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Abstract Purpose This study aimed to identify risk factors for rebleeding within 180 days post-discharge in blunt splenic injury patients managed without splenectomy or embolization. Materials and methods A retrospective analysis was conducted using Taiwan’s National Health Insurance Research Database. Adult patients aged ≥ 18 years with blunt splenic injury (ICD-9-CM codes 865.01–865.09) from 2000 to 2012 were included. Patients who died, underwent splenectomy (ICD-9-OP codes 41.5, 41.42,41.43, and 41.95) or transcatheter arterial embolization (TAE) (ICD-9-OP codes 39.79 and 99.29) on the first admission were excluded. The primary endpoint was rebleeding, which was identified if patients underwent splenectomy or TAE at 180 days after discharge. Multivariate logistic regression was used to identify risk factors, which were validated in a separate cohort. Results Of 6,140 patients, 80 (1.302%) experienced rebleeding within 180 days. Five significant risk factors were identified: age 2 points had significantly higher rebleeding rates (risk-identifying cohort: 2.2% vs. 0.6%, OR 3.790, p

Abstract Retinal vein occlusion (RVO) is a common retinal vascular disease that causes visual impairment. However, there is limited evidence regarding the relationship between sinusitis and risk of RVO. This study investigated the association between sinusitis and the subsequent risk of RVO disease. A retrospective cohort study was conducted and patients with sinusitis or RVO were selected from the National Health Insurance Research Database (NHIRD) of Taiwan. In this population-based study, we identified a total of 131,532 sinusitis patients, who were matched with 263,064 non-sinusitis individuals based on sex and age. The Cox proportional hazard regression was applied to demonstrate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) of main outcomes. Our results showed that the crude hazard ratio (cHR) for the risk of RVO was 1.35 (95% CI: 1.20–1.52) in the sinusitis cohort compared with the non-sinusitis cohort. After adjustment for demographics and comorbidities in the multivariable cox regression, the adjusted hazard ratio (aHR) was 1.28 (95% CI: 1.13–1.44). Moreover, statistically significant differences were observed in the 14-year cumulative incidence of RVO (p

Because the distribution volume and mechanism of extracellular and intravascular MR contrast media differ considerably, the enhancement pattern of chronic myocardial infarction with extracellular or intravascular media might also be different. This study aims to investigate the differences in MR enhancement patterns of chronic myocardial infarction between extracellular and intravascular contrast media.Twenty pigs with myocardial infarction underwent cine MRI, first pass perfusion MRI and delayed enhancement MRI with extracellular or intravascular media at four weeks after coronary occlusion. Myocardial blood flow (MBF) was determined with microsphere measurement. The infarction histopathological changes were evaluated by hematoxylin and eosin staining and Masson's trichrome method.Cine MRI revealed the reduced wall thickening in chronic infarction compared with normal myocardium. Moreover, significant wall thinning in chronic infarction was observed in cine MRI. Peak first-pass signal intensity didn't significantly differ between chronic infarction and normal myocardium no matter what kinds of contrast media. At the following delayed enhancement phase, extracellular media-enhanced signal intensity was significantly higher in chronic infarction than in normal myocardium. Conversely, intravascular media-enhanced signal intensity was almost equivalent among chronic infarction and normal myocardium. At four weeks after infarction, MBF in chronic infarction approached to that in normal myocardium. Large thick-walled vessels were detected at peri-infarction zones. The cardiomyocytes were replaced by scar tissue consisting of dilated blood vessels and discrete fibers of collagen.Chronic infarction was characterized by the significantly reduced wall thickening and the definite wall thinning. First-pass myocardial perfusion defect was not detected in chronic infarction with two media due to the significantly recovered MBF and well-developed collateral vessels. Infarction remodeling enlarged the extracellular compartment, which was available for extracellular media but not accessible to intravascular media. Extracellular media identified chronic infarction as the hyper-enhancement; nonetheless, intravascular media didn't provide delayed enhancement.

BackgroundPatients 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.PurposeThis 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.MethodsA 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.ResultsA 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.ConclusionNurses 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.

In today’s dynamic business landscape, companies need to enhance problem-solving efficiency to produce products or services to meet evolving customer needs. Fostering creative talent and utilizing Group Decision Support Systems (GDSS) have become crucial in the management of human resources and marketing. While empirical studies demonstrate the positive impact of GDSS on learning, a gap exists in understanding its correlation with outcomes like enhanced creativity. Thus, qualitative research is needed to uncover the cognitive processes for favorable results with the adoption of GDSS. We explored the relationship between Project-Based Learning (PBL), GDSS deployment, and outcomes in a cross-organizational study. Results highlighted PBL activities facilitated by GDSS and the key benefits of digital learning, and managerial and academic considerations were proposed.

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-β-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.

