The modulation of hypoxia-inducible factor-1α/plasminogen activator inhibitor-1 axis in human gingival fibroblasts stimulated with cyclosporine A

Background/PurposeThe prominent side effect of the immunosuppressive drug cyclosporine A (CsA) is gingival overgrowth. Hypoxia-inducible factor (HIF)-1α regulates a wide variety of profibrogenic genes, which are closely associated with tissue fibrosis. The aim of this study was to compare HIF-1α expression in normal gingival tissues and CsA-induced gingival overgrowth specimens and further explore the potential mechanisms that may lead to induction of HIF-1α expression.MethodsFifteen CsA-induced gingival overgrowth specimens and five normal gingival tissues were examined by immunohistochemistry. Western blot was used to investigate the effects of CsA on the expression of HIF-1α in cultured human gingival fibroblasts. The effects of CsA on plasminogen activator inhibitor (PAI)-1 expression were evaluated in environmental hypoxia.ResultsHIF-1α staining in gingival tissue was stronger in CsA-induced gingival overgrowth group than normal gingival group (p < 0.05). The expression of HIF-1α was significantly higher in CsA-induced gingival overgrowth specimens with higher levels of inflammatory infiltrates (p = 0.041). CsA was found to upregulate HIF-1α protein in a dose-dependent manner (p < 0.05). Hypoxia increased CsA-induced PAI-1 protein expression than normoxic conditions (p < 0.05).ConclusionThese results suggest that HIF-1α expression is significantly upregulated in CsA-induced gingival overgrowth specimens. The activation of HIF-1α may promote fibrogenesis by an increase of PAI-1 expression and a subsequent elevation of extracellular matrix production in gingival tissues

Noninvasive Wireless Sensor PFMT Device for Pelvic Floor Muscle Training

[[abstract]]Urinary incontinence is a common problem among adults. Studies have shown up to 70% improvement in stress incontinence symptoms following appropriately performed pelvic floor exercise. This improvement is evident across all age groups. In this study, we cooperated with a doctor of the Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taiwan. We developed a noninvasive device with the purpose of helping patients commence and perform pelvic floor muscle training (PFMT). This device consists of a PFMT device, an Arduino control board, a force sensor, a Bluetooth device, and an SD card. The objectives of this study are to train patients to inhibit detrusor contraction voluntarily and to contract periurethral muscles selectively. The system records and analyzes sensor data and provides voice prompts during PFMT exercise for patients at hospitals or their homes. Meanwhile, it tracks patients’ PFMT exercise at home, and doctors can contact patients for additional visitation(s) if necessary.[[incitationindex]]SCI[[booktype]]紙

Environmental Tax Reform, R&D Subsidies and CO2 Emissions: View Double Dividend Hypothesis

This study investigated whether environmental taxes achieve the double dividend of coexistence of economic growth and environmental protection. The research method used dynamic industrial relations models to estimate the influence of environmental taxes influence on the economy and environment. The goal was to conduct an objective analysis with scientific data. The conclusions provide a clue indicating that environmental taxes could only be used to facilitate short-term coexistence between economic growth and environmental protection. Once entering the mid-term and long term, the lack of innovation and technical progress would eventually cause economic development and environmental protection to diverge, which is why studies are yet to reach a consensus. The results suggest that although using environmental taxes to promote economic development and environmental protection can achieve the double dividend in the short term, in the midterm, the first dividend disappears unless a solution for improved energy efficiency and technical innovation can be determined immediately. Furthermore, to sustain its economic development and environmental protection efforts, Taiwan must first optimize its industrial structure, which can only be achieved through advanced research and development. Keywords: Environmental Tax Reform, R&D Subsidies, CO2 Emissions, Double Dividend Hypothesis JEL Classifications: C67, D57, Q50, Q5

A hematoma confined to the center of the abdomen

Spontaneous rupture of a hepatocellular carcinoma is a rare and lethal complication in the emergency department. A caudate lobe hepatoma rupture is even rarer. It can be treated with vascular embolization, surgical intervention or supportive care. A 70-year-old woman with underlying hepatocellular carcinoma presented to our emergency department with severe abdominal pain encompassing the entire region for half a day. Abdominal computer tomography scans with and without contrast medium revealed a large hematoma confined to the lesser sac of the abdomen. It was initially diagnosed as a ruptured aneurysm. A ruptured caudate lobe hepatoma with acute hemorrhage into the lesser sac was diagnosed after reviewing and discussing the imaging findings with the radiologist. The patient was treated with supportive care without vascular embolization or surgical intervention because there was no imaging evidence of active contrast extravasation and the vital signs were within the normal range. After reviewing the literature, our case appears to be the second only case treated with supportive care and discharged without complications

REG3A overexpression functions as a negative predictive and prognostic biomarker in rectal cancer patients receiving CCRT

Background. Concurrent chemoradiotherapy (CCRT) is suggested before resection surgery in the control of rectal cancer. Unfortunately, treatment outcomes are widely variable and highly patientspecific. Notably, rectal cancer patients with distant metastasis generally have a much lower survival rate. Accordingly, a better understanding of the genetic background of patient cohorts can aid in predicting CCRT efficacy and clinical outcomes for rectal cancer before distant metastasis. Methods. A published transcriptome dataset (GSE35452) (n=46) was utilized to distinguish prospective genes concerning the response to CCRT. We recruited 172 rectal cancer patients, and the samples were collected during surgical resection after CCRT. Immunohistochemical (IHC) staining was performed to evaluate the expression level of regenerating family member 3 alpha (REG3A). Pearson's chi-squared test appraised the relevance of REG3A protein expression to clinicopathological parameters. The Kaplan-Meier method was utilized to generate survival curves, and the log-rank test was performed to compare the survival distributions between two given groups. Results. Employing a transcriptome dataset (GSE35452) and focusing on the inflammatory response (GO: 0006954), we recognized that REG3A is the most significantly upregulated gene among CCRT nonresponders (log2 ratio=1.2472, p=0.0079). Following IHC validation, high immunoexpression of REG3A was considerably linked to advanced post-CCRT tumor status (p<0.001), post-CCRT lymph node metastasis (p=0.042), vascular invasion (p=0.028), and low-grade tumor regression (p=0.009). In the multivariate analysis, high immunoexpression of REG3A was independently correlated with poor disease-specific survival (DSS) (p=0.004) and metastasis-free survival (MeFS) (p=0.045). The results of the bioinformatic analysis also supported the idea that REG3A overexpression is implicated in rectal carcinogenesis. Conclusion. In the current study, we demonstrated that REG3A overexpression is correlated with poor CCRT effectiveness and inferior patient survival in rectal cancer. The predictive and prognostic utility of REG3A expression may direct patient stratification and decisionmaking more accurately for those patients

Overexpression of Dehydrogenase/Reductase 9 Predicts Poor Response to Concurrent Chemoradiotherapy and Poor Prognosis in Rectal Cancer Patients

Objective: To reduce the risk of locoregional recurrence, the addition of neoadjuvant concurrent chemoradiotherapy (CCRT) is recommended before surgical management for rectal cancer patients. However, despite identical tumor histology, individual patient response to neoadjuvant CCRT varies greatly. Accordingly, a comprehensive molecular characterization that is used to predict CCRT efficacy is instantly needed.Methods: Pearson’s chi-squared test was utilized to correlate dehydrogenase/reductase 9 (DHRS9) expression with clinicopathological features. Survival curves were created applying the Kaplan-Meier method, and the log-rank test was conducted to compare prognostic utility between high and low DHRS9 expression groups. Multivariate Cox proportional hazards regression analysis was applied to identify independent prognostic biomarkers based on variables with prognostic utility at the univariate level.Results: Utilizing a public transcriptome dataset, we identified that the DHRS9 gene is the most considerably upregulated gene related to epithelial cell differentiation (GO: 0030855) among rectal cancer patients with CCRT resistance. Employing immunohistochemical staining, we also demonstrated that high DHRS9 immunoexpression is considerably associated with an aggressive clinical course and CCRT resistance in our rectal cancer cohort. Among all variables with prognostic utility at the univariate level, only high DHRS9 immunoexpression was independently unfavorably prognostic of all three endpoints (all p ≤ 0.048) in the multivariate analysis. In addition, applying bioinformatic analysis, we also linked DHRS9 with unrevealed functions, such as keratan sulfate and mucin synthesis which may be implicated in CCRT resistance.Conclusion: Altogether, DHRS9 expression may serve as a helpful predictive and prognostic biomarker and assist decision-making for rectal cancer patients who underwent neoadjuvant CCRT

Theoretically-Efficient and Practical Parallel DBSCAN

The DBSCAN method for spatial clustering has received significant attention due to its applicability in a variety of data analysis tasks. There are fast sequential algorithms for DBSCAN in Euclidean space that take $O(n\log n)$ work for two dimensions, sub-quadratic work for three or more dimensions, and can be computed approximately in linear work for any constant number of dimensions. However, existing parallel DBSCAN algorithms require quadratic work in the worst case, making them inefficient for large datasets. This paper bridges the gap between theory and practice of parallel DBSCAN by presenting new parallel algorithms for Euclidean exact DBSCAN and approximate DBSCAN that match the work bounds of their sequential counterparts, and are highly parallel (polylogarithmic depth). We present implementations of our algorithms along with optimizations that improve their practical performance. We perform a comprehensive experimental evaluation of our algorithms on a variety of datasets and parameter settings. Our experiments on a 36-core machine with hyper-threading show that we outperform existing parallel DBSCAN implementations by up to several orders of magnitude, and achieve speedups by up to 33x over the best sequential algorithms

Hepatitis B virus genotypes and evolutionary profiles from blood donors from the northwest region of China

Hepatitis B virus (HBV) is prevalent in China and screening of blood donors is mandatory. Up to now, ELISA has been universally used by the China blood bank. However, this strategy has sometimes failed due to the high frequency of nucleoside acid mutations. Understanding HBV evolution and strain diversity could help devise a better screening system for blood donors. However, this kind of information in China, especially in the northwest region, is lacking. In the present study, serological markers and the HBV DNA load of 11 samples from blood donor candidates from northwest China were determined. The HBV strains were most clustered into B and C genotypes and could not be clustered into similar types from reference sequences. Subsequent testing showed liver function impairment and increasing virus load in the positive donors. This HBV evolutionary data for China will allow for better ELISA and NAT screening efficiency in the blood bank of China, especially in the northwest region