Taiwanese dermatological association (TDA) consensus for the management of pemphigus.

Pemphigus is an uncommon but life-threatening autoimmune blistering disease characterized by the presence of antibodies against desmogleins. Without effective treatment, pemphigus can result in significant morbidity and mortality. Existing consensus statements on pemphigus management from international medical groups provide varying guidelines, especially on treatment. Thus, on January 4, 2020, a panel of seven dermatology experts from the Taiwanese Dermatological Association (TDA) and one rheumatology expert convened to develop a consensus for the management of pemphigus. These experts with extensive experience in pemphigus management were recommended by their respective teaching hospitals and primary care clinics in Taiwan and by the TDA. The meeting reviewed the available consensus statements from international dermatology groups, including the European Dermatology Forum (EDF), the European Academy of Dermatology and Venereology (EADV), and the International Bullous Diseases Consensus Group. Using these guidelines as a basis for discussion and consensus formulation, these experts formulated their consensus statement that provides practical, concise but comprehensive recommendations as to the diagnosis, treatment, and monitoring of pemphigus patients in Taiwan. This consensus serves as a clinical reference for physicians for the management of pemphigus in Taiwan or wherever it may be applicable.

Increased HIF-1α expression in T cells and associated with enhanced Th17 pathway in systemic lupus erythematosus.

BACKGROUND/PURPOSE: Recent emerging evidence indicates that dysfunction of metabolic remodeling underlies aberrant T cell immune responses in systemic lupus erythematosus (SLE). This study was undertaken to investigate the expression of HIF-1α, a regulator of metabolic reprogramming, in T cells from SLE. METHODS: HIF-1α expression in T lymphocytes from SLE patients was examined by quantitative polymerase chain reaction (PCR) and the protein expression was analyzed with intracellular staining in flow cytometry. HIF-1α was overexpressed in murine CD4 T cells via transducing T cells with HIF-1α containing lentivirus. The expression of HIF-1α, metabolic- and Th17-associated genes in T cells from SLE patients and its association with clinical manifestation was analyzed. RESULTS: HIF-1α expression is increased in CD4 T cells from SLE patients both in intracellular staining and quantitative PCR analysis. In addition, there is enhanced HIF-1α expression in Th17-skewing murine T cells, and lentivirus-mediated HIF-1α overexpression promotes Th17 differentiation. Moreover, HIF-1α gene expression is positively correlated with the expression of glycolysis- and IL-17-associated genes in SLE patients. CONCLUSION: HIF-1α expression is increased in T cells from SLE patients, and is positively correlated with glycolysis- and Th17- associated pathway, implicating HIF-1α contributes to the activation of Th17 cells in SLE, and represents a potential novel therapeutic target.

The interaction-induced dipole of H2-H: New ab initio results and spherical tensor analysis.

We present numerical results for the dipole induced by interactions between a hydrogen molecule and a hydrogen atom, obtained from finite-field calculations in an aug-cc-pV5Z basis at the unrestricted coupled-cluster level including all single and double excitations in the exponential operator applied to a restricted Hartree-Fock reference state, with the triple excitations treated perturbatively, i.e., UCCSD(T) level. The Cartesian components of the dipole have been computed for nine different bond lengths r of H2 ranging from 0.942 a.u. to 2.801 a.u., for 16 different separations R between the centers of mass of H2 and H between 3.0 a.u. and 10.0 a.u., and for 19 angles θ between the H2 bond vector r and the vector R from the H2 center of mass to the nucleus of the H atom, ranging from 0° to 90° in intervals of 5°. We have expanded the interaction-induced dipole as a series in the spherical harmonics of the orientation angles of the H2 bond axis and of the intermolecular vector, with coefficients DλL(r, R). For the geometrical configurations that we have studied in this work, the most important coefficients DλL(r, R) in the series expansion are D01(r, R), D21(r, R), D23(r, R), D43(r, R), and D45(r, R). We show that the ab initio results for D23(r, R) and D45(r, R) converge to the classical induction forms at large R. The convergence of D45(r, R) to the hexadecapolar induction form is demonstrated for the first time. Close agreement between the long-range ab initio values of D01(r0 = 1.449 a.u., R) and the known analytical values due to van der Waals dispersion and back induction is also demonstrated for the first time. At shorter range, D01(r, R) characterizes isotropic overlap and exchange effects, as well as dispersion. The coefficients D21(r, R) and D43(r, R) represent anisotropic overlap effects. Our results for the DλL(r, R) coefficients are useful for calculations of the line shapes for collision-induced absorption and collision-induced emission in the infrared and far-infrared by gas mixtures containing both H2 molecules and H atoms.

