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Abstract Background Benign prostatic hyperplasia (BPH) is a prevalent condition in aging males, leading to bladder outlet obstruction (BOO) and associated urinary symptoms. With increasing life expectancy, the incidence of BPH and its co-morbidities, like inguinal hernia, has risen. This study explores the efficacy of combining transurethral resection of the prostate (TURP) and inguinal hernioplasty in a single surgical session to address both conditions, potentially reducing the need for multiple hospitalizations and surgical interventions. Methods This retrospective study at Chi Mei Medical Center included patients from 2014 to 2023 who underwent concurrent TURP and inguinal hernioplasty. A total of 85 patients met the criteria defined for this study. Preoperative, intraoperative, and postoperative characteristics were meticulously documented. Outcomes evaluated included the duration of the surgery, incidence of intraoperative and postoperative complications, duration of Foley catheterization, length of hospital stay, and treatment efficacy. Additionally, we conducted a comparative assessment of the surgical outcomes between two distinct techniques for inguinal hernia repair: open hernioplasty and laparoscopic hernioplasty (LH). Results In 85 patients who met the criteria, the mean age was 71.1 ± 7.8 years. The study reported no significant intraoperative complications, and postoperative care was focused on monitoring for blood loss, infection, and managing pain. The average postoperative hospital stay was 2.9 ± 1.0 days and the mean duration of catheterization was 51.6 ± 16.7 h, with a minimal complication rate observed during the one-year follow-up. A significant reduction in both operative duration and catheterization interval was observed in patients undergoing LH as opposed to those receiving open hernioplasty. Conclusion Concurrent TURP and inguinal hernioplasty effectively manage BOO due to BPH and inguinal hernias with minimal complications, suggesting a viable approach to reducing hospital stays and surgical interventions. Laparoscopic techniques, in particular, offer benefits in operative efficiency and recovery time, making combined surgery a feasible option for selected patients.

PurposeThis study investigates the complex relationship between body mass index (BMI) and bladder cancer outcomes, utilizing Taiwan’s national database. Bladder cancer remains a significant health concern, especially in Taiwan, prompting a comprehensive retrospective analysis to explore the impact of obesity on survival outcomes.Materials and methodsA meticulous exclusion process, based on Taiwan National Health Insurance System Database, refined the initial dataset of 15,086 bladder cancer patients to 10,352. Categorizing patients into BMI groups (underweight, normal weight, and obesity), the study examined baseline characteristics, comorbidities, and survival outcomes. The analysis involved Cox regression and subgroup assessments stratified by clinical stage.ResultsAmong our patients, 71.5% are male, 78.5% are over 60 years of age, and 18.8% are between 45 and 60 years old. Despite a higher prevalence of comorbidities, obesity patients exhibited a more favorable prognosis, supporting the obesity paradox. The overall and specific mortality ratio of obesity patients were 0.76 fold and 0.82-fold compared with normal-weight patients (overall: 95% confidence interval [CI], 0.71–0.82, p

Transarterial chemoembolisation (TACE) is used for unresectable hepatocellular carcinoma (HCC) treatment, but TACE-induced hypoxia leads to poor prognosis. The anti-cancer effects of soybean isoflavones daidzein derivatives 7,3′,4′-trihydroxyisoflavone (734THIF) and 7,8,4′-trihydroxyisoflavone (784THIF) were evaluated under hypoxic microenvironments. Molecular docking of these isomers with cyclooxygenase-2 (COX-2) and vascular endothelial growth factor receptor 2 (VEGFR2) was assessed. About 40 μM of 734THIF and 784THIF have the best effect on inhibiting the proliferation of HepG2 cells under hypoxic conditions. At a concentration of 40 μM, 784THIF significantly inhibits COX-2 expression in pre-hypoxia conditions compared to 734THIF, with an inhibition rate of 67.73%. Additionally, 40 μM 784THIF downregulates the expression of hypoxic, inflammatory, and metastatic-related proteins, regulates oxidative stress, and inhibits the expression of anti-apoptotic proteins. The uptake by HepG2 confirmed higher 784THIF level and slower degradation characteristics under post- or pre-hypoxic conditions. In conclusion, our results showed that 784THIF had better anti-cancer effects and cellular uptake than 734THIF.

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Abstract Cholangiocarcinoma is the most common malignant bile duct tumor in Southeast Asia. The special location of cholangiocarcinoma leads to it being difficult to diagnose. Currently, the progress in clinical prognosis outcomes remains abysmal owing to the lack of definitive diagnostic criteria. Therefore, uncovering the potential markers for cholangiocarcinoma is a pressing issue. Ubiquitin-conjugating enzyme E2 C (UBE2C) is a critical ubiquitination enzyme; it is involved in the tumorigenesis of various malignancies and affects the patient’s prognosis. However, there is currently no relevant literature to indicate whether UBE2C is related to the clinical survival outcome of cholangiocarcinoma patients. In this report, we mined the published cholangiocarcinoma transcriptome data set (GSE26566), compared it with the ubiquitination-associated gene (GO:0016567), and identified that UBE2C was highly expressed in cholangiocarcinoma tumor tissue. Moreover, high expression of UBE2C was markedly correlated with surgical margin, primary tumor, histological variants, and histological grade. More specifically, high expression of UBE2C was negatively associated with overall survival, disease-specific survival, local recurrence-free survival, and metastasis-free survival in patients with cholangiocarcinoma. Our findings demonstrate that UBE2C may provide a potential therapeutic marker and prognostic factor for cholangiocarcinoma patients.

Abstract Cartilage oligomeric matrix protein (COMP) interacts with various extracellular matrix proteins in tissues. Elevated COMP levels recently linked to worse overall survival in multiple cancer types. COMP's significance in intrahepatic cholangiocarcinoma (iCCA) remains uncertain. Here we report a retrospective study to explore COMP's impact on iCCA outcomes. We collected 182 patients' iCCA tumor tissues. COMP overexpression was associated with adverse factors like R1 resection (p = 0.008), advanced T stage (p

