HIV Replication Under High-Level Cabotegravir Is Associated with the Appearance of 3'-PPT Mutations, Circular DNA Transcription and Recombination.

The HIV integrase inhibitor, dolutegravir (DTG), in the absence of eliciting integrase (int) resistance, has been reported to select mutations in the virus 3'-polypurine tract (3'-PPT) adjacent to the 3'-LTR U3. An analog of DTG, cabotegravir (CAB), has a high genetic barrier to drug resistance and is used in formulations for treatment and long-acting pre-exposure prophylaxis. We examined whether mutations observed for DTG would emerge in vitro with CAB.

Medicaid coverage continuity is associated with lymphoma stage among children and adolescents/young adults.

Lymphoma is the third leading cause of cancer among children and adolescents/young adults (AYAs) in the United States, with later-stage diagnoses often being linked to worse outcomes. Continuous health insurance coverage is crucial for facilitating early cancer detection and diagnosis. Among Medicaid-insured children and AYAs diagnosed with lymphoma, this study examines whether the timing of Medicaid enrollment and coverage continuity are associated with stage at diagnosis.

miR-127/3p Inhibits Cell Migration in Lung Adenocarcinoma Under Hypoxic and Normal Oxygen Conditions.

MicroRNAs are small noncoding nucleotides that serve as intracellular and extracellular signaling molecules. A previous collaboration found miR-127/3p circulation in the blood of breast cancer patients correlated with improved patient recovery and prognosis. While this study exclusively focused on breast cancer patients, data mining of the TCGA databases indicated that miR-127/3p may be positively associated with outcomes in other cancer types.

Association Between Medicaid Coverage Continuity and Survival in Patients With Newly Diagnosed Pediatric and Adolescent Cancers.

Purpose: Many patients with cancer do not gain Medicaid coverage until a cancer diagnosis, which can reduce access to early cancer detection and timely treatment, potentially driving inferior survival. Little is known about whether continuous Medicaid coverage prediagnosis through postdiagnosis ( gaining Medicaid at/after diagnosis) provides survival benefits for pediatric/adolescent oncology patients.

Materials And Methods: We identified patients newly diagnosed with cancer at age 21 years or younger in a large pediatric health system between 2007 and 2016.

Approaches to determination of the mechanism of the Rieske monooxygenase salicylate 5-hydroxylase.

Rieske oxygenases catalyze an exceptionally broad range of discrete types of reactions despite the utilization of a highly conserved quaternary structure and metal cofactor complement. Oxygen activation within this family occurs at a mononuclear Fe site, which is located approximately 12 Å from a one-electron reduced Rieske-type iron-sulfur cluster. Electron transfer from the Rieske cluster to the mononuclear iron site occurs during O activation and product formation.

Health Insurance Continuity and Mortality in Children and Adolescents/Young Adults with Blood Cancer.

Background: Many uninsured patients do not receive Medicaid coverage until a cancer diagnosis, potentially delaying access to care for early cancer detection and treatment. We examine the association of Medicaid enrollment timing and patterns with survival among children and adolescents/young adults (AYAs) diagnosed with blood cancers, where disease onset can be acute and early detection is critical.

Methods: We identified 28,750 children and AYAs (0-39 years) newly diagnosed with blood cancers from the 2006-2013 SEER-Medicaid data.

Long-term quality of life after hematopoietic cell transplant for sickle cell disease in childhood: A STELLAR interim analysis.

We prospectively collected PROMIS©25 and PROMIS©29 surveys in the Sickle Cell Transplant Evaluation of Long Term and Late Effects Registry (STELLAR). Mobility and social participation T-scores were decreased; all other domains were within the norm.

HIV Immunocapture Reveals Particles Expressed in Semen Under Integrase Strand Transfer Inhibitor-Based Therapy Are Largely Myeloid Cell-Derived and Disparate.