Chromoblastomycosis in Taiwan: A report of 30 cases and a review of the literature.

Chromoblastomycosis (CBM) is an implantation mycosis characterized by the presence of pigmented muriform cells in tissue. CBM is endemic in Taiwan, but only three formal cases have been reported to date because of underreporting. To describe and update its epidemiologic features, we report a series of 30 cases between 2003 and 2016 at a single medical center. Patients were predominately male (2.75:1). The mean age of onset was 65.9 years, and disease duration ranged from 2 months to 20 years. Diabetes was the most common comorbidity, and extremities were the most frequent sites of involvement. The lesions presented as papuloplaque, verrucous, cicatricial, targetoid, or mixed types. The dermoscopic features were variable, including red dots, white vague areas, black globules, and sand-like patterns. Among 10 Fonsecaea isolates further identified by sequencing the ITS regions of ribosomal DNA, nine were F. monophora and one was F. nubica. All but one patient received either systemic antifungal agents, surgical excision, or both. Surgical excision achieved a higher complete remission rate than the other forms of treatment did.

Urinary incontinence in female outpatients in Singapore.

INTRODUCTION AND HYPOTHESIS: The aims of this study were to determine the prevalence, symptom characteristics, risk factors and impact on quality of life (QoL) of urinary incontinence (UI) in female outpatients in Singapore, to describe the attitudes of these women towards UI, and to investigate the barriers to healthcare-seeking behaviour in symptomatic women. METHODS: This was a cross-sectional study in a convenience sample and 249 women enrolled from outpatient clinics. A modified self-administered questionnaire which included two validated instruments (the International Consultation on Incontinence Questionnaire-Urinary Incontinence short form and the Incontinence Impact Questionnaire-7) was used. RESULTS: Questionnaires from 230 women were included in the analysis. The overall prevalence of UI was 41.74% (95% CI 35.49-48.26%). Most of the symptomatic women suffered from mild UI and the most common subtype was stress UI. Age (OR 1.03, 95% CI 1.00-1.05), vaginal delivery (OR 2.67, 95% CI 1.43-4.97) and being sexually active (OR 2.41, 95% CI 1.31-4.43) were associated with UI. Among symptomatic women, only 41.25% (95% CI 30.82-52.53%) had sought medical attention before. The most common barrier to healthcare-seeking behaviour was embarrassment. The median QoL score was 33.33, indicating a mild impact of UI on QoL. QoL score was associated with UI severity (p < 0.001). CONCLUSIONS: Despite the high prevalence of UI, only about 41% of UI sufferers had sought medical attention before. Common barriers included embarrassment, fear of surgery and misconceptions. This study emphasizes the need for policy development for UI prevention and management in Singapore.

Computationally efficient method for estimation of angle of arrival with non-uniform reconfigurable receiver arrays.

The main focus of this paper is the design and formulation of a computationally efficient approach to the estimation of the angle of arrival with non-uniform reconfigurable receiver arrays. Subsequent to demodulation and matched filtering, the main signal processing task is a double-integration operation. The simplicity of this algorithm enables the implementation of the estimation procedure with simple operational amplifier (op-amp) circuits for real-time realization. This technique does not require uniform and structured array configurations, and is most effective for the estimation of angle of arrival with dynamically reconfigurable receiver arrays.

Optimization of computation efficiency in underwater acoustic navigation system.

This paper presents a technique for the estimation of the relative bearing angle between the unmanned underwater vehicle (UUV) and the base station for the homing and docking operations. The key requirement of this project includes computation efficiency and estimation accuracy for direct implementation onto the UUV electronic hardware, subject to the extreme constraints of physical limitation of the hardware due to the size and dimension of the UUV housing, electric power consumption for the requirement of UUV survey duration and range coverage, and heat dissipation of the hardware. Subsequent to the design and development of the algorithm, two phases of experiments were conducted to illustrate the feasibility and capability of this technique. The presentation of this paper includes system modeling, mathematical analysis, and results from laboratory experiments and full-scale sea tests.

