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Introduction This study, for the first time to our knowledge, evaluated the efficacy of ropeginterferon alfa-2b, a long-acting pegylated interferon (IFN)-alfa, in the treatment of COVID-19. Methods We retrospectively evaluated ropeginterferon alfa-2b administered subcutaneously at a single dose of 250 µg for the treatment of mild and moderate COVID-19. Primary outcome was to compare the overall negative conversion time from the confirmed, last positive SARS-CoV-2 RT-PCR to the first RT-PCR negative conversion between patients receiving ropeginterferon alfa-2b plus standard of care (SOC) and those receiving SOC alone. Results Thirty-five patients with mild COVID-19 and 37 patients with moderate disease were included. Of them, 19 patients received SOC plus ropeginterferon alfa-2b and 53 patients received SOC alone. All patients with moderate disease in the ropeginterferon alfa-2b group showed RT-PCR negative conversion within 8 days, while a significant portion of patients in the SOC alone group failed to do so. For patients with moderate disease and age ≤ 65 years old, the ropeginterferon alfa-2b group had statistically significant shorter median RT-PCR conversion time than the SOC alone group (7 vs. 11.5 days, p

Excessive stress is one of the main causes of mental illness. Long-term exposure of stress could affect one's physiological wellbeing (such as hypertension) and psychological condition (such as depression). Multisensory information such as heart rate variability (HRV) and pH can provide suitable information about mental and physical stress. This paper proposes a novel approach for stress condition monitoring using disposable flexible sensors. By integrating flexible amplifiers with a commercially available flexible polyvinylidene difluoride (PVDF) mechanical deformation sensor and a pH-type chemical sensor, the proposed system can detect arterial pulses from the neck and pH levels from sweat located in the back of the body. The system uses organic thin film transistor (OTFT)-based signal amplification front-end circuits with modifications to accommodate the dynamic signal ranges obtained from the sensors. The OTFTs were manufactured on a low-cost flexible polyethylene naphthalate (PEN) substrate using a coater capable of Roll-to-Roll (R2R) deposition. The proposed system can capture physiological indicators with data interrogated by Near Field Communication (NFC). The device has been successfully tested with healthy subjects, demonstrating its feasibility for real-time stress monitoring.

自 1994 年《師資培育法》公布施行後，師資培育管道轉趨多元，師資培育的品質呈現良莠參差。復加上近年來少子女化現象加劇，更使得現行的師資培育機制面臨不少的挑戰。近年來全球對靈性的關注漸增，靈性取向的生涯諮商成為新興思潮。不少研究指出靈性高的個體能從人生全景出發，尋找及整合人生的意義，且有較大的信心進行生涯選擇。既然教師工作是一門富含靈性的助人職業，則職前教育階段師資生的靈性研究更攸關其 生涯抉擇。本研究的問題意識在於究竟當今師資生對於選擇教師工作的動機是基於謀職需要或是出於生涯召喚（career calling）？目前相關研究的進展如何，可有進一步的啟發 ? 本研究採取文獻分析法，從分析靈性取向相關文獻著手，首先探討靈性與師資生生涯發展的關係，其次探究師資生靈性取向生涯召喚的研究現況，並彙整分析國內外靈性及生涯召喚相關量表之發展趨勢。本研究發現師資生有別於於一般大學生，未來的教職具有濃厚的助人及利他色彩，而目前師資職前教育階段尚缺乏靈性取向的生涯發展之相關研究。建議主管教育行政機關、師培大學應轉向關注師資生的內在特質、強化對職前教育 階段師資生之靈性取向生涯輔導，而有志為師者宜審慎面對生涯抉擇及召喚。 Ever since the “Teacher Education Law” was implemented by Ministry of Education in 1994, teacher quality control has encountered challenges, because the teacher-training system changed from a one-track model to a multiple-track model. The decrease in the national birth rate is also affecting job opportunities in the education workplace, making teacher education today face even greater challenges. In recent years, global attention to spirituality has gradually increased, and the career consultation of spiritual orientation has become an emerging issue. Many studies have pointed out that individuals who are spiritually-oriented usually have greater confidence in career choices. Since teaching is a spiritually-oriented job, spiritual studies of preservice teachers are very relevant to their career choices. This study investigates what the prime motivation of being a teacher is, and in view of it, whether it is from a pragmatic need or from career calling. The study also discusses how we get more inspiration from related research. Literature analysis explores the relationship between spirituality and career development of pre-service teachers. In addition, the study reviews the spiritually-oriented career calling scales in order to understand the development trend. The main results are twofold. One of the results shows that pre-service teachers possess more helping and altruistic traits than general college students. The other one result is that there are too few literature reviews referring to spiritually-oriented career development. The recommendation is that the Ministry of Education and universities should pay more attention on the internal traits of pre-service teachers and strengthen spiritually-oriented career guidance and counseling. Finally, this study provides preservice teachers with a way to qualitatively examine their career calling.

