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Background Several studies have examined gut microbiota and sarcopenia using 16S ribosomal RNA amplicon sequencing; however, this technique may not be able to identify altered specific species and functional capacities of the microbes. We performed shotgun metagenomic sequencing to compare the gut microbiome composition and function between individuals with and without sarcopenia. Methods Participants were from a community‐based observational study conducted among the residents of rural areas in China. Appendicular skeletal muscle mass was assessed using direct segmental multi‐frequency bioelectrical impedance and grip strength using a Jamar Hydraulic Hand dynamometer. Physical performance was evaluated using the Short Physical Performance Battery, 5‐time chair stand test and gait speed with the 6 m walk test. Sarcopenia and its severity were diagnosed according to the Asian Working Group for Sarcopenia 2019 algorithm. The gut microbiome was profiled by shotgun metagenomic sequencing to determine the microbial composition and function. A gut microbiota‐based model for classification of sarcopenia was constructed using the random forest model, and its performance was assessed using the area under receiver‐operating characteristic curve (AUC). Results The study sample included 1417 participants (women: 58.9%; mean age: 63.3 years; sarcopenia prevalence: 10.0%). β‐diversity indicated by Bray–Curtis distance (genetic level: P = 0.004; taxonomic level of species: P = 0.020), but not α‐diversity indicated by Shannon index (genetic level: P = 0.962; taxonomic level of species: P = 0.922), was significantly associated with prevalent sarcopenia. After adjusting for potential confounders, participants with sarcopenia had higher relative abundance of Desulfovibrio piger (P = 0.003, Q = 0.090), Clostridium symbiosum (P < 0.001, Q = 0.035), Hungatella effluvii (P = 0.003, Q = 0.090), Bacteroides fluxus (P = 0.002, Q = 0.089), Absiella innocuum (P = 0.002, Q = 0.072), Coprobacter secundus (P = 0.002, Q = 0.085) and Clostridium citroniae (P = 0.001, Q = 0.060) than those without sarcopenia. The relative abundance of six species (Desulfovibrio piger, Clostridium symbiosum, Hungatella effluvii, Bacteroides fluxus, Absiella innocuum, and Clostridium citroniae) was also positively associated with sarcopenia severity. A differential species‐based model was constructed to separate participants with sarcopenia from controls. The value of the AUC was 0.852, suggesting that model has a decent discriminative performance. Desulfovibrio piger ranked the highest in this model. Functional annotation analysis revealed that the phenylalanine, tyrosine, and tryptophan biosynthesis were depleted (P = 0.006, Q = 0.071), while alpha‐Linolenic acid metabolism (P = 0.008, Q = 0.094), furfural degradation (P = 0.001, Q = 0.029) and staurosporine biosynthesis (P = 0.006, Q = 0.072) were enriched in participants with sarcopenia. Desulfovibrio piger was significantly associated with staurosporine biosynthesis (P < 0.001). Conclusions This large population‐based observational study provided empirical evidence that alterations in the gut microbiome composition and function were observed among individuals with sarcopenia.

Background In southern Europe, the risk of cancer in patients with end-stage kidney disease receiving dialysis has not been well quantified. The aim of this study was to assess the overall pattern of risk for de novo malignancies (DNMs) among dialysis patients in the Friuli Venezia Giulia region, north-eastern Italy. Methods A population-based cohort study among 3407 dialysis patients was conducted through a record linkage between local healthcare databases and the cancer registry (1998–2013). Person-years (PYs) were calculated from 30 days after the date of first dialysis to the date of DNM diagnosis, kidney transplant, death, last follow-up or December 31, 2013, whichever came first. The risk of DNM, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Results During 10,798 PYs, 357 DNMs were diagnosed in 330 dialysis patients. A higher than expected risk of 1.3-fold was found for all DNMs combined (95% CI: 1.15–1.43). The risk was particularly high in younger dialysis patients (SIR = 1.88, 95% CI: 1.42–2.45 for age 40–59 years), and it decreased with age. Moreover, significantly increased DNM risks emerged during the first 3 years since dialysis initiation, especially within the first year (SIR = 8.52, 95% CI: 6.89–10.41). Elevated excess risks were observed for kidney (SIR = 3.18; 95% CI: 2.06–4.69), skin non-melanoma (SIR = 1.81, 95% CI: 1.46–2.22), oral cavity (SIR = 2.42, 95% CI: 1.36–4.00), and Kaposi’s sarcoma (SIR = 10.29, 95% CI: 1.25–37.16). Conclusions The elevated risk for DNM herein documented suggest the need to implement a targeted approach to cancer prevention and control in dialysis patients.