As use of human immunodeficiency virus (HIV) integrase strand transfer inhibitors (INSTI) increases and formulations are being developed for maintenance therapies and chemoprophylaxis, assessing virus suppression under INSTI-based regimens in prevention-relevant biologic compartments, such as the male genital tract, is timely. We used cell-source marker virion immunocapture to examine amplification of particle RNA then assessed the phylogenetic relatedness of seminal and blood viral sequences from men with HIV who were prescribed INSTI-based regimens. Seminal plasma immunocaptures yielded amplifiable virion RNA from 13 of 24 (54%) men, and the sequences were primarily associated with markers indicative of macrophage and resident dendritic cell sources.

Association Between Medicare Site-Based Payment Policy, Physician Practice Characteristics, and Vertical Integration Among Oncologists.

Purpose: Medicare's differential payments for services delivered in physician offices versus hospital outpatient settings incentivize hospital-physician integration (ie, vertical integration) across many specialties, but evidence for oncologists is mixed. We examined the association of Medicare site-based payment policy and physician practice characteristics, including service volume and diversity, with vertical integration among oncologists in 2013-2019.

Methods: Using the Medicare Provider Utilization and Payment Data and Medicare Data on Provider Practice and Specialty in 2013-2019, we extracted nonintegrated medical/hematologic oncologists (hereafter oncologists) in 2013 and followed them through 2019.

Weekly Oral Tenofovir Alafenamide Protects Macaques from Vaginal and Rectal Simian HIV Infection.

Pre-exposure prophylaxis (PrEP) with a weekly oral regimen of antiretroviral drugs could be a suitable preventative option for individuals who struggle with daily PrEP or prefer not to use long-acting injectables. We assessed in macaques the efficacy of weekly oral tenofovir alafenamide (TAF) at doses of 13.7 or 27.

Immunocapture of cell surface proteins embedded in HIV envelopes uncovers considerable virion genetic diversity associated with different source cell types.

HIV particles in the blood largely originate from activated lymphocytes and can overshadow variants which may be expressed from other cell types. Investigations of virus persistence must be able to distinguish cells refractory to viral clearance that serve as reservoirs. To investigate additional cell types that may be associated with in vivo HIV expression we developed a virus particle immunomagnetic capture method targeting several markers of cellular origin that become embedded within virion envelopes during budding.

An Exploratory Analysis of the Cost-Effectiveness of a Multi-cancer Early Detection Blood Test Compared with Standard of Care Screening in Ontario, Canada.

Background: Determining whether multi-cancer early detection (MCED) tests are cost effective is important in deciding whether they should be included in the clinical path of cancer care, especially for cancers where screening tools do not exist.

Research Objective: The main objective of this study is to determine the cost effectiveness of including a MCED screening regimen together with existing provincial screening protocols for selected cancers that are prevalent in Ontario, Canada, among average risk persons aged 50-75 years. The selected cancers include breast, colorectal, lung, esophageal, liver, pancreatic, stomach, and ovarian.

Extended Postexposure Protection Against Vaginal Simian/Human Immunodeficiency Virus Infection With Tenofovir Alafenamide Fumarate/Elvitegravir Inserts in Macaques.

Vaginal inserts that can be used on demand before or after sex may be a desirable human immunodeficiency virus (HIV) prevention option for women. We recently showed that inserts containing tenofovir alafenamide fumarate (TAF, 20 mg) and elvitegravir (EVG, 16 mg) were highly protective against repeated simian/human immunodeficiency virus (SHIV) vaginal exposures when administered to macaques 4 hours before or after virus exposure (93% and 100%, respectively). Here, we show in the same macaque model that insert application 8 hours or 24 hours after exposure maintains high efficacy (94.

Utilization of cardiac tests in anthracycline-treated cancer survivors differs between young adults and children: A claims-based analysis.

Background: The Children's Oncology Group Guidelines recommend a cardiacechocardiogram, or comparable functional imaging, following therapy completion in survivors of childhood/adolescent cancers exposed to anthracyclines.

Methods: Using the 2009-2019 Merative™ MarketScan® Commercial Database, we examined real-world utilization of cardiac testing among 1609 anthracycline-treated survivors of childhood/adolescent cancers.

