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PurposeWe evaluated the impact of partial volume correction (PVC) methods on the quantification of longitudinal [18F]GTP1 tau positron-emission tomography (PET) in Alzheimer's disease and the suitability of describing the tau pathology burden temporal trajectories using linear mixed-effects models (LMEM).MethodsWe applied van Cittert iterative deconvolution (VC), 2-compartment, and 3-compartment, and the geometric transfer matrix plus region-based voxelwise methods to data acquired in an Alzheimer's disease natural history study over 18 months at a single imaging site. We determined the optimal PVC method by comparing the standardized uptake value ratio change (%ΔSUVR) between diagnostic and tau burden-level groups and the longitudinal repeatability derived from the LMEM. The performance of LMEM analysis for calculating %ΔSUVR was evaluated in a natural history study and in a multisite clinical trial of semorinemab in prodromal to mild Alzheimer's disease by comparing results to traditional per-visit estimates.ResultsThe VC, 2-compartment, and 3-compartment PVC methods had similar performance, whereas region-based voxelwise overcorrected regions with a higher tau burden. The lowest within-subject variability and acceptable group separation scores were observed without PVC. The LMEM-derived %ΔSUVR values were similar to the per-visit estimates with lower variability.ConclusionThe results indicate that the tested PVC methods do not offer a clear advantage or improvement over non-PVC images for the quantification of longitudinal [18F]GTP1 PET data. LMEM offers a robust framework for the longitudinal tau PET quantification with low longitudinal test-retest variability.Clinical trial registrationNCT02640092 and NCT03289143.

Elder mistreatment disproportionately affects racial and ethnic minority older adults, particularly Chinese older adults in the U.S. who face increased risks due to cultural disparities, intergenerational conflicts, and socioeconomic disparities. This study investigated the longitudinal association of elder mistreatment with cognitive functioning among Chinese older adults in the Greater Chicago area (N = 2,811). Self-reported elder mistreatment and cognitive performance were assessed across four waves of the study. Latent growth curve modeling analysis showed that respondents reporting previous mistreatment instances at baseline exhibited better initial functioning status (B = 0.07, p < .05); however, those reporting mistreatment incidents at three follow-ups showed a faster cognitive decline compared to those without such reports (B = −0.04, p < .05). Recent and potentially cumulative experiences of elder mistreatment have a negative effect on cognitive decline. Sociocultural contexts need to be considered when addressing elder mistreatment issues within the Chinese minority community. [ABSTRACT FROM AUTHOR]

Background: Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients. Methods: This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients. Results: RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71–22.92) versus 9.59 (6.57–13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7. Conclusion: Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the structural, microvascular, and functional progression of normal tension glaucoma (NTG) with or without high myopia by examining longitudinal changes in optical coherence tomography angiography (OCTA) and visual field (VF) parameters. Methods: We evaluated 61 NTG eyes and classified 25 of the eyes with axial lengths (ALs) of ≥26 mm as highly myopic. We assessed the rate of change in OCTA parameters, namely radial peripapillary capillary (RPC) vessel density (VD), parafovea VD, deep parafovea VD, retinal nerve fibre layer (RNFL) thickness, and ganglion cell complex thickness. We evaluated the correlation of the rate of change in OCTA parameters with VF loss and AL. Results: Among the 61 NTG eyes, rates of loss of RPC VD, parafovea VD, deep parafovea VD, and RNFL thickness were significantly different from zero despite the nonsignificant rate of change in VF mean deviation (MD). Changes in these OCTA parameters did not differ significantly in highly myopic NTG eyes. The rate of change in VF MD was significantly correlated with the rate of change in parafovea VD in highly myopic and non‐highly myopic NTG eyes. In highly myopic NTG eyes, AL was negatively correlated with the rates of loss of RNFL thickness, VF MD, and VF PSD. Conclusion: NTG eyes with a relatively stable VF exhibited loss of VD and RNFL thickness. VF progression in NTG was correlated with decreasing parafovea VD, indicating a structure–function correlation. Greater AL may indicate faster VF loss and RNFL thinning in highly myopic NTG eyes. [ABSTRACT FROM AUTHOR]

Although it is well established that moderate-to-vigorous physical activity (MVPA) buffers against declines in cognitive health, less is known about the benefits of light physical activity (LPA). Research on the role of LPA is crucial to advancing behavioral interventions to improve late life health outcomes, including cognitive functioning, because this form of physical activity remains more feasible and amenable to change in old age. Our study examined the extent to which increases in LPA frequency protected against longitudinal declines in cognitive functioning and whether such a relationship becomes pronounced in old age when opportunities for MVPA are typically reduced. We analyzed 9-year data from the national Midlife in the United States Study (n = 2,229; Mage = 56 years, range = 33–83; 56% female) using autoregressive models that assessed whether change in LPA frequency predicted corresponding changes in episodic memory and executive functioning in middle and later adulthood. Increases in LPA frequency predicted less decline in episodic memory (β = 0.06, p =.004) and executive functioning (β = 0.14, p <.001) over the 9-year follow-up period, even when controlling for moderate and vigorous physical activity. Effect sizes for moderate and vigorous physical activity were less than half that observed for LPA. Moderation models showed that, for episodic memory, the benefits of increases in LPA frequency were more pronounced at older ages. Findings suggest that increases in LPA over extended periods of time may help slow age-related cognitive declines, particularly in later life when opportunities for MVPA are often diminished. [ABSTRACT FROM AUTHOR]

Objectives: To explore the oxygen metabolism level of different types of lesions in relapsing–remitting multiple sclerosis (RRMS) patients by oxygen extraction fraction (OEF) both cross-sectionally and longitudinally. Methods: Forty-six RRMS patients and forty-one healthy controls (HC) went MRI examination. The quantitative susceptibility mapping (QSM) and OEF map were reconstructed from a 3D multi-echo gradient echo sequence. MS lesions in white matter were classified as contrast-enhancing lesions (CELs) on post-gadolinium T1-weighted sequence, paramagnetic rim lesions (PRLs), hyperintense lesions and non-hyperintense lesions on QSM, respectively. The susceptibility and OEF of different types of lesions were compared. The susceptibility and OEF values were measured and compared among different types of lesions. Among these RRMS patients, seventeen had follow-up MRI and 232 lesions, and baseline to follow-up longitudinal changes in susceptibility and OEF were measured. Results: PRLs had higher susceptibility and lower OEF than CELs, hyperintense lesions, and non-hyperintense lesions. The hyperintense lesions had higher susceptibility and lower OEF than non-hyperintense lesions. In longitudinal changes, PRLs had susceptibility increased (P < 0.001) and OEF decreased (P < 0.001). The hyperintense lesions showed significant decreases in susceptibility (P = 0.020), and non-hyperintense lesions showed significant increases in OEF during follow-up (P = 0.005). Notably, hyperintense lesions may convert to PRLs or non-hyperintense lesions as time progresses, accompanied by changes of OEF and susceptibility in the lesions. Conclusion: This study revealed tissue damage and oxygen metabolism level in different types of MS lesions. The OEF may contribute to further understanding the evolution of MS lesions. [ABSTRACT FROM AUTHOR]

Abstract Background Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients. Methods This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients. Results RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71–22.92) versus 9.59 (6.57–13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P 0.7. Conclusion Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.

