Two-stage deep-learning-based colonoscopy polyp detection incorporating fisheye and reflection correction.

BACKGROUND AND AIM: Colonoscopy is a useful method for the diagnosis and management of colorectal diseases. Many computer-aided systems have been developed to assist clinicians in detecting colorectal lesions by analyzing colonoscopy images. However, fisheye-lens distortion and light reflection in colonoscopy images can substantially affect the clarity of these images and their utility in detecting polyps. This study proposed a two-stage deep-learning model to correct distortion and reflections in colonoscopy images and thus facilitate polyp detection. METHODS: Images were collected from the PolypSet dataset, the Kvasir-SEG dataset, and one medical center's patient archiving and communication system. The training, validation, and testing datasets comprised 808, 202, and 1100 images, respectively. The first stage involved the correction of fisheye-related distortion in colonoscopy images and polyp detection, which was performed using a convolutional neural network. The second stage involved the use of generative and adversarial networks for correcting reflective colonoscopy images before the convolutional neural network was used for polyp detection. RESULTS: The model had higher accuracy when it was validated using corrected images than when it was validated using uncorrected images (96.8% vs 90.8%, P < 0.001). The model's accuracy in detecting polyps in the Kvasir-SEG dataset reached 96%, and the area under the receiver operating characteristic curve was 0.94. CONCLUSION: The proposed model can facilitate the clinical diagnosis of colorectal polyps and improve the quality of colonoscopy.

Temporal Trends of Inflammatory Bowel Diseases in Taiwan from 2016 to 2020: A Population-Based Study.

BACKGROUND: There are scanty population-based studies investigating the incidence and prevalence rates of inflammatory bowel disease (IBD) in Taiwan. AIMS: This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in Taiwan between 2016 and 2020. METHODS: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan. RESULTS: A total of 2595 patients with catastrophic IBD illness were registered from 2016 to 2020 in Taiwan (CD, 880; UC, 1715). The male-to-female ratio in the study sample was 1.83:1 for CD and 1.69:1 for UC. The median age of those registered with CD and UC was 37 and 47 years, respectively. The incidence rate of CD was 0.65 per 100,000 persons in 2016 and it was increased to 0.81 per 100,000 persons in 2020. The incidence rate of UC was 1.16 per 100,000 persons in 2016 and it was increased to 1.53 in 2020. Overall, the incidence of IBD was increase from 1.81 per 100,000 persons to 2.34 per 100,000 persons between 2016 and 2020. Overall, the prevalence rates of IBD was increase from 14.95 per 100,000 persons to 20.02 per 100,000 persons between 2016 and 2020. CONCLUSION: The epidemiological stages of IBD in Taiwan was considered in the acceleration in incidence stage, during which incidence rises and prevalence is relatively low. Understanding these geographical differences is important for the rising global burden of IBD.

Intraprocedure Artificial Intelligence Alert System for Colonoscopy Examination.

Colonoscopy is a valuable tool for preventing and reducing the incidence and mortality of colorectal cancer. Although several computer-aided colorectal polyp detection and diagnosis systems have been proposed for clinical application, many remain susceptible to interference problems, including low image clarity, unevenness, and low accuracy for the analysis of dynamic images; these drawbacks affect the robustness and practicality of these systems. This study proposed an intraprocedure alert system for colonoscopy examination developed on the basis of deep learning. The proposed system features blurred image detection, foreign body detection, and polyp detection modules facilitated by convolutional neural networks. The training and validation datasets included high-quality images and low-quality images, including blurred images and those containing folds, fecal matter, and opaque water. For the detection of blurred images and images containing folds, fecal matter, and opaque water, the accuracy rate was 96.2%. Furthermore, the study results indicated a per-polyp detection accuracy of 100% when the system was applied to video images. The recall rates for high-quality image frames and polyp image frames were 95.7% and 92%, respectively. The overall alert accuracy rate and the false-positive rate of low quality for video images obtained through per-frame analysis were 95.3% and 0.18%, respectively. The proposed system can be used to alert colonoscopists to the need to slow their procedural speed or to perform flush or lumen inflation in cases where the colonoscope is being moved too rapidly, where fecal residue is present in the intestinal tract, or where the colon has been inadequately distended.