The present study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population‐based cancer registry data. The analysis was based on 5192 children with cancer (age 0‐14 years) from 6 prefectural cancer registries in Japan and 21 295 children diagnosed in England during 1993‐2010. Differences in incidence rates between the 2 countries were measured with Poisson regression models. Overall survival was estimated using the Kaplan–Meier method. Incidence rates for Hodgkin lymphoma, renal tumors and Ewing sarcomas in England were more than twice as high as those in Japan. Incidence of germ cell tumors, hepatic tumors, neuroblastoma and acute myeloid leukemia (AML) was higher in Japan than in England. Incidence of all cancers combined decreased in Japan throughout the period 1993 to 2010, which was mainly explained by a decrease in registration of neuroblastoma in infants. For many cancers, 5‐year survival improved in both countries. The improvement in survival in chronic myeloid leukemia (CML) was particularly dramatic in both countries. However, 5‐year survival remained less than 80% in 2005‐2008 in both countries for AML, brain tumors, soft tissue sarcomas, malignant bone tumors and neuroblastoma (age 1‐14 years). There were significant differences in incidence of several cancers between countries, suggesting variation in genetic susceptibility and possibly environmental factors. The decrease in incidence for all cancers combined in Japan was related to the cessation of the national screening program for neuroblastoma. The large improvement in survival in CML coincided with the introduction of effective therapy (imatinib). For many of childhood cancers, 5‐year survival improved in Japan and England. The improvement in survival in chronic myeloid leukaemia (CML) was particularly dramatic in both countries.

INTRODUCTION To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)‐related plasma biomarkers among older adults. METHODS This population‐based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aβ), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models. RESULTS The number of chronic diseases was associated with dementia (multivariable‐adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non‐amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non‐amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aβ and NfL (p < 0.05). DISCUSSION Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD‐related plasma biomarkers in older adults. Highlights We used hierarchical clustering to generate five clusters of multimorbidity. The presence and load of multimorbidity were associated with dementia and mild cognitive impairment. Multimorbidity clusters were differentially associated with subtypes of dementia and Alzheimer's disease plasma biomarkers.

Background and Purpose Emerging evidence has linked impaired kidney function with dementia in older adults, but the neuropathological pathways underlying their association remain poorly understood. We sought to examine the relationships of kidney function with dementia and plasma biomarkers in a Chinese rural population. Methods This population‐based study used data from the baseline examination of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND‐China) cohort (March–September 2018; n = 5715). Kidney function was assessed using estimated glomerular filtration rate (eGFR) based on serum creatinine level. Dementia, Alzheimer's disease (AD) and vascular dementia (VaD) were diagnosed according to the international criteria. Plasma biomarkers were measured using the SIMOA platform in a subsample (n = 1446). Data were analyzed using logistic, general linear, and mediation models. Results Of the 5715 participants, 306 were diagnosed with dementia, including 195 with AD and 100 with VaD. Impaired kidney function (eGFR <60 vs. ≥90 mL/min/1.73 m2) was associated with multivariable‐adjusted odds ratios of 2.24 (95% confidence interval [CI] 1.44–3.46) for all‐cause dementia, 1.85 (1.07–3.18) for AD, and 2.49 (1.16–5.22) for VaD. In the biomarker subsample, impaired kidney function was significantly associated with higher plasma amyloid‐β (Aβ)40 (β‐coefficient = 54.36, 95% CI 43.34–65.39), Aβ42 (β‐coefficient = 3.14, 95% CI 2.42–3.86), neurofilament light chain (β‐coefficient = 10.62, 95% CI 5.62–15.62), and total tau (β‐coefficient = 0.68, 95% CI 0.44–0.91), and a lower Aβ42/Aβ40 ratio (β‐coefficient = −4.11, 95% CI −8.08 to −0.14). The mediation analysis showed that plasma total tau significantly mediated 21.76% of the association between impaired kidney function and AD (p < 0.05). Conclusion Impaired kidney function is associated with dementia and plasma biomarkers among rural‐dwelling older Chinese adults, and the association with AD is partly mediated by plasma biomarkers for neurodegeneration.