Background/Objective: This study aims to utilize advanced artificial intelligence (AI) image recog-nition technologies to establish a robust system for identifying features in lung computed tomog-raphy (CT) scans, thereby detecting respiratory infections such as SARS-CoV-2 pneumonia. Spe-cifically, the research focuses on developing a new model called Residual-Dense-Attention Gates U-Net (RDAG U-Net) to improve accuracy and efficiency in identification. Methods: This study employed Attention U-Net, Attention Res U-Net, and the newly developed RDAG U-Net model. RDAG U-Net extends the U-Net architecture by incorporating ResBlock and DenseBlock modules in the encoder to retain training parameters and reduce computation time. The training dataset in-cludes 3,520 CT scans from an open database, augmented to 10,560 samples through data en-hancement techniques. The research also focused on optimizing convolutional architectures, image preprocessing, interpolation methods, data management, and extensive fine-tuning of training parameters and neural network modules. Result: The RDAG U-Net model achieved an outstanding accuracy of 93.29% in identifying pulmonary lesions, with a 45% reduction in computation time compared to other models. The study demonstrated that RDAG U-Net performed stably during training and exhibited good generalization capability by evaluating loss values, model-predicted lesion annotations, and validation-epoch curves. Furthermore, using ITK-Snap to convert 2D pre-dictions into 3D lung and lesion segmentation models, the results delineated lesion contours, en-hancing interpretability. Conclusion: The RDAG U-Net model showed significant improvements in accuracy and efficiency in the analysis of CT images for SARS-CoV-2 pneumonia, achieving a 93.29% recognition accuracy and reducing computation time by 45% compared to other models. These results indicate the potential of the RDAG U-Net model in clinical applications, as it can accelerate the detection of pulmonary lesions and effectively enhance diagnostic accuracy. Additionally, the 2D and 3D visualization results allow physicians to understand lesions' morphology and distribution better, strengthening decision support capabilities and providing valuable medical diagnosis and treatment planning tools.

This study proposes a bile duct stent based on indirect 3D printing technology. Four ratio materials were synthesized from lactic acid (LA) and glycolide (GA) monomers by melt polymerization: PLA, PLGA (70:30), PLGA (50:50), and PLGA (30:70). The four kinds of material powders were preliminarily degraded, and the appearance was observed with an optical microscope (OM) and a camera. The weight and appearance of the four materials changed significantly after four weeks of degradation, which met the conditions for materials to be degraded within 4–6 weeks. Among them, PLGA (50:50) lost the most—the weight dropped to 13.4%. A stent with an outer diameter of 10 mm and an inner diameter of 8 mm was successfully manufactured by indirect 3D printing technology, demonstrating the potential of our research. Then, the degradation experiment was carried out on a cylindrical stent with a diameter of 6 mm and a height of 3 mm. The weight loss of the sample was less than that of the powder degradation, and the weight loss of PLGA (50:50) was the largest—the weight dropped to 79.6%. The nano-indenter system measured the mechanical properties of materials. Finally, human liver cancer cells Hep-3B were used to conduct in vitro cytotoxicity tests on the scaffolds to test the biocompatibility of the materials. A bile duct stent meeting commercial size requirements has been developed, instilling confidence in the potential of our research for future medical applications.

Abstract Background With the advance in genome-wide analyses, genetic alternations have been found to play an important role in carcinogenesis and aggressiveness of UC. Through bioinformatic analysis of gene expression profiles of urinary bladder urothelial carcinoma (UBUC) from publicly available GEO dataset (GSE31684), Zinc finger and SCAN domain containing 4 (ZSCAN4) was identified as a significant downregulated gene in muscle-invasive bladder cancer when compared with non-muscle-invasive bladder cancer. Methods The expression of ZSCAN4 was evaluated by immunohistochemistry in 340 upper urinary tract urothelial carcinomas (UTUCs) and 295 UBUCs. The expression profiles of ZSCAN4 and potential signaling pathways were analyzed bioinformatically. Results In UTUC, low expression of ZSCAN4 was significantly associated with advanced primary pT stage (P = 0.011), increased nodal metastasis (P = 0.002) and increased vascular invasion (P = 0.019). In UBUC, low expression of ZSCAN4 was significantly correlated with advanced primary pT stage (P

Objectives: Inadequate treatment of scrub typhus results in severe complications such as septic shock and is also associated with a high median mortality rate of 6%. However, there has been no conclusive evidence about the superiority of different antibiotics in managing scrub typhus in terms of efficacy and tolerability. Methods: We conducted a network meta-analysis (NMA) using the frequentist method. The included participants were pediatric and adult patients infected with scrub typhus. The primary outcome was the cure rate in the patients included. The subgroup analysis was done according to pediatric or adult patients. Results: Overall, 14 randomized controlled trials (RCTs) with 1264 participants were included in this study. The NMA revealed that all the investigated antibiotics were associated with cure rates similar to those of doxycycline. The chloramphenicol and minocycline were ranked to be associated with the highest cure rate in the pediatric subgroup and adult subgroup, respectively. Second-generation quinolones, including ofloxacin, ciprofloxacin, and chloramphenicol, were associated with significantly lower adverse event rates than doxycycline. Conclusion: The current updated NMA provides evidence for the efficacy of chloramphenicol and minocycline in scrub typhus management. However, future large-scale RCTs with longer follow-up times are warranted.

This study proposed a composite tibia defect scaffold with radial gradient porosity, utilizing finite element analysis to assess stress in the tibial region with significant critical-sized defects. Simulations for scaffolds with different porosities were conducted, designing an optimal tibia defect scaffold with radial gradient porosity for repairing and replacing critical bone defects. Radial gradient porosity scaffolds resulted in a more uniform stress distribution, reducing titanium alloy stiffness and alleviating stress shielding effects. The scaffold was manufactured using selective laser melting (SLM) technology with stress relief annealing to simplify porous structure fabrication. The study used New Zealand white rabbits’ tibia defect sites as simulation parameters, reconstructing the 3D model and implanting the composite scaffold. Finite element analysis in ANSYS-Workbench simulated forces under high-activity conditions, analyzing stress distribution and strain. In the simulation, the titanium alloy scaffold bore a maximum stress of 122.8626 MPa, while the centrally encapsulated HAp material delivered 27.92 MPa. The design demonstrated superior structural strength, thereby reducing stress concentration. The scaffold was manufactured using SLM, and the uniform design method was used to determine a collection of optimum annealing parameters. Nanoindentation and compression tests were used to determine the influence of annealing on the elastic modulus, hardness, and strain energy of the scaffold.

The challenges of respiratory infections persist as a global health crisis, placing substantial stress on healthcare infrastructures and necessitating ongoing investigation into efficacious treatment modalities. The persistent challenge of respiratory infections, including COVID-19, underscores the critical need for enhanced diagnostic methodologies to support early treatment interventions. This study introduces an innovative two-stage data analytics framework that leverages deep learning algorithms through a strategic combinatorial fusion technique, aimed at refining the accuracy of early-stage diagnosis of such infections. Utilizing a comprehensive dataset compiled from publicly available lung X-ray images, the research employs advanced pre-trained deep learning models to navigate the complexities of disease classification, addressing inherent data imbalances through methodical validation processes. The core contribution of this work lies in its novel application of combinatorial fusion, integrating select models to significantly elevate diagnostic precision. This approach not only showcases the adaptability and strength of deep learning in navigating the intricacies of medical imaging but also marks a significant step forward in the utilization of artificial intelligence to improve outcomes in healthcare diagnostics. The study’s findings illuminate the path toward leveraging technological advancements in enhancing diagnostic accuracies, ultimately contributing to the timely and effective treatment of respiratory diseases.

