Special Issue "Bioinformatics Study in Human Diseases: Integration of Omics Data for Personalized Medicine".

The field of bioinformatics has made remarkable strides in recent years, revolutionizing our approach to understanding and treating human diseases [...].

Safety evaluation of Plukenetia volubilis seeds: a metabolomic profiling and network toxicology approach.

Sacha Inchi (Plukenetia volubilis) seeds and oil have been integrated into daily diets. However, scientific reports have raised concerns regarding potential health risks associated with saponins and alkaloids in this seeds. This study employed a combination analysis using proton-NMR, GC-MS, LC-QTOF, and GNPS molecular networking to evaluate the chemical composition of these seeds. In silico toxicology analysis and in vitro cytotoxicity assays were conducted to investigate the potential toxicity effects of Sacha Inchi seeds and their contained metabolites. The results revealed that major components of these seeds are oils (linoleic, linolenic, and oleic acids) and sugars, with minor amounts of phytosterols and trigonelline, a pyridine alkaloid. GNPS analysis suggested the absence of saponins, instead, it identified trigonelline and a few other nitrogen-containing metabolites (amino acids and oligopeptides). In silico toxicology analysis indicated that this sample did not exhibit toxicity. Furthermore, in vitro cytotoxicity screening demonstrated no cytotoxic effects against NIH-3T3 cells, even at 400 µg mL-1. In general, these findings collectively indicated the absence of saponins, the presence of phytosterols and trigonellin (a pyridine alkaloid), and a low safety risk related to saponin and alkaloid content in the Sacha Inchi seeds.

Predictive model for contralateral inguinal hernia repair within three years of primary repair: a nationwide population-based cohort study.

BACKGROUND: Limited reports have discussed the risk factors for contralateral inguinal hernia (CIH) repair. We generated a risk factor scoring system to predict CIH within 3 years after unilateral inguinal hernia repair. METHODS: We extracted the admission data of patients aged ≥ 18 years who underwent primary unilateral inguinal hernia repair without any other operation from the National Health Insurance Research Database. Patients were randomly divided into 80% and 20% validation cohorts. Multivariate analysis with a logistic regression model was used to generate the scoring system, which was used in the validation group. RESULTS: Overall, 170,492 adult men were included, with a median follow-up of 87 months. The scoring system ranged from 0-5 points, composited with age (< 45 years, 0 points; 45-65 years, 2 points; 65-80 years, 3 points; > 80 years, 2 points) and two comorbidities (cirrhosis and prostate disease: 1 point each). The areas under receiver operating characteristic (ROC) curves were 0.606 and 0.551 for the derivation and validation groups, respectively. The rates and adjusted odds ratios (OR) of CIH repair in the derivation group were 3.0% at 0-2 points, 5.5% (1.854, p < 0.001) at 3, 6.7% (2.279, p < 0.001) at 4, and 6.9% (2.348, p < 0.001) at 5, with similar results in the validation group [2.3% at 0-2 points, 3.8% (1.668, p < 0.001) at 3, 5.4% (2.386, p < 0.001) at 4, and 6.8% (3.033, p < 0.001) at 5]. CONCLUSIONS: The CIH scoring system effectively predicted CIH repair within three years of primary unilateral inguinal hernia repair. Surgeons could perform laparoscopic surgery with CIH scores > 2 points which enables easier contralateral exploration and repair during the same surgery, without additional incisions, to minimize the need for future surgeries. However, further prospective validation of this scoring system is required.

The impact of fatigue severity and depression level on the quality of life in individuals with Parkinson's disease in Taiwan.

