Dyadic Appraisals of Family Decisions and Health Tasks in Midlife-Older Couples.

Shared appraisals and collaboration within couples play important roles in optimizing health. Less is known about concordance regarding collaboration, factors associated with concordance, and implications for health. Data from 2,761 couples from the Health and Retirement Study (2014/2016 and 2016/2018 waves) were examined to determine within-couple concordance in completion of two tasks (family decisions and medical forms). The majority of couples were concordant regarding who makes family decisions (69.7%) and who completes medical forms (64.4%); 62% agreed they make family decisions collaboratively versus 25.5% completing medical forms collaboratively. Concordance was significantly associated with greater marital support and longer marital duration. Concordance was not significantly associated with depressive symptoms 2 years later, but the link between concordance in making major family decisions and self-rated health differed by age and gender. Future research at the intersection of concordance and collaboration may shed important light on how older couples navigate tasks and decisions.

Potential Inflammatory Markers Related to the Conversion to Alzheimer's Disease in Female Patients With Late-Life Depression.

Background: Inflammation has been postulated as a mediating factor in the development of Alzheimer's disease (AD) pathology. We investigated candidate inflammatory markers related to conversion to AD among patients with depression. Methods: A longitudinal study was conducted with older women with depression who were at least 55 years of age, with a mean follow-up period of 5.73 years. At baseline, 9 inflammatory cytokines were measured using the immunoreactivity method. During follow-up, patients with depression who complained of cognitive impairment were evaluated and diagnosed with AD conversion. Association of the cytokines with conversion to AD was analyzed using multivariable Cox proportional hazards regression with adjusting covariates. For clinical applicability, the optimal cutoff value was determined using the minimum p value approach for the conversion to AD and was used to plot an AD-free survival curve. Results: Among 132 participants, 34 patients with depression (25.76%) developed AD during their follow-up period. Higher levels of interleukin (IL) 1ß at baseline (hazard ratio = 3.30 [95% CI, 1.11-9.78], p = .031) and lower levels of IL-10 (p < .001) were significantly associated with an increased risk of progression to AD. The survival curve plotted by the cutoff value of ≥0.25 pg/mL for IL-1ß and ≤0.15 pg/mL for IL-10 suggested adjusted hazard ratios of 8.96 (95% CI, 3.48-23.09; p < .001) for IL-1ß and 10.99 (p < .001) for IL-10, respectively. Conclusions: This study demonstrated that IL-1ß and IL-10 were associated with conversion to AD among patients with late-life depression, suggesting their potential as predictive markers of the transition to AD from depression.

Many patients with depression, more than expected, have been observed to be converted to Alzheimer's disease (AD) in the real world. We investigated potential inflammatory blood surrogate markers regarding progression from depression in late life to AD in 132 older Korean women with depression over a period of 1 to 18 years. Higher levels of the proinflammatory cytokine IL-1ß and lower levels of the anti-inflammatory cytokine IL-10 were associated with a higher risk of transition from depression to AD. These findings suggest that these markers could serve to predict the onset of AD in individuals with depression.

Analysis of eligibility criteria in Alzheimer's and related dementias clinical trials.

Overly restrictive clinical trial eligibility criteria can reduce generalizability, slow enrollment, and disproportionately exclude historically underrepresented populations. The eligibility criteria for 196 Alzheimer's Disease and Related Dementias (AD/ADRD) trials funded by the National Institute on Aging were analyzed to identify common criteria and their potential to disproportionately exclude participants by race/ethnicity. The trials were categorized by type (48 Phase I/II pharmacological, 7 Phase III/IV pharmacological, 128 non-pharmacological, 7 diagnostic, and 6 neuropsychiatric) and target population (51 AD/ADRD, 58 Mild Cognitive Impairment, 25 at-risk, and 62 cognitively normal). Eligibility criteria were coded into the following categories: Medical, Neurologic, Psychiatric, and Procedural. A literature search was conducted to describe the prevalence of disparities for eligibility criteria for African Americans/Black (AA/B), Hispanic/Latino (H/L), American Indian/Alaska Native (AI/AN) and Native Hawaiian/Pacific Islander (NH/PI) populations. The trials had a median of 15 criteria. The most frequent criterion were age cutoffs (87% of trials), specified neurologic (65%), and psychiatric disorders (61%). Underrepresented groups could be disproportionately excluded by 16 eligibility categories; 42% of trials specified English-speakers only in their criteria. Most trials (82%) contain poorly operationalized criteria (i.e., criteria not well defined that can have multiple interpretations/means of implementation) and criteria that may reduce racial/ethnic enrollment diversity.

