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The COVID-19 pandemic has had a profound impact globally, particularly in high-risk populations such as those with underlying health conditions. In response to the evolving pandemic landscape and the recent surge in confirmed cases in Taiwan, the Taiwan Association of Family Medicine (TAFM) established a consensus on COVID-19 vaccine recommendations for vulnerable groups through a comprehensive literature review, expert panel discussions, and a practice-oriented formulation procedure to develop evidence-based guidance. Its key findings highlight the increased risk of severe COVID-19 outcomes among individuals with disorders such as diabetes, obesity, chronic kidney disease, cardiovascular disease, and respiratory illness. It emphasizes the safety and effectiveness of COVID-19 vaccines, particularly mRNA vaccines, in these high-risk populations. It particularly underscores the critical role of family medicine physicians in the COVID-19 response, including routine screening, health education, vaccination delivery, and continuous research to optimize strategies. Ongoing monitoring, adaptation, and collaborative efforts will be essential to ensure the continued effectiveness of these recommendations in the evolving COVID-19 landscape. In conclusion, the TAFM consensus recommendations provide a robust framework to guide healthcare providers and policymakers in tailoring vaccination efforts to address the unique needs of vulnerable groups in Taiwan and are an applicable template for neighboring countries., Competing Interests: Conflicts of interest The authors have no financial or nonfinancial conflicts of interest to declare., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

We employed an untargeted proteo-metabolomic approach to profile circulating biomarkers in plasma samples from the I-Lan Longitudinal Aging Study, aiming to identify biomarkers and pathways associated with physio-cognitive decline syndrome (PCDS). In 115 propensity score-matched PCDS case-control pairs, pathway analyses implicated dysregulation of fatty acid metabolism and inflammation in PCDS pathogenesis. Sex-specific associations were observed, with disruptions in central carbon metabolism (elevated PKM, MDH1, and GAPDH; decreased MINPP1) and tyrosine metabolism (decreased MIF, DBH; increased thyroxine) characterizing in men. In contrast, perturbations in glutathione and phenylalanine metabolism, including increased ANPEP, GSTP1, and decreased pyroglutamic acid, were identified in women. Results suggest that dysregulated energy and redox homeostasis likely contribute to PCDS development. Notably, ANPEP, PKM, and MIF emerged as potential biomarkers, elucidating the muscle-brain crosstalk framework. Our findings provide insights into potential molecular mechanisms underlying PCDS and the muscle-brain crosstalk, marking progress toward elucidating biomarkers in the journey of healthy aging., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: Elevated circulatory phosphate levels are linked to age-related muscle dysfunction, yet the mechanisms remain unclear. This study investigated the hypothesis that inflammation plays a role in connecting elevated phosphate levels to muscular dysfunction in middle-aged and older individuals and explored potential sex-based differences in these associations., Methods: The study, based on the I-Lan Longitudinal Aging Study Cohort, analyzed individuals' serum phosphate and hsCRP levels. Sex-specific analyses explored links between circulatory phosphate, inflammation, and muscle profiles (mass, handgrip strength, and walking speed). The study also examined potential mediation or synergistic effects of inflammation in the circulatory phosphate-muscle relationship., Results: The study included 2006 participants (mean age: 65.5 ± 6.5 years; 49.8 % men). Women exhibited higher circulatory phosphate levels than men. Linear analyses revealed that higher phosphate levels were significantly associated with weaker handgrip strength but not with reduced muscle mass in both men and women. In women, circulatory phosphate was not associated with inflammation (hsCRP levels), while in men, higher phosphate levels were significantly associated with higher hsCRP levels. In men, a synergistic effect was observed, where the combination of high hsCRP and elevated phosphate levels had a more pronounced impact on reducing handgrip strength than either factor alone., Conclusions: This study highlights a sex-specific association of inflammation in the mechanisms of hyperphosphatemia-related muscle weakness. The findings emphasize the importance of managing both hyperphosphatemia and chronic inflammation to mitigate their collective impact on muscle function, particularly in older men. Addressing these factors is crucial for promoting muscle health in later life., Competing Interests: Declaration of competing interest All authors declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To develop an intrinsic capacity (IC) score and to investigate the association between IC transition with overall and cause-specific mortality, incident disability and healthcare utilization., Design: Retrospective cohort study SETTING AND PARTICIPANTS: Data from 1852 respondents aged ≥ 65 years who completed the 1999 and 2003 surveys of the Taiwan Longitudinal Study on Aging were analyzed., Measurements: Transitions of IC score were categorized into three groups: (1) Improved IC (IC 2003-1999 >0), (2) Stable IC (IC 2003-1999 = 0), (3) Worsened IC (IC 2003-1999 <0). Cox regression and subdistribution hazard models were used to investigate IC transitions and 4-year overall and cause-specific mortality, respectively. Logistic regression were employed to develop weighted IC score (wIC, 0-16) and assess its association with incident disability and healthcare utilization. Similar analysis were repeated using non-weighted IC (nIC, 0-8) to ensure robustness., Results: Comparing to decreased wIC group, stable or increased wIC participants had significantly lower 4-year all-cause mortality, and death from infection, cardiometabolic/cerebrovascular diseases, organ failure and other causes. (Hazard ratio (HR) ranged from 0.36 to 0.56, 95% CI ranged from 0.15 to 1.00, p ≤ 0.049 in the stable wIC group; HR ranged from 0.41 to 0.51, 95% CI ranged from 0.22 to 0.94, p ≤ 0.034 in the increased wIC group). Moreover, individuals with stable or increased wIC demonstrated lower risk of incident disability and hospitalization. (Odds ratio (OR) = ranged from 0.34 to 0.70, 95% CI ranged from 0.19 to 1.00, p ≤ 0.048). Participants with stable wIC also exhibited reduced risk of emergency department visits (OR = 0.58, 95% CI = 0.41 to 0.82, p = 0.002). These results were generally consistent in the nIC model., Conclusion: Participants with stable or increased IC experienced significantly lower all-cause and most cause-specific mortality, incident disability, and healthcare utilization, which was independent of baseline IC and comorbidities. The findings remained consistent across weighted and non-weighted IC model., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: A number of tools exist to aid surgeons in risk assessment, including the Charlson Comorbidity Index (CCI), the Elixhauser Comorbidity Index (ECI), and various measures of frailty, such as the Hospital Frailty Risk Score (HFR). While all of these tools have been validated for general use, the best risk assessment tool is still debated. Risk assessment is particularly important in elective surgery, such as total joint arthroplasty. The aim of this study is to compare the predictive power of the CCI, ECI, and HFR in the setting of total knee arthroplasty (TKA)., Methods: All patients who underwent TKA were identified via International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code from the National Readmissions Database, years 2016 to 2019. Patient demographics, perioperative complications, and hospital-associated outcomes were recorded. Receiver operating characteristic (ROC) curves were created and area under the curves (AUCs) evaluated to gauge the predictive capabilities of each risk assessment tool (CCI, ECI, and HFR) across a range of outcomes., Results: A total of 1,930,803 patients undergoing TKA were included in our analysis. For mortality, ECI was most predictive (0.95 AUC), while HFR and CCI were 0.75 and 0.74 AUC, respectively. For periprosthetic fractures, ECI was 0.78 AUC, HFR was 0.68 AUC, and CCI was 0.66 AUC. For joint infections, the ECI was 0.78 AUC, the HFR was 0.63 AUC, and the CCI was 0.62 AUC. For 30-day readmission, ECI was 0.79 AUC, while HFR and CCI were 0.6 AUC. For 30-day reoperation, ECI was 0.69 AUC, while HFR was 0.58 AUC and CCI was 0.56 AUC., Conclusions: Our analysis shows that ECI is superior to CCI and HFR for predicting 30-day postoperative outcomes following TKA. Surgeons should consider assessing patients using ECI prior to TKA., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Blood pressure or flow measurements have been associated with vascular health and cognitive function. We proposed that energetic hemodynamic parameters may provide a more nuanced understanding and stronger correlation with cognitive function, in comparisons with conventional aortic and carotid pressure and flow parameters. The study comprised 1858 participants, in whom we assessed cognitive function via MoCA method, and measured central aortic and carotid pressure and flow waveforms. In addition to various pressure and flow parameters, we calculated energetic hemodynamic parameters through integration of pressure multiplying flow with respect to time. Energetic hemodynamic parameters, particularly aortic and carotid mean and pulsatile energy and pulsatility index (PI), were significantly associated with MoCA score more than any aortic and carotid pressure and flow parameters, after adjusting for age, sex, education, depression score, heart rate, BMI, HDL-cholesterol, and glucose levels. MoCA exhibited a strong positive relationship with carotid mean energy (standardized beta = 0.053, P = 0.0253) and a negative relationship with carotid energy PI (standardized beta = -0.093, P = 0.0002), exceeding the association with all traditional pressure- or flow-based parameters. Aortic pressure reflection coefficient at the aorto-carotid junction was positively correlated with mean carotid energy and negatively correlated with PI. Aortic characteristic impedance positively correlated with carotid energy PI but not mean energy. Our research indicates that energetic hemodynamic parameters, particularly carotid mean energy and carotid energy PI, have a stronger association with MoCA scores than traditional pressure- or flow-based metrics. This correlation with cognitive function is notably influenced by the properties of the aorto-carotid interface., (© 2024. The Author(s).)