Purpose: Young age is associated with poor prognosis in ductal carcinoma in situ (DCIS) of female breast and controversy exists regarding the optimal treatment modality for young patients. We aimed to compare treatment outcomes among breast conserving surgery (BCS), BCS with adjuvant radiotherapy (BCS + RT), and total mastectomy (MT) for young DCIS women. Methods: PubMed, Cochrane, and Embase were searched for studies reporting comparative results among BCS, BCS + RT, or MT in ≤50 years old (y/o) DCIS females. Study quality was assessed and meta-analysis with subgroup analysis was performed to pool the effect sizes of the outcomes-of-interest. Results: We included 3 randomized control trials and 18 observational studies. For DCIS women ≤50 y/o, RT following BCS significantly reduced the risk for ipsilateral breast tumor recurrence (IBTR) (HR = 0.66, 95% CI 0.50–0.87). However, the benefit was less robust in extremely young patients and with long follow-ups. RT revealed no statistically significant preventive effect on ipsilateral invasive recurrence (HR = 1.38, 95% CI 0.98–1.94). On the other hand, MT yielded the lowest IBTR (BCS + RT vs MT: HR = 4.4, 95% CI 2.06–9.40), both in ipsilateral DCIS recurrence and ipsilateral invasive recurrence. There was great heterogeneity and could not reach an evident conclusion concerning survival outcomes. Conclusion: This study highlighted the varying effect of RT for young DCIS females. The local control benefit of MT was definite without survival differences observed. Our study provided a moderate certainty of evidence to guide the treatment for young DCIS women. Further age-specific prospective trial is warranted.

The global incidence of early-onset colorectal cancer (EO-CRC) is increasing. Although the mortality rate is relatively stable, some comorbidities have been associated with a higher mortality rate. This study estimated the mortality risk in patients with EO-CRC with various comorbidities using real-world data to identify the high-risk group using Cox proportional regression for overall and cancer-specific mortality. The incidence rate of EO-CRC significantly increased from 6.04 per 100,000 population in 2007 to 12.97 per 100,000 population in 2017. The five-year overall mortality rate was 101.50 per 1000 person year and the cancer-specific mortality rate was 94.12 per 1000 person year. Patients with cerebrovascular disease (CVD) had a higher mortality risk (hazard ratio (HR): 1.68; 95% confidence interval (CI): 1.25-2.28; p=0.0007). After subgroup analyses based on age, sex, clinical stage, and treatment type, patients with CVD had a higher overall mortality risk compared to non-CVD patients, except for patients undergoing surgery and chemotherapy. Patients with chronic kidney disease had a higher mortality risk in the early clinical stages (HR: 2.31; 95% CI: 1.08-4.96; p=0.0138). Patients who underwent radiotherapy had a higher overall mortality risk (HR: 1.38; 95% CI: 1.04-1.85; p=0.0285) than those without liver disease. Identifying specific comorbidity mortality risks in patients with EO-CRC allows for risk stratification when screening target groups and may lower disease mortality.

Abstract Background Current pharmacologic prophylactic strategies for migraine have exhibited limited efficacy, with response rates as low as 40%–50%. In addition to the limited efficacy, the acceptability of those pharmacologic prophylactic strategies were unacceptable. Although noninvasive brain/nerve stimulation strategies may be effective, the evidence has been inconsistent. The aim of this network meta-analysis (NMA) was to compare strategies of noninvasive brain/nerve stimulation for migraine prophylaxis with respect to their effectiveness and acceptability. Methods The PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov , ClinicalKey, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov databases were systematically searched to date of June 4th, 2021 for randomized controlled trials (RCTs). Patients with diagnosis of migraine, either episodic migraine or chronic migraine, were included. All NMA procedures were conducted under the frequentist model. Results Nineteen RCTs were included (N = 1493; mean age = 38.2 years; 82.0% women). We determined that the high frequency repetitive transcranial magnetic stimulation (rTMS) over C3 yielded the most decreased monthly migraine days among all the interventions [mean difference = − 8.70 days, 95% confidence intervals (95%CIs): − 14.45 to − 2.95 compared to sham/control groups]. Only alternating frequency (2/100 Hz) transcutaneous occipital nerve stimulation (tONS) over the Oz (RR = 0.36, 95%CIs: 0.16 to 0.82) yielded a significantly lower drop-out rate than the sham/control groups did. Conclusions The current study provided a new direction for the design of more methodologically robust and larger RCTs based on the findings of the potentially beneficial effect on migraine prophylaxis in participants with migraine by different noninvasive brain/nerve stimulation, especially the application of rTMS and tONS. Trial registration CRD42021252638. The current study had been approval by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center (TSGHIRB No. B-109-29).

Urothelial carcinoma (UC), which includes urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC), is one of the most common malignancies worldwide. Accordingly, a comprehensive understanding of the underlying mechanism governing UC development is compulsory. Aberrant CCAAT/enhancer-binding protein delta (CEBPD), a transcription factor, displays an oncogene or tumor suppressor depending on tumor type and microenvironments. However, CEBPD has been reported to possess a clear oncogenic function in UC through multiple regulation pathways. Genomic amplification of CEBPD triggered by MYC-driven genome instability is frequently examined in UC that drives CEBPD overexpression. Upregulated CEBPD transcriptionally suppresses FBXW7 to stabilize MYC protein and further induces hexokinase II (HK2)-related aerobic glycolysis that fuels cell growth. Apart from the MYC-dependent pathway, CEBPD also downregulates the level of hsa-miR-429 to enhance HK2-associated glycolysis and induce angiogenesis driven by vascular endothelial growth factor A (VEGFA). Additionally, aggressive UC is attributed to the tumor metastasis regulated by CEBPD-induced matrix metalloproteinase-2 (MMP2) overexpression. Furthermore, elevated CEBPD induced by cisplatin (CDDP) is identified to have dual functions, namely, CDDP-induced chemotherapy resistance or drive CDDP-induced antitumorigenesis. Given that the role of CEBPD in UC is getting clear but pending a more systemic reappraisal, this review aimed to comprehensively discuss the underlying mechanism of CEBPD in UC tumorigenesis.