Cultural values and parental psychology: A multilevel analysis from the Joint Effort Toddler Temperament Consortium.

The present study aims to gain a greater understanding of the manner in which culture may impact parenting and, thus, child development by examining the relationship between cultural values, socialization goals (SGs), and parental ethnotheories (PEs). Specifically, this study examined links between cultural value dimensions (i.e., individualism/collectivism, power distance, masculinity/femininity, uncertainty avoidance, indulgence/restraint, and long-term/short-term orientation; Hofstede et al., 2010) and autonomous as well as relational SGs and PEs. We examined data collected from mothers of toddlers (N = 865) between 17 and 40 months of age (M = 26.88 months, SD = 5.65 months; 52% boys) from 14 nations represented in the Joint Effort Toddler Temperament Consortium. We hypothesized that: (a) Cultural values consistent with independent cultural ideals would be positively associated with SGs and PEs representative of greater autonomy and independence, and (b) Cultural values consistent with interdependent ideals would be positively associated with SGs and PEs representative of greater interrelatedness. Multilevel modeling was used to regress parental psychology on Hofstede's cultural values. Support for these hypotheses was somewhat mixed; higher ratings of culture-level indulgence were associated with higher autonomous PEs, as well as with higher relational and autonomous SGs. Furthermore, higher ratings of culture-level masculinity were associated with lower relational PEs and with lower autonomous SGs. The results suggest differences in the effects for cultural values associated with parenting versus cultural values associated with child outcomes and highlight considerations related to dichotomous cultural frameworks. The findings help explain both individual- and country-level variations in aspects of parental psychology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Clinicopathological and molecular features of genome-stable colorectal cancers.

Colorectal cancers (CRCs) are traditionally divided into those with either chromosomal instability (CIN) or microsatellite instability (MSI). By utilizing TCGA data, the Laird team found a subset of CRCs, namely, genome-stable CRCs (GS CRCs), which lack both CIN and MSI. Although the molecular features of GS CRCs have been described in detail, the clinicopathological features are not well defined. A total of 437 CRCs were analyzed for copy number variation (CNV) statuses in eight genes (ARID1A, EGFR, FGFR1, KDM5B, MYBL2, MYC, SALL4, and SETDB1) using droplet-digital PCR. CRCs that showed CNV in ≤ one gene and no MSI were defined as GS-like CRCs. Clinicopathological and molecular features of GS-like CRCs were compared with those of CIN-like CRCs. GS-like CRCs comprised 4.6% of CRCs and showed a predilection toward the proximal colon, lower nuclear optical density, KRAS mutation, PIK3CA mutation, and aberrant expression of KRT7. Survival analysis showed no significant difference between the three subgroups. Through our study, the GS-like subtype was found to comprise a minor proportion of CRCs and have proclivity toward a proximal bowel location, hypochromatic tumor nuclei, aberrant KRT7 expression, and a high frequency of KRAS and PIK3CA mutations.

Pragmatic nationwide master observational trial based on genomic alterations in advanced solid tumors: KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II study protocol KCSG AL-22-09.

BACKGROUND: Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform. METHODS: The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment. DISCUSSION: This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers. TRIAL REGISTRATION: NCT05525858.

Effectiveness of a healthy lifestyle program based on a mobile serious game for childhood cancer survivors: A quasi-randomized trial.

