Multiple polygenic risk scores can improve the prediction of systemic lupus erythematosus in Taiwan.

OBJECTIVE: To identify new genetic variants associated with SLE in Taiwan and establish polygenic risk score (PRS) models to improve the early diagnostic accuracy of SLE. METHODS: The study enrolled 2429 patients with SLE and 48 580 controls from China Medical University Hospital in Taiwan. A genome-wide association study (GWAS) and PRS analyses of SLE and other three SLE markers, namely ANA, anti-double-stranded DNA antibody (dsDNA) and anti-Smith antibody (Sm), were conducted. RESULTS: Genetic variants associated with SLE were identified through GWAS. Some novel genes, which have been previously reported, such as RCC1L and EGLN3, were revealed to be associated with SLE in Taiwan. Multiple PRS models were established, and optimal cut-off points for each PRS were determined using the Youden Index. Combining the PRSs for SLE, ANA, dsDNA and Sm yielded an area under the curve of 0.64 for the optimal cut-off points. An analysis of human leucocyte antigen (HLA) haplotypes in SLE indicated that individuals with HLA-DQA1*01:01 and HLA-DQB1*05:01 were at a higher risk of being classified into the SLE group. CONCLUSIONS: The use of PRSs to predict SLE enables the identification of high-risk patients before abnormal laboratory data were obtained or symptoms were manifested. Our findings underscore the potential of using PRSs and GWAS in identifying SLE markers, offering promise for early diagnosis and prediction of SLE.

Utility of polygenic scores across diverse diseases in a hospital cohort for predictive modeling.

Polygenic scores estimate genetic susceptibility to diseases. We systematically calculated polygenic scores across 457 phenotypes using genotyping array data from China Medical University Hospital. Logistic regression models assessed polygenic scores' ability to predict disease traits. The polygenic score model with the highest accuracy, based on maximal area under the receiver operating characteristic curve (AUC), is provided on the GeneAnaBase website of the hospital. Our findings indicate 49 phenotypes with AUC greater than 0.6, predominantly linked to endocrine and metabolic diseases. Notably, hyperplasia of the prostate exhibited the highest disease prediction ability (P value = 1.01 × 10-19, AUC = 0.874), highlighting the potential of these polygenic scores in preventive medicine and diagnosis. This study offers a comprehensive evaluation of polygenic scores performance across diverse human traits, identifying promising applications for precision medicine and personalized healthcare, thereby inspiring further research and development in this field.

Genome-wide association study identifies DRAM1 associated with Tourette syndrome in Taiwan.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. Several susceptibility loci associated with TS have been identified previously in populations of European descent using genome-wide association studies (GWAS). However, the exact pathogenic mechanism underlying TS is unknown; additionally, the results of previous GWAS for TS were based on Western populations, which may not translate to other populations. Therefore, we conducted a GWAS in Taiwanese patients with TS and chronic tic disorders (CTDs), with an aim to elucidate the genetic basis and potential risk factors for TS in this population. METHODS: GWAS was performed on a Taiwanese TS/CTDs cohort with a sample size of 1,007 patients with TS and 25,522 ancestry-matched controls. Additionally, polygenic risk score was calculated and assessed. RESULTS: Genome-wide significant locus, rs12313062 (p=1.43 × 10-8) and other 9 single nucleotide polymorphisms, were identified in chromosomes 12q23.2, associated with DRAM1 and was a novel susceptibility locus identified in TS/CTDs group. DRAM1, a lysosomal transmembrane protein regulated by p53, modulates autophagy and apoptosis, with potential implications for neuropsychiatric conditions associated with autophagy disruption. CONCLUSIONS: This study conducted the first GWAS for TS in a Taiwanese population, identifying a significant locus on chromosome 12q23.2 associated with DRAM1. These findings provide novel insights into the neurobiology of TS and potential directions for future research in this area.

Menarche-a journey into womanhood: age at menarche and health-related outcomes in East Asians.