Background: Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake., Methods: An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (<1.0 g/kg/day) was done. The intervention group consumed protein-enriched soup (24-30 g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition., Results: In this trial, 97 out of 100 randomized participants (mean age: 64.65 ± 4.84 years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3 months of intervention, significant improvements in waist circumference (83.48 ± 10.22 vs. 82.5 ± 9.88 vs. 82.37 ± 9.42 cm, P for trend = 0.046), 6-min walking distance (525.65 ± 58.46 vs. 534.47 ± 51.87 vs. 552.02 ± 57.66 m, P for trend = 0.001), five-time sit-to-stand time (7.63 ± 1.63 vs. 6.81 ± 1.8 vs. 6.4 ± 1.42 s, P for trend <0.001), grip strength (26.74 ± 6.54 vs. 27.53 ± 6.99 vs. 28.52 ± 7.09 kg, P for trend <0.001), and MNA score (26.8 ± 2.14 vs. 27.73 ± 1.74 vs. 27.55 ± 1.72, P for trend <0.001) were discerned within the intervention group. The intervention demonstrated a significant reduction in serum triglyceride (105.32 ± 49.84 vs. 101.36 ± 42.58 vs. 93.43 ± 41.49 mg/dL, P for trend = 0.023), increased HDL-C (60.04 ± 16.21 vs. 60 ± 17.37 vs. 62.55 ± 18.27 mg/dL, P for trend = 0.02), and DHEA-S levels (97.11 ± 54.39 vs. 103.39 ± 56.75 vs. 106.83 ± 60.56 μg/dL, P for trend = 0.002). Serum myostatin did not differ in both groups, but serum leptin levels significantly increased (9118.88 ± 5811.68 vs. 11508.97 ± 7151.08 vs. 11220.80 ± 7190.71 pg/mL, P for trend = 0.016) in controls. The intervention group showed greater improvements in 6 min walking distance (β = 0.71, 95% CI: 6.88 to 40.79, P = 0.006), five-time sit-to-stand test (β = -0.87, 95% CI: -1.59 to -0.15, P = 0.017), MNA score (β = 0.96, 95% CI: 0.20 to 1.71, P = 0.013), serum triglycerides (β = -15.01, 95% CI: -27.83 to -2.20, P = 0.022), LDL-C (β = -9.23, 95% CI: -16.98 to -1.47, P = 0.020), and DHEA-S levels (β = 9.98, 95% CI: 0.45 to 19.51, P = 0.04) than controls., Conclusions: Protein-enriched soup with weekly exercise over 12 weeks significantly improved physical performance, lipid profile, and DHEA-S levels among middle-aged and older adults with inadequate protein intake, while studies assessing long-term benefits of the intervention are needed., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background & Aims: Sarcopenic obesity (SO) and dynapenic obesity (DO) represent two manifestations of excessive fat accumulation concurrent with compromised muscle mass and function, thereby necessitating an examination of their implications for health. This study aims to investigate the relationship between SO/DO and mortality, taking into account various adiposity measures and existing sarcopenia criteria, with further stratified analyses based on age and gender., Methods: The study sample comprised 1779 older adults residing in the community from the I-Lan Longitudinal Aging Study (ILAS). Body composition was assessed via dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was adhered to the 2019 consensus of the Asian Working Group for Sarcopenia, while adiposity was measured by waist circumference (WC), body mass index (BMI), and fat percentage. SO/DO was defined as the coexistence of sarcopenia/dynapenia and obesity. Multivariate Cox proportional hazard regression models were adopted to examine the association between SO or DO, defined by WC, BMI, fat percentage, and mortality., Results: This 11-year follow-up study of 1779 participants aged 63.9 ± 9.2 years involved 15,068 person-years and 229 deaths. WC-defined SO (HR 1.9, 95% CI 1.1-3.3, p = 0.021) and WC-defined DO (HR 1.4, 95% CI 1.1-1.9, p = 0.022) significantly increased mortality risk, whereas definitions employing alternative adiposity metrics exhibited no statistical significance. WC-defined SO was associated with increased risk of mortality among middle-aged adults, while WC-defined DO was associated with increased risk of mortality among older adults. In sex-specific analysis, WC-defined DO was also associated with increased risk of mortality in men (HR 1.6, 95% CI 1.1-2.4, p = 0.019), while defined by other measurements showed no associations in both sexes., Conclusions: The study identified a significant link between SO/DO, defined by WC, and an 11-year mortality risk, advocating for WC-defined adiposity as an obesity measure and personalized interventions considering SO and DO's distinct impacts on mortality in middle-aged and older adults., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: This study aimed to use the Social Vulnerability Index (SVI) to encapsulate the complex and multidimensional nature of social determinants and their influence on alcohol intake and mortality in middle-aged and older individuals., Design: Cohort study., Setting and Participants: Data were obtained from the Taiwan Longitudinal Study on Aging (TLSA), with 3945 study participants aged 50 years and older., Methods: The TLSA questionnaire defined SVI (51 items including living conditions, social support, socially oriented activities of daily living, social engagement and leisure, empowerment of life, satisfaction about life, and socioeconomic status) and alcohol intake (behavior as well as type and frequency of alcohol intake). Multivariate Cox proportional hazard models were used to estimate the association between alcohol intake and mortality, stratified by sex and SVI groups., Results: Men with high social vulnerability and high alcohol intake exhibit an elevated mortality risk [adjusted hazard ratio (aHR), 1.51; 95% CI, 1.01-2.24], whereas notably, women in similar social circumstances but with moderate alcohol intake face a quintupled mortality risk (>35 g/wk; aHR, 5.67; 95% CI, 2.37-13.61). The impact of alcohol and social vulnerability on mortality was more pronounced in men younger than 65. Among them, those with high social vulnerability and moderate (35-140 g/wk; aHR, 2.83; 95% CI, 1.50-5.36) to high (>140 g/wk; aHR, 2.24; 95% CI, 1.15-4.35) alcohol intake was associated with an increased risk of mortality., Conclusions and Implications: Various factors throughout the life course of both men and women significantly impact the risk of all-cause mortality due to alcohol intake, underscoring the importance of social vulnerability as a determinant of both alcohol intake behavior and mortality risk., Competing Interests: Disclosures All authors declare no conflict of interest., (Copyright © 2024 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: This longitudinal cohort study aimed to examine the effect of intrinsic capacity (IC) and multimorbidity on the development of new disabilities., Methods: The study utilized data from 1,009 participants without disabilities from the I-Lan Longitudinal Aging Study. Multivariable logistic regressions were employed to assess the predictive capability of IC (ranging from 0 to 100) and multimorbidity for incident disability over a 7-year follow-up period., Results: Both low IC (OR 4.9, 95 % CI 2.1-11.1, p < 0.001) and multimorbidity (OR 4.5, 95 % CI 2.2-9.2, p < 0.001) significantly predicted incident disability over the 7-year period. A one-point increase in IC reduced the risk of incident disability by 10 % (OR 0.9, 95 % CI 0.8-0.9, p < 0.001). Among IC subdomains, both better locomotion (OR 0.96, 95 % CI 0.94-0.99, p = 0.014) and psychology (OR 0.97, 95 %CI 0.94-1.00, p = 0.049) significantly reduced the risk of incident disability. Rapid declines in IC significantly predicted incident disability (OR 4.1, 95 % CI 1.8-9.3, p = 0.001), whereas the onset of new multimorbidity or changes in the number of chronic conditions did not demonstrate a significant association with incident disability. The interaction terms between IC and multimorbidity, both categorically (low IC * multimorbidity, p = 0.959) and numerically (IC (per point) * multimorbidity, p = 0.660) were all statistically insignificant., Conclusions: IC exhibited better predictive capacity for 7-year incident disability compared to multimorbidity, so health care services targeting older adults should adopt an integrated care approach that combines both function- and disease-centric strategies., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Sarcopenia and intrinsic capacity (IC) declines pose significant challenges to healthy aging, particularly in the rapidly growing octogenarian population. This study aimed to elucidate the relationship between sarcopenia and declines in IC across multiple cohorts of community-dwelling older adults., Methods: Data from four Taiwanese cohorts were analyzed. Sarcopenia was diagnosed based on the Asian Working Group for Sarcopenia (AWGS) 2019 criteria (algorithm 1: categorized as either having possible sarcopenia or not (robust); algorithm 2: categorized as robust, possible sarcopenia or sarcopenia). IC was operationalized using the World Health Organization's Integrated Care for Older People (ICOPE) framework (step 1 and step 2), encompassing six domains: locomotion, vitality, vision, hearing, cognition, and psychological well-being. Multivariable logistic regression models were adopted to assess the association between sarcopenia and IC decline., Results: Among 599 octogenarians (median age 82.2 years, 54.8% male), the prevalence of possible sarcopenia (algorithm 1) was 64.6%. When adopting algorithm 2, the prevalence of possible sarcopenia and sarcopenia was 46,2% and 32.1%, respectively. After adjusting for covariates, participants with possible sarcopenia or sarcopenia (algorithm 2) were more likely to exhibit declines in vitality (ICOPE Step 1: possible sarcopenia aOR 3.65, sarcopenia aOR 4.74; ICOPE Step 2: possible sarcopenia aOR 5.11, sarcopenia aOR 14.77) and cognition (ICOPE Step 1: possible sarcopenia aOR 2.40, sarcopenia aOR 2.12; ICOPE Step 2: possible sarcopenia aOR 2.02, sarcopenia aOR 2.51) compared to robust individuals., Conclusions: This study underscores the robust association between sarcopenia and declines in vitality and cognition among octogenarians, highlighting the importance of sarcopenia screening and management in promoting healthy longevity in this vulnerable population., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objective: This study aimed to evaluate the efficacy of integrated multidomain interventions and primary health care on intrinsic capacity (IC) and related biomarkers., Design: An ancillary analysis from the Taiwan Integrated Geriatric Care (TIGER) study: a randomized controlled trial., Setting and Participants: A total of 398 community-dwelling older adults aged ≥65 years with ≥3 chronic conditions., Methods: Participants were randomized into the 12-month pragmatic multidomain intervention or usual care groups. The primary outcome was the change in IC and its subdomains (locomotion, cognition, vitality, psychological, and sensory) at baseline and 3-, 6-, 9-, and 12-month follow-ups. Generalized linear mixed models were used to evaluate the multidomain intervention effects on these changes., Results: The intervention arm had greater improvement in IC than the usual care arm (overall difference 1.5; 95% CI 0.5-2.5; P = .005), mainly from subdomains of locomotion (overall difference 1.4; 95% CI 0.5-2.4; P = .004) and cognition (2.9; 95% CI 2.1-3.7; P < .001). Changes in neutrophil-to-lymphocyte ratio (NLR -2.4; 95% CI -3.9 to -0.8, P = .003), serum levels of albumin (35.1; 95% CI 23.1-47.2; P < .001), dehydroepiandrosterone sulfate (DHEA-S 2.8; 95% CI 1.9-3.8; P < .001), free androgen index (FAI 1.5; 95% CI 1.1-1.9; P < .001), and vitamin D (4.0; 95% CI 2.0-6.1; P < .001) were associated with changes in IC over time., Conclusions and Implications: The incorporation of multidomain interventions into primary health care significantly enhanced IC over the 12-month program. Changes in NLR, FAI, and serum levels of albumin, DHEA-S, vitamin D were associated with changes in IC over time., Trial Registration: ClinicalTrials.gov Identifier: NCT03528005., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The neuroanatomical changes driving both cognitive and mobility impairments, an emerging preclinical dementia syndrome, are not fully understood. We examined gray-matter volumes (GMVs) and structural covariance networks (SCNs) abnormalities in community-based older people preceding the conversion to physio-cognitive decline syndrome (PCDS)., Methods: Voxel-wise brain GMV and established SCNs were compared between PCDS and non-PCDS converters., Results: The study included 343 individuals (60.2 ± 6.9 years, 49.6% men) with intact cognitive and mobility functions. Over an average 5.6-year follow-up, 116 transitioned to PCDS. Identified regions with abnormal GMVs in PCDS converters were over cerebellum and caudate, which served as seeds for SCNs establishment. Significant differences in cerebellum-based (to right frontal pole and left middle frontal gyrus) and caudate-based SCNs (to right caudate putamen, right planum temporale, left precentral gyrus, right postcentral gyrus, and left parietal operculum) between converters and nonconverters were observed., Discussion: This study reveals early neuroanatomic changes, emphasizing the cerebellum's role, in dual cognitive and mobility impairments., Highlights: Neuroanatomic precursors of dual cognitive and mobility impairments are identified. Cerebellar GMV reductions and increased right caudate GMV precede the onset of PCDS. Altered cerebellum- and caudate-based SCNs drive PCDS transformation. This research establishes a foundation for understanding PCDS as a specific dementia syndrome., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: The intricate relationship between social determinants, e.g., social frailty, biomarkers and healthy aging remains largely unexplored, despite the potential for social frailty to impact both intrinsic capacity (IC) and functional ability in the aging process., Design: Retrospective longitudinal cohort study., Setting and Participants: Participants aged 50+ years from the Social Environment and Biomarkers of Aging Study (SEBAS) in Taiwan, stratified into three age groups: 50-64, 65-74 and 75+., Measurements: Social frailty was defined based on a score derived from four domains: exclusion from general resources, social resources, social activity, and fulfillment of basic social needs. The scores were categorized as score=0 (no social frailty), 1 (social pre-frailty), and 2+ (social frailty). Multivariable logistic regression and Cox proportional hazard models were employed to examine the dose-responsive relationship between social frailty, low IC, functional and psychological health, and mortality., Results: Of 1015 study participants, 24.9% and 7.9% were classified as social pre-frailty and social frailty, respectively. No significant differences were observed in most biomarkers between those with social frailty and those without. A dose-responsive relationship was found between social frailty and increased risk of low IC (social pre-frailty: aOR 2.20 [95% CI 1.59-3.04]; social frailty: 5.73 [3.39-9.69]). Similar results were found for functional and psychological health. However, no significant association between social frailty and all-cause mortality was found at the 4-year follow-up (social pre-frailty: aHR 1.52 [95% CI 0.94-2.43]; social frailty: 1.59 [0.81-3.09])., Conclusions: The significant association between social frailty and low IC, functional limitations, cognitive declines, and depressive symptoms underscores the pressing need for research on intervention strategies to enhance healthy aging in the lifespan course., Competing Interests: All authors declared no financial conflict of interest.