CPEB2-dependent translation of long 3'-UTR Ucp1 mRNA promotes thermogenesis in brown adipose tissue.

Expression of mitochondrial proton transporter uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) is essential for mammalian thermogenesis. While human UCP1 mRNA exists in a long form only, alternative polyadenylation creates two different isoforms in mice with 10% of UCP1 mRNA found in the long form (Ucp1L) and ~90% in the short form (Ucp1S). We generated a mouse model expressing only Ucp1S and found that it showed impaired thermogenesis due to a 60% drop in UCP1 protein levels, suggesting that Ucp1L is more efficiently translated than Ucp1S. In addition, we found that ß3 adrenergic receptor signaling promoted the translation of mouse Ucp1L and human Ucp1 in a manner dependent on cytoplasmic polyadenylation element binding protein 2 (CPEB2). CPEB2-knockout mice showed reduced UCP1 levels and impaired thermogenesis in BAT, which was rescued by ectopic expression of CPEB2. Hence, long 3'-UTR Ucp1 mRNA translation activated by CPEB2 is likely conserved and important in humans to produce UCP1 for thermogenesis.

Colorectal Polyp Image Detection and Classification through Grayscale Images and Deep Learning.

Colonoscopy screening and colonoscopic polypectomy can decrease the incidence and mortality rate of colorectal cancer (CRC). The adenoma detection rate and accuracy of diagnosis of colorectal polyp which vary in different experienced endoscopists have impact on the colonoscopy protection effect of CRC. The work proposed a colorectal polyp image detection and classification system through grayscale images and deep learning. The system collected the data of CVC-Clinic and 1000 colorectal polyp images of Linkou Chang Gung Medical Hospital. The red-green-blue (RGB) images were transformed to 0 to 255 grayscale images. Polyp detection and classification were performed by convolutional neural network (CNN) model. Data for polyp detection was divided into five groups and tested by 5-fold validation. The accuracy of polyp detection was 95.1% for grayscale images which is higher than 94.1% for RGB and narrow-band images. The diagnostic accuracy, precision and recall rates were 82.8%, 82.5% and 95.2% for narrow-band images, respectively. The experimental results show that grayscale images achieve an equivalent or even higher accuracy of polyp detection than RGB images for lightweight computation. It is also found that the accuracy of polyp detection and classification is dramatically decrease when the size of polyp images small than 1600 pixels. It is recommended that clinicians could adjust the distance between the lens and polyps appropriately to enhance the system performance when conducting computer-assisted colorectal polyp analysis.

An International Study on the Diagnostic Accuracy of the Japan Narrow-Band Imaging Expert Team Classification for Colorectal Polyps Observed with Blue Laser Imaging.

BACKGROUND: The Japan narrow-band imaging Expert Team (JNET) classification of colorectal polyps based on magnifying endoscopy is used in Japan, but not worldwide. The objective of this study was to clarify differences of diagnostic accuracy between JNET users in Japan and non-JNET users in other countries. METHODS: A total of 185 colorectal tumors were assessed. Six endoscopists (3 each from Japan and Taiwan) participated in the study. The Japanese endoscopists normally used the JNET classification and the Taiwanese endoscopists normally used the narrow-band imaging International Colorectal Endoscopic classification for diagnosis of colorectal tumors. After receiving a lecture on the JNET classification, they all observed one blue laser imaging magnified image per lesion and performed diagnosis based on the JNET classification. RESULTS: Diagnostic ability was equivalent for Type 1, Type 2A, and Type 2B. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of Type 3 for deep submucosal invasive carcinoma was, respectively, 44.4, 98.3, 57.1, and 97.2% in Group J and 70.0, 94.7, 40.4, and 98.4% in Group T. The PPV for diagnosis of Type 3 with a high confidence was significantly higher in Group J than in Group T (81.8% [55.4-94.6] vs. 44.4% [33.6-50.9], p < 0.05). CONCLUSIONS: The PPV for Type 3 differed between the 2 groups, suggesting the need to become familiar with differentiation between Type 2B and Type 3.