Background: Patients diagnosed with Parkinson's disease undergo alterations in physical, psychological, and social functionality, with the psychological domain being particularly predisposed to inducing fatigue and depressive symptoms. Understanding the alterations occurring within a patient's body and mind and how these influence their overall quality of life is crucial. Purpose: This study sought to explore the predictive capacity of fatigue severity, the presence of depressive symptoms, and diverse demographic factors on the quality of life among individuals with Parkinson's disease. Methods: A cross-sectional correlational study was conducted at a teaching hospital in southern Taiwan. The research utilized a questionnaire survey to interview 133 study participants, focusing on the Quality of Life Scale, Depression Scale, Fatigue Severity Scale, Social Support Scale, and demographic attributes. Results: A total of 130 valid questionnaires were obtained. The results showed that Hoehn and Yahr stage, fatigue severity, and depression status could predict quality of life, explaining 51.1% of the total variance. These findings suggest that patients at advanced Hoehn and Yahr stages, experiencing more severe fatigue, and exhibiting higher levels of depression, tended to report a lower overall quality of life. Our findings suggest that, in addition to Hoehn and Yahr stage, the severity of fatigue and levels of depression significantly impact the quality of life in individuals with Parkinson's disease. Conclusion: Nurses need to understand the "stressful life events" and the changes in appearance and physical function that patients with Parkinson's disease face due to chronic degenerative diseases. Hence, apart from addressing patients' physiological needs, healthcare professionals should also offer appropriate care for psychological issues, such as depressive symptoms. Encouraging patients to participate in "counseling groups" can further bolster their social support networks, enhancing their overall well-being and addressing comorbidities associated with chronic degenerative diseases.

From Sea to Science: Coral Aquaculture for Sustainable Anticancer Drug Development.

Marine natural products offer immense potential for drug development, but the limited supply of marine organisms poses a significant challenge. Establishing aquaculture presents a sustainable solution for this challenge by facilitating the mass production of active ingredients while reducing our reliance on wild populations and harm to local environments. To fully utilize aquaculture as a source of biologically active products, a cell-free system was established to target molecular components with protein-modulating activity, including topoisomerase II, HDAC, and tubulin polymerization, using extracts from aquaculture corals. Subsequent in vitro studies were performed, including MTT assays, flow cytometry, confocal microscopy, and Western blotting, along with in vivo xenograft models, to verify the efficacy of the active extracts and further elucidate their cytotoxic mechanisms. Regulatory proteins were clarified using NGS and gene modification techniques. Molecular docking and SwissADME assays were performed to evaluate the drug-likeness and pharmacokinetic and medicinal chemistry-related properties of the small molecules. The extract from Lobophytum crassum (LCE) demonstrated potent broad-spectrum activity, exhibiting significant inhibition of tubulin polymerization, and showed low IC50 values against prostate cancer cells. Flow cytometry and Western blotting assays revealed that LCE induced apoptosis, as evidenced by the increased expression of apoptotic protein-cleaved caspase-3 and the populations of early and late apoptotic cells. In the xenograft tumor experiments, LCE significantly suppressed tumor growth and reduced the tumor volume (PC3: 43.9%; Du145: 49.2%) and weight (PC3: 48.8%; Du145: 7.8%). Additionally, LCE inhibited prostate cancer cell migration, and invasion upregulated the epithelial marker E-cadherin and suppressed EMT-related proteins. Furthermore, LCE effectively attenuated TGF-ß-induced EMT in PC3 and Du145 cells. Bioactivity-guided fractionation and SwissADME validation confirmed that LCE's main component, 13-acetoxysarcocrassolide (13-AC), holds greater potential for the development of anticancer drugs.

Genetic association of diabetic retinopathy with long noncoding RNA CDKN2B-AS1 gene polymorphism.

AIM: We attempted to test the influences of cyclin dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene polymorphisms on the susceptibility to Diabetic retinopathy (DR). METHODS: Five single-nucleotide polymorphisms (SNPs) of the CDKN2B-AS1 gene, rs564398, rs1333048, rs1537373, rs2151280, and rs8181047 were examined in 280 DR cases and 455 DR-free diabetic controls. RESULTS: Among these loci tested, we demonstrated that diabetic carriers of at least one polymorphic allele (G) of rs2151280 (AG and GG; AOR, 1.613; 95% CI, 1.040-2.501; p = 0.033) are more susceptible to proliferative DR but not non-proliferative DR. This genetic association with the risk of developing proliferative DR was further strengthened in homozygotes for the polymorphic allele (G) of rs2151280 (GG; AOR, 2.194; 95% CI, 1.117-4.308; p = 0.023). We detected a significant association of the polymorphic allele (G) of rs2151280 with proliferative DR patients (OR, 1.503; 95% CI, 1.112-2.033; p = 0.008) but not with the entire DR or non-proliferative DR group. Moreover, as compared to those who do not possess the polymorphic allele of rs2151280 (AA), DR patients carrying at least one polymorphic allele of rs2151280 (AG + GG) exhibited a lower glomerular filtration rate and HDL cholesterol level, revealing a promotive role of rs2151280 in renal and cardiovascular complications of diabetes. CONCLUSION: Taken together, our findings implicate an impact of CDKN2B-AS1 gene polymorphisms on the progression of DR.

