Therapeutic benefits of maintaining CDK4/6 inhibitors and incorporating CDK2 inhibitors beyond progression in breast cancer.

The combination of CDK4/6 inhibitors (CDK4/6i) and endocrine therapy has revolutionized treatment for hormone receptor-positive (HR+) metastatic breast cancer. However, the emergence of resistance in most patients often leads to treatment discontinuation with no consensus on effective second-line therapies. The therapeutic benefits of maintaining CDK4/6i or incorporating CDK2 inhibitors (CDK2i) after disease progression remain unclear.

Caregiving-Related Depression Increases Neuroinflammation in Spousal Caregivers to Individuals With Cognitive Impairment: A Longitudinal Study.

Background: The caregiving burden of the spousal caregivers (SCGs) to individuals with cognitive impairment poses public health challenges with adverse psychosocial and physiological effects. However, few studies have investigated the neurobiological impact of caregiving, particularly through the investigation of neuroinflammation and neurodegeneration.

Methods: Using data from a longitudinal cohort at Chungnam National University Hospital, the relationship between caregiving burden, neuroinflammation, and neurodegeneration was examined in 38 older adult couples over a 16-month period.

Reliability and Validity of a Tablet-Based Neuropsychological Test (the Hellocog) for Screening Dementia.

Objective: To address the gap in timely diagnosis of dementia due to limited screening tools, we investigated the validity and reliability of the Hellocog, computerized neuropsychological test based on tablets for screening dementia. The higher the probability score on the Hellocog, the higher the likelihood of dementia.

Methods: This study included 100 patients with dementia and 100 individuals with normal cognition who were aged 60 years or older and free of other major psychiatric, neurological, or medical conditions.

Investigating Heterogeneous Cell-Cycle Progression Using Single-Cell Imaging Approaches.

Investigating cell-cycle progression has been challenging due to the complex interconnectivity of regulatory processes and inherent cell-to-cell heterogeneity, which often require synchronization procedures. However, recent advancements in cell-cycle sensors and single-cell imaging techniques have turned this heterogeneity into an advantage for investigating the molecular mechanisms underlying diverse responses. This has led to significant progress in our understanding of cell-cycle regulation.

Exploring age-related changes in saccades during cognitive tasks in healthy adults.

Introduction: Although eye movements such as saccades are related to internal cognitive processes and are independent of visual processing, few studies have investigated whether non-visual cognitive tasks simultaneously affect horizontal and vertical saccades in younger and older adults.

Methods: We recruited 28 younger adults aged 20-29 years and 26 older adults aged >60 years through advertisements in community settings. All participants were free of major psychiatric, neurological, or ocular diseases.

Non-canonical pathway for Rb inactivation and external signaling coordinate cell-cycle entry without CDK4/6 activity.

Cyclin-dependent kinases 4 and 6 (CDK4/6) are critical for initiating cell proliferation by inactivating the retinoblastoma (Rb) protein. However, mammalian cells can bypass CDK4/6 for Rb inactivation. Here we show a non-canonical pathway for Rb inactivation and its interplay with external signals.

Sequential activation of E2F via Rb degradation and c-Myc drives resistance to CDK4/6 inhibitors in breast cancer.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are key therapeutic agents in the management of metastatic hormone-receptor-positive breast cancer. However, the emergence of drug resistance limits their long-term efficacy. Here, we show that breast cancer cells develop CDK4/6i resistance via a sequential two-step process of E2F activation.

Angiopoietin-2 blockade suppresses growth of liver metastases from pancreatic neuroendocrine tumors by promoting T cell recruitment.

Improving the management of metastasis in pancreatic neuroendocrine tumors (PanNETs) is critical, as nearly half of patients with PanNETs present with liver metastases, and this accounts for the majority of patient mortality. We identified angiopoietin-2 (ANGPT2) as one of the most upregulated angiogenic factors in RNA-Seq data from human PanNET liver metastases and found that higher ANGPT2 expression correlated with poor survival rates. Immunohistochemical staining revealed that ANGPT2 was localized to the endothelial cells of blood vessels in PanNET liver metastases.