Background: Impaired intrinsic capacity (IC), which affects approximately 90% of older adults, is associated with a significantly heightened risk of frailty and cognitive decline. Existing evidence suggests that multidomain interventions have the potential to enhance cognitive performance and yield positive effects on physical frailty., Objective: To examine roles of baseline IC and its subdomains on the efficacy of multidomain interventions in promoting healthy aging in older adults., Design: a cluster-randomized controlled trial., Setting and Participants: 1,054 community-dwelling older adults from 40 community-based clusters across Taiwan., Intervention: A 12-month pragmatic multidomain intervention of exercise, cognitive training, nutritional counseling and chronic condition management., Measurements: Baseline IC was measured by 5 subdomains, including cognition (Montreal Cognitive Assessment, MoCA), sensory (visual and hearing impairment), vitality (handgrip strength or Mini-Nutritional Assessment-short form), psychological well-being (Geriatric Depression Scale-5), and locomotion (6m gait speed). Outcomes of interest were cognitive performance (MoCA scores) and physical frailty (CHS frailty score) over a follow-up period of 6 and 12 months., Results: Of all participants (mean age:75.1±6.4 years, 68.6% female), about 90% participants had IC impairment at baseline (2.0±1.2 subdomains). After covariate adjustment using a generalized linear mixed model (GLMM), the multidomain intervention significantly prevented cognitive declines and physical frailty, particularly in those with IC impairment ≥ 3 subdomains (MoCA: coefficient: 1.909, 95% CI: 0.736 ~ 3.083; CHS frailty scores: coefficient = -0.405, 95% CI: -0.715 ~ -0.095). To assess the associations between baseline poor capacity in each IC subdomain and MoCA/CHS frailty scores over follow-up, a 3-way interaction terms (time*intervention*each poorer IC subdomains) were added to GLMM models. Significant improvements in MoCA scores were shown for participants with poorer baseline cognition (coefficient= 1.138, 95% CI: 0.080 ~ 2.195) and vitality domains (coefficient= 1.651, 95% CI: 0.541 ~ 2.760). The poor vitality domain also had a significant modulating effect on the reduction of CHS frailty score after the 6- and 12-month intervention period (6 months: coefficient= -0.311, 95% CI: -0.554 ~ -0.068; 12 months: coefficient= -0.257, 95% CI: -0.513 ~ -0.001)., Conclusion and Implications: A multidomain intervention in community-dwelling older adults improves cognitive decline and physical frailty, with its effectiveness influenced by baseline IC, highlighting the importance of personalized strategies for healthy aging., Competing Interests: All authors declare no competing interests.