Objectives microRNA (miRNA) expression patterns have provided new insight as biomarkers of prognosis as well as novel therapeutic targets for several neoplasms. However, the role of exosomal miRNA in the prognosis of oral squamous cell carcinoma (OSCC) has not yet been completely clarified. Paired primary tumor and normal oral epithelial cells from OSCC patients were obtained, and the exosomal miRNA profiles between them were compared by miRNA microarray analysis. The miRNA levels in the serum exosomes of OSCC patients were verified by real-time quantitative reverse transcription PCR (qRT-PCR) analysis. Finally, the biological functions and the potential as a prognostic marker of the selected miRNA candidates were analyzed in the OSCC cells and patients, respectively. Results Exosomal miR-155 and miR-21 were significantly upregulated, and exosomal miR-126 was dramatically downregulated in the primary OSCC cells and the serum of OSCC patients. In the analysis of oncogenic behaviors, coculture with either miR-155-rich or miR-21-rich exosomes could promote cell proliferation and invasion accompanied with downregulation of PTEN and Bcl-6 tumor suppressors. Moreover, treatment with miR-126-rich exosomes inhibited oncogenic behaviors and oncogene EGFL7 expression in OSCC cells. Finally, exosomal miR-126 was reduced in the serum of the late-staged OSCC patients, and downregulation of blood exosomal miR-126 was associated with poor survival in OSCC patients. Conclusion Exosomal miR-155 and miR-21 are oncogenic miRNAs which suppress PTEN and Bcl-6 expression, and exosomal miR-126 acts as a tumor suppressor which downregulates EGFL7 in OSCC. Furthermore, blood exosomal miRNAs may serve as biomarkers for the diagnosis and prognosis of OSCC.

A free flap is a tissue reconstruction procedure where healthy tissue is harvested to cover up vital structures after wound debridement. Microvascular anastomoses are carried out to join the arteries and veins of the flap with recipient vessels near the target site. Continuous monitoring is required to identify the flap failure and enable early intervention to salvage the flap. Although there are medical instruments that can assist surgeons in monitoring flap viability, high upfront costs and time-consuming data interpretation have hindered the use of such technologies in practice. Surgeons still rely largely on the clinical examination to monitor flaps after operations. This paper presents a low-cost, low-power (6.6 mW), and miniaturized Hamlyn StO 2 (tissue oxygen saturation) sensor that can be embodied as a plaster and attached to a flap for real-time monitoring. Similar to the design of oxygen saturation (SpO 2 /SaO 2 ) sensors, the Hamlyn StO 2 sensor was designed based on photoplethysmography (PPG), but with a different target of quantifying tissue perfusion rather than capturing pulsatile flow. To understand the spectral response to oxygenation/deoxygenation and vascular flow, an active in vitro silicone phantom was developed. The new sensor was validated using the silicone phantom and compared with a commercially available photospectroscopy and laser Doppler machine (O2C, LEA, Germany). In addition, in vivo experiments were conducted using a brachial pressure cuff forearm ischemia model. The experiment results have shown a high correlation between the proposed sensor and the O2C machine (r = 0.672 and p

To date, there has been no policy analysis or review of the effectiveness of the current nurse practitioner (NP) scope of practice regulations in Taiwan. The purpose is of this article was to provide a policy analysis of NP scope of practice regulations in Taiwan.The Longest policy cycle model was used to analyze the NP scope of practice regulations. Policy formation, policy implementation, and policy modification are three steps in this model. Policy formation and policy implementation are described in the first two sections. Regarding policy modification, we used the data collected from a research grant to evaluate the implementation of the NP scope of practice regulations to present the effectiveness of the policy endorsement in Taiwan.The impact of health care services provided by NPs was positive from the viewpoint of the hospital. The top-ranking impact was reducing physicians' workload and increasing the effectiveness of communication and coordination among the team.The economic value of advanced practice nurses needs to be identified, as it can result in optimal professional growth. The Taiwan Association of Nurse Practitioners can design the metrics to measure NPs' contribution and to analyze the financial benefits bestowed by the NP profession based on the study results.

Objective Technologies facilitating continuous free tissue flap monitoring such as near infrared spectroscopy (NIRS) have been shown to improve flap salvage rates. However, the size and associated costs of such technology create a barrier to wider implementation. The aim of this study was to develop and validate a wearable sensor for continuous tissue oxygenation monitoring. Materials and Methods A forearm ischemia model was designed by using a brachial pressure cuff inflation protocol. Twenty healthy subjects were recruited. The forearm tissue oxygenation of each subject was monitored throughout the pressure cuff protocol by using a new optical sensor (Imperial College London), and a gold standard tissue spectrometry system (O2C, Medizintecknik, LEA, Germany). Data were processed to allow quantitative deoxygenation episode comparisons between inflations and sensor modalities. Results The correlation between O2C and optical sensor oxygenation measurements was moderate (average R = 0.672, p Conclusion This study demonstrates the ability of a small optical sensor to detect and quantify tissue oxygenation changes and assess the presence of pulsatile blood flow. Low power, miniaturized electronics make the device capable of deployment in a wearable form which may break down the barriers for implementation in postoperative flap monitoring.

The prospect of roll-to-roll (R2R) processable Organic Thin Film Transistors (OTFTs) and circuits has attracted attention due to their mechanical flexibility and low cost of manufacture. This work will present a flexible electronics application for pH sensing with flexible and wearable signal processing circuits. A transimpedance amplifier was designed and fabricated on a polyethylene naphthalate (PEN) substrate prototype sheet that consists of 54 transistors. Different types and current ratios of current mirrors were initially created and then a suitable simple 1:3 current mirror (200nA) was selected to present the best performance of the proposed OTFT based transimpedance amplifier (TIA). Finally, this transimpedance amplifier was connected to a customized needle-based pH sensor that was induced as microfluidic collector for potential disease diagnosis and healthcare monitoring.

