Narrow-band imaging is an image-enhanced form of endoscopy used to observed microstructures and capillaries of the mucosal epithelium which allows for real-time prediction of histologic features of ...colorectal polyps. However, narrow-band imaging expertise is required to differentiate hyperplastic from neoplastic polyps with high levels of accuracy. We developed and tested a system of computer-aided diagnosis with a deep neural network (DNN-CAD) to analyze narrow-band images of diminutive colorectal polyps.
We collected 1476 images of neoplastic polyps and 681 images of hyperplastic polyps, obtained from the picture archiving and communications system database in a tertiary hospital in Taiwan. Histologic findings from the polyps were also collected and used as the reference standard. The images and data were used to train the DNN. A test set of images (96 hyperplastic and 188 neoplastic polyps, smaller than 5 mm), obtained from patients who underwent colonoscopies from March 2017 through August 2017, was then used to test the diagnostic ability of the DNN-CAD vs endoscopists (2 expert and 4 novice), who were asked to classify the images of the test set as neoplastic or hyperplastic. Their classifications were compared with findings from histologic analysis. The primary outcome measures were diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic time. The accuracy, sensitivity, specificity, PPV, NPV, and diagnostic time were compared among DNN-CAD, the novice endoscopists, and the expert endoscopists. The study was designed to detect a difference of 10% in accuracy by a 2-sided McNemar test.
In the test set, the DNN-CAD identified neoplastic or hyperplastic polyps with 96.3% sensitivity, 78.1% specificity, a PPV of 89.6%, and a NPV of 91.5%. Fewer than half of the novice endoscopists classified polyps with a NPV of 90% (their NPVs ranged from 73.9% to 84.0%). DNN-CAD classified polyps as neoplastic or hyperplastic in 0.45 ± 0.07 seconds—shorter than the time required by experts (1.54 ± 1.30 seconds) and nonexperts (1.77 ± 1.37 seconds) (both P < .001). DNN-CAD classified polyps with perfect intra-observer agreement (kappa score of 1). There was a low level of intra-observer and inter-observer agreement in classification among endoscopists.
We developed a system called DNN-CAD to identify neoplastic or hyperplastic colorectal polyps less than 5 mm. The system classified polyps with a PPV of 89.6%, and a NPV of 91.5%, and in a shorter time than endoscopists. This deep-learning model has potential for not only endoscopic image recognition but for other forms of medical image analysis, including sonography, computed tomography, and magnetic resonance images.
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A growing body of studies has documented the pathological influence of impaired alternative splicing (AS) events on numerous diseases, including cancer. In addition, the generation of alternatively ...spliced isoforms is frequently noted to result in drug resistance in many cancer therapies. To gain comprehensive insights into the impacts of AS events on cancer biology and therapeutic developments, this paper highlights recent findings regarding the therapeutic routes of targeting alternative-spliced isoforms and splicing regulators to treatment strategies for distinct cancers.
Drug-metabolizing enzymes (DMEs) and membrane transporters play important roles in the absorption, distribution, metabolism, and excretion processes that determine the pharmacokinetics of drugs. ...Inflammation has been shown to regulate the expression and function of these drug-processing proteins. Given that inflammation is a common feature of many diseases, in this review, the general mechanisms for inflammation-mediated regulation of DMEs and transporters are described. Also, evidences regarding the aberrant expression of these drug-processing proteins in several inflammatory diseases and age-related disorders are provided.
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•The roles of drug-metabolizing enzymes and transporters (the drug-processing proteins) in pharmacokinetics are introduced.•General mechanisms for the inflammation-mediated regulation of drug-processing proteins are described.•Examples for the regulation of drug-processing proteins in inflammation-related diseases are summarized.
Gastric cancer is the second leading cause of cancer-related death worldwide. The correlation of Helicobacter pylori and the etiology of gastric cancer was substantially certain. Cholesterol-rich ...microdomains (also called lipid rafts), which provide platforms for signaling, are associated with H. pylori-induced pathogenesis leading to gastric cancer. Patients who have been prescribed statins, inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, have exhibited a reduced risk of several types of cancer. However, no studies have addressed the effect of statins on H. pylori-associated gastric cancer from the antineoplastic perspective. In this study, we showed that treatment of gastric epithelial cells with simvastatin reduced the level of cellular cholesterol and led to attenuation of translocation and phosphorylation of H. pylori cytotoxin-associated gene A (CagA), which is recognized as a major determinant of gastric cancer development. Additionally, a nationwide case-control study based on data from the Taiwanese National Health Insurance Research Database (NHIRD) was conducted. A population-based case-control study revealed that patients who used simvastatin exhibited a significantly reduced risk of gastric cancer (adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.70-0.83). In patients exhibiting H. pylori infection who were prescribed simvastatin, the adjusted OR for gastric cancer was 0.25 (95% CI = 0.12-0.50). Our results combined an in vitro study with a nationwide population analysis reveal that statin use might be a feasible approach to prevent H. pylori-associated gastric cancer.
Helicobacter pylori(H.pylori)infection is highly associated with the occurrence of gastrointestinal diseases,including gastric inflammation,peptic ulcer,gastric cancer,and gastric mucosa-associated ...lymphoid-tissue lymphoma.Although alternative therapies,including phytomedicines and probiotics,have been used to improve eradication,current treatment still relies on a combination of antimicrobial agents,such as amoxicillin,clarithromycin,metronidazole,and levofloxacin,and antisecretory agents,such as proton pump inhibitors(PPIs).A standard triple therapy consisting of a PPI and two antibiotics(clarithromycin and amoxicillin/metronidazole)is widely used as the first-line regimen for treatment of infection,but the increased resistance of H.pylori to clarithromycin and metronidazole has significantly reduced the eradication rate using this therapy and bismuth-containing therapy or 10-d sequential therapy has therefore been proposed to replace standard triple therapy.Alternatively,levofloxacin-based triple therapy can be used as rescue therapy for H.pylori infection after failure of first-line therapy.The increase in resistance to antibiotics,including levofloxacin,may limit the applicability of such regimens.However,since resistance of H.pylori to amoxicillin is generally low,an optimized high dose dual therapy consisting of a PPI and amoxicillin can be an effective first-line or rescue therapy.In addition,the concomitant use of alternative medicine has the potential to provide additive or synergistic effects against H.pylori infection,though its efficacy needs to be verified in clinical studies.
There are limited therapeutic options for patients with Dravet syndrome (DS). The equilibrative nucleoside transporters 1 (ENT1) mediate both the influx and efflux of adenosine across the cell ...membrane exerted beneficial effects in the treatment of epilepsy. This study aimed to evaluate the anticonvulsant effect of the ENT1 inhibitor in an animal model of DS (Scn1a
mice). J7 (5 mg/kg) treatment was efficacious in elevating seizure threshold in Scn1a
mice after hyperthermia exposure. Moreover, the J7 treatment significantly reduced the frequency of spontaneous excitatory post-synaptic currents (sEPSCs, ~35% reduction) without affecting the amplitude in dentate gyrus (DG) granule cells. Pretreatment with the adenosine A1 receptor (A1R) antagonist, DPCPX, abolished the J7 effects on sEPSCs. These observations suggest that the J7 shows an anticonvulsant effect in hyperthermia-induced seizures in Scn1a
mice. This effect possibly acts on presynaptic A1R-mediated signaling modulation in granule cells.
The efficacy of treatment of Helicobacter pylori infection has decreased steadily because of increasing resistance to clarithromycin, metronidazole, and levofloxacin. Resistance to amoxicillin is ...generally low, and high intragastric pH increases the efficacy of amoxicillin, so we investigated whether a combination of a high-dose proton pump inhibitor and amoxicillin (dual therapy) was more effective than standard first-line or rescue therapies in eradicating H pylori.
We performed a large-scale multihospital trial to compare the efficacy of a high-dose dual therapy (HDDT) with that of standard therapies in treatment-naive (n = 450) or treatment-experienced (n = 168) patients with H pylori infection. Treatment-naive patients were randomly assigned to groups given HDDT (rabeprazole 20 mg and amoxicillin 750 mg, 4 times/day for 14 days, group A1), sequential therapy for 10 days (group B1), or clarithromycin-containing triple therapy for 7 days (group C1). Treatment-experienced patients were randomly assigned to groups given HDDT for 14 days (group A2), sequential therapy for 10 days (B2), or levofloxacin-containing triple therapy for 7 days (C2). H pylori infection was detected by using the (13)C-urea breath test. We evaluated factors associated with treatment outcomes.
In the intention-to-treat analysis, H pylori was eradicated in 95.3% of patients in group A1 (95% confidence interval CI, 91.9%-98.8%), 85.3% in B1 (95% CI, 79.6%-91.1%), and 80.7% in group C1 (95% CI, 74.3%-87.1%). Infection was eradicated in 89.3% of patients in group A2 (95% CI, 80.9%-97.6%), 51.8% in group B2 (95% CI, 38.3%-65.3%), and 78.6% (95% CI, 67.5%-89.7%) in group C2. The efficacy of HDDT was significantly higher than that of currently recommended regimens, irrespective of CYP2C19 genotype. Bacterial resistance to drugs was associated with treatment failure. There were no significant differences between groups in adverse events or patient adherence.
HDDT is superior to standard regimens as empirical first-line or rescue therapy for H pylori infection, with similar safety profiles and tolerability. ClinicalTrials.gov number: NCT01163435.
Most UAVs rely on GPS for localization in an outdoor environment. However, in GPS-denied environment, other sources of localization are required for UAVs to conduct feedback control and navigation. ...LiDAR has been used for indoor localization, but the sampling rate is usually too low for feedback control of UAVs. To compensate this drawback, IMU sensors are usually fused to generate high-frequency odometry, with only few extra computation resources. To achieve this goal, a real-time LiDAR inertial odometer system (RTLIO) is developed in this work to generate high-precision and high-frequency odometry for the feedback control of UAVs in an indoor environment, and this is achieved by solving cost functions that consist of the LiDAR and IMU residuals. Compared to the traditional LIO approach, the initialization process of the developed RTLIO can be achieved, even when the device is stationary. To further reduce the accumulated pose errors, loop closure and pose-graph optimization are also developed in RTLIO. To demonstrate the efficacy of the developed RTLIO, experiments with long-range trajectory are conducted, and the results indicate that the RTLIO can outperform LIO with a smaller drift. Experiments with odometry benchmark dataset (i.e., KITTI) are also conducted to compare the performance with other methods, and the results show that the RTLIO can outperform ALOAM and LOAM in terms of exhibiting a smaller time delay and greater position accuracy.
Protein-bound uremic toxins, such as p-cresol sulfate (PCS), can be accumulated with declined renal function and aging and is closely linked with central nervous system (CNS) diseases. In the ...periphery, PCS has effects on oxidative stress and inflammation. Since oxidative stress and inflammation have substantial roles in the pathogenesis of neurological disorders, the CNS effects of PCS were investigated in unilateral nephrectomized C57/BL/6 mice. Unlike intact mice, unilateral nephrectomized mice showed increased circulating levels of PCS after exogenous administration. Upon PCS exposure, the unilateral nephrectomized mice developed depression-like, anxiety-like, and cognitive impairment behaviors with brain PCS accumulation in comparison with the nephrectomy-only group. In the prefrontal cortical tissues, neuronal cell survival and neurogenesis were impaired along with increased apoptosis, oxidative stress, and neuroinflammation. Circulating brain-derived neