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Purpose: Cancer survivors commonly report cognitive declines after cancer therapy. Due to the complex etiology of cancer-related cognitive decline (CRCD), predicting who will be at risk of CRCD remains a clinical challenge. We developed a model to predict breast cancer survivors who would experience CRCD after systematic treatment., Methods: We used the Thinking and Living with Cancer study, a large ongoing multisite prospective study of older breast cancer survivors with complete assessments pre-systemic therapy, 12 months and 24 months after initiation of systemic therapy. Cognition was measured using neuropsychological testing of attention, processing speed, and executive function (APE). CRCD was defined as a 0.25 SD (of observed changes from baseline to 12 months in matched controls) decline or greater in APE score from baseline to 12 months (transient) or persistent as a decline 0.25 SD or greater sustained to 24 months. We used machine learning approaches to predict CRCD using baseline demographics, tumor characteristics and treatment, genotypes, comorbidity, and self-reported physical, psychosocial, and cognitive function., Results: Thirty-two percent of survivors had transient cognitive decline, and 41% of these women experienced persistent decline. Prediction of CRCD was good: yielding an area under the curve of 0.75 and 0.79 for transient and persistent decline, respectively. Variables most informative in predicting CRCD included apolipoprotein E4 positivity, tumor HER2 positivity, obesity, cardiovascular comorbidities, more prescription medications, and higher baseline APE score., Conclusions: Our proof-of-concept tool demonstrates our prediction models are potentially useful to predict risk of CRCD. Future research is needed to validate this approach for predicting CRCD in routine practice settings., (© The Author(s) 2024. Published by Oxford University Press.)

Bereavement increases in prevalence as people age and is associated with multiple psychological and health risks, including cardiovascular risk. Religious and existential variables may play an important role in the health impacts of bereavement. Theorized pathways linking religious and existential variables with health have suggested these associations are due to intermediary psychosocial variables, but have not been tested in bereavement. This research empirically tested these pathways in a bereaved population. In N = 73 adults within 1 year of bereavement (mean age = 64.36), this study examined associations between (1) religious and existential characteristics (religious and spiritual struggles, intrinsic religiosity, and existential quest) and intermediary psychosocial variables (depression, loneliness, and difficulties in emotion regulation), and between (2) intermediary psychosocial variables and bereavement-relevant health outcomes (self-reported health, change in health since last year, grief severity, and cardiovascular biomarkers). Cardiovascular biomarkers (heart rate, heart rate variability, and blood pressure) were collected before, during, and after a laboratory grief recall emotion elicitation. Anticipated associations between self-reported religious and existential characteristics and intermediary variables, and between intermediary variables and self-reported bereavement-relevant outcomes, were consistently observed. However, associations between intermediary variables and cardiovascular biomarkers were largely unobserved. This study examined the role of religious and existential variables in whole-person health after bereavement and is among the first to include biomarkers of cardiovascular risk. Results suggest that although religious and existential variables are associated with important bereavement-related outcomes, these associations may be "skin-deep," and extensions to cardiovascular functioning should be re-examined., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Purpose: Several studies have reported sleep disturbances during the COVID-19 virus pandemic. Little data exist about the impact of the pandemic on sleep and mental health among older women with breast cancer. We sought to examine whether women with and without breast cancer who experienced new sleep problems during the pandemic had worsening depression and anxiety., Methods: Breast cancer survivors aged ≥60 years with a history of nonmetastatic breast cancer (n = 242) and frequency-matched noncancer controls (n = 158) active in a longitudinal cohort study completed a COVID-19 virus pandemic survey from May to September 2020 (response rate 83%). Incident sleep disturbance was measured using the restless sleep item from the Center for Epidemiological Studies-Depression Scale (CES-D). CES-D score (minus the sleep item) captured depressive symptoms; the State-Anxiety subscale of the State Trait Anxiety Inventory measured anxiety symptoms. Multivariable linear regression models examined how the