Latent space search based multimodal optimization with personalized edge-network biomarker for multi-purpose early disease prediction.

Considering that cancer is resulting from the comutation of several essential genes of individual patients, researchers have begun to focus on identifying personalized edge-network biomarkers (PEBs) using personalized edge-network analysis for clinical practice. However, most of existing methods ignored the optimization of PEBs when multimodal biomarkers exist in multi-purpose early disease prediction (MPEDP). To solve this problem, this study proposes a novel model (MMPDENB-RBM) that combines personalized dynamic edge-network biomarkers (PDENB) theory, multimodal optimization strategy and latent space search scheme to identify biomarkers with different configurations of PDENB modules (i.e. to effectively identify multimodal PDENBs). The application to the three largest cancer omics datasets from The Cancer Genome Atlas database (i.e. breast invasive carcinoma, lung squamous cell carcinoma and lung adenocarcinoma) showed that the MMPDENB-RBM model could more effectively predict critical cancer state compared with other advanced methods. And, our model had better convergence, diversity and multimodal property as well as effective optimization ability compared with the other state-of-art methods. Particularly, multimodal PDENBs identified were more enriched with different functional biomarkers simultaneously, such as tissue-specific synthetic lethality edge-biomarkers including cancer driver genes and disease marker genes. Importantly, as our aim, these multimodal biomarkers can perform diverse biological and biomedical significances for drug target screen, survival risk assessment and novel biomedical sight as the expected multi-purpose of personalized early disease prediction. In summary, the present study provides multimodal property of PDENBs, especially the therapeutic biomarkers with more biological significances, which can help with MPEDP of individual cancer patients.

Fit-for-Purpose Ki-67 Immunohistochemistry Assays for Breast Cancer.

New therapies are being developed for breast cancer, and in this process, some "old" biomarkers are reutilized and given a new purpose. It is not always recognized that by changing a biomarker's intended use, a new biomarker assay is created. The Ki-67 biomarker is typically assessed by immunohistochemistry (IHC) to provide a proliferative index in breast cancer. Canadian laboratories assessed the analytical performance and diagnostic accuracy of their Ki-67 IHC laboratory-developed tests (LDTs) of relevance for the LDTs' clinical utility. Canadian clinical IHC laboratories enrolled in the Canadian Biomarker Quality Assurance Pilot Run for Ki-67 in breast cancer by invitation. The Dako Ki-67 IHC pharmDx assay was employed as a study reference assay. The Dako central laboratory was the reference laboratory. Participants received unstained slides of breast cancer tissue microarrays with 32 cases and performed their in-house Ki-67 assays. The results were assessed using QuPath, an open-source software application for bioimage analysis. Positive percent agreement (PPA, sensitivity) and negative percent agreement (NPA, specificity) were calculated against the Dako Ki-67 IHC pharmDx assay for 5%, 10%, 20%, and 30% cutoffs. Overall, PPA and NPA varied depending on the selected cutoff; participants were more successful with 5% and 10%, than with 20% and 30% cutoffs. Only 4 of 16 laboratories had robust IHC protocols with acceptable PPA for all cutoffs. The lowest PPA for the 5% cutoff was 85%, for 10% was 63%, for 20% was 14%, and for 30% was 13%. The lowest NPA for the 5% cutoff was 50%, for 10% was 33%, for 20% was 50%, and for 30% was 57%. Despite many years of international efforts to standardize IHC testing for Ki-67 in breast cancer, our results indicate that Canadian clinical LDTs have a wide analytical sensitivity range and poor agreement for 20% and 30% cutoffs. The poor agreement was not due to the readout but rather due to IHC protocol conditions. International Ki-67 in Breast Cancer Working Group (IKWG) recommendations related to Ki-67 IHC standardization cannot take full effect without reliable fit-for-purpose reference materials that are required for the initial assay calibration, assay performance monitoring, and proficiency testing.

Does the radical GPRI strongly depend on the population scheme? A comparative study to predict radical attack on unsaturated molecules with the radical general-purpose reactivity indicator.

The reactivity of 22 unsaturated molecules undergoing attack by a methyl radical (⋅CH3) have been elucidated using the condensed radical general-purpose reactivity indicator (condensed radical GPRI) appropriate for relatively nucleophilic or electrophilic molecules. Using the appropriate radical GPRI equation for electrophilic attack or nucleophilic radical attack, seven different population schemes were used to assign the most reactive atoms in each of the 22 molecules. The results show that the condensed radical GPRI is sensitive to the population scheme chosen, but less sensitive than the radical Fukui function. Therefore, the reliability of these methods depends on the population scheme. Our investigation indicates that the condensed radical GPRI is most accurate in predicting the dominant products of the methyl radical addition reactions on a variety of unsaturated molecules when the Hirshfeld, Merz-Singh-Kollman, or Voronoi deformation density population schemes are used. Furthermore, for all populations schemes in the majority of instances where the radical Fukui function failed the radical GPRI was able to identify the most reactive atom under certain reactivity conditions.

Transitioning from Subtyping to Precision Medicine in Parkinson's Disease: A Purpose-Driven Approach.

The International Parkinson and Movement Disorder Society (MDS) created a task force (TF) to provide a critical overview of the Parkinson's disease (PD) subtyping field and develop a guidance on future research in PD subtypes. Based on a literature review, we previously concluded that PD subtyping requires an ultimate alignment with principles of precision medicine, and consequently novel approaches were needed to describe heterogeneity at the individual patient level. In this manuscript, we present a novel purpose-driven framework for subtype research as a guidance to clinicians and researchers when proposing to develop, evaluate, or use PD subtypes. Using a formal consensus methodology, we determined that the key purposes of PD subtyping are: (1) to predict disease progression, for both the development of therapies (use in clinical trials) and prognosis counseling, (2) to predict response to treatments, and (3) to identify therapeutic targets for disease modification. For each purpose, we describe the desired product and the research required for its development. Given the current state of knowledge and data resources, we see purpose-driven subtyping as a pragmatic and necessary step on the way to precision medicine. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Working with companies that manufacture breastmilk substitutes: An EAACI position paper.

Breastmilk is the optimal source of nutrition for infants and should ideally be provided exclusively for the first 6 months of life, and alongside complementary food until 2 years of life. However, there are circumstances where a breastmilk substitute (BMS) may be required. This includes maternal and/or child conditions or personal preference. Whilst these circumstances should never be used as an opportunity to promote BMS, healthcare professionals (HCPs) need to have the knowledge of suitable alternatives and should always be guided by scientific and health motives when recommending a BMS. The Task Force 'Milk Formula Industry Sponsorship' from the European Academy of Allergy and Clinical Immunology (EAACI), provides with this publication recommendations for EAACI interactions with the BMS manufacturers and how this will be supervised.

Purpose in life and cognitive performance and informant ratings of cognitive decline, affect, and activities.

OBJECTIVE: To examine (1) the association between purpose in life and multiple domains of cognitive function and informant-rated cognitive decline, affect, and activities; (2) whether these associations are moderated by sociodemographic factors, cognitive impairment, or depression; (3) whether the associations are independent of other aspects of well-being and depressive symptoms. METHOD: As part of the 2016 Harmonized Cognitive Assessment Protocol from the Health and Retirement Study, participants completed a battery of cognitive tests and nominated a knowledgeable informant to rate their cognitive decline, affect, and activities. Participants with information available on their purpose in life from the 2014/2016 Leave Behind Questionnaire were included in the analytic sample (N = 2,812). RESULTS: Purpose in life was associated with better performance in every cognitive domain examined (episodic memory, speed-attention, visuospatial skills, language, numeric reasoning; median ß =.10, p <.001; median d =.53). Purpose was likewise associated with informant-rated cognitive decline and informant-rated affective and activity profiles beneficial for cognitive health (median ß =.18, p < .001; median d =.55). There was little evidence of moderation by sociodemographic or other factors (e.g., depression). Life satisfaction, optimism, positive affect, and mastery were generally associated with cognition. When tested simultaneously with each other and depressive symptoms, most dimensions were reduced to non-significance; purpose remained a significant predictor. CONCLUSIONS: Purpose in life is associated with better performance across numerous domains of cognition and with emotional and behavioral patterns beneficial for cognitive health that are observable by knowledgeable others. These associations largely generalize across demographic and clinical groups and are independent of other aspects of well-being.

What Are Doctors For? A Call for Compassion-Based Metrics as a Measure of Physician Value.