STUDY QUESTION: Are there associations of age at menarche (AAM) with health-related outcomes in East Asians? SUMMARY ANSWER: AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through observational studies, polygenic risk scores, genetic correlations, and Mendelian randomization (MR), with additional findings indicating a causal effect of BMI and T2D on earlier AAM. WHAT IS KNOWN ALREADY: Puberty timing is linked to adult disease risk, but research predominantly focuses on European populations, with limited studies in other groups. STUDY DESIGN, SIZE, DURATION: We performed an AAM genome-wide association study (GWAS) with 57 890 Han Taiwanese females and examined the association between AAM and 154 disease outcomes using the Taiwanese database. Additionally, we examined genetic correlations between AAM and 113 diseases and 67 phenotypes using Japanese GWAS summary statistics. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed AAM GWAS and gene-based GWAS studies to obtain summary statistics and identify potential AAM-related genes. We applied phenotype, polygenic risk scores, and genetic correlation analyses of AAM to explore health-related outcomes, using multivariate regression and linkage disequilibrium score regression analyses. We also explored potential bidirectional causal relationships between AAM and related outcomes through univariable and multivariable MR analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen lead single-nucleotide polymorphisms and 24 distinct genes were associated with AAM in Taiwan. AAM was genetically associated with later menarche and menopause, greater height, increased osteoporosis risk, but lower BMI, and reduced risks of T2D, glaucoma, and uterine fibroids in East Asians. Bidirectional MR analyses indicated that higher BMI/T2D causally leads to earlier AAM. LIMITATIONS, REASONS FOR CAUTION: Our findings were specific to Han Taiwanese individuals, with genetic correlation analyses conducted in East Asians. Further research in other ethnic groups is necessary. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides insights into the genetic architecture of AAM and its health-related outcomes in East Asians, highlighting causal links between BMI/T2D and earlier AAM, which may suggest potential prevention strategies for early puberty. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by China Medical University, Taiwan (CMU110-S-17, CMU110-S-24, CMU110-MF-49, CMU111-SR-158, CMU111-MF-105, CMU111-MF-21, CMU111-S-35, CMU112-SR-30, and CMU112-MF-101), the China Medical University Hospital, Taiwan (DMR-111-062, DMR-111-153, DMR-112-042, DMR-113-038, and DMR-113-103), and the Ministry of Science and Technology, Taiwan (MOST 111-2314-B-039-063-MY3, MOST 111-2314-B-039-064-MY3, MOST 111-2410-H-039-002-MY3, and NSTC 112-2813-C-039-036-B). The funders had no influence on the data collection, analyses, or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

At least one in a dozen stars shows evidence of planetary ingestion.

Stellar chemical compositions can be altered by ingestion of planetary material1,2 and/or planet formation, which removes refractory material from the protostellar disk3,4. These 'planet signatures' appear as correlations between elemental abundance differences and the dust condensation temperature3,5,6. Detecting these planet signatures, however, is challenging owing to unknown occurrence rates, small amplitudes and heterogeneous star samples with large differences in stellar ages7,8. Therefore, stars born together (that is, co-natal) with identical compositions can facilitate the detection of planet signatures. Although previous spectroscopic studies have been limited to a small number of binary stars9-13, the Gaia satellite14 provides opportunities for detecting stellar chemical signatures of planets among co-moving pairs of stars confirmed to be co-natal15,16. Here we report high-precision chemical abundances for a homogeneous sample of ninety-one co-natal pairs of stars with a well defined selection function and identify at least seven instances of planetary ingestion, corresponding to an occurrence rate of eight per cent. An independent Bayesian indicator is deployed, which can effectively disentangle the planet signatures from other factors, such as random abundance variation and atomic diffusion17. Our study provides evidence of planet signatures and facilitates a deeper understanding of the star-planet-chemistry connection by providing observational constraints on the mechanisms of planet engulfment, formation and evolution.