Objectives This study examines how family relationships convey risk or resilience for pain outcomes for aging African Americans, and to replicate and extend analyses across 2 nationally representative studies of aging health. Methods African American participants in Midlife in the United States (MIDUS, N  = 755) and the Health and Retirement Study (HRS, N  = 2,585) self-reported chronic pain status at 2006 waves and then again 10 years later. Logistic regression was used to estimate the odds of pain incidence and persistence explained by family, intimate partner, and parent–child strain and support, as well as average support and average strain across relationships. Results On average, MIDUS participants were younger (M  = 52.35, SD  = 12.06; 62.1% female) than HRS (M  = 66.65, SD  = 10.92; 63.7% female). Family support and average support were linked to decreased odds of pain incidence in MIDUS, but only when tested without accounting for strain, whereas parent–child strain was a risk factor for pain incidence in HRS, as was average strain. Family support protected against pain persistence in MIDUS, whereas average support was linked to reduced odds of pain persisting in HRS. Discussion Chronic pain outcomes are worse for African Americans for a number of reasons, but parent–child strain may contribute to the risk of new pain developing over time for older adults. Conversely, family support may offer a protective benefit for pain incidence and persistence among aging African Americans. Findings implicate family relationships as a potential target of pain management interventions. [ABSTRACT FROM AUTHOR]

A better understanding of the impact of lifestyle factors on cognitive function in older adults is critical for developing intervention strategies to achieve successful aging. Moreover, older adults who fulfill the World Health Organization criteria for anemia have a significantly higher risk of developing dementia. In the current study, we aimed to assess the buffering effects of lifestyle on cognitive function in older Chinese adults through a nationally representative survey. The sample consisted of 1201 participants (mean age: 82.39 ± 12.08 years, 52.1% female) from the 2011/2012 and 2014 waves of the Chinese Longitudinal Healthy Longevity Survey. Multiple linear regression analyses were used to explore the relationship between changes in lifestyle factors and the rate of cognitive function changes, as well as the effects of the interaction between lifestyle factors and anemia on cognitive function changes. Increased levels of participation in leisure activities, social activities, and dietary diversity delayed cognitive decline. Persistent anemia accelerated cognitive decline, while frequent participation in leisure activities delayed cognitive decline due to anemia. The increased levels of participation in leisure activities, social activities, and dietary diversity can alleviate the cognitive decline caused by aging itself, and more frequently participation in leisure activities can also alleviate the adverse effects of anemia on cognitive function in older adults. [ABSTRACT FROM AUTHOR]

Objectives Theoretical perspectives on aging suggest that when people experience declines in later life, they often selectively focus on maintaining aspects of their lives that are most meaningful and important to them. The social domain is one of these selected areas. The current study examines people's reports of control over their daily stressors over 10 years, predicting that the declines in control that are often observed in later life will not be observed for stressors involving interpersonal conflict and tensions with social partners. Methods Adults ranging from 35 to 86 years old at baseline (N = 1,940), from the National Study of Daily Experiences, reported control over interpersonal and noninterpersonal daily stressors across 8 consecutive days at 2 time points, about 10 years apart. Results Findings from multilevel models indicate that for noninterpersonal stressors, perceived control decreased over time. In contrast, perceived control over interpersonal conflicts and tensions remained robust over time. No cross-sectional baseline age differences were found for levels of interpersonal and noninterpersonal stressor control. Discussion Results are consistent with socioemotional selectivity and underscore the importance of interpersonal relationships in later adulthood. Understanding how people select and preserve certain aspects of control in their daily life can help guide efforts toward maximizing gains and minimizing losses in domains that matter most to people as they grow older. [ABSTRACT FROM AUTHOR]

Objectives This study proposes and evaluates a scenario wherein cognitive demands experienced at work can amplify the positive cross-lagged association of a shift in control beliefs following changes in episodic memory. Methods From the Health and Retirement Study (2006–2018) for 9,998 participants aged 50 or above, we used repeated observations of memory and control beliefs, assessed with the Telephone Interview for Cognitive Status-modified (TICS-m) and self-mastery and perceived constraints questionnaires. A dual-Latent Change Score Model estimated the cross-lagged effects between memory and control beliefs, separately for individuals with prior high cognitive job demands and those without. Results A decline in memory led to decreased control beliefs in terms of perceived constraints, only among those with experiences in cognitively demanding jobs. Discussion High cognitive job demands may lead to a more cognitively oriented awareness of aging, thus amplifying the impact of memory decline on control constraints. [ABSTRACT FROM AUTHOR]

Purpose: Foot deformities are prevalent in children with cerebral palsy, but there is limited research on the progression of foot posture during growth. Our study aimed to evaluate the change in dynamic foot posture in children with cerebral palsy. Methods: Children with cerebral palsy, aged 17–40 months, were recruited to participate in this Institutional Review Board–approved prospective longitudinal study by having serial foot posture evaluations. The coronal plane index and foot segmental impulses were measured with dynamic pedobarography. Data were compared between children stratified by Gross Motor Function Classification System level and typically developing children using serial Welch's t -tests across time with Holm correction for multiple comparisons. Results: In total, 33 children (54 limbs) were included in the analysis (21 bilateral and 12 unilateral; Gross Motor Function Classification System: I-13, II-14, III-4, IV-2. Children completed 16.9 (± 4.4) evaluations (initial age 2.9 (± 0.7) and final age 18.6 (± 1.7) years)). Early valgus foot posture normalizes in children at Gross Motor Function Classification System levels I/II and persists in children at levels III/IV who do not have foot surgery. For most young children, foot posture development is variable. Conclusion: Foot posture in young children with cerebral palsy begins in valgus and tends to normalize in youth who walk without an assistive device. Conservative management of foot deformity is recommended in early childhood. Level of evidence: Level II, prognostic study. [ABSTRACT FROM AUTHOR]

Abstract Background Despite the recognized high symptom prevalence in haemodialysis population, how these symptoms change over time and its implications for clinical practice and research is poorly understood. Methods Prevalent haemodialysis patients in the SHAREHD trial reported 17 POS-S Renal symptoms (none, mild, moderate, severe and overwhelming) at baseline, 6, 12 and 18 months. To assess the prevalence change at population level in people reporting moderate or worse symptoms at baseline, the absolute change in prevalence was estimated using multi-level mixed effects probit regression adjusting for age, sex, time on haemodialysis and Charlson Comorbidity Score. To assess changes at individual level, the proportion of people changing their symptom score every 6 months was estimated. Results Five hundred fifty-two participants completed 1725 questionnaires at four timepoints. Across all 17 symptoms with moderate or worse symptom severity at baseline, the majority of the change in symptom prevalence at population level occurred in the ‘severe’ category. The absolute improvement in prevalence of the ‘severe’ category was ≤ 20% over 18 months in eleven of the seventeen symptoms despite a large degree of relatively balanced movement of individuals in and out of severe category every six months. Examples include depression, skin changes and drowsiness, which had larger proportion (75–80%) moving in and out of severe category each 6 months period but 20% were observed in six symptoms, driven by a 9 to 18% difference between movement in and movement out of severe category. All symptoms had > 50% of people in severe group changing severity within 6 months. Conclusions Changes in the severity of existing symptoms under standard care were frequent, often occurring within six months. Certain symptoms exhibited clinically meaningful shifts at both the population and individual levels. This highlighted the need to consider improvements in symptom severity when determining sample size and statistical power for trials. By accounting for potential symptom improvements with routine care, researchers can design trials capable of robustly detecting genuine treatment effects, distinguishing them from spontaneous changes associated with standard haemodialysis.

This article presents a longitudinal study of a second language (L2) French speaker's (Aurelia) use of the construction tu vois ('you see') over 15 months. Research on first language (L1) French has shown that tu vois has been subject to grammaticalization, whereby the construction in spoken language frequently serves as a discourse marker rather than a complement-taking predicate construction expressing visual perception. Drawing on longitudinal Conversation Analysis, I qualitatively and quantitatively analyze Aurelia's use of tu vois in relation to its turn position and interactional purposes. I document a similar change happening in Aurelia's use of the construction over time as what has been observed in L1 French: While she initially deploys tu vois exclusively in its 'literal' sense of visual perception and with a complement (tu vois X, 'you see X'), she eventually starts using it as a semantically bleached discourse marker for interaction-organizational and interpersonal purposes. A few 'hybrid' cases demonstrate the progressive nature of this change, and indicate further similarities between L2 acquisition and L1 grammaticalization processes. I discuss possible reasons for the documented change and address implications of the findings for research on both the development of L2 grammar-for-interaction and language change more generally. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Alzheimer's Disease COMposite Score (ADCOMS) is more sensitive in clinical trials than conventional measures when assessing pre‐dementia. This study compares ADCOMS trajectories using clustered progression characteristics to better understand different patterns of decline. METHODS: Post‐baseline ADCOMS values were analyzed for sensitivity using mean‐to‐standard deviation ratio (MSDR), partitioned by baseline diagnosis, comparing with the original scales upon which ADCOMS is based. Because baseline diagnosis was not a particularly reliable predictor of progression, individuals were also grouped into similar ADCOMS progression trajectories using clustering methods and the MSDR compared for each progression group. RESULTS: ADCOMS demonstrated increased sensitivity for clinically important progression groups. ADCOMS did not show statistically significant sensitivity or clinical relevance for the less‐severe baseline diagnoses and marginal progression groups. CONCLUSIONS: This analysis complements and extends previous work validating the sensitivity of ADCOMS. The large data set permitted evaluation–in a novel approach–by the clustered progression group. [ABSTRACT FROM AUTHOR]