Modern measures of physician value are couched in terms of productivity, volume, finance, outcomes, cure rates, and acquisition of an increasingly vast knowledge base. This inherently feeds burnout and imposter syndrome as physicians experience an inability to measure up to unrealistic standards set externally and perceived internally. Ancient and modern wisdom suggests that where populations fail to flourish, at root is a failure to grasp a vision or true purpose. Traditional philosophical conceptions of a physician's purpose center around compassion, empathy, and humanism, which are a key to thwarting burnout and recovering professional satisfaction. New compassion-based metrics are urgently needed and will positively impact physician well-being and improve population health.

The built environment, purpose-specific walking behaviour and overweight: evidence from Wuhan metropolis in central China.

The impact of objective and subjective environmental factors on health outcomes has been a topic of significant debate, with a growing body of research acknowledging the role of a physically active lifestyle in promoting health. However, consensus regarding their precise influence remains elusive. This study contributes to these discussions by exploring how individual health outcomes correlate with transport and leisure walking behaviours, set against both the objective and subjective aspects of environmental influences in the context of Wuhan, an inland Chinese megacity. Street view images, multi-source geospatial data and a questionnaire survey were employed to characterise the "5D + Greenery" objective and perceived characteristics of the neighbourhood environment. Multi-group structural equation modelling was utilised to unravel the complex relationship and gender heterogeneity among environmental factors, purpose-specific walking, and overweight. Our results suggest that both objective land use diversity and perceived convenience are significantly associated with overweight. The accessibility of local service facilities and visible greenery promote both transport and leisure walking. While perceived neighbourhood safety encourages transport walking, perceived walkability is positively correlated with leisure walking. Notably, leisure walking, usually considered beneficial, presents a positive association with overweight conditions, acting as a mediation. Gender disparities exist in pathways between the environment and purpose-specific walking, as well as weight. The findings lend support to the planning of an activity-supporting built environment as a crucial strategy for obesity prevention.

Purpose in life and cognitive health: a 28-year prospective study.

OBJECTIVES: To examine the prospective association between purpose in life measured at three points across middle and older adulthood and cognitive outcomes assessed 8-28 years later. DESIGN: Prospective Study. SETTING: Wisconsin Longitudinal Study of Aging (WLS). PARTICIPANTS: WLS participants who reported on their purpose in life at Round 4 (1992-1994; Mage = 52.58), Round 5 (2003-2007; Mage = 63.74), and/or Round 6 (2010-2012; Mage = 70.25) and were administered a cognitive battery at Round 7 (2020; Mage = 79.94) were included in the analysis (N = 4,632). MEASUREMENTS: Participants completed the Ryff measure of purpose in life and were administered the telephone interview for cognitive status and measures of verbal fluency, digit ordering, and numeric reasoning. RESULTS: Purpose in life measured at age 52 was related to better global cognitive function and verbal fluency but unrelated to dementia at age 80. In contrast, purpose in life at ages 63-70 was associated with lower likelihood of dementia, as well as better global cognitive function and verbal fluency at age 80. The effect sizes were modest (median Beta coefficient = .05; median odds ratio = .85). A slightly steeper decline in purpose in life between ages 52 and 70 was found for individuals with dementia at age 80. CONCLUSIONS: Purpose in life is associated with healthier cognitive function measured up to 28 years later. Individuals with lower purpose, especially in their 60s or older, and with steeper declines in purpose, are more likely to have dementia at age 80.

A systematic review of psychosocial protective factors against suicide and suicidality among older adults.

BACKGROUND: Research on suicide rarely focuses on protective factors. The goal of this systematic review was to assess the evidence of the associations between protective factors and reduced suicidality among older adults. METHOD: First, a scoping review was conducted to identify pertinent terms that refer to various protective factors against suicidality. A systematic review, following the PRISMA guidelines, was then conducted on a selection of 15 protective factors (e.g., perceived control, well-being and quality of life, life satisfaction, purpose-in-life, resilience, coping, religiosity, hope, self-regulation, sense of belonging, mattering, positive relationship, social support, social connectedness, and social participation), with separate searches performed on each factor in five databases. Empirical studies were eligible if participants were adults aged 60 years and over, and if the studies reported predictive statistical analysis. RESULTS: A total of 70 studies were retained for the review. Suicidal ideation was the main outcome measure (91%). Significant associations were consistently observed between all protective factors and reduced suicidal ideations or behaviors, particularly for purpose-in-life, resilience, and positive relationships, indicating that these are solid components for suicide prevention. Using scales, instead of a single item, to measure protective factors (e.g. life satisfaction) was more efficient to capture the associations. On the other hand, results were similar whether studies used subjective (e.g., sense of belonging) or objective (e.g., social connectedness) measures. CONCLUSION: Protective factors were inversely associated with suicidal ideation. Improving protective factors is essential for the development of late-life suicide prevention and interventions, instead of merely focusing on risk factors.

