Evaluating artificial intelligence-enhanced digital urine cytology for bladder cancer diagnosis.

BACKGROUND: This study evaluated the diagnostic effectiveness of the AIxURO platform, an artificial intelligence-based tool, to support urine cytology for bladder cancer management, which typically requires experienced cytopathologists and substantial diagnosis time. METHODS: One cytopathologist and two cytotechnologists reviewed 116 urine cytology slides and corresponding whole-slide images (WSIs) from urology patients. They used three diagnostic modalities: microscopy, WSI review, and AIxURO, per The Paris System for Reporting Urinary Cytology (TPS) criteria. Performance metrics, including TPS-guided and binary diagnosis, inter- and intraobserver agreement, and screening time, were compared across all methods and reviewers. RESULTS: AIxURO improved diagnostic accuracy by increasing sensitivity (from 25.0%-30.6% to 63.9%), positive predictive value (PPV; from 21.6%-24.3% to 31.1%), and negative predictive value (NPV; from 91.3%-91.6% to 95.3%) for atypical urothelial cell (AUC) cases. For suspicious for high-grade urothelial carcinoma (SHGUC) cases, it improved sensitivity (from 15.2%-27.3% to 33.3%), PPV (from 31.3%-47.4% to 61.1%), and NPV (from 91.6%-92.7% to 93.3%). Binary diagnoses exhibited an improvement in sensitivity (from 77.8%-82.2% to 90.0%) and NPV (from 91.7%-93.4% to 95.8%). Interobserver agreement across all methods showed moderate consistency (κ = 0.57-0.61), with the cytopathologist demonstrating higher intraobserver agreement than the two cytotechnologists across the methods (κ = 0.75-0.88). AIxURO significantly reduced screening time by 52.3%-83.2% from microscopy and 43.6%-86.7% from WSI review across all reviewers. Screening-positive (AUC+) cases required more time than negative cases across all methods and reviewers. CONCLUSIONS: AIxURO demonstrates the potential to improve both sensitivity and efficiency in bladder cancer diagnostics via urine cytology. Its integration into the cytopathological screening workflow could markedly decrease screening times, which would improve overall diagnostic processes.

Nuclear export signal mutation of epidermal growth factor receptor enhances malignant phenotypes of cancer cells.

Nuclear epidermal growth factor receptor (EGFR) has been shown to be correlated with drug resistance and a poor prognosis in patients with cancer. Previously, we have identified a tripartite nuclear localization signal (NLS) within EGFR. To comprehensively determine the functions and underlying mechanism of nuclear EGFR and its clinical implications, we aimed to explore the nuclear export signal (NES) sequence of EGFR that is responsible for interacting with the exportins. We combined in silico prediction with site-directed mutagenesis approaches and identified a putative NES motif of EGFR, which is located in amino acid residues 736-749. Mutation at leucine 747 (L747) in the EGFR NES led to increased nuclear accumulation of the protein via a less efficient release of the exportin CRM1. Interestingly, L747 with serine (L747S) and with proline (L747P) mutations were found in both tyrosine kinase inhibitor (TKI)-treated and -naïve patients with lung cancer who had acquired or de novo TKI resistance and a poor outcome. Reconstituted expression of the single NES mutant EGFRL747P or EGFRL747S, but not the dual mutant along with the internalization-defective or NLS mutation, in lung cancer cells promoted malignant phenotypes, including cell migration, invasiveness, TKI resistance, and tumor initiation, supporting an oncogenic role of nuclear EGFR. Intriguingly, cells with germline expression of the NES L747 mutant developed into B cell lymphoma. Mechanistically, nuclear EGFR signaling is required for sustaining nuclear activated STAT3, but not for Erk. These findings suggest that EGFR functions are compartmentalized and that nuclear EGFR signaling plays a crucial role in tumor malignant phenotypes, leading to tumorigenesis in human cancer.

Prenatal and early-life antibiotic exposure and the risk of atopic dermatitis in children: A nationwide population-based cohort study.