Discovery of prognostic biomarkers for predicting lung cancer metastasis using microarray and survival data.

BACKGROUND: Few studies have investigated prognostic biomarkers of distant metastases of lung cancer. One of the central difficulties in identifying biomarkers from microarray data is the availability of only a small number of samples, which results overtraining. Recently obtained evidence reveals that epithelial-mesenchymal transition (EMT) of tumor cells causes metastasis, which is detrimental to patients' survival. RESULTS: This work proposes a novel optimization approach to discovering EMT-related prognostic biomarkers to predict the distant metastasis of lung cancer using both microarray and survival data. This weighted objective function maximizes both the accuracy of prediction of distant metastasis and the area between the disease-free survival curves of the non-distant and distant metastases. Seventy-eight patients with lung cancer and a follow-up time of 120 months are used to identify a set of gene markers and an independent cohort of 26 patients is used to evaluate the identified biomarkers. The medical records of the 78 patients show a significant difference between the disease-free survival times of the 37 non-distant- and the 41 distant-metastasis patients. The experimental results thus obtained are as follows. 1) The use of disease-free survival curves can compensate for the shortcoming of insufficient samples and greatly increase the test accuracy by 11.10%; and 2) the support vector machine with a set of 17 transcripts, such as CCL16 and CDKN2AIP, can yield a leave-one-out cross-validation accuracy of 93.59%, a test accuracy of 76.92%, a large disease-free survival area of 74.81%, and a mean survival prediction error of 3.99 months. The identified putative biomarkers are examined using related studies and signaling pathways to reveal the potential effectiveness of the biomarkers in prospective confirmatory studies. CONCLUSIONS: The proposed new optimization approach to identifying prognostic biomarkers by combining multiple sources of data (microarray and survival) can facilitate the accurate selection of biomarkers that are most relevant to the disease while solving the problem of insufficient samples.

SCMHBP: prediction and analysis of heme binding proteins using propensity scores of dipeptides.

BACKGROUND: Heme binding proteins (HBPs) are metalloproteins that contain a heme ligand (an iron-porphyrin complex) as the prosthetic group. Several computational methods have been proposed to predict heme binding residues and thereby to understand the interactions between heme and its host proteins. However, few in silico methods for identifying HBPs have been proposed. RESULTS: This work proposes a scoring card method (SCM) based method (named SCMHBP) for predicting and analyzing HBPs from sequences. A balanced dataset of 747 HBPs (selected using a Gene Ontology term GO:0020037) and 747 non-HBPs (selected from 91,414 putative non-HBPs) with an identity of 25% was firstly established. Consequently, a set of scores that quantified the propensity of amino acids and dipeptides to be HBPs is estimated using SCM to maximize the predictive accuracy of SCMHBP. Finally, the informative physicochemical properties of 20 amino acids are identified by utilizing the estimated propensity scores to be used to categorize HBPs. The training and mean test accuracies of SCMHBP applied to three independent test datasets are 85.90% and 71.57%, respectively. SCMHBP performs well relative to comparison with such methods as support vector machine (SVM), decision tree J48, and Bayes classifiers. The putative non-HBPs with high sequence propensity scores are potential HBPs, which can be further validated by experimental confirmation. The propensity scores of individual amino acids and dipeptides are examined to elucidate the interactions between heme and its host proteins. The following characteristics of HBPs are derived from the propensity scores: 1) aromatic side chains are important to the effectiveness of specific HBP functions; 2) a hydrophobic environment is important in the interaction between heme and binding sites; and 3) the whole HBP has low flexibility whereas the heme binding residues are relatively flexible. CONCLUSIONS: SCMHBP yields knowledge that improves our understanding of HBPs rather than merely improves the prediction accuracy in predicting HBPs.

Bronchial asthma is associated with increased risk of chronic kidney disease.