PURPOSE: This study aimed to develop and evaluate the effectiveness of a healthy lifestyle program based on a mobile serious game (HLP-MSG) to enhance the lifestyles of childhood cancer survivors (CCSs). METHODS: This program proceeded in two stages: development and evaluation, using a non-synchronized design with a quasi-randomized trial. The participants were CCSs aged 6-13 years whose treatment was terminated at least 12 months prior. Data were collected at baseline, and post-intervention, with a follow-up after four weeks using the Child Healthy Lifestyle Profile (CHLP). The experimental (n = 26) and control groups (n = 25) were compared. Data were analyzed using descriptive statistics, chi-squared tests, t-tests, and repeated-measures ANOVA. RESULTS: The HLP-MSG promoted a healthy lifestyle by solving 26 quests, including seven sub-elements (nutrition, exercise, hygiene, interpersonal relationships, stress management, meaning of life, and health responsibility). This study revealed significant differences in the interaction between measurement time and group assignment in the CHLP (p = .006) and physical activity (p = .013), one of the seven sub-dimensions. CONCLUSIONS: A healthy lifestyle program based on a mobile serious game is a feasible health education modality to enhance the physical, psychological, social, and spiritual health of CCSs. IMPLICATIONS TO PRACTICE: The findings add to scientific evidence on a mobile serious game for health education among CCSs. The HLP-MSG provides an evolutionary educational modality that can be delivered non-face-to-face to promote CCSs' continuous healthy behavior maintenance. Moreover, the HLP-MSG is adolescent-friendly and can be utilized as a healthcare tool for parents and children to cooperate.

Heterogeneous Effects of Volunteering on Frailty in Later Life: A Panel Quantile Regression Approach.

OBJECTIVES: Decades of research indicate that volunteering is associated with better health for the volunteer beyond the selection effects based on health. However, little is known about potential heterogeneity in health outcomes associated with volunteering in the context of good or poor health. This study addresses this gap by focusing on the frailty index (FI) to investigate the volunteering-health nexus across the population frailty distribution ranging from fit to frail. METHODS: Using nationally representative data from the Health and Retirement Study (person N = 34,986; 198,218 person-wave observations), we estimated unconditional quantile regression models with panel fixed effects to estimate changes in FI associated with changes in the share of volunteers in the population across the frailty distribution observed across the study period (1998-2020). RESULTS: Our findings demonstrated that the volunteering-FI association was heterogeneous across the frailty distribution. The association was the most potent at the higher end of the frailty distribution, suggesting that efforts to promote volunteering may yield greater benefits for older adults experiencing high levels of frailty. DISCUSSION: The current study findings provide unique and compelling evidence in support of earlier calls for considering volunteering as a public health intervention. The study findings are discussed in the context of population health outcomes and health disparities.

Do friends get under the skin?: Everyday social encounters and cardiovascular functioning among Black and White adults in the United States.

OBJECTIVE: Studies have shown that contact with friends enhances emotional health, but little is known about whether friends influence cardiovascular health. This study investigated (a) whether encounters with friends and the quality of these encounters were associated with cardiovascular reactivity in everyday life and (b) whether these associations varied by race. METHOD: Participants were from the Stress and Well-being in Everyday Life Study which included Black (n = 76; aged = 34-76) and White (n = 87, aged = 34-91) adults residing in the United States. Participants provided background and social network information in a baseline interview, followed by a 4-day ecological momentary assessment in which they reported social encounters every 3 hr. Concurrently, participants wore an electrocardiogram monitor which collected physiological data in real time. To assess cardiovascular reactivity, heart rate variability (HRV) was analyzed. RESULTS: Multilevel models revealed that at times when individuals encountered friends (particularly positive encounters), they exhibited a momentary reduction in HRV (within-person association). But those with more friend encounters during the study period (particularly positive encounters) had higher HRV than those with fewer friend encounters during the study period (between-person association). These links were observed only among Black adults, but not among White adults. CONCLUSIONS: This study contributes to the conceptual model of social integration and enriches the literature on racial disparities in cardiovascular health from a social perspective. Findings highlight the implications of engagement with friends for momentary cardiovascular reactivity and suggest that friends may be more salient for Black adults' cardiovascular health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial.