Cell division cycle 37 (CDC37) modulates disease progression and bortezomib resistance in multiple myeloma by regulating X-box binding protein 1, nuclear factor-kappa-B, etc. This study aimed to explore the prognostic implication of CDC37 before and after bortezomib-based induction treatment in multiple myeloma patients. CDC37 was detected from plasma cells of bone marrow by reverse transcription-quantitative polymerase chain reaction at baseline and after bortezomib-based induction treatment in 82 multiple myeloma patients, and in 20 disease controls and 20 healthy controls. CDC37 was increased in multiple myeloma patients versus disease controls and healthy controls (both P < 0.001). In multiple myeloma patients, CDC37 was related to increased serum creatinine (P = 0.017) and beta-2-microglobulin (P = 0.027), as well as unfavorable revised International Staging System stage (P = 0.041). Notably, CDC37 was reduced after bortezomib-based induction treatment versus that at baseline (P < 0.001). Furthermore, CDC37 at baseline was reduced in patients who achieved complete response versus those who did not achieve that (P = 0.023). Additionally, CDC37 after bortezomib-based induction treatment was also decreased in patients who achieved complete response (P < 0.001) and objective response (P = 0.001) versus those who did not reach them. Meanwhile, CDC37 at baseline only predicted worse progression-free survival (P = 0.033). Notably, CDC37 after bortezomib-based induction treatment estimated both shorter progression-free survival (P = 0.006) and overall survival (P = 0.005), which was confirmed by multivariate regression analysis. CDC37 decreases after bortezomib-based induction treatment, while its higher expression reflects unsatisfactory induction treatment response and survival in multiple myeloma. [ABSTRACT FROM AUTHOR]

Objectives Existing literature on the effects of psychological resources on health-protective behaviors in coronavirus disease 2019 (COVID-19) and other contexts has focused heavily on cross-sectional relationships. Informed by self-determination theory, the current study aims to overcome this limitation by investigating the cross-sectional and longitudinal relationships among loneliness, purpose in life, and protective behaviors before and during the COVID-19 pandemic in the U.S. older adults. Methods This study uses data from the 2016 and 2020 waves of the Health and Retirement Study, a nationally representative longitudinal panel study of older adults in the United States. The working sample size was 2,649. A path model and a cross-lagged panel model were applied for the analyses. Results Purpose in life fully mediated the negative impact of loneliness on protective behaviors when measured cross-sectionally. Moreover, prepandemic loneliness was associated with a decrease in purpose in life over time. On the other hand, prepandemic purpose in life was associated with a decrease in loneliness and an increase in protective behaviors over time. Discussion Our cross-sectional finding on the mediating role of purpose in life reveals a psychological mechanism useful for future interventions. Furthermore, the longitudinal influence of prepandemic loneliness on purpose in life deserves both scholarly and clinical attention. Most importantly, the longitudinal effects of purpose in life on loneliness and protective behaviors provide guidance for preparing older adults during normal times to cope with loneliness and to comply more with recommended measures during future health crises (such as the COVID-19 pandemic). [ABSTRACT FROM AUTHOR]

Interα-trypsin inhibitor heavy chain H4 (ITIH4) modulates inflammation and immunity, which take part in the pathogenesis of ankylosing spondylitis (AS). The current research intended to discover the clinical value of serum ITIH4 quantification for AS management. Serum ITIH4 among 80 AS patients before current treatment initiation (baseline) at weeks (W) 4, 8 and 12 after treatment was detected by ELISA. Serum ITIH4 from 20 disease controls (DCs) and 20 healthy controls (HCs) was detected. ITIH4 expression was lower in AS patients than in DCs (p = 0.002) and HCs (p < 0.001). Among AS patients, ITIH4 was negatively associated with C-reactive protein (CRP) (r = −0.311, p = 0.005), bath AS disease activity index (BASDAI) (r = −0.223, p = 0.047), total pack pain (r = −0.273, p = 0.014) and AS disease activity score (ASDAS) (CRP) (r = −0.265, p = 0.018). Meanwhile, ITIH4 was negatively related to tumor necrosis factor (TNF)-α (r = −0.364, p = 0.001), interleukin (IL)-1β (r = −0.251, p = 0.025), IL-6 (r = −0.292, p = 0.009) and IL-17A (r = −0.254, p = 0.023). After treatment, the assessment of the spondylitis arthritis international society 40 response rate was 28.7% at W4, 46.3% at W8 and 55.0% at W12; ITIH4 showed an increasing trend from baseline to W12 (p < 0.001). Furthermore, ITIH4 at W8 (p = 0.020) and W12 (p = 0.035), but not at baseline or W4 (both p > 0.05), was enhanced in response patients vs. nonresponse patients. Additionally, ITIH4 at W12 was increased in AS patients receiving TNF inhibitors vs. those receiving nonsteroidal anti-inflammatory drugs (NSAIDs) (p = 0.024). Serum ITIH4 increases after treatment, and its augmentation is correlated with lower disease activity, decreased inflammation and enhanced treatment response in AS patients. [ABSTRACT FROM AUTHOR]

Objective: Histone deacetylase 4 (HDAC4) regulates lipid accumulation, inflammation, endothelial injury, and atherosclerosis to participate in the pathogenesis of cardiovascular diseases. This study aimed to explore the value of serum HDAC4 change before and after percutaneous coronary intervention (PCI) in predicting major adverse cardiovascular events (MACE) risk in acute coronary syndrome (ACS) patients. Methods: HDAC4 from serum was detected by enzyme-linked immunosorbent assay in 340 ACS patients at baseline, day (D)1, D3, and D7 after PCI, and from 30 healthy controls (HCs). MACE was recorded during follow-up. Results: HDAC4 was decreased in ACS patients versus HCs (P < 0.001). In ACS patients, HDAC4 was negatively related to total cholesterol (P = 0.025), low-density lipoprotein cholesterol (P = 0.007), C-reactive protein (P < 0.001), cardiac troponin I (P < 0.001), and hyperlipidemia history (P = 0.015). Additionally, HDAC4 was lowest in ST-elevation myocardial infarction (STEMI) patients, followed by non-STEMI patients, and highest in unstable angina patients (P = 0.010). After PCI, HDAC4 was decreased from baseline to D1, then increased until D7 (P < 0.001). Furthermore, HDAC4 at baseline (P = 0.002), D1 (P < 0.001), D3 (P < 0.001), and D7 (P < 0.001) were all reduced in patients who experienced MACE versus those who did not. Meanwhile, high HDAC4 at baseline (P = 0.036), D1 (P = 0.010), D3 (P = 0.012), and D7 (P = 0.012) estimated decreased accumulating MACE risk by Kaplan–Meier curve. Multivariate logistic analysis revealed that HDAC4 at D1 was independently linked to lower MACE risk (odds ratio = 0.957, P = 0.039). Conclusion: Serum HDAC4 is decreased from baseline to D1, then elevated until D7, and its increased level correlates with lower MACE risk in ACS patients receiving PCI. [ABSTRACT FROM AUTHOR]

