Evaluation of Long-Term Performance of Six PM Sensor Types.

From July 2019 to January 2021, six models of PM air sensors were operated at seven air quality monitoring sites across the U.S. in Arizona, Colorado, Delaware, Georgia, North Carolina, Oklahoma, and Wisconsin.

Small-molecule modulation of β-arrestins.

β-arrestins are multifunctional regulators of G protein-coupled receptor (GPCR) signaling, orchestrating diverse downstream signaling events and physiological responses across the vast GPCR superfamily. While GPCR pharmacology has advanced to target orthosteric and allosteric sites, as well as G proteins and GRKs, comparable chemical tools to study β-arrestins remain lacking. Here, we report the discovery of small-molecule inhibitors that selectively target β-arrestins and delineate their mechanism of action through integrated pharmacological, biochemical, biophysical, and structural analyses.

Beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy.

Beta-arrestins (βarrs) are key regulators and transducers of G-protein coupled receptor signaling; however, little is known of how βarrs communicate with their downstream effectors. Here, we use cryo-electron microscopy to elucidate how βarr1 recruits and activates non-receptor tyrosine kinase Src. βarr1 binds Src SH3 domain via two distinct sites: a polyproline site in the N-domain and a non-proline site in the central crest region.

Diagnostic yield of exome and genome sequencing after non-diagnostic multi-gene panels in patients with single-system diseases.

Background: Though next-generation sequencing (NGS) tests like exome sequencing (ES), genome sequencing (GS), and panels derived from exome and genome data (EGBP) are effective for rare diseases, the ideal diagnostic approach is debated. Limited research has explored reanalyzing raw ES and GS data post-negative EGBP results for diagnostics.

Results: We analyzed complete ES/GS raw sequencing data from Mayo Clinic's Program for Rare and Undiagnosed Diseases (PRaUD) patients to assess whether supplementary findings could augment diagnostic yield.

Executive Function as a Predictor of Pain Perception in Healthy Young Adults.

Objective: Pain's impact on executive function is understood and specific cognitive abilities may contribute to coping with pain, though past work is confounded by chronic pain populations. This study aims to understand how executive functioning may predict the experience of pain among healthy adults. It was hypothesized that poorer executive functioning would predict more intense pain perception.

Development of a flipped learning course to deliver and scale molecular variant evaluation education: A quality improvement initiative.

Over the past several decades, molecular genetic testing volumes have grown and testing has expanded from single-gene assays to multigene panels, exome sequencing, and genome sequencing. The number of molecular genetic variants that require manual interpretation has grown simultaneously, resulting in an increased demand for education on molecular variant evaluation (MVE). To meet this growing need, a team of genetic counselors and educational experts undertook a quality improvement (QI) initiative with the objectives of assessing, standardizing, and scaling access to MVE education, without increasing instructor time to deliver the education.

Characteristics of drug-involved black women under community supervision; implications for retention in HIV clinical trials and healthcare.

This study examined retention and its relationship to mental health, substance use, and social determinants of health in a randomized clinical trial of a behavioral HIV/sexually transmitted infection prevention intervention with drug-involved Black women ( = 348) under community supervision programs in New York City. Using secondary analysis, we used logistic models to test the association between factors related to mental health, substance use, and social determinants of health and follow-up assessment completion (three, six, and 12 months). Participants who were diagnosed with schizophrenia had lower odds of retention.

Evidence of Help-Seeking Behaviors Among Black Women Under Community Supervision in New York City: A Plea for Culturally Tailored Intimate Partner Violence Interventions.

Background: Black women involved in the legal system disproportionately experience intimate partner violence (IPV); however, current research does not satisfactorily describe the risk and protective factors associated with IPV among Black women under community supervision.

Methods: We conducted a subgroup analysis of Black women ( = 128) using data from a randomized controlled trial that evaluated the feasibility and efficacy of two IPV screening and prevention programs for women under community supervision. Participants in the original study were randomized into two IPV prevention conditions-computerized or case manager Women Initiating New Goals of Safety (WINGS).

Self-docking and cross-docking simulations of G protein-coupled receptor-ligand complexes: Impact of ligand type and receptor activation state.

G protein-coupled receptors (GPCR) are the largest family of cell surface receptors in vertebrates. Their abundance and role in nearly all physiological systems make GPCR the largest protein family targeted for development of pharmaceuticals. Ligand discovery aimed at identification of chemical tools and drug leads is aided by molecular docking simulations that allow critical analysis of the potential interactions between small molecules and proteins in resulting complexes.

Characterization of the High-Affinity Fuzzy Complex between the Disordered Domain of the E7 Oncoprotein from High-Risk HPV and the TAZ2 Domain of CBP.

