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In this study, we proposed a three-dimensional (3D) printed porous (termed as 3DPP) scaffold composed of bioceramic (beta-tricalcium phosphate (β-TCP)) and thermoreversible biopolymer (pluronic F-127 (PF127)) that may provide bone tissue ingrowth and loading support for bone defect treatment. The investigated scaffolds were printed in three different ranges of pore sizes for comparison (3DPP-1: 150–200 μm, 3DPP-2: 250–300 μm, and 3DPP-3: 300–350 μm). The material properties and biocompatibility of the 3DPP scaffolds were characterized using scanning electron microscopy, X-ray diffractometry, contact angle goniometry, compression testing, and cell viability assay. In addition, micro-computed tomography was applied to investigate bone regeneration behavior of the 3DPP scaffolds in the mini-pig model. Analytical results showed that the 3DPP scaffolds exhibited well-defined porosity, excellent microstructural interconnectivity, and acceptable wettability (θ < 90°). Among all groups, the 3DPP-1 possessed a significantly highest compressive force 273 ± 20.8 Kgf (* p < 0.05). In vitro experiment results also revealed good cell viability and cell attachment behavior in all 3DPP scaffolds. Furthermore, the 3DPP-3 scaffold showed a significantly higher percentage of bone formation volume than the 3DPP-1 scaffold at week 8 (* p < 0.05) and week 12 (* p < 0.05). Hence, the 3DPP scaffold composed of β-TCP and F-127 is a promising candidate to promote bone tissue ingrowth into the porous scaffold with decent biocompatibility. This scaffold particularly fabricated with a pore size of around 350 μm (i.e., 3DPP-3 scaffold) can provide proper loading support and promote bone regeneration in bone defects when applied in dental and orthopedic fields.

Lupus nephritis (LN) is a common manifestation of systemic lupus erythematosus (SLE), affecting about half of the patients. This research uses genotype–phenotype associations to identify genetic markers, enhancing our understanding of LN pathogenesis. This study used genotype–phenotype association to explore genetic variants linked to LN in a Taiwanese cohort from the Taiwan Precision Medicine Initiative (TPMI). Genotyping was performed on 244 SLE and 63 LN patients using the TPM array. Genomic DNA underwent quality control via the Axiom Analysis Suite. Chi-squared tests identified significant variants, which were annotated and assessed for functional impacts using the 1000 Genomes Project, gnomAD, enabling comprehensive genetic analysis. This study on a Taiwanese cohort (LN, SLE, LN/SLE) identified four significant genetic variants (p-values < 10 −6 ) associated with LN: rs1025129 in HGF, rs80282109 in BACH2, rs516119 in SOX1, and rs134545 in TTC28. These variants may affect LN pathogenesis through splicing junction changes and gene expression regulation, highlighting their potential as biomarkers. Our research identified four novel variants (rs134545, rs516119, rs1025129, rs80282109) in LN patients through a genotype–phenotype study on a Taiwanese population, suggesting their roles in LN pathogenesis and supporting their potential as new disease biomarkers.

BackgroundConsidering the involvement of genetics in migraine pathogenesis in diverse ethnic populations, genome-wide association studies (GWAS) are being conducted to identify migraine-susceptibility genes. However, limited surveys have focused on the onset age of migraine (AoM) in Asians. Therefore, in this study, we aimed to identify the susceptibility loci of migraine considering the AoM in an Asian population.MethodsWe conducted a GWAS in 715 patients with migraine of Han Chinese ethnicity, residing in Taiwan, to identify the susceptibility genes associated with AoM. Based on our standard demographic questionnaire, the population was grouped into different subsets. Single-nucleotide polymorphism (SNP) associations were examined using PLINK in different AoM onset groups.ResultsWe discovered eight novel susceptibility loci correlated with AoM that reached the GWAS significance level in the Han Chinese population. First, rs146094041 in ESRRG was associated with AoM ≤ 12 years. The other SNPs including rs77630941 in CUX1, rs146778855 in CDH18, rs117608715 in NOL3, rs150592309 in PRAP1, and rs181024055 in NRAP were associated with the later AoM.ConclusionsTo our knowledge, this is the first GWAS to investigate the AoM in an Asian Han Chinese population. Our newly discovered susceptibility genes may have prospective associations with migraine pathogenesis.

In Taiwan, light motorcycles (LMCs) with cylinder capacities between 50 and 250 cc are widely used for daily commute. These vehicles are operated in a mixed traffic environment and prohibited on highways. In light of increasing motorcycle casualties, we conducted a multicentre study to analyse rider factors affecting injury severity. Riders hospitalised upon LMC crashes were contacted. Information on demographics, comorbidities, and riding behaviours was collected through questionnaires and linked to hospital data. The injury severity score (ISS) and length of hospitalisation (LOH) were used as injury severity measures. In total, 725 patients (mean age: 37.7 years; 64% men) completed their questionnaires. Multivariate analysis results showed that age ≥ 65 years, half-face helmets, protective clothing, collisions with a bus/truck or car, and fatigue riding were risk factors for having an ISS of ≥9. Age ≥ 65 years; motorcycle crashes ≥2 times in the previous year; anaemia; rural crashes; half-face helmets; protective boots; collisions with a bus/truck, car, or a stationary object; alcohol/stimulating refreshment consumption; and fatigue riding were risk factors for increased LOH. A protective factor was individuals working in commerce. Collisions with opening car doors caused low risks of having an ISS of ≥9 and a short LOH. Certain factors were significantly associated with riders' injury severity and related medical resource consumption. Because of differences in the power output, use, and riding environment, risk factors for severe injuries in LMC crashes are dissimilar from those for heavy motorcycles (cylinder capacities > 250 cc) in developed countries and deserve more attention for injury prevention. Further in-depth evaluation of significant factors based on this study's results can yield valuable information to reduce severe injuries after LMC crashes in countries and areas with a high dependency on motorcycles, even considering the popularity of electric motorcycles.

Background and Objectives: In recent years, bipolar disorder (BD), a multifaceted mood disorder marked by severe episodic mood fluctuations, has been shown to have an impact on disability-adjusted life years (DALYs). The increasing prevalence of BD highlights the need for better diagnostic tools, particularly those involving genetic insights. Genetic association studies can play a crucial role in identifying variations linked to BD, shedding light on its genetic underpinnings and potential therapeutic targets. This study aimed to identify novel genetic variants associated with BD in the Taiwanese Han population and to elucidate their potential roles in disease pathogenesis. Materials and Methods: Genotyping was conducted using the Taiwan Precision Medicine Array (TPM Array) on 128 BD patients and 26,122 control subjects. Following quality control, 280,177 single nucleotide polymorphisms (SNPs) were analyzed via chi-square tests, and linkage disequilibrium (LD) analyses were employed to examine the associations among key SNPs. Results: Eleven SNPs reached significance (p < 10−5), with the variant rs11156606 in the ABCD1 gene—implicated in fatty acid metabolism—emerging as a prominent finding. LD analysis revealed that rs11156606 is strongly linked with rs73640819, located in the 3′ untranslated region, suggesting a regulatory role in gene expression. Additionally, rs3829533 in the MTHFSD gene was found to be in strong LD with the missense variants rs3751800 and rs3751801, indicating potential alterations in protein function. Conclusion: These findings enhance the genetic understanding of BD within a Taiwanese cohort by identifying novel risk-associated variants and support the potential for using these markers in early diagnosis and targeted therapeutic strategies.

Background and Objectives: Genomic studies have identified several SNP loci associated with schizophrenia in East Asian populations. Environmental factors, particularly urbanization, play a significant role in schizophrenia development. This study aimed to identify schizophrenia susceptibility loci and characterize their biological functions and molecular pathways in Taiwanese urban Han individuals. Materials and Methods: Participants with schizophrenia were recruited from the Taiwan Precision Medicine Initiative at Tri-Service General Hospital. Genotype–phenotype association analysis was performed, with significant variants annotated and analyzed for functional relevance. Results: A total of 137 schizophrenia patients and 26,129 controls were enrolled. Ten significant variants (p < 1 × 10−5) and 15 expressed genes were identified, including rs1010840 (SOWAHC and RGPD6), rs11083963 (TRPM4), rs11619878 (LINC00355 and LINC01052), rs117010638 (AGBL1 and MIR548AP), rs1170702 (LINC01680 and LINC01720), rs12028521 (KAZN and PRDM2), rs12859097 (DMD), rs1556812 (ATP11A), rs78144262 (LINC00977), and rs9997349 (ENPEP). These variants and associated genes are involved in immune response, blood pressure regulation, muscle function, and the cytoskeleton. Conclusions: Identified variants and associated genes suggest a potential genetic predisposition to schizophrenia in the Taiwanese urban Han population, highlighting the importance of potential comorbidities, considering population-specific genetic and environmental interactions.

The present study was to investigate the rheological property, printability, and cell viability of alginate–gelatin composed hydrogels as a potential cell-laden bioink for three-dimensional (3D) bioprinting applications. The 2 g of sodium alginate dissolved in 50 mL of phosphate buffered saline solution was mixed with different concentrations (1% (0.5 g), 2% (1 g), 3% (1.5 g), and 4% (2 g)) of gelatin, denoted as GBH-1, GBH-2, GBH-3, and GBH-4, respectively. The properties of the investigated hydrogels were characterized by contact angle goniometer, rheometer, and bioprinter. In addition, the hydrogel with a proper concentration was adopted as a cell-laden bioink to conduct cell viability testing (before and after bioprinting) using Live/Dead assay and immunofluorescence staining with a human corneal fibroblast cell line. The analytical results indicated that the GBH-2 hydrogel exhibited the lowest loss rate of contact angle (28%) and similar rheological performance as compared with other investigated hydrogels and the control group. Printability results also showed that the average wire diameter of the GBH-2 bioink (0.84 ± 0.02 mm (*** p < 0.001)) post-printing was similar to that of the control group (0.79 ± 0.05 mm). Moreover, a cell scaffold could be fabricated from the GBH-2 bioink and retained its shape integrity for 24 h post-printing. For bioprinting evaluation, it demonstrated that the GBH-2 bioink possessed well viability (>70%) of the human corneal fibroblast cell after seven days of printing under an ideal printing parameter combination (0.4 mm of inner diameter needle, 0.8 bar of printing pressure, and 25 °C of printing temperature). Therefore, the present study suggests that the GBH-2 hydrogel could be developed as a potential cell-laden bioink to print a cell scaffold with biocompatibility and structural integrity for soft tissues such as skin, cornea, nerve, and blood vessel regeneration applications.