The classical morphological features of follicular lymphoma (FL) are well-recognized. However, identifying some morphological variants, such as FL with hyaline-vascular Castleman disease (HVCD) like features (FL-HVCD), is challenging. Hence, we report a 57-year-old male with FL-HVCD who presented with nontender swelling of the bilateral lower limbs, caused by enlarged intra-abdominal lymph nodes with venous compression. The excised lymph nodes showed onionskin-like mantle zones and hyalinized blood vessels, which was consisted with HVCD. Oral medications were prescribed; however, the patient was lost to follow-up after 6 months and was readmitted with anemia, thrombocytopenia, and leukocytosis 3 years later. A bone marrow biopsy was done, and the patient was diagnosed as having overt FL with bone marrow involvement. Physicians should be careful if HCVD patients present with systemic symptoms or generalized lymphadenopathy. Excluding the possibility of lymphoma is necessary because the different treatment strategy and prognosis from HVCD.

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.

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.

Skin plays an important role as a defense mechanism against environmental pathogens in organisms such as humans or animals. Once the skin integrity is disturbed by a wound, pathogens can penetrate easily into a deeper part of the body to induce disease. By this means, it is important for the skin to regenerate quickly upon injury to regain its protective barrier function. Traditionally, scientists use rodents or mammals as experimental animals to study skin wound healing. However, due to concerns about animal welfare and increasing costs of laboratory animals, such as rodents, scientists have considered alternative methods of implementing replace, reduce, and refine (3Rs) in experimentation. Moreover, several previous studies on skin wound healing in fish used relatively expensive medical-grade lasers with a low calculation efficiency of the wound area, which led to human judgment errors. Thus, this study aimed to develop a new alternative model for skin wound healing by utilizing zebrafish together with a new rapid and efficient method as an alternative in investigating skin wound healing. First, in order to fulfill the 3Rs concept, the pain in the tested zebrafish was evaluated by using a 3D locomotion assay. Afterward, the obtained behavior data were analyzed using the Kruskal–Wallis test, followed by Dunn’s multiple comparisons tests; later, 3 watts was chosen as the power for the laser, since the wound caused by the laser at this power did not significantly alter zebrafish swimming behaviors. Furthermore, we also optimized the experimental conditions of zebrafish skin wound healing using a laser engraving machine, which can create skin wounds with a high reproducibility in size and depth. The wound closure of the tested zebrafish was then analyzed by using a two-way ANOVA, and presented in 25%, 50%, and 75% of wound-closure percentages. After imparting wounds to the skin of the zebrafish, wound images were collected and used for deep-learning training by convolutional neural networks (CNNs), either the Mask-RCNN or U-Net, so that the computer could calculate the area of the skin wounds in an automatic manner. Using ImageJ manual counting as a gold standard, we found that the U-Net performance was better than the Mask RCNN for zebrafish skin wound judgment. For proof-of-concept validation, a U-Net trained model was applied to study and determine the effect of different temperatures and the administration of antioxidants on the skin wound-healing kinetics. Results showed a significant positive correlation between the speed of wound closure and the exposure to different temperatures and administration of antioxidants. Taken together, the laser-based skin ablation and deep learning-based wound-size measurement methods reported in this study provide a faster, reliable, and reduced suffering protocol to conduct skin wound healing in zebrafish for the first time.

Abstract Background Sjögren’s syndrome may be a risk factor for carotid artery stenosis. Bilateral common carotid artery occlusion (BCCAO) in a patient with Sjögren’s syndrome was not reported before. In this report, we describe a female with Sjögren’s syndrome who had acute visual loss due to ocular ischemic syndrome (OIS) with BCCAO. Case presentation A 50-year-old female with Sjögren’s syndrome visited our clinic with acute visual loss in the left eye. The best corrected visual acuity (BCVA) was 2/100 in the left eye, and the intraocular pressure (IOP) was normal in both eyes. Ocular ischemic change was observed during the ophthalmic examination. Aortography and computed tomography angiography (CTA) showed nearly total occlusion of the bilateral CCA. Thus, OIS with BCCAO was diagnosed. The vision in the left eye improved to 30/100 after carotid artery stenting for the left common carotid artery. Conclusions BCCAO may be present in patients with Sjögren’s syndrome. Large vessel abnormalities should be considered when acute visual loss is found in a patient with Sjögren’s syndrome.