BACKGROUND: Bronchial asthma influences some chronic diseases such as coronary heart disease, diabetes mellitus, and hypertension, but the impact of asthma on vital diseases such as chronic kidney disease is not yet verified. This study aims to clarify the association between bronchial asthma and the risk of developing chronic kidney disease. METHODS: The National Health Research Institute provided a database of one million random subjects for the study. A random sample of 141 064 patients aged ≥18 years without a history of kidney disease was obtained from the database. Among them, there were 35 086 with bronchial asthma and 105 258 without asthma matched for sex and age for a ration of 1:3. After adjusting for confounding risk factors, a Cox proportional hazards model was used to compare the risk of developing chronic kidney disease during a three-year follow-up period. RESULTS: Of the subjects with asthma, 2 196 (6.26%) developed chronic kidney disease compared to 4 120 (3.91%) of the control subjects. Cox proportional hazards regression analysis revealed that subjects with asthma were more likely to develop chronic kidney disease (hazard ratio [HR]: 1.56; 95% CI: 1.48-1.64; p < 0.001). After adjusting for sex, age, monthly income, urbanization level, geographic region, diabetes mellitus, hypertension, hyperlipidemia, and steroid use, the HR for asthma patients was 1.40 (95% CI: 1.33-1.48; p = 0.040). There was decreased HRs in steroid use (HR: 0.56; 95% CI: 0.62-0.61; p < 0.001) in the development of chronic kidney disease. Expectorants, bronchodilators, anti-muscarinic agents, airway smooth muscle relaxants, and leukotriene receptor antagonists may also be beneficial in attenuating the risk of chronic kidney disease. CONCLUSIONS: Patients with bronchial asthma may have increased risk of developing chronic kidney disease. The use of steroids or non-steroidal drugs in the treatment of asthma may attenuate this risk.

Increased risk of major depression subsequent to a first-attack and non-infection caused urticaria in adolescence: a nationwide population-based study.

BACKGROUND: Non-infection caused urticaria is a common ailment in adolescents. Its symptoms (e.g., unusual rash appearance, limitation of daily activities, and recurrent itching) may contribute to the development of depressive stress in adolescents; the potential link has not been well studied. This study aimed to investigate the risk of major depression after a first-attack and non-infection caused urticaria. METHODS: This study used the Taiwan Longitudinal Health Insurance Database. A total of 5,755 adolescents hospitalized for a first-attack and non-infection caused urticaria from 2005 to 2009 were recruited as the study group, together with 17,265 matched non-urticarial enrollees who comprised the control group. Patients who had any history of urticaria or depression prior to the evaluation period were excluded. Each patient was followed for one year to identify the occurrence of depression. Cox proportional hazards models were generated to compute the risk of major depression, adjusting for the subjects' sociodemographic characteristics. Depression-free survival curves were also analyzed. RESULTS: Thirty-four (0.6%) adolescents with non-infection caused urticaria and 59 (0.3%) non-urticarial control subjects suffered a new-onset episode of major depression during the study period. The stratified Cox proportional analysis showed that the crude hazard ratio (HR) of depression among adolescents with urticaria was 1.73 times (95% CI, 1.13-2.64) than that of the control subjects without urticaria. Moreover, the HR were higher in physical (HR: 3.39, 95% CI 2.77-11.52) and allergy chronic urticaria (HR: 2.43, 95% CI 3.18-9.78). CONCLUSION: Individuals who have a non-infection caused urticaria during adolescence are at a higher risk of developing major depression.

Intravesical Instillation of Hyaluronic Acid With Epidermal Growth Factor for Restoring Urothelial Denudation and Alleviating Oxidative Stress in Lipopolysaccharide-Induced Interstitial Cystitis of Rats.

PURPOSE: To investigate the efficacy of an intravesical instillation of hyaluronic acid (HA) combined with epidermal growth factor (EGF) for the treatment of interstitial cystitis (IC) using a lipopolysaccharide (LPS)-induced IC animal model. METHODS: A total of 24 female Sprague-Dawley rats were randomized to 4 groups: sham control, IC, HA, and treatment (HA/ EGF) groups. A polyethylene-50 tube was placed inside the bladder of each animal. IC was induced by twice-weekly instillations of LPS for 3 weeks, which resulted in chronic injury of the urothelium. Animals in the sham control group only received saline instillation. Treatment solutions of HA and HA/EGF were given on days 0, 7, and 14 after IC induction (400 µL of HA in a concentration of 0.4 mg/0.5 mL and 400 µL of NewEpi, a commercialized HA/EGF mixture containing 2 µg of EGF and 0.4 mg of sodium hyaluronate). Animals were sacrificed on day 21 for further examinations. RESULTS: The HA/EGF group showed visible improvement in hematuria with a significant reduction of red blood cells in the urine compared to the HA group. Histological examination revealed that HA/EGF treatment reversed the abnormalities developed in IC, including infiltration of inflammatory cells, irregular re-epithelialization, and fibrotic tissue. Moreover, HA/ EGF significantly reduced the levels of proinflammation cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1ß) and substantially lowered the elevated oxidative stress biomarker malondialdehyde, yet restored the levels of antioxidant enzymes glutathione peroxidase and superoxide dismutase, with superior results than HA treatment. Cystometry studies indicated that HA/EGF significantly prolonged intercontraction interval and increased micturition volume. CONCLUSION: HA/EGF has been demonstrated as a more effective treatment for enhancing the urothelium lining and reducing inflammatory changes to alleviate clinical symptoms associated with IC in rats, compared to HA alone.