BACKGROUND: Atopic dermatitis (AD) contributes to substantial social and financial costs in public health care systems. Antibiotic exposure during pregnancy has been proposed as a risk factor, but findings remain inconsistent. The aim of this study was to investigate the association between prenatal antibiotic use and childhood AD. METHODS: We performed a population-based cohort study using data collected from the Taiwan Maternal and Child Health Database from 2009 to 2016. Associations were determined using Cox proportional hazards model and were adjusted for several potential covariates, including maternal atopic disorders and gestational infections. Children with and without maternal predispositions of atopic diseases and postnatal antibiotic/acetaminophen exposures within 1 year were stratified to identify the subgroups at risk. RESULTS: A total of 1,288,343 mother-child pairs were identified and 39.5% received antibiotics prenatally. Maternal antibiotic use during pregnancy was slightly positively associated with childhood AD (aHR 1.04, 95% CI 1.03-1.05), especially in the first and second trimesters. An apparent dose-response pattern was observed with an 8% increased risk when the exposure was ≥5 courses prenatally (aHR 1.08, 95% CI 1.06-1.11). Subgroup analysis showed the positive association remained significant regardless of postnatal infant antibiotic use, but the risk attenuated to null in infants who were not exposed to acetaminophen (aHR 1.01, 95% CI 0.96-1.05). The associations were higher in children whose mothers were without AD compared to those whose mothers were with AD. In addition, postnatal antibiotic or acetaminophen exposure of infants was associated with an increased risk of developing AD after 1 year of age. CONCLUSION: Maternal antibiotic use during pregnancy was associated with an increased risk of childhood AD in a dose-related manner. Further research may be warranted to investigate this variable using a prospectively designed study, and also to examine whether or not this association is specifically related to pregnancy.

Investigating the Current Status of SARS-CoV-2 Antibodies in Hospital Staff.

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 had reported over 676 million cases by March 2023. The main aim of this study is to investigate whether the levels of anti-S and anti-N antibodies could precisely indicate the degree of protection against SARS-CoV-2 and affect the probability or time of contracting COVID-19. In this study, a serosurveillance study was conducted in healthcare workers (HCWs) at a regional hospital in Taiwan to evaluate their antibody levels based on infection and vaccination status. Of 245 HCWs enrolled, all have been vaccinated prior to infection. Of these, 85 participants were infected by SARS-CoV-2, while 160 participants were not infected at the time of blood sample collection. The level of anti-SARS-CoV-2 S antibody was significantly higher in the infected HCWs than in the non-infected participants (p < 0.001). It is worth noting that the mean duration between the administration of the last dose of the vaccine and the occurrence of SARS-CoV-2 infection was 5.61 ± 2.95 months. Our follow-up survey revealed that the non-infected group had significantly higher levels of antibodies compared to the infected group (all p < 0.001). In conclusion, this study suggests that the level of antibodies could serve as a reflection of the protective efficacy against SARS-CoV-2 infection. It has the implication for vaccine decision-making policies in the future.

Multi-omics and experimental analysis unveil theragnostic value and immunological roles of inner membrane mitochondrial protein (IMMT) in breast cancer.

BACKGROUND: The inner membrane mitochondrial protein (IMMT) is a central unit of the mitochondrial contact site and cristae organizing system (MICOS). While researchers continue to demonstrate the physiological function of IMMT in regulating mitochondrial dynamics and preserving mitochondrial structural integrity, the roles of IMMT in clinicopathology, the tumor immune microenvironment (TIME), and precision oncology in breast cancer (BC) remain unclear. METHODS: Multi-omics analysis was used here to evaluate the diagnostic and prognostic value of IMMT. Web applications aimed at analyzing the whole tumor tissue, single cells, and spatial transcriptomics were used to examine the relationship of IMMT with TIME. Gene set enrichment analysis (GSEA) was employed to determine the primary biological impact of IMMT. Experimental verification using siRNA knockdown and clinical specimens of BC patients confirmed the mechanisms behind IMMT on BC cells and the clinical significance, respectively. Potent drugs were identified by accessing the data repositories of CRISPR-based drug screenings. RESULTS: High IMMT expression served as an independent diagnostic biomarker, correlated with advanced clinical status, and indicated a poor relapse-free survival (RFS) rate for patients with BC. Although, the contents of Th1, Th2, MSC, macrophages, basophil, CD4 + T cell and B cell, and TMB levels counteracted the prognostic significance. Single-cell level and whole-tissue level analyses revealed that high IMMT was associated with an immunosuppressive TIME. GSEA identified IMMT perturbation as involved in cell cycle progression and mitochondrial antioxidant defenses. Experimental knockdown of IMMT impeded the migration and viability of BC cells, arrested the cell cycle, disturbed mitochondrial function, and increased the ROS level and lipid peroxidation. The clinical values of IMMT were amenable to ethnic Chinese BC patients, and can be extrapolated to some other cancer types. Furthermore, we discovered that pyridostatin acted as a potent drug candidate in BC cells harboring an elevated IMMT expression. CONCLUSION: This study combined a multi-omics survey with experimental verification to reveal the novel clinical significance of IMMT in BC, demonstrating its role in TIME, cancer cell growth and mitochondrial fitness, and identified pyridostatin as a promising drug candidate for the development of precision medicine.

