Alzheimer's disease (AD) is a progressive neurodegenerative condition, and early intervention can help slow its progression. However, integrating multi-dimensional information and deep convolutional networks increases the model parameters, affecting diagnosis accuracy and efficiency and hindering clinical diagnostic model deployment. Multi-modal neuroimaging can offer more precise diagnostic results, while multi-task modeling of classification and regression tasks can enhance the performance and stability of AD diagnosis. This study proposes a Hierarchical Attention-based Multi-task Multi-modal Fusion model (HAMMF) that leverages multi-modal neuroimaging data to concurrently learn AD classification tasks, cognitive score regression, and age regression tasks using attention-based techniques. Firstly, we preprocess MRI and PET image data to obtain two modal data, each containing distinct information. Next, we incorporate a novel Contextual Hierarchical Attention Module (CHAM) to aggregate multi-modal features. This module employs channel and spatial attention to extract fine-grained pathological features from unimodal image data across various dimensions. Using these attention mechanisms, the Transformer can effectively capture correlated features of multi-modal inputs. Lastly, we adopt multi-task learning in our model to investigate the influence of different variables on diagnosis, with a primary classification task and a secondary regression task for optimal multi-task prediction performance. Our experiments utilized MRI and PET images from 720 subjects in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. The results show that our proposed model achieves an overall accuracy of 93.15% for AD/NC recognition, and the visualization results demonstrate its strong pathological feature recognition performance.
Purpose: This study aimed to investigate the alteration trends and overlaps of positive features in benign and malignant thyroid nodules of different sizes based on the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS). Patients and Methods: 1337 patients with 1558 thyroid nodules were retrospectively recruited from November 2021 to December 2023. These nodules were divided into three groups according to maximum diameter: A (≤10 mm), B (10-20 mm), and C (≥20 mm). C-TIRADS positive features were compared between benign and malignant thyroid nodules of different sizes. In addition, the trends of positive features with changes in nodule size among malignant thyroid nodules were analyzed. Results: The incidence of positive features in malignant thyroid nodules was higher than that in benign. As benign nodules grow, the incidence of all positive features showed a linear decreasing trend (Z values were 72.103, 101.081, 17.344, 33.909, and 129.304, P values < 0.001). With the size of malignant thyroid nodules increased, vertical orientation, solid, marked hypoechogenicity, and ill-defined/irregular margins/extrathyroidal extension showed a linear decreasing trend (Z = 148.854, 135.378, 8.590, and 69.239, respectively; P values < 0.05), while suspicious microcalcifications showed a linear increasing trend (Z = 34.699, P<0.001). In terms of overlapping characteristics, group A had a significantly higher overlapping rate than the other two groups, and the overlapping rate of solid indicators remained the highest among all three groups (P < 0.05). Conclusion: Differences in positive features were observed between thyroid nodules of different sizes. Except for suspicious microcalcifications, the incidence of other four positive features decreased with increasing nodule size. In addition, a negative correlation was observed between the overlap rate and nodule size. These results may provide a basis for sonographers to upgrade or downgrade thyroid nodules based on their own experience.
Nickel (Ni), a component of urease, is a micronutrient essential for plant growth and development, but excess Ni is toxic to plants. Tomato (Solanum lycopersicum L.) is one of the important vegetables worldwide. Excessive use of fertilizers and pesticides led to Ni contamination in agricultural soils, thus reducing yield and quality of tomatoes. However, the molecular regulatory mechanisms of Ni toxicity responses in tomato plants have largely not been elucidated. Here, we investigated the molecular mechanisms underlying the Ni toxicity response in tomato plants by physio-biochemical, transcriptomic and molecular regulatory network analyses. Ni toxicity repressed photosynthesis, induced the formation of brush-like lateral roots and interfered with micronutrient accumulation in tomato seedlings. Ni toxicity also induced reactive oxygen species accumulation and oxidative stress responses in plants. Furthermore, Ni toxicity reduced the phytohormone concentrations, including auxin, cytokinin and gibberellic acid, thereby retarding plant growth. Transcriptome analysis revealed that Ni toxicity altered the expression of genes involved in carbon/nitrogen metabolism pathways. Taken together, these results provide a theoretical basis for identifying key genes that could reduce excess Ni accumulation in tomato plants and are helpful for ensuring food safety and sustainable agricultural development.
