Nickel-Catalyzed Enantioselective C(sp)-C(sp) Cross-Electrophile Coupling of -Sulfonyl Styrenyl Aziridines with Alkyl Bromides.

Herein, we report the first example of a highly enantioselective alkylative aziridine ring opening. Under the catalysis of a chiral nickel/pyridine-imidazoline complex, asymmetric C(sp)-C(sp) cross-electrophile coupling between racemic -sulfonyl styrenyl aziridines and readily available primary alkyl bromides furnishes a variety of highly enantioenriched phenethylamine derivatives with complete regiocontrol and good functional group tolerance. Preliminary mechanistic studies support a reaction pathway consisting of regioselective iodolysis of aziridines and subsequent enantioconvergent coupling of the generated β-amino benzyl iodides with alkyl bromides.

Associations of Major Lifetime and Everyday Discrimination with Cognitive Function among Middle-Aged and Older Adults.

Objectives: We investigated the associations of lifetime and everyday discrimination with cognitive function.

Methods: Data were from the Chicago Community Adult Health Study (n=2952, mean age=43 years [SD=17]). We fitted multivariable linear regression models to quantify the discrimination-cognition associations.

Interactions among neighborhood conditions, sleep quality, and episodic memory across the adult lifespan.

Objectives: On average, adults racialized as non-Hispanic Black and Hispanic sleep more poorly than adults racialized as non-Hispanic White (hereafter, Black, Hispanic, White), but associations between factors that may moderate sleep-memory associations in these groups, such as neighborhood conditions, are unclear. Poorer neighborhood conditions (e.g.

Lifetime Trauma Exposure and Arthritis in Older Adults.

Objective: Experiencing potentially traumatic events across one's lifecourse increases risk for poor physical health outcomes. Existing models emphasize the effects of any lifetime trauma exposure, risk accumulation (multiple traumas over time), and sensitive periods of exposure (specific exposure timepoints leading to lasting consequences). We examined how different indices of trauma exposure across the lifecourse were associated with later life arthritis, a common and debilitating health condition.

The Association Between Physical Activity and Cognition in a Racially/Ethnically Diverse Cohort of Older Adults: Results From the Kaiser Healthy Aging and Diverse Life Experiences Study.

Objective: Most prior research on physical activity (PA) and cognition is based on predominantly white cohorts and focused on associations of PA with mean (average) cognition versus the distribution of cognition. Quantile regression offers a novel way to quantify how PA affects cognition across the entire distribution.

Methods: The Kaiser Healthy Aging and Diverse Life Experiences study includes 30% white, 19% black, 25% Asian, and 26% Latinx adults age 65+ living in Northern California (n = 1600).

Comparison of approaches to control for intracranial volume in research on the association of brain volumes with cognitive outcomes.

Most neuroimaging studies linking regional brain volumes with cognition correct for total intracranial volume (ICV), but methods used for this correction differ across studies. It is unknown whether different ICV correction methods yield consistent results. Using a brain-wide association approach in the MRI substudy of UK Biobank (N = 41,964; mean age = 64.

Evaluation of racial and ethnic heterogeneity in the associations of sleep quality and sleep apnea risk with cognitive function and cognitive decline.

Introduction: The prevalence of poor sleep quality and sleep apnea differs by race and ethnicity and may contribute to racial disparities in cognitive aging. We investigated whether sleep quality and sleep apnea risk were associated with cognitive function and decline and whether the associations differed by race/ethnicity.

Methods: Participants from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE; = 1690; mean age: 75.

Syntheses of Cannabinoid Metabolites: Ajulemic Acid and HU-210.

Cannabinoid metabolites have been reported to be more potent than their parent compounds. Among them, ajulemic acid (AJA) is a side-chain analog of Δ-THC-11-oic acid, which would be a good template structure for the discovery of more potent analogues. Herein, we optimized the key allylic oxidation step to introduce the C-11 hydroxy group with a high yield.

State home and community-based services expenditures and unmet care needs in the United States: Has everyone benefitted equally?