development of sleep disturbance affected changes in depressive or anxiety symptoms from the most recent prepandemic survey to the pandemic survey, controlling for covariates., Results: The prevalence of sleep disturbance during the pandemic was 22.3%, with incident sleep disturbance in 10% and 13.5% of survivors and controls, respectively. Depressive and anxiety symptoms significantly increased during the pandemic among women with incident sleep disturbance (vs. no disturbance) (β = 8.16, p < 0.01 and β = 6.14, p < 0.01, respectively), but there were no survivor-control differences in the effect., Conclusion: Development of sleep disturbances during the COVID-19 virus pandemic may negatively affect older women's mental health, but breast cancer survivors diagnosed with the nonmetastatic disease had similar experiences as women without cancer., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

A growing body of literature has emphasized the importance of biobehavioral processes - defined as the interaction of behavior, psychology, socioenvironmental factors, and biological processes - for clinical outcomes among transplantation and cellular therapy (TCT) patients. TCT recipients are especially vulnerable to distress associated with pandemic conditions and represent a notably immunocompromised group at greater risk for SARS-CoV-2 infection with substantially worse outcomes. The summation of both the immunologic and psychologic vulnerability of TCT patients renders them particularly susceptible to adverse biobehavioral sequelae associated with the Covid-19 pandemic. Stress and adverse psychosocial factors alter neural and endocrine pathways through sympathetic nervous system and hypothalamic-pituitary-adrenal axis signaling that ultimately affect gene regulation in immune cells. Reciprocally, global inflammation and immune dysregulation related to TCT contribute to dysregulation of neuroendocrine and central nervous system function, resulting in the symptom profile of depression, fatigue, sleep disturbance, and cognitive dysfunction. In this article, we draw upon literature on immunology, psychology, neuroscience, hematology and oncology, Covid-19 pathophysiology, and TCT processes to discuss how they may intersect to influence TCT outcomes, with the goal of providing an overview of the significance of biobehavioral factors in understanding the relationship between Covid-19 and TCT, now and for the future. We discuss the roles of depression, anxiety, fatigue, sleep, social isolation and loneliness, and neurocognitive impairment, as well as specific implications for sub-populations of interest, including pediatrics, caregivers, and TCT donors. Finally, we address protective psychological processes that may optimize biobehavioral outcomes affected by Covid-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Knight, Taylor, Rentscher, Henley, Uttley, Nelson, Turcotte, McAndrew, Amonoo, Mohanraj, Kelly and Costanzo.)

Research with animals and humans has demonstrated that chronic stress exposure can impact key biological aging pathways such as inflammation and DNA damage, suggesting a mechanism through which stress may increase risk for age-related disease. However, it is less clear whether these effects extend to other hallmarks of the aging process, such as cellular senescence. Male SCID mice were exposed to 14 days of restraint stress, with ( n  ​= ​6) or without ( n  ​= ​10) propranolol administration, or a non-stress control condition ( n  ​= ​10). Normal femoral bone marrow leukocytes were isolated from engrafted leukemia cells that had been injected prior to the stressor, as the mice were also under a cancer challenge. We performed whole genome transcriptional profiling to assess indicators of biological aging: cell stress, DNA damage repair, cellular senescence markers p16 INK4a and p21, and the pro-inflammatory senescence-associated secretory phenotype (SASP). ANCOVAs that adjusted for tumor load and Fisher's pairwise comparisons revealed that stressed mice had enhanced p16 INK4a ( p  ​= ​.02) and p21 ( p  ​= ​.004), lower DNA damage repair ( p  ​< ​.001), and higher SASP ( p  ​= ​.03) gene expression than control mice. Stressed mice also showed up-regulated beta-adrenergic (CREB) and inflammatory (NF- к B, AP-1) and down-regulated cell stress (Nrf2) transcription factor activity relative to control mice ( p s ​< ​.01). Propranolol reversed CREB and Nrf2 activity ( p s ​< ​.03). Findings suggest that chronic stress exposure can impact several key biological aging pathways within bone marrow leukocytes and these effects may be partially mediated by sympathetic beta-adrenergic receptor activation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Introduction: Social isolation and loneliness (SI/L) are growing problems with serious health implications for older adults, especially in light of the COVID-19 pandemic. We examined transcripts from semi-structured interviews with 97 older adults (mean age 83 