Abstract Background The detection rate of Barcelona Clinic Liver Cancer (BCLC) very-early-stage hepatocellular carcinoma (HCC) is increasing because of advances in surveillance and improved imaging technologies for high-risk populations. Surgical resection (SR) and radiofrequency ablation (RFA) are both first‐line treatments for very-early-stage HCC, but the differences in clinical outcomes between patients treated with SR and RFA remain unclear. This study investigated the prognosis of SR and RFA for very-early‐stage HCC patients with long‐term follow‐up. Methods This study was retrospectively collected data on the clinicopathological characteristics, overall survival (OS), and disease-free survival (DFS) of 188 very-early-stage HCC patients (≤ 2 cm single HCC). OS and DFS were analyzed using the Kaplan–Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. Results Of the 188 HCC patients, 103 received SR and 85 received RFA. The median follow‐up time was 56 months. The SR group had significantly higher OS than the RFA group (10-year cumulative OS: 55.2% and 31.3% in the SR and RFA groups, respectively). No statistically significant difference was observed in DFS between the SR and RFA groups (10-year cumulative DFS: 45.9% and 32.6% in the SR and RFA groups, respectively). After PSM, the OS in the SR group remained significantly higher than that in the RFA group (10-year cumulative OS: 54.7% and 42.2% in the SR and RFA groups, respectively). No significant difference was observed in DFS between the SR and RFA groups (10-year cumulative DFS: 43.0% and 35.4% in the SR and RFA groups, respectively). Furthermore, in the multivariate Cox regression analysis, treatment type (hazard ratio (HR): 0.54, 95% confidence interval (CI): 0.31–0.95; P = 0.032) and total bilirubin (HR: 1.92; 95% CI: 1.09–3.41; P = 0.025) were highly associated with OS. In addition, age (HR: 2.14, 95% CI: 1.36–3.36; P = 0.001) and cirrhosis (HR: 1.79; 95% CI: 1.11–2.89; P = 0.018) were strongly associated with DFS. Conclusion For patients with very-early-stage HCC, SR was associated with significantly higher OS rates than RFA. However, no significant difference was observed in DFS between the SR and RFA groups.

Abstract Background The effect of diabetic retinopathy (DR) on the development of sight-threatening cataracts was assessed using the National Health Insurance Research Database of Taiwan. Methods Patients diagnosed with diabetes mellitus (DM) and DR were enrolled in the study group. Age- and sex-matched DM individuals without DR and patients without DM served as the DM control group and non-DM control group, respectively, both with 1:4 ratios. The outcome was set as the performance of cataract surgery. Cox proportional hazard regression was used to calculate the adjusted hazard ratio (aHR) of DR considering multiple factors underlying cataract formation. Results A total of 3297 DR patients, 13,188 DM control patients and 13,188 non-DM control subjects were enrolled. The study group included 919 events of sight-threatening cataracts (27.87%), the DM control group included 1108 events (8.40%), and the non-DM control group included 957 events (7.26%). A multivariable analysis indicated that the study group presented a higher aHR of cataract surgery (2.93, 95% CI: 2.60–3.30) and a higher cumulative probability of cataract surgery than both the DM control and non-DM control groups (both log rank P

Abstract Background Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). Methods We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. Results We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7 and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68–26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01–0.34), p = 0.004, and 0.07 (0.01–0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85–922), p = 0.008, and 17.9 (1.05–306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2 and 74.6% in high LC3 expression patients and 0 and 0% in those with low LC3 expression. Conclusion High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.

Abstract Background Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups. Methods We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis. Results In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM. Conclusion The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.

Abstract Background Patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) are recommended to undergo transcatheter arterial chemoembolization (TACE). However, TACE in combination with radiofrequency ablation (RFA) is not inferior to surgical resection (SR), and the benefits of surgical resection (SR) for BCLC stage B HCC remain unclear. Hence, this study aims to compare the impact of SR, TACE+RFA, and TACE on analyzing overall survival (OS) in BCLC stage B HCC. Methods Overall, 428 HCC patients were included in BCLC stage B, and their clinical data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Results One hundred forty (32.7%) patients received SR, 57 (13.3%) received TACE+RFA, and 231 (53.9%) received TACE. The OS was significantly higher in the SR group than that in the TACE+RFA group [hazard ratio (HR): 1.78; 95% confidence incidence (CI): 1.15–2.75, p = 0.009]. The OS was significantly higher in the SR group than that in the TACE group (HR: 3.17; 95% CI: 2.31–4.36, p

Sacha inchi is a source of quality commercial oil in Taiwan. Oil extraction results in sacha inchi residue have not been utilized and not much investigated. Different edible seeds and nuts have different levels of nutrients. This study aims (a) to determine the oil, moisture, ash, protein, carbohydrate, type of fatty acid, resveratrol, and type of sugar in edible seeds and nuts, including sacha inchi residue, and (b) to determine the model to predict the five macronutrients using NIR spectroscopy. The samples used were candlenut, peanut, sesame, sunflower, sacha inchi residue, and black bean. Determination was conducted using NIR spectroscopy, NMR spectroscopy, LC-MS/MS, and HPLC-ELSD. NIR spectroscopy prediction results show that candlenut is rich in oil, and sacha inchi residue is rich in minerals, protein, and moisture. The correct prediction model for oil and moisture is principal component regression, while partial least squares are for ash, protein, and carbohydrates. NMR spectroscopy results showed that all samples were rich in polyunsaturated fatty acids. Sacha inchi residue is rich in omega 3. LC-MS/MS results showed that all samples contained resveratrol, and its highest level was found in sesame. HPLC-ELSD results showed eight types of sugars in the samples. High sucrose was found in sacha inchi residue, sunflower, sesame, and candlenut. The results are expected to provide information on nutrient levels in seeds and nuts to consumers and people who deal with nutrition. Also, results are expected to increase the economic value of sacha inchi residue as a source of diversification of food products in Taiwan.