Recurrence of Diabetic Foot Complications: A Domino Effect Leading to Lethal Consequences-Insights From a National Longitudinal Study.

Background: Foot complications are common in people with diabetes mellitus (DM), leading to increased health care utilization, heightened mortality risk, and notable recurrence rates even after treatment. This retrospective cohort study aimed to investigate the impact of repeated occurrence of DM-related foot complications on the risk of all-cause mortality and to identify the potential risk factors associated with repeated events. Methods: People with DM admitted with foot complications (ulcer, skin and soft tissue infection, or osteomyelitis) from 2012 to 2014 were identified from Taiwan's National Health Insurance Research Database, with a 3-year follow-up for repeated events. We categorized the study subjects based on their cumulative number of hospital admissions with foot complications. Logistic regression was conducted to explore the potential risk factors associated with repeated diabetic foot events. Kaplan-Meier curves and Cox proportional hazard models were used to examine the associations between repeated diabetic foot events and all-cause mortality. Results: In this study, 28 754 eligible individuals were enrolled and classified into 3 groups: no repeated diabetic foot events (76.1%), 1 repeated event (16.0%), and 2 or more repeated events (7.9%). Logistic regression revealed that advanced age, male sex, congestive heart failure, dyslipidemia, hypertension, nephropathy, retinopathy, neuropathy, peripheral vascular disease, diabetes-related preventable hospitalizations, and outpatient visits due to diabetic foot were significantly associated with repeated events of diabetic foot complications. Compared with those with no repeated events, the adjusted hazard ratios for all-cause mortality were 1.26 (95% CI, 1.19-1.34) for 1 repeated event and 1.36 (95% CI, 1.26-1.47) for 2 or more repeated events. Conclusions: The significant association between repeated diabetic foot and elevated mortality risk highlights the critical necessity for proactive and targeted patient care within clinical practice. More research to delve into the predictive factors related to the repeated occurrence of diabetic foot is needed to provide additional insights for prevention strategies.

Three-Month Excessive Body Weight Loss < 37.7% as a Predictor of Mid-term Suboptimal Outcomes Postlaparoscopic Sleeve Gastrectomy: Risk Factors and the Impact of Neutrophil-to-Lymphocyte Ratio on Adipocyte Function.

INTRODUCTION: This study aimed to evaluate the impact of achieving < 37.7% excess body-weight loss (EBWL) within 3 months of postlaparoscopic sleeve gastrectomy (LSG) on clinical outcomes and its correlation with adipocyte function. METHODS: Patients (n = 176) who underwent LSG between January 2019 and January 2023 were included. Weight loss and status of health markers were monitored postoperatively. The cohort was stratified based on EBWL < 37.7% at 3 months or not. Variables including neutrophil-to-lymphocyte ratio (NLR), insulin resistance, and comorbidities were analyzed. Omental visceral and subcutaneous adipose tissue samples were used to analyze the differences in adipocyte function by western blot. RESULTS: Patients with EBWL < 37.7% at 3 months post-LSG (suboptimal group) comprised less likelihood of achieving ≥ 50% EBWL than those who achieved ≥ 37.7% EBWL (optimal group) at 6 months (42.55% vs. 95.52% in optimal group, p < 0.001), 12 months (85.11% vs. 99.25% in optimal group, p < 0.001) and 24 months (77.14% vs. 94.74% in optimal group, p = 0.009) post-LSG. High BMI (OR = 1.222, 95% CI 1.138-1.312, p < 0.001), NLR ≥ 2.36 (OR = 2.915, 95% CI 1.257-6.670, p = 0.013), and female sex (OR = 3.243, 95% CI 1.306-8.051, p = 0.011) significantly predicted EBWL < 37.7% at 3 months post-LSG. Patients with NLR ≥ 2.36 had significantly lower adipose triglyceride lipase in omental fat (p = 0.025). CONCLUSION: EBWL < 37.7% at 3 months post-LSG is a strong predictor of subsequent suboptimal weight loss. High BMI, NLR ≥ 2.36, and female sex are risk factors in predicting EBWL < 37.7% at 3 months post-LSG. These findings may offer a reference to apply adjuvant weight loss medications to patients who are predisposed to suboptimal outcomes.