Objective: This study aimed to (1) investigate the clinical practice for the management of sarcopenia among healthcare professionals in Asia, (2) determine the characteristics of clinical care provided by geriatricians versus by other healthcare professionals, and (3) clarify the awareness of sarcopenia., Methods: From December 1 to 31, 2022, an online survey was completed by 1990 healthcare professionals in Asia. The survey comprises demographics and institutional characteristics, basic sarcopenia-related details, and sarcopenia-related assessment and treatment details., Results: The mean respondent age was 44.2 ± 10.7 years, 36.4% of the respondents were women, and the mean years of experience in clinical practice were 19.0 ± 10.6 years. The percentages of respondents who were aware of the term "sarcopenia", its definition and the importance of its management were high, at 99.3%, 91.9%, and 97.2%, respectively. The percentages of respondents who had screened patients for, diagnosed patients with, and treated patients for sarcopenia were 42.4%, 42.9%, and 58.8%, respectively. Medical doctors had higher performance rates compared to allied health professionals (45.5% vs. 40.5% for screening, 56.8% vs. 34.5% for diagnosis, and 65.0% vs. 55.0% for treatment) (P < 0.001). Especially, among medical doctors, geriatricians had significantly higher rates compared to non-geriatricians (64.3% vs. 34.1% for screening; 76.7% vs. 44.8% for diagnosis; 82.7% vs. 54.4% for treatment, respectively) (P < 0.001)., Conclusion: Although the importance of the concept and management of sarcopenia is well recognized, there is a gap in its detection and management in clinical practice between medical doctors and allied health professionals, and also between geriatricians and non-geriatricians. Many geriatricians collaborate with other healthcare professionals to appropriately manage sarcopenia. In the future, educating all medical staff on the proper management of sarcopenia is necessary., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Agricultural land is the most basic input factor for agricultural production and an essential component of terrestrial ecosystems, which plays a vital role in achieving carbon neutrality. Giving full play to the carbon-neutral contribution of agricultural land is a crucial part of China's economic transformation and green development. It incorporates carbon and pollution emissions from agricultural land use into the unexpected outputs of the Green and Low-carbon Utilization Efficiency of Agricultural Land (GLUEAL) evaluation system. The study utilized several advanced analytical tools, including the super-efficient Slacks-Based Measure (SBM) model, Exploratory Spatial-Temporal Data Analysis (ESTDA) method, Geodetector, and Geographically and Temporally Weighted Regression (GTWR) model. The objective was to examine the spatial-temporal evolution of GLUEAL and identify the factors that influenced it in all 31 provinces of China from 2005 to 2020. The results show that: (1) The overall spatial-temporal evolution of GLUEAL showed an increasing trend, but the disparity between provinces and regions became wider. (2) Most provinces have not yet made significant spatial and temporal jumps. They have high spatial cohesion with specific "path-dependent" characteristics. (3) The Geodetector results reveal that the Number of Rural Labor Force with Higher Education (NRLFHE) and Technology Support for Agriculture (TSA) have insufficient explanatory power on average for GLUEAL. Agricultural Economic Development Level (AEDL), Urbanization Level (UL), Multiple Crop Index (MCI), Planting Structure (PS), Degree of Crop Damage (DCD), Financial support for agriculture (FSA), and Agricultural mechanization level (AML) had stronger explanatory power on average for GLUEAL and were important factors influencing GLUEAL levels. (4) The average influence of AEDL, UL, FSA, and AML on GLUEAL changed from negative to positive. The average influence of MCI and DCD on GLUEAL was negative, and the average influence of PS on GLUEAL changed from positive to negative. This study provides a comprehensive description of the spatial and temporal evolution of GLUEAL in China. It reveals the key factors influencing GLUEAL and analyzes their spatial variations and impact patterns. These findings offer robust evidence for government policymakers to formulate policy measures for sustainable agricultural development and optimized resource allocation, promoting the transformation of agricultural land towards green and low-carbon practices and advancing the achievement of sustainable development goals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Endobronchial metastases (EBM) are defined as bronchoscopically visible lesions histopathologically identical to extrapulmonary tumors. We summarized the literature on endobronchial metastasis of colorectal cancer and give a brief review., Method: We present a rare case with an episode mistaken for sarcoidosis and unexpectedly identified as colon cancer by bronchoscopic biopsy. A 53-year-old man with dry cough and dyspnea had diffuse micro lung nodules and lymphadenopathy on CT and PET/CT. He was diagnosed with sarcoidosis and took steroid therapy, but the symptoms could not be alleviated. Bronchoscopy was suggested. He was finally identified with colon cancer by bronchoscopic biopsy, which was confirmed by endoscopic biopsy. We summarise the clinical manifestations, imaging, prognosis of EMB of colorectal cancer., Result: EBM are rare. Colorectal cancer is common in EBM and the frequency is increasing., Conclusion: EBM should be distinguished from primary lung cancer, sarcoidosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We investigated whether advanced brain biological age is associated with accelerated age-related physical and/or cognitive functional decline: mobility impairment no disability (MIND), cognitive impairment no dementia (CIND), and physio-cognitive decline syndrome (PCDS). We constructed a brain age prediction model using gray matter features from the magnetic resonance imaging of 1482 healthy individuals (aged 18-92 years). Predicted and chronological age differences were obtained (brain age gap [BAG]) and analyzed in another 1193 community-dwelling population aged ≥50 years. Among the 1193 participants, there were 501, 346, 148, and 198 in the robust, CIND, MIND, and PCDS groups, respectively. Participants with PCDS had significantly larger BAG (BAG = 2.99 ± 8.97) than the robust (BAG = -0.49 ± 9.27, p = 0.002; η 2 = 0.014), CIND (BAG = 0.47 ± 9.16, p = 0.02; η 2 = 0.01), and MIND (BAG = 0.36 ± 9.69, p = 0.036; η 2 = 0.013) groups. Advanced brain aging is involved in the pathophysiology of the co-occurrence of physical and cognitive decline in the older people. The PCDS may be a clinical phenotype reflective of accelerated biological age in community-dwelling older individuals., Competing Interests: Disclosure statement The author(s) declared no potential conflicts of interest with respect to the research, authorship, and /or publication of this article., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Chronic diseases often lead to metabolic disorders, causing anabolic resistance and increased energy consumption, which result in cachexia. Cachexia, in turn, can lead to major clinical consequences such as impaired quality of life, shortened life expectancy, and increased healthcare expenditure. Existing international diagnostic criteria for cachexia employ thresholds derived from Western populations, which may not apply to Asians due to differing body compositions. To address this issue, the Asian Working Group for Cachexia (AWGC) was initiated. The AWGC comprises experts in cachexia research and clinical practice from various Asian countries and aims to develop a consensus on diagnostic criteria and significant clinical outcomes for cachexia in Asia. The AWGC, composed of experts in cachexia research and clinical practice from several Asian countries, undertook three-round Delphi surveys and five meetings to reach a consensus. Discussions were held on etiological diseases, essential diagnostic items for cachexia, including subjective and objective symptoms and biomarkers, and significant clinical outcomes. The consensus highlighted the importance of multiple diagnostic factors for cachexia, including chronic diseases, either or both weight loss or low body mass index, and at least one of the following: anorexia, decreased grip strength (<28 kg in men and <18 kg in women), or elevated C-reactive protein levels (>5 mg/L [0.5 mg/dL]). The AWGC proposed a significant weight change of 2% or more over a 3-6 month period and suggested a tentative cut-off value of 21 kg/m 2 for low body mass index in diagnosing cachexia. Critical clinical outcomes were determined to be mortality, quality of life as assessed by tools such as EQ-5D or the Functional Assessment of Anorexia/Cachexia Therapy, and functional status as measured by the Clinical Frailty Scale or Barthel Index, with significant emphasis on patient-reported outcomes. The AWGC consensus offers a comprehensive definition and user-friendly diagnostic criteria for cachexia, tailored specifically for Asian populations. This consensus is set to stimulate future research and enhance the multidisciplinary approach to managing cachexia. With plans to develop further guidelines for the optimal treatment, prevention, and care of cachexia in Asians, the AWGC criteria are expected to drive research across chronic co-morbidities and cancer in Asia, leading to future refinement of diagnostic criteria., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Dementia development is a complex process in which the occurrence and sequential relationships of different diseases or conditions may construct specific patterns leading to incident dementia., Objective: This study aimed to identify patterns of disease or symptom clusters and their sequences prior to incident dementia using a novel approach incorporating machine learning methods., Methods: Using Taiwan's National Health Insurance Research Database, data from 15,700 older people with dementia and 15,700 nondementia controls matched on age, sex, and index year (n=10,466, 67% for the training data set and n=5234, 33% for the testing data set) were retrieved for analysis. Using machine learning methods to capture specific hierarchical disease triplet clusters prior to dementia, we designed a study algorithm with four steps: (1) data preprocessing, (2) disease or symptom pathway selection, (3) model construction and optimization, and (4) data visualization., Results: Among 15,700 identified older people with dementia, 10,466 and 5234 subjects were randomly assigned to the training and testing data sets, and 6215 hierarchical disease triplet clusters with positive correlations with dementia onset were identified. We subsequently generated 19,438 features to construct prediction models, and the model with the best performance was support vector machine (SVM) with the by-group LASSO (least absolute shrinkage and selection operator) regression method (total corresponding features=2513; accuracy=0.615; sensitivity=0.607; specificity=0.622; positive predictive value=0.612; negative predictive value=0.619; area under the curve=0.639). In total, this study captured 49 hierarchical disease triplet clusters related to dementia development, and the most characteristic patterns leading to incident dementia started with cardiovascular conditions (mainly hypertension), cerebrovascular disease, mobility disorders, or infections, followed by neuropsychiatric conditions., Conclusions: Dementia development in the real world is an intricate process involving various diseases or conditions, their co-occurrence, and sequential relationships. Using a machine learning approach, we identified 49 hierarchical disease triplet clusters with leading roles (cardio- or cerebrovascular disease) and supporting roles (mental conditions, locomotion difficulties, infections, and nonspecific neurological conditions) in dementia development. Further studies using data from other countries are needed to validate the prediction algorithms for dementia development, allowing the development of comprehensive strategies to prevent or care for dementia in the real world., (©Shih-Tsung Huang, Fei-Yuan Hsiao, Tsung-Hsien Tsai, Pei-Jung Chen, Li-Ning Peng, Liang-Kung Chen. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 26.07.2023.)