It has been shown that phosphodiesterase 5 (PDE5) inhibitors have anticancer effects in a variety of malignancies in both in vivo and in vitro experiments. The role of cGMP elevation in colorectal carcinoma (CRC) has been extensively studied. Additionally, DNA topoisomerase II (Topo II) inhibition is a well-established mechanism of action that mediates the effects of several approved anticancer drugs such as doxorubicin and mitoxantrone. Herein, we present 9-benzylaminoacridine derivatives as dual inhibitors of the PDE5 and Topo II enzymes. We synthesized 31 derivatives and evaluated them against PDE5, whereby 22 compounds showed micromolar or sub-micromolar inhibition. The anticancer activity of the compounds was evaluated with the NCI 60-cell line testing. Moreover, the effects of the compounds on HCT-116 colorectal carcinoma (CRC) were extensively studied, and potent compounds against HCT-116 cells were studied for their effects on Topo II, cell cycle progression, and apoptosis. In addition to exhibiting significant growth inhibition against HCT116 cells, compounds 11, 12, and 28 also exhibited the most superior Topo II inhibitory activity and low micromolar PDE5 inhibition and affected cell cycle progression. Knowing that compounds that combat cancer through multiple mechanisms are among the best candidates for effective therapy, we believe that the current class of compounds merits further optimization and investigation to unleash their full therapeutic potential.

Abstract Background To evaluate the potential risk factor of visual-threatening posterior capsule opacification (PCO) via the analysis of National Health Insurance Research Database in Taiwan. Patients and methods A total of 8571 patients (3767 male and 4804 female) were recruited in the study group and 17,142 patients (7534 male and 9608 female) in the control group. Patients undergoing cataract surgery, acrysof single-piece intraocular lens implantation and Nd:YAG capsulotomy were selected as the study group. After exclusion which aimed to standardize the ocular condition and exclude the possibility that patients undergoing cataract surgery and Nd:YAG capsulotomy in different eyes, each patient in the study group was age-gender matched to two patients undergoing cataract surgery but without Nd:YAG capsulotomy. The demographic data, systemic disease, and ocular co-morbidities were obtained and analyzed. Adjusted odds ratio (OR) of each demographic data and co-morbidities to the development of visual-threatening PCO, and adjusted OR of co-morbidities to visual-threatening PCO develop within 1 year postoperatively. Results The dry eye disease (DED), glaucoma, uveitis, age-related macular degeneration (AMD), hyperlipidemia, peptic ulcer disease and liver disease showed significant crude OR while the DED, glaucoma, AMD, hyperlipidemia and peptic ulcer disease revealed a significant adjusted OR. In the subgroup analysis, the DED, glaucoma, AMD, and hyperlipidemia still illustrated a higher adjusted OR to develop visual-threatening PCO within 1 year after the cataract surgery. Conclusion The DED, glaucoma, AMD, hyperlipidemia and peptic ulcer disease may serve as the risk factor for the developing of visual-threatening PCO.

Parkinson disease (PD) is the second-most common neurodegenerative disease. The characteristic pathology of progressive dopaminergic neuronal loss in people with PD is associated with iron accumulation and is suggested to be driven in part by the novel cell death pathway, ferroptosis. A unique modality of cell death, ferroptosis is mediated by iron-dependent phospholipid peroxidation. The mechanisms of ferroptosis inhibitors enhance antioxidative capacity to counter the oxidative stress from lipid peroxidation, such as through the system xc−/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis and the coenzyme Q10 (CoQ10)/FSP1 pathway. Another means to reduce ferroptosis is with iron chelators. To date, there is no disease-modifying therapy to cure or slow PD progression, and a recent topic of research seeks to intervene with the development of PD via regulation of ferroptosis. In this review, we provide a discussion of different cell death pathways, the molecular mechanisms of ferroptosis, the role of ferroptosis in blood–brain barrier damage, updates on PD studies in ferroptosis, and the latest progress of pharmacological agents targeting ferroptosis for the intervention of PD in clinical trials.