HCS-Neurons: identifying phenotypic changes in multi-neuron images upon drug treatments of high-content screening.

BACKGROUND: High-content screening (HCS) has become a powerful tool for drug discovery. However, the discovery of drugs targeting neurons is still hampered by the inability to accurately identify and quantify the phenotypic changes of multiple neurons in a single image (named multi-neuron image) of a high-content screen. Therefore, it is desirable to develop an automated image analysis method for analyzing multi-neuron images. RESULTS: We propose an automated analysis method with novel descriptors of neuromorphology features for analyzing HCS-based multi-neuron images, called HCS-neurons. To observe multiple phenotypic changes of neurons, we propose two kinds of descriptors which are neuron feature descriptor (NFD) of 13 neuromorphology features, e.g., neurite length, and generic feature descriptors (GFDs), e.g., Haralick texture. HCS-neurons can 1) automatically extract all quantitative phenotype features in both NFD and GFDs, 2) identify statistically significant phenotypic changes upon drug treatments using ANOVA and regression analysis, and 3) generate an accurate classifier to group neurons treated by different drug concentrations using support vector machine and an intelligent feature selection method. To evaluate HCS-neurons, we treated P19 neurons with nocodazole (a microtubule depolymerizing drug which has been shown to impair neurite development) at six concentrations ranging from 0 to 1000 ng/mL. The experimental results show that all the 13 features of NFD have statistically significant difference with respect to changes in various levels of nocodazole drug concentrations (NDC) and the phenotypic changes of neurites were consistent to the known effect of nocodazole in promoting neurite retraction. Three identified features, total neurite length, average neurite length, and average neurite area were able to achieve an independent test accuracy of 90.28% for the six-dosage classification problem. This NFD module and neuron image datasets are provided as a freely downloadable MatLab project at http://iclab.life.nctu.edu.tw/HCS-Neurons. CONCLUSIONS: Few automatic methods focus on analyzing multi-neuron images collected from HCS used in drug discovery. We provided an automatic HCS-based method for generating accurate classifiers to classify neurons based on their phenotypic changes upon drug treatments. The proposed HCS-neurons method is helpful in identifying and classifying chemical or biological molecules that alter the morphology of a group of neurons in HCS.

Targeting type 2 inflammation in bullous pemphigoid: current and emerging therapeutic approaches.

Bullous pemphigoid (BP) is one of the most common autoimmune bullous diseases and mainly affects an elderly population with multi-morbidity. Due to the frailty of many BP patients, existing treatment options are limited. The blisters associated with BP result from IgG and IgE autoantibodies binding to the central components of hemidesmosome, BP180, and BP230, stimulating a destructive inflammatory process. The known characteristic features of BP, such as intense pruritus, urticarial prodrome, peripheral eosinophilia, elevated IgE, as well as recent expanding evidence from in vitro and in vivo studies implicate type 2 inflammation as an important driver of BP pathogenesis. Type 2 inflammation is an inflammatory pathway involving a subset of CD4+ T cells that secrete IL-4, IL-5, and IL-13, IgE-secreting B cells, and granulocytes, such as eosinophils, mast cells, and basophils. It is believed that effectors in type 2 inflammation may serve as novel and effective treatment targets for BP. This review focuses on recent understandings of BP pathogenesis with a particular emphasis on the role of type 2 inflammation. We summarize current clinical evidence of using rituximab (B-cell depletion), omalizumab (anti-IgE antibody), and dupilumab (anti-IL-4/13 antibody) in the treatment of BP. The latest advances in emerging targeted therapeutic approaches for BP treatment are also discussed.