BACKGROUND: The efficacy and prognosis of immune checkpoint inhibitors (ICIs) remain unresolved issues. Here, we assessed the treatment characteristics and efficacy of ICIs in non-small cell lung cancer (NSCLC) using real-world data and evaluated the predictive value of factors, including programmed death-ligand 1 (PD-L1) expression, for the clinical outcome of ICIs in NSCLC. METHODS: Analyzed data was collected from hospitalized patients in the West China Hospital of Sichuan University between January 2017 and March 2023. The Kaplan-Meier method was utilized for analyzing real-world progression-free survival (rwPFS), while Cox regression models was employed to access the correlation between the efficacy of immunotherapy and sociodemographic characteristics, disease information, and characteristics of ICI treatment. RESULTS: A total of 545 patients were included in the retrospective study and characteristics of immunotherapy varied significantly among PD-L1 expression groups. The median rwPFS for the entire population was 9.76 months. Subgroup analyses revealed that patients with high PD-L1 expression, early TNM stage, first-line immunotherapy, EGFR wild-type and those who have not received radiotherapy and targeted therapy previously were more likely to have better rwPFS. Furthermore, multivariate Cox regression analyses identified PD-L1 expression, EGFR mutation status and previous radiotherapy as the most influential predictors of the response to ICI treatment. CONCLUSIONS: This study presents the real-world experience of Chinese NSCLC patients undergoing ICI treatment, offering guidance for clinical decision-making based on various patient conditions, preferences, and indications for ICIs, through the evaluation of immunotherapy efficacy and predictors in NSCLC patients.
The droplet-based nanogenerator (DNG) is a highly promising technology for harvesting high-entropy water energy in the era of the Internet of Things. Yet, despite the exciting progress made in recent years, challenges have emerged unexpectedly for the AC-type DNG-based energy system as it transitions from laboratory demonstrations to real-world applications. In this work, we propose a high-performance DNG system based on the total-current nanogenerator concept to address these challenges. This system utilizes the water-charge-shuttle architecture for easy scale-up, employs the field effect to boost charge density of the triboelectric layer, adopts an on-solar-panel design to improve compatibility with solar energy, and is equipped with a novel DC-DC buck converter as power management circuit. These features allow the proposed system to overcome the existing bottlenecks of DNG and empower the system with superior performances compared with previous ones. Notably, with the core architecture measuring only 15 cm × 12.5 cm × 0.3 cm in physical dimensions, this system reaches a record-high open-circuit voltage of 4200 V, capable of illuminating 1440 LEDs, and can charge a 4.7 mF capacitor to 4.5 V in less than 24 min. In addition, the practical potential of the proposed DNG system is further demonstrated through a self-powered, smart greenhouse application scenario. These demonstrations include the continuous operation of a thermohygrometer, the operation of a Bluetooth plant monitor, and the all-weather energy harvesting capability. This work will provide valuable inspiration and guidance for the systematic design of next-generation DNG to unlock the sustainable potential of distributed water energy for real-world applications.
STUDY OBJECTIVES: This study aims to investigate the unique characteristics and clinical significance of the nocturnal sleep onset rapid eye movement period (nSOREMP) in the Chinese population with narcolepsy, enhancing our understanding and management of the disorder globally. METHODS: This retrospective analysis investigated narcolepsy in Chinese patients from six hospitals, using International Classification of Sleep Disorders. A parallel retrospective analysis of the Chinese Clinical Sleep Database (CCSD) focused on polysomnography (PSG) records was conducted to evaluate nSOREMP prevalence in other sleep disorders. RESULTS: The study found a 2.51% nSOREMP prevalence in other sleep disorders of CCSD. Significant differences in age, N2 and rapid eye movement (REM) percentages, REM latency, and various indexes were noted among narcolepsy with/without nSOREMP, and other sleep disorders with nSOREMP of CCSD. nSOREMP prevalence in NT1 was 33.33% and in NT2, 28.30%. Noteworthy disparities in NT1 included N2 percentages, REM latency, and SOREMPs in Multiple Sleep Latency Test (MSLT). In NT2, differences were significant in age, sleep latency, N2 and REM latencies, arousal index, mean sleep latency in MSLT, and MSLT SOREMPs. CONCLUSIONS: This study highlights the distinct characteristics of nSOREMP in the Chinese population. Patients exhibiting symptoms suggestive of the onset of narcolepsy are advised to undergo an MSLT, irrespective of the occurrence of SOREMP during nocturnal PSG.