Purpose of the Research: The study aimed to examine the correlation between underlying medical conditions and gait analysis parameters as well as determine the key determiners of fall risk., Materials and Methods: This was a cross-sectional study. A total of 120 hospitalized older adults, recruited from a medical center in northern Taiwan, completed three instruments: the Timed Up and Go (TUG) test, a demographic questionnaire, and the Morse Fall Scale. The inferential statistics were subjected to the chi-square test, Mann-Whitney U test, Kruskal-Wallis test, and Spearman's rank correlation coefficient analysis to determine the correlations among the demographic variables, gait analysis parameters, and fall risk in elderly inpatients. Logistic regression was used to analyze the predictors of elderly inpatients' fall risk., Results: The results showed that longer TUG test times, slower walking speeds, or shorter stride lengths are related to higher fall risk. The new finding was that longer TUG test times and slow gait speeds were correlated with lower gastrointestinal as well as hepatobiliary and pancreatic diseases., Conclusions: This study confirms that gait analysis parameters are significantly correlated with fall risk among older inpatients and that TUG is an important indicator of frailty, prefrailty, or metabolic state. Early detection of the symptoms of gastrointestinal disorders and the provision of adequate nutrition could potentially improve inpatients' gait and prevent falls., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier B.V.)

Despite decades of research, there are no medications approved by the United States Food and Drug Administration to treat stimulant use disorders. Self-administration procedures are widely used to screen candidate medications for stimulant use disorder, although preclinical reductions in stimulant self-administration have not translated to meaningful reductions in stimulant use in humans. One possible reason for this discordance is that most preclinical studies evaluate candidate medications under conditions that promote predictable, and well-regulated patterns of drug-taking rather than the dysregulated and/or compulsive patterns of drug-taking characteristic of a stimulant use disorder. A subset of rats ("high-responders") that self-administer 3,4-methelyendioxypyrovalerone (MDPV), a monoamine uptake inhibitor, develop high levels of dysregulated drug-taking consistent with behaviors related to stimulant use disorders. Because MDPV acts on dopamine, serotonin (5-HT), and sigma receptor systems, the current studies compared the potency and effectiveness of a dopamine D 3 receptor partial agonist (VK4-40) or antagonist (VK4-116), a sigma receptor antagonist (BD1063), a dopamine D 2 /D 3 /sigma receptor antagonist (haloperidol), and a 5-HT 2C receptor agonist (CP-809,101) to reduce MDPV (0.0032-0.1 mg/kg/infusion) self-administration in high- and low-responding rats as well as rats self-administering cocaine (0.032-1 mg/kg/infusion). VK4-40, VK4-116, haloperidol, and CP-809,101 were equipotent and effective at reducing drug-taking in all three groups of rats, including the high-responders; however, VK4-116 and CP-809,101 were less potent at reducing drug-taking in female compared with male rats. Together, these studies suggest that drugs targeting dopamine D 3 or 5-HT 2C receptors can effectively reduce dysregulated patterns of stimulant use, highlighting their potential utility for treating stimulant use disorders. SIGNIFICANCE STATEMENT: There are no United States Food and Drug Administration-approved treatments for stimulant use disorder, perhaps in part because candidate medications are most often evaluated in preclinical models using male subjects with well-regulated drug-taking. In an attempt to better model aberrant drug taking, this study found compounds acting at dopamine D 3 or 5-HT 2C receptors can attenuate drug-taking in male and female rats that self-administered two different stimulants and exhibited either a high or low substance use disorder-like phenotype., (U.S. Government work not protected by U.S. copyright.)

Objectives: To investigate sex-specific associations between social isolation and psychological outcomes and biomarkers among community-dwelling middle-aged and older adults using a nationally representative population-based cohort study., Methods: Data from 757 participants from the Social Environment and Biomarkers of Aging Study (SEBAS) were retrieved for analysis, and all participants were stratified by sex. The associations between social isolation and psychological outcomes (loneliness, depressive symptoms, and cognitive impairment) at the 4-year follow-up were examined by multivariate logistic regression models, and associations between social isolation and biomarkers at the 4-year follow-up were examined by multivariate generalized linear models (GLMs)., Results: For men, social isolation was not associated with the development of loneliness. However, being married (adjusted odds ratio (aOR) 0.32 [95% confidence interval (CI) 0.13-0.74], p<0.001) was associated with a lower risk of loneliness, indicating potential protective effects of marriage for men. On the other hand, social isolation was associated with a 2-fold higher risk of loneliness in women (aOR 2.26 [1.01-5.09], p<0.001). Social isolation was not associated with depressive symptoms after adjusting for other demographics. For men, being married (aOR 0.51 [0.26-0.99], p<0.05) or having good self-reported health (aOR 0.44 [0.21-0.92], p<0.05) was protective against depressive symptoms. For women, only good self-reported health (aOR 0.30 [0.13-0.70], p<0.01) provided protective effects against depressive symptoms. Similarly, other demographic factors (being married and having a higher educational level) but not social isolation were associated with lower risks of cognitive impairment. No significant associations were noted between social isolation and selected biomarkers., Conclusions: Sex-different associations between social isolation and loneliness were noted; the effects of demographic factors, such as being married, self-reported health status, and high education levels, on subsequent loneliness, depression, and cognitive function were also sex-different. Further intervention studies are needed to explore sex-specific approaches to deal with the interplay of social isolation, loneliness, psychological outcomes and other demographic factors., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

This study aimed to explore the biological features and mortality risk of intrinsic capacity (IC) and functional ability (FA). Based on data from 1839 participants from the I-Lan Longitudinal Aging Study, multivariable Cox proportional hazard models were used to evaluate the predictive ability of IC (range 0-100) and FA (range 0-100) on 10-year mortality. Of 2038 repeated measurements for IC within a 7-year observational period, multivariable logistic regression was used to compare biological features of participants with maintained, improved and rapidly deteriorated IC. A 1-point increased IC value was associated with a 5% (HR 0.95, 95% CI 0.93-0.97, p < 0.001) decrease in mortality risk. Low IC (HR 1.94, 95% CI 1.39-2.70, p < 0.001) was associated with higher mortality risk. Hyperglycemia (OR 1.40, 95% CI 1.09-1.81, p = 0.010), low serum levels of DHEA-S (OR 3.33, 95% CI 1.32-8.41, p = 0.011), and high serum levels of C-reactive protein (OR 1.45, 95% CI 1.05-2.00, p = 0.023) were associated with low IC at baseline. Low serum levels of DHEA-S (middle tertile OR 1.84, 95% CI 1.15-2.95, p = 0.012; lowest tertile OR 2.25, 95% CI 1.34-3.77, p = 0.002) and vitamin D deficiency (OR 1.82, 95% CI 1.02-3.27, p = 0.044) were associated with rapid deterioration of IC. IC and FA predicted 10-year mortality, whereas chronic inflammation, hyperglycemia, and low DHEA-S were associated with low IC status. Low DHEA-S and vitamin D deficiency may be considered as potential biomarkers of rapid IC declines, which implies underlying biological mechanisms of healthy aging.