Integrating OpenPose and SVM for Quantitative Postural Analysis in Young Adults: A Temporal-Spatial Approach.

Noninvasive tracking devices are widely used to monitor real-time posture. Yet significant potential exists to enhance postural control quantification through walking videos. This study advances computational science by integrating OpenPose with a Support Vector Machine (SVM) to perform highly accurate and robust postural analysis, marking a substantial improvement over traditional methods which often rely on invasive sensors. Utilizing OpenPose-based deep learning, we generated Dynamic Joint Nodes Plots (DJNP) and iso-block postural identity images for 35 young adults in controlled walking experiments. Through Temporal and Spatial Regression (TSR) models, key features were extracted for SVM classification, enabling the distinction between various walking behaviors. This approach resulted in an overall accuracy of 0.990 and a Kappa index of 0.985. Cutting points for the ratio of top angles (TAR) and the ratio of bottom angles (BAR) effectively differentiated between left and right skews with AUC values of 0.772 and 0.775, respectively. These results demonstrate the efficacy of integrating OpenPose with SVM, providing more precise, real-time analysis without invasive sensors. Future work will focus on expanding this method to a broader demographic, including individuals with gait abnormalities, to validate its effectiveness across diverse clinical conditions. Furthermore, we plan to explore the integration of alternative machine learning models, such as deep neural networks, enhancing the system's robustness and adaptability for complex dynamic environments. This research opens new avenues for clinical applications, particularly in rehabilitation and sports science, promising to revolutionize noninvasive postural analysis.

The Genetic Variants of Long Noncoding RNA MEG3 and Its Association to the Clinical Features of Diabetic Retinopathy.

PURPOSE: This study aimed to investigate the potential correlation between the single-nucleotide polymorphism (SNP) of maternally expressed gene 3 (MEG3) and the clinical manifestations of diabetic retinopathy (DR). METHODS: Five loci of MEG3 SNPs including rs4081134 (G/A), rs10144253 (T/C), rs7158663 (G/A), rs3087918 (T/G) and rs11160608 (A/C) were genotyped by TaqMan allelic discrimination in 457 non-DR patients and 280 DR individuals. RESULTS: The distribution frequency of MEG3 SNP rs7158663 GA (AOR: 0.683, 95% CI: 0.478-0.975, p = 0.036) and MEG3 SNP rs7158663 GA + AA (AOR: 0.686, 95% CI: 0.487-0.968, p = 0.032) were significantly lower in the DR group. And the MEG3 SNP rs7158663 GA + AA (AOR: 0.610, 95% CI: 0.377-0.985, p = 0.043) demonstrated a significantly lower distribution frequency in the male DR group. Besides, the DR patients with MEG3 SNP rs7158663 GA + AA genotype showed a significantly lower HbA1c level than the DR patients with MEG3 SNP rs7158663 GG genotype (7.29 ± 1.23 versus 7.74 ± 1.49, p = 0.013). Moreover, in the analysis using data from gene expression data series database, a higher MEG3 level was significantly correlated to a lower miR-182 level in the database (p = 0.0114). CONCLUSIONS: In this study, the distribution frequency of MEG3 SNP rs7158663 GA + AA genotype was lower in DR, while the DR would develop under lower HbA1c level in DM patients with this MEG3 SNP variant.

Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Detrusor Hyperactivity with Impaired Contractility via Transient Potential Vanilloid Channels: A Rat Model for Ovarian Hormone Deficiency.