A New Biorecognition-Element-Free IDµE Sensor for the Identification and Quantification of E. coli.

The label-free biosensor has emerged as an effective tool for the purpose of early detection of causative pathogens such as Escherichia coli as a preventive measure. In this study, a biorecognition-element-free interdigitated microelectrode (IDµE) sensor is designed and developed with this in mind, with good reliability and affordability. Results show that the designed sensor can identify E. coli with good selectivity using an impedance and capacitance of 7.69 MHz. At its optimum impedance of 1.3 kHz, the IDµE sensor can reliably quantify E. coli in a range of measurement (103.2~106 cfu/mL), linearity (R2 = 0.97), sensitivity (18.15 kΩ/log (cfu/mL)), and limit of detection (103.2 cfu/mL). In summary, the IDµE sensor developed possesses high potential for industrial and clinical applications.

STAT3 Inactivation and Induction of Apoptosis Associate With Fluoxetine-inhibited Epithelial-mesenchymal Transition and Growth of Triple-negative Breast Cancer In Vivo.

BACKGROUND/AIM: Breast cancer (BC) is the most common cancer and second leading cause of death in women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive type of BC, while the treatment option is limited and has long been considered as a major unmet need. Meta-analysis indicated the anti-tumor potential of anti-depressants, especially selective serotonin-reuptake inhibitors (SSRIs). The SSRI fluoxetine has been shown to suppress BC and ovarian cancer cell growth; however, whether it suppresses tumor progression in vivo is unclear. MATERIALS AND METHODS: We established an 4T1 bearing animal model, an orthotopic TNBC model, to identify the mechanism and therapeutic efficacy of fluoxetine. RESULTS: Tumor growth evaluated by caliper and computed tomography scan demonstrated the inhibition effect by fluoxetine treatment. Immunohistochemistry showed that the expression of STAT3-mediated epithelial-to-mesenchymal transition (EMT) proteins and apoptosis-related proteins was decreased. CONCLUSION: Fluoxetine may induce an anti-TNBC effect via inactivating STAT3 signaling transduction and triggering the caspase-mediated apoptotic pathway.

Current and Developing Liquid Biopsy Techniques for Breast Cancer.

Breast cancer is the most commonly diagnosed cancer and leading cause of cancer mortality among woman worldwide. The techniques of diagnosis, prognosis, and therapy monitoring of breast cancer are critical. Current diagnostic techniques are mammography and tissue biopsy; however, they have limitations. With the development of novel techniques, such as personalized medicine and genetic profiling, liquid biopsy is emerging as the less invasive tool for diagnosing and monitoring breast cancer. Liquid biopsy is performed by sampling biofluids and extracting tumor components, such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell-free mRNA (cfRNA) and microRNA (miRNA), proteins, and extracellular vehicles (EVs). In this review, we summarize and focus on the recent discoveries of tumor components and biomarkers applied in liquid biopsy and novel development of detection techniques, such as surface-enhanced Raman spectroscopy (SERS) and microfluidic devices.

A Novel Role of Arrhythmia-Related Gene KCNQ1 Revealed by Multi-Omic Analysis: Theragnostic Value and Potential Mechanisms in Lung Adenocarcinoma.

The early diagnosis, prognostic prediction, and personalized therapy of lung adenocarcinoma (LUAD) remains a challenging issue. KCNQ1 (potassium voltage-gated channel subfamily Q Member 1) is implicated in long QT syndrome (LQTS) and cardiac arrhythmia, while its significance in LUAD remains unclear. In this study, we aimed to explore the significance of KCNQ1 in terms of clinical value, tumor immunity, underlying mechanisms, and a precision medicine approach by means of multi-omics analysis. The association of KCNQ1 with LUAD was first explored. Both altered variants and high expression of KCNQ1 in a TCGA-LUAD cohort indicated a favorable outcome. KCNQ1 levels had a negative correlation with tumor proliferation index Ki67 levels. siRNA-knockdown of KCNQ1 promoted the migration ability of lung cancer cells. KCNQ1 levels were decreased in LUAD tissue compared to normal tissue. A receiver operating characteristic (ROC) curve indicated good diagnostic efficiency of KCNQ1. High KCNQ1 is associated with an immunoactive profile of immune infiltration and immunomodulators and is involved in the inhibition of the cell cycle and DNA replication. Lapatinib was identified as a potent drug for LUAD in the context of low KCNQ1. This study unveiled the significance of KCNQ1 in diagnosis and prognosis and provided a corresponding precision medicine strategy for LUAD.

Epigenetic therapy combination of UNC0638 and CI-994 suppresses breast cancer via epigenetic remodeling of BIRC5 and GADD45A.

BACKGROUND: There is currently a growing interest in the roles of epigenetic mechanisms in the diagnosis, prognosis, and therapies associated with precision oncology for breast cancer (BC). This study aimed to demonstrate the clinical significance of euchromatic histone lysine methyltransferase 2 (EHMT2), histone deacetylase 1 (HDAC1) and HDAC2 in BC, to evaluate the antitumor effectiveness of a combination of the selective inhibitors UNC0638 and CI-994 (U+C), and to clarify the underlying mechanisms. METHODS: Multi-omic analysis was used to study the clinical significance of the biomarkers of interest. The effects of U+C treatment were evaluated by detecting cell viability, cell cycle, apoptosis, and representative gene expressions. RNA-Seq and Gene Set Enrichment Analysis (GSEA) were employed to identify over-represented genes associated with the treatment. Chromatin immunoprecipitation and qPCR (ChIP-qPCR) assay were applied to verify epigenetic profiling on the identified promoters. RESULTS: The significance of elevated expressions of EHMT2, HDAC1, and HDAC2 in tumor tissue and BC basal-like subtype in predicting a poor prognosis was noted. The U+C combined treatment showed an enhanced suppressive effect as compared to single agent treatment, perturbed the cell cycle, induced apoptosis, reduced expressions of the genes representing anti-apoptosis, stemness, drug resistance and basal-like state, while increasing luminal-like state genes. In addition, the combined U+C treatment suppressed xenograft tumor growth. The epigenetic reprogramming of histones was identified in the down-regulated BIRC5 and upregulated GADD45A. CONCLUSION: These findings demonstrate that selectively targeting EHMT2, HDAC1, and HDAC2 by concurrent U+C treatment suppresses BC tumor progression via epigenetic remodeling of BIRC5 and GADD45A.

Epigenetic Regulation of Breast Cancer Stem Cells Contributing to Carcinogenesis and Therapeutic Implications.

Globally, breast cancer has remained the most commonly diagnosed cancer and the leading cause of cancer death among women. Breast cancer is a highly heterogeneous and phenotypically diverse group of diseases, which require different selection of treatments. Breast cancer stem cells (BCSCs), a small subset of cancer cells with stem cell-like properties, play essential roles in breast cancer progression, recurrence, metastasis, chemoresistance and treatments. Epigenetics is defined as inheritable changes in gene expression without alteration in DNA sequence. Epigenetic regulation includes DNA methylation and demethylation, as well as histone modifications. Aberrant epigenetic regulation results in carcinogenesis. In this review, the mechanism of epigenetic regulation involved in carcinogenesis, therapeutic resistance and metastasis of BCSCs will be discussed, and finally, the therapies targeting these biomarkers will be presented.

MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients.

(1) Background: methionine cycle is not only essential for cancer cell proliferation but is also critical for metabolic reprogramming, a cancer hallmark. Hepatic and extrahepatic tissues methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A that catalyze the formation of S-adenosylmethionine (SAM), the principal biological methyl donor. Glycine N-methyltransferase (GNMT) further utilizes SAM for sarcosine formation, thus it regulates the ratio of SAM:S-adenosylhomocysteine (SAH). (2) Methods: by analyzing the TCGA/GTEx datasets available within GEPIA2, we discovered that breast cancer patients with higher MAT2A had worse survival rate (p = 0.0057). Protein expression pattern of MAT1AA, MAT2A and GNMT were investigated in the tissue microarray in our own cohort (n = 252) by immunohistochemistry. MAT2A C/N expression ratio and cell invasion activity were further investigated in a panel of breast cancer cell lines. (3) Results: GNMT and MAT1A were detected in the cytoplasm, whereas MAT2A showed both cytoplasmic and nuclear immunoreactivity. Neither GNMT nor MAT1A protein expression was associated with patient survival rate in our cohort. Kaplan-Meier survival curves showed that a higher cytoplasmic/nuclear (C/N) MAT2A protein expression ratio correlated with poor overall survival (5 year survival rate: 93.7% vs. 83.3%, C/N ratio ≥ 1.0 vs. C/N ratio < 1.0, log-rank p = 0.004). Accordingly, a MAT2A C/N expression ratio ≥ 1.0 was determined as an independent risk factor by Cox regression analysis (hazard ratio = 2.771, p = 0.018, n = 252). In vitro studies found that breast cancer cell lines with a higher MAT2A C/N ratio were more invasive. (4) Conclusions: the subcellular localization of MAT2A may affect its functions, and elevated MAT2A C/N ratio in breast cancer cells is associated with increased invasiveness. MAT2A C/N expression ratio determined by IHC staining could serve as a novel independent prognostic marker for breast cancer.

Recent Discoveries of Macromolecule- and Cell-Based Biomarkers and Therapeutic Implications in Breast Cancer.

Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer-related mortality in women worldwide. Breast cancer is fairly heterogeneous and reveals six molecular subtypes: luminal A, luminal B, HER2+, basal-like subtype (ER-, PR-, and HER2-), normal breast-like, and claudin-low. Breast cancer screening and early diagnosis play critical roles in improving therapeutic outcomes and prognosis. Mammography is currently the main commercially available detection method for breast cancer; however, it has numerous limitations. Therefore, reliable noninvasive diagnostic and prognostic biomarkers are required. Biomarkers used in cancer range from macromolecules, such as DNA, RNA, and proteins, to whole cells. Biomarkers for cancer risk, diagnosis, proliferation, metastasis, drug resistance, and prognosis have been identified in breast cancer. In addition, there is currently a greater demand for personalized or precise treatments; moreover, the identification of novel biomarkers to further the development of new drugs is urgently needed. In this review, we summarize and focus on the recent discoveries of promising macromolecules and cell-based biomarkers for the diagnosis and prognosis of breast cancer and provide implications for therapeutic strategies.

Fabrication of Double Emission Enhancement Fluorescent Nanoparticles with Combined PET and AIEE Effects.

The major challenge in the fabrication of fluorescent silica nanoparticles (FSNs) based on dye-doped silica nanoparticles (DDSNs) is aggregation-caused fluorescence quenching. Here, we constructed an FSN based on a double emission enhancement (DEE) platform. A thio-reactive fluorescence turn-on molecule, N-butyl-4-(4-maleimidostyryl)-1,8-naphthalimide (CS), was bound to a silane coupling agent, (3-mercaptopropyl)-trimethoxysilane (MPTMS), and the product N-butyl-4-(3-(trimethoxysilyl-propylthio)styryl)-1,8-naphthalimide (CSP) was further used to fabricate a core-shell nanoparticle through the Stöber method. We concluded that the turn-on emission by CSP originated from the photoinduced electron transfer (PET) between the maleimide moiety and the CSP core scaffold, and the second emission enhancement was attributed to the aggregation-induced emission enhancement (AIEE) in CSP when encapsulated inside a core-shell nanoparticle. Thus, FSNs could be obtained through DEE based on a combination of PET and AIEE effects. Systematic investigations verified that the resulting FSNs showed the traditional solvent-independent and photostable optical properties. The results implied that the novel FSNs are suitable as biomarkers in living cells and function as fluorescent visualizing agents for intracellular imaging and drug carriers.

Anatomical Versus Non-anatomical Resection for Hepatocellular Carcinoma, a Propensity-matched Analysis Between Taiwanese and Japanese Patients.

BACKGROUND/AIM: The aim of the study was to compare the outcomes of anatomical resection (AR) versus non-anatomical resection (NAR) for Japanese and Taiwanese patients with single, resectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A propensity score matched (PSM) analysis was performed to compare the outcomes of the AR group to those of the NAR group. Tumor size <5 cm, T1 or T2 grade, without evidence of extrahepatic metastasis, invasion of portal or hepatic veins, or direct invasion of adjacent organs, were included in the study. RESULTS: A total of 385 cases (Taiwanese 105, Japanese 280) were analyzed. After PSM, a total of 152 cases remain (Taiwan and Japan both 76 cases). Disease-free survival (DFS) and overall survival (OS) data were not significantly different between the two groups at 5 years follow-up. CONCLUSION: AR of HCC in Japanese patients has a similar 5-year DFS and OS as NAR of HCC in Taiwanese patients.

An Immunosensor for the Detection of ULBP2 Biomarker.

Pancreatic cancer (PC) is a global health problem that features a very high mortality rate. The UL16 binding protein 2 (ULBP2) is a new biomarker for PC detection. This study develops a simple, reliable, and inexpensive immunosensor for the detection of the ULBP2 antigen while also investigating the effects of an array configuration of connected sensors and zinc oxide (ZnO) nanoparticles on the immunosensor's sensitivity. The ULBP2 antibody was immobilized onto the screen-printed carbon electrode (SPCE) surfaces of three different sensors: a simple SPCE (ULBP2-SPCE); an SPCE array, which is a series of identical SPCE connected to each other at different arrangements of rows and columns (ULBP2-SPCE-1x2 and ULBP2-SPCE-1x3); and an SPCE combined with ZnO nanoparticles (ULBP2-ZnO/SPCE). Impedance spectrum measurements for the immunosensors to ULBP2 antigen were conducted and compared. According to the result, the array configurations (ULBP2-SPCE-1x2 and ULBP2-SPCE-1x3) show an improvement of sensitivity compared to the ULBP2-SPCE alone, but the improvement is not as significant as that of the ULBP2-ZnO/SPCE configuration (ULBP2-ZnO/SPCE > ULBP2-SPCE: 18 times larger). The ULBP2-ZnO/SPCE immunosensor has a low limit of detection (1 pg/mL) and a high sensitivity (332.2 Ω/Log(pg/mL)), excellent linearity (R2 = 0.98), good repeatability (coefficients of variation = 5.03%), and is stable in long-term storage (retaining 95% activity after 28 days storage). In an array configuration, the immunosensor has an increased signal-to-noise ratio (ULBP2-SPCE-1x3 > ULBP2-SPCE: 1.5-fold) and sensitivity (ULBP2-SPCE-1x3 > ULBP2-SPCE: 2.6-fold). In conclusion, either the modification with ZnO nanoparticles onto the sensor or the use of an array configuration of sensors can enhance the immunosensor's sensitivity. In this study, the best immunosensor for detecting ULBP2 antigens is the ULBP2-ZnO/SPCE immunosensor.

Impact of mycoplasma pneumonia infection on urticaria: A nationwide, population-based retrospective cohort study in Taiwan.

Mycoplasma pneumonia (MP) infection might be pathogenically closely related to urticaria. This study is a nationwide population-based cohort study from 1997 to 2013, which investigated the association between MP infection and urticaria in Taiwan. A total of 1,175 patients were included for the study group, and 2,350 for the control group. Multivariate Cox regression analysis was performed to estimate the adjusted hazard ratio (aHR) for urticaria. Result showed that 254 patients with new-onset urticaria were involved in the study group and 465 incident cases in the control group. The incidence rates (per 100,000 person-months) of urticaria were 37.2 and 32.5 in the study and control groups, respectively. The relative risk is 1.1 (95% CI = 1.0-1.3) indicating no significant correlation between MP and urticaria. The multivariate analysis revealed that the risk of urticaria with MP infection (aHR = 1.1, P = 0.1058) had no statistically significance difference compared to the control group. However, the risk of urticaria in MP-infected patients aged between 20 and 59 years old was found to have increased (aHR = 1.6, 95% CI = 1.1-2.2) prior to a diagnosis.

