Targeting chromosomally unstable tumors with a selective KIF18A inhibitor.

Chromosome instability is a prevalent vulnerability of cancer cells that has yet to be fully exploited therapeutically. To identify genes uniquely essential to chromosomally unstable cells, we mined the Cancer Dependency Map for genes essential in tumor cells with high levels of copy number aberrations. We identify and validate KIF18A, a mitotic kinesin, as a vulnerability of chromosomally unstable cancer cells.

Early COVID-19 Vaccine Initiation and Completion Among Cancer Survivors and Barriers to Vaccine Completion: Implications for Future COVID-19 Vaccination Uptake Rates.

Purpose: Cancer survivors are considered by public health officials as a high-risk group in the United States for severe complications from COVID-19. We aimed to characterize patterns of early uptake of the COVID-19 vaccine among cancer survivors and to determine modifiable barriers to vaccine completion that can be addressed to ensure future booster adherence.

Methods: Cross-sectional data of vaccine uptake by summer 2021 was extracted from adult cancer survivors enrolled in the "All of Us" research program.

Alcohol and Cannabis Use Associated with Cardiometabolic Biomarkers among "All of Us" Cancer Survivors.

Background: Cancer survivors are at increased risk for cardiometabolic comorbidities following cancer treatment, which may be further exacerbated by cannabis and alcohol use. We aimed to examine the direct relationships of cannabis, alcohol, and the co-use of both substances with cardiometabolic risk factors and to explore disparities by race/ethnicity and sex.

Methods: Cross-sectional data were extracted from adult cancer survivors in the "All of Us" from 2018 to 2022.

Disparities Between Rural and Urban Communities: Response to 18 Months of Diet and Exercise Versus Control for Knee Osteoarthritis and Overweight or Obesity.

Objective: The study objective was to determine whether the clinical response of older adults with knee osteoarthritis and overweight or obesity to 18 months of diet and exercise (D + E) or attention control (C) interventions differed between participants from rural versus urban communities.

Methods: Participants were 823 older adults (mean age, 64.6 years; 77% women) with knee osteoarthritis and overweight or obesity who resided in rural (n = 410) and urban (n = 413) counties in North Carolina.

College student perceptions of pharmacist-provided hormonal contraception.

Background: North Carolina immunizing pharmacists are authorized to provide oral and transdermal hormonal contraception to eligible patients. In March 2022, implementation of this enhanced patient care service began statewide, after approval of standing orders and published training from the North Carolina Association of Pharmacists. Two pharmacy locations on a college campus began offering pharmacist-provided hormonal contraception shortly after approval.

Attributions toward artificial agents in a modified Moral Turing Test.

Advances in artificial intelligence (AI) raise important questions about whether people view moral evaluations by AI systems similarly to human-generated moral evaluations. We conducted a modified Moral Turing Test (m-MTT), inspired by Allen et al. (Exp Theor Artif Intell 352:24-28, 2004) proposal, by asking people to distinguish real human moral evaluations from those made by a popular advanced AI language model: GPT-4.

Racial/Ethnic Disparities: Discrimination's Impact on Health-Related Quality of Life-An All of Us Cancer Survivors' Cross-sectional Study.

Background: Discrimination is associated with worse mental and physical health outcomes. However, the associations among cancer survivors are limited.

Objective: We examined whether discrimination is associated with HRQoL and whether adjusting for it reduces racial/ethnic disparities in HRQoL among cancer survivors.

Identification of the KIF18A alpha-4 helix as a therapeutic target for chromosomally unstable tumor cells.

The mitotic kinesin, KIF18A, is required for proliferation of cancer cells that exhibit chromosome instability (CIN), implicating it as a promising target for treatment of a subset of aggressive tumor types. Determining regions of the KIF18A protein to target for inhibition will be important for the design and optimization of effective small molecule inhibitors. In this study, we used cultured cell models to investigate the effects of mutating S284 within the alpha-4 helix of KIF18A, which was previously identified as a phosphorylated residue.

Identification of the KIF18A alpha-4 helix as a therapeutic target for chromosomally unstable tumor cells.

The mitotic kinesin, KIF18A, is required for proliferation of cancer cells that exhibit chromosome instability (CIN), implicating it as a promising target for treatment of a subset of aggressive tumor types. Determining regions of the KIF18A protein to target for inhibition will be important for the design and optimization of effective small molecule inhibitors. In this study, we investigated the effects of mutating S284 within the alpha-4 helix of KIF18A, which was previously identified as a phosphorylated residue.

Modification of the neck-linker of KIF18A alters Microtubule subpopulation preference.

Kinesins support many diverse cellular processes, including facilitating cell division through mechanical regulation of the mitotic spindle. However, how kinesin activity is controlled to facilitate this process is not well understood. Interestingly, posttranslational modifications have been identified within the enzymatic region of all 45 mammalian kinesins, but the significance of these modifications has gone largely unexplored.

Clinical, Health-Related Quality of Life, and Gait Differences Among Obesity Classes in Adults With Knee Osteoarthritis.

Objective: The purpose of this study was to determine whether clinical, health-related quality of life (HRQL), and gait characteristics in adults with knee osteoarthritis (OA) differed by obesity category.

Methods: This cross-sectional analysis of 823 older adults (mean age 64.6 years, SD 7.

COVID-19 Vaccine Hesitancy Among Parents: A Qualitative Study.