Identification of Genetic Variants for Risk Prediction and Early Diagnosis of Age-Related Macular Degeneration in the Taiwanese Population.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. The prevalence and phenotypes of AMD differ among populations, including between people in Taiwan and other regions. We performed a genome-wide association study to identify genetic variants and to develop genetic models to predict the risk of AMD development and progression in the Taiwanese population. In total, 4039 patients with AMD and 16,488 non-AMD controls (aged ≥ 65 years) were included. We identified 31 AMD-associated variants (p < 5 × 10-8) on chromosome 10q26, surrounding PLEKHA1-ARMS2-HTRA1. Two genetic models were constructed using the clump and threshold method. Model 1 included the single nucleotide polymorphism rs11200630 and showed a 1.31-fold increase in the risk of AMD per risk allele (95% confidence interval (CI) = 1.20-1.43, p < 0.001). In model 2, 1412 single-nucleotide polymorphisms were selected to construct a polygenic risk score (PRS). Individuals with the top 5% PRS had a 1.40-fold higher AMD risk compared with that of individuals with a PRS in the bottom quartile (95% CI = 1.04-1.89, p = 0.025). Moreover, the PRS in the upper quartile was related to a decreased age at AMD diagnosis by 0.62 years (95% CI = -1.15, -0.09, p = 0.023). Both genetic models provide useful predictive power for populations at high risk of AMD, affording a basis for identifying patients requiring close follow-up and early intervention.

Genetic susceptibility to prostate cancer in Taiwan: A genome-wide association study.

We conducted the first genome-wide association study (GWAS) of prostate cancer (PCa) in Taiwan with 1844 cases and 80,709 controls. Thirteen independent single-nucleotide polymorphisms (SNPs) reached genome-wide significance (p < 5 × 10-8 ). Among these, three were distinct from previously identified loci: rs76072851 in CORO2B gene (15q23), odds ratio (OR) = 1.54, 95% confidence interval (CI), 1.36-1.76, p = 5.30 × 10-11 ; rs7837051, near two long noncoding RNA (lncRNA) genes, PRNCR1 and PCAT2 (8q24.21), OR = 1.41 (95% CI, 1.31-1.51), p = 8.77 × 10-21 ; and rs56339048, near an lncRNA gene, CASC8 (8q24.21), OR = 1.25 (95% CI, 1.16-1.35), p = 2.14 × 10-8 . We refined the lead SNPs for two previously identified SNPs in Taiwanese: rs13255059 (near CASC8), p = 9.02 × 10-43 , and rs1456315 (inside PRNCR1), p = 4.33 × 10-42 . We confirmed 35 out of 49 GWAS-identified East Asian PCa susceptibility SNPs. In addition, we identified two SNPs more specific to Taiwanese than East Asians: rs34295433 in LAMC1 (1q25.3) and rs6853490 in PDLIM5 (4q22.3). A weighted genetic risk score (GRS) was developed using the 40 validated SNPs and the area under the receiver-operating characteristic curve for the GRS to predict PCa was 0.67 (95% CI, 0.63-0.71). These identified SNPs provide valuable insights into the molecular mechanisms of prostate carcinogenesis in Taiwan and underscore the significant role of genetic susceptibility in regional differences in PCa incidence.

Identification of the efficacy of parentage testing based on bi-allelic autosomal single nucleotide polymorphism markers in Taiwanese population.

Parentage testing is crucial for forensic DNA analysis, using short tandem repeats (STRs). Single nucleotide polymorphisms (SNPs) with high minor allele frequency (MAF) are promising for human identification. This study aimed to develop SNP markers for parentage testing in the Taiwanese population and compare their accuracy with STRs. The TPMv1 SNP microarray (714,457 SNPs) was used to screen 180,000 Taiwanese individuals and analyze the SNP data using PLINK. After quality control, allelic distribution, and MAF considerations, a set of SNPs with significant inheritance information was selected. Parentage testing was conducted on 355 single parent-child pairs using both STRs and SNPs, employing three kinship algorithms: identity by descent, kinship-based inference for genome-wide association studies, and the combined paternity index/probability of paternity (CPI/PP). An Affymetrix signature probe for kinship testing (ASP) was also used. Based on the quality control and selection criteria, 176 SNPs with MAF > 0.4995 were selected from the Taiwanese population. The CPI/PP results calculated using SNPs were consistent with the STR results. The accuracy of the SNPs used in the single-parent-child parentage testing was > 99.99%. The set of 176 SNPs had a higher identification rate in the single parent-child parentage test than in the ASP. The CPI/PP value calculated using 176 SNPs was also more accurate than that calculated using ASP. Our findings suggest that these 176 SNPs could be used for single-parent-child parentage identification in the Taiwanese population.

The genome-wide association study of serum IgE levels demonstrated a shared genetic background in allergic diseases.