BACKGROUND: Timely detection of modifiable risk factors for postoperative pulmonary complications (PPCs) could inform ventilation strategies that attenuate lung injury. We sought to develop, validate, and internally test machine learning models that use intraoperative respiratory features to predict PPCs. METHODS: We analysed perioperative data from a cohort comprising patients aged 65 yr and older at an academic medical centre from 2019 to 2023. Two linear and four nonlinear learning models were developed and compared with the current gold-standard risk assessment tool ARISCAT (Assess Respiratory Risk in Surgical Patients in Catalonia Tool). The Shapley additive explanation of artificial intelligence was utilised to interpret feature importance and interactions. RESULTS: Perioperative data were obtained from 10 284 patients who underwent 10 484 operations (mean age [range] 71 [65-98] yr; 42% female). An optimised XGBoost model that used preoperative variables and intraoperative respiratory variables had area under the receiver operating characteristic curves (AUROCs) of 0.878 (0.866-0.891) and 0.881 (0.879-0.883) in the validation and prospective cohorts, respectively. These models outperformed ARISCAT (AUROC: 0.496-0.533). The intraoperative dynamic features of respiratory dynamic system compliance, mechanical power, and driving pressure were identified as key modifiable contributors to PPCs. A simplified model based on XGBoost including 20 variables generated an AUROC of 0.864 (0.852-0.875) in an internal testing cohort. This has been developed into a web-based tool for further external validation (https://aorm.wchscu.cn/). CONCLUSIONS: These findings suggest that real-time identification of surgical patients' risk of postoperative pulmonary complications could help personalise intraoperative ventilatory strategies and reduce postoperative pulmonary complications.
Machine Learning , Postoperative Complications , Humans , Aged , Female , Postoperative Complications/prevention & control , Male , Aged, 80 and over , Lung Diseases/etiology , Lung Diseases/prevention & control , Risk Assessment/methods , Prospective Studies , Cohort Studies , Risk Factors , Monitoring, Intraoperative/methods
While significant progress has been achieved in utilizing remote sensing technologies for landslide investigation in China, there remains a notable gap in consolidating information on applicable conditions, application stages, and workflows across various remote sensing methodologies. This paper proposes a comprehensive framework for active landslide detection, incorporating multiple stages and data sources, successfully implemented in a vast region of southwestern China. Furthermore, detailed discussions are provided on the effects of the geometric distortion, land cover type, and various InSAR methods on the accuracy of active landslide identification results. Additionally, the paper delves into the advantages of integrated remote sensing technology in active landslide investigation, encompassing the assessment of current landslide activity status, precise delineation of boundaries, identification of different deformation stages, and determination of damage patterns. Through comprehensive analysis of multisource data, it enhances understanding of the active landslide process, ultimately contributing to the mitigation of casualties and property damage.
BACKGROUND: Age is a significant risk factor of diabetes mellitus (DM). With the develop of population aging, the incidence of DM remains increasing. Understanding the epidemiology of DM among elderly individuals in a certain area contributes to the DM interventions for the local elderly individuals with high risk of DM. AIM: To explore the prevalence of DM among elderly individuals in the Lugu community and analyze the related risk factors to provide a valid scientific basis for the health management of elderly individuals. METHODS: A total of 4816 elderly people who came to the community for physical examination were retrospectively analyzed. The prevalence of DM among the elderly was calculated. The individuals were divided into a DM group and a non-DM group according to the diagnosis of DM to compare the differences in diastolic blood pressure (DBP) and systolic blood pressure (SBP), fasting blood glucose, body mass index (BMI), waist-to-hip ratio (WHR) and incidence of hypertension (HT), coronary heart disease (CHD), and chronic kidney disease (CKD). RESULTS: DM was diagnosed in 32.70% of the 4816 elderly people. The BMI of the DM group (25.16 ± 3.35) was greater than that of the non-DM group (24.61 ± 3.78). The WHR was 0.90 ± 0.04 in the non-DM group and 0.90 ± 0.03 in the DM group, with no significant difference. The left SBP and SBP in the DM group were 137.9 mmHg ± 11.92 mmHg and 69.95 mmHg ± 7.75 mmHg, respectively, while they were 126.6 mmHg ± 12.44 mmHg and 71.15 mmHg ± 12.55 mmHg, respectively, in the non-DM group. These findings indicate higher SBP and lower DBP in DM patients than in those without DM. In the DM group, 1274 patients were diagnosed with HT, accounting for 80.89%. Among the 3241 non-DM patients, 1743 (53.78%) were hypertensive and 1498 (46.22%) were nonhypertensive. The DM group had more cases of HT than did the non-DM group. There were more patients with CHD or CKD in the DM group than in the non-DM group. There were more patients who drank alcohol more frequently (≥ 3 times) in the DM group than in the non-DM group. CONCLUSION: Older adults in the Lugu community are at a greater risk of DM. In elderly individuals, DM is closely related to high BMI and HT, CHD, and CKD. Physical examinations should be actively carried out for elderly people to determine their BMI, SBP, DBP, and other signs, and sufficient attention should be given to abnormalities in the above signs before further diagnosis.