KRAS G12C mutation is prevalent in ~4% of colorectal cancer (CRC) and is associated with poor prognosis. Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C-positive CRC at 400 mg. Epidermal growth factor receptor has been recognized as a major upstream activator of RAS-MAPK signaling, a proposed key mechanism of resistance to KRAS G12C inhibition in CRC. Here, we report on divarasib plus cetuximab (epidermal growth factor receptor inhibitor) in patients with KRAS G12C-positive CRC (n = 29) from arm C of an ongoing phase 1b trial. The primary objective was to evaluate safety. Secondary objectives included preliminary antitumor activity. The safety profile of this combination was consistent with those of single-agent divarasib and cetuximab. Treatment-related adverse events led to divarasib dose reductions in four patients (13.8%); there were no treatment withdrawals. The objective response rate was 62.5% (95% confidence interval: 40.6%, 81.2%) in KRAS G12C inhibitor-naive patients (n = 24). The median duration of response was 6.9 months. The median progression-free survival was 8.1 months (95% confidence interval: 5.5, 12.3). As an exploratory objective, we observed a decline in KRAS G12C variant allele frequency associated with response and identified acquired genomic alterations at disease progression that may be associated with resistance. The manageable safety profile and encouraging antitumor activity of divarasib plus cetuximab support the further investigation of this combination in KRAS G12C-positive CRC.ClinicalTrials.gov identifier: NCT04449874.

A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer.

PURPOSE: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). MATERIALS AND METHODS: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. RESULTS: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). CONCLUSION: GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Revisiting the caregiver stress process: Does family caregiving really lead to worse mental health outcomes?

While the act of caregiving is often characterized as a stressful experience detrimental to mental health, recent studies are challenging this view by reporting robust health and well-being benefits linked to family caregiving. The current study attempted to provide an explanation of this apparent paradox by focusing on the role played by family health problems in the association between being a caregiver and mental health. Framed within the life course perspective and focusing on caregiving provided to aging mothers, the current study aimed 1) to demonstrate how the linkage between caregiving and depression reported in earlier studies may be misleading and 2) to further investigate whether caregiving to an aging mother may lead to any mental health benefits. Using longitudinal data drawn from the nationally representative US Health and Retirement Study, I follow adult children 50 and older who had a living mother during the observation period (N = 4812; 18,442 person-wave observations). A series of within-between random effects models were estimated to explicate how health conditions of aging mothers (i.e., disability and dementia) and caregiving transitions of adult children were associated with changes in depressive symptoms of adult children. Findings demonstrated that caregiving transitions were unrelated to depressive symptoms among adult children once the model controlled for the confounding effects of having their mother experience disability and dementia. Further, caregiving behavior was found to buffer the direct detrimental effect of maternal disability on adult children's depressive symptoms. This study adds to the growing body of research that cautions against characterizing caregiving as a chronic stressor detrimental to mental health and further echoes earlier calls for a more balanced portrayal of caregiving in policy reports and research literature.

Interplay between Local Moment and Itinerant Magnetism in the Layered Metallic Antiferromagnet TaFe1.14Te3.

Two-dimensional antiferromagnets have garnered considerable interest for the next generation of functional spintronics. However, many bulk materials from which two-dimensional antiferromagnets are isolated are limited by their air sensitivity, low ordering temperatures, and insulating transport properties. TaFe1+yTe3 aims to address these challenges with increased air stability, metallic transport, and robust antiferromagnetism. Here, we synthesize TaFe1+yTe3 (y = 0.14), identify its structural, magnetic, and electronic properties, and elucidate the relationships between them. Axial-dependent high-field magnetization measurements on TaFe1.14Te3 reveal saturation magnetic fields ranging between 27 and 30 T with saturation magnetic moments of 2.05-2.12 µB. Magnetotransport measurements confirm that TaFe1.14Te3 is metallic with strong coupling between magnetic order and electronic transport. Angle-resolved photoemission spectroscopy measurements across the magnetic transition uncover a complex interplay between itinerant electrons and local magnetic moments that drives the magnetic transition. We demonstrate the ability to isolate few-layer sheets of TaFe1.14Te3, establishing TaFe1.14Te3 as a potential platform for two-dimensional spintronics.

Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation.

BACKGROUND: Divarasib (GDC-6036) is a covalent KRAS G12C inhibitor that was designed to have high potency and selectivity. METHODS: In a phase 1 study, we evaluated divarasib administered orally once daily (at doses ranging from 50 to 400 mg) in patients who had advanced or metastatic solid tumors that harbor a KRAS G12C mutation. The primary objective was an assessment of safety; pharmacokinetics, investigator-evaluated antitumor activity, and biomarkers of response and resistance were also assessed. RESULTS: A total of 137 patients (60 with non-small-cell lung cancer [NSCLC], 55 with colorectal cancer, and 22 with other solid tumors) received divarasib. No dose-limiting toxic effects or treatment-related deaths were reported. Treatment-related adverse events occurred in 127 patients (93%); grade 3 events occurred in 15 patients (11%) and a grade 4 event in 1 patient (1%). Treatment-related adverse events resulted in a dose reduction in 19 patients (14%) and discontinuation of treatment in 4 patients (3%). Among patients with NSCLC, a confirmed response was observed in 53.4% of patients (95% confidence interval [CI], 39.9 to 66.7), and the median progression-free survival was 13.1 months (95% CI, 8.8 to could not be estimated). Among patients with colorectal cancer, a confirmed response was observed in 29.1% of patients (95% CI, 17.6 to 42.9), and the median progression-free survival was 5.6 months (95% CI, 4.1 to 8.2). Responses were also observed in patients with other solid tumors. Serial assessment of circulating tumor DNA showed declines in KRAS G12C variant allele frequency associated with response and identified genomic alterations that may confer resistance to divarasib. CONCLUSIONS: Treatment with divarasib resulted in durable clinical responses across KRAS G12C-positive tumors, with mostly low-grade adverse events. (Funded by Genentech; ClinicalTrials.gov number, NCT04449874.).

Total neoadjuvant therapy with short-course radiotherapy Versus long-course neoadjuvant chemoradiotherapy in Locally Advanced Rectal cancer, Korean trial (TV-LARK trial): study protocol of a multicentre randomized controlled trial.

BACKGROUND: For locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT) may enhance tumour response, reduce recurrence, and improve patient compliance compared to upfront surgery. Recent studies have shown that chemoradiotherapy (CRT) followed by consolidation chemotherapy leads to higher rate of pathologic complete response (pCR) than induction chemotherapy followed by CRT. However, an optimal TNT regimen that maximise the pCR rate and minimise toxicity has not been established. Therefore, the aim of this trial was to investigate whether preoperative short-course radiotherapy followed by chemotherapy with four cycles of CAPOX can double the pCR rate compared to a standard schedule of long-course preoperative CRT in patients with LARC. METHODS: This is a multi-centre, prospective, open label, randomised controlled trial. Patients with clinical primary tumour stage 3 and higher or regional node-involved rectal cancer located within 10 cm from the anal verge were randomly assigned equally to short-course radiotherapy (25 Gy in 5 fractions over 1 week) followed by four cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) (TNT) or CRT (50.4 Gy in 28 fractions over 5 weeks, concurrently with concomitant oral capecitabine 825 mg/m2 twice a day). After preoperative treatment, total mesorectal excision was performed 2-4 weeks in the TNT group and 6-10 weeks in the CRT group, followed by optional additional adjuvant chemotherapy. The primary endpoint is the pCR rate, and secondary endpoints include disease-related treatment failure, quality of life, and cost-effectiveness. Assuming a pCR rate of 28% and 15% in the TNT and CRT groups, respectively, and one-side alpha error rate of 0.025 and power of 80%, 348 patients will be enrolled considering 10% dropout rate. DISCUSSION: The TV-LARK trial will evaluate the superiority of employed TNT regimen against the standard CRT regimen for patients with LARC. We aimed to identify a TNT regimen that will improve the pCR rate and decrease systemic recurrence in these patients. TRIAL REGISTRATION: Cris.nih.go.kr ID: KCT0007169 (April 08, 2022). The posted information will be updated as needed to reflect the protocol amendments and study progress.