There is limited evidence for the effects of diet on cardiometabolic profiles during the pubertal transition. We collected repeated measures of diet quality and cardiometabolic risk factors among Mexican youth. This analysis included 574 offspring of the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort followed up to three time points. Dietary Approaches to Stop Hypertension (DASH), alternate Mediterranean Diet (aMedDiet), and Children’s Dietary Inflammatory Index (C-DIITM) scores were computed from food frequency questionnaires. Higher DASH and aMedDiet scores reflect a higher diet quality, and lower C-DII scores reflect an anti-inflammatory diet. Cardiometabolic risk factors were lipid profile, glucose homeostasis, blood pressure, and waist circumference. Linear mixed models were used between quartiles of each diet score and outcomes. Compared to the first quartile, the fourth DASH quartile was inversely associated with log serum insulin (μIU/mL) [β = −0.19, p = 0.0034] and log-Homeostatic Model Assessment of Insulin Resistance [β = −0.25, p = 0.0008]. Additionally, log serum triglycerides (mg/dL) was linearly associated with aMedDiet score [β = −0.03, p = 0.0022]. Boys in the highest aMedDiet quartile had higher serum high-density lipoprotein cholesterol (mg/dL) [β = 4.13, p = 0.0034] compared to the reference quartile. Higher diet quality was associated with a better cardiometabolic profile among Mexican youth.

Introduction Multidomain intervention approaches have emerged as a potential strategy to reduce dementia risk. We sought to describe the baseline assessment approaches, health conditions, and risk profiles for brain aging of participants in the randomized controlled Multimodal INterventions to delay Dementia and disability in rural China (MIND‐China). Methods MIND‐China engaged residents who were ≥60 years of age and living in rural communities in the western Shandong province. In March to September 2018, all participants underwent the core module assessments via face‐to‐face interviews, clinical examinations, neuropsychological testings, and laboratory tests. Specific modules of examination were performed for sub‐samples, including brain magnetic resonance imaging scans, genetic and blood biochemical markers, actigraphy testing, cardiopulmonary coupling analysis for sleep quality and disturbances, audiometric testing, and optical coherence tomography examination. We performed descriptive analysis. Results In total, 5765 participants (74.9% of all eligible residents) undertook the baseline assessments. The mean age was 70.9 years (standard deviation, 5.9), 57.2% were women, 40.6% were illiterate, and 88.3% were farmers. The overall prevalence of common chronic diseases was 67.2% for hypertension, 23.4% for dyslipidemia, 23.5% for heart disease, 14.4% for diabetes mellitus, and 5.4% for dementia. The prevalence rates of hypertension, diabetes mellitus, dyslipidemia, obesity, heart disease, depressive symptoms, and dementia were higher in women than in men (P < .05). Overall, 87.1% of the participants had at least two of the 15 chronic diseases (89.3% in women vs 84.2% in men, P < .001). Participants examined for the specific modules were younger, more likely to be women, and more educated than those not examined. Discussion Comprehensive baseline assessments of participants in MIND‐China provide extremely valuable data sources for interdisciplinary research into the complex relationships of aging, health, brain aging, and functional consequences among older adults living in the rural communities. Highlights MIND‐China is a multimodal intervention study among rural residents ≥60 years of age. At baseline, 5765 participants undertook the interdisciplinary assessments. The baseline assessments consisted of core module and specific modules. Specific modules included brain magnetic resonance imaging (MRI), blood biomarkers, ActiGraph, cardiopulmonary coupling (CPC), pure‐tone audiometry (PTA), and optical coherence tomography (OCT).

Background Low handgrip strength (HGS) is a measure of poor skeletal muscle performance and a marker of ill health and frailty. Muscle quality (MQ) is a measure of muscle strength relative to muscle mass. We aimed to develop normative data for HGS and MQ, report age‐related prevalence of low HGS and MQ, and determine the relationship with age, anthropometry, and body composition for women in Australia. Methods This cross‐sectional analysis included data from 792 women (ages 28–95 years) assessed by the Geelong Osteoporosis Study. Duplicate measures of HGS were performed for each hand with a dynamometer (Jamar) and the mean of maximum values used for analyses. Dual energy X‐ray absorptiometry‐derived lean mass for the arms was used to calculate MQ as HGS/lean mass (kg/kg). Body mass index (BMI) was categorized as normal (BMI < 25.0 kg/m2), overweight (25.0–29.9 kg/m2), and obese (>30.0 kg/m2). Fat mass index (FMI) was calculated as whole body fat/height2 (kg/m2) and appendicular lean mass index (ALMI) as lean mass of arms and legs/height2 (kg/m2). Results Mean (±SD) of HGS values for normal BMI, overweight, and obese groups were 25 (±7), 24 (±7), and 24 (±7) kg, P = 0.09, and for MQ, 12 (±3), 11 (±3), and 10 (±3) kg/kg, P < 0.001. Our data indicated a quadratic relationship between age and HGS or MQ. Mean HGS and MQ remained stable until the fifth age decade then declined steadily with increasing age; therefore, we used data for women (n = 283) aged 28–49 years as the young adult reference group, with mean (SD) values for HGS 28 (±6) kg and MQ 12 (±3) kg/kg. The prevalence of low (T‐score < −2) HGS and MQ for women 80 years and older was 52.2% and 39.6%, respectively. In multivariable models, age‐adjusted HGS was associated with FMI (B = −0.13, P = 0.004) and ALMI (1.03, <0.001) while age‐adjusted MQ was associated with BMI (−0.15, <0.001) but not with FMI. In a sensitivity analysis, the same pattern remained after the removal of 129 women who reported hand and/or arm pain. Conclusions Mean HGS and MQ declined with advancing age in older women. Our data suggest that while mean HGS increased with appendicular lean mass and decreased with body fat mass, there was no association with BMI. By contrast, MQ decreased with increasing BMI, but not with increasing adiposity.

