Accounting for 10-20% of breast cancer cases, triple-negative breast cancer (TNBC) is associated with a disproportionate number of breast cancer deaths. One challenge in studying TNBC is its genomic profile: with the exception of TP53 loss, most breast cancer tumors are characterized by a high number of copy number alterations (CNAs), making modeling the disease in whole animals challenging. We computationally analyzed 186 CNA regions previously identified in breast cancer tumors to rank genes within each region by likelihood of acting as a tumor driver.
View Article and Find Full Text PDFWhole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous coronavirus infection, the emergence of novel variants and the presence of large zoonotic reservoirs harboring novel heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female mouse model of coronavirus disease to evaluate inactivated vaccine performance against either homologous challenge with SARS-CoV-2 or heterologous challenge with a bat-derived coronavirus that represents a potential emerging disease threat.
View Article and Find Full Text PDFRNA viruses quickly evolve subtle genotypic changes that can have major impacts on viral fitness and host range, with potential consequences for human health. It is therefore important to understand the evolutionary fitness of novel viral variants relative to well-studied genotypes of epidemic viruses. Competition assays are an effective and rigorous system with which to assess the relative fitness of viral genotypes.
View Article and Find Full Text PDFInactivated whole virus SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide (Alum) are among the most widely used COVID-19 vaccines globally and have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous virus infection in healthy recipients, the emergence of novel SARS-CoV-2 variants and the presence of large zoonotic reservoirs provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes including vaccine-associated enhanced respiratory disease (VAERD). To evaluate this possibility, we tested the performance of an inactivated SARS-CoV-2 vaccine (iCoV2) in combination with Alum against either homologous or heterologous coronavirus challenge in a mouse model of coronavirus-induced pulmonary disease.
View Article and Find Full Text PDFNeurol Clin Pract
February 2023
Purpose Of Review: Clinical trials for Huntington disease (HD) have primarily focused on managing chorea and, more recently, the development of disease-modifying therapies (DMTs). Nonetheless, understanding health services among patients with HD is essential for assessing new therapeutics, development of quality metrics, and overall quality of life of patients and families with HD. Health services assess health care utilization patterns, outcomes, and health care-associated costs, which can help shape the development of therapeutics and aid in policies that affect patients with a specific condition.
View Article and Find Full Text PDFJ Public Health Manag Pract
November 2021
Context: Coronavirus disease 2019 (COVID-19) incidence rates are 2- to 5-fold higher among persons incarcerated in the United States than in the general population.
Program Or Policy: We describe an outbreak investigation of COVID-19 at a jail (jail A) in Alameda County during March 2020-March 2021.
Implementation: To prevent COVID-19 cases among incarcerated persons and employees, staff at jail A and the county public health department worked to develop and recommend infection control measures implemented by jail A including, but not limited to, face covering use among incarcerated persons and staff; cohorting incarcerated persons at a higher risk of severe COVID-19 in dedicated housing units; quarantining all newly detained individuals for 14 days; and offering testing for all symptomatic incarcerated persons, newly incarcerated persons at day 2 and day 10, and all persons who resided in a housing unit where a COVID-19 case was detected.
Despite the immense impact of wildlife trafficking, comparisons of the profits, costs, and seriousness of crime consistently rank wildlife trafficking lower relative to human trafficking, drug trafficking and weapons trafficking. Using the published literature and current events, we make the case, when properly viewed within the context of COVID-19 and other zoonotic diseases transmitted from wildlife, that wildlife trafficking is the most costly and perhaps the most serious form of trafficking. Our synthesis should raise awareness of the seriousness of wildlife trafficking for humans, thereby inducing strategic policy decisions that boost criminal justice initiatives and resources to combat wildlife trafficking.
View Article and Find Full Text PDFControversy remains whether to perform a pharyngeal flap simultaneously with a tonsillectomy in patients with velopharyngeal insufficiency. The aim of this study is to revisit the speech outcomes and complications associated with the combined superiorly based pharyngeal flap and tonsillectomy procedure, while comparing pain outcomes. We hypothesize that the combined procedure will improve speech outcomes with minimal complications, but patients will experience more pain in the combined procedure.
View Article and Find Full Text PDFCrim Behav Ment Health
April 2021
Background: There has been little research into whether personality traits increase vulnerability to serious forms of recurring victimisation, such as commercial sexual exploitation of young people.
Aims: To investigate whether impulsivity, emotional dysregulation or high psychopathy scale scores indicative of personality traits increase vulnerability to commercial sexual exploitation.
Methods: Data were used from the longitudinal Pathways to Desistance Study 1170 justice-involved men who were aged 14-19 at baseline data collection.
Our ability to discover effective drug combinations is limited, in part by insufficient understanding of how the transcriptional response of two monotherapies results in that of their combination. We analyzed matched time course RNAseq profiling of cells treated with single drugs and their combinations and found that the transcriptional signature of the synergistic combination was unique relative to that of either constituent monotherapy. The sequential activation of transcription factors in time in the gene regulatory network was implicated.
View Article and Find Full Text PDFHigh-throughput experiments produce increasingly large datasets that are difficult to analyze and integrate. While most data integration approaches focus on aligning metadata, data integration can be achieved by abstracting experimental results into gene sets. Such gene sets can be made available for reuse through gene set enrichment analysis tools such as Enrichr.
View Article and Find Full Text PDFVitamin B12 deficiency is common in older individuals. Circulating vitamin B12 concentration can be used to diagnose deficiency, but this test has substantial false positive and false negative rates. We conducted genome-wide association studies (GWAS) in which we resolved total serum vitamin B12 into the fractions bound to transcobalamin and haptocorrin: two carrier proteins with very different biological properties.
View Article and Find Full Text PDFBackground: Trained medical interpreters are instrumental to patient satisfaction and quality of care. They are especially important in student-run clinics, where many patients have limited English proficiency. Because student-run clinics have ties to their medical schools, they have access to bilingual students who may volunteer to interpret, but are not necessarily formally trained.
View Article and Find Full Text PDFBreast cancer is the most common cancer in women with 232,670 new cases estimated in the USA for 2014. Approaches for reducing breast cancer risk include lifestyle modification, chemoprevention, and prophylactic surgery. Lifestyle modification has a variety of health benefits with few associated risks and is appropriate for all women regardless of breast cancer risk.
View Article and Find Full Text PDFThe concomitant increase in obesity and asthma in recent years has led to the classification of two obese-asthma phenotypes, characterized by the age of asthma onset and atopy. Asthma tends to be more severe, harder to control, and more resistant to standard medications among members of these two groups. Because of the limited effectiveness of inhaled corticosteroids, dietary changes and weight loss measures must be considered in the management of these patients.
View Article and Find Full Text PDFPeptide nanostructures present a wide range of opportunities for applications in biomedicine and bionanotechnology; hence experimental and theoretical studies aiming at determination of thermo-mechanical stability of peptide-based nanostructures are critical for the design and development of their technological applications. Here, we present a homogeneous deformation method combined with the finite elasticity theory and molecular dynamics simulations (MD) for the calculation of second-order anisotropic elastic constants for a membrane model made up of self-assembled cyclic peptide nanotubes. We have computed the values of all anisotropic elastic constants at 300 K.
View Article and Find Full Text PDFMany hospitals are working to improve the work environment for their staff. Research has indicated a linkage between work environment characteristics and patient outcomes and this research along with the nursing shortage has been the impetus for focusing on improving the work environment. The authors described the experience of an academic medical center hospital in achieving Magnet hospital status.
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