This study explores low-intensity extracorporeal shock wave therapy (LiESWT)'s efficacy in alleviating detrusor hyperactivity with impaired contractility (DHIC) induced by ovarian hormone deficiency (OHD) in ovariectomized rats. The rats were categorized into the following four groups: sham group; OVX group, subjected to bilateral ovariectomy (OVX) for 12 months to induce OHD; OVX + SW4 group, underwent OHD for 12 months followed by 4 weeks of weekly LiESWT; and OVX + SW8 group, underwent OHD for 12 months followed by 8 weeks of weekly LiESWT. Cystometrogram studies and voiding behavior tracing were used to identify the symptoms of DHIC. Muscle strip contractility was evaluated through electrical-field, carbachol, ATP, and KCl stimulations. Western blot and immunofluorescence analyses were performed to assess the expressions of various markers related to bladder dysfunction. The OVX rats exhibited significant bladder deterioration and overactivity, alleviated by LiESWT. LiESWT modified transient receptor potential vanilloid (TRPV) channel expression, regulating calcium concentration and enhancing bladder capacity. It also elevated endoplasmic reticulum (ER) stress proteins, influencing ER-related Ca2+ channels and receptors to modulate detrusor muscle contractility. OHD after 12 months led to neuronal degeneration and reduced TRPV1 and TRPV4 channel activation. LiESWT demonstrated potential in enhancing angiogenic remodeling, neurogenesis, and receptor response, ameliorating DHIC via TRPV channels and cellular signaling in the OHD-induced DHIC rat model.

Taurine Rescues Cancer-induced Atrophy in Human Skeletal Muscle Cells via Ameliorating the Inflammatory Tumor Microenvironment.

BACKGROUND/AIM: Cancer cachexia is a wasting syndrome that has a devastating impact on the prognosis of patients with cancer. It is well-documented that pro-inflammatory cytokines are involved in the progression of this disorder. Therefore, this study was conducted to investigate the protective effect of taurine, an essential nonprotein amino acid with great anti-inflammatory properties, in attenuating muscle atrophy induced by cancer. MATERIALS AND METHODS: Conditioned media (CM) derived from T24 human bladder carcinoma cells with or without 5 mM taurine were incubated with human skeletal muscle cells (HSkMCs) and their differentiation was examined. The intracellular reactive oxygen species (ROS), morphology, and the catabolic pathway were monitored. RESULTS: T24-derived CM with high levels of TNF-α and IL-6 caused aberrant ROS accumulation and formation of atrophic myotubes by HSkMCs. In T24 cancer cells, taurine significantly inhibited the production of TNF-α and IL-6. In HSkMCs, taurine increased ROS clearance during differentiation and preserved the myotube differentiation ability impaired by the inflammatory tumor microenvironment. In addition, taurine ameliorated myotube atrophy by regulating the Akt/FoxO1/MuRF1 and MAFbx signaling pathways. CONCLUSION: Taurine rescues cancer-induced atrophy in human skeletal muscle cells by ameliorating the inflammatory tumor microenvironment. Taurine supplementation may be a promising approach for intervening with the progression of cancer cachexia.

Mitochondrial calcium uniporter as biomarker and therapeutic target for breast cancer: Prognostication, immune microenvironment, epigenetic regulation and precision medicine.