Immunoglobulin E (IgE) synthessis is highly related to a variety of atopic diseases, and several genome-wide association studies (GWASs) have demonstrated the association between genes and IgE level. In this study, we conducted the largest genome-wide association study of IgE involving a Taiwanese Han population. Eight independent variants exhibited genome-wide significance. Among them, an intronic SNP of CD28, rs1181388, and an intergenic SNP, rs1002957030, on 11q23.2 were identified as novel signals for IgE. Seven of the loci were replicated successfully in a meta-analysis using data on Japanese population. Among all the human leukocyte antigen (HLA) regions, HLA-DQA1*03:02 - HLA-DQB1*03:03 was the most significant haplotype (OR = 1.25, SE = 0.02, FDR = 1.6 × 10-14), corresponding to HLA-DQA1 Asp160 and HLA-DQB1 Leu87 amino acid residues. The genetic correlation showed significance between IgE and allergic diseases including asthma, atopic dermatitis, and pollinosis. IgE PRS was significantly correlated with total IgE levels. Furthermore, the top decile IgE polygenic risk score (PRS) group had the highest risk of asthma for the Taiwan Biobank and Biobank Japan cohorts. IgE PRS may be used to aid in predicting the occurrence of allergic reactions before symptoms occur and biomarkers are detectable. Our study provided a more comprehensive understanding of the impact of genomic variants, including complex HLA alleles, on serum IgE levels.

Assessment of Tilapia Skin Collagen for Biomedical Research Applications in Comparison with Mammalian Collagen.

Collagen is an important material for biomedical research, but using mammalian tissue-derived collagen carries the risk of zoonotic disease transmission. Marine organisms, such as farmed tilapia, have emerged as a safe alternative source of collagen for biomedical research. However, the tilapia collagen products for biomedical research are rare, and their biological functions remain largely unexamined. In this study, we characterized a commercial tilapia skin collagen using SDS-PAGE and fibril formation assays and evaluated its effects on skin fibroblast adhesion, proliferation, and migration, comparing it with commercial collagen from rat tails, porcine skin, and bovine skin. The results showed that tilapia skin collagen is a type I collagen, similar to rat tail collagen, and has a faster fibril formation rate and better-promoting effects on cell migration than porcine and bovine skin collagen. We also confirmed its application in a 3D culture for kidney cells' spherical cyst formation, fibroblast-induced gel contraction, and tumor spheroid interfacial invasion. Furthermore, we demonstrated that the freeze-dried tilapia skin collagen scaffold improved wound closure in a mouse excisional wound model, similar to commercial porcine or bovine collagen wound dressings. In conclusion, tilapia skin collagen is an ideal biomaterial for biomedical research.

The largest genome-wide association study for breast cancer in Taiwanese Han population.

PURPOSE: Breast cancer is a molecularly heterogeneous disease, and multiple genetic variants contribute to its development and prognosis. Most of previous genome-wide association studies (GWASs) and polygenic risk scores (PRSs) analyses focused on studying breast cancers of Caucasian populations, which may not be applicable to other population. Therefore, we conducted the largest breast cancer cohort of Taiwanese population to fill in the knowledge gap. METHODS: A total of 152,534 Participants recruited by China Medical University Hospital between 2003 and 2019 were filtered by several patient selection criteria and GWAS quality control steps, resulting in the inclusion of 2496 cases and 9984 controls for this study. We then conducted GWAS for all breast cancers and PRS analyses for all breast cancers and the four breast cancer subtypes, including luminal A, luminal B, basal-like, and HER2-enriched. RESULTS: The GWAS analyses identified 113 SNPs, 50 of which were novel. The PRS models for all breast cancers and the luminal A subtype showed positively correlated trends between the PRS and the risk of developing breast cancer. The odds ratios (95% confidence intervals) for the groups with the highest PRS in all breast cancers and the luminal A subtype were 5.33 (3.79-7.66) and 3.55 (2.13-6.14), respectively. CONCLUSION: In summary, we explored the association of genetic variants with breast cancer in the largest Taiwanese cohort and developed two PRS models that can predict the risk of developing any breast cancer and the luminal A subtype in Taiwanese women.

Metabolic Dysfunction-Associated Steatotic Liver Disease Facilitates Hepatitis B Surface Antigen Seroclearance and Seroconversion.

BACKGROUND & AIMS: Hepatitis B surface antigen (HBsAg) seroclearance is the goal of functional cure for hepatitis B virus (HBV) infection. However, the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on this favorable outcome remains unclear. METHODS: Patients with chronic hepatitis B (CHB) were consecutively recruited. MASLD was defined by the newly proposed disease criteria. Cumulative incidences and associated factors of HBsAg seroclearance/seroconversion were compared between the MASLD and non-MASLD groups. RESULTS: From 2006 to 2021, 4084 treatment-naive hepatitis B e antigen (HBeAg)-negative CHB patients were included. At baseline, CHB patients with concurrent MASLD (n = 887) had significantly lower levels of HBsAg and HBV DNA than the non-MASLD group (n = 3197). During a median follow-up of 5.0 years, MASLD was associated with a higher likelihood of HBsAg seroclearance (adjusted hazard ratio [aHR], 1.43; 95% confidence interval [CI], 1.10-1.85; P = .007), and the accumulation of individual metabolic dysfunctions additively facilitated HBsAg seroclearance. In addition, a higher rate of HBsAg seroconversion was observed in patients with MASLD versus those without MASLD (aHR, 1.37; 95% CI, 1.00-1.86; P = .049). In sensitivity analysis, patients with intermittent MASLD had an intermediate probability of HBsAg seroclearance. After balancing clinical and virologic profiles by inverse probability of treatment weighting (IPTW), MASLD was still associated with a higher HBsAg seroclearance rate (IPTW-adjusted HR, 1.41; 95% CI, 1.09-1.84; P = .010). CONCLUSIONS: In untreated HBeAg-negative CHB patients, concurrent MASLD is associated with higher rates of HBsAg seroclearance and seroconversion. Metabolic dysfunctions have additive effects on the functional cure of CHB.

Predicting subsolid pulmonary nodules before percutaneous needle biopsy: a comparison of artificial neural network and biopsy results.

AIM: To establish an artificial neural network (ANN) model to predict subsolid nodules (SSNs) before percutaneous core-needle biopsy (PCNB). The results of the two methods were compared to provide guidance on the treatment of SSNs. MATERIALS AND METHODS: This was a single-centre retrospective study using data from 1,459 SSNs between 2013 and 2021. The ANN was developed using data from patients who underwent surgery following computed tomography (CT) (SFC) and validated using data from patients who underwent surgery following biopsy (SFB). The prediction results of the ANN for the PCNB group and the histopathological results obtained after biopsy were compared with the histopathological results of lung nodules in the same group after surgery. Additionally, the choice of predictors for PCNB was analysed using multivariate analysis. RESULTS: There was no significant difference between the accuracies of the ANN and PCNB in the SFB group (p=0.086). The sensitivity of PCNB was lower than that of the ANN (p=0.000), but the specificity was higher (p=0.001). PCNB had better diagnostic ability than the ANN. The incidence of precursor lesions and non-neoplastic lesions in the SFB group was lower than that in the SFC group (p=0.000). A history of malignant tumours, size (2-3 cm), volume (>400 cm3) and mean CT value (≥-450 HU) are important factors for selecting PCNB. CONCLUSIONS: Both ANN and PCNB have comparable accuracy in diagnosing SSNs; however, PCNB has a slightly higher diagnostic ability than ANN. Selecting appropriate patients for PCNB is important for maximising the benefit to SSN patients.

Cardiovascular and Neurological Outcomes in Patients Treated with Edoxaban for Atrial Fibrillation and Characteristics in Patients with Cancer.