years) to identify linguistic features of SI/L. Methods: Natural Language Processing (NLP) methods were used to identify relevant interview segments (responses to specific questions), extract the type and number of social contacts and linguistic features such as sentiment, parts-of-speech, and syntactic complexity. We examined: (1) associations of NLP-derived assessments of social relationships and linguistic features with validated self-report assessments of social support and loneliness; and (2) important linguistic features for detecting individuals with higher level of SI/L by using machine learning (ML) models. Results: NLP-derived assessments of social relationships were associated with self-reported assessments of social support and loneliness, though these associations were stronger in women than in men. Usage of first-person plural pronouns was negatively associated with loneliness in women and positively associated with emotional support in men. ML analysis using leave-one-out methodology showed good performance (F1 = 0.73, AUC = 0.75, specificity = 0.76, and sensitivity = 0.69) of the binary classification models in detecting individuals with higher level of SI/L. Comparable performance were also observed when classifying social and emotional support measures. Using ML models, we identified several linguistic features (including use of first-person plural pronouns, sentiment, sentence complexity, and sentence similarity) that most strongly predicted scores on scales for loneliness and social support. Discussion: Linguistic data can provide unique insights into SI/L among older adults beyond scale-based assessments, though there are consistent gender differences. Future research studies that incorporate diverse linguistic features as well as other behavioral data-streams may be better able to capture the complexity of social functioning in older adults and identification of target subpopulations for future interventions. Given the novelty, use of NLP should include prospective consideration of bias, fairness, accountability, and related ethical and social implications., Competing Interests: KS, YY, and H-CK are employees of IBM. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Badal, Nebeker, Shinkawa, Yamada, Rentscher, Kim and Lee.)

Background: Allogeneic hematopoietic cell transplantation (HCT) is a widely used treatment for hematologic cancers, with survival rates ranging from 25% to 78%. Known risk factors for chronic graft-versus-host disease (cGVHD), a serious and common long-term complication, disease relapse, and mortality following HCT have been identified, but much of the variability in HCT outcomes is unexplained. Biobehavioral symptoms including depression, sleep disruption, and fatigue are some of the most prevalent and distressing for patients; yet research on biobehavioral risk factors for HCT outcomes is limited. This study evaluated patient-reported depression, sleep disruption, and fatigue as risk factors for cGVHD, disease relapse, and mortality., Methods: Adults receiving allogeneic HCT for a hematologic malignancy (N = 241) completed self-report measures of depression symptoms, sleep quality, and fatigue (severity, interference) pre-HCT and 100 days post-HCT. Clinical outcomes were monitored for up to 6 years., Results: Cox proportional hazard models (2-tailed) adjusting for patient demographic and medical characteristics revealed that high pre-HCT sleep disruption (Pittsburgh Sleep Quality Index >9; hazard ratio [HR] = 2.74, 95% confidence interval [CI] = 1.27 to 5.92) and greater post-HCT fatigue interference (HR = 1.32, 95% CI = 1.05 to 1.66) uniquely predicted increased risk of mortality. Moderate pre-HCT sleep disruption (Pittsburgh Sleep Quality Index 6-9) predicted increased risk of relapse (HR = 1.99, 95% CI = 1.02 to 3.87). Biobehavioral symptoms did not predict cGVHD incidence., Conclusions: Biobehavioral symptoms, particularly sleep disruption and fatigue interference, predicted an increased risk for 6-year relapse and mortality after HCT. Because these symptoms are amenable to treatment, they offer specific targets for intervention to improve HCT outcomes., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for many hematologic conditions. Despite advances in conditioning and supportive measures, however, there remain significant comorbidities that threaten survivorship. Adverse effects of stress-related biobehavioral processes-defined here as the interactions of behavioral, psychological, and socioenvironmental factors with biology-impact immune recovery and function and are particularly salient in the HCT context, given the importance of immune reconstitution for improved survivorship. However, biobehavioral processes have been underinvestigated in this vulnerable group compared with other cancer populations. Here the Biobehavioral Research Special Interest Group (SIG) of the American Society for Transplantation and Cellular Therapy provides an expert review