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Bacterial keratitis (BK), a painful and fulminant bacterial infection of the cornea, is the most common type of vision-threatening infectious keratitis (IK). A rapid clinical diagnosis by an ophthalmologist may often help prevent BK patients from progression to corneal melting or even perforation, but many rural areas cannot afford an ophthalmologist. Thanks to the rapid development of deep learning (DL) algorithms, artificial intelligence via image could provide an immediate screening and recommendation for patients with red and painful eyes. Therefore, this study aims to elucidate the potentials of different DL algorithms for diagnosing BK via external eye photos. External eye photos of clinically suspected IK were consecutively collected from five referral centers. The candidate DL frameworks, including ResNet50, ResNeXt50, DenseNet121, SE-ResNet50, EfficientNets B0, B1, B2, and B3, were trained to recognize BK from the photo toward the target with the greatest area under the receiver operating characteristic curve (AUROC). Via five-cross validation, EfficientNet B3 showed the most excellent average AUROC, in which the average percentage of sensitivity, specificity, positive predictive value, and negative predictive value was 74, 64, 77, and 61. There was no statistical difference in diagnostic accuracy and AUROC between any two of these DL frameworks. The diagnostic accuracy of these models (ranged from 69 to 72%) is comparable to that of the ophthalmologist (66% to 74%). Therefore, all these models are promising tools for diagnosing BK in first-line medical care units without ophthalmologists.

Prostate cancer (PCa) is the second most commonly diagnosed cancer worldwide and the 5th leading cause of death from cancer for men in Taiwan. The incidence of synchronous metastatic PCa in Taiwan is higher than U.S. and Europe. We aim to present the latest life expectancy (LE), loss of LE, and lifetime cost associated with PCa in Taiwan. The PCa data are based on Taiwan Cancer Registry and National Health Insurance Database. Total 30,207 new cases of PCa were recorded during 2008-2019 nationwide. LE, estimated loss of LE and lifetime cost were stratified by age, cancer stage, Gleason score, grade group and serum PSA level at diagnosis. We compared LE and healthcare cost outcomes between synchronous metastatic PCa patients in 3 age groups. Among the 30,207 new cases, the low to intermediate risk groups, high-risk groups, and regional and metastatic PCa accounted for 54.1%, 13.2%, and 32.6% of cases, respectively. A considerable proportion of synchronous metastatic PCa was noted in Taiwan when compared with the U.S. For synchronous metastatic PCa, the highest LE is 9.22 years for ages 20-64 years, followed by ages 65-74 (8.29 years) and ages 75-89 years (4.58 years). The loss of LE in the three age groups is 13.63, 6.75, and 3.87 years, respectively. The healthcare cost of synchronous metastatic PCa in all age groups is higher than the average cost for PCa patients in Taiwan. This study provides real-world evidence to support health care policy-making and clinical decisions regarding PCa. Due to the high proportion of synchronous metastatic PCa in Taiwan, the findings of this analysis emphasize the importance of early detection of PCa, which can save LE and decrease the total cost burden on the healthcare system.

Non-small cell lung cancer is the predominant type of lung cancer, resulting in high mortality worldwide. Digoxin, a cardiac glycoside, has recently been suggested to be a novel chemotherapeutic agent. Src is an oncogene that plays an important role in cancer progression and is therefore a potential target for cancer therapy. Here, we investigated whether digoxin could suppress lung cancer progression through the inhibition of Src activity. The effects of digoxin on lung cancer cell functions were investigated using colony formation, migration and invasion assays. Western blotting and qPCR assays were used to analyze the mRNA and protein expression levels of Src and its downstream proteins, and a cell viability assay was used to measure cellular cytotoxicity effects. The results of the cell function assays revealed that digoxin inhibited the proliferation, invasion, migration, and colony formation of A549 lung cancer cells. Similar effects of digoxin were also observed in other lung cancer cell lines. Furthermore, we found that digoxin significantly suppressed Src activity and its protein expression in a dose- and time-dependent manner as well as reduced EGFR and STAT3 activity. Our data suggest that digoxin is a potential anticancer agent that may suppress lung cancer progression through inhibiting Src and the activity of related proteins.