Objectives: Addressing parental/caregivers' coronavirus disease 2019 (COVID-19) vaccine hesitancy is critical to improving vaccine uptake in children. Common concerns have been previously reported through online surveys, but qualitative data from KII and focus groups may add much-needed context. Our objective was to examine factors impacting pediatric COVID-19 vaccine decision-making in Black, Spanish-speaking, and rural white parents/caregivers to inform the content design of a mobile application to improve pediatric COVID-19 vaccine uptake.

Current practice of cancer predisposition testing in pediatric patients with CNS tumors in the United States.

An estimated 8.6% of all pediatric patients with central nervous system tumors (CNSTs) have underlying hereditary cancer predisposition (HCP). Identifying HCP affects risk assessment and medical management options for the patients and their family members.

A collaborative approach to improving representation in viral genomic surveillance.

The lack of routine viral genomic surveillance delayed the initial detection of SARS-CoV-2, allowing the virus to spread unfettered at the outset of the U.S. epidemic.

ACDC: a general approach for detecting phenotype or exposure associated co-expression.

Background: Existing module-based differential co-expression methods identify differences in gene-gene relationships across phenotype or exposure structures by testing for consistent changes in transcription abundance. Current methods only allow for assessment of co-expression variation across a singular, binary or categorical exposure or phenotype, limiting the information that can be obtained from these analyses.

Methods: Here, we propose a novel approach for detection of differential co-expression that simultaneously accommodates multiple phenotypes or exposures with binary, ordinal, or continuous data types.

Modification of the Neck Linker of KIF18A Alters Microtubule Subpopulation Preference.

Kinesins support many diverse cellular processes, including facilitating cell division through mechanical regulation of the mitotic spindle. However, how kinesin activity is controlled to facilitate this process is not well understood. Interestingly, post-translational modifications have been identified within the enzymatic region of all 45 mammalian kinesins, but the significance of these modifications has gone largely unexplored.

Travel history among persons infected with SARS-CoV-2 variants of concern in the United States, December 2020-February 2021.

The first three SARS-CoV-2 phylogenetic lineages classified as variants of concern (VOCs) in the United States (U.S.) from December 15, 2020 to February 28, 2021, Alpha (B.

Effect of Diet and Exercise on Knee Pain in Patients With Osteoarthritis and Overweight or Obesity: A Randomized Clinical Trial.

Importance: Some weight loss and exercise programs that have been successful in academic center-based trials have not been evaluated in community settings.

Objective: To determine whether adaptation of a diet and exercise intervention to community settings resulted in a statistically significant reduction in pain, compared with an attention control group, at 18-month follow-up.

Design, Setting, And Participants: Assessor-blinded randomized clinical trial conducted in community settings in urban and rural counties in North Carolina.

A collaborative approach to improve representation in viral genomic surveillance.

Unlabelled: The lack of routine viral genomic surveillance delayed the initial detection of SARS-CoV-2, allowing the virus to spread unfettered at the outset of the U.S. epidemic.

Emergence of the adolescent obesity epidemic in the United States: five-decade visualization with humanoid avatars.

Background/objectives: Body size and shape have increased over the past several decades with one in five adolescents now having obesity according to objective anthropometric measures such as weight, height, and body mass index (BMI). The gradual physical changes and their consequences may not be fully appreciated upon visual inspection by those managing the long-term health of adolescents. This study aimed to develop humanoid avatars representing the gradual changes in adolescent body size and shape over the past five decades and to align avatars with key BMI percentile cut points for underweight, normal weight, overweight, and obesity.

Characteristics of nursing home residents and healthcare personnel with repeated severe acute respiratory coronavirus virus 2 (SARS-CoV-2) tests positive ≥90 days after initial infection: Four US jurisdictions, July 2020-March 2021.

One in six nursing home residents and staff with positive SARS-CoV-2 tests ≥90 days after initial infection had specimen cycle thresholds (Ct) <30. Individuals with specimen Ct<30 were more likely to report symptoms but were not different from individuals with high Ct value specimens by other clinical and testing data.

SARS-CoV-2 Outbreak among Malayan Tigers and Humans, Tennessee, USA, 2020.

We report an outbreak of severe acute respiratory syndrome coronavirus 2 involving 3 Malayan tigers (Panthera tigris jacksoni) at a zoo in Tennessee, USA. Investigation identified naturally occurring tiger-to-tiger transmission; genetic sequence change occurred with viral passage. We provide epidemiologic, environmental, and genomic sequencing data for animal and human infections.

Surface‒Aerosol Stability and Pathogenicity of Diverse Middle East Respiratory Syndrome Coronavirus Strains, 2012‒2018.

Middle East respiratory syndrome coronavirus (MERS-CoV) infects humans and dromedary camels and is responsible for an ongoing outbreak of severe respiratory illness in humans in the Middle East. Although some mutations found in camel-derived MERS-CoV strains have been characterized, most natural variation found across MERS-CoV isolates remains unstudied. We report on the environmental stability, replication kinetics, and pathogenicity of several diverse isolates of MERS-CoV, as well as isolates of severe acute respiratory syndrome coronavirus 2, to serve as a basis of comparison with other stability studies.

One Health Investigation of SARS-CoV-2 Infection and Seropositivity among Pets in Households with Confirmed Human COVID-19 Cases-Utah and Wisconsin, 2020.

Approximately 67% of U.S. households have pets.

Genomic Surveillance for SARS-CoV-2 Variants Circulating in the United States, December 2020-May 2021.

SARS-CoV-2, the virus that causes COVID-19, is constantly mutating, leading to new variants (1). Variants have the potential to affect transmission, disease severity, diagnostics, therapeutics, and natural and vaccine-induced immunity. In November 2020, CDC established national surveillance for SARS-CoV-2 variants using genomic sequencing.