Association of endoscopic ultrasonographic parameters and gastrointestinal stromal tumors (GISTs): can endoscopic ultrasonography be used to screen gastric GISTs for potential malignancy?

BACKGROUND: Previous research shows that only 10-30% of gastrointestinal stromal tumors (GISTs) are malignant. Nonetheless, some reports suggest that all of them have some degree of potential for malignancy. Endoscopic ultrasonography (EUS) is a useful technique for differentiation of subepithelial lesions in the gastrointestinal tract. We explored EUS characteristics that might predict the malignancy potential of GISTs. METHODS: In this retrospective review of the medical records from 1999 through 2007, patients who had gastric stromal tumors diagnosed prior to surgery using EUS were enrolled. The EUS images, procedure records and tissue histopathology were reviewed. All patients were positive for C-kit. RESULTS: Of the 110 patients enrolled, 57 were males, and 53 were females. Most (67%) of the GISTs were located in the gastric body. The lesion size ranged from 6.3 to 150 mm (mean ± SD: 39.73 ± 22.49 mm). The high-risk GIST group had 19 (17.3%) patients, the intermediate-risk group had 12 (10.9%) patients and the low/very low-risk group had 79 (71.8%) patients. Thirty patients had cystic lesions (27.3%), while six patients had calcification in the lesion (5.5%). Additionally, 27 patients (24.5%) had surface ulceration visible on endoscopy. GISTs at high risk for malignancy were highly associated with lesion size (p < 0.0001), cystic change (p = 0.015) and surface ulceration (p = 0.036) but not with calcification (p = 0.667). We also found that mitosis was associated with lesion size (p < 0.0001) rather than other parameters. Age was not predictive of malignancy potential (p = 0.316). However, tumor size is the only one independent risk factor for malignancy (p ≤ 0.0001). CONCLUSIONS: The preliminary results show that large gastric GISTs with cystic change and surface ulceration may associate with a risk of malignancy, warranting more aggressive management. Nevertheless, the tumor size is more important than other factors.

Plasminogen activator inhibitor-1 is independently associated with non-alcoholic fatty liver disease whereas leptin and adiponectin vary between genders.

BACKGROUND AND AIM: Alterations of adipocytokine levels and clinical parameters in non-alcoholic fatty liver disease (NAFLD) are crucial for the prognosis and complications of the diseases. However, the key adipocytokines independently associated with NAFLD have not been identified, and we aimed to investigate them. METHODS: This study was conducted on a consecutive series of 210 Taiwanese NAFLD patients and 420 sex- and age-matched controls. Fatty liver was diagnosed by magnetic resonance spectroscopy. The enrolled subjects' body mass indexes, homeostasis model of assessment-insulin resistance, uric acid, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, blood pressure, metabolic syndrome (yes/no), alanine aminotransferase, aspartate aminotransferase-to-platelet ratio indexes, leptin, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were analyzed to determine their association with NAFLD. RESULTS: Univariate analysis showed that all of the aforementioned factors were associated with NAFLD, whereas multivariate analysis revealed that only PAI-1 (odds ratio: 1.39, P = 0.039) was independently associated with NAFLD. Subgroup analysis showed that females consistently had higher leptin (P < 0.001) and adiponectin (P < 0.001) levels than males, whereas their PAI-1 levels were similar. Males with NAFLD had higher leptin but lower adiponectin levels than their subgroup counterparts (all P < 0.001). Among the female subgroups, hyperleptinemia and hypoadiponectinemia were only observed in the NAFLD patients ≥ 45 years. CONCLUSIONS: PAI-1 is independently associated with NAFLD after adjusting for other factors, including leptin and adiponectin. Male and female NAFLD patients show distinct patterns of leptin and adiponectin alterations; special attention is required when evaluating these alterations in female NAFLD patients < 45 years.

The Trend of Inflammatory Bowel Diseases in Taiwan: A Population-Based Study.