Prostate adenocarcinoma (PRAD) is the most common histological subtype of prostate cancer. Post-treatment biochemical recurrence is a challenging issue. ATAD1 (ATPase Family AAA Domain Containing 1) plays a vital role in mitochondrial proteostasis and apoptosis activity, while its clinical value in PRAD and its impact on the tumor microenvironment (TME) remain unanswered. In this study, we aimed to investigate the clinical value and possible mechanisms of ATAD1 in PRAD via multi-omics analysis. Using cBioPortal, we confirmed that ATAD1 alteration was associated with gene expression and unfavorable DFS. Deep deletion predominantly occurred in PRAD. By integrating DriverDBv3 and GEPIA2, we noted ATAD1 downregulation in PRAD tissues compared to normal tissues, associated with unfavorable DFS in PRAD patients. DNA repair genes ATM, PARP1and BRCA2 had positive associations with ATAD1 expression. We found that the generalization value of ATAD1 could be applied to other cancers such as KIRC and UCEC. In addition, LinkedOmics identified that the functional involvement of ATAD1 participates in mitochondrial structure and cell cycle progression. Using TIMER analysis, we demonstrated that ATAD1 downregulation correlated with an immunosuppressive TME. Furthermore, we accessed a GSE55062 dataset on UALCAN and discovered the involvement of ERG-mediated transcriptional repression on ATAD1 downregulation. Cross-association screening of shATAD1 efficacy vs. altered mRNAs identified 190 perturbed mRNAs. Then, functional enrichment analysis using the Metascape omics tool recognized that shATAD1-perturbed mRNAs are primarily in charge of the activation of Wnt/β-catenin pathway and lipid metabolic processes. In conclusion, multi-omics results reveal that ATAD1 downregulation is a clinical biomarker for pathological diagnosis and prognosis for patients with PRAD. Reduced ATAD1 may be involved in the enhanced activity of mitochondria and cell cycle, as well as possibly shaping an immunosuppressive TME. ERG serves as an upstream transcriptional repressor of ATAD1. Downstream mechanisms of ATAD1 are involved in Wnt/β-catenin pathway and lipid metabolic processes.

The two objectives of this systematic review were to examine the following: (1) the difference in sensory processing areas (auditory, visual, vestibular, touch, proprioceptive, and multi-sensory) between children with and without developmental coordination disorder (DCD), and (2) the relationship between sensory processing and motor coordination in DCD. The following databases were comprehensively searched for relevant articles: PubMed, Science Direct, Web of Science, and Cochrane library. There were 1107 articles (published year = 2010 to 2021) found in the initial search. Full-text articles of all possibly relevant citations were obtained and inspected for suitability by two authors. The outcome measures were sensory processing impairments and their relationship with motor coordination. A total of 10 articles met the inclusion criteria. Children with DCD showed significant impairments in visual integration, tactile integration, proprioceptive integration, auditory integration, vestibular integration, and oral integration processes when compared with typically developing children. Evidence also supported that sensory processing impairments were associated with poor motor coordination in DCD. Preliminary support indicated that DCD have sensory processing impairments in visual, tactile, proprioceptive, auditory, and vestibular areas, which might contribute to participation restriction in motor activities. It is important to apply sensory integration therapy in rehabilitation programs for DCD in order to facilitate participation in daily activities.

Parkinson disease (PD) is the second most common neurodegenerative disease without known disease modification therapy to slow down disease progression. This disease has pathological features of Lewy bodies with α-synuclein aggregation being the major component and selective dopaminergic neuronal loss over the substantia nigra. Although the exact etiology is still unknown, mitochondrial dysfunction has been shown to be central in PD pathophysiology. Type 2 diabetes mellitus has recently been connected to PD, and anti-diabetic drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), have been shown to possess neuroprotective effects in PD animal models. The GLP-1RA liraglutide is currently under a phase 2 clinical trial to measure its effect on motor and non-motor symptoms in PD patients. In this study, we used an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to test the possible mechanism of the GLP-1RA liraglutide in the pathogenesis of PD. We show that the neurobehavioral and motor dysfunction caused by the mitochondrial complex I inhibitor, MPTP, can be partially reversed by liraglutide. The GLP-1RA can protect mice from apoptosis of substantia nigra neurons induced by MPTP. MPTP treatment led to imbalanced mitochondrial fusion and fission dynamics, altered mitochondrial morphology, impeded autophagy flux, increased α-synuclein accumulation, and elevated oxidative stress. Specifically, the normalizing of mitochondrial fusion-fission dynamic-related proteins and enhancement of autophagy flux after administration of liraglutide is associated with improving neuronal survival. This suggests that GLP-1RAs may provide potential beneficial effects for PD caused by mitochondrial dysfunction through improvement of mitochondrial morphology balance and enhancing damaged organelle degradation.

Background Nurses’ knowledge regarding palliative and end-of-life (EOL) care has been documented, but the competence of nurses in Taiwan has not been deeply analyzed and may affect the use of EOL care. Purpose We aimed to (1) assess the palliative care knowledge, competence and attitude of nurses in a general hospital and (2) examine the paths connecting nurses’ demographic characteristics, previous experiences, knowledge, competence, and attitude. Method A correlational, cross-sectional survey design was implemented to recruit 682 eligible nurses. The questionnaires included demographic information and palliative and EOL care knowledge, attitude, and competence scales. Path analysis was employed for statistical analysis using structural equation modeling. Results Overall, 76% of the questions assessing palliative and hospice knowledge were answered correctly. Nurses’ palliative attitudes were divided into “positive perception” and “negative perception”. “Positive perception” was highly correlated with competence (r = 0.48, p < 0.001), but “negative perception” was not significantly correlated with competence (r = −0.07, p = 0.25). “Positive perception” (β = −0.01, p = 0.84) and competence (β = 0.02, p = 0.80) were not related to palliative knowledge. “Negative perception”, however, was negatively associated with palliative knowledge (β = −0.20, p < 0.01). Conclusions This study suggests continuing education to decrease nurses’ “negative perception” attitude regarding the provision of information to patients and families to provide better palliative and EOL care. Implications for Practice Nurses’ attitudes and competences with respect to palliative care and EOL care are critical. Areas for further research and advanced palliative and EOL care-related education and training are suggested and may be applied in future clinical interventions.