Background: Despite the recognized high symptom prevalence in haemodialysis population, how these symptoms change over time and its implications for clinical practice and research is poorly understood. Methods: Prevalent haemodialysis patients in the SHAREHD trial reported 17 POS-S Renal symptoms (none, mild, moderate, severe and overwhelming) at baseline, 6, 12 and 18 months. To assess the prevalence change at population level in people reporting moderate or worse symptoms at baseline, the absolute change in prevalence was estimated using multi-level mixed effects probit regression adjusting for age, sex, time on haemodialysis and Charlson Comorbidity Score. To assess changes at individual level, the proportion of people changing their symptom score every 6 months was estimated. Results: Five hundred fifty-two participants completed 1725 questionnaires at four timepoints. Across all 17 symptoms with moderate or worse symptom severity at baseline, the majority of the change in symptom prevalence at population level occurred in the 'severe' category. The absolute improvement in prevalence of the 'severe' category was ≤ 20% over 18 months in eleven of the seventeen symptoms despite a large degree of relatively balanced movement of individuals in and out of severe category every six months. Examples include depression, skin changes and drowsiness, which had larger proportion (75–80%) moving in and out of severe category each 6 months period but < 5% difference between movement in and out of severe category resulting in relatively static prevalence over time. Meanwhile, larger changes in prevalence of > 20% were observed in six symptoms, driven by a 9 to 18% difference between movement in and movement out of severe category. All symptoms had > 50% of people in severe group changing severity within 6 months. Conclusions: Changes in the severity of existing symptoms under standard care were frequent, often occurring within six months. Certain symptoms exhibited clinically meaningful shifts at both the population and individual levels. This highlighted the need to consider improvements in symptom severity when determining sample size and statistical power for trials. By accounting for potential symptom improvements with routine care, researchers can design trials capable of robustly detecting genuine treatment effects, distinguishing them from spontaneous changes associated with standard haemodialysis. [ABSTRACT FROM AUTHOR]

Childhood is a period of pronounced improvements in children's ability to remember connections between details of an event (i.e. binding ability). However, the mechanisms supporting these changes remain unclear. Prior evidence is mixed, with some proposing that improvements in the ability to identify previous connections (i.e. increases in hits) account for memory changes, whereas other evidence suggests changes are additionally supported by the ability to identify inaccurate connections (i.e. decreases in false alarms). To disentangle the role of each process, we investigated changes in hits and false alarms within the same paradigm. The present study of 200 4-to-8-year-old children (100 female) used a cohort sequential design to assess longitudinal change in binding ability. Developmental trajectories of d', hit, and false alarm rates were examined using latent growth analysis. Findings demonstrated non-linear improvements in children's binding ability from age 4-to-8-years. Improvements were differentially supported by hits and false alarms. Hit rates improved non-linearly from 4-to-8-years, with greater growth from 4-to-6-years. False alarm rates did not significantly change from 4-to-6-years, but significantly decreased from 6-to-8-years. Overall, findings show improvements in binding ability are predominantly supported by increased hit rates between 4-to-6-years and by both increasing hit rates and decreasing false alarms rates between 6-to-8-years. Together, these results suggest that binding development is non-linear and that mechanisms underlying improvements differ across childhood. [ABSTRACT FROM AUTHOR]

Shoulder arthroplasty (SA), including hemiarthroplasty, reverse and anatomical total SA (TSA), improves quality of life by reducing shoulder pain and restoring function in patients not only with irreparable rotator cuff tears and/or cuff tear arthropathy but also with osteoarthritis posttraumatic arthritis, proximal humeral fractures, etc. Given the rapid developments in artificial joints and improvements in postoperative outcomes, the number of SA surgeries is increasing worldwide. Therefore, we investigated changes in trends over time in Korea. We analyzed the longitudinal changes in the incidence of SA including anatomic and reverse TSA, hemiarthroplasty, and shoulder revision arthroplasty (SRA) by changes in the Korean age profile, surgical facilities, and geographical regions using the Korean Health Insurance Review and Assessment Service database from 2010 to 2020. Data were also collected from the National Health Insurance Service and the Korean Statistical Information Service. From 2010 to 2020, the TSA rate per 1,000,000 person-years increased from 10.571 to 101.372 (time trend = 1.252; 95% CI 1.233-1.271, P <.001). The shoulder hemiarthroplasty (SH) rate per 1,000,000 person-years decreased from 6.414 to 3.685 (time trend = 0.933; 95% CI 0.907-0.960, P <.001). The SRA rate per 1,000,000 person-years increased from 0.792 to 2.315; the increase was significant (time trend = 1.133; 95% CI 1.101-1.166, P <.001). Overall, TSA and SRA are increasing and SH is decreasing. For both total TSA and SRA, steep increases are evident in the numbers of patients in their 70s and older than 80 years. The SH trend is decreasing regardless of differences in age groups, surgical facilities, and geographical regions. SRA is preferentially performed in Seoul. [ABSTRACT FROM AUTHOR]

PurposeWe evaluated the impact of partial volume correction (PVC) methods on the quantification of longitudinal [18F]GTP1 tau positron-emission tomography (PET) in Alzheimer's disease and the suitability of describing the tau pathology burden temporal trajectories using linear mixed-effects models (LMEM).MethodsWe applied van Cittert iterative deconvolution (VC), 2-compartment, and 3-compartment, and the geometric transfer matrix plus region-based voxelwise methods to data acquired in an Alzheimer's disease natural history study over 18 months at a single imaging site. We determined the optimal PVC method by comparing the standardized uptake value ratio change (%ΔSUVR) between diagnostic and tau burden–level groups and the longitudinal repeatability derived from the LMEM. The performance of LMEM analysis for calculating %ΔSUVR was evaluated in a natural history study and in a multisite clinical trial of semorinemab in prodromal to mild Alzheimer's disease by comparing results to traditional per-visit estimates.ResultsThe VC, 2-compartment, and 3-compartment PVC methods had similar performance, whereas region-based voxelwise overcorrected regions with a higher tau burden. The lowest within-subject variability and acceptable group separation scores were observed without PVC. The LMEM-derived %ΔSUVR values were similar to the per-visit estimates with lower variability.ConclusionThe results indicate that the tested PVC methods do not offer a clear advantage or improvement over non-PVC images for the quantification of longitudinal [18F]GTP1 PET data. LMEM offers a robust framework for the longitudinal tau PET quantification with low longitudinal test–retest variability.Clinical trial registrationNCT02640092 and NCT03289143.

BackgroundAdverse psychosocial factors play an important role in cardio-cerebral vascular disease (CCVD). The aim of this study was to evaluate the impact of the cumulative burden of loneliness on the risk of CCVD in the Chinese older adult.MethodsA total of 6,181 Chinese older adult over the age of 62 in the monitoring survey of the fourth Sample Survey of the Aged Population in Urban and Rural China (SSAPUR) were included in this study. The loneliness cumulative burden (scored by cumulative degree) was weighted by the loneliness score for two consecutive years (2017–2018) and divided into low- and high-burden groups. The outcome was defined as the incidence of CCVD 1 year later (2018–2019). A multivariate logistic regression model was used to examine the relationship between the cumulative burden of loneliness and the new onset of CCVD.ResultsAmong participants, 18.9% had a higher cumulative burden of loneliness, and 11.5% had a CCVD incidence within 1 year. After multivariate adjustment, the risk of developing CCVD in the high-burden group was approximately 37% higher than that in the low-burden group (OR 1.373, 95%CI 1.096–1.721; p = 0.006). Similar results were obtained when calculating the burden based on cumulative time. Longitudinal change in loneliness was not significantly associated with an increased risk of CCVD. A higher cumulative burden of loneliness may predict a higher risk of developing CCVD in older adult individuals aged 62–72 years or in those with diabetes.ConclusionThe cumulative burden of loneliness can be used to assess the risk of new-onset CCVD in the older adult in the short term.

To analyze the longitudinal change in the Australian government's attitude towards the Belt and Road Initiative (BRI), various sources on the BRI have been examined. The findings indicate a shift in the Australian government's attitude from positive to negative since 2013. This change can be attributed to several factors, including the influence of the United States, the presence of a conservative and xenophobic culture within Australian society, the longstanding policy of maintaining “cold political relations and hot economic ties” between Australia and China, and the political struggle between political parties in Australia. To address this issue, it is recommended to clarify the true nature of the BRI, adjust international cooperation models, enhance the standardization of international BRI cooperation mechanisms, and expedite the development of the BRI discourse system. This research may provide a political, economic, and cultural perspective on the deteriorating Sino-Australian relationship in terms of BRI cooperation.