INTRODUCTION: Mitochondrial calcium uniporter (MCU) is a central subunit of MCU complex that regulate the levels of calcium ions within mitochondria. A comprehensive understanding the implications of MCU in clinical prognostication, biological understandings and therapeutic opportunity of breast cancer (BC) is yet to be determined. OBJECTIVES: This study aims to investigate the role of MCU in predictive performance, tumor progression, epigenetic regulation, shaping of tumor immune microenvironment, and pharmacogenetics and the development of anti-tumor therapy for BC. METHODS: The downloaded TCGA datasets were used to identify predictive ability of MCU expressions via supervised learning principle. Functional enrichment, mutation landscape, immunological profile, drug sensitivity were examined using bioinformatics analysis and confirmed by experiments exploiting human specimens, in vitro and in vivo models. RESULTS: MCU copy numbers increase with MCU gene expression. MCU expression, but not MCU genetic alterations, had a positive correlation with known BC prognostic markers. Higher MCU levels in BC showed modest efficacy in predicting overall survival. In addition, high MCU expression was associated with known BC prognostic markers and with malignancy. In BC tumor and sgRNA-treated cell lines, enrichment pathways identified the involvement of cell cycle and immunity. miR-29a was recognized as a negative epigenetic regulator of MCU. High MCU levels were associated with increased mutation levels in oncogene TP53 and tumor suppression gene CDH1, as well as with an immunosuppressive microenvironment. Sigle-cell sequencing indicated that MCU mostly mapped on to tumor cell and CD8 T-cells. Inter-databases verification further confirmed the aforementioned observation. miR-29a-mediated knockdown of MCU resulted in tumor suppression and mitochondrial dysfunction, as well as diminished metastasis. Furthermore, MCU present pharmacogenetic significance in cellular docetaxel sensitivity and in prediction of patients' response to chemotherapeutic regimen. CONCLUSION: MCU shows significant implication in prognosis, outcome prediction, microenvironmental shaping and precision medicine for BC. miR-29a-mediated MCU inhibition exerts therapeutic effect in tumor growth and metastasis.

Assessing risk of recurrent small bowel obstruction after non-operative management in patients with history of intra-abdominal surgery: a population-based comprehensive analysis in Taiwan.

BACKGROUND: Despite a significant 30% ten-year readmission rate for SBO patients, investigations into recurrent risk factors after non-operative management are scarce. The study aims to generate a risk factor scoring system, the 'Small Bowel Obstruction Recurrence Score' (SBORS), predicting 6-month recurrence of small bowel obstruction (SBO) after successful non-surgical management in patients who have history of intra-abdominal surgery. METHODS: We analyzed data from patients aged ≥ 18 with a history of intra-abdominal surgery and diagnosed with SBO (ICD-9 code: 560, 568) and were successful treated non-surgically between 2004 and 2008. Participants were divided into model-derivation (80%) and validation (20%) group. RESULTS: We analyzed 23,901 patients and developed the SBORS based on factors including the length of hospital stay > 4 days, previous operations > once, hemiplegia, extra-abdominal and intra-abdominal malignancy, esophagogastric surgery and intestino-colonic surgery. Scores > 2 indicated higher rates and risks of recurrence within 6 months (12.96% vs. 7.27%, OR 1.898, p < 0.001 in model-derivation group, 12.60% vs. 7.05%, OR 1.901, p < 0.001 in validation group) with a significantly increased risk of mortality and operative events for recurrent episodes. The SBORS model demonstrated good calibration and acceptable discrimination, with an area under curve values of 0.607 and 0.599 for the score generation and validation group, respectively. CONCLUSIONS: We established the effective 'SBORS' to predict 6-month SBO recurrence risk in patients who have history of intra-abdominal surgery and have been successfully managed non-surgically for the initial obstruction event. Those with scores > 2 face higher recurrence rates and operative risks after successful non-surgical management.

Association between Mastery Motivation, Executive Function, and Daily Participation of Young Children with and without Global Developmental Delays.

This study aimed to examine the group differences in participation level between children with and without global delays and to explore the associations between mastery motivation, executive function, and participation in young children with and without global developmental delays (GDD). Methods: we recruited 26 children with GDD aged 2 to 5 years and 26 children with sex- and mental age-matched developing typically (TD). The participants were assessed child development using the standardized developmental test, and their mothers were asked to fill in questionnaires, including the revised Dimension of Mastery Questionnaire (DMQ 18) with preschool version to assess mastery motivation, the Behavior Rating Inventory of Executive Function with preschool version (BRIEF-P) to assess executive function, and the Young Children's Participation and Environment Measure (YC-PEM) used to obtain participation levels. Results and conclusions: young children with GDD showed significantly lower participation levels at home, daycare, and community than TD group. We found that for young children, child mastery pleasure, health condition, and total persistence were significant predictors of child participation. Therefore, coaching parents to observe and facilitate their children's motivation and executive function, as well as child developmental abilities, is important in order to enhance children's participation in daily activities.

Association of sodium-glucose cotransporter 2 inhibitors with the incidence of corneal diseases in type 2 diabetes mellitus.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors revealed the protective function on various systemic diseases. This study aimed to determine whether the usage of SGLT2 inhibitors associates with incidences of superficial keratopathy and infectious keratitis in type 2 diabetes mellitus (T2DM) patients. A retrospective cohort study with the usage of National Health Insurance Research Database of Taiwan was conducted. The T2DM patients were divided into the SGLT2 inhibitors and control groups according to the usage of SGLT2 inhibitors or not. The major outcomes were defined as the occurrence of superficial keratopathy and infectious keratitis. There were 766 and 1037 episodes of superficial keratopathy in the SGLT2 inhibitors and control groups and SGLT2 inhibitors group showed a significantly lower incidence of superficial keratopathy than the control group (aHR: 0.721, 95% CI: 0.656-0.791, P < 0.0001). Also, there were 166 and 251 infectious keratitis events in the SGLT2 inhibitors and control groups and patients in the SGLT2 inhibitors group revealed a significantly lower infectious keratitis incidence than those in the control group (aHR: 0.654, 95% CI: 0.537-0.796, P < 0.0001). In addition, the patients that received SGLT2 inhibitors demonstrated lower cumulative incidences of both superficial keratopathy and infectious keratitis compared to the non-SGLT2 inhibitors users (both P < 0.0001). In conclusion, the usage of SGLT2 inhibitors correlates to lower incidence of superficial keratopathy and infectious keratitis in T2DM individuals, which is more significant in patients with persistent SGLT2 inhibitors application.

Test-Retest Reliability, Criterion-Related Validity, and Ecological Validity of the Test of Visual-Motor Skills, Third Edition, in Kindergarten Children With Developmental Coordination Disorder.

IMPORTANCE: Establishing empirical evidence on the psychometric properties of the Test of Visual-Motor Skills (3rd ed.; TVMS-3) is helpful for guiding its use as an assessment of visual-motor integration (VMI) skills in kindergarten children with developmental coordination disorder (DCD). OBJECTIVE: To investigate the test-retest reliability, criterion-related validity, and ecological validity of the TVMS-3 in Taiwanese kindergarten children with DCD. DESIGN: A nonexperimental, descriptive, correlational design. SETTING: A hospital in Central Taiwan. PARTICIPANTS: Fifty-seven kindergarten children with DCD were recruited in the study. OUTCOMES AND MEASURES: Intraclass correlation coefficient, percentage of minimal detectable change, and paired t test (Wilcoxon signed rank test) were used to investigate the test-retest reliability of the TVMS-3. The correlations (Pearson's r) between the TVMS-3 accuracy score and the scores of each of the four domains and the adaptive behavior composite score of the Vineland Adaptive Behavior Scales (3rd ed.; Vineland-3) were calculated, respectively, to examine criterion-related validity and ecological validity. RESULTS: The accuracy score of the TVMS-3 had excellent test-retest reliability and acceptable random measurement error. Moreover, it showed good criterion-related validity and sufficient ecological validity with the Vineland-3 in Taiwanese kindergarten children with DCD. CONCLUSIONS AND RELEVANCE: The accuracy score of the TVMS-3 is applicable to Taiwanese kindergarten children with DCD in clinical and research settings. Plain-Language Summary: The accuracy score of the Test of Visual-Motor Skills (3rd ed.; TVMS-3) is a useful assessment tool to detect deficits in visual-motor integration for Taiwanese kindergarten children with developmental coordination disorder. The TVMS-3 has excellent test-retest reliability, good criterion-related validity, and sufficient ecological validity.

Heteronemin promotes iron-dependent cell death in pancreatic cancer.