The quality factor of a resonant sensor affects its bandwidth, peak amplitude as well as sensitivity. Real time control of the quality factor is highly useful for a number of sensing applications, not least dual mode ultrasound systems. This paper reports a new methodology whereby a resonant sensor is coupled to an external electrical resonator making the system a collective coupled system to reduce the quality factor of a high-Q resonant sensor. By suitably controlling the parameters of the external circuit, one can control the quality factor of the resonant sensor. This offers the potential of an ultrasound resonator to be used for both therapeutic (narrowband) and diagnostic (broadband) modalities in real-time

Sensor embodiment and packaging are particularly important for implantable systems. One key element is the development of flexible electronics. Traditional electronics, based on rigid silicon technologies, is associated with a number of intrinsic disadvantages. The inherent brittleness of inorganic semiconductors and stiffness of Si wafer-based devices represent a major issue when interfaced with tissues. This is because our internal organs are complex and they have innate responses to reject foreign bodies. Furthermore, tissues are soft, and they undergo constant motion and deformation. In this chapter, we will discuss current progress in flexible printed circuit board (FPC/FPCB) technologies and provide a review of new fabrication techniques and materials for making soft devices and interconnects suitable for implantable applications. Issues related to geometrical designs for mechanically resilient flexible devices, hermetic packaging, biocompatibility and encapsulation are addressed.

CD105 is rich in endothelium cells and is involved in angiogenesis. Higher microvascular density of tumor is also related to the prognosis in a variety of cancers. In this present study, patients with positive N classification, advanced T classification, advanced TNM stage, extracapsular spread of lymph nodes (ECS), and perineural invasion had significantly higher levels of peripheral vein (pCD105) and venous return from tumor (tCD105) in 71 patients with OSCC compared to 13 healthy volunteers. Those with higher pCD105 or tCD105 levels had significantly poorer 5-year disease-specific survival rate (DDS) and overall survival rate (OS). The tCD105 and pCD105 levels and ECS were the independent prognostic factors by the multivariate analysis according to the Cox regression model in 5-year DDS and OS rate. SAS and SCC4 cells treated with CD105 showed the increase in migration, invasion, and proliferation in vitro and in vivo. Furthermore, CCL20 expression participated in CD105-elicited cell motility in oral cancer cells. In conclusion, higher level of circulating CD105 is related to adverse pathological features among patients with OSCC. It is also a useful marker for evaluating the prognosis and targeting therapeutics of OSCC.

Objective: To determine whether microcytic erythrocytes influence the accuracy of automated platelet (PLT) counting. Methods: We divided a total of 206 K 2 ethylenediaminetetraacetic acid (EDTA)–anticoagulated blood samples into 4 groups, as follows: In group 1 (control group), normal mean corpuscular volume (MCV > 80 fL) and PLT count equal or greater than 140,000/μL (n = 45); group 2, normal MCV, reduced PLT count (< 140 x 10 3 /μL, n = 41); group 3, microcytic samples with normal PLT count (n = 68); and group 4, microcytic samples with reduced PLT count (n = 49). We also compared the platelet counting using electroimpedance (PLT-EI), platelet count using fluorescent optical (PLT-FO), and platelet-count manual (PLT-M) methods, using the Sysmex XE 2100 automatic analyzer. Results: Despite highly significant overall correlations between PLT-EI and PLT-FO, PLT-EI and PLT-M, and PLT-FO and PLT-M (r = 0.95 [all P

Blood flow and perfusion monitoring are critical appraisal to ensure survival of tissue flap after reconstructive surgery. Many techniques have been developed over the years: from optical to chemical, invasive or not, they all have limitations in their price, risks and adaptiveness to the patient. A wireless wearable self-calibrated device, based on near infrared spectroscopy (NIRS) was developed for blood flow and perfusion monitoring contingent on tissue oxygen saturation (StO2). The use of such device is particularly relevant in the case of free flap myocutaneous reconstructive surgery; postoperative monitoring of the flap is crucial for a prompt intervention in case of thrombosis. Although failure rate is low, the rate of additional surgery following anastomosis problem is about 50%. NIRS has shown promising results for the monitoring of free flap, however lack of adaptation to its environment (ambient light) and users (body mass index (BMI), skin tone, alcohol and smoking habits or physical activity level) hinders the practical use of this technique. To overcome those limitations, a self-calibrated approach is introduced. Tested with is chaemia and cold water experiments on healthy subjects of different skin tones, its ability to personalize its calibration is demonstrated. Furthermore, using a vascular phantom, it is also able to detect pulses, differentiate venous and arterial coloured-like fluids with distinct clusters and detect significant changes in simulated partial venous occlusion. Placed in the trained classifier, partial occlusion data showed similar results between predicted and true classification. Further analysis from partial occlusion data showed that distinct clusters for 75% and 100% occlusion emerged.

A simple and reliable method using HPLC/MS/MS has been developed for determination of thiamphenicol and florfenicol in foods of animal origin, such as pork, porcine liver, porcine kidney, beef, bovine liver, fish, and chicken. The HPLC separation was performed on a Waters XTerra phenyl column (100 2.1 mm, 3.5 m) with a gradient mobile phase system of 0.1 formic acidmethanol at a flow rate 0.35 mL/min. Negative ionization produced the molecular ions at m/z 354 and 356 for thiamphenicol and florfenicol, respectively. Two characteristic transition reactions (m/z 354185, 290 and m/z 356336, 185) in the selected reaction monitoring mode were tested for detection and confirmation of thiamphenicol and florfenicol simultaneously. The analytes were extracted with ethyl acetate and defatted with n-hexane by liquidliquid extraction. The recoveries of thiamphenicol and florfenicol by the developed method were 72.597.6. The limits of determination were 1.0 ng/g (ppb) for both compounds.

This study is to determine the impact of virus in surgical outcomes among patients of head and neck cancer with N3 lymph node metastasis. A retrospective analysis was conducted for 32 patients with operable N3 neck metastasis undergoing surgical treatment between January 1987 and October 2006. The nuclei of the tumor cells were investigated for the presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) DNAs and were taken into account as the variable for survival analysis. The primary sites were oropharynx in 11 patients, tongue in 3, buccal mucosa in 1, hypopharynx in 8 and unknown primary in 9. The five-year cumulative overall survival rate was 40.7% and 5-year cumulative regional control rate was 55.8%. The 5-year cumulative overall survival rate of patients with unknown primary site (72.9%) and HPV or EBV positive in the tumor (77.8%) were significantly higher than those patients with known primary site (31.3%) and HPV or EBV negative in the tumor (27.4%), respectively (P = 0.0335 and P = 0.0348, log rank test). In conclusion, surgery with adjuvant therapy offers reasonable outcomes for operable N3 node in head and neck cancer in our cohort. In addition, patients with HPV or EBV positive in the tumor have a better survival.

Background and Objectives Our objective was to evaluate the clinical significance of angiopoietin-1 (Ang-1) and Ang-2 expression in recurrent but operable squamous cell carcinoma of the oral cavity (OCSCC). Patients and Methods Formalin-fixed, paraffin-embedded tissues from 40 patients who underwent surgical intervention for local or local-regional recurrent OCSCC between 1995 and 2005 were immunohistochemically analyzed for Ang-1 and Ang-2 expression. Results The recurrent TNM staging classified 5 patients as stage I, 4 as stage II, 2 as stage III, and 29 as stage IV. The actuarial 3-year disease-free survival rate was 43.1% with a mean follow-up of 18.4 months (ranged 1–70 months). High expression of Ang-1 was significantly correlated with positive nodal stage (P = 0.041). Patients with more advanced recurrent stage of the tumors (P = 0.0036) and high expression of Ang-2 (P = 0.045) showed lower actuarial 3-year disease-free survival. However, Cox's regression analysis revealed that only recurrent tumor (rT) stage was an independent prognostic factor for survival (P = 0.019, 95% CI = 1.473–82.017, relative risk = 10.992). Conclusions Recurrent OCSCC with high Ang-1 or Ang-2 expression in the tumor bed exhibits aggressive tumor behavior. However, the salvage outcome depends on the rT stage. J. Surg. Oncol. 2008;97:273–277. © 2007 Wiley-Liss, Inc.

This paper proposes a novel concept of using a multiple PPG and ECG based sensing platform aimed for monitoring the progress of diabetic peripheral neuropathy (DPN). It explores the use of PPG sensor to capture pulse arrival time (PAT). Based on the same principal of using Brachial-ankle pulse wave velocity (baPWV) to assess DPN, this paper proposes a platform which integrated two PPG sensors and one 2-lead ECG sensor to detect the difference in PAT (pulse arrive time on the finger compare to the time when the pulse reaches the ankle) as a surrogate measure for evaluating the progression of DPN. Preliminary results show that PAT increases when a pressure was applied onto upper leg using a blood pressure cuff simulating arterial stiffness/DPN. It shows that PDN can potentially be quantified by measuring PAT by using the proposed platform.

Objectives: The purpose of this article is to investigate the expressions of vascular endothelial growth factor (VEGF) and endoglin (CD105) in the biopsy tissues of squamous cell carcinoma of the tongue in early tumor stages and their relationship with the clinicopathologic features. Study Design and Methods: The authors conducted retrospective clinical and biologic studies. Immunohistochemistry was used to study the expressions of VEGF and CD105 in the biopsy tissues taken from 94 patients with T1 and T2 tongue cancers. The expressions of VEGF and CD105 were analyzed and correlated to the clinicopathologic features of these patients. Results: High expressions of VEGF and CD105 significantly correlated with a relatively advanced tumor stage (P = .001 and P < .001), positive nodal status (P < .001 and P < .001), presence of tumor necrosis (P = .022 and P = .01), and greater tumor thickness (P < .001 and P < .001), respectively. In addition, high expression of CD105 correlated with the presence of perineural invasion (P = .003). However, the expression of VEGF and CD105 did not significantly correlate with age, gender, vascular invasion, or histologic grading. The cumulative 5-year disease-free survival rate significantly correlated with low expression of VEGF (P = .003), CD105 (P < .001), positive nodal status (P < .001), a relatively advanced tumor stage (P = .024), greater tumor thickness (P = .023), and presence of tumor necrosis (P = .003). Nonetheless, Cox's regression analysis revealed that only the expression of CD105 was an independent prognostic predictor for survival (P < .001). Conclusions: Higher expression of either CD105 or VEGF in the tumor bed implicates a more aggressive potential for T1 and T2 tongue cancers, and the expression of CD105 is a useful predictive prognostic factor in early tongue cancer.