BACKGROUND AND AIM: The purpose of this study was to estimate the sex- and age-specific incidence rates of inflammatory bowel diseases (IBD) in Taiwan. Site-specific cancer occurred in patients with IBD would be reported, too. METHODS: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan. RESULTS: Between 2000 and 2010, the overall incidence rate of Crohn's disease (CD) and ulcerative colitis (UC) was 0.208 and 0.838 per 100,000 person-years. For male, the incidence rate of CD was 0.195 (95 % CI 0.113-0.276) per 100,000 persons in 2000 and increased to 0.318 (95 % CI 0.216-0.421) per 100,000 persons in 2010. For female, the incidence rate of CD was 0.092 (95 % CI 0.035-0.149) per 100,000 persons in 2000 and increased to 0.210 (95 % CI 0.128-0.293) per 100,000 persons in 2010. For male, the incidence rate of UC was 0.690 (95 % CI 0.537-0.843) per 100,000 persons in 2000 and increased to 1.351 (95 % CI, 1.140-1.562) per 100,000 persons in 2010. For female, the incidence rate of UC was 0.386 (95 % CI 0.269-0.503) per 100,000 persons in 2000 and increased to 0.858 (95 % CI 0.691-1.024) per 100,000 persons in 2010. Among the CD patients, 0.19 % had colorectal cancers (1/519). Among the UC patients, 0.24 % had colorectal cancers (5/2098). CONCLUSIONS: This nationwide population-based longitudinal epidemiological study of IBD in Taiwan provides data for future global comparisons.

Factors that influence cecal intubation rate during colonoscopy in deeply sedated patients.

BACKGROUND AND AIM: The technical performance of colonoscopy performed in deeply sedated patients differs from that performed without sedation or under minimal to moderate sedation. The aim of this study is to evaluate the factors affecting cecal intubation during colonoscopy performed under deep sedation. METHODS: A total of 5352 consecutive subjects who underwent a screening colonoscopy as part of a health check-up between January 2008 and December 2008 at an academic hospital were reviewed. All endoscopies were performed with deep sedation using combination propofol or propofol alone. Data collected included characteristics of the patients (age, gender, body mass index, bowel habits, history of abdominal or pelvic surgery, quality of bowel preparation, and presence/absence of colonic diverticula) and characteristics of the colonoscopists (experience level, colonoscopy procedure volume, and instrument handling method). These factors were analyzed to evaluate their impact on cecal intubation rates. RESULTS: The crude cecal intubation rate was 98% and the adjusted cecal intubation rate was 98.3%. The mean cecal intubation time was 5.6 ± 3.2 min. Multivariate logistic regression analysis demonstrated that patient age greater than 60 years, constipation, poor colon preparation and a two-person colonoscopy procedure were independently associated with lower cecal intubation rates. CONCLUSIONS: Colonoscopy performed under deep sedation by experienced colonoscopists results in high cecal intubation rates. Among the significant patient-related predictors influencing the cecal intubation, the quality of the bowel preparation was the only modifiable factor. When performed by experienced hands, the one-person method was associated with higher cecal intubation rates than the two-person method.

Secreted Neutrophil Gelatinase-Associated Lipocalin Shows Stronger Ability to Inhibit Cyst Enlargement of ADPKD Cells Compared with Nonsecreted Form.

Polycystic kidney disease (PKD) is one of the most common inherited diseases and is characterized by the development of fluid-filled cysts along multiple segments of the nephron. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of PKD, which is caused by mutations in either PKD1 or PKD2 genes that encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. As ADPKD progresses, cysts enlarge and disrupt normal kidney architecture, eventually leading to kidney failure. Our previous study showed that overexpression of exogenous kidney-specific neutrophil gelatinase-associated lipocalin (NGAL) reduced cyst progression and prolonged the lifespan of ADPKD mice (Pkd1L3/L3, 2L3 for short). In this study, we attempted to explore the underlying mechanism of reduced cyst progression in the presence of NGAL using immortalized 2L3 cells. The results of MTT and BrdU incorporation assays showed that recombinant mouse NGAL (mNGAL) protein significantly decreased the viability and proliferation of 2L3 cells. Flow cytometry and western blot analyses showed that mNGAL inhibited activation of the ERK and AKT pathways and induced apoptosis and autophagy in 2L3 cells. In addition, a 3D cell culture platform was established to identify cyst progression in 2L3 cells and showed that mNGAL significantly inhibited cyst enlargement in 2L3 cells. Overexpression of secreted mNGAL (pN + LS) and nonsecreted mNGAL (pN - LS) repressed cell proliferation and cyst enlargement in 2L3 cells and had effects on markers involved in proliferation, apoptosis, and autophagy. However, secreted mNGAL had a more pronounced and consistent effect than that of nonsecreted form. These results reveal that secreted mNGAL has stronger ability to inhibit cyst enlargement of ADPKD cells than that of nonsecreted form. These findings could help to identify strategies for the future clinical treatment of ADPKD.