Introduction: With the evolution of radiotherapy techniques and a better understanding of clinicopathological factors, we aimed to evaluate the treatment effect of post-operative radiotherapy (PORT) and associated predictive factors in patients with completely resected pN2 stage III non-small cell lung cancer (R0 pN2-stage III NSCLC). Material and Method: The cancer registration database of a single medical center was searched for R0 pN2-stage III NSCLC. Clinicopathological factors and information about post-operative therapies, including PORT and adjuvant systemic treatment, were retrospectively collected and analyzed. The Kaplan-Meier method and a Cox regression model were applied for time-to-event analysis, with disease-free survival (DFS) being the primary outcome. Results: From 2010 to 2021, 82 R0 pN2-stage III NSCLC patients were evaluated, with 70.1% of tumors harboring epidermal growth factor receptor mutations (EGFR mut.). PORT was performed in 73.2% of cases, and the median dose was 54 Gy. After a median follow-up of 42 months, the 3-year DFS and overall survival (OS) rates were 40.6% and 77.3%, respectively. Distant metastasis (DM) was the main failure pattern. In the overall cohort, DFS was improved with PORT (3-year DFS: 44.9% vs. 29.8%; HR: 0.552, p = 0.045). Positive predictive factors for PORT benefit, including EGFR mut., negative extranodal extension, positive lymphovascular invasion, 1–3 positive lymph nodes, and a positive-to-dissected lymph node ratio ≤0.22, were recognized. OS improvement was also observed in subgroups with less lymph node burden. Conclusions: For R0 pN2-stage III NSCLC, PORT prolongs DFS and OS in selected patients. Further studies on predictive factors and the development of nomograms guiding the application of PORT are highly warranted, aiming to enhance the personalization of lung cancer treatment.

Intrahepatic cholangiocarcinoma (IHCC) is the second most common malignant neoplasm of the liver. In spite of the increasing incidence worldwide, it is relatively rare in Western countries. IHCC is relatively common in Eastern and Southeastern Asia. Patients with IHCC are usually diagnosed at an advanced stage, therefore, the clinical outcome is dismal. Dysregulation of urea cycle metabolic enzyme expression is found in different types of cancers. Nevertheless, a comprehensive evaluation of genes related to the urea cycle (i.e., GO:0000050) has not been conducted in IHCC. By performing a comparative analysis of gene expression profiles, we specifically examined genes associated with the urea cycle (GO:0000050) in a publicly accessible transcriptomic dataset (GSE26566). Interestingly, CPS1 was identified as the second most prominently down-regulated gene in this context. Tumor tissues of 182 IHCC patients who underwent curative-intent hepatectomy were enrolled. The expression level of CPS1 protein in our IHCC cohort was assessed by immunohistochemical study. Subsequent to that, statistical analyses were carried out to examine the expression of CPS1 in relation to various clinicopathological factors, as well as to assess its impact on survival outcomes. We noticed that lower immunoreactivity of CPS1 in IHCC was associated with tumor progression (pT status) with statistical significance (p = 0.003). CPS1 underexpression was not only negatively correlated to overall survival (OS), disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS) in univariate analysis but also an independent prognosticator to forecast poorer clinical outcome for all prognostic indices (OS, DSS, LRFS and MeFs) in patients with IHCC (all p ≤ 0.001). These results support that CPS1 may play a crucial role in IHCC oncogenesis and tumor progression and serve as a novel prognostic factor and a potential diagnostic and theranostic biomarker.

Background: Colorectal cancer is one of the leading cancers worldwide. This study aimed to investigate the mortality differences between 2 primary tumor locations, the proximal/distal colon and rectosigmoid junction (RSJ)/rectum, after adjusting for comorbidities. Methods: The Taiwan Cancer Registry linked with Taiwan’s National Health Insurance Research Database was used to estimate the 5-year mortality rate among patients with colorectal cancer. A total of 73 769 individuals were enrolled in the study, which included 44 234 patients with proximal and distal colon cancers and 29 535 patients with RSJ and rectal cancers. Potential mortality risk was calculated using Cox regression analysis. Results: The mortality rates due to the location of the cancer in the proximal/distal colon and RSJ/rectum were 45.27% and 42.20%, respectively. After adjustment for age, sex, comorbidities, and clinical stages, the proximal/distal colon had a 1.03-fold higher 5-year overall mortality rate than RSJ/rectal cancer (95% confidence interval = 1.00–1.05). Proximal and distal colon cancers had a worse prognosis and survival than RSJ and rectal colon cancers in women and older patients (⩾70 years). Comorbidities had different effects on mortality in the proximal/distal colon and RSJ/rectum. Conclusions: Tumor location is associated with the prognosis of patients with colorectal cancer. It is important to treat patients beyond their cancer treatment, and to manage their comorbidities.

Abstract Background The homologous recombination (HR) pathway is involved in DNA damage response (DDR), which is crucial to cancer cell survival after treatment with DNA damage agents. O6-methylguanine DNA methyltransferase (MGMT) is associated with cisplatin (CDDP) resistance in cancer cells; however, the underlying mechanisms remain unclear. Here, we explored the interactions between MGMT and the HR pathway in CDDP-activated DDR and their clinical implications in nasopharyngeal carcinoma (NPC). Methods Human NPC cells were assessed using loss-of-function approaches in vitro. The expression correlations between MGMT and major proteins of the HR pathway were analyzed through Western blotting, quantitative real-time PCR, and bioinformatic analysis by using a public database. The physical interactions between MGMT and HR proteins were studied using co-immunoprecipitation and immunofluorescence analyses. Cell comet tails and γ-H2AX expression levels were examined to evaluate double-strand break (DSB) formation. Established immunofluorescence and reporter analyses were conducted to measure HR activity. Xenograft and cell viability studies were used to assess the therapeutic potential of MGMT inhibition in combination with CDDP and poly(ADP-ribose) polymerase (PARP) inhibitor, respectively. Results Among major proteins of the HR pathway, MGMT suppression inhibited CDDP-induced RAD51 expression. Bioinformatic analyses showed a positive correlation between MGMT and RAD51 expression in patients with NPC. Moreover, MGMT physically interacted with BRCA1 and regulated CDDP-induced BRCA1 phosphorylation (ser 988). In functional assays, MGMT inhibition increased CDDP-induced DSB formation through attenuation of HR activity. NPC xenograft studies demonstrated that MGMT inhibition combined with CDDP treatment reduced tumor size and downregulated RAD51 expression and BRCA1 phosphorylation. Furthermore, MGMT suppression increased PARP inhibitor–induced cell death and DSB formation in NPC cells. Conclusion MGMT is crucial in the activation of the HR pathway and regulates DDR in NPC cells treated with CDDP and PARP inhibitor. Thus, MGMT is a promising therapeutic target for cancer treatments involving HR-associated DDR.

Background: Cholangiocarcinoma (CCA) is a malignant tumor with an increasing incidence worldwide. Although radiation therapy has improved the therapeutic efficiency of CCA treatment, differential expression of genes among cholangiocarcinoma subtypes has been revealed through precise sequencing. However, no specific molecular therapeutic targets or biomarkers have been figured out for use in precision medicine, and the exact mechanism by which antitumorigenic effects occur is still unclear. Therefore, it is necessary to conduct further studies on the development and mechanisms associated with CCA. Methods: We examined the clinical data and pathological features of patients with cholangiocarcinomas. We investigated the associations between DNA Topoisomerase II Alpha (TOP2A) expression and patient outcomes, such as metastasis-free survival (MFS) and disease-specific survival (DSS), as well as clinical characteristics and pathological results. Results: TOP2A expression was shown to be upregulated in CCA tissue sections by immunohistochemistry staining and data mining. Moreover, we observed that the TOP2A expression correlated with clinical features, such as the primary tumor stage, histological variants, and patients with hepatitis. Furthermore, high expression of TOP2A was associated with worse survival outcomes in terms of the overall survival (p < 0.0001), disease-specific survival (p < 0.0001), and metastasis-free survival (p < 0.0001) compared with patients in the low TOP2A expression group. This indicates that a high level of TOP2A expression is related to an unfavorable prognosis. Conclusions: Our results show that TOP2A is highly expressed in CCA tissues, and its upregulation is correlated with the primary disease stage and poor prognosis significantly. Consequently, TOP2A is a prognostic biomarker and a novel therapeutic target for the treatment of CCA.