Abstract Background Physical activity promotes health and is particularly important during middle and older age for decreasing morbidity and mortality. We assessed the correlates of changes over time in moderate-to-vigorous physical activity (MVPA) in Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL: mean [SD] age 49.2 y [11.5]) and compared them to a cohort of primarily White adults from the Framingham Heart Study (FHS: mean [SD] 46.9 y [9.2]). Methods Between 2008 and 2019, we assessed accelerometry-based MVPA at two time points with an average follow-up of: 7.6 y, SD 1.3 for HCHS/SOL, and 7.8 y, SD 0.7 for FHS. We used multinomial logistic regression to relate socio-demographic and health behaviors with changes in compliance with 2018 US recommendations for MVPA from time 1 to time 2 (remained active or inactive; became active or inactive) across the two cohorts. Results In HCHS/SOL mean MVPA was 22.6 (SD, 23.8) minutes at time 1 and dropped to 16.7 (19.0) minutes at time 2. In FHS Mean MVPA was 21.7 min (SD, 17.7) at time 1 and dropped to 21.3 min (SD, 19.2) at time 2. Across both cohorts, odds of meeting MVPA guidelines over time were about 6% lower in individuals who had lower quality diets vs. higher, about half in older vs. younger adults, about three times lower in women vs. men, and 9% lower in individuals who had a higher vs. lower BMI at baseline. Cohorts differed in how age, gender, income, education, depressive symptoms, marital status and perception of general health and pain associated with changes in physical activity. High income older Hispanics/Latino adults were more likely to become inactive at the follow-up visit as were HCHS/SOL women who were retired and FHS participants who had lower levels of education and income. Higher depressive symptomology was associated with becoming active only in HCHS/SOL women. Being male and married was associated with becoming inactive in both cohorts. Higher perception of general health and lower perception of pain were associated with remaining active only in FHS adults. Conclusions These findings highlight potentially high-risk groups for targeted MVPA intervention.

Abstract Background Higher fasting plasma glucose (FPG) levels were associated with an increased risk of all-cause mortality; however, the associations between long-term FPG trajectory groups and mortality were unclear, especially among individuals with a normal FPG level at the beginning. The aims of this study were to examine the associations of FPG trajectories with the risk of mortality and identify modifiable lifestyle factors related to these trajectories. Methods We enrolled 50,919 individuals aged ≥ 20 years old, who were free of diabetes at baseline, in the prospective MJ cohort. All participants completed at least four FPG measurements within 6 years after enrollment and were followed until December 2011. FPG trajectories were identified by group-based trajectory modeling. We used Cox proportional hazards models to examine the associations of FPG trajectories with mortality, adjusting for age, sex, marital status, education level, occupation, smoking, drinking, physical activity, body mass index, baseline FPG, hypertension, dyslipidemia, cardiovascular disease or stroke, and cancer. Associations between baseline lifestyle factors and FPG trajectories were evaluated using multinomial logistic regression. Results We identified three FPG trajectories as stable (n = 32,481), low-increasing (n = 17,164), and high-increasing (n = 1274). Compared to the stable group, both the low-increasing and high-increasing groups had higher risks of all-cause mortality (hazard ratio (HR) = 1.18 (95% CI 0.99–1.40) and 1.52 (95% CI 1.09–2.13), respectively), especially among those with hypertension. Compared to participants with 0 to 1 healthy lifestyle factor, those with 6 healthy lifestyle factors were more likely to be in the stable group (ORlow-increasing = 0.61, 95% CI 0.51–0.73; ORhigh-increasing = 0.20, 95% CI 0.13–0.32). Conclusions Individuals with longitudinally increasing FPG had a higher risk of mortality even if they had a normal FPG at baseline. Adopting healthy lifestyles may prevent individuals from transitioning into increasing trajectories.

Abstract Background Whether past disaster experiences affect the association between changes in social isolation and depressive symptoms is largely unknown. This study examined the association between changes in social isolation and depressive symptoms among survivors who experienced earthquake damage in the aftermath of the Great East Japan Earthquake (GEJE). Methods We analyzed longitudinal data from 10,314 participants who responded to self-report questionnaires on the Lubben Social Network Scale-6 (LSNS-6) and the Center for Epidemiological Studies-Depressive Scale (CES-D) in both the baseline survey (FY2013 to FY2015) and follow-up survey (FY2017 to FY2019) after the GEJE. According to changes in the presence of social isolation (

Abstract BACKGROUND The Alzheimer's Disease COMposite Score (ADCOMS) is more sensitive in clinical trials than conventional measures when assessing pre‐dementia. This study compares ADCOMS trajectories using clustered progression characteristics to better understand different patterns of decline. METHODS Post‐baseline ADCOMS values were analyzed for sensitivity using mean‐to‐standard deviation ratio (MSDR), partitioned by baseline diagnosis, comparing with the original scales upon which ADCOMS is based. Because baseline diagnosis was not a particularly reliable predictor of progression, individuals were also grouped into similar ADCOMS progression trajectories using clustering methods and the MSDR compared for each progression group. RESULTS ADCOMS demonstrated increased sensitivity for clinically important progression groups. ADCOMS did not show statistically significant sensitivity or clinical relevance for the less‐severe baseline diagnoses and marginal progression groups. CONCLUSIONS This analysis complements and extends previous work validating the sensitivity of ADCOMS. The large data set permitted evaluation–in a novel approach–by the clustered progression group.

ABSTRACTObjective Cell division cycle 37 (CDC37) modulates disease progression and bortezomib resistance in multiple myeloma by regulating X-box binding protein 1, nuclear factor-kappa-B, etc. This study aimed to explore the prognostic implication of CDC37 before and after bortezomib-based induction treatment in multiple myeloma patients.Methods CDC37 was detected from plasma cells of bone marrow by reverse transcription-quantitative polymerase chain reaction at baseline and after bortezomib-based induction treatment in 82 multiple myeloma patients, and in 20 disease controls and 20 healthy controls.Results CDC37 was increased in multiple myeloma patients versus disease controls and healthy controls (both P

Objectives From a theoretical point of view, older adults may not necessarily face a greater risk of becoming lonely than middle-aged adults but are more likely at a disadvantage in fighting loneliness. Therefore, in this study, we differentiate between the risk of becoming lonely and the risk of remaining lonely. Methods A large longitudinal data set representative of the German noninstitutionalized population from 40 to 85 years of age (N = 15,408; 49% female participants) was used in the analysis. Lagged logistic regression models were estimated to investigate the effect of earlier experiences of severe loneliness on the risk of being lonely after three years across middle age and late adulthood. Individual differences in health, views on aging, and social activities were taken into account to explore their role in age differences in the risk of remaining lonely. Results The analysis revealed marginal age differences in the risk of becoming lonely but a marked age gradient regarding the risk of remaining lonely. Lonely older adults who were older than 75 years of age were more likely to remain lonely after three years than lonely middle-aged adults. Controlling for individual differences in health, views on aging as social loss, and social activities accounted for this age difference. Discussion Interventions against loneliness may prioritize older age groups because losses in capacities, shifts in motivations, and a degraded opportunity structure render it increasingly less likely that older adults leave a state of loneliness on their own accord. [ABSTRACT FROM AUTHOR]

Background and Objective: Weight and muscle loss are predictors of poor outcomes in chronic obstructive pulmonary disease. However, to our knowledge, no study has investigated the predictors of longitudinal weight loss or its composition from functional and morphological perspectives. Methods: This longitudinal observational study with a median follow‐up period of 5 years (range: 3.0–5.8 years) included patients with COPD and ever‐smokers at risk of COPD. Using chest computed tomography (CT) images, airway and emphysematous lesions were assessed as the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the percentage of low attenuation volume (LAV%). Muscle mass was estimated using cross‐sectional areas (CSAs) of the pectoralis and erector spinae muscles, and fat mass was estimated using the subcutaneous fat thickness at the level of the 8th rib measured using chest CT images. Statistical analyses were performed using the linear mixed‐effects models. Results: In total, 114 patients were enrolled. Their body mass index remained stable during the study period while body weight and muscle CSA decreased over time and the subcutaneous fat thickness increased. Reduced forced expiratory volume in 1 s and peak expiratory flow (PEF) at baseline predicted the future decline in muscle CSA. Conclusion: Severe airflow limitation predicted future muscle wasting in patients with COPD and ever‐smokers at risk of COPD. Airflow limitation with a PEF slightly below 90% of the predicted value may require intervention to prevent future muscle loss. [ABSTRACT FROM AUTHOR]

The present study examines the association between gray matter volume and cognition. Studies that have examined this issue have focused primarily on older adults, whereas the present study examines the issue across the entire adult lifespan. A total of 463 adults, ages 20–88 at first assessment, were followed longitudinally across three assessments over 8–10 years. Significant individual differences in a general cognition measure comprised of measures of speed of processing, working memory, and episodic memory were observed, as well as in measures of cortical and subcortical gray matter. Parallel process latent growth curve modeling showed a reliable relationship between decreases in cortical matter and cognitive decline across the entire adult lifespan, which persisted after controlling for age effects. Implications of these findings in relation to progression toward dementia, risk assessment, cognitive intervention, and environmental factors are discussed, as well as implications for theories of cognitive aging. [ABSTRACT FROM AUTHOR]

The article departs from a unique data set covering 44 villages over the period 2002 to 2013/2015 and finds that polarization in living standards has fallen dramatically, largely based on access to agricultural output markets. Rural differentiation with respect to land access has, however, increased rapidly, showing the importance of contextualizing improvements in living standards in relation to land access. The spatial distribution of these patterns varies greatly. Theoretically, the article shows that perspectives of both differentiation and broad-based growth are relevant for the study of African smallholder agriculture. Market participation in the short term leads to livelihood improvements, but over time enhances differentiation with respect to access to land. [ABSTRACT FROM AUTHOR]

The purpose of the study was to examine a bivariate latent change score model of depressive symptoms and functional limitations (activities of daily living) among centenarian or near-centenarian survivors over four waves using the Health and Retirement Study. Four hundred and sixty participants who eventually survived to age 98 or older were included by calculating their death age. Data from the time when the participants were in their 80s were analyzed. The mean age at baseline (1994) was 85.5 years. The observation interval was 2 years, from 1994 to 2000. Including age, gender, and education as a covariate, eight different models were conducted to examine the bivariate effects among depressive symptoms and functional limitations. Of the eight models, the bivariate model of depressive symptoms predicting change in functional limitations fitted the data best. The parameter estimates of the final model indicated significant predictive pathways from depressive symptoms to subsequent changes in depressive symptoms and functional limitations. This study tested the bidirectional relationship between depressive symptoms and functional limitations among centenarian survivors in their 80s, which uncovered that depressive symptoms is a dominant variable among the two constructs. Our findings add to a lacking number of longitudinal studies with oldest old adults. [ABSTRACT FROM AUTHOR]

Background: Higher fasting plasma glucose (FPG) levels were associated with an increased risk of all-cause mortality; however, the associations between long-term FPG trajectory groups and mortality were unclear, especially among individuals with a normal FPG level at the beginning. The aims of this study were to examine the associations of FPG trajectories with the risk of mortality and identify modifiable lifestyle factors related to these trajectories. Methods: We enrolled 50,919 individuals aged ≥ 20 years old, who were free of diabetes at baseline, in the prospective MJ cohort. All participants completed at least four FPG measurements within 6 years after enrollment and were followed until December 2011. FPG trajectories were identified by group-based trajectory modeling. We used Cox proportional hazards models to examine the associations of FPG trajectories with mortality, adjusting for age, sex, marital status, education level, occupation, smoking, drinking, physical activity, body mass index, baseline FPG, hypertension, dyslipidemia, cardiovascular disease or stroke, and cancer. Associations between baseline lifestyle factors and FPG trajectories were evaluated using multinomial logistic regression. Results: We identified three FPG trajectories as stable (n = 32,481), low-increasing (n = 17,164), and high-increasing (n = 1274). Compared to the stable group, both the low-increasing and high-increasing groups had higher risks of all-cause mortality (hazard ratio (HR) = 1.18 (95% CI 0.99–1.40) and 1.52 (95% CI 1.09–2.13), respectively), especially among those with hypertension. Compared to participants with 0 to 1 healthy lifestyle factor, those with 6 healthy lifestyle factors were more likely to be in the stable group (ORlow-increasing = 0.61, 95% CI 0.51–0.73; ORhigh-increasing = 0.20, 95% CI 0.13–0.32). Conclusions: Individuals with longitudinally increasing FPG had a higher risk of mortality even if they had a normal FPG at baseline. Adopting healthy lifestyles may prevent individuals from transitioning into increasing trajectories. Highlights: Among individuals with normal levels of fasting plasma glucose (FPG) at baseline, those who experienced upward trends in FPG over a 6-year period had a higher risk of mortality compared to individuals with relatively low and stable FPG levels. Individuals with hypertension were more vulnerable to the adverse effects of increasing FPG trajectories on mortality. Adopting healthy lifestyles may prevent participants with normal FPG levels at baseline from developing a higher risk of mortality. [ABSTRACT FROM AUTHOR]

Aim: Our previous study discovered that cell division control protein 42 (CDC42) correlated with decreased disease activity and risk of developing rheumatoid arthritis (RA), along with repressed T helper type 17 cell differentiation. This study aimed to further estimate the longitudinal change of serum CDC42 and its association with treatment outcomes to tumor necrosis factor inhibitor (TNFi) in RA. Methods: CDC42 was detected in serum by ELISA at week (W)0, W6, W12, and W24 in 88 RA patients undergoing TNFi treatment, and after enrollment in 20 disease controls (DCs) and 20 healthy controls (HCs). Results: CDC42 was lower in RA patients compared with DCs and HCs (both p <.001); meanwhile, it negatively related to C‐reactive protein (p =.011) and DAS28 score (p =.006). Regarding TNFi type, 40.9%, 33.0%, 17.0%, and 9.1% of patients received adalimumab, etanercept, golimumab, and infliximab, respectively. Notably, CDC42 was increased from W0 to W24 in RA patients receiving TNFi treatment (p <.001), also in patients receiving adalimumab (p <.001), etanercept (p <.001), golimumab (p <.001), and infliximab (p =.001). Furthermore, CDC42 at W24 was higher in patients with a clinical response to TNFi treatment compared with those without (p =.023); CDC42 at W12 (p =.027) and W24 (p =.002) was elevated in patients with clinical low disease activity in response to TNFi treatment versus those without; whereas CDC42 at W12 (p =.074) and W24 (p =.068) only showed an increasing trend in patients with clinical remission with TNFi treatment, but did not achieve statistical significance. Conclusion: Circulating CDC42 is elevated during TNFi administration; its increase reflects good 24‐week TNFi treatment responses in RA patients. [ABSTRACT FROM AUTHOR]

Circulating tumor cell (CTC) exerts diagnostic and prognostic value in colorectal cancer (CRC) patients. This study intended to further investigate the longitudinal change of CTC count, and its correlation with the prognosis of immune checkpoint inhibitor (ICI)-based treatments in unresectable, metastatic CRC patients. Fifty-six unresectable, metastatic CRC patients receiving ICI-based treatments were enrolled. CTC count was assessed by the CellSearch system at baseline and month (M)2 in their peripheral blood samples. Forty-one (73.2%) and sixteen (28.5%) patients had CTC count ≥1 and ≥5 at baseline, respectively. Meanwhile, CTC count at M2 was decreased versus that at baseline (median (interquartile range): 1.0 (0.0–3.0) versus 3.0 (0.0–5.0)) (p < 0.001). Besides, increased CTC count at baseline (p = 0.009) and M2 (p = 0.006) associated with a reduced overall response rate. Baseline CTC count ≥5 related to worse progression-free survival (PFS) (p = 0.007), but baseline CTC count ≥1 did not; additionally, baseline CTC count ≥1 (p = 0.043) and ≥5 (p = 0.016) linked to shorter overall survival (OS). Furthermore, M2 CTC count ≥1 (p = 0.002) and ≥5 (p < 0.001) both correlated with poor PFS; meanwhile, M2 CTC count ≥1 (p = 0.006) and ≥5 (p < 0.001) also related to worse OS. After adjustment, only CTC count at M2 ≥ 5 independently associated with unsatisfactory PFS (hazard ratio (HR)=3.218, p = 0.011) and OS (HR = 3.229, p = 0.038). CTC count is decreased during ICI-based treatments, its reduction represents satisfactory treatment outcomes in unresectable, metastatic CRC patients. Notably, the CTC count at 5 as a cutting threshold after a two-month treatment has an impressive prognostic value. [ABSTRACT FROM AUTHOR]