Assessing Opportunities and Barriers to Improving the Secondary Use of Health Care Data at the National Level: Multicase Study in the Kingdom of Saudi Arabia and Estonia.

BACKGROUND: Digitization shall improve the secondary use of health care data. The Government of the Kingdom of Saudi Arabia ordered a project to compile the National Master Plan for Health Data Analytics, while the Government of Estonia ordered a project to compile the Person-Centered Integrated Hospital Master Plan. OBJECTIVE: This study aims to map these 2 distinct projects' problems, approaches, and outcomes to find the matching elements for reuse in similar cases. METHODS: We assessed both health care systems' abilities for secondary use of health data by exploratory case studies with purposive sampling and data collection via semistructured interviews and documentation review. The collected content was analyzed qualitatively and coded according to a predefined framework. The analytical framework consisted of data purpose, flow, and sharing. The Estonian project used the Health Information Sharing Maturity Model from the Mitre Corporation as an additional analytical framework. The data collection and analysis in the Kingdom of Saudi Arabia took place in 2019 and covered health care facilities, public health institutions, and health care policy. The project in Estonia collected its inputs in 2020 and covered health care facilities, patient engagement, public health institutions, health care financing, health care policy, and health technology innovations. RESULTS: In both cases, the assessments resulted in a set of recommendations focusing on the governance of health care data. In the Kingdom of Saudi Arabia, the health care system consists of multiple isolated sectors, and there is a need for an overarching body coordinating data sets, indicators, and reports at the national level. The National Master Plan of Health Data Analytics proposed a set of organizational agreements for proper stewardship. Despite Estonia's national Digital Health Platform, the requirements remain uncoordinated between various data consumers. We recommended reconfiguring the stewardship of the national health data to include multipurpose data use into the scope of interoperability standardization. CONCLUSIONS: Proper data governance is the key to improving the secondary use of health data at the national level. The data flows from data providers to data consumers shall be coordinated by overarching stewardship structures and supported by interoperable data custodians.

Social participation and mental well-being: Does purpose in life mediate the association among older adults?

OBJECTIVES: We investigated the association of social participation with mental well-being among older people and whether purpose in life mediates the potential association. METHOD: Cross-sectional (n = 1014) and longitudinal (n = 660, four-year follow-up) data comprised of three age cohorts (75, 80, and 85 years) of community-dwelling people. Life satisfaction was measured with the Satisfaction with Life Scale, depressive symptoms with the Centre for Epidemiologic Studies Depression Scale, and purpose in life with the Scales of Psychological Well-Being purpose in life subscale. Social participation was assessed with questions concerning the frequency of meeting close friends and acquaintances, and volunteering. The data were analyzed using structural equation modeling. RESULTS: Higher social participation was associated with higher life satisfaction and fewer depressive symptoms both cross-sectionally and after a four-year follow-up. Higher purpose in life mediated the associations of more social participation with higher life satisfaction and fewer depressive symptoms cross-sectionally. In the longitudinal data, the mediation effect was not observed. CONCLUSION: Older people with frequent social participation who had a sense of purpose in their lives will likely have higher mental well-being than those with less social participation. Enabling and supporting them to conduct purposeful actions in social contexts may help maintain their mental well-being.

Adaptation and validation of the Claremont Purpose Scale to measure Chinese adolescents' purpose in life.

Despite purpose measures being developed for adolescents, quantitative research investigating purposes prior to late adolescence and in non-Western societies remains nascent. This study evaluated the psychometric soundness of the Claremont Purpose Scale among Chinese adolescents. An initial prestudy (n = 34) was conducted to ensure linguistic equivalence. Subsequently, Study 1 (n = 1691) assessed the scale's reliability and factor structure, also investigating its functional equivalence across gender, adolescence stages, and language versions at the item level. Study 2 (n = 7842) investigated the scale's construct, convergent, predictive, and incremental validity, as well as tested for the scale's measurement invariance across different groups at the scale level. The results support the scale's use as a tool for researchers and practitioners to understand and cultivate purpose in adolescents.

Preparing for Artificial General Intelligence (AGI) in Health Professions Education: AMEE Guide No. 172.