Epigenetic insights into colorectal cancer: comprehensive genome-wide DNA methylation profiling of 294 patients in Korea.

DNA methylation regulates gene expression and contributes to tumorigenesis in the early stages of cancer. In colorectal cancer (CRC), CpG island methylator phenotype (CIMP) is recognized as a distinct subset that is associated with specific molecular and clinical features. In this study, we investigated the genomewide DNA methylation patterns among patients with CRC. The methylation data of 1 unmatched normal, 142 adjacent normal, and 294 tumor samples were analyzed. We identified 40,003 differentially methylated positions with 6,933 (79.8%) hypermethylated and 16,145 (51.6%) hypomethylated probes in the genic region. Hypermethylated probes were predominantly found in promoter-like regions, CpG islands, and N shore sites; hypomethylated probes were enriched in open-sea regions. CRC tumors were categorized into three CIMP subgroups, with 90 (30.6%) in the CIMP-high (CIMP-H), 115 (39.1%) in the CIMP-low (CIMP-L), and 89 (30.3%) in the non-CIMP group. The CIMP-H group was associated with microsatellite instabilityhigh tumors, hypermethylation of MLH1, older age, and rightsided tumors. Our results showed that genome-wide methylation analyses classified patients with CRC into three subgroups according to CIMP levels, with clinical and molecular features consistent with previous data. [BMB Reports 2023; 56(10): 563-568].

Volunteering and Changes in Cardiovascular Biomarkers: Longitudinal Evidence From the Health and Retirement Study.

Background and Objectives: Growing body of research shows that volunteering is beneficial for those served, the volunteers, and the larger communities. However, major challenges remain that hinder the practical implications for volunteer activity as a public health intervention, including potential selection effects, lack of longitudinal studies that adjust for baseline characteristics, and a paucity of studies that consider multiple physical health outcomes in a single model. Research Design and Methods: Data from 2006 to 2016 waves of the Health and Retirement Study (2006-2016) were used (N = 18,847). Outcome-wide analyses were utilized to evaluate if changes in volunteering between 2006/2008 (t0) and 2010/2012 (t1) were associated with 7 cardiovascular disease biomarkers 4 years later (2014/2016, t2). These models were adjusted for demographic factors, socioeconomic status, health behaviors, chronic conditions, baseline biomarkers, and volunteering. Additionally, selection into volunteering and attrition were taken into account. Results: Compared with nonvolunteers, volunteering more than 200 hr a year was associated with a lower risk for clinically high diastolic blood pressure. In addition, increased volunteering effort (change from 1 to 99 hr at t0 to >100 hr at t1) was associated with a lower likelihood of clinically high systolic and diastolic blood pressure levels. Sustained high volunteering (>100 hr at both t0 and t1) was associated with lower diastolic blood pressure. Discussion and Implications: The current study adds to the evidence on the health benefits of volunteering for adults 50 and older by inferring a potential causal link between high-intensity volunteering and reduced blood pressure.

Neighborhood Cohesion Across the Life Course and Effects on Cognitive Aging.