Tumor necrosis factor (TNF)-α is a proinflammatory cytokine involved in the pathogenesis of sarcopenia, but its short half-life and inconsistent reproducibility limit the potential of TNF-α to be an ideal sarcopenia biomarker. Anti-TNF-α, a natural consequent autoantibody to TNF-α, is an indicator of relatively prolonged TNF-α exposure, has more stable concentrations than TNF-α and should be a better alternative as a biomarker of sarcopenia. Data from 484 participants from the I-Lan Longitudinal Aging Study were used for this study, and sarcopenia was defined by the Asian Working Group for Sarcopenia 2019 consensus. Plasma levels of anti-TNF-α were determined by a sandwich ELISA approach, and levels of TNF-α were determined by an immunoassay. Compared to nonsarcopenic participants, 43 sarcopenic participants had higher levels of anti-TNF-α (0.73 ± 0.19 vs. 0.79 ± 0.25 OD, p = 0.045). Plasma levels of anti-TNF-α were positively correlated with TNF-α (r = 0.24, p < 0.001), and plasma levels of anti-TNF-α were positively correlated with adiposity (r = 0.16, p < 0.001) and negatively correlated with lean body mass (r = -0.14, p = 0.003). Individuals with increasing levels of anti-TNF-α had higher odds of being sarcopenic (OR 5.4, 95 % CI: 1.1-25.8, p = 0.035), and these associations were stronger among women and younger adults. An association between TNF-α and sarcopenia was noted only in middle-aged adults (OR 6.2, 95 % CI: 1.8-21.7, p = 0.004). Plasma anti-TNF-α levels were positively correlated with TNF-α and were significantly associated with sarcopenia. Anti-TNF-α may be a more appropriate biomarker than TNF-α for sarcopenia, but further investigations are needed to confirm its roles in sarcopenia diagnosis and treatment response evaluation., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Studies have demonstrated associations between inflammatory biomarkers and cognitive function in people with dementia or stroke, but little is known regarding these associations in healthy middle-aged and older populations., Objectives: This study aims to examine associations between inflammatory biomarkers (both vascular and systemic) and cognitive performance in stroke- and dementia-free middle-aged and older adults without apolipoprotein E4 (ApoE ε4) allele carriers., Design: A cross-sectional study., Setting: Social Environment and Biomarkers of Aging Study (SEBAS) 2006., Participants: A total of 983 participants aged 53 years and older., Measurements: Composite cognitive function assessment, including the Short Portable Mental Status Questionnaire, the Rey Auditory Verbal Learning Test, and the Wechsler Adult Intelligence Scale. Overnight venous blood sampling for 6 inflammatory biomarkers (C-reactive protein, interleukin-6, fibrinogen, homocysteine, intercellular adhesion molecule-1 and E-selectin) and ApoE genotyping., Results: Among 983 participants (mean age: 65.8±9.5 years), 808 were non-ApoE e4 allele carriers and were stroke- and dementia-free. Higher log fibrinogen was associated with poorer cognitive function after adjustment for potential confounding factors in non-ApoE e4 allele carriers and stroke- and dementia-free populations (unstandardized coefficients β= -1.553, P value= 0.003). In participants aged 65 years or older, both of elevated fibrinogen and homocysteine were associated with poorer cognitive function (β= -2.288, P value= 0.015; β= -1.331, P value= 0.012, respectively). Elevated log CRP was significantly associated with lower cognitive function only in women (β= -0.514, P value= 0.024)., Conclusion: Higher serum levels of fibrinogen were negatively associated with cognitive function, which was independent of ApoE genotyping and prior cerebrovascular events in dementia-free community-dwelling older adults. Further studies are needed to validate the roles of fibrinogen in the pathophysiology of dementia and elucidate the underlying mechanisms., Competing Interests: The authors have no commercial associations or sources of support that might pose a conflict of interest.

Objectives: To discern the diagnostic accuracy between the updated diagnostic consensus of the Asian Working Group for Sarcopenia (AWGS) in 2019 (AWGS 2019) and the previous AWGS 2014 guidelines., Design: A prospective population-based cohort study., Setting and Participants: The study included 731 older community-dwelling adults aged ≥ 65 years who participated in face-to-face interviews and were followed up for 11-year mortality until 31 Mar 2022., Measurements: We utilized a handgrip strength dynamometer to measure participants' muscle strength, while their walking speed was determined by a timed 6-meter walk test at their usual pace. Additionally, muscle mass was measured using dual-energy X-ray absorptiometry scanning. Sarcopenia was defined as the presence of low muscle mass in combination with weakness and/or slowness both by AWGS 2014 and 2019 criteria., Results: The present study followed 731 participants (mean age 73.4 ± 5.4 years, men predominant 52.8%) over a period of 11 years, yielding 5927 person-years and 159 deaths. Prevalence of sarcopenia defined by AWGS 2019 and 2014 criteria were 8.5% and 6.8%, respectively. Sarcopenia defined by AWGS 2019 (HR 1.62, 95% CI 1.04-2.54, p=0.034) but not AWGS 2014 was significantly associated with mortality in community-living older adults after adjusting for potential confounders such as age, sex, education, drinking, disease burden and serum level of testosterone. The study also found that the AWGS 2019 criteria had a better model fitness than AWGS 2014 criteria in predicting mortality., Conclusion: AWGS 2019 criteria outperformed AWGS 2014 in identifying sarcopenia risk and predicting mortality. Screening for sarcopenia in older adults may improve health outcomes by identifying those at increased mortality risk., Competing Interests: All authors declared no conflict of interests.

Objectives: To explore the associations of (1) the frailty phenotype or frailty index transition with cause-specific mortality, and (2) different combinations of transition in frailty phenotype and frailty index with all-cause mortality., Design: Retrospective cohort study., Setting and Participants: Data from 3529 respondents aged >50 years who completed the 1999 and 2003 surveys of the Taiwan Longitudinal Study on Aging were analyzed., Methods: Cox regression and subdistribution hazard models were constructed to investigate frailty phenotype or frailty index transitions (by categories of frailty phenotype, absolute and percentage changes in frailty index, and combined categories of the 2 measurements) and subsequent 4-year all-cause and cause-specific mortality, respectively., Results: Among the frailty phenotype transition groups, the improved frailty group had overall mortality risk comparable to that of the maintained robustness/prefrailty group [hazard ratio (HR): 0.9; 95% CI: 0.7-1.2] and lower risk of mortality due to organ failure (HR: 0.4; 95% CI: 0.2-0.8; P = .015), whereas the worsened frailty group had the highest risk of all-cause mortality and death from infection, malignancy, cardiometabolic/cerebrovascular diseases, and other causes (HR: 1.8-3.7; all P < .03). The rapidly increased frailty index group had significantly higher all-cause and every cause-specific mortality than the decreased frailty index group (HR: 1.8-7.7; all P < .05). When frailty phenotype and frailty index transition groups were combined, participants with worsened frailty/rapidly increased frailty index had increased risk under the same frailty index/frailty phenotype transition condition, particularly for large changes in each factor (HR: 1.5-2.2; P < .01 for worsened frailty; 1.7-4.5, P < .03 for rapidly increased frailty index)., Conclusions and Implications: We found that considering both frailty phenotype and frailty index provided best mortality prediction. These associations were independent of baseline frailty status and comorbidities. Nevertheless, even capturing transitions in frailty phenotype or frailty index only can provide good mortality prediction, which supported adopting these approaches in different clinical settings., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Despite the recognized impact of intrinsic capacity (IC) impairment on healthy aging, international comparisons in different sociocultural contexts are scarce. This study aimed to compare IC impairment among community-dwelling older adults in Japan and Taiwan to explore the context of healthy aging in different countries., Design: Comparative observational study., Setting: National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) in Japan and Longitudinal Aging Study of Taipei (LAST) in Taiwan., Participants: 794 individuals (age range, 60.0-86.5 years) from NILS-LSA and 1,358 (60.0-96.7 years) from LAST., Measurements: IC impairment was evaluated across the domains of locomotion, cognition, vitality, sensory capacity, and psychological well-being. Participants were categorized as having impaired IC or healthy. We investigated associations between IC impairment, falls, and all-cause mortality., Results: IC impairment was present in 54.9% and 37.3% of participants in the NILS-LSA and LAST cohorts, respectively. Male NILS-LSA participants with impaired IC (odds ratio [OR]:1.50, 95% confidence interval [CI]:1.03-2.20), with hearing loss (OR:1.98, 95% CI:1.00-3.90) were more likely to fall. In LAST, impaired locomotion (OR:2.14, 95% CI:1.46-3.14) increased the risk of falls. Men with impaired IC (hazard ratio [HR]; 2.14, 95% CI:1.10-4.15) and visual impairment (HR:2.21, 95% CI:1.15-4.25) and women with impaired psychological well-being (HR:4.94, 95% CI:1.28-18.97) in the NILS-LSA cohort had greater risk for all-cause mortality; however, this was not shown for LAST participants., Conclusion: The prevalence and distribution of IC impairment and associated biomarkers differed significantly between participants in Japan and Taiwan. However, the associations with adverse outcomes remained similar, emphasizing the need for tailored interventions for healthy aging., Competing Interests: None.