to inform research directions explicating the biological correlates of behavioral symptoms and evaluate the impact of these on HCT outcomes. The goal of this expert review is to provide a foundation for advancing science that effectively integrates behavioral and biological processes to optimize quality of life and improve clinical outcomes for HCT recipients., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The coronavirus pandemic (COVID-19) has had multilevel effects on non-COVID-19 health and health care, including deferral of routine cancer prevention and screening and delays in surgical and other procedures. Health and health care use has also been affected by pandemic-related loss of employer-based health insurance, food and housing disruptions, and heightened stress, sleep disruptions and social isolation. These disruptions are projected to contribute to excess non-COVID-19 deaths over the coming decades. At the same time municipalities, health systems and individuals are making changes in response to the pandemic, including modifications in the environmental to promote health, implementation of telehealth platforms, and shifts towards greater self-care and using remote platforms to maintain social connections. We used a multi-level biopsychosocial model to examine the available literature on the relationship between COVID-19-related changes and breast cancer prevention to identify current gaps in knowledge and identify potential opportunities for future research. We found that COVID-19 has impacted several aspects of social and economic life, through a variety of mechanisms, including unemployment, changes in health care delivery, changes in eating and activity, and changes in mental health. Some of these changes should be reduced, while others should be explored and enhanced.

Chronic stress can accelerate biological aging, offering one mechanism through which stress may increase age-related disease risk. Chronic activation of the sympathoadrenal system increases cellular energy production, resulting in cell stress that can initiate cellular senescence, a permanent state of cell growth arrest. Our previous research linked psychosocial stress with increased expression of senescence marker p16 INK4a ; however, less is known about the role of protective psychosocial factors in biological aging. We examined relationship closeness (perceived interconnectedness with one's spouse) as a protective buffer of the effects of stress on expression of the p16 INK4a -encoding gene ( CDKN2A ) and transcription control pathways activated under cell stress. Seventy parents ( M age =43.2) completed interview-based and questionnaire measures of psychosocial stress and relationship closeness. Blood samples assessed CDKN2A expression and inferred activity of a priori -selected transcription factors Nrf2 and heat shock factors (HSFs) via genome-wide transcriptome profiling. Random intercept models adjusting for age, sex, and ethnicity/race revealed that perceived stress was associated with elevated CDKN2A expression for parents with low but not high closeness. Secondary bioinformatics analyses linked the interaction of perceived stress and relationship closeness to Nrf2 and HSF-1 activity. Findings identify relationship closeness as a protective factor that may buffer the impact of stress on cellular stress and senescence pathways.

Prior to the 1990s, the predominant view of stress and coping defined stress as occurring when an individual perceives a situation as a challenge, threat, or loss and evaluates her capacity to respond based on her available resources. As an expansion of this intrapersonal perspective, the last 20 years have seen the emergence of two prominent interpersonal perspectives on stress and coping that account for the importance of social relationships in the coping process: the Systemic Transactional Model (STM) of dyadic coping and communal coping. In this article, I outline these two perspectives and highlight their points of convergence and divergence. I propose that one difference between the models is that communal coping involves an explicit focus on a communal or shared appraisal process, in which relationship partners view a problem or stressor as "ours" rather than "yours" or "mine." I review existing methods for assessing communal coping (e.g., self-report, language use, behavioral observation) across laboratory, intervention, and real-world settings and summarize empirical evidence for the prognostic significance of communal coping for relationship and health functioning. I propose the utility of incorporating measurement of shared appraisal into future research on dyadic coping with stress, because of its potential to impact health through its influence on primary and secondary stress appraisal processes and physiological stress response systems. Finally, I outline biological and behavioral pathways through which communal coping may influence health as directions for future research.