What is the impact of one's chronic illness on his or her spouse's future chronic illness: a community-based prospective cohort study.

Background: Integrating a joint approach to chronic disease management within the context of a couple has immense potential as a valuable strategy for both prevention and treatment. Although spousal concordance has been reported in specific chronic illnesses, the impact they cumulatively exert on a spouse in a longitudinal setting has not been investigated. We aimed to determine whether one's cumulative illness burden has a longitudinal impact on that of their spouse.

Predicting Survival Outcomes in Post-Cardiac Arrest Syndrome: The Impact of Combined Sequential Organ Failure Assessment Score and Serum Lactate Measurement.

BACKGROUND Post-cardiac arrest syndrome (PCAS) is a major concern and shares pathophysiology with sepsis. Sequential organ failure assessment (SOFA) scores and serum lactate levels, as suggested in the Survival Sepsis Guidelines, have shown significant predictive value for prognosis in patients with sepsis. This retrospective study aimed to evaluate combined use of the SOFA score and serum lactate measurement on survival prognosis in PCAS.

The impact of the COVID-19 pandemic on depression in community-dwelling older adults: a prospective cohort study.

Background: There are growing concerns about the impact of the COVID-19 pandemic on the mental health of older adults. We examined the effect of the pandemic on the risk of depression in older adults.

Methods: We analyzed data from the prospective cohort study of Korean older adults, which has been followed every 2 years.

Kinetics of RTK activation determine ERK reactivation and resistance to dual BRAF/MEK inhibition in melanoma.

The combination of BRAF and MEK inhibitors (BRAFi/MEKi) has shown promising response rates in treating BRAF-mutant melanoma by inhibiting ERK activation. However, treatment efficacy is limited by the emergence of drug-tolerant persister cells (persisters). Here, we show that the magnitude and duration of receptor tyrosine kinase (RTK) activation determine ERK reactivation and persister development.

Angiopoietin-2-Dependent Spatial Vascular Destabilization Promotes T-cell Exclusion and Limits Immunotherapy in Melanoma.

Unlabelled: T-cell position in the tumor microenvironment determines the probability of target encounter and tumor killing. CD8+ T-cell exclusion from the tumor parenchyma is associated with poor response to immunotherapy, and yet the biology that underpins this distinct pattern remains unclear. Here we show that the vascular destabilizing factor angiopoietin-2 (ANGPT2) causes compromised vascular integrity in the tumor periphery, leading to impaired T-cell infiltration to the tumor core.

A normative study of the gait features measured by a wearable inertia sensor in a healthy old population.

Background: Gait function impairments are associated with the risk of various medical conditions in older adults. As gait function declines with advancing age, normative data are required for proper interpretation of gait function in older adults.

Research Purpose: This study aimed to construct age-stratified normative data of non-dimensionally normalized temporal and spatial gait features in healthy older adults.

Shared Risk Factors for Depressive Disorder Among Older Adult Couples in Korea.

Importance: Although couples may share many risk factors for depressive disorders in their lifetime, whether these factors mediate the shared risk of depressive disorders has rarely been investigated.

Objectives: To identify the shared risk factors for depressive disorder in couples and investigate their mediating roles in the shared risk of depressive disorders among older adult couples.

Design, Setting, And Participants: This nationwide, multicenter, community-based cohort study assessed 956 older adults from the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) and a cohort of their spouses (KLOSCAD-S) between January 1, 2019, to February 28, 2021.

CDK4/6 initiates Rb inactivation and CDK2 activity coordinates cell-cycle commitment and G1/S transition.

External signaling controls cell-cycle entry until cells irreversibly commit to the cell cycle to ensure faithful DNA replication. This process is tightly regulated by cyclin-dependent kinases (CDKs) and the retinoblastoma protein (Rb). Here, using live-cell sensors for CDK4/6 and CDK2 activities, we propose that CDK4/6 initiates Rb inactivation and CDK2 activation, which coordinates the timing of cell-cycle commitment and sequential G1/S transition.