Objectives: To evaluate the associations between cardiovascular disease (CVD) risk burden (estimated by the World Health Organization (WHO) algorithm) and cognitive impairments (e.g., incident dementia, global and domain-specific impairments) among CVD-, dementia- and disability-free, community-dwelling middle-aged and older adults during an 8-year follow-up., Design: A community-based longitudinal cohort study., Setting: Yuanshan township in Yi-Lan County, Taiwan., Participants: A total of 889 community-dwelling residents aged 50 years or older., Measurements: Age, sex, educational level, employment status, alcohol status, body mass index, physical activity, gait speed, depressive symptoms, WHO region-specific CVD risk scores (10-year CV risk, low: <10% vs. moderate-to-high: ≥ 10%), Chinese version of the Mini-Mental State Examination (MMSE), verbal memory by the delay-free recall in the Chinese Version Verbal Learning Test (CVVLT), language function by the Boston Naming Test and the category (animal) Verbal Fluency Test, visuospatial function by the Taylor Complex Figure Test, executive function by the digit backward and the Clock Drawing Test., Results: Compared to those with low CVD risk, middle-aged and older adults with moderate-to-high CVD risk were at greater risk for cognitive impairments with respect to the MMSE (adjusted odds ratio (aOR) 1.60 [95% confidence interval (CI) 1.19-2.15], P=0.002), verbal memory (aOR 1.97 [1.43-2.70], P< 0.001) and language (aOR 1.99 [1.46-2.70], P< 0.001), as well as incident dementia (aOR 2.40 [1.33-4.33], P=0.004). After adjusting for all covariates, CVD risk was not associated with other domains of cognitive impairment., Conclusions: Among healthy, community-dwelling, middle-aged and older adults, those with moderate-to-high cardiovascular risk burden were significantly associated with incident dementia and global and domain-specific cognitive impairments (verbal memory and language), which suggests the existence of a relationship between early cognitive deficits and CVD risk burden. Further studies are needed to elucidate the pathophysiological mechanism of the link between CVD risk burden and cognitive impairment., Competing Interests: The authors declare that they have no financial interests, relationships, or affiliations relevant to the subject of this manuscript.

Background: Oligonol® is a low-molecular-weight polyphenol that has biological effects on metabolism in animals. However, little is known about its roles in muscle function and muscle quality in middle-aged and older adults., Methods: 120 participants were enrolled for study based on 1:1 randomization. Participants in the intervention group were provided 200 mg oligonol® prepared as capsules, and 200 mg placebo (dextrin) was provided in control group., Results: Data from 103 participants (52 in the intervention group and 51 in the control group) were available for analysis. The mean age of all participants was 64.0 ± 8.2 years, and two-thirds of the participants were females. Baseline demographic characteristics, functional assessment, laboratory data and muscle parameters were similar between groups. Hip circumference decreased (p = 0.009) during the study period, and the 6-m walking speed increased (p = 0.001) in women in the intervention group. In contrast, 6-m walking speed, 6-min walking distance and handgrip strength were significantly improved in men in the intervention group, but increased total body fat percentage (p = 0.038) and decreased mid-thigh cross-muscle area (CMA) (p = 0.007) were observed in the control group. Compared to the control group, the 12-week interval change in the percentage of mid-thigh CMA was maintained in men in the intervention group but was significantly decreased in the control group (p = 0.03, 95% CI:0.002-0.05)., Conclusions: Oligonol supplementation (200 mg per day) significantly improved physical performance and muscle mass in men. Further studies are needed to confirm the potential favorable effects of oligonol® supplementation., Competing Interests: Declaration of Competing Interest All authors have declared that no support from any organisation for the submitted work, no financial relationships with any organisations that might have an interest in the submitted work in the previous three years and no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: To investigate the relationship between dietary diversity and healthy aging (in terms of mobility performance, physical functions, cognitive functions, and depressive symptoms) among community-dwelling middle-aged and older adults by using a nationally representative population-based cohort study., Methods: Data from 3213 study participants in the Taiwan Longitudinal Study on Aging (TLSA) were retrieved for analysis, and all participants were divided into five groups according to the quintile of dietary variety scores (DVSs). In the 4-year follow-up study, multivariate logistic regression models were applied to investigate the associations between DVS subgroups and declines in mobility performance, physical function (activities of daily living (ADLs) and instrumental activities of daily living (IADLs)), cognitive function and depressive symptoms., Results: In this study, the DVS quintile identified people who were significantly vulnerable in diet quality. Among those in the lowest DVS quintile, the proportions consuming seafood, eggs, and beans/legumes per week were 0.3 %, 7.8 % and 12.6 %, respectively, while among those in the highest DVS quintile, the proportions were 40.2 %, 83.1 %, and 82.7 %, respectively. "Inverse" dose-response associations were observed between the DVS and the risks of decline in mobility performance, physical function (ADLs and IADLs), cognitive function, and depressive symptoms. These risks decreased with the higher DVS quintile group as compared to the lowest DVS quintile group. Even after adjustments for demographics, health behaviors (e.g., physical activity) and comorbidities, participants in the highest DVS quintile group were still associated with the lowest risk of decline in ADLs (adjusted odds ratio (aOR) 0.59 [95 % confidence interval (CI) 0.37-0.94], p < 0.05) and IADLs (aOR 0.53 [0.39-0.73], p < 0.01). However, no such association was observed in the risk of worsened mobility performance, cognitive function and depressive symptoms., Conclusions: In conclusion, higher dietary diversity has protective effects in declines in multidimensional outcomes associated with healthy aging, particularly physical functions (ADL and IADL), among community-dwelling middle-aged and older adults. Intervention studies are needed to confirm the causal relationships between dietary diversity and healthy aging., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

PCR testing is increasingly important for microbial control in SPF facilities. However, most current PCR methods are timeconsuming and require compromise between high sensitivity and high multiplexing. We developed a one-tube multiplex nested PCR strategy (MN-PCR) for simultaneous direct (that is, without culturing) detection of multiple pathogens. We first aligned sequences for the 16S rDNA genes of selected target bacteria and a panel of closely related organisms. From these data, we designed a pair of universal primers and multiple sets of species-specific PCR primers to amplify the target sequences; the universal primers were modified to include various degenerate bases and locked nucleic acids. In a single tube, 16S rDNA sequences were amplified by using the nested PCR primers under high temperature (that is, above 65°C) during the first stage of the MN-PCR procedure, when the target-species-specific PCR primers do not support amplification due to their short length. In addition, the concentration of the nested PCR primers during the first stage was adjusted to ensure that they were consumed and did not yield visible bands themselves. During the second stage, the enriched 16S rDNA sequences then served as templates for amplification of the species-specific fragments by using the multiple PCR primers at low annealing temperatures (that is, below 60°C). The results showed that our MN-PCR method detected as little as 1 fg of target bacterial DNA in a 20-μL reaction volume, whereas conventional multiplex PCR detected a minimum of 1 pg only. Compared with traditional multiplex PCR assays, our MN-PCR system is an effective and efficient culture-free process.