Advancing Treatment in Bullous Pemphigoid: A Comprehensive Review of Novel Therapeutic Targets and Approaches.

Bullous pemphigoid is one of the most common autoimmune bullous diseases occurring primarily in the elderly. Pathogenic autoantibodies against BP180 and BP230 at the dermal-epidermal junction cause subepidermal blisters, erosions, and intense pruritus, all of which adversely affect the patients' quality of life and may increase their morbidity and mortality. Current systemic treatment options for bullous pemphigoid are limited to corticosteroids and immunosuppressants, which can have substantial side effects on these vulnerable patients that even exceed their therapeutic benefits. Therefore, more precisely, targeting therapies to the pathogenic cells and molecules in bullous pemphigoid is an urgent issue. In this review, we describe the pathophysiology of bullous pemphigoid, focusing on autoantibodies, complements, eosinophils, neutrophils, proteases, and the T helper 2 and 17 axes since they are crucial in promoting proinflammatory environments. We also highlight the emerging therapeutic targets for bullous pemphigoid and their latest discoveries in clinical trials or experimental studies. Further well-designed studies are required to establish the efficacy and safety of these prospective therapeutic options.

Characterization of hemodialysis fistulas experienced abrupt thrombosis and determination of a proper follow-up protocol: A retrospective cohort study and an interventionist's perspective.

Abrupt thrombosis is a form of thrombosis that occurs unexpectedly and without being preceded by hemodialysis fistula (AVF) dysfunction during dialysis. We found that AVFs with a history of abrupt thrombosis (abtAVF) appeared to have more episodes of thrombosis and required more frequent interventions than those without such history. Therefore, we sought to characterize the abtAVFs and examined our follow-up protocols to determine which one is optimal. We performed a retrospective cohort study using routinely collected data. The thrombosis rate, AVF loss rate, thrombosis-free primary patency, and secondary patency were calculated. Additionally, the restenosis rates of the AVFs under the follow-up protocol/sub-protocols and the abtAVFs were determined. The thrombosis rate, procedure rate, AVF loss rate, thrombosis-free primary patency, and secondary patency of the abtAVFs were 0.237/pt-yr, 2.702/pt-yr, 0.027/pt-yr, 78.3%, and 96.0%, respectively. The restenosis rate for AVFs in the abtAVF group and the angiographic follow-up sub-protocol were similar. However, the abtAVF group had a significantly higher thrombosis rate and AVF loss rate than AVFs without a history of abrupt thrombosis (n-abtAVF). The lowest thrombosis rate was observed for n-abtAVFs, followed up periodically under the outpatient or angiographic sub-protocols. AVFs with a history of abrupt thrombosis had a high restenosis rate, and periodic angiographic follow-up with a mean interval of 3 months was presumed appropriate. For selected populations, such as salvage-challenging AVFs, periodic outpatient or angiographic follow-up was mandatory to extend their usable lives for hemodialysis.

Quantitative physical examination indicators to detect patients with stenosis at a high risk of thrombosis at hemodialysis vascular access sites: A retrospective case-control study.

BACKGROUND: Quantitative physical examination (PE) indicators, including palpable pulsatility length and outflow scores, can be used to quantify stenosis severity at hemodialysis vascular access sites. It is known that the risk of high-shear-related thrombosis is increased when the minimal luminal diameter (MLD) of stenosis decreases. At present, MLD is measured using sonography or angiography. This study sought to determine the relationship between quantitative PE indicators and MLD and report their diagnostic performance in detecting patients with stenosis at a high risk of thrombosis. METHODS: We performed a retrospective case-control study using routinely collected data. We used the post-stenosis palpable pulsatility length (sPPL) and pulse-and-thrill based outflow score to assess the severity of AVF inflow and outflow stenosis, respectively. We recorded paired quantitative PE indicators and MLD before and after angioplasty in patients enrolled over a 4-month period. RESULTS: A total of 249 paired PE indicators and MLD measurements were obtained from 163 patients. A receiver operating characteristic curve analysis showed that an MLD cutoff value of <1.55 mm and an MLD of <1.95 mm discriminated sPPL = 0 and PESOS (physical examination significant outflow stenosis)/1- of the outflow score, respectively, from all other measurements, with the area under the curve values of 0.8922 and 0.9618, respectively. With sPPL = 0 and PESOS/1- of the outflow score as diagnostic tools to detect inflow stenosis with an MLD of ⩽1.5 mm and outflow stenosis with an MLD of ⩽1.9 mm at vascular access sites, sensitivity = 86.00% and 88.46%; specificity = 97.67% and 92.11%; positive predictive values of 97.73% and 92.00% and negative predictive values of 85.71% and 88.61%, respectively, were observed. CONCLUSIONS: Our preliminary results showed that physical examination can potentially be a diagnostic tool in detecting patients with stenosis who are at a high risk of thrombosis at hemodialysis vascular access sites with high diagnostic accuracy.