The impact of global budgeting in Taiwan on inpatients with unexplained fever.

Unexplained fever is one of the most common and difficult diagnostic problems faced daily by clinicians. This study evaluated the differences in health service utilization, health care expenditures, and quality of care provided to patients with unexplained fever before and after global budget (GB) implementation in Taiwan.The National Health Insurance Research Database was used for analyzing the health care expenditures and quality of care before and after implementation of the GB system. Patients diagnosed as having unexplained fever during 2000-2001 were recruited; their 2000-2001 and 2004-2005 data were considered baseline and postintervention data, respectively.Data of 259 patients with unexplained fever were analyzed. The mean lengths of stay (LOSs) before and after GB system implementation were 4.22 ±â€Š0.35 days and 5.29 ±â€Š0.70 days, respectively. The mean costs of different health care expenditures before and after implementation of the GB system were as follows: the mean diagnostic, drug, therapy, and total costs increased respectively from New Taiwan Dollar (NT$) 1440.05 ±â€ŠNT$97.43, NT$3249.90 ±â€ŠNT$1108.27, NT$421.03 ±â€ŠNT$100.03, and NT$13,866.77 ±â€ŠNT$2,114.95 before GB system implementation to NT$2224.34 ±â€ŠNT$238.36, NT$4272.31 ±â€ŠNT$1466.90, NT$2217.03 ±â€ŠNT$672.20, and NT$22,856.41 ±â€ŠNT$4,196.28 after implementation. The mean rates of revisiting the emergency department within 3 days and readmission within 14 days increased respectively from 10.5% ±â€Š2.7% and 8.3% ±â€Š2.4% before implementation to 6.3% ±â€Š2.2% and 4.0% ±â€Š1.7% after implementation.GB significantly increased LOS and incremental total costs for patients with unexplained fever; but improved the quality of care.

Role of Cancer Stem Cells in Cholangiocarcinoma and Therapeutic Implications.

Cholangiocarcinoma (CCA) is the second most common type of liver cancer, and is highly aggressive with very poor prognosis. CCA is classified into intrahepatic cholangiocarcinoma (iCCA) and extra-hepatic cholangiocarcinoma (eCCA), which is further stratified into perihilar (pCCA) and distal (dCCA). Cancer stem cells (CSCs) are a subpopulation of cancer cells capable of tumor initiation and malignant growth, and are also responsible for chemoresistance. Thus, CSCs play an important role in CCA carcinogenesis. Surface markers such as CD133, CD24, CD44, EpCAM, Sox2, CD49f, and CD117 are important for identifying and isolating CCA CSCs. CSCs are present in the tumor microenvironment (TME), termed 'CSC niche', where cellular components and soluble factors interact to promote tumor initiation. Epithelial-to-mesenchymal transition (EMT) is another important mechanism underlying carcinogenesis, involved in the invasiveness, metastasis and chemoresistance of cancer. It has been demonstrated that EMT plays a critical role in generating CSCs. Therapies targeting the surface markers and signaling pathways of CCA CSCs, proteins involved in TME, and immune checkpoint proteins are currently under investigation. Therefore, this review focuses on recent studies on the roles of CSCs in CCA; the possible therapeutic strategies targeting CSCs of CCA are also discussed.

Yolk Sac Tumor in an Eight-Year-Old Girl: A Case Report and Literature Review.

Yolk sac tumor (YST), which most frequently arises in the gonads as a type of germ cell tumor, is rare in children but is highly malignant. It has been suggested that alpha-fetoprotein (AFP) can be applied as a feasible tumor marker because its level was elevated in >90% of YST. The treatment generally involves debulking surgery of tumors followed by systemic chemotherapy. Metastasis process of YST in children is different from that in adults and thus the treatment option is required. In this study, we described a rare case of YST in terms of the clinical manifestation, imaging, and histopathology findings, diagnosis and treatment in an 8-year-old girl. Furthermore, it is important to investigate more thoroughly a patient with history of intermittent abdominal pain and fever with previously multiple accesses, because these might be the critical signs for YST that should be alarmed for early treatment. Although YST is rare in children, pediatric physicians should be aware of this and prompt treatment should be addressed.