshop 15 Problem 1 data present the opportunity to explore whether gene expression data from microarrays can be utilized to define useful phenotypes for linkage analysis in complex diseases. We utilize expression profiles for multiple genes that have been associated with a disease to develop a composite 'risk profile' that can be used to map other loci involved in the same disease process.

Summary of Genetic Analysis Workshop 15: Group 9 linkage analysis of the CEPH expression data.

Group 9 participants carried out linkage analysis of the Centre d'Etude de Polymorphism Humain (CEPH) expression data, using strategies that ranged from focused investigation of a small number of traits to full genome scans of all available traits. Results from five key areas encompass the most important results within and across the 17 participating groups. First, both extensive genetic heterogeneity and poor predictability of mapping results based on heritability have key implications for study design.