Background/Objectives: Emerging infectious diseases pose significant global threats due to their rapid transmission, limited therapeutic options, and profound socioeconomic impact. Conventional diagnostic techniques that rely on sequencing and polymerase chain reactions (PCR) frequently lack the speed necessary to efficiently respond to rapidly evolving pathogens. This study describes the development of BioInnovate AI to overcome these limitations using machine learning to expedite PCR assay development. Methods: The ability of BioInnovate AI to predict optimal PCR reagents across multiple pathogens was assessed. Additionally, random forest classifier, light gradient boosting machine (LGBM), and gradient boosting classifier models were evaluated for their ability to predict effective PCR primer–probe combinations. Performance metrics, including the area under the curve (AUC), sensitivity, specificity, accuracy, and F1 score, were assessed to identify the optimal model for platform integration. Results: All machine learning models performed well, with the LGBM model achieving the highest metrics (AUC: 0.97, sensitivity: 0.93, specificity: 0.91). BioInnovate AI significantly reduced PCR assay development time by approximately 90%, enabling rapid design and reagent optimization for multiple pathogens. Conclusions: BioInnovate AI provides a rapid, accurate, and efficient method for PCR reagent design, significantly enhancing global diagnostic preparedness by optimizing primers and probes for the timely detection of infectious diseases.

Histone deacetylase (HDAC) inhibitors have emerged as a new class of anti-tumor agents for various types of tumors, including glioblastoma. We found that a novel HDAC inhibitor, MPT0B291, significantly reduced the cell viability and increased cell death of human and rat glioma cell lines, but not in normal astrocytes. We also demonstrated that MPT0B291 suppressed proliferation by inducing G1 phase cell cycle arrest and increased apoptosis in human and rat glioma cell lines by flow cytometry and immunocytochemistry. We further investigated the anti-tumor effects of MPT0B291 in xenograft (mouse) and allograft (rat) models. The IVIS200 images and histological analysis indicated MPT0B291 (25 mg/kg, ) reduced tumor volume. Mechanistically, MPT0B291 increased phosphorylation and acetylation/activation of p53 and increased mRNA levels of the apoptosis related genes PUMA, Bax, and Apaf1 as well as increased protein level of PUMA, Apaf1 in C6 cell line. The expression of cell cycle related gene p21 was also increased and Cdk2, Cdk4 were decreased by MPT0B291. Our study highlights the anti-tumor efficacy of a novel compound MPT0B291 on glioma growth.

Fourteen-day rehospitalization with new traumatic spinal cord injury (tSCI) diagnosis is used as an indicator for the diagnostic quality of the first hospitalization. In this nationwide population-based cohort study, we identified risk factors for this indicator. We conducted a nested case-control study by using the data of patients who received a first hospitalization for trauma between 2001 and 2011. The data were retrieved from Taiwan's National Health Insurance Research Database. Variables including demographic and trauma characteristics were compared between patients diagnosed with tSCI at the first hospitalization and those receiving a 14-day rehospitalization with new tSCI diagnosis. Of the 23 617 tSCI patients, 997 had 14-day rehospitalization with new tSCI diagnosis (incidence rate, 4.22%). The risk of 14-day rehospitalization with new tSCI diagnosis was significantly lower in patients with severe (injury severity score [ISS] = 16-24; odds ratio [OR], 0.17; 95% confidence interval [CI], 0.13-0.21) and profound (ISS > 24; OR, 0.11; 95% CI, 0.07-0.18) injuries. Interhospital transfer (OR, 8.20; 95% CI, 6.48-10.38) was a significant risk factor, along with injuries at the thoracic (OR, 1.62; 95% CI, 1.21-2.18), lumbar (OR, 1.30; 95% CI, 1.02-1.65), and multiple (OR, 3.23; 95% CI, 1.86-5.61) levels. Brain (OR, 2.82), chest (OR, 2.99), and abdominal (OR, 2.74) injuries were also identified as risk factors. In addition, the risk was higher in patients treated at the orthopedic department (OR, 2.26; 95% CI, 1.78-2.87) and those of other surgical disciplines (OR, 1.89; 95% CI, 1.57-2.28) than in those treated at the neurosurgery department. Delayed tSCI diagnoses are not uncommon, particularly among trauma patients with ISSs < 16 or those who are transferred from lower-level hospitals. Further validation and implementation of evidence-based decision rules is essential for improving the diagnostic quality of traumatic thoracolumbar SCI.