INTRODUCTION We quantified the association of mild (ie, involving one or two body systems) and complex (ie, involving ≥3 systems) multimorbidity with structural brain changes in older adults. METHODS We included 390 dementia‐free participants aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen who underwent brain magnetic resonance imaging at baseline and after 3 and/or 6 years. Using linear mixed models, we estimated the association between multimorbidity and changes in total brain tissue, ventricular, hippocampal, and white matter hyperintensities volumes. RESULTS Compared to non‐multimorbid participants, those with complex multimorbidity showed the steepest reduction in total brain (β*time −0.03, 95% CI −0.05, −0.01) and hippocampal (β*time −0.05, 95% CI −0.08, −0.03) volumes, the greatest ventricular enlargement (β*time 0.03, 95% CI 0.01, 0.05), and the fastest white matter hyperintensities accumulation (β*time 0.04, 95% CI 0.01, 0.07). DISCUSSION Multimorbidity, particularly when involving multiple body systems, is associated with accelerated structural brain changes, involving both neurodegeneration and vascular pathology. Highlights Multimorbidity accelerates structural brain changes in cognitively intact older adults These brain changes encompass both neurodegeneration and cerebrovascular pathology The complexity of multimorbidity is associated with the rate of brain changes’ progression

Background Adequate cytology is limited by insufficient cytologists in a large‐scale cervical cancer screening. We aimed to develop an artificial intelligence (AI)‐assisted cytology system in cervical cancer screening program. Methods We conducted a perspective cohort study within a population‐based cervical cancer screening program for 0.7 million women, using a validated AI‐assisted cytology system. For comparison, cytologists examined all slides classified by AI as abnormal and a randomly selected 10% of normal slides. Each woman with slides classified as abnormal by either AI‐assisted or manual reading was diagnosed by colposcopy and biopsy. The outcomes were histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Results Finally, we recruited 703 103 women, of whom 98 549 were independently screened by AI and manual reading. The overall agreement rate between AI and manual reading was 94.7% (95% confidential interval [CI], 94.5%‐94.8%), and kappa was 0.92 (0.91‐0.92). The detection rates of CIN2+ increased with the severity of cytology abnormality performed by both AI and manual reading (Ptrend < 0.001). General estimated equations showed that detection of CIN2+ among women with ASC‐H or HSIL by AI were significantly higher than corresponding groups classified by cytologists (for ASC‐H: odds ratio [OR] = 1.22, 95%CI 1.11‐1.34, P < .001; for HSIL: OR = 1.41, 1.28‐1.55, P < .001). AI‐assisted cytology was 5.8% (3.0%‐8.6%) more sensitive for detection of CIN2+ than manual reading with a slight reduction in specificity. Conclusions AI‐assisted cytology system could exclude most of normal cytology, and improve sensitivity with clinically equivalent specificity for detection of CIN2+ compared with manual cytology reading. Overall, the results support AI‐based cytology system for the primary cervical cancer screening in large‐scale population. This study aims to assess the role of Artificial Intelligence (AI) in the detection of early cervical cancer in a low resource setting. Our results showed that AI‐assisted cytology could identify most of negative cytology, and showed higher positive predictive value for CIN2 or worse when compared with cytologists. This study indicates that AI‐assisted cytology could be very useful tool as a primary screening method in a large‐scale cervical cancer screening program to improve its effectiveness.