Background: Infections caused by multi-drug-resistant Gram-negative bacteria (MDR-GNB) are an emerging problem globally. Colistin is the last-sort antibiotic for MDR-GNB, but its toxicity limits its clinical use. We aimed to test the efficacy of colistin-loaded micelles (CCM-CL) against drug-resistant Pseudomonas aeruginosa and compare their safety with that of free colistin in vitro and in vivo. Materials and methods: We incorporated colistin into chelating complex micelles (CCMs), thus producing colistin-loaded micelles (CCM-CL), and conducted both safety and efficacy surveys to elucidate their potential uses. Results: In a murine model, the safe dose of CCM-CL was 62.5%, which is much better than that achieved after the intravenous bolus injection of ‘free’ colistin. With a slow drug infusion, the safe dose of CCM-CL reached 16 mg/kg, which is double the free colistin, 8 mg/kg. The area under the curve (AUC) levels for CCM-CL were 4.09- and 4.95-fold higher than those for free colistin in terms of AUC0-t and AUC0-inf, respectively. The elimination half-lives of CCM-CL and free colistin groups were 12.46 and 102.23 min, respectively. In the neutropenic mice model with carbapenem-resistant Pseudomonas aeruginosa pneumonia, the 14-day survival rate of the mice treated with CCM-CL was 80%, which was significantly higher than the 30% in the free colistin group (p < 0.05). Conclusions: Our results showed that CCM-CL, an encapsulated form of colistin, is safe and effective, and thus may become a drug of choice against MDR-GNB.

Abstract Background and purpose The aim of this study is to decipher the underlying mechanisms of CCAAT/enhancer‐binding protein delta (CEBPD)‐enhanced glycolysis as well as the biological significance of CEBPD and MYC coamplification in urothelial carcinoma (UC). Methods In vitro analyses were conducted to examine the effects of altered CEBPD or MYC expression on UC cells. The in vivo effects of CEBPD overexpression in a high‐glucose environment on tumour growth were investigated in xenografted induced diabetic severe combined immunodeficiency/beige mice. Data mining was used to cross‐validate the associations between CEBPD and MYC copy number and transcriptional expression, quantitative reverse transcription‐polymerase chain reaction, immunohistochemistry, chromogenic in situ hybridization, and in situ hybridization targeting microRNA were performed on 635 UC patient samples and xenograft samples. UC patient survival in relation to diabetes was validated by using the National Health Insurance Research Database. Results CEBPD and MYC coamplification (29.6%) occurred at a high frequency, MYC expression promoted chromosomal instability, facilitating CEBPD copy number gain and expression. CEBPD promoted glucose uptake and lactate production by upregulating SLC2A1 and HK2, leading to mitochondrial fission, increased extracellular acidification rate and decreased oxygen consumption rate to fuel cell growth. CEBPD upregulated HK2 expression through multiple regulation pathways including MYC stabilization, suppression of FBXW7 transactivation and MYC‐independent transcriptional suppression of hsa‐miR‐429. Clinical and xenografted experiments confirmed the growth advantage of CEBPD in relation to glucose metabolic dysregulation and the significant correlations between the expression of these genes. Conclusions We confirmed that CEBPD has an oncogenic role in UC by activating AKT signalling and initiating metabolic reprogramming from mitochondrial oxidative phosphorylation to glycolysis to satisfy glucose addiction. These novel CEBPD‐ and MYC‐centric multilayered positive feedback loops enhance cancer growth that could complement theranostic approaches.

Background: Abnormal extracellular matrix (ECM) remodeling plays an essential role in urothelial carcinoma (UC) invasiveness and metastasis. Focusing on the ECM structural constituent (GO: 0005201), we recognized a significant upregulation of the fibulin 2 gene (FBLN2) during UC progression in a published UC transcriptome (GSE31684). Thus, we aimed to investigate the roles of FBLN2 expression and its prognostic value in upper urinary tract UC (UTUC) and urinary bladder UC (UBUC) in our large, well-characterized cohort.Patients and Methods: Clinicopathological data and formalin-fixed paraffin-embedded UC tissues were analyzed retrospectively. We determined FBLN2 expression using immunohistochemical staining assessed by H-scores. FBLN2 expression correlated with clinicopathological features and patient outcomes, including metastasis-free survival (MFS) and disease-specific survival (DSS). Statistical analyses were performed using Pearson's chi-square test, Kaplan–Meier estimates of DSS and MFS, and the Cox proportional hazards model. We used Ingenuity Pathway Analysis (IPA) to clarify the functional significance of dysregulated FBLN2 in UC.Results: Data from 295 UBUC and 340 UTUC patients were available for the final evaluation. Pearson's chi-square test showed that high FBLN2 immunoexpression significantly correlated with adverse pathologic variables, such as advanced pathologic tumor stage, high histological grade, perineural invasion, vascular invasion, lymph node metastasis, and increased mitotic rate (all p < 0.05). Kaplan–Meier analysis demonstrated associations of high FBLN2 expression with worse DSS (p < 0.001) and MFS (p < 0.001). Furthermore, multivariate analysis identified high FBLN2 expression as an independent predictive risk factor for DSS [hazard ratio (HR) in UBUC, 2.306, p = 0.014; in UTUC, 2.561, p = 0.012] and MFS (HR in UBUC, 2.493, p = 0.001; in UTUC, 2.837, p = 0.001). IPA demonstrated that multiple signaling pathways were enriched, including the oxidative phosphorylation, mitochondrial dysfunction, and regulation of the epithelial–mesenchymal transition pathways.Conclusion: High FBLN2 expression was associated with adverse pathologic features and worse oncological outcomes and may serve as a prognostic biomarker for UC.

Nanotechnology utilizes engineered materials and devices which function with biological systems at the molecular level and could transform the management of neurodegenerative diseases (NDs) by provoking, reacting to, and intermingling with target sites to stimulate physiological responses while minimizing side effects. Blood–brain barrier (BBB) protects the brain from harmful agents, and transporting drugs across the BBB is a major challenge for diagnosis, targeting, and treatment of NDs. The BBB provides severe limitations for diagnosis and treatment of Alzheimer’s disease (AD), Parkinson’s disease (PD), and various other neurological diseases. Conventional drug delivery systems generally fail to cross the BBB, thus are inefficient in treatment. Although gradual development through research is ensuring the progress of nanotheranostic approaches from animal to human modeling, aspects of translational applicability and safety are a key concern. This demands a deep understanding of the interaction of body systems with nanomaterials. There are various plant-based nanobioactive compounds which are reported to have applicability in the diagnosis and treatment of these NDs. This review article provides an overview of applications of nanotheranostics in AD and PD. The review also discusses nano-enabled drug delivery systems and their current and potential applications for the treatment of various NDs.

(Purpose) Previous studies have pointed out the significance of IgG Fc binding protein (FCGBP) in carcinogenesis, cancer progression, and tumor immunity in certain malignancies. However, its prognostic values, molecular interaction, and immune characteristics in the head and neck squamous cell carcinoma (HNSC) remained unclear. (Methods) To evaluate the potential role of the FCGBP gene, we used GEPIA2 and UALCAN platforms to explore the differential levels, survivals, and genetic alteration through cBioPortal (based on The Cancer Genome Atlas dataset). STRING, GeneMania, and TIMER2.0 identified the interacting networks. LinkedOmics performed Gene enrichment analysis, and TISIDB and TIMER2.0 evaluated the role of FCGBP in the tumor microenvironment. (Results) The expression level of FCGBP is lower in cancer tissues. A high FCGBP level is significantly associated with better overall- and disease-specific-survivals, regardless of human papillomavirus infection. Low FCGBP levels correlated to a higher tumor protein p53 (TP53) mutation rate (p = 0.018). FCGBP alteration significantly co-occurred with that of TP53 (q = 0.037). Interacting networks revealed a significant association between FGFBP and trefoil factor 3 (TFF3), a novel prognostic marker in various cancers, at transcriptional and translational levels. Enrichment analyses identified that the top gene sets predominantly related to immune and inflammatory responses. Further investigation found that the FCGBP mRNA level positively correlated to the infiltration rates of B cells, Th17/CD8+ T lymphocytes, T helper follicular cells, mast cells, and expression levels of various immune molecules and immune checkpoints in HNSC. (Conclusions) We found that the FCGBP mRNA level negatively correlated to TP53 mutation status while positively correlated to the TFF3 level. Additionally, FCGBP may regulate the tumor microenvironment. These findings support the FCGBP as a potential biomarker to estimate HNSC prognoses.

Early administration of proper antibiotics is considered to improve the clinical outcomes of Staphylococcus aureus bacteremia (SAB), but routine clinical antimicrobial susceptibility testing takes an additional 24 h after species identification. Recent studies elucidated matrix-assisted laser desorption/ionization time-of-flight mass spectra to discriminate methicillin-resistant strains (MRSA) or even incorporated with machine learning (ML) techniques. However, no universally applicable mass peaks were revealed, which means that the discrimination model might need to be established or calibrated by local strains’ data. Here, a clinically feasible workflow was provided. We collected mass spectra from SAB patients over an 8-month duration and preprocessed by binning with reference peaks. Machine learning models were trained and tested by samples independently of the first six months and the following two months, respectively. The ML models were optimized by genetic algorithm (GA). The accuracy, sensitivity, specificity, and AUC of the independent testing of the best model, i.e., SVM, under the optimal parameters were 87%, 75%, 95%, and 87%, respectively. In summary, almost all resistant results were truly resistant, implying that physicians might escalate antibiotics for MRSA 24 h earlier. This report presents an attainable method for clinical laboratories to build an MRSA model and boost the performance using their local data.

Background and Purpose: This research aimed to excavate the alternative mechanism of CEBPD on tumor growth and explore the biological significance of the CEBPD/hsa-miR-429/VEGFA axis on angiogenesis in urothelial carcinoma (UC). Methods: Quantitative RT-PCR, immunoblotting assay and tube formation examined the effect of hsa-miR-429 mimic or/and inhibitor on VEGFA expression and angiogenesis in CEBPD-overexpressing UC-derived cells. The association between CEBPD, hsa-miR-429, VEGFA and microvascular density (MVD) and clinical outcome were evaluated in 296 patients with UBUC and 340 patients with UTUC, respectively. Results: The increase in the transcript and protein of VEGFA as well as HUVECs tube formation was diminished upon the treatment of hsa-miR-429 mimic in CEBPD-overexpressing BFTC909 and TCCSUP. Nevertheless, the inhibited regulation of hsa-miR-429 mimic on the expression of VEGFA and ability of HUVECs tube formation was rescued by the combined incubation with hsa-miR-429 inhibitor in these two UC-derived cell lines. Furthermore, the clinical correlations showed that the higher level of VEGFA or MVD has a positive correlation with the expression of CEBPD and a negative relation to hsa-miR-429 and leads to tumor aggressiveness with worse disease-specific, metastasis-free survival in UBUC and UTUC cohorts. Conclusions: We decipher the oncogenic mechanism of CEBPD on angiogenesis through the hsa-miR-429 inhibition to stabilize the expression of VEGFA in UC. The novel research unveiled the modulation of the CEBPD/hsa-miR-429/VEGFA axis on the progression of UC and could be accessible to theranostic biomarkers.

The objective of this study aimed to develop biodegradable calcium alginate microspheres carrying doxorubicin (Dox) at the micrometer-scale for sustained release and the capacity of pH regulatory for transarterial chemoembolization. Ultrasonic atomization and CaCl2 cross-linking technologies were used to prepare the microspheres. A 4-by-5 experiment was first designed to identify imperative parameters. The concentration of CaCl2 and the flow rate of the pump were found to be critical to generate microspheres with a constant volume median diameter (~39 μm) across five groups with different alginate: NaHCO3 ratios using each corresponding flow rate. In each group, the encapsulation efficiency was positively correlated to the Dox-loading %. Fourier-transform infrared spectroscopy showed that NaHCO3 and Dox were step-by-step incorporated into the calcium alginate microspheres successfully. Microspheres containing alginate: NaHCO3 = 1 exhibited rough and porous surfaces, high Young’s modulus, and hardness. In each group with the same alginate: NaHCO3 ratio, the swelling rates of microspheres were higher in PBS containing 10% FBS compared to those in PBS alone. Microspheres with relatively high NaHCO3 concentrations in PBS containing 10% FBS maintained better physiological pH and higher accumulated Dox release ratios. In two distinct hepatocellular carcinoma-derived cell lines, treatments with microspheres carrying Dox demonstrated that the cell viabilities decreased in groups with relatively high NaHCO3 ratios in time- and dose-dependent manners. Our results suggested that biodegradable alginate microspheres containing relatively high NaHCO3 concentrations improved the cytotoxicity effects in vitro.

The current processes used in clinical microbiology laboratories take ~24 h for incubation to identify the bacteria after the blood culture has been confirmed as positive and fa further ~24 h to report the results of antimicrobial susceptibility tests (ASTs). Patients with suspected bloodstream infection are treated with empiric broad-spectrum antibiotics but delayed targeted antimicrobial therapy. This study aimed to develop a method with a significantly shortened turnaround time for clinical application by identifying the optimal incubation period of a subculture. A total of 188 positive blood culture samples obtained from Nov. 2019 to Aug. 2020 were included. Compared to the conventional 24-h incubation for bacterial identification, our approach achieved 96.1% and 97.4% identification accuracy after shortening the incubation time to 4.5 and 3.5 h for gram-positive (GP) and gram-negative (GN) bacterial samples, respectively. Samples from short-term incubation without any intermediate step or process were directly subjected to analysis with the Phoenix M50 AST. Compared to the conventional disk diffusion AST, the category agreements for GP (excluding Streptococcus spp.), Streptococcus spp., and GN bacterial samples were 91.8%, 97.5%, and 92.7%, respectively. Our approach significantly reduced the average turnaround time from 48 h to 28 h for reporting bacterial identity and decreased average AST from 72 h to 50.3 h compared to the conventional methods. Accordingly, this approach allows a physician to prescribe the appropriate antibiotic(s) ~21.7 h earlier, thereby improving patient outcomes.

This paper developed a rotatable multi-axis motion platform combined with virtual reality (VR) immersion for flight simulation purposes. The system could simulate the state of the flight operation. The platform was mainly comprised of three crank linkage mechanisms to replace an expensive six degrees of freedom (DoF) Stewart platform. Then, an independent subsystem which could rotate ±180° was installed at the center of the platform. Therefore, this platform exhibited 4-DoF movement, such as heave, roll, pitch, and yaw. In the servo motor control unit, Visual Studio C# was applied as the software to establish a motion control system to interact with the motion controller and four sets of servo motors. Ethernet Control Automation Technology (EtherCAT) was utilized to communicate the commands and orders between a PC and each servo motor. The optimum controller parameters of this system were obtained using Simulink simulation and verified by experiment. The multiple sets of servo motors and crank linkage mechanisms were synchronized with flight VR imagery. For VR imagery, the software Unity was used to design the flying digital content. The controller was used to transmit the platform’s spatial information to meet the direction of the pilot commands and to compensate the direction of the deviation in spatial coordinates. To achieve synchronized response and motion with respect to the three crank linkage mechanism platform and VR imagery on the tester’s goggle view, the relation of the spatial coordinate of VR imagery and three crank linkage mechanisms was transformed to angular displacement, speed and acceleration which were used to command the motor drive system. As soon as the position of the VR imagery changed, the computer instantly synchronized the VR imagery information to the multi-axis platform and performed multi-axis dynamic motion synchronously according to its commanded information. The testers can thus immerse in the VR image environment by watching the VR content, and obtain a flying experience.

Environmental and economic concerns are driving the demand for electric vehicles. However, their development for mass transportation hinges largely on improvements in the separators in lithium-ion batteries (LIBs), the preferred energy source. In this study, innovative separators for LIBs were fabricated by near-field electrospinning (NFES) and the sol-gel method. Using NFES, poly (vinylidene fluoride) (PVDF) fibers were fabricated. Then, PVDF membranes with pores of 220 nm and 450 nm were sandwiched between a monolayer and bilayer of the electrospun fibers. Nanoceramic material with organic resin, formed by the sol-gel method, was coated onto A4 paper, rice paper, nonwoven fabric, and carbon synthetic fabric. Properties of these separators were compared with those of a commercial polypropylene (PP) separator using a scanning electron microscope (SEM), microtensile testing, differential scanning calorimetry (DSC), ion-conductivity measurement, cyclic voltammetry (CV), and charge-discharge cycling. The results indicate that the 220 nm PVDF membrane sandwiched between a bilayer of electrospun fibers had excellent ionic conductivity (~0.57 mS/cm), a porosity of ~70%, an endothermic peak of ~175 °C, better specific capacitance (~356 mAh/g), a higher melting temperature (~160 °C), and a stable cycle performance. The sol-gel coated nonwoven fabric had ionic conductivity, porosity, and specific capacitance of ~0.96 mS/cm., ~64%, and ~220 mAh/g, respectively, and excellent thermal stability despite having a lower specific capacitance (65% of PP separator) and no peak below 270 °C. The present study provides a significant step toward the innovation of materials and processes for fabricating LIB separators.

In this study, near-infrared (NIR) technology was utilized to develop a low-cost real-time near infrared (NIR) guiding device for cannulation. A portable device that can be used by medical practitioners and also by students for their skills development training in performing cannulation. Methods. First, is the development of a reflectance type optical vein finder using three (3) light emitting diode (LED) lights with 960 nm wavelength, complementary metal-oxide-semiconductor-infrared (CMOS-IR) sensor camera with 1920 × 1080 UXGA (1080P), IR filter set for the given wavelength, and an open-source image processing software. Second, is the actual in-vitro human testing in two sites: the arm and dorsal hand of 242 subjects. The following parameters were included, such as gender, age, mass index (BMI), and skin tone. In order to maximize the assessment process towards the device, the researchers included the arm circumference. This augmented subcutaneous vein imaging study using the develop vein finder device compared the difference in the captured vein images through visual and digital imaging approaches. The human testing was performed in accordance with the ethical standards of the Trinity University of Asia—Institutional Ethics Review Committee (TUA—IERC). Results. The NIR imaging system of the developed vein finder in this study showed its capability as an efficient guiding device through real-time vein pattern recognition, for both sites. Improved captured vein images were observed, having 100% visibility of vein patterns on the dorsal hand site. Fourteen (5.79%) out of 242 subjects reported non-visible peripheral subcutaneous veins in the arm sites. Conclusions. The developed vein finder device with the NIR technology and reflected light principle with low-energy consumption was efficient for real-time peripheral subcutaneous vein imaging without the application of a tourniquet. This might be utilized as a guiding device in locating the vein for the purpose of cannulation, at a very low cost as compared to the commercially available vein finders. Moreover, it may be used as an instructional device for student training in performing cannulation.

Cell cycle deregulation is common in human hepatocellular carcinoma (HCC). To ensure proper cell cycle controlling, cyclin/cyclin-dependent kinases (CDK) complexes are tightly regulated by CDK inhibitors (CKIs) in normal cells. However, insufficient cyclin-dependent kinase inhibitor 1B (CDKN1B, also known as p27Kip1) and CDKN1C (p57Kip2) proteins are characteristics of high-risk HCC. In two HCC-derived cell lines with distinct genetic backgrounds, we identified a small natural compound, goniothalamin (GTN), serving as an inducer of CKIs. In TP53-mutated (Y220C) and retinoblastoma 1 (RB1)-positive Huh-7 cells, GTN stabilized CDKN1B protein levels by targeting the degradation of its specific E3 ubiquitin ligase (S-phase kinase-associated protein 2). Alternatively, in TP53- and RB1-negative Hep-3B cells, GTN increased CDKN1C transcription and its subsequent translation by acting as a histone deacetylase inhibitor. In both cell lines, GTN induced G0/G1 cell cycle arrest, delayed S phase entry of cells and inhibited anchorage-independent cell growth which might be attributed to the upregulation of CKIs and downregulation of several positive cell cycle regulators, including CDC28 protein kinase regulator subunit 1B, cyclin E1 and D1, cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, E2F transcription factor 1 and/or transcription factor Dp-1. Therefore, GTN might represent a novel class of anticancer drug that induces CKIs through post-translational and epigenetic modifications.