Abstract Context Clinical trials have investigated the role of antiresorptive agents, including bisphosphonates and denosumab, in patients with primary breast cancer receiving adjuvant endocrine therapy, aiming for better bone protection and/or improving survival. Objective To summarize the clinical effects of antiresorptive agents in patients with early breast cancer receiving endocrine therapy. Methods We systematically reviewed and synthesized the clinical benefits and harms of antiresorptive agents in patients with early breast cancer receiving endocrine therapy by calculating the risk ratios (RRs). Results In the pooled meta-analysis, antiresorptive agents had significant clinical benefits on disease recurrence (RR 0.78, 95% CI 0.67-0.90) and locoregional recurrence (RR 0.69, 95% CI 0.49-0.95) in patients with breast cancer receiving endocrine therapy. Early use of antiresorptive agents has a beneficial effect on secondary endocrine therapy resistance instead of primary resistance. Safety analysis revealed that potential risk for osteonecrosis of the jaw (ONJ, RR 3.29, 95% CI 1.12-9.68) with antiresorptive agents; however, there is an insignificant difference in arthralgia. The subgroup analyses revealed that intervention with bisphosphonates might have profound clinical benefits, but also increased the occurrence of ONJ. A network meta-analysis further supported the clinical effects of early antiresorptive agent use compared with delayed use or placebo. Conclusion Using antiresorptive agents early in patients with breast cancer receiving adjuvant endocrine therapy may provide additional benefits in risk reduction of recurrence, but there is a potential risk of ONJ.

In 1996, the National Health Insurance Administration of Taiwan applied a restrictive reimbursement criteria for erythropoiesis-stimulating agents (ESAs) use in patients with chronic kidney disease. The maximal ESAs dosage allowed by insurance is capped at 20,000 U of epoetin per month. Nephrologists avoided the use of high ESA dosages to achieve a hemoglobin level of 10–11 g/dL using iron supplementation. We assessed the association of anemia and iron parameters with mortality among peritoneal dialysis (AIM-PD) patients. A retrospective cohort study was conducted based on the Taiwan Renal Registry Data System. From January 1, 2000 to December 31, 2008, we enrolled 4356 well-nourished PD patients who were older than 20 years and had been receiving PD for more than 12 months. All patients were divided into subgroups according to different hemoglobin, ferritin and transferrin saturation (TSAT) values. Patients were followed until death or December 31, 2008. In a median 2.9-year study period, 694 (15.9%) patients died. By multivariate adjustment, a hemoglobin level lower than 10 g/dL was significantly associated with a higher risk for all-cause and cardiovascular deaths. Moreover, a serum ferritin level higher than 800 ng/mL was associated with a higher risk for all-cause deaths, and a TSAT value between 20 and 50% was associated with the lowest all-cause mortality. In conclusions, we recommend avoiding a low hemoglobin level and a serum ferritin level of more than 800 ng/mL and maintaining a TSAT value between 20 and 50%, as these conditions were associated with lower risks of all-cause mortality in the AIM-PD study.

Cancer stem cells (CSCs) represent a unique sub-population of tumor cells with the ability to initiate tumor growth and sustain self-renewal. Although CSC biomarkers have been described for various tumors, only a few markers have been identified for nasopharyngeal carcinoma (NPC). In this study, we show that CD24+ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/β-catenin signaling pathway. CD24+ cells possess typical CSC characteristics that include enhanced cell proliferation, increased colony and sphere formation, maintenance of cell differentiation potential in prolonged culture, and enhanced resistance to chemotherapeutic drugs. Notably, CD24+ cells produce tumors following inoculation of as few as 500 cells in immunodeficient NOD/SCID mice. CD24+ cells further show increased invasion ability in vitro, which correlates with enhanced expression of matrix metalloproteinase 2 and 9. In summary, our results suggest that CD24 represents a novel CSC biomarker in NPC.

This study investigated the shielding effectiveness (SE) of glass materials with conductive coatings by establishing a 3000 × 3000 × 3000 mm electromagnetic pulse (EMP)—shielded room according to the EMP shielding requirements in the US military standard MIL-STD-188-125-1. The EMP SE of conductive-coated glass samples was measured and verified with the broadband EMP conditions of 10 kHz∼1 GHz. The conductive thin film coating on the glass was made by mixing conductive materials, including In2O3, SnO2, Ta2O5, NbO, SiO2, TiO2, and Al2O3, at different ratios. The mixed solutions were then coated onto the glass targets to facilitate conductive continuity between the conductive oxides and the shielding metal structure. The glass samples had dimensions of 1000 × 600 mm, which had electrolytic conductivity σ = 4.0064 × 103∼4.7438 × 103 (S/cm), 74∼77% transmittance, and 6.4∼6.8 Ω/□ film resistance. The experimental results indicated that the glass had SE of 35∼40 dB under 1 GHz EMP, satisfying the US National Coordinating Center for Communications’ Level 3 shielding protection requirement of at least 30 dB. The glass attenuated energy density by more than 1000 times, which is equivalent to shielding over 97% of EMP energy. Accordingly, the glass materials can be used as high-transmittance conductive glass for windows of automobiles, vessels, and aircrafts to protect from EMPs.