OBJECTIVES: Greater neighborhood cohesion is associated with better cognitive function in adulthood and may serve as a protective factor against cognitive impairment and decline. We build on prior work by examining the effects of perceived neighborhood cohesion across the life course on level and change in cognitive function in adulthood. METHODS: Utilizing longitudinal data from the Health and Retirement Study (1998-2016) and its Life History Mail Survey, we leveraged data from 3,599 study participants (baseline age: 51-89) who participated in up to 10 waves. Respondents provided retrospective ratings of neighborhood cohesion at childhood (age 10), young adulthood (age at the first full-time job), early midlife (age 40), and concurrently at baseline (i.e., late midlife/adulthood); they completed the modified version of the Telephone Interview for Cognitive Status. We fit a univariate latent growth curve model of change in cognitive function across waves and tested whether neighborhood cohesion during each recollected life stage predicted level and change in cognitive function. RESULTS: Greater neighborhood cohesion during childhood and late midlife/adulthood each predicted higher cognitive function at baseline but not the rate of cognitive decline. The final model showed that greater neighborhood cohesion in childhood and in late midlife/adulthood remained significantly associated with higher baseline cognitive function, even after accounting for one another. DISCUSSION: Findings provide insight into life-course neighborhood contextual influences on cognitive aging. Our results emphasize the need for more research to understand the life-course dynamics between neighborhood environments and cognitive aging.

Personalised circulating tumour DNA assay with large-scale mutation coverage for sensitive minimal residual disease detection in colorectal cancer.

BACKGROUND: Postoperative minimal residual disease (MRD) detection using circulating-tumour DNA (ctDNA) requires a highly sensitive analysis platform. We have developed a tumour-informed, hybrid-capture ctDNA sequencing MRD assay. METHODS: Personalised target-capture panels for ctDNA detection were designed using individual variants identified in tumour whole-exome sequencing of each patient. MRD status was determined using ultra-high-depth sequencing data of plasma cell-free DNA. The MRD positivity and its association with clinical outcome were analysed in Stage II or III colorectal cancer (CRC). RESULTS: In 98 CRC patients, personalised panels for ctDNA sequencing were built from tumour data, including a median of 185 variants per patient. In silico simulation showed that increasing the number of target variants increases MRD detection sensitivity in low fractions (<0.01%). At postoperative 3-week, 21.4% of patients were positive for MRD by ctDNA. Postoperative positive MRD was strongly associated with poor disease-free survival (DFS) (adjusted hazard ratio 8.40, 95% confidence interval 3.49-20.2). Patients with a negative conversion of MRD after adjuvant therapy showed significantly better DFS (P < 0.001). CONCLUSION: Tumour-informed, hybrid-capture-based ctDNA assay monitoring a large number of patient-specific mutations is a sensitive strategy for MRD detection to predict recurrence in CRC.

Predicting the chemotherapeutic response of colorectal cancer liver metastasis using shear-wave elastography.

PURPOSE: The aim of this study was to assess the role of the shear-wave velocity (SWV) value in predicting chemotherapeutic response and progression-free survival (PFS) in patients with colorectal cancer liver metastasis (CRLM). METHODS: In this prospective single-center study, participants with CRLM scheduled for chemotherapy were enrolled between May 2018 and June 2021. SWV measurements were obtained using shear-wave elastography at the CRLM site before and after initiating chemotherapy. Based on the Response Evaluation Criteria in Solid Tumors, the participants were categorized by chemotherapeutic response into responders (complete remission and partial remission) and non-responders (stable disease and progressive disease). Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the performance of changes in SWV measurements in predicting the chemotherapeutic response of CRLM. In addition, a Cox proportional hazards model was used to identify variables associated with PFS. RESULTS: In total, 67 participants (40 men; mean age, 62.3±10.1 years) were enrolled, including 34 responders and 33 non-responders. The area under the ROC curve, sensitivity, and negative predictive value of the SWV measurement in predicting non-responders were 0.840, 97.0%, and 95.2%, respectively, using a cutoff value of a 13% decrease. Additionally, a change in SWV values was independently associated with PFS (hazard ratio, 1.020), non-responder status, and the presence of five or more CRLMs. CONCLUSION: A change in SWV values measured after chemotherapy demonstrated meaningful diagnostic performance in predicting non-responsiveness among patients with CRLM. Additionally, a change in SWV values was independently associated with PFS.