Neuroprotective effects of granulocyte-colony stimulating factor in a novel transgenic mouse model of SCA17.

Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant inherited disorder characterized by degeneration of spinocerebellar tracts and selected brainstem neurons owing to the expansion of a CAG repeat of the human TATA-binding protein (hTBP) gene. To gain insight into the pathogenesis of this hTBP mutation, we generated transgenic mice with the mutant hTBP gene driven by the Purkinje specific protein (Pcp2/L7) gene promoter. Mice with the expanded hTBP allele developed ataxia within 2-5 months. Behavioral analysis of L7-hTBP transgenic mice showed reduced fall latency in a rotarod assay. Purkinje cell degeneration was identified by immunostaining of calbindin and IP3R1. Reactive gliosis and neuroinflammation occurred in the transgenic cerebellum, accompanied by up-regulation of GFAP and Iba1. The L7-hTBP transgenic mice were thus confirmed to recapitulate the SCA17 phenotype and were used as a disease model to explore the potential of granulocyte-colony stimulating factor in SCA17 treatment. Our results suggest that granulocyte-colony stimulating factor has a neuroprotective effect in these transgenic mice, ameliorating their neurological and behavioral deficits. These data indicate that the expression of the mutant hTBP in Purkinje cells is sufficient to produce cell degeneration and an ataxia phenotype, and constitutes a good model for better analysis of the neurodegeneration in SCA17.

Balloon-assisted enteroscopy with prophylactic polypectomy for Peutz-Jeghers syndrome: experience in Taiwan.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a very rare disease that often causes severe complications such as bowel obstruction or gastrointestinal tract bleeding. In the past, it was usually treated by using surgical intervention despite the associated complications. Balloon-assisted enteroscopy (BAE) has been documented as an effective and safe method for the diagnosis and treatment of small bowel lesions. Hence, we conducted this study to verify whether BAE is useful for patients with PJS. AIM: To evaluate the safety and efficacy of BAE with prophylactic polypectomy in patients with PJS. METHODS AND PATIENTS: From August 2005 to February 2010, 6 consecutive patients were diagnosed with PJS after pathological and clinical examination, and underwent BAE examination and polypectomy at Chang Gung Memorial Hospital, an academic tertiary referral center. RESULTS: Six consecutive patients (4 men and 2 women) diagnosed with PJS underwent BAE with polypectomy. BAE was performed 17 times for complete examination of the entire small bowel. The range of the diameter of the removed polyps was 1-6 cm. No immediate complications such as hemorrhage or hollow organ perforation were noted during the procedure, and no patient developed intussusception during the follow-up period (32 ± 17.5 months). CONCLUSION: BAE with polypectomy is useful for patients with PJS in order to reduce the complications of the condition.

Discovering gapped binding sites of yeast transcription factors.

A gapped transcription factor-binding site (TFBS) contains one or more highly degenerate positions. Discovering gapped motifs is difficult, because allowing highly degenerate positions in a motif greatly enlarges the search space and complicates the discovery process. Here, we propose a method for discovering TFBSs, especially gapped motifs. We use ChIP-chip data to judge the binding strength of a TF to a putative target promoter and use orthologous sequences from related species to judge the degree of evolutionary conservation of a predicted TFBS. Candidate motifs are constructed by growing compact motif blocks and by concatenating two candidate blocks, allowing 0-15 degenerate positions in between. The resultant patterns are statistically evaluated for their ability to distinguish between target and nontarget genes. Then, a position-based ranking procedure is proposed to enhance the signals of true motifs by collecting position concurrences. Empirical tests on 32 known yeast TFBSs show that the method is highly accurate in identifying gapped motifs, outperforming current methods, and it also works well on ungapped motifs. Predictions on additional 54 TFs successfully discover 11 gapped and 38 ungapped motifs supported by literature. Our method achieves high sensitivity and specificity for predicting experimentally verified TFBSs.