Objective: To test whether the impacts of Medicaid's Home and Community-Based Services (HCBS) expenditures have been equitable.

Data Sources And Study Setting: This is a secondary data analysis. We linked annual data on state-level Medicaid HCBS expenditures with individual data from U.

Spouses of individuals living with mild cognitive impairment or dementia in the United States: A descriptive, population-based study.

Background: Little is known about the population of individuals who live with a spouse with cognitive impairment (CI) or dementia.

Methods: Using the US Health and Retirement Study, 2000 to 2018, we estimated the population of adults ≥ 50 years old co-residing with a spouse with probable CI/dementia. We described their socio-demographic and health characteristics and quantified socio-demographic inequities.

A long and resilient life: the role of coping strategies and variability in their use in lifespan among women.

Objectives: Associations of stress-related coping strategies with lifespan among the general population are understudied. Coping strategies are characterized as being either adaptive or maladaptive, but it is unknown the degree to which variability in tailoring their implementation to different contexts may influence lifespan.

Method: Women (N = 54,353; M= 47) completed a validated coping inventory and reported covariate information in 2001.

The Synthesis of Biphasic Metabolites of Carfentanil.

Carfentanil is an ultra-potent synthetic opioid. The Russian police force used both carfentanil and remifentanil to resolve a hostage incident in Moscow. This reported use sparked an interest in the pharmacology and toxicology of carfentanil in the human body, and data on its metabolites were later published.

Estimated effects of amyloid reduction on cognitive change: A Bayesian update across a range of priors.

Introduction: The results of the CLARITY-AD, GRADUATE I and II, and TRAILBLAZER-ALZ 2 trials have rekindled discussion on the impact of amyloid-targeting drugs. We use a Bayesian approach to quantify how rational observers would have updated their prior beliefs based on new trial results.

Methods: We used publicly available data from the CLARITY-AD, GRADUATE I and II, and TRAILBLAZER-ALZ 2 trials to estimate the effect of reducing amyloid on the clinical dementia rating scale, sum of boxes (CDR-SB) score.

Association of cancer history with structural brain aging markers of Alzheimer's disease and related dementias risk.

Introduction: Cancer survivors are less likely than comparably aged individuals without a cancer history to develop Alzheimer's disease and related dementias (ADRD).

Methods: In the UK Biobank, we investigated associations between cancer history and five structural magnetic resonance imaging (MRI) markers for ADRD risk, using linear mixed-effects models to assess differences in mean values and quantile regression to examine whether associations varied across the distribution of MRI markers.

Results: Cancer history was associated with smaller mean hippocampal volume (b = -19 mm , 95% CI = -36, -1) and lower mean cortical thickness in the Alzheimer's disease signature region (b = -0.

Timing and level of educational attainment and late-life cognition in the KHANDLE study.

Introduction: The timing of educational attainment may modify its effects on late-life cognition, yet most studies evaluate education only at a single time point.

Methods: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study cohort participants (N = 554) reported educational attainment (dichotomized at any college education) at two time points, and we classified them as having low, high, or later-life high educational attainment. Linear mixed-effects models estimated associations between educational attainment change groups and domain-specific cognitive outcomes (z-standardized).

Cost-effectiveness analysis of transarterial chemoembolization combined with lenvatinib as the first-line treatment for advanced hepatocellular carcinoma.

Results from the LAUNCH trial suggest transarterial chemoembolization (TACE) in combination with lenvatinib is significantly more effective than lenvatinib as a first-line treatment option for advanced hepatocellular carcinoma (HCC). However, the cost of TACE is substantial. This study compares the cost-effectiveness of TACE in combination with lenvatinib (TACE-LEN) with that of lenvatinib alone as the first-line treatment for advanced HCC from the perspective of the Chinese healthcare system.

Cost-effectiveness analysis of zolbetuximab plus mFOLFOX6 as the first-line treatment for CLDN18.2-positive, HER2-negative advanced gastric or Gastroesophageal Adenocarcinoma.

The SPOTLIGHT trial demonstrated that zolbetuximab plus mFOLFOX6 (ZOL-FO) as a first-line regimen compared with placebo plus mFOLFOX6 (PLB-FO) conferred clinical benefits to patients with CLDN18.2-positive, HER2-negative advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. However, due to the high cost of zolbetuximab, whether ZOL-FO is cost-effective compared with PLB-FO is unclear.

The Mediating Roles of Neurobiomarkers in the Relationship Between Education and Late-Life Cognition.

Background: The mediating roles of neuropathologies and neurovascular damage in the relationship between early-life education and later-life cognitive function are unknown.

Objective: To examine whether Alzheimer's and neurovascular biomarkers mediate the relationships between education and cognitive functions.

Methods: Data were from 537 adults aged 55-94 in the Alzheimer's Disease Neuroimaging Initiative 3.

The cost-effectiveness of cemiplimab plus chemotherapy as the first-line treatment for advanced non-small cell lung cancer.

The EMPOWER-LUNG 3 clinical trial has shown that cemiplimab plus chemotherapy (CCT) significantly extended overall survival (OS) and progression-free survival (PFS) for patients with advanced non-small cell cancer (NSCLC) compared to placebo plus chemotherapy (PCT). However, the cost-effectiveness of this new treatment option remains unknown. Thus, we evaluated the cost-effectiveness of CCT versus (vs.

Excess Mortality With Alzheimer Disease and Related Dementias as an Underlying or Contributing Cause During the COVID-19 Pandemic in the US.

Importance: Adults with Alzheimer disease and related dementias (ADRD) are particularly vulnerable to the direct and indirect effects of the COVID-19 pandemic. Deaths associated with ADRD increased substantially in pandemic year 1. It is unclear whether mortality associated with ADRD declined when better prevention strategies, testing, and vaccines became widely available in year 2.

Effects of Induced Optimism on Subjective States, Physical Activity, and Stress Reactivity.

This study examined effects of experimentally-induced optimism on physical activity and stress reactivity with community volunteers. Using an intervention to induce short-term optimism, we conducted two harmonized randomized experiments, performed simultaneously at separate academic institutions. All participants were randomized to either the induced optimism intervention or to a neutral control activity using essay-writing tasks.

Estimated Effects of Amyloid Reduction on Cognitive Change: A Bayesian Update across a Range of Priors.

Introduction: Results of the CLARITY-AD and GRADUATE I and II trials rekindled discussion on the impact of amyloid-targeting drugs. We use a Bayesian approach to quantify how a rational observer would have updated their prior beliefs based on new trial results.

Methods: We used publicly available data from the CLARITY-AD and GRADUATE I & II trials to estimate the effect of reducing amyloid on CDR-SB score.

Pragmatic approaches to handling practice effects in longitudinal cognitive aging research.

Introduction: The challenge of accounting for practice effects (PEs) when modeling cognitive change was amplified by the COVID-19 pandemic, which introduced period and mode effects that may bias the estimation of cognitive trajectory.

Methods: In three Kaiser Permanente Northern California prospective cohorts, we compared predicted cognitive trajectories and the association of grip strength with cognitive decline using three approaches: (1) no acknowledgment of PE, (2) inclusion of a wave indicator, and (3) constraining PE based on a preliminary model (APM) fit using a subset of the data.

Results: APM-based correction for PEs based on balanced, pre-pandemic data, and with current age as the timescale produced the smallest discrepancy between within-person and between-person estimated age effects.

COVID-19 Mortality by Race and Ethnicity in US Metropolitan and Nonmetropolitan Areas, March 2020 to February 2022.

Importance: Prior research has established that Hispanic and non-Hispanic Black residents in the US experienced substantially higher COVID-19 mortality rates in 2020 than non-Hispanic White residents owing to structural racism. In 2021, these disparities decreased.

Objective: To assess to what extent national decreases in racial and ethnic disparities in COVID-19 mortality between the initial pandemic wave and subsequent Omicron wave reflect reductions in mortality vs other factors, such as the pandemic's changing geography.