Prediction and analysis of protein solubility using a novel scoring card method with dipeptide composition.

BACKGROUND: Existing methods for predicting protein solubility on overexpression in Escherichia coli advance performance by using ensemble classifiers such as two-stage support vector machine (SVM) based classifiers and a number of feature types such as physicochemical properties, amino acid and dipeptide composition, accompanied with feature selection. It is desirable to develop a simple and easily interpretable method for predicting protein solubility, compared to existing complex SVM-based methods. RESULTS: This study proposes a novel scoring card method (SCM) by using dipeptide composition only to estimate solubility scores of sequences for predicting protein solubility. SCM calculates the propensities of 400 individual dipeptides to be soluble using statistic discrimination between soluble and insoluble proteins of a training data set. Consequently, the propensity scores of all dipeptides are further optimized using an intelligent genetic algorithm. The solubility score of a sequence is determined by the weighted sum of all propensity scores and dipeptide composition. To evaluate SCM by performance comparisons, four data sets with different sizes and variation degrees of experimental conditions were used. The results show that the simple method SCM with interpretable propensities of dipeptides has promising performance, compared with existing SVM-based ensemble methods with a number of feature types. Furthermore, the propensities of dipeptides and solubility scores of sequences can provide insights to protein solubility. For example, the analysis of dipeptide scores shows high propensity of α-helix structure and thermophilic proteins to be soluble. CONCLUSIONS: The propensities of individual dipeptides to be soluble are varied for proteins under altered experimental conditions. For accurately predicting protein solubility using SCM, it is better to customize the score card of dipeptide propensities by using a training data set under the same specified experimental conditions. The proposed method SCM with solubility scores and dipeptide propensities can be easily applied to the protein function prediction problems that dipeptide composition features play an important role. AVAILABILITY: The used datasets, source codes of SCM, and supplementary files are available at http://iclab.life.nctu.edu.tw/SCM/.

The effects of oxaloacetate on hydrogen peroxide generation from ascorbate and epigallocatechin gallate in cell culture media: potential for altering cell metabolism.

Several phenolic compounds as well as ascorbate can oxidise in certain cell culture media (especially Dulbecco's modified Eagle's medium (DMEM)) to generate hydrogen peroxide. Addition of oxaloacetate decreased the levels of H(2)O(2) detected and the oxaloacetate was depleted. Oxaloacetate was approximately as effective as pyruvate in decreasing H(2)O(2) levels and more effective than α-ketoglutarate. Our data raise important issues to consider when interpreting the behaviour and metabolism of cells in culture (which are both altered by the oxidative stress of cell culture) and their apparent response to addition of autooxidisable compounds such as ascorbate and epigallocatechin gallate.

A transurethral catheter-based ultrasound system for multi-modal fusion.

Current methods of prostate cancer diagnosis and therapy rely on accurate imaging of the prostate using real-time ultrasound. Transurethral ultrasound (TUUS) may improve upon the current gold standard through improved 3D visualization and co-registration (fusion) with CT and MRI. A prototype transurethral ultrasound (TUUS) catheter-based transducer array and system was developed, featuring 32 elements with a diameter of 18F (6mm). A robust, multi-channel ultrasound transceiver was also developed to enable TUUS imaging using pulse-echo and frequency-based signal processing methods. The feasibility of a TUUS imaging system suitable for multi-modal image fusion and novel ultrasound signaling techniques was demonstrated.