Results: The cumulative incidence of receiving an initial cardiac test by 5.

A Genetics-Focused Lens on Social Constructs in Pharmacy Education.

Objective: Incorporating diversity, equity, inclusion, and anti-racism principles into clinical and didactic education is essential because each influence cognitive and affective attitudes in pharmacy practice. Educators must learn from the past to enlighten the future. For example, race is a social construct, not a biological construct.

Gender-affirming pharmacotherapy and additional health considerations: A contemporary review.

Background: Transgender and gender-diverse (TGD) individuals in the United States face health care disparities compounded with discrimination and limited access to necessary medical services. Gender-affirming interventions have been shown to mitigate gender dysphoria and psychiatric comorbidities, yet United States legislation limiting such interventions has increased. As medication experts, pharmacists can facilitate access to care and appropriate use of gender-affirming hormone therapy (GAHT) and educate other health care providers on best practices for caring for TGD individuals in a variety of settings.

A perspective on In vitro developmental neurotoxicity test assay results: An expert panel review.

For decades, there has been increasing concern about the potential developmental neurotoxicity (DNT) associated with chemicals. Regulatory agencies have historically utilized standardized in vivo testing to evaluate DNT. Owing to considerations including higher-throughput screening for DNT, reduction in animal use, and potential cost efficiencies, the development of alternative new approach methods (NAMs) occurred; specifically, the advent of the DNT in vitro test battery (DNT IVB).

Nuclear Resonance Vibrational Spectroscopy Definition of Peroxy Intermediates in Catechol Dioxygenases: Factors that Determine Extra- versus Intradiol Cleavage.

The extradiol dioxygenases (EDOs) and intradiol dioxygenases (IDOs) are nonheme iron enzymes that catalyze the oxidative aromatic ring cleavage of catechol substrates, playing an essential role in the carbon cycle. The EDOs and IDOs utilize very different Fe and Fe active sites to catalyze the regiospecificity in their catechol ring cleavage products. The factors governing this difference in cleavage have remained undefined.

Are children with sickle cell disease at particular risk from the harmful effects of air pollution? Evidence from a large, urban/peri-urban cohort.

Introduction: Pathophysiologic pathways of sickle cell disease (SCD) and air pollution involve inflammation, oxidative stress, and endothelial damage. It is therefore plausible that children with SCD are especially prone to air pollution's harmful effects.

Methods: Patient data were collected from a single-center, urban/peri-urban cohort of children with confirmed SCD.

Implementation of a heart failure educational intervention for patients with recent admissions for acute decompensated heart failure.

Purpose: This study examined whether implementation of a heart failure (HF) education class targeted at patients and their caregivers decreased worsening HF, emergency department (ED) visits and hospital admissions, and improved patient quality of life and confidence in disease state management.

Methods: Patients with HF and a recent hospital admission for acute decompensated heart failure (ADHF) were offered an educational course covering HF pathophysiology, medications, diet, and lifestyle modifications. Patients completed surveys before and 30 days after completion of the educational course.

Testing Theory-Based Messages to Encourage Women at Average Risk for Breast Cancer to Consider Biennial Mammography Screening.

Background: The US Preventive Services Task Force does not recommend routine annual mammography screening for women aged 40-49 at average risk. Little research has been done to develop theory-based communication interventions to facilitate informed decision-making about reducing potentially low-value mammography screening.

Purpose: Evaluate the effects of theory-based persuasive messages on women's willingness to consider delaying screening mammography until age 50 or have mammograms biennially.

Complete Genome Sequences of Chop, DelRio, and GrandSlam, Three Phages Isolated from Soil in Central Arkansas.

Chop, DelRio, and GrandSlam are phage with a morphotype isolated from soil in Arkansas using the host Gordonia terrae 3612. All three are temperate, and their genomes share at least 96% nucleotide identity. These phage are assigned to cluster DI based on gene content similarity to other sequenced actinobacteriophage.