Background and Objectives Although elective neck dissection has become a popular treatment modality for early oral cancer among most head and neck surgeons, a large portion of patients revealed pathological N0 postoperatively. Our study is aimed to evaluate the expressions of the angiogenic factors, vascular endothelial growth factor (VEGF), and CD105 (endoglin) on the prediction of neck metastasis for clinical N0 patients in early oral cancer. Patients and Methods Between July 1996 and July 2005, the preoperative biopsy specimens among 176 patients who underwent surgical treatment for early oral cancer were retrieved for the immunohistochemical study for VEGF and CD105. Results High expressions of CD105 and VEGF significantly correlated with positive nodal metastasis, respectively (P

Matrix metalloproteinases (MMPs) are the proteases responsible for tissue remodeling during liver fibrosis caused by various disorders including biliary atresia. However, information regarding the relative contribution of these proteases to liver fibrosis is still limited. We studied matrix metalloproteinase-2 (MMP-2), -7, -9 and -13 mRNA expressions in the liver tissue of early-stage biliary atresia at the time of Kasai's procedure, late-stage biliary atresia at the time of liver transplantation with advanced fibrosis and nondiseased control without liver fibrosis. The results of real-time quantitative reverse transcriptase-PCR analysis revealed that only MMP-2 and -7 expressions were significantly different between groups. MMP-2 was significantly higher in Liver Transplantation group than both in Control (P=0.010) and in Kasai's Procedure (P=0.001) groups, whereas the difference of MMP-2 expression between Control and Kasai's Procedure was not significant. However, the relative expression level of MMP-7 was sequentially elevated when comparing Control, Kasai's Procedure and Liver Transplantation groups, and there was significant (P=0.019) difference when comparing Control and Liver Transplantation groups. Moreover, the fold difference in MMP-7 mRNA was much higher than that in MMP-2 mRNA between groups. The expressions of MMP-7 were further confirmed by agarose gel electrophoresis and Western blotting. Immunohistochemical analysis revealed a significant positive correlation of the scores of MMP-7 immunostaining with the stages of liver fibrosis. In situ hybridization demonstrated that the bile ductular epithelial cells, Kupffer cells and hepatocytes were the major producers of matrix metalloproteinase-7 in the liver. Our results imply that MMP-7 is a major MMP associated with the tissue remodeling during the progression of liver fibrosis in biliary atresia.

Background/purpose Transforming growth factor-beta (TGF-β) 1 and 2 and their receptors TβR-I, TβR-II, and TβR-III are powerful profibrogenic mediators in the body. Their expression has not been completely elucidated in the progress of liver fibrosis associated with biliary atresia (BA). Methods The authors compared the cytokine expression in the liver of 3 patients with BA at Kasai's procedure (KP) and in 3 patients at liver transplantation (LT). Two liver samples from children with no liver disorders served as normal controls (CO). Real-time quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) was used to confirm the findings of relative mRNA expression of TGF-β1 and 2 and their receptors. An immunohistochemistry and an enzyme-linked immunoassay (ELISA) were used to localize the liver cells that express TGF-β2 and to quantitate the protein expression among groups. Results Compared with controls, both TGF-β1 and TGF-β2 mRNA expression increased in the liver during the progress of liver fibrosis in patients with KP and LT on the array. Only TGF-β2 showed a significant increase in expression in LT compared with KP and CO ( P = .001 for TGF-β2 and P = 0.054 for TGF-β1). Both TβR-I and TβR-II showed no significant change among groups; TβR-III decreased significantly in LT compared with CO ( P = .011). TGF-β2 immunostaining was mainly localized in the bile duct epithelium and was remarkably higher in LT in which the proliferating bile ductules and the hepatocytes contributed to the increase in immunostaining and possibly to significantly higher plasma TGF-β2 protein levels in LT than in KP. Conclusions This study identified TGF-β2 as the most actively transcribed TGF-β gene during the progress of liver fibrosis in BA and found a reciprocal relationship of upregulation of TGF-β2 with downregulation of TβR-III in LT.

Advanced liver cirrhosis frequently occurs in infants with biliary atresia despite early surgical correction. The aetiology is unknown, but may involve many cytokines and liver cells including hepatic stellate cells (HSCs). A cytokine expression array and real-time quantitative reverse transcription-polymerase chain reaction (QRT-PCR) were used to study cytokine expression during the progression of liver fibrosis in biliary atresia. A Delta-like 1 homologue (DLK1) gene was identified and this gene was up-regulated during the early stage, and down-regulated during the late stage, of biliary atresia, similar to the expression pattern of the procollagen α1(I) gene. Further characterization with immunohistochemistry, confocal microscopy, and in situ hybridization revealed that the DLK1 protein was mainly present in the cytoplasm of smooth muscle actin-positive mesenchymal cells that were morphologically and immunohistochemically identical to activated HSCs/myofibroblasts, whereas DLK1 mRNA was present only in hepatocytes. As DLK1 is a negative regulator of adipocyte differentiation and may control cell fate during differentiation, overexpression of DLK1 protein in HSCs in the early stage of biliary atresia suggests that DLK1 may be implicated in the transformation of HSCs from fat-storing cells to myofibroblasts and in fibrogenesis associated with biliary atresia. Copyright © 2004 John Wiley & Sons, Ltd.

Functional inactivation of tumor susceptibility gene tsg101 leads to cellular transformation and tumorigenesis in mice. While human TSG101 is located in a region where frequent loss of heterozygosity can be detected in a variety of cancers, no genomic deletion in TSG101 gene has been reported, casting a doubt on the role of TSG101 as a classical tumor suppressor. Some studies have revealed that TSG101 is a frequent target of splicing defects, which correlate with cellular stress and p53 status. Furthermore, recent reports have identified TSG101 as a part of the MDM2/p53 regulatory circuitry, a well-recognized circuitry that upon deregulation results in tumorigenesis. Interestingly, overexpression of tsg101 from an adventitious promoter also leads to neoplastic transformation. On the basis of this information, we have analysed TSG101 gene expression in 20 human papillary thyroid carcinomas (PTCs) by immunohistochemistry and demonstrated that the overexpression of TSG101 protein is closely associated with human PTCs. Further sequence analysis reveals no mutation in cDNA region encoding steadiness box in these PTC specimens, indicating that the upregulation of TSG101 protein is not caused by the alteration of this region. In situ hybridization analysis confirms that overexpression of TSG101 also occurs at the transcriptional level. In addition, semi-quantitative RT-PCR and subsequent Southern hybridization verify that the amounts of TSG101 transcripts are indeed lower in three normal thyroid tissues than in PTC specimens. Here we report the upregulation of TSG101 expression in PTC cells, providing the first evidence of the association of TSG101 overexpression with human tumors and suggesting that upregulation of TSG101 steady-state level might play a role in mediating tumorigenesis of human PTC.

Photoplethysmography (PPG) is a well established method of measuring Heart Rate Variability (HRV) and blood oxygen saturation (SpO2) at the fingers, forehead or other areas of the body where pulsatile flow is present. However, obtaining reliable tissue oxygen saturation (StO2) from optical devices is more challenging due to a number of factors including motion and signal-to-noise ratio. Instrumentation of such devices as miniaturised wearable platforms would allow the device to be worn freely by patients in hospitals or at home. The purposes of this paper are to present: 1) a bespoke, low power StO2 sensor, 2) preliminary comparison to a commercially available photospectroscopy and laser Doppler machine (Oxygen 2 See, Medizintechnik, LEA, Germany) using a pressure cuff forearm ischaemia model, and 3) validation of fluid (blood) flow/relative haemoglobin measurements using a novel forearm phantom.

This paper presents a novel blind collision detection and material characterisation scheme for a compliant robotic arm. By the incorporation of a simple MEMS accelerometer at each joint, the robot is able to detect collision, identify the material of an obstacle, and create a map of the environment. Detailed hardware design is provided, illustrating its value for building a compact and economical robot platform. The proposed method does not require the additional use of vision sensor for mapping the environment, and hence is termed as `blind' collision detection and environment mapping. Based on the shock wave and vibration signals, the proposed algorithm is able to classify a range of materials encountered. Detailed laboratory evaluation was performed with controlled obstacle collision from different orientation and locations with varying force and materials. The proposed method has achieved 98% detection sensitivity while maintaining 77% specificity. Furthermore, by using sound feature extraction and machine learning techniques, the classifier produces an accuracy of 98% for classifying four different impact materials. In this paper, we also demonstrate its use for detailed environment mapping by using the proposed method.

The results of comparative DC simulation tests confirm that a proposed modification to the feedback circuit of a Flipped Voltage Follower (FVF), to produce a type of ‘Folded’ Flipped Voltage Follower (FFVF), is capable of maximising the linear DC operating range for given values of supply rail voltage and operating current.

Objective To evaluate the prevalence of human papillomavirus (HPV) and the prognostic significance of epidermal growth factor receptor (EGFR), p53, and p16 among patients with oropharyngeal carcinoma. Design Retrospective study. Setting Academic Institute of Otolaryngology, Kaohsiung, Taiwan. Patients Two hundred seventy-four patients who were diagnosed as having oropharyngeal carcinoma underwent testing for the presence of the HPV genome in the nuclei of their tumor cells from January 1, 1992, through March 31, 2008. Interventions The HPV genome was detected by performing polymerase chain reaction–based assays and in situ hybridization on tumor tissue from paraffin blocks. Immunohistochemistry staining for p16, p53, and EGFR was also performed. Main Outcome Measures We used the Fisher exact test to evaluate the correlation between the clinicopathological variables and the presence of HPV in tumor cells. Survival analysis was based on the Kaplan-Meier method. Results We detected HPV in 45 of the 274 patients (16.4%); of these, HPV-16 and -18 were identified in 42 (93.3%) of the HPV-positive tumors. The HPV-positive oropharyngeal cancers were more likely to occur in females, nonsmoking individuals, and those who did not chew betel quid. The HPV-positive tumors significantly expressed p16 and were inversely associated with EGFR and p53 expression (all, P P = .008) and had negative expression of EGFR ( P = .01), low expression of p53 ( P = .01), and high expression of p16 ( P = .04) had a better prognosis. Conclusion Our results suggest that HPV, EGFR, p53, and p16 are useful biomarkers in predicting the clinical outcomes of oropharyngeal cancer.

Osteopontin is a tumor-associated protein that promotes tumor development and metastasis. The preoperative blood samples of 94 oral squamous cell carcinoma (OSCC) patients and 28 healthy individuals were analyzed for plasma osteopontin levels, and another 256 paraffin-embedded OSCC specimens were analyzed by osteopontin immunostaining. The patients with advanced tumor (T) stage (T3/T4 vs. T1/T2) and positive nodal (N) status had significantly higher plasma levels of osteopontin (both p0.001). Positive osteopontin immunostaining also correlated significantly with advanced T stage (p0.001), positive N status (p0.001), advanced TNM stage (p0.001) and male gender (p=0.016). Unfavorable cumulative 5-year overall survival rates correlated significantly with positive osteopontin immunostaining (p0.001), advanced T stage (p0.001), positive N status (p0.001) and advanced TNM stage (p0.001). However, Cox regression analysis revealed that T stage and N status were independent prognostic factors for survival (both p0.001) and osteopontin immunostaining was marginally significant for survival (p=0.056). The present study demonstrated that high expression level of osteopontin in either the plasma or the tumor of the patients with OSCC was associated with tumor progression, suggesting that osteopontin expression is an important prognostic factor for OSCC.

Objectives To identify the expression of estrogen receptors in malignant minor salivary gland tumors of the sinonasal tract. Study Design Case series with chart review. Subjects and Methods A retrospective review of a pathology database identified 17 patients with malignant salivary gland tumors between December 1987 and January 2006. Clinicopathologic data were collected, and immunohistochemical staining for estrogen receptor α and β was performed. Results Among these malignant tumors, adenoid cystic carcinoma was the predominant histologic type. In addition to epistaxis and nasal obstruction, the headache, facial, or ocular symptoms were also commonly noted in this cohort. Seventy-five percent of cases of adenoid cystic carcinoma were positive for estrogen receptor α. In contrast, only 17 percent of cases of adenoid cystic carcinoma were positive for estrogen receptor β. Conclusion Malignant minor salivary gland tumors of the sinonasal tract are rare disease entities. In the present series, adenoid cystic carcinoma was the most common form of tumor, but the prognosis was poor. Most of the cases were positive for expression of estrogen receptor α, which suggests that hormone therapy may have a role in the management of certain minor salivary gland tumors of the paranasal sinus and nasal cavity.

Background Osteopontin (OPN) is considered to be a tumor-related protein associated with tumor aggressiveness and metastasis. Methods Immunohistochemistry was used to study the clinical significance of OPN expression in T1 and T2 tongue cancers. Results Positive OPN expression significantly correlated with higher tumor classification (T) (p = .004), positive nodal classification (N) (p < .001), greater tumor thickness (p < .001), and presence of tumor necrosis (p = .016), respectively. The unfavorable cumulative 5-year disease-free survival rate significantly correlated with positive OPN expression (p < .001), T2 (p = .024), positive N (p < .001), greater tumor thickness (p = .023), and positive tumor necrosis (p = .003). However, taking CD105 into consideration, only CD105 expression was the independent prognostic factor for survival by Cox's regression analysis. Conclusion Overexpression of OPN in the tumors implicated a more aggressive tumor behavior and was an important factor for survival. In addition, there might be relationship between OPN and CD105 expressions in angiogenesis. © 2008 Wiley Periodicals, Inc. Head Neck, 2008

Human papillomavirus (HPV) is frequently detected in squamous cell carcinoma of tonsil (TSCC) among the Western population. However, the only reported study on Chinese patients in the English literature demonstrated absence of HPV in TSCC. To evaluate the prevalence and clinical significance of HPV-related TSCC in Taiwan, we performed PCR with MY09/MY11 consensus primers and in situ hybridization to study 111 TSCC samples. The results showed that only 12.6% TSCC were HPV-positive. The favorable 5-year survival rate correlated significantly with HPV positivity (p=0.007), female (p=0.046), and early tumor (T) stage (p

Aim Biliary intervention may augment chemokine expression and inflammatory cell infiltration and aggravates liver injury in cholestatic rats. We tested the efficacy of glucocorticoid pretreatment to prevent the complications. Methods A model of biliary intervention was established in rats without (sham) or with bile duct ligation (BDL). Before biliary intervention, rats were randomly assigned to receiving intravenous injection of dexamethasone (DX group) or normal saline (NS group). Plasma levels of monocyte chemoattractant protein–1 (MCP-1) and macrophage inflammatory protein–2 (MIP-2) were measured with enzyme-linked immunosorbent assay, and liver messenger RNA of these chemokines was quantified with real-time quantitative reverse transcriptase–polymerase chain reaction. Monocytes, Kupffer cells, and neutrophils in the rat liver were characterized with antibodies to ectodermal dysplasia 1 (ED1), ED2, and myeloperoxidase, respectively. Results By 3 hours after biliary intervention, plasma MCP-1 and MIP-2 proteins in BDL-NS rats were significantly higher than in BDL-DX. At 3 hours, liver MCP-1 and MIP-2 messenger RNA levels were significantly upregulated in BDL-NS than in BDL-DX. The amount of ED1-, ED2- and myeloperoxidase-staining cells were significantly greater in BDL-NS than in BDL-DX. Most of the changes returned to baseline levels by 24 hours. Conclusion Glucocorticoid pretreatment suppresses chemokine expression and inflammatory cell infiltration, which may consequently alleviate liver injury in cholestatic rats receiving biliary intervention.