BACKGROUND: Direct oral anticoagulants (DOACs) outperform warfarin in vascular and bleeding events in atrial fibrillation (AF) patients. Yet, effects of DOACs on congestive heart failure (CHF) and Alzheimer's disease (AD) remain less explored. METHODS: Using the Taiwan National Health Insurance Research Database, a nationwide retrospective cohort study was conducted. The study matched 5,683 non-valvular atrial fibrillation (NVAF) edoxaban patients with 11,366 warfarin patients, and 703 NVAF with cancer (NVAF-C) edoxaban patients with 1,406 warfarin patients. Vasular and non-vascular outcomes, with focuses on CHF and AD, were compared between the edoxaban and warfarin users. RESULTS: Edoxaban significantly lowered adjusted hazrad ratio (aHR) of all-cause mortality, hospitalization for gastrointestinal bleeding, and CHF (0.37, 0.74, and 0.26, respectively, in NVAF; 0.39, 0.67, and 0.31, respectively, in NVAF-C, all p < 0.05), compared to warfarin. Edoxaban was associated with significantly lower aHRs of acute myocardial infarction, peripheral artery disease, venous thromboembolism, pulmonary embolism, and AD (0.71, 0.48, 0.55, 0.20, and 0.66, respectively; all p < 0.05) in NVAF patients versus warfarin. However, edoxaban had higher aHR of hospitalized bleeding (1.19, p = 0.002) than warfarin in NVAF patients, but not in NVAF-C patients. CONCLUSIONS: Edoxaban demonstrated lowered CHF risks in both NVAF and NVAF-C patients, and reduced AD occurrence in NVAF patients versus warfarin. These findings advocate for edoxaban's use in AF cases. CLINICAL PERSPECTIVE: What Is New?: The study reveals that in patients with atrial fibrillation (AF), edoxaban, a direct oral anticoagulant (DOAC), demonstrates significant advantages over warfarin. Notably, edoxaban is associated with a reduced risk of congestive heart failure (CHF) and Alzheimer's disease (AD) when compared to warfarin.Clinical Implications?: These findings have important clinical implications. Edoxaban appears to be a superior anticoagulant choice for AF patients, as it lowers the risk of CHF and AD. This highlights the potential of edoxaban to improve patient outcomes and underscores its relevance for managing AF cases.

Identification of 13 Novel Loci in a Genome-Wide Association Study on Taiwanese with Hepatocellular Carcinoma.

Liver cancer is caused by complex interactions among genetic factors, viral infection, alcohol abuse, and metabolic diseases. We conducted a genome-wide association study and polygenic risk score (PRS) model in Taiwan, employing a nonspecific etiology approach, to identify genetic risk factors for hepatocellular carcinoma (HCC). Our analysis of 2836 HCC cases and 134,549 controls revealed 13 novel associated loci such as the FAM66C gene, noncoding genes, liver-fibrosis-related genes, metabolism-related genes, and HCC-related pathway genes. We incorporated the results from the UK Biobank and Japanese database into our study for meta-analysis to validate our findings. We also identified specific subtypes of the major histocompatibility complex that influence both viral infection and HCC progression. Using this data, we developed a PRS to predict HCC risk in the general population, patients with HCC, and HCC-affected families. The PRS demonstrated higher risk scores in families with multiple HCCs and other cancer cases. This study presents a novel approach to HCC risk analysis, identifies seven new genes associated with HCC development, and introduces a reproducible PRS model for risk assessment.

Asymmetric nanoporous membranes for ethanol/water pervaporation separation and their design.

To explore the design of pervaporation membranes for ethanol recovery, zeolite nanosheets with different surface characteristics on the feed and permeate sides are investigated via molecular dynamics simulations. The results demonstrate the significant role of the permeate-side surface in the separation performance. By adopting an asymmetric membrane design with a hydrophobic feed-side surface and a hydrophilic one on the permeate side, the separation factor can be enhanced by nearly three-fold as compared to that of both hydrophobic surfaces, with an improved permeation flux.

Prevalence of falls, injury from falls and associations with chronic diseases among community-dwelling older adults in Guangzhou, China: a cross-sectional study.