MAGIIC-PRO: detecting functional signatures by efficient discovery of long patterns in protein sequences.

This paper presents a web service named MAGIICPRO,which aims to discover functional signatures of a query protein by sequential pattern mining. Automatic discovery of patterns from unaligned biological sequences is an important problem in molecular biology. MAGIIC-PRO is different from several previously established methods performing similar tasks in two major ways. The first remarkable feature of MAGIIC-PRO is its efficiency in delivering long patterns. With incorporating a new type of gap constraints and some of the state-of-theart data mining techniques, MAGIIC-PRO usually identifies satisfied patterns within an acceptable response time. The efficiency of MAGIIC-PRO enables the users to quickly discover functional signatures of which the residues are not from only one region of the protein sequences or are only conserved in few members of a protein family. The second remarkable feature of MAGIIC-PRO is its effort in refining the mining results. Considering large flexible gaps improves the completeness of the derived functional signatures. The users can be directly guided to the patterns with as many blocks as that are conserved simultaneously. In this paper,we show by experiments that MAGIIC-PRO is efficient and effective in identifying ligand-binding sites and hot regions in protein-protein interactions directly from sequences. The web service is availableat http://biominer.bime.ntu.edu.tw/magiicproand a mirror site at http://biominer.cse.yzu.edu.tw/magiicpro.

E1DS: catalytic site prediction based on 1D signatures of concurrent conservation.

Large-scale automatic annotation of protein sequences remains challenging in postgenomics era. E1DS is designed for annotating enzyme sequences based on a repository of 1D signatures. The employed sequence signatures are derived using a novel pattern mining approach that discovers long motifs consisted of several sequential blocks (conserved segments). Each of the sequential blocks is considerably conserved among the protein members of an EC group. Moreover, a signature includes at least three sequential blocks that are concurrently conserved, i.e. frequently observed together in sequences. In other words, a sequence signature is consisted of residues from multiple regions of the protein sequence, which echoes the observation that an enzyme catalytic site is usually constituted of residues that are largely separated in the sequence. E1DS currently contains 5421 sequence signatures that in total cover 932 4-digital EC numbers. E1DS is evaluated based on a collection of enzymes with catalytic sites annotated in Catalytic Site Atlas. When compared to the famous pattern database PROSITE, predictions based on E1DS signatures are considered more sensitive in identifying catalytic sites and the involved residues. E1DS is available at http://e1ds.ee.ncku.edu.tw/ and a mirror site can be found at http://e1ds.csbb.ntu.edu.tw/.

A power-efficient bio-potential acquisition device with DS-MDE sensors for long-term healthcare monitoring applications.

This work describes a power-efficient bio-potential acquisition device for long-term healthcare applications that is implemented using novel microelectromechanical dry electrodes (MDE) and a low power bio-potential processing chip. Using micromachining technology, an attempt is also made to enhance the sensing reliability and stability by fabricating a diamond-shaped MDE (DS-MDE) that has a satisfactory self-stability capability and superior electric conductivity when attached onto skin without any extra skin tissue injury technology. To acquire differential bio-potentials such as ECG signals, the proposed processing chip fabricated in a standard CMOS process has a high common mode rejection ratio (C.M.R.R.) differential amplifier and a 12-bit analog-to-digital converter (ADC). Use of the proposed system and integrate simple peripheral commercial devices can obtain the ECG signal efficiently without additional skin tissue injury and ensure continuous monitoring more than 70 hours with a 400 mAh battery.

Treatment decision for potential bleeders in obscure gastrointestinal bleeding during double-balloon enteroscopy.