The marine environment has been recognized as a prolific source of potent bioactive compounds with significant anticancer properties. Among these, heteronemin, a sesterterpenoid-type natural product, has shown promise. This study delves into the potential of heteronemin as a ferroptotic agent against pancreatic cancer, using the Panc-1 cell line as a model. The cytotoxic potential of heteronemin was assessed using cell viability assays. Furthermore, its effect on lipid peroxidation was determined spectrophotometrically, while the changes it induced in autophagy- and ferritin-related protein expressions were evaluated using immunoblotting techniques. Various cell-based tests were employed to scrutinize its anticancer efficacy. Heteronemin displayed a notable cytotoxic effect, reducing cell viability by 50% at a concentration of 55 nM. This cytotoxicity was discernibly linked to ferroptosis, as evidenced by the reversal of cell death upon treatment with the ferroptosis inhibitor, ferrostatin-1. Heteronemin treatment led to a marked increase in ferroptosis markers and malondialdehyde (MDA) levels. Conversely, the expression of glutathione peroxidase-4 (GPX4), a key anti-ferroptotic protein, was suppressed. Furthermore, significant modulations in the expression of ferritinophagy- and iron-related proteins such as Atg5, Atg7, FTL, STEAP3, and DMT-1 were evident post-treatment (p < 0.05). This study underscores the potential of heteronemin as a ferroptosis inducer in pancreatic cancer cells. Given its robust cytotoxicity, heteronemin emerges as a promising lead compound for further exploration in cancer therapeutics.

Unveiling the multifaceted nexus of subjective aging, biological aging, and chronological age: Findings from a nationally representative cohort study.

OBJECTIVES: This study aims to investigate how subjective aging influences the psychological and behavioral responses of older individuals, specifically focusing on the associations between subjective aging and longitudinal changes in biological age. METHODS: This is a retrospective cohort study retrieving data from the Taiwan Longitudinal Study on Aging (TLSA), over a 4-year follow-up period. Subjective aging is assessed by asking participants if they perceive themselves as old, while frailty is measured using a frailty index comprising 34 deficits from various domains. Participants are categorized into three groups based on their chronological age. The association between subjective aging and transition of biological age (as indicated by an increased frailty index) from 2011 to 2015 is examined using logistic regression models. RESULTS: The study consisted of 2412 participants, who were categorized into middle-age (n = 1,082), young-old (n = 779), and old-old (n = 551) groups. Among them, individuals exhibiting subjective aging at baseline were more likely to be older in chronological age, female, illiterate, and unemployed, compared to those without subjective aging. The adjusted odds ratios (aORs) for the association between subjective aging and an increased biological age were 1.72 [95% CI: 0.88-3.34], 1.61 [0.77-3.37], and 1.08 [0.65-1.80], in the middle-age, young-old, and old-old groups, respectively. DISCUSSIONS: No significant associations were found between changes in biological age and subjective aging across various chronological age groups. Notably, within the younger age group, a discernible trend towards an association was observed, indicating the potential age-related nuances in the complex interrelation between subjective age, biological aging, and chronological aging.

Effects of declines in personal mastery on self-perceived mobility, physical function, cognitive function, and depressive symptoms: a 6-year follow-up study from the Social Environment and Biomarkers of Aging Study.

OBJECTIVES: As the psychosocial competence, personal mastery helps individuals to cope with stressful life events, and this study aims to examine impacts of declines in personal mastery on healthy aging among community-dwelling middle-aged and older adults using a nationally representative cohort. METHODS: Data from 648 study participants in the Social Environment and Biomarkers of Aging Study (SEBAS) were retrieved for analysis. All participants were divided into four groups based on their baseline and changes of personal mastery (measured by the Pearlin mastery score) during the 6-year follow-up. Multivariate logistic regression models were adopted to examine associations between declines in personal mastery and indicators for healthy aging (declines in self-perceived mobility, physical function (activities of daily living (ADLs) and instrumental activities of daily living (IADLs)), cognitive function and depressive symptoms). RESULTS: After adjustments for demographics and comorbidities, those with declines in personal mastery were associated with greater risks of declines in self-perceived mobility (adjusted odds ratio (aOR) 1.50 [95% confidence interval 1.01-2.22], p < 0.05). Although the point estimate in the unadjusted models indicated similar associations between declines in personal mastery and declines in ADLs, IADLs, cognitive function or depressive symptoms, these outcomes did not reach statistical significance in the adjusted model. CONCLUSIONS: Declines in personal mastery were negatively associated with indicators related to healthy aging (particularly locomotion) in a 6-year follow-up. Further investigations are needed to explore the effects of preventing declines in personal mastery in promoting healthy aging over time.