Introduction: As a developing country with the largest older adult population in the world, strengthening the research on falls among the older adults is undoubtedly an urgent item in China. This study aimed to explore the prevalence and risk factors associated with falls and injury from falls among community-dwelling older adults in Guangzhou, China, particularly focusing on their associations with chronic diseases. Methods: A total of 1,629 participants aged 65 years and above were selected from 11 counties in Guangzhou by the multi-stage stratified random sampling method in 2021. Socio-demographic characteristics, health and lifestyle factors, the status of falls, and injury from falls were measured by structured questionnaires through face-to-face interviews. Chi-square tests and logistic regression analysis were used to identify factors associated with falls and injury from falls. Chord diagrams were used to explore their associations with chronic diseases. Results: A total of 251 participants (15.41%, 95% CI: 13.98%-17.25%) reported falls, and 162 participants (9.46%, 95% CI:7.72%-11.55%) indicated an injury from falls. Logistic regression analysis showed the results as follows: female patients (adjusted OR = 1.721, 95% CI: 1.681-1.761) aged ≥80 years (1.910, 1.847-1.975), unemployed (1.226, 1.171-1.284), uninsured (1.555, 1.448-1.671), average monthly household income of 2,001-4,000 CNY (1.878, 1.827-1.930), number of services provided by the community health center ≥13 times per year (1.428, 1.383-1.475), illness within 2 weeks (1.633, 1.595-1.672), high-intensity physical activity (2.254, 2.191-2.32), sedentary (1.094, 1.070-1.117), and number of chronic disease illnesses ≥3 (1.930, 1.870-1.993). Meanwhile, those risk factors were also associated with injury from falls. The older adults with medium-intensity physical activity were at lower risk (0.721, 0.705-0.737) of falls and higher risk (1.086, 1.057-1.117) of being injured from falls. Chord diagrams showed the correlations between chronic diseases and falls and injury from falls among community-dwelling older adults in Guangzhou, China. Conclusion: The high prevalence of falls is found among community-dwelling older adults in Guangzhou, China, which is related to multiple factors such as demographic variables, lifestyle, and health status, especially for chronic diseases. Therefore, targeted interventions should be developed and implemented urgently.

A deep learning-based pipeline for analyzing the influences of interfacial mechanochemical microenvironments on spheroid invasion using differential interference contrast microscopic images.

Metastasis is the leading cause of cancer-related deaths. During this process, cancer cells are likely to navigate discrete tissue-tissue interfaces, enabling them to infiltrate and spread throughout the body. Three-dimensional (3D) spheroid modeling is receiving more attention due to its strengths in studying the invasive behavior of metastatic cancer cells. While microscopy is a conventional approach for investigating 3D invasion, post-invasion image analysis, which is a time-consuming process, remains a significant challenge for researchers. In this study, we presented an image processing pipeline that utilized a deep learning (DL) solution, with an encoder-decoder architecture, to assess and characterize the invasion dynamics of tumor spheroids. The developed models, equipped with feature extraction and measurement capabilities, could be successfully utilized for the automated segmentation of the invasive protrusions as well as the core region of spheroids situated within interfacial microenvironments with distinct mechanochemical factors. Our findings suggest that a combination of the spheroid culture and DL-based image analysis enable identification of time-lapse migratory patterns for tumor spheroids above matrix-substrate interfaces, thus paving the foundation for delineating the mechanism of local invasion during cancer metastasis.

Review of PINK1-Parkin-mediated mitochondrial autophagy in Alzheimer's disease.

Mitochondrial autophagy plays an important role in maintaining the complexity of mitochondrial functions and removing damaged mitochondria, of which the PINK1-Parkin signal pathway is one of the most classical pathways. Thus, a comprehensive and in-depth interpretation of the PINK1-Parkin signal pathway might deepen our understanding on the impacts of mitochondrial autophagy. Alzheimer's disease (AD) is a classical example of neurodegenerative disease. Research on the pathogenesis and treatments of AD has been a focus of scientific research because of its complexity and the limitations of current drug therapies. It was reported that the pathogenesis of AD might be related to mitochondrial autophagy due to excessive deposition of Aß protein and aggravation of the phosphorylation of Tau protein. Two key proteins in the PINK1-Parkin signaling pathway, PINK1 and Parkin, have important roles in the folding and accumulation of Aß protein and the phosphorylation of Tau protein. In addition, the intermediate signal molecules in the PINK1-Parkin signal pathway also have certain effects on AD. In this paper, we first described the role of PINK1-Parkin signal pathway on mitochondrial autophagy, then discussed and analyzed the effect of the PINK1-Parkin signal pathway in AD and other metabolic diseases. Our aim was to provide a theoretical direction to further elucidate the pathogenesis of AD and highlight the key molecules related to AD that could be important targets used for AD drug development.