Expanded indications for patients with preoperatively suspected prostate cancer (PC) undergoing theranostic robotic-assisted laparoscopic radical prostatectomy (T-RARP) are reported. We aimed to build a nomogram of T-RARP to predict final pathologically proven PC. This study reviewed data of 153 patients that underwent T-RARP for suspected PC performed by the same surgeon. Patients' preoperative demographic and clinical characteristics included age, prostate-specific antigen (PSA) level, PSA density (PSAD), history of acute urinary retention (AUR), abnormal digital rectal examination (DRE) of the prostate, and Prostate Imaging Reporting and Data System (PI-RADS) classification at 3-T multiparametric magnetic resonance imaging (MRI). Logistic regression with backward elimination was used to select potential risk factors. Based on Harrell's guidelines, we chose seven variables for our final model: Age, DRE corresponding with MRI, AUR, PSAD, prostate-specific antigen velocity (PSAV), PI-RADS, and biopsy pathology. A nomogram for prediction of adenocarcinoma was developed. The original C-index for the nomogram was 0.80 (95% confidence interval=0.74-0.89). The cut-off of the nomogram score for predicting PC was 50 (sensitivity=55.4%; specificity=91.9%). The receiver operating characteristic curve of the model analysis showed an area under the curve of 0.801. A nomogram was produced using age, DRE-corresponding MRI, AUR, PSAD, PSAV, PI-RADS, and biopsy pathology. A preoperative nomogram prediction of prostate adenocarcinoma can help the patient and his family understand the possibility of PC and assist them in their decision-making.

The study aimed to investigate the therapeutic impact of intravesical instillation of dehydrated human amnion-chorion membrane (HACM) extracts based on the primary pathological feature of interstitial cystitis (IC). We divided 15 female Sprague-Dawley rats into three groups: sham control, IC, and treatment group. IC was induced by 400-µL lipopolysaccharide (1 µg/µL), and it was replaced with normal saline in the sham control group. After IC induction, 300 µL dehydrated HACM extracts (3 mg/kg) were instilled into rats’ urinary bladder weekly for 3 weeks. General histology, inflammatory cytokines, NF-κB, oxidative markers, and western blots results were examined. The urothelial denudation, mast-cell infiltration, and tissues fibrosis were all ameliorated. The elevated TNF-α, IL-1β, IL-6, IL-8, and NF-κB were all down-regulated by dehydrated HACM extracts (p < 0.05). For reactive oxygen species, increased malondialdehyde, decreased superoxide dismutase, and decreased glutathione peroxidase were all reversed (p < 0.05). In apoptosis of IC, elevated Bax and suppressed Bcl-2 were improved (p < 0.05) after instillation. In fibrosis, dysregulated TGFβ/R-Smads/Snail was corrected by the instillation of dehydrated HACM (p < 0.05). In conclusion, dehydrated HACM extracts could be a powerful remedy in treating IC by reconstructing the damaged urothelium, reducing mast-cell infiltration and inflammatory reactions, and ameliorating fibrotic changes.

Dimethyl sulfoxide (DMSO) is an amphipathic molecule that displays a diversity of antitumor activities. Previous studies have demonstrated that DMSO can modulate AP-1 activity and lead to cell cycle arrest at the G1 phase. HLJ1 is a newly identified tumor and invasion suppressor that inhibits tumorigenesis and cancer metastasis. Its transcriptional activity is regulated by the transcription factor AP-1. However, the effects of DMSO on HLJ1 are still unknown. In the present study, we investigate the antitumor effects of DMSO through HLJ1 induction and demonstrate the mechanisms involved. Low-HLJ1-expressing highly invasive CL1-5 lung adenocarcinoma cells were treated with various concentrations of DMSO. We found that DMSO can significantly inhibit cancer cell invasion, migration, proliferation, and colony formation capabilities through upregulation of HLJ1 in a concentration-dependent manner, whereas ethanol has no effect. In addition, the HLJ1 promoter and enhancer reporter assay revealed that DMSO transcriptionally upregulates HLJ1 expression through an AP-1 site within the HLJ1 enhancer. The AP-1 subfamily members JunD and JunB were significantly upregulated by DMSO in a concentration-dependent manner. Furthermore, pretreatment with DMSO led to a significant increase in the percentage of UV-induced apoptotic cells. Our results suggest that DMSO may be an important stimulator of the tumor suppressor protein HLJ1 through AP-1 activation in highly invasive lung adenocarcinoma cells. Targeted induction of HLJ1 represents a promising approach for cancer therapy, which also implied that DMSO may serve as a potential lead compound or coordinated ligand for the development of novel anticancer drugs.