Background: The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability. Methods: TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes. Results: A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus. Conclusion: Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.
Hydrocephalus , Ischemic Stroke , Tuberculosis, Meningeal , Humans , Adult , Tuberculosis, Meningeal/complications , Tuberculosis, Meningeal/epidemiology , Tuberculosis, Meningeal/drug therapy , Ischemic Stroke/complications , Risk Factors , Inflammation/complications , Hydrocephalus/complications
BACKGROUND: The Neutrophil-to-lymphocyte ratio (NLR) holds relevance in cancer immunotherapy outcomes, yet its validation remains limited. Thus, we conducted an umbrella review to comprehensively assess the association between pretreatment NLR and immunotherapy outcomes, along with evaluating their credibility and strength. METHODS: Electronic databases, including PubMed, Web of Science, Embase, Scopus, and Cochrane, were systematically searched for eligible systematic reviews and meta-analyses. Quality assessment and evidence grading utilized AMSTAR, GRADE, and additional classification criteria, following PRISMA and PRIOR guidelines. RESULTS: Thirty unique meta-analyses were included, with 24 associations (80%) exhibiting statistical significance. Notably, associations between pretreatment NLR and the prognosis of renal cell carcinoma, hepatocellular carcinoma, melanoma, and non-small cell lung cancer garnered highly suggestive or convincing evidence grading. CONCLUSIONS: Elevated pretreatment NLR correlates with poor outcomes in cancer immunotherapy, suggesting its potential as a biomarker for identifying appropriate treatment populations and predicting clinical outcomes. Nevertheless, further validation through prospective cohort studies is warranted.
Immunotherapy , Lymphocytes , Neoplasms , Neutrophils , Humans , Immunotherapy/methods , Lymphocytes/immunology , Meta-Analysis as Topic , Neoplasms/therapy , Neoplasms/immunology , Neutrophils/immunology , Prognosis , Treatment Outcome
BACKGROUND: Non-neuronal cholinergic system (NNCS) contributes to various inflammatory airway diseases. However, the role of NNCS in severe asthma (SA) remains largely unexplored. OBJECTIVE: To explore airway NNCS in SA. METHODS: In this prospective cohort study based on the Australasian Severe Asthma Network in a real-world setting, patients with SA (n = 52) and non-SA (n = 104) underwent clinical assessment and sputum induction. The messenger RNA (mRNA) levels of NNCS components and proinflammatory cytokines in the sputum were detected using real-time quantitative polymerase chain reaction, and the concentrations of acetylcholine (Ach)-related metabolites were evaluated using liquid chromatography coupled with tandem mass spectrometry. Asthma exacerbations were prospectively investigated during the next 12 months. The association between NNCS and future asthma exacerbations was also analyzed. RESULTS: Patients with SA were less controlled and had worse airway obstruction, a lower bronchodilator response, higher doses of inhaled corticosteroids, and more add-on treatments. The sputum mRNA levels of NNCS components, such as muscarinic receptors M1R-M5R, OCT3, VACHT, and ACHE; proinflammatory cytokines; and Ach concentration in the SA group were significantly higher than those in the non-SA group. Furthermore, most NNCS components positively correlated with non-type (T) 2 inflammatory profiles, such as sputum neutrophils, IL8, and IL1B. In addition, the mRNA levels of sputum M2R, M3R, M4R, M5R, and VACHT were independently associated with an increased risk of moderate-to-severe asthma exacerbations. CONCLUSION: This study indicated that the NNCS was significantly activated in SA, leading to elevated Ach and was associated with clinical features, non-T2 inflammation, and future exacerbations of asthma, highlighting the potential role of the NNCS in the pathogenesis of SA. CLINICAL TRIAL REGISTRATION: ChiCTR-OOC-16009529 (http://www.chictr.org.cn).
Notorious Zn dendrites and severe parasitic side reactions severely disrupt the anode-electrolyte interface during Zn plating/stripping, resulting in uncontrollable Zn deposition and limiting the application of aqueous zinc-ion batteries (AZIBs). Although the construction of an artificial interface is a highly desirable strategy, it is often limited by slow Zn2+ transport kinetics. To address these issues, we present a bifunctional polymer coating (PEPM) constructed from highly conductive PEDOT:PSS and monolayer MoS2, where the introduced PEDOT plays an important role in driving the fast Zn ion transfer kinetics as a zincophilic site and 2D MoS2 acts as a buffer layer to induce uniform Zn nucleation. With this corrosion inhibition and nucleation-oriented coating, the mobility of Zn2+ flux and the uniformity of Zn deposition were significantly improved, resulting in a stable plating/stripping performance at an ultra-low overpotential (<50 mV) of 2000 h and a high average coulombic efficiency (>99.4%) of 1000 cycles without significant dendrite formation. The proposed strategy provides a cost-efficient remedy and opens a new avenue for the development of dendrite-free zinc anodes.
BACKGROUND: Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE. METHODS: Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared. RESULTS: Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403-0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420-1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%]). CONCLUSIONS: In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited.
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Pleural Effusion, Malignant , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors/adverse effects , Lung Neoplasms/complications , Lung Neoplasms/drug therapy , Pleural Effusion, Malignant/drug therapy , Pleural Effusion, Malignant/pathology , Retrospective Studies , Female
Subglottic masses is very rare. The clinical data of five cases of subglottic mass in our hospital from 2017 to 2022 were summarized, and their clinical manifestations, auxiliary examination findings, treatment plan and pathological features were analyzed. Among the 5 patients, 1 case was subglottic pleomorphic adenoma, 1 case was subglottic granuloma, 1 case was subglottic breast cancer metastasis, 1 case was subglottic primary adenoid cystic carcinoma, and 1 case was immunoglobulin G4-related disease. No recurrence was observed in the patients so far. Subglottic mass is easy to be missed. Therefore, when the lesion is suspected in this area, the examination of ear, nose and throat should be carried out systematically to detect the lesion early and improve the prognosis.
Adenoma, Pleomorphic , Carcinoma, Adenoid Cystic , Immunoglobulin G4-Related Disease , Laryngeal Neoplasms , Humans , Carcinoma, Adenoid Cystic/diagnosis , Carcinoma, Adenoid Cystic/therapy , Laryngeal Neoplasms/diagnosis , Laryngeal Neoplasms/therapy , Neck
BACKGROUND: Multimorbidity is becoming an increasingly serious public health challenge in the aging population. The impact of nutrients on multimorbidity remains to be determined and was explored using data from a UK cohort study. METHOD: Our research analysis is mainly based on the data collected by the United Kingdom Women's Cohort Study (UKWCS), which recruited 35,372 women aged 35-69 years at baseline (1995 to 1998), aiming to explore potential associations between diet and chronic diseases. Daily intakes of energy and nutrients were estimated using a validated 217-item food frequency questionnaire at recruitment. Multimorbidity was assessed using the Charlson comorbidity index (CCI) through electronic linkages to Hospital Episode Statistics up to March 2019. Cox's proportional hazards models were used to estimate associations between daily intakes of nutrients and risk of multimorbidity. Those associations were also analyzed in multinomial logistic regression as a sensitivity analysis. In addition, a stratified analysis was conducted with age 60 as the cutoff point. RESULTS: Among the 25,389 participants, 7,799 subjects (30.7%) were confirmed with multimorbidity over a median follow-up of 22 years. Compared with the lowest quintile, the highest quintile of daily intakes of energy and protein were associated with 8% and 12% increased risk of multimorbidity respectively (HR 1.08 (95% CI 1.01, 1.16), p-linearity = 0.022 for energy; 1.12 (1.04, 1.21), p-linearity = 0.003 for protein). Higher quintiles of daily intakes of vitamin C and iron had a slightly lowered risk of multimorbidity, compared to the lowest quintile. A significantly higher risk of multimorbidity was found to be linearly associated with higher intake quintiles of vitamin B12 and vitamin D (p-linearity = 0.001 and 0.002, respectively) in Cox models, which became insignificant in multinomial logistic regression. There was some evidence of effect modification by age in intakes of iron and vitamin B1 associated with the risk of multimorbidity (p-interaction = 0.006 and 0.025, respectively). CONCLUSIONS: Our findings highlight a link between nutrient intake and multimorbidity risk. However, there is uncertainty in our results, and more research is needed before definite conclusions can be reached.