Human pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer type with a very high mortality rate. Inflammatory cytokine such as tumor necrosis factor- alpha (TNF-α) plays a pivotal role in the progression of PDAC. Recently, suppression of cell invasion by preventive agents has received considerable attention in the prevention of metastatic tumors. Several clinical studies suggested that natural forms or analogues of fat-soluble vitamins such as vitamin A and vitamin D can work as anti-cancer agents to inhibit the development of cancer. In this study, our results demonstrated that co-treatment of 13-cis retinoic acid (13-cis RA) and 1,25-dihydroxyvitamin D3 (1,25-VD3) significantly inhibited TNF-α mediated cell invasion in PDAC in vitro. Cotreatment of 13-cis RA and 1,25-VD3 also inhibited TNF-α mediated expression of matrix metalloproteinase-9 (MMP-9) protein through blocking c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-κB) signaling pathways. Our results demonstrated that treatment of TNF-α lead to a decreased expression of tissue inhibitor of metalloproteinase- 3 (TIMP-3) protein and an induction of MMP-9 protein and cell invasion through an upregulation of microRNA-221 (miR-221) in human PDAC cells. Moreover, treatment of SP600125 (a specific inhibitor of JNK pathway) or cotreatment of 13-cis RA and 1,25-VD3 significantly induced a decreased expression of miR-221 and an increased expression of TIMP-3 protein. These results suggest that 13-cis RA and 1,25-VD3 significantly suppress TNF-α mediated cell invasion and therefore potentially act as preventive agents against PDAC.

Background: Plenty of evidence suggested that chronic low-grade inflammation triggered by innate immunity activation contributes to the pathogenesis of type 2 diabetes (T2D). Using the trans-mitochondrial cybrid cell model, we have demonstrated that mitochondria independently take part in the pathological process of insulin resistance (IR) and pro-inflammatory phenotype in cybrid cells harboring mitochondrial haplogroup B4, which are more likely to develop T2D. The mitochondrial network is more fragmented, and the expression of fusion-related proteins is low in Cybrid B4. We also discovered the causal role of mitochondrial dynamics (mtDYN) proteins in regulating IR in this cybrid model, and the bidirectional interaction between mtDYN and mitochondrial oxidative stress is considered etiologically important. In this study, we further investigated whether mtDYN bridges the gap between nutrient excess and chronic inflammation in T2D.Methods: Trans-mitochondrial cybrid cells derived from the 143B human osteosarcoma cell line were cultured in a medium containing glucose (25 mM) with or without saturated fatty acid (0.25 mM BSA-conjugated palmitate), and the expression of innate immunity/inflammasome molecules was compared between cybrid B4 (the major T2D-susceptible haplogroup among the Chinese population) and cybrid D4 (the major T2D-resistant haplogroup among the Chinese population). We investigated the causal relationship between mtDYN and nutrient excess-induced inflammation in cybrid B4 by genetic manipulation of mtDYN and by pharmacologically inhibiting mitochondrial fission using the Drp1 inhibitor, mdivi-1, and metformin.Results: Under nutrient excess with high fatty acid, cybrid B4 presented increased mitochondrial pro-fission profiles and enhanced chronic inflammation markers (RIG-I, MDA5, MAVS) and inflammasome (NLRP3, Caspase-1, IL-1β), whereas the levels in cybrid D4 were not or less significantly altered. In cybrid B4 under nutrient excess, overexpression of fusion proteins (Mfn1 or Mfn2) significantly repressed the expression of innate immunity/inflammasome-related molecules, while knockdown had a less significant effect. On the contrary, knockdown of fission proteins (Drp1 or Fis1) significantly repressed the expression of innate immunity/inflammasome-related molecules, while overexpression had a less significant effect. In addition, Drp1 inhibitor mdivi-1 and metformin inhibited mitochondrial fission and attenuated the pro-inflammation expression as well.Conclusion: Our results discovered the causal relationship between mtDYN and nutrient excess-induced chronic inflammation in a diabetes-susceptible cell model. Targeting mtDYN by direct interfering pro-fission can be a therapeutic intervention for chronic inflammation in T2D.