The TSG101 protein has been implicated in multiple biological functions including regulation of gene transcription, vesicular trafficking, cellular growth and differentiation. However, the cellular signals that control TSG101 functions are unclear. Here, we demonstrate that TSG101 is upregulated during keratinocyte differentiation in both human foreskin tissue and reconstructed organotypic skin cultures. In addition, we found that TSG101 siRNA inhibits calcium-induced early differentiation of human foreskin keratinocytes, indicating an essential and downstream role for TSG101 in this process. Furthermore, the PKC agonist TPA promotes expression of TSG101 and keratin 10 in keratinocytes under low calcium conditions, while co-treatment with the PKC inhibitor GF 109203X blocks TPA-induced TSG101 and keratin 10 upregulation. Previous work has established that the TSG101 gene is controlled by a TATA-less promoter that harbors a Sp1-binding site. Here we show that both calcium and TPA activate PKC, stimulate phosphorylation of Sp1, and augment the activity of the TSG101 promoter in a manner dependent on its Sp1-binding site. Release of calcium from intracellular stores with thapsigargin, an endoplasmic reticulum Ca2+-ATPase inhibitor that elevates intracellular free Ca2+ without activating PKC, does not affect Sp1 phosphorylation and TSG101 promoter activity. Taken together, these data suggest that an intracellular calcium store independent PKC-Sp1 signaling pathway induces early keratinocyte differentiation through upregulation of TSG101.

Paclitaxel (Taxol) is an antineoplastic agent that specifically targets microtubules and arrests cells at the G2/M phase of the cell cycle. In addition to mitotic arrest, the activation of c-Jun N-terminal kinase (JNK) signaling pathway has been demonstrated to be involved in the process leading to apoptosis. In an attempt to explore what genes are transcriptionally regulated by the activated JNK signaling pathway upon paclitaxel treatment, we used cDNA microarrays to analyse the changes of gene expression in human ovarian cancer cells that were treated with paclitaxel and/or the JNK inhibitor SP600125. Among 20 genes that were specifically regulated by the paclitaxel-activated JNK pathway, interleukin (IL)-6 was shown to elicit function through the JAK-STAT signaling pathway in an autocrine and/or paracrine fashion. Subsequently, we identified that 87.5% of eight tested ovarian cancer lines secreted detectable levels of IL-6, which could be further upregulated 2-3.2 fold by 1 microM paclitaxel. Dissection on regulatory pathways for IL-6 indicated that (i) when ovarian cancer cells were treated with paclitaxel at low but clinically achievable concentrations (exemplified by 1 microM in this study), the JNK signaling pathway was the major stimulator of IL-6 gene regulation and (ii) at suprapharmacologically high concentrations (exemplified by 50 microM), paclitaxel exerted lipopolysaccharide-like effects, most likely through the Toll-like receptor 4 signaling pathway. Collectively, these results suggest that paclitaxel upregulates functional IL-6 expression in human ovarian cancer cells through multiple signaling pathways.

Neuroblastoma is an extremely malignant solid tumor in children, characterized by spontaneous differentiation and regression. An epidermal growth factor-like homeotic protein, delta-like (dlk), has been involved in differentiation of neuroblastoma cell lines, but is unknown in in vivo expression of neuroblastoma. By using in situ hybridization and immunohistochemistry, dlk mRNA and protein expression were studied in formalin-fixed archival tissues from 10 patients with neuroblastoma, five with ganglioneuroblastoma, and five with ganglioneuroma. Three adrenal tissues from children died of diseases other than adrenal tumors and one from an adult with pheochromocytoma were severed as normal and disease controls. The results showed strong immunoreactive dlk staining in endothelial cells in neuroblastoma, ganglioneuroblastoma and ganglioneuroma. Dlk was detectable in mature neuromatous stroma and gangliocytes of ganglioneuroma, but not in neuroblasts of neuroblastoma and ganglioneuroblastoma, neither in gangliocytes of ganglioneuroblastoma. In contrast, dlk mRNA expression was mainly observed in the gangliocytes, but was less intense in the neuroblasts and neuromatous stroma cells. Endothelial cells were essentially devoid of dlk mRNA expression. The findings indicated that there is differential expression of dlk gene and protein among neuroblastoma, ganglioneuroblastoma and ganglioneuroma. The stronger expression of dlk in gangliocytes in ganglioneuroma, in contrast to weaker or no expression in gangliocytes in ganglioneuroblastoma and neuroblasts in neuroblastoma, suggests upregulation of dlk during differentiation of neuroblastoma into more benign form. Furthermore, higher dlk protein expression in the tumor endothelium than in the endothelium of normal adrenal gland implies that dlk may regulate the endothelial function in neuroblastic tumors.

To evaluate the roles of p53 and p21 expression in the squamous cell carcinoma of hypopharyngeal cancer, we performed the immunohistochemical studies in 58 patients with hypopharyngeal cancer. We found significant correlation between a high expression of p53 and a histological grade of well differentiation, advanced tumor (T) and TNM stage. Furthermore, low expression of p21 correlated significantly with advanced TNM stage and positive nodal status. Cox's regression analysis revealed tumor stage and nodal status were the only prognostic factors for survival. Therefore, we concluded that p53 and p21 are useful markers in predicting some clinicopathological features in hypopharyngeal cancer.