Objectives: Frailty has been shown to predict adverse outcomes in several diseases. We aimed to evaluate the associations between frailty profiles, both severity and subtype, and dementia risk in a community-based population with asymptomatic (without stroke and dementia) cerebral small vessel disease (CSVD)., Methods: Individuals with asymptomatic CSVD were recruited from the community-based I-Lan Longitudinal Aging Study between 2011 and 2014 (baseline) and were followed up between 2018 and 2019. All participants underwent CSVD assessment by 3T brain MRI, as well as physical and cognitive assessments at baseline. Univariate and multivariate logistic regression analyses were performed to evaluate the associations between each factor and dementia conversion at follow-up., Results: Among 261 participants with asymptomatic CSVD (64.8 [50.0-89.1, 8.4] years; 136 [52.1%] men), 13 (5.0%) developed dementia during a mean follow-up of 5.7 (0.7) years. Dementia converters were less likely to be robust (30.8% vs. 61.5%) and more likely to be pre-frail/frail (69.2% vs. 38.5%) than non-converters (p = 0.040). Meanwhile, there was significantly more frequent mobility frailty (53.8% vs. 19.8%, p = 0.009), but a similar prevalence of non-mobility frailty in dementia converters compared with non-converters. Univariate analyses showed that neither frailty severity nor CSVD burden was associated with a higher risk of dementia; it was the frailty subtype, the mobility frailty, which was significantly associated with dementia conversion in participants with asymptomatic CSVD, with an odds-ratio of 4.8 (95% CI = 1.5-14.8, p = 0.007). The significance remained after adjusting for age, sex, education and baseline cognitive function, respectively., Conclusion: Mobility frailty was associated with a higher risk of incident dementia in individuals with subclinical CSVD. Mobility frailty might be involved in the pathology of cognitive decline in CSVD and potentially serve as a marker to identify people at risk of cognitive impairment at an early stage of CSVD., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Carotid-femoral pulse wave velocity (cf-PWV), an index of mainly distal aortic stiffness, has been inconsistently associated with cognitive function. Excess pressure, derived from the arterial reservoir-excess pressure analysis, may integrate the pulsatile load of the proximal aorta. The present study examined whether increased excess pressure is associated with cognitive function impairment in community adults., Methods: A total of 992 community participants (69.5% females; mean age: 67.3 years; education 13.6 years) without cerebrovascular disease or dementia received the Montreal Cognitive Assessment (MoCA) to evaluate global cognition. Arterial reservoir and excess pressure, arterial stiffness, and wave reflections were assessed, using carotid tonometry and aortic Doppler flowmetry., Results: Excess pressure integral (XSPI), percentage XSPI, cf-PWV, characteristic impedance (Zc), and forward and backward pressure amplitude (Pf, Pb, respectively) were significantly higher in 197 participants (19.9%) with a low MoCA score (<26 or <25, depending on level of education). In multivariable analyses, XSPI (standardized odds ratio, 95% confidence interval, 1.30, 1.06-1.59), and percentage XSPI (1.27, 1.06-1.52) but not cf-PWV (1.04, 0.85-1.26) were significantly associated with a low MoCA. Further analysis revealed that Pf and Zc were the major determinants of XSPI (partial R2: Pf = 0.656, Zc = 0.467) and percentage XSPI (Pf = 0.459, Zc = 0.371). In contrast, age, instead of Pf and Zc, was the major determinant of cf-PWV (partial R2: age = 0.187)., Conclusions: Excess pressure (XSPI/percentage XSPI), mainly determined by the pulsatile hemodynamics of the proximal aorta, was significantly associated with cognitive function impairment in middle-aged and elderly community adults., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To explore associations between PCDS, incident dementia and mortality risk and evaluate the potential of its reversibility., Methods: 963 participants from the I-Lan Longitudinal Aging Study were followed up for 6 years for analysis. A subsample of 513 participants was invited to participate 3 years earlier. The 1.5 standard deviation lower age- and education-matched norms of neuropsychiatric assessments determined cognitive impairment. Weakness and slowness were defined by the Asian Working Group for Sarcopenia 2019. PCDS was defined as cognitive impairment plus mobility impairment, i.e., weakness and/or slowness., Results: The prevalence of PCDS was 19.0% among 1709 participants aged 63.5 ± 9.0 years (from 50 to 90 years) and increased with age (14.7% in people aged 50-64 years, 19.5% in people aged 65-74 years, 36.7% in people aged 75-84 years and 45.5% in people aged ≥ 85 years, p for trend <0.001). 13.6% and 8.3% of participants had improved PCDS conditions in 513 participants at 3-year and in 963 participants at 6-year assessments. Of 118 participants with PCDS at baseline,36 (30.5%) returned to non-PCDS in 6 years. Being female and having good nutrition were potential associated factors. During the mean follow-up period of 5.9 ± 0.9 years, 182 deaths occurred in the 10,065 person-years. PCDS could predict the 6-year risk of mortality (HR 1.56, 95% CI 1.02-2.39, p = 0.012) and 6-year incident dementia (OR 3.42, 95% CI: 1.41-8.29, p = 0.007)., Conclusions: PCDS significantly predict 6-year mortality and 6-year incident dementia. Reversibility of PCDS made it as an optimal target for intervention and prevention., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic has had strong adverse impacts on vulnerable populations, such as frail older adults. The success of COVID-19 vaccine development, together with extensive global public health efforts, has brought hope to the control of the COVID-19 pandemic. Nevertheless, challenges in COVID-19 vaccine development and vaccination strategies among older people remain. This article reviews vaccinations in older adults, compares COVID-19 vaccine platforms, the efficacy and safety of COVID-19 vaccines in frail older people in long-term care settings, and the challenges of COVID-19 vaccine development and policy making for vaccination strategies in older adults., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Depression has been reported as a risk factor for dementia, as well as the continuation of dementia development. This study aimed to stratify older people with dementia (PwD) into three groups (no depression, early depression and recent depression) to compare their inpatient health care utilization and to explore related clinical impacts., Methods: Overall, 11,612 PwD were identified from Taiwan's National Health Insurance Research Database and were further divided into 9,257 PwD without depression, 1,179 PwD with recent depression (< 2 years from dementia diagnosis), and 1,176 PwD with early depression (> 2 years from dementia diagnosis). Three matched cohort pairs (Cohort 1: no depression versus recent depression, Cohort 2: no depression versus early depression, and Cohort 3: recent depression versus early depression) were constructed to compare inpatient health care utilization three years after dementia onset., Results: The incidence of hospitalization related to mental illness among PwD with a recent or early depression onset were significantly higher than their matched cohort without depression. The recent depression group had a greater rate ratio (RR) with a longer length of stay due to depression (RR: 8.29, 95% CI: 2.74-25.12) compared to the no depression group, and the early depression group had 4.24 times (95% CI: 1.56-11.59) and 6.40 times (95% CI: 2.18-18.82) longer length of stay than the no depression group due to depression, and mood disorders., Conclusions: Depression significantly increased inpatient health care utilization of depression and mood disorder among older PwD with early depression., (Copyright © 2022. Published by Elsevier B.V.)

Hyoscine-N-butylbromide (HBB) is the most used antiperistaltic agent during esophagogastroduodenoscopy (EGD). However, almost half of the elderly have a contraindication to HBB. We aimed to evaluate L-menthol's antiperistaltic effect and safety for EGD in the elderly with contraindication to HBB. This prospective, randomized, double-blind, placebo-controlled study screened 86 elderly patients (≥ 65 years old) scheduled to undergo EGD, and 52 of them with contraindication to HBB were enrolled. The participants were randomized to receive L-menthol (n = 26) or a placebo (n = 26), which was locally sprayed on the gastric antrum endoscopically. The proportion of patients with no or mild peristalsis after medication and at the end of EGD was significantly higher in the L-menthol group (76.9%) than in the placebo group (11.5%, p < 0.001). L-Menthol administration significantly reduced peristaltic grade, improved contraction parameters, and eased intragastric examination relative to the placebo (p < 0.001, respectively). Hemodynamic changes, adverse events, and discomfort levels of patients were similar between the two groups. L-Menthol is an effective and safe alternative antiperistaltic medication for EGD in elderly patients with contraindication to HBB. Further large, randomized trials are required to clarify whether L-menthol can lead to better detection yield in the elderly.Clinical trial registration: The study was registered at ClinicalTrials.gov (NCT04593836)., (© 2022. The Author(s).)

Background: Sarcopenia, defined as age-related diminution of muscle mass and strength, is a key determinant of frailty status and progression. We investigated the hypothesis that changing masseter muscle structure with advancing age may contribute to the development of frailty., Methods: Study data were excerpted from the I-Lan Longitudinal Aging Study, a research cohort of community-dwelling residents aged ≥53 years from Yilan (I-Lan) County, Taiwan. The study sample comprised 56 subjects classified as frail, 41 pre-frail, and 41 robust, according to Cardiovascular Health Study criteria; all groups were matched by age and sex. Masseter muscle volume was quantified based on T1-weighted magnetic resonance imaging, and adjusted for height to derive the masseter volume index (MVI). Appendicular skeletal muscle mass index (SMI) was determined by dual-energy X-ray absorptiometry, and used to derive the height-adjusted skeletal mass index (SMI). Nutrition status was assessed with the Mini-Nutritional Assessment (MNA) form., Results: The MVI was significantly smaller in frail versus pre-frail subjects. Among frail individuals, only the MVI was significantly correlated with MNA scores. MVI, but not SMI, was associated with increased risk of being frail versus pre-frail. An MVI cut-off score of 9.5 cm 3 /m 2 in males discriminated frail from pre-frail status with acceptable sensitivity and specificity. Low MVI was associated with the frailty criteria of slowness., Conclusions: MVI is a potential clinical index for evaluating phenotypic frailty. Diminished masseter muscle volume may predispose pre-frail/frail elders to depletion of physical reserves, consequent to its detrimental effect on oral functioning and nutrient intake., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Aging is a complex process involving functional decline, reduced physiological reserve, increased multimorbidity, and impaired homeostasis, all of which collectively generate various health risks for older adults. To predict short-term mortality of non-critical older patients in the observation room of the emergency department (ED) based on function-centric approach instead of disease-centric one., Methods: We conducted a prospective study enrolling 831 patients aged 75 years and older between 2018 and 2020. Comprehensive geriatric assessment was performed on all patients, and the results were integrated into the care planning process., Results: In total 831 patients (mean age: 84.8 ± 5.8 years) were enrolled and the post-discharge mortality rate was 3.3% (28 deaths) after 3 months, and 5.4% (45 deaths) after 6 months. The independent predictors of 3-month mortality were malnutrition (adjusted odds ratio [OR], 4.77; p < 0.05), incontinence (adjusted OR, 2.58; p < 0.05) and multimorbidity (adjusted OR, 1.51; p < 0.001). For 6-month mortality, malnutrition (adjusted OR, 4.20; p < 0.01), multimorbidity (adjusted OR, 1.40; p < 0.001) and activities of daily living (adjusted OR, 0.99; p < 0.05) were all independent predictors., Conclusion: Although ED aims to treat acute and life-threatening conditions, older persons with geriatric syndromes are also at a substantially high risk of adverse outcomes, even mortality. Transitioning of the ED from disease-centric to function-centric services is important for responding to the changing health care needs of super-aged societies., (Copyright © 2022 Elsevier B.V. All rights reserved.)