The intrinsically disordered N-terminal region of the E7 protein from high-risk human papillomavirus (HPV) strains is responsible for oncogenic transformation of host cells through its interaction with a number of cellular factors, including the TAZ2 domain of the transcriptional coactivator CREB-binding protein. Using a variety of spectroscopic and biochemical tools, we find that despite its nanomolar affinity, the HPV16 E7 complex with TAZ2 is disordered and highly dynamic. The disordered domain of HPV16 E7 protein does not adopt a single conformation on the surface of TAZ2 but engages promiscuously with its target through multiple interactions involving two conserved motifs, termed CR1 and CR2, that occupy an extensive binding surface on TAZ2.

Pharmacoresponsiveness of spontaneous recurrent seizures and the comorbid sleep disorder of epileptic Kcna1-null mice.

Drug resistant epilepsy affects ∼30% of people with epilepsy and is associated with epilepsy syndromes with frequent and multiple types of seizures, lesions or cytoarchitectural abnormalities, increased risk of mortality and comorbidities such as cognitive impairment and sleep disorders. A limitation of current preclinical models is that spontaneous seizures with comorbidities take time to induce and test, thus making them low-throughput. Kcna1-null mice exhibit all the characteristics of drug resistant epilepsy with spontaneous seizures and comorbidities occurring naturally; thus, we aimed to determine whether they also demonstrate pharmacoresistanct seizures and the impact of medications on their sleep disorder comorbidity.

Rare TBX4 Variant Causing Pulmonary Arterial Hypertension With Small Patella Syndrome in an Adult Man.

Small patella syndrome presents with small or absent patellae and may result in pulmonary arterial hypertension, typically in children. A pathogenic canonical splice site variant, c.1021+1G>A in the T-box transcription factor 4 () gene, currently not included in commercial gene panel, was detected in an adult with pulmonary arterial hypertension and absent patellae.

Fast track dialysis: Improving emergency department and hospital throughput for patients requiring hemodialysis.

Objective: To describe the impact of a novel communication and triage pathway called fast track dialysis (FTD) on the length of stay (LOS), resource utilization, and charges for unscheduled hemodialysis for end stage renal disease (ESRD) patients presenting to the emergency department (ED).

Methods: Prospective and retrospective cohorts of ESRD patients meeting requirements of routine or urgent hemodialysis at a tertiary academic hospital from September 25th, 2016 to September 25th, 2018 in 1 year cohorts. Two sample t-tests were used to compare most outcomes of the cohorts with a Mann-Whitney U test used for skewed data.

Babesia sp. infection in a zoo-housed polar bear (Ursus maritimus).

A 28-year-old female polar bear (Ursus maritimus) housed in a zoo in Upstate New York presented with acute inappetence and lethargy. The bear's condition rapidly deteriorated, and because laboratory testing indicated severe hepatic and renal disease, the bear was humanely euthanized. Examination of a blood smear from a sample collected just prior to euthanasia revealed the presence of intra-erythrocytic inclusions, which were identified as Babesia sp.

Evidence for vertical transmission of Mycoplasma haemocanis, but not Ehrlichia ewingii, in a dog.

A 2-year-old female intact pregnant Beagle was evaluated after the owner surrendered her to a shelter. Prepartum and 2 months postpartum at the time of routine spay, the dam was whole-blood polymerase chain reaction (PCR) positive for Ehrlichia ewingii. She was also whole-blood PCR positive for Mycoplasma haemocanis prepartum and continuously for 5 months thereafter.

Presentation of a Rare Malignancy: Leiomyosarcoma of the Prostate.

Prostatic leiomyosarcoma is an aggressive malignancy with a high risk of metastasis and a poor prognosis that poses unique diagnostic and treatment challenges.

Development and Verification of an RNA Sequencing (RNA-Seq) Assay for the Detection of Gene Fusions in Tumors.

We assessed the performance characteristics of an RNA sequencing (RNA-Seq) assay designed to detect gene fusions in 571 genes to help manage patients with cancer. Polyadenylated RNA was converted to cDNA, which was then used to prepare next-generation sequencing libraries that were sequenced on an Illumina HiSeq 2500 instrument and analyzed with an in-house developed bioinformatic pipeline. The assay identified 38 of 41 gene fusions detected by another method, such as fluorescence in situ hybridization or RT-PCR, for a sensitivity of 93%.

Spindle cell rhabdomyosarcoma of bone with FUS-TFCP2 fusion: confirmation of a very recently described rhabdomyosarcoma subtype.

Aims: Rhabdomyosarcomas of bone are extremely rare, with fewer than 10 reported cases. A very rare subtype of spindle cell/sclerosing rhabdomyosarcoma harbouring a FUS-TFCP2 fusion and involving both soft tissue and bone locations has been reported very recently. We report only the fourth case of this unusual, clinically aggressive rhabdomyosarcoma.