Eating , Multimorbidity , Female , Humans , Aged , Cohort Studies , Prospective Studies , Vitamins , Iron
BACKGROUND: While circulating metabolites have been increasingly linked to cancer risk, the causality underlying these associations remains largely uninterrogated. METHODS: We conducted a comprehensive 2-sample Mendelian randomization (MR) study to evaluate the potential causal relationship between 913 plasma metabolites and the risk of seven cancers among European-ancestry individuals. Data on variant-metabolite associations were obtained from a genome-wide association study (GWAS) of plasma metabolites among 14,296 subjects. Data on variant-cancer associations were gathered from large-scale GWAS consortia for breast (N = 266,081), colorectal (N = 185,616), lung (N = 85,716), ovarian (N = 63,347), prostate (N = 140,306), renal cell (N = 31,190), and testicular germ cell (N = 28,135) cancers. MR analyses were performed with the inverse variance-weighted (IVW) method as the primary strategy to identify significant associations at Bonferroni-corrected P < 0.05 for each cancer type separately. Significant associations were subjected to additional scrutiny via weighted median MR, Egger regression, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and reverse MR analyses. Replication analyses were performed using an independent dataset from a plasma metabolite GWAS including 8,129 participants of European ancestry. RESULTS: We identified 94 significant associations, suggesting putative causal associations between 66 distinct plasma metabolites and the risk of seven cancers. Remarkably, 68.2% (45) of these metabolites were each associated with the risk of a specific cancer. Among the 66 metabolites, O-methylcatechol sulfate and 4-vinylphenol sulfate demonstrated the most pronounced positive and negative associations with cancer risk, respectively. Genetically proxied plasma levels of these two metabolites were significantly associated with the risk of lung cancer and renal cell cancer, with an odds ratio and 95% confidence interval of 2.81 (2.33-3.37) and 0.49 (0.40-0.61), respectively. None of these 94 associations was biased by weak instruments, horizontal pleiotropy, or reverse causation. Further, 64 of these 94 were eligible for replication analyses, and 54 (84.4%) showed P < 0.05 with association patterns consistent with those shown in primary analyses. CONCLUSIONS: Our study unveils plausible causal relationships between 66 plasma metabolites and cancer risk, expanding our understanding of the role of circulating metabolites in cancer genetics and etiology. These findings hold promise for enhancing cancer risk assessment and prevention strategies, meriting further exploration.
Carcinoma, Renal Cell , Kidney Neoplasms , Lung Neoplasms , Male , Humans , Genome-Wide Association Study , Mendelian Randomization Analysis , Lung Neoplasms/epidemiology , Lung Neoplasms/genetics
Introduction: Lung cancer is a leading cause of cancer deaths globally. Despite favorable recommendations, low-dose computed tomography (LDCT) lung screening adoption remains low in China. Barriers such as limited infrastructure, costs, distance, and personnel shortages restrict screening access in disadvantaged regions. We initiated a telemedicine-enabled lung cancer screening (LCS) program in a medical consortium to serve people at risk in underserved communities. The objective of this study was to describe the implementation and initial results of the program. Methods: From 2020 to 2021, individuals aged 40-80 years were invited to take LCS by mobile computed tomography (CT) units in three underserved areas in Western China. Numerous CT scans were remotely reported by radiologists aided by artificial intelligence (AI) diagnostic systems. Abnormal cases were tracked through an integrated hospital network for follow-up. A retrospective cohort study documented participant demographics, health history, LDCT results, and outcomes. Descriptive analysis was conducted to report baseline characteristics and first-year follow-up results. Results: Of the 28,728 individuals registered in the program, 19,517 (67.94%) participated in the screening. The study identified 2.68% of participants with high-risk pulmonary nodules and diagnosed 0.55% with lung cancer after a 1-year follow-up. The majority of high-risk participants received timely treatment in hospitals. Conclusions: This study demonstrated mobile CT units with remote AI assistance improved access to LCS in underserved areas, with high participation and early detection rates. Our implementation supports the feasibility of deploying telemedicine-enabled LCS to increase access to a large scale of basic radiology and diagnostic services in resource-limited settings. Clinical Trial Registration Number: ChiCTR1900024623.