Background: Whether past disaster experiences affect the association between changes in social isolation and depressive symptoms is largely unknown. This study examined the association between changes in social isolation and depressive symptoms among survivors who experienced earthquake damage in the aftermath of the Great East Japan Earthquake (GEJE). Methods: We analyzed longitudinal data from 10,314 participants who responded to self-report questionnaires on the Lubben Social Network Scale-6 (LSNS-6) and the Center for Epidemiological Studies-Depressive Scale (CES-D) in both the baseline survey (FY2013 to FY2015) and follow-up survey (FY2017 to FY2019) after the GEJE. According to changes in the presence of social isolation (< 12 of LSNS-6) at two time points, participants were categorized into four groups: “not socially isolated,” “improved socially isolated,” “newly socially isolated,” and “continuously socially isolated.” At the follow-up survey, a CES-D score of ≥ 16 indicates the presence of depressive symptoms. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were estimated using the logistic regression analysis to examine the influence of the change in social isolation over four years on depressive symptoms. Results: Participants who were newly socially isolated had a significantly higher prevalence of depressive symptoms than those who were not socially isolated (AOR = 1.89, 95% CI = 1.61 − 2.23). In addition, AORs were highest for those who were continuously socially isolated and had experienced house damage (AOR = 2.17, 95% CI = 1.73 − 2.72) and those who were newly socially isolated and had not experienced the death of family members due to the GEJE (AOR = 1.88, 95%CI = 1.60 − 2.22). Conclusion: Our longitudinal findings suggest that being newly or continuously socially isolated is associated with a risk of depressive symptoms, not only among those who had experienced house damage or the death of a family member, but also those who had not, in the disaster-affected area. Our study underlines the clinical importance of social isolation after a large-scale natural disaster and draws attention to the need for appropriate prevention measures. [ABSTRACT FROM AUTHOR]

The goal of this study was to test whether interpersonal dysfunction, characterized by loneliness and/or dissatisfaction with relationships, is an imminent predictor of financial exploitation vulnerability (FEV) among adults age 50+ within a 6-month observation period. This study also tests whether FEV prospectively predicts interpersonal dysfunction. Twenty-six adults aged 50 or older completed a study involving baseline data collection and 13 follow-ups over 6 months. Linear mixed models were used for primary analyses. After adjustment for demographic, psychological and cognitive covariates, there were between-person effects of FEV and interpersonal dysfunction across follow-ups, suggesting that those with generally higher interpersonal dysfunction compared to other participants also reported greater FEV (B(SE) = 1.09(.33), p =.003). There was a within-person effect (B(SE) =.08(.03), p =.007) of elevated interpersonal dysfunction predicting greater FEV two weeks later across all follow-ups. Within-person effect of FEV was not predictive of interpersonal dysfunction (B(SE) =.25(.15), p =.10). There was also a significant effect of age (B(SE) = –.06(.02), p =.007), such that older individuals had lower FEV throughout follow-ups. Among adults age 50+, individuals with higher interpersonal dysfunction relative to others in the study reported greater FEV throughout the 6-month observation period. Increased loneliness and social dissatisfaction, relative to one's average level, predicts subsequent increases in FEV, and may be an imminent risk factor for exploitation. [ABSTRACT FROM AUTHOR]

IntroductionAmyloid pathology in cognitively normal adults is associated with subjective cognitive decline, potentially reflecting awareness of Alzheimer's-related memory deficits. To clarify the mechanism underlying this relationship, we used mediational analyses to determine the role of depression, anxiety, and actual memory performance.MethodsTo assess amyloid deposition, we imaged 85 cognitively normal adults with florbetapir positron emission tomography imaging. Subjective cognitive decline was measured using a multidimensional instrument that assessed seven subjective memory domains. Mediational measures included assessments of actual memory performance (current and retrospective longitudinal change), depression, and anxiety.ResultsThe relationship between amyloid and subjective cognitive decline was mediated by poorer memory performance and greater retrospective memory decline, not depression or anxiety. The mediational roles were significant for domains associated with memory function and memory-related anxiety.DiscussionIn individuals harboring amyloid, self-reported beliefs of declining memory likely indicate early self-awareness of actual worsening function rather than depression or anxiety.

BackgroundIs posttreatment functional status prognostic of overall survival in patients with head and neck cancer (HNC).MethodsIn an HNC clinical trial, 495 patients had two posttreatment functional assessments measuring diet, public eating, and speech within 6 months. Patients were grouped by impairment (highly, moderately, modestly, or not impaired) and determined if they improved, declined, or did not change from the first assessment to the second. Multivariable Cox models estimated overall mortality.ResultsAcross all three scales, the change in posttreatment patient function strongly predicted overall survival. In diet, patients who declined to highly impaired had three times the mortality of patients who were not impaired at both assessments (hazard ratio [HR] = 3.60; 95% confidence interval, 2.02-6.42). For patients improving from highly impaired, mortality was statistically similar to patients with no impairment (HR = 1.38; 95% CI, 0.82-2.31).ConclusionsPosttreatment functional status is a strong prognostic marker of survival in patients with HNC.

Introduction: Acculturation‐related characteristics, that is, factors directly connected to culture and familial relationships, are associated with engaged research participation within Latino communities. Despite this, little empirical data exists on whether acculturation changes over time in older Latinos, which has potential implications for Alzheimer's disease and related dementias (ADRD) research study design including longer duration clinical trial implementation. Methods: Self‐identified Latinos (n = 222; mean age = 71, 76% female) participating in one of three ongoing longitudinal community‐based cohort studies of aging who reported their nativity outside of the United States/District of Columbia (US/DC) contributed, on average, 4.0 ± 1.2 years of annually collected data. This included acculturation‐related characteristics of total, language‐, and social‐based scores from the Short Acculturation Scale for Hispanics (SASH) and total and domain‐specific scores from an abbreviated Sabogal Familism questionnaire. We used ordinal mixed effects models and linear mixed effects models (as appropriate) to assess change in acculturation metrics after adjusting for age, sex, education, income, and duration of time in the US/DC. Results: Although none of the SASH metrics changed over time (P‐values ≥ 0.25), all Familism metrics declined over time (P‐values ≤ 0.044). Additionally, select participant‐based characteristics including years of education were significantly (and differentially) associated with level of, but not change in, acculturation‐related outcomes. Discussion: Results suggest that specific acculturation‐related factors (i.e., familism) change over time in older Latinos, and participant‐based characteristics associated with baseline levels of (but not change in) acculturation more generally. Thus, acculturation‐related characteristics are not all static, trait‐like qualities but rather a multi‐faceted, and at times evolving, construct. Considering this dynamic phenotyping is important when contextualizing older Latinos' lived experience, and when designing, adapting, and conducting ADRD clinical trials and other health‐related interventions. [ABSTRACT FROM AUTHOR]

Background Parkinson's disease (PD) increases risk for dementia and cascading adverse outcomes. The eight-item Montreal Parkinson Risk of Dementia Scale (MoPaRDS) is a rapid, in-office dementia screening tool. We examine predictive validity and other characteristics of the MoPaRDS in a geriatric PD cohort by testing a series of alternative versions and modelling risk score change trajectories. Methods Participants were 48 initially non-demented PD patients (Mage = 71.6 years, range = 65--84) from a three-year, threewave prospective Canadian cohort study. A dementia diagnosis at Wave 3 was used to stratify two baseline groups: PD with Incipient Dementia (PDID) and PD with No Dementia (PDND). We aimed to predict dementia three years prior to diagnosis using baseline data for eight indicators that harmonized with the original report, plus education. Results Three MoPaRDS items (age, orthostatic hypotension, mild cognitive impairment [MCI]) discriminated the groups both independently and as a composite three-item scale (area under the curve [AUC] = 0.88). The eight-item MoPaRDS reliably discriminated PDID from PDND (AUC = 0.81). Education did not improve predictive validity (AUC = 0.77). Performance of the eight-item MoPaRDS varied across sex (AUCfemales = 0.91; AUCmales = 0.74), whereas the three-item configuration did not (AUCfemales = 0.88; AUCmales = 0.91). Risk scores of both configurations increased over time. Conclusions We report new data on the application of the MoPaRDS as a dementia prediction tool for a geriatric PD cohort. Results support the viability of the full MoPaRDS, and indicate that an empirically determined brief version is a promising complement. [ABSTRACT FROM AUTHOR]

Summary: In observational cohort studies, there is frequently interest in modeling longitudinal change in a biomarker (ie, physiological measure indicative of metabolic dysregulation or disease; eg, blood pressure) in the absence of treatment (ie, medication), and its association with modifiable risk factors expected to affect health (eg, body mass index). However, individuals may start treatment during the study period, and consequently biomarker values observed while on treatment may be different than those that would have been observed in the absence of treatment. If treated individuals are excluded from analysis, then effect estimates may be biased if treated individuals differ systematically from untreated individuals. We addressed this concern in the setting of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), an observational cohort study that employed a complex survey sampling design to enable inference to a finite target population. We considered biomarker values measured while on treatment to be missing data, and applied missing data methodology (inverse probability weighting (IPW) and doubly robust estimation) to this problem. The proposed methods leverage information collected between study visits on when individuals started treatment, by adapting IPW and doubly robust approaches to model the treatment mechanism using survival analysis methods. This methodology also incorporates sampling weights and uses a bootstrap approach to estimate standard errors accounting for the complex survey sampling design. We investigated variance estimation for these methods, conducted simulation studies to assess statistical performance in finite samples, and applied the methodology to model temporal change in blood pressure in HCHS/SOL. [ABSTRACT FROM AUTHOR]

BACKGROUND:Quantitative-chemical-shift-encoded (CSE)-MRI methods have been applied to the liver. The feasibility and potential utility CSE-MRI in monitoring changes in pancreatic proton density fat fraction (PDFF) have not yet been demonstrated. PURPOSE:To use quantitative CSE-MRI to estimate pancreatic fat changes during a weight-loss program in adults with severe obesity and nonalcoholic fatty liver disease (NAFLD). To explore the relationship of reduction in pancreatic PDFF with reductions in anthropometric indices. STUDY TYPE:Prospective/longitudinal. POPULATION:Nine adults with severe obesity and NAFLD enrolled in a weight-loss program. FIELD STRENGTH/SEQUENCE:CSE-MRI fat quantification techniques and multistation-volumetric fat/water separation techniques were performed at 3 T. ASSESSMENT:PDFF values were recorded from parametric maps colocalized across timepoints. STATISTICAL TESTS:Rates of change of log-transformed variables across time were determined (linear-regression), and their significance assessed compared with no change (Wilcoxon test). Rates of change were correlated pairwise (Spearman's correlation). RESULTS:Mean pancreatic PDFF decreased by 5.7% (range 0.7-17.7%) from 14.3 to 8.6%, hepatic PDFF by 11.4% (2.6-22.0%) from 14.8 to 3.4%, weight by 30.9 kg (17.3-64.2 kg) from 119.0 to 88.1 kg, body mass index by 11.0 kg/m2 (6.3-19.1 kg/m2 ) from 44.1 to 32.9 kg/m2 , waist circumference (WC) by 25.2 cm (4.0-41.0 cm) from 133.1 to 107.9 cm, HC by 23.5 cm (4.5-47.0 cm) from 135.8 to 112.3 cm, visceral adipose tissue (VAT) by 2.9 L (1.7-5.7 L) from 7.1 to 4.2 L, subcutaneous adipose tissue (SCAT) by 4.0 L (2.9-7.4 L) from 15.0 to 11.0 L. Log-transformed rate of change for pancreatic PDFF was moderately correlated with log-transformed rates for hepatic PDFF, VAT, SCAT, and WC (ρ = 0.5, 0.47, 0.45, and 0.48, respectively), although not statistically significant. DATA CONCLUSION:Changes in pancreatic PDFF can be estimated by quantitative CSE-MRI in adults undergoing a weight-loss surgery program. Pancreatic and hepatic PDFF and anthropometric indices decreased significantly. LEVEL OF EVIDENCE:2 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:1092-1102.

Estimates of longitudinal change in the parameters of latent (i.e. unobserved) variables, including means, are affected by non-response on the items or indicators of the latent variable. This study used Monte Carlo simulation and a numeric example to compare four ordinal item non-response methods: non-negative matrix factorization (NNMF), multiple imputation with conditional proportional odds model (POM), full information maximum likelihood (FIML) and complete-case analysis, when estimating the longitudinal change in latent variable means. The mean squared error for the NNMF method was more than 40% lower than for the FIML and POM methods when the latent variable correlations over time were strong, percentage of missing data was 25% or more, and sample size was large. The NNMF method is a promising method to address item non-response. It is relatively efficient when sample size is large, and the percentage of missing data is high but has limitations under other data-analytic conditions. [ABSTRACT FROM AUTHOR]

Abstract Background Data on changes in lung function in eosinophilic chronic obstructive pulmonary disease (COPD) are limited. We investigated the longitudinal changes in forced expiratory volume in 1 s (FEV1) and effects of inhaled corticosteroid (ICS) in Korean COPD patients. Methods Stable COPD patients in the Korean COPD subgroup study (KOCOSS) cohort, aged 40 years or older, were included and classified as eosinophilic and non-eosinophilic COPD based on blood counts of eosinophils (greater or lesser than 300 cells/μL). FEV1 changes were analyzed over a 3-year follow-up period. Results Of 627 patients who underwent spirometry at least twice during the follow up, 150 and 477 patients were classified as eosinophilic and non-eosinophilic, respectively. ICS-containing inhalers were prescribed to 40% of the patients in each group. Exacerbations were more frequent in the eosinophilic group (adjusted odds ratio: 1.49; 95% confidence interval: 1.10–2.03). An accelerated FEV1 decline was observed in the non-eosinophilic group (adjusted annual rate of FEV1 change: − 12.2 mL/y and − 19.4 mL/y for eosinophilic and non-eosinophilic groups, respectively). In eosinophilic COPD, the adjusted rate of annual FEV1 decline was not significant regardless of ICS therapy, but the decline rate was greater in ICS users (− 19.2 mL/y and − 4.5 mL/y, with and without ICS therapy, respectively). Conclusions The annual rate of decline in FEV1 was favorable in eosinophilic COPD compared to non-eosinophilic COPD, and ICS therapy had no beneficial effects on changes in FEV1.

Among older men, characteristics that predict longitudinal changes in trabecular bone score (TBS) are different from characteristics that predict changes in bone mineral density (BMD). Most notably, weight loss is strongly associated with concomitant loss in BMD but with concomitant increases in TBS, when measured on Hologic densitometers. INTRODUCTION:Our objective was to compare and contrast predictors of changes in TBS, total hip BMD, and lumbar spine BMD. METHODS:Our study population was 3969 Osteoporotic Fractures in Men (MrOS) cohort participants (mean age 72.8 years) with repeat measures of TBS, lumbar spine and total hip BMD, body mass index (BMI) less than 37 kg/m2, and no use of bisphosphonate or glucocorticoid medications. TBS was scored (Med-Imaps Software version 2.1) and BMD measured on Hologic densitometers. RESULTS:One thousand four hundred forty-four men had a TBS decrease > 0.04 units (estimated least significant change for TBS), 795 men had a TBS increase > 0.04 units, and 1730 men had TBS change ≤ 0.04 units over mean follow-up of 4.6 years. Older age was not associated with TBS change, but was associated with greater decline in lumbar spine and total hip BMD. Compared to stable weight, > 10% weight loss was strongly associated with an increase in TBS [effect size = 1.24 (95% CI 1.12, 1.36)] and strongly associated with a decrease in total hip BMD [- 1.16 (95% CI - 1.19, - 1.03)]. Other predictors discordant for longitudinal changes of TBS and BMD included baseline BMI, walk speed, and ACE inhibitor use. CONCLUSIONS:Predictors of changes in TBS are different from predictors of changes in lumbar spine and total hip BMD. At least when assessed on Hologic densitometers, weight loss is associated with subsequent declines in spine and total hip BMD but subsequent increase in TBS. Faster walk speed may protect against loss of hip BMD, but is not associated with longitudinal changes of TBS.