Association of Low Emotional and Tangible Support With Risk of Dementia Among Adults 60 Years and Older in South Korea.

Importance: The association between social support and dementia risk has been debated. Most previous prospective studies have not differentiated the subtypes of social support.

Objective: To examine whether the association between social support and risk of dementia differs by subtype of social support and by sex.

ES-RED (Early Seizure Recurrence in the Emergency Department) Calculator: A Triage Tool for Seizure Patients.

Seizure is a common neurological presentation in patients visiting the emergency department (ED) that requires time for evaluation and observation. Timely decision and disposition standards for seizure patients need to be established to prevent overcrowding in the ED and achieve patients' safety. Here, we conducted a retrospective cohort study to predict early seizure recurrence in the ED (ES-RED).

Association between serum free hemoglobin level and cerebral white matter hyperintensity volume in older adults.

The association between serum free hemoglobin (sfHb) level and white matter hyperintensity (WMH) volume is controversial. This study is to examine this association considering nonlinearity, sex dimorphism, and WMH type. We enrolled 704 older adults among the participants of the Korean Longitudinal Study on Cognitive Aging and Dementia and visitors to the Dementia Clinic of Seoul National University Bundang Hospital.

Exploration of Cognitive Outcomes and Risk Factors for Cognitive Decline Shared by Couples.

Importance: Although couples could share many risk factors of cognitive disorders in their lifetime, whether shared risk factors mediate the shared risk of cognitive disorders has rarely been investigated.

Objective: To identify the risk factors of cognitive decline shared within couples and investigate their mediating roles in the shared risk of cognitive disorders and cognitive functions within couples.

Design, Setting, And Participants: A prospective cohort study was launched in November 1, 2010, and 784 participants were followed up every 2 years until December 31, 2020.

Aurora kinase A inhibition reverses the Warburg effect and elicits unique metabolic vulnerabilities in glioblastoma.

Aurora kinase A (AURKA) has emerged as a drug target for glioblastoma (GBM). However, resistance to therapy remains a critical issue. By integration of transcriptome, chromatin immunoprecipitation sequencing (CHIP-seq), Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq), proteomic and metabolite screening followed by carbon tracing and extracellular flux analyses we show that genetic and pharmacological AURKA inhibition elicits metabolic reprogramming mediated by inhibition of MYC targets and concomitant activation of Peroxisome Proliferator Activated Receptor Alpha (PPARA) signaling.

The Impact of the COVID-19 Pandemic on Tourists' WTP: Using the Contingent Valuation Method.

This study estimated tourists' willingness to pay (WTP) for tourist sites or facilities in the prolonged COVID-19 pandemic by applying the dichotomous choice-contingent valuation method to two different tourism destination types. A survey was conducted among domestic tourists in South Korea who had visited destinations within the last six months. We conducted a logistic regression with 1283 effective samples.

Mood disorders increase mortality mainly through dementia: A community-based prospective cohort study.

Objective: The effects of mood disorders on mortality may be mediated by their effects on the risk of dementia, and interventions to reduce the occurrence of dementia may reduce their overall mortality. This study aimed to investigate the direct effects of depressive and bipolar disorders on the 6-year risk of mortality and also their indirect effects on mortality due to their effect on the risk of dementia.

Methods: A total of 5101 Koreans were selected from a community-based prospective cohort study, and 6-year risks of mortality and dementia in participants with depressive and bipolar disorders were estimated by Cox proportional hazard analysis.

Inhibitors of Coronavirus 3CL Proteases Protect Cells from Protease-Mediated Cytotoxicity.

We describe a mammalian cell-based assay to identify coronavirus 3CL protease (3CLpro) inhibitors. This assay is based on rescuing protease-mediated cytotoxicity and does not require live virus. By enabling the facile testing of compounds across a range of 15 distantly related coronavirus 3CLpro enzymes, we identified compounds with broad 3CLpro-inhibitory activity.