Generative Artificial Intelligence (GenAI) caught Health Professions Education (HPE) institutions off-guard, and they are currently adjusting to a changed educational environment. On the horizon, however, is Artificial General Intelligence (AGI) which promises to be an even greater leap and challenge. This Guide begins by explaining the context and nature of AGI, including its characteristics of multi-modality, generality, adaptability, autonomy, and learning ability. It then explores the implications of AGI on students (including personalised learning and electronic tutors) and HPE institutions, and considers some of the context provided by AGI in healthcare. It then raises the problems to address, including the impact on employment, social risks, student adaptability, costs, quality, and others. After considering a possible timeline, the Guide then ends by indicating some first steps that HPE institutions and educators can take to prepare for AGI.

Improvement of Dynamic Characteristics of Purpose-Built Vehicles Using Semi-Active Suspension System.

The diversification of mobility into services such as smart stores and conference rooms has accelerated the development of purpose-built vehicles (PBVs)-vehicles designed for specific purposes that utilize an extended electric vehicle chassis and autonomous driving technology. Despite the standards on speed bump dimensions stipulated by the National Land Transportation Act of the Republic of Korea, real-world speed bumps feature varying widths and heights that deviate from these standards. In this study, a velocity equation was derived via regression analysis to achieve the desired dynamic characteristics for a PBV passing over speed bumps with varying shapes through two types of semi-active suspension control: proportional-integral-differential (PID) and linear-quadratic-regulator (LQR). For a cargo-transport PBV, the PID and LQR controllers increased the velocity by 23.74% and 50.74%, respectively, under different speed bump widths and by 19.44% and 38.31%, respectively, under different speed bump heights. Moreover, an analysis of the vibration dose value (VDV), an indicator of ride comfort, revealed that the VDVs calculated using the velocity equation were within an acceptable error range of 10% above the target VDV. These findings provide insights into the speed control required for different types of autonomous PBVs to ensure ride comfort, as well as minimize the driving duration, depending on the specific purpose of the vehicle.

Flourishing, religion, and burnout among caregivers working in pediatric palliative care.

INTRODUCTION: Providers working with children who are dying are especially prone to burnout. Encouraging models of human flourishing may mitigate burnout and improve quality of care. However, models of job satisfaction and human flourishing have not been well-described. This project explores factors that promote human flourishing among caregivers working with children in pediatric palliative care in South Africa. METHODS: A convenience sample of caregivers working in pediatric palliative care were invited to complete an anonymous, confidential survey comprised of validated instruments. The survey also included open-ended questions to explore opinions and attitudes about satisfaction, struggles, and coping. RESULTS: Twenty-nine people from a variety of occupations and work environments completed the survey. The prevalence of burnout was 3/29 (10%). Life satisfaction was associated with private religious activities (P = .38, P < .05), and carrying religion into all aspects of life (P = .44, P < .05). Burnout was not associated with life satisfaction. Qualitative analysis of the open-ended questions revealed the following themes as factors contributing to their joy in work: being able to make a difference, finding meaning and purpose, having a relationship with the children and their families, and with the multi-disciplinary team. The greatest challenges in their work were identified as the lack of resources, challenges within their team, and emotional demands. CONCLUSIONS: Despite job stress and working with terminally ill children, several factors were associated with flourishing. These findings are particularly relevant to enhance caregiving in the resource-challenged setting of pediatric palliative care in South Africa.

Social connection and self-neglect: A case for broader exploration.

Self-neglect (SN) is the most common report to Adult Protective Services (APS) and is associated with significant morbidity and mortality risks for older adults. Lack of instrumental support is a well-evidenced etiologic factor in the development and continuation of SN, but little is known about other modifiable social connection characteristics. The social connection framework, provides a host of evidence-based characteristics across structure, function, quality missing from SN studies that could be identified if explored. These factors could provide prevention and intervention targets related to poor health. We present a narrative case study using quantitative and qualitative data to explore social connection across structure, function, and quality in the context of SN. The findings highlight the complexity of social connection that may be frequently observed in SN cases reported to APS. Strategic utilization of direct and indirect social interventions to support social connection in this case is presented and provides general considerations that may be generalizable to other SN cases. Thoughts for future research on social connection in this population are provided.

Psychosocial factors associated with 7-year change in cognition among middle-aged and older Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) and Sociocultural ancillary studies.