Abstract Background To investigate the effect of scleral buckling (SB) on the morphology and density of human corneal endothelial cells (HCEC). Methods In this retrospective cross-sectional study, 26 patients who had undergone SB due to rhegmatogenous retinal detachment were enrolled, in which 15 patients received encircling while the other 11 segment types of SB. The postoperative status of affected eye, preoperative status of affected eye, and the contralateral healthy eye was served as the study, control and contralateral groups. The images of the corneal endothelium was obtained by specular microscopy at least three months postoperatively and analyzed. Results Postoperative best-corrected visual acuity of the study group was worse than that of another two groups (P

Background and Objectives: Flail chest typically results from major trauma to the thoracic cage and is accompanied by multiple rib fractures. It has been well documented that surgical fixation of rib fractures can decrease both morbidity and mortality rates. This study aimed to evaluate the effectiveness of a dedicated APS Rib Fixation System, which features a pre-contoured design based on anatomical rib data of the Asian population. Materials and Methods: We reviewed 43 consecutive patients, who underwent surgical stabilization for flail chest with the traditional Mini bone plate (n = 20), APS plate (n = 13), or Mini + APS (n = 10). Demographic and injury variables were documented. We used X-ray radiography to determine plate fractures and screw dislocations after surgical fixation. Results: No statistical differences were noted in the demographic or injury variables. APS plates demonstrated fewer cases of plate fractures and screw dislocations than Mini plates (OR = 0.091, p = 0.008). Conclusions: The pre-contoured design of the APS plate demonstrated a superior rib implant failure rate as compared to the traditional Mini bone plate. Our study indicates that the APS plate may serve as an effective surgical tool for the treatment of flail chest.

Transcatheter aortic valve implantation (TAVI) has evolved to be the treatment of choice for patients with severe aortic stenosis and high perioperative risk. Cardiogenic shock is one of the most severe complications during the TAVI procedure, especially as the prognosis of cardiogenic shock secondary to aortic stenosis is very poor. This situation can be challenging, while extracorporeal membranous oxygenation (ECMO) can be a treatment option. Here, we reported on an 88-year-old female patient who had been diagnosed as non-ST-elevation myocardial infarction (NSTEMI) and critical aortic valve stenosis (AS) with a logistic Euroscore of 25%. Percutaneous coronary angioplasty (PCI) was performed smoothly and developed tachy-brady arrhythmia of atrial fibrillation then cardiac arrest at the beginning of the TAVI procedure. A v-a ECMO was installed at her left femoral side. Afterward, the TAVI procedure was completed accordingly; her consciousness recovered and Levosimendan therapy enhanced her left-ventricular ejection fraction (LVEF) from 22% to 40%. Five days after TAVI, ECMO was replaced by intra-aortic balloon pumping (IABP) and it was removed 3 days later. A minor complication of this therapy, e.g., muscular weakness in her left leg, was noted. The patient underwent rehabilitation for about 2 months, and was discharged from hospital with a wheel chair and clear consciousness. At the 24 month follow-up she was in good recovery and was able to walk upstairs to the second floor again. Our experience suggests that one indication of prophylactic use of ECMO is for patients with an unstable hemodynamic condition.

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease affecting more than 1% of the population over 65 years old. The etiology of the disease is unknown and there are only symptomatic managements available with no known disease-modifying treatment. Aging, genes, and environmental factors contribute to PD development and key players involved in the pathophysiology of the disease include oxidative stress, mitochondrial dysfunction, autophagic–lysosomal imbalance, and neuroinflammation. Recent epidemiology studies have shown that type-2 diabetes (T2DM) not only increased the risk for PD, but also is associated with PD clinical severity. A higher rate of insulin resistance has been reported in PD patients and is suggested to be a pathologic driver in this disease. Oral diabetic drugs including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to provide neuroprotective effects in both PD patients and experimental models; additionally, antidiabetic drugs have been demonstrated to lower incidence rates of PD in DM patients. Among these, the most recently developed drugs, SGLT2 inhibitors may provide neuroprotective effects through improving mitochondrial function and antioxidative effects. In this article, we will discuss the involvement of mitochondrial-related oxidative stress in the development of PD and potential benefits provided by antidiabetic agents especially focusing on sglt2 inhibitors.

Many active substances from marine organisms are produced by symbiotic microorganisms such as bacteria, fungi, and algae. Secondary metabolites from marine actinomycetes exhibited several biological activities and provided interesting drug leads. This study reported the isolation of Lu01-M, a secondary metabolite from the marine actinomycetes Streptomyces sp., with potent anti-proliferative activity against prostate cancers. Lu01-M blocked cell proliferation with IC50 values of 1.03 ± 0.31, 2.12 ± 0.38, 1.27 ± 0.25 μg/mL in human prostate cancer PC3, DU145, and LNCaP cells, respectively. Lu01-M induced cytotoxic activity through multiple mechanisms including cell apoptosis, necroptosis, autophagy, ER stress, and inhibiting colony formation and cell migration. Lu01-M induced cell cycle arrest at the G2/M phase and DNA damage. However, the activity of autophagy induced survival response in cancer cells. Our findings suggested that Lu01-M holds the potential to be developed as an anti-cancer agent against prostate cancers.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as a chronic bladder disorder with suprapubic pain (pelvic pain) and pressure and/or discomfort related to bladder filling accompanied by lower urinary tract symptoms, such as urinary frequency and urgency without urinary tract infection (UTI) lasting for at least 6 weeks. IC/BPS presents significant bladder pain and frequency urgency symptoms with unknown etiology, and it is without a widely accepted standard in diagnosis. Patients’ pathological features through cystoscopy and histologic features of bladder biopsy determine the presence or absence of Hunner lesions. IC/PBS is categorized into Hunner (ulcerative) type IC/BPS (HIC/BPS) or non-Hunner (nonulcerative) type IC/BPS (NHIC/BPS). The pathophysiology of IC/BPS is composed of multiple possible factors, such as chronic inflammation, autoimmune disorders, neurogenic hyperactivity, urothelial defects, abnormal angiogenesis, oxidative stress, and exogenous urine substances, which play a crucial role in the pathophysiology of IC/BPS. Abnormal expressions of several urine and serum specimens, including growth factor, methylhistamine, glycoprotein, chemokine and cytokines, might be useful as biomarkers for IC/BPS diagnosis. Further studies to identify the key molecules in IC/BPS will help to improve the efficacy of treatment and identify biomarkers of the disease. In this review, we discuss the potential medical therapy and assessment of therapeutic outcome with urinary biomarkers for IC/BPS.