One of the most common means for diagnosis is through medical laboratory testing, which primarily uses venous blood as a sample. This requires an invasive method by cannulation that needs proper vein selection. The use of a vein finder would help the phlebotomist to easily locate the vein, preventing possible pre-analytical error in the specimen collection and even more discomfort and pain to the patient. This paper is a review of the scientific publications on the different developed low-cost vein finder prototypes utilizing camera assisted near infrared (NIR) light technology. Methods: Electronic databases were searched online, these included PubMed (PMC), MEDLINE, Science Direct, ResearchGate, and Institute of Electrical and Electronics Engineers (IEEE) Xplore digital library. Specifically, publications with the terms vein finder prototype, NIR technology, vein detection, and infrared imaging were screened. In addition, reference lists were used to further review related publications. Results: Cannulation challenges medical practitioners because of the different factors that can be reduced by the utilization of a vein finder. A limited number of publications regarding the assessment of personnel performing cannulation were observed. Moreover, variations in methodology, number of patients, type of patients according to their demographics and materials used in the assessment of the developed prototypes were noted. Some studies were limited with regard to the actual human testing of the prototype. Conclusions: The development of a low-cost effective near infrared (NIR) vein finder remains in the phase of improvement. Since, it is being challenged by different human factors, increasing the number of parameters and participants/human for actual testing of the prototypes must also be taken into consideration for possible commercialization. Finally, it was noted that publications regarding the assessment of the performance of phlebotomists using vein finders were limited.

Traumatic spinal cord injury (tSCI) may involve new-onset anxiety and depression post-discharge. However, long-term population-based studies have lacked access to follow-up conditions in terms of new-onset anxiety and depression. The objective of this study was to estimate the long-term risk of new-onset anxiety and depression post-discharge.The Longitudinal Health Insurance Database 2000 (LHID2000) from Taiwan's National Health Insurance Research Database was used in this study. Individuals with tSCI were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes of 806 and 952 from 1999-2008. The comparison cohort (other health conditions group) was randomly selected from the LHID2000 and was 1:1 matched by age, sex, index year, and comorbidities to reduce the selection bias. All study participants were retrospectively followed for a maximum of 3 years until the end of follow-up, death, or new-onset anxiety (ICD-9-CM: 309.2-309.4) or depression (ICD-9-CM: 296.2, 296.5, 296.82, 300.4, 309.0-309.1, and 311). Persons who were issued a catastrophic illness card for tSCI were categorized as having a severe level of SCI (Injury Severity Score [ISS] ≥16). Poisson regression was used to estimate the incidence rate ratios of anxiety or depression between patients with tSCI and other health conditions. The relative risk of anxiety or depression was estimated using a Cox regression analysis, which was adjusted for potential confounding factors.Univariate analyses showed that the tSCI patients (n = 3556) had a 1.33 times greater incidence of new-onset anxiety or depression (95% confidence interval [CI]: 1.12-1.57) compared to the other health conditions group (n = 3556). After adjusting for potential risk factors, the tSCI patients had a significant 1.29-fold increased risk of anxiety or depression compared to the group with other health conditions (95% CI: 1.09-1.53). Individuals with tSCI, including patients who were under the age of 35, patients who were males, patients who had a low income, and patients without a Charlson Comorbidity Index score, all had a higher long-term risk of anxiety or depression than the other health conditions group (IRRs: 1.84, 1.63, 1.29, and 1.39, respectively). For all tSCI patients, those with an Injury Severity Score (ISS) ≥16 had an almost 2-fold higher risk of anxiety or depression (adjusted Hazard Ratio: 1.85; 95% CI: 1.17-2.92) compared to those with ISS

In general, over 70% absorbed nicotine is metabolized to cotinine and trans-3′-hydroxycotinine by cytochrome oxidase P450, and nicotine is also a major addictive and the psychoactive component in cigarettes. As a xenobiotic metabolism, hydrophobic compounds are usually converted into more hydrophilic products through enzyme systems such as cytochrome oxidase P450, sulfotransferases, and UDP-glucuronosyltransferases to deliver drug metabolites out of the cell during the drug metabolic process. In this study, an electrodeless electrochemical oxidation (EEO) reaction via Fenton reaction by producing free radical to react with nicotine to immediately monitor the oxidative products and metabolic derivatives of nicotine by tandem mass spectrometer (MS) is done. Fenton reaction generates free radicals via ferrous ion (Fe2+) and hydrogen peroxide (H2O2) to oxidize DNA and to degrade proteins in cells. In the EEO method, the oxidative products of nicotine including cotinine, cotinine-N-oxide, trans-3′-hydroxycotinine, nornicotine, norcotinine, 4-oxo-4-(3-pyridyl)-butanoic acid, 4-hydroxy-4-(3-pyridyl)-butanoic acid, and nicotine-N′-oxide were detected by tandem mass spectrometer to simulate the changes of nicotine and its derivatives in a time-dependent manner.

Background: The global burden of respiratory diseases such as influenza, tuberculosis, and viral pneumonia necessitates rapid, accurate diagnostic tools to improve healthcare responses. Current methods, including RT-PCR and chest radiography, face limitations in accuracy, speed, accessibility, and cost-effectiveness, especially in resource-constrained settings, often delaying treatment and increasing transmission. Methods: This study introduces an Enhanced Multi-Model Deep Learning (EMDL) approach to address these challenges. EMDL integrates an ensemble of five pre-trained deep learning models (VGG-16, VGG-19, ResNet, AlexNet, and GoogleNet) with advanced image preprocessing (histogram equalization and contrast enhancement) and a novel multi-stage feature selection and optimization pipeline (PCA, SelectKBest, Binary Particle Swarm Optimization (BPSO), and Binary Grey Wolf Optimization (BGWO)). Results: Evaluated on two independent chest X-ray datasets, EMDL achieved high accuracy in the multiclass classification of influenza, pneumonia, and tuberculosis. The combined image enhancement and feature optimization strategies significantly improved diagnostic precision and model robustness. Conclusions: The EMDL framework provides a scalable and efficient solution for accurate and accessible pulmonary disease diagnosis, potentially improving treatment efficacy and patient outcomes, particularly in resource-limited settings. [ABSTRACT FROM AUTHOR]