INTRODUCTION: Few studies have examined the associations of psychosocial factors with cognitive change in Hispanics/Latinos. METHODS: Data from the Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL INCA) and Sociocultural studies were used (n = 2,155; ages ≥45 years). Psychosocial exposures included intrapersonal (ethnic identity, optimism, purpose in life), interpersonal (family cohesion, familism, social networks, social support), and social factors (ethnic discrimination, loneliness, subjective social status). Survey-linear regression models examined associations between psychosocial exposures and 7-year cognitive change (global cognition [GC], verbal learning, memory, word fluency [WF], and digit symbol substitution [DSS]). RESULTS: Familism predicted decline in GC, verbal learning, and memory; family cohesion predicted DSS decline; and loneliness predicted memory decline. Ethnic identity was protective against decline in GC and memory, optimism and social support were protective against decline in memory, and purpose in life was protective against WF decline. DISCUSSION: Psychosocial factors are differentially related to cognitive changes. Culturally relevant factors should be explored in Hispanic/Latino cognitive aging research. HIGHLIGHTS: Psychosocial factors are differentially related to cognitive changes in Latinos. Role of culturally relevant factors on cognition should be further explored. Familism predicted decline in global cognition, verbal learning, and memory. Ethnic identity predicted increase in global cognition and memory.

Transformative impact of positive psychotherapy-based hope placement program on life goals and hope level of individuals with multiple sclerosis.

AIM: This study aimed to assess the impact of a positive psychotherapy-based hope placement program on life goal setting and hope levels in individuals diagnosed with multiple sclerosis (MS). METHOD: A Solomon Four-Group experimental design was used, involving 50 individuals diagnosed with MS who sought treatment at a university hospital's neurology outpatient clinic. Experimental (1-2) and control (1-2) groups were randomized, and pretests were administered exclusively to the experimental and control groups. Data were collected using a Personal Information Form, the Herth Hope Scale, and the Scale for Determining Life Goals in the Context of Positive Psychotherapy. A 5-week/10-session Positive Psychotherapy-Based Hope Placement Program was conducted online for the Experimental groups. The research was conducted in the form of group therapy. Post-tests were administered to all groups upon program completion. RESULTS: The experimental 1-2 group exhibited statistically significant improvements in the Scale for Identifying Life Goals in the Context of Positive Psychotherapy and Herth Hope Scale scores (p < .05). The Positive Psychotherapy-Based Hope Placement Program effectively enhances hope levels and life goal setting for individuals diagnosed with MS. CONCLUSION: The results indicate that the program increased the sense of purpose in life and elevated levels of hope among MS patients. These findings suggest that positive psychotherapy-based interventions significantly improve the quality of life for MS patients. CLINICAL OR METHODOLOGICAL SIGNIFICANCE OF THIS ARTICLE: This study examines the impact of a Positive Psychotherapy-based hope placement program on determining hope and life purpose in patients with Multiple Sclerosis (MS). This research shows that HOPP (Hope Placement Program), an intervention based on Positive Psychotherapy, can significantly improve the quality of life of MS patients. These findings support the consideration of Positive Psychotherapy-based approaches as a potential therapeutic option that can positively influence the life experiences of MS patients. Therefore, this article makes an important contribution to researchers interested in using Positive Psychotherapy-based interventions in clinical practice and related research.

Purpose in life moderates the relationship between loneliness and caregiving stress among family caregivers of people with mental health problems.

OBJECTIVE: Providing care to others can exert a profound impact on caregivers' sense of purpose or meaning in life, thereby reciprocally influencing the caregivers' overall health and well-being. This study aims to investigate whether the sense of purpose in life moderates the association between loneliness and caregiving stress among family caregivers of people with mental health problems. METHODS: A sample of family caregivers of people with mental health problems (N = 468, 57.1 % female) drawn from the 2020 survey of the Caregiving in the U.S. was investigated. Descriptive statistics, correlation analysis, and a multiple regression with an interaction term were performed. RESULTS: Higher levels of loneliness were associated with enhanced caregiving stress. Moreover, after demographic and care-related factors were controlled for, the association between loneliness and caregiving stress was moderated by purpose in life; namely, as the sense of purpose in life increased, so did the intensity of the relationship between loneliness and caregiving stress. CONCLUSION: Reducing loneliness or strengthening the sense of purpose helps alleviate caregiving stress, and lonely family caregivers with a strong sense of purpose deserve extra attention.