This study explores text conversion to motion using large language models like the generative pre-trained transformer (GPT) series and other artificial intelligence (AI) technologies like Large Language Model Meta AI (LLaMA) and the T5 model. It analyzes the structure and functions of these models in detail, comparing their effectiveness in generating motion videos. Various techniques like root mean square normalization (RMSNorm) and absolute encoding were employed to identify the best method for text-to-motion conversion. The findings indicate that the T5 model generates actions based on textual descriptions, especially in presenting critical motions and avoiding unnecessary movements, offering valuable insights for future advancements in motion generation technology. [ABSTRACT FROM AUTHOR]

Mounting evidence suggests that ferroptosis is not just a consequence but also a fundamental contributor to the development and progression of Parkinson’s disease (PD). Ferroptosis is characterized as iron-dependent regulated cell death caused by excessive lipid peroxidation, leading to plasma membrane rupture, release of damage-associated molecular patterns, and neuroinflammation. Due to the crucial role of intracellular iron in mediating the production of reactive oxygen species and the formation of lipid peroxides, ferroptosis is intimately controlled by regulators involved in many aspects of iron metabolism, including iron uptake, storage and export, and by pathways constituting the antioxidant systems. Translational and transcriptional regulation of iron homeostasis and redox status provide an integrated network to determine the sensitivity of ferroptosis. We herein review recent advances related to ferroptosis, ranging from fundamental mechanistic discoveries and cutting-edge preclinical animal studies, to clinical trials in PD and the regulation of neuroinflammation via ferroptosis pathways. Elucidating the roles of ferroptosis in the survival of dopaminergic neurons and microglial activity can enhance our understanding of the pathogenesis of PD and provide opportunities for the development of novel prevention and treatment strategies.

Treatment of pancreatic cancer by inhibiting the aberrant activation of the survival signaling pathways has received considerable attention. We investigated the probable action of DHA on the suppression of cell proliferation in human pancreatic ductal adenocarcinoma (PDAC) cells. Our results demonstrated that DHA dose-dependently inhibited cell proliferation through an induction of cell cycle arrest in human PDAC cells. DHA suppressed the expression of phosphorylated-Rb (p-Rb), cyclin D1, cyclin E, cyclin A, E2F1 and c-Myc proteins. Blocking the activation of STAT3 signaling pathway led to an inactivation of CAMKII and increased phosphorylation of c-Myc (T58) protein accompanied with decreased expression of c-Myc protein. Treatment of DHA effectively inhibited cell survival through decreased phosphorylation levels of EGFR, STAT3 and CAMKII proteins. The mechanisms of action were associated with increased phosphorylation levels of c-Myc (T58) and instability of c-Myc proteins. DHA inhibited cell survival through an increased GSSG/GSH ratio and oxidative stress level in HPAF-II cells. DHA induced cell apoptosis through increased expression of Bax, c-caspase 3 and c-PARP proteins in HPAF-II cells. Moreover, treatment of DHA significantly inhibited nucleotide synthesis. In conclusion, DHA might significantly suppress the proliferation of PDAC cells and therefore have potential as an anti-cancer therapeutic agent.

E3 ubiquitin-linked enzyme MARCH5, also known as membrane-associated circular finger 5, is an enzyme encoded by the human MARCH5 gene. The main objective of this study was to visualize the prognosis of MARCH5 in breast cancer and to determine the relationship between MARCH5 expression and tumor immunity. MARCH5 expression was significantly higher in several cancers, including breast cancer (BRCA), compared with corresponding normal tissues. Not only was high MARCH5 expression associated with poorer overall survival, but also MARCH5 expression was positively correlated with the number of tumor-infiltrating immune cells in BRCA malignant tissues. Furthermore, MARCH5 expression showed a strong correlation with various immune markers of BRCA, suggesting its role in regulating tumor immunity. MARCH5 is a useful prognostic biomarker in several cancers, and its expression is highly correlated with tumor immune cell infiltration, and increased MARCH5 expression may serve as a new biomarker for BRCA diagnosis and prognosis.