Double-balloon enteroscopy (DBE) is an effective tool for diagnosing and treating obscure gastrointestinal bleeding. The aim is to describe how outcomes differ with patient setting (with DBE diagnosis and intervention, with DBE diagnosis but without intervention, and without DBE diagnosis), and thus demonstrate the value of endoscopic intervention when encountering potential bleeder during DBE. From November 2003 to January 2008, 90 patients with obscure gastrointestinal bleeding presented with DBE at our tertiary referral center. A total of 113 DBE procedures were carried out. Overall diagnostic yield was 75.6% (68/90). Endoscopic intervention was performed in 58 (85.3%) of the 68 patients with potential bleeder. The 90 patients were divided into three settings: with endoscopic diagnosis and intervention (n = 58), with endoscopic diagnosis but without intervention (n = 10), and without endoscopic diagnosis (n = 22). Rebleeding rates for the three groups were 22.4%, 60%, and 22.7%, respectively. For the 35 patients diagnosed with vascular lesions, the rebleeding rates in patients with and without endoscopic intervention, were 38.5% (10/26) and 66.7% (6/9), respectively. One (0.9%) severe adverse event occurred during the 113 procedures, and the patient died. DBE is an effective tool for diagnosing and treating obscure gastrointestinal bleeding. DBE involves relatively safe procedures and has an acceptable complication rate. When potential bleeders are encountered during the procedure, especially for vascular lesions, therapeutic intervention should be attempted, since the intervention-related complication rate is acceptable, and such intervention can reduce the rebleeding rate and enhance the cost-effectiveness of DBE.

Hydrodynamics-based transfection of pancreatic duodenal homeobox 1 DNA improves hyperglycemia and is associated with limited complications in diabetic mice.

The biohazards caused by the viral delivery of pancreatic duodenal homeobox gene 1 (Pdx1) to the murine liver limits its application. We aimed to evaluate the feasibility of hydrodynamics-based transfection (HBT) with Pdx1 in improving hyperglycemia. Murine hepatocellular carcinoma (Hepa1-6) cells were transfected with the Pdx1-expressing plasmid, pcDNA3.1/V5-His A (pcDNA)-Pdx1. Hepatic delivery of pcDNA-Pdx1 or pcDNA in streptozocin- induced diabetic mice was achieved by HBT. The sequential serum glucose and alanine aminotransferase (ALT) levels were assessed. On the 3(rd) day after transfection, the transfection efficiency in the Hepa1-6 cells and the mice livers was 5% and 0.35 %, respectively. At 1 wk after HBT, asides from hepatic expression of insulin, the diabetic mice transfected with pcDNA-Pdx1 had a significantly lower sugar (211 +/- 61.6 vs. 413 +/- 62 mg/dL; p = 0.002) level than those transfected with pcDNA; however, the difference diminished afterward. No significant difference in the ALT levels was observed between the 2 groups. No mortality was noted in the mice transfected with pcDNA-Pdx1. The hypoglycemic effect of Pdx1 delivered by HBT was transient and associated with negligible complications. In studies on the short-term biological effects of Pdx1 in vivo, HBT is a potential alternative to viral delivery of Pdx1 to the murine liver.

iPDA: integrated protein disorder analyzer.

This article presents a web server iPDA, which aims at identifying the disordered regions of a query protein. Automatic prediction of disordered regions from protein sequences is an important problem in the study of structural biology. The proposed classifier DisPSSMP2 is different from several existing disorder predictors by its employment of position-specific scoring matrices with respect to physicochemical properties (PSSMP), where the physicochemical properties adopted here especially take the disorder propensity of amino acids into account. The web server iPDA integrates DisPSSMP2 with several other sequence predictors in order to investigate the functional role of the detected disordered region. The predicted information includes sequence conservation, secondary structure, sequence complexity and hydrophobic clusters. According to the proportion of the secondary structure elements predicted, iPDA dynamically adjusts the cutting threshold of determining protein disorder. Furthermore, a pattern mining package for detecting sequence conservation is embedded in iPDA for discovering potential binding regions of the query protein, which is really helpful to uncovering the relationship between protein function and its primary sequence. The web service is available at http://biominer.bime.ntu.edu.tw/ipda and mirrored at http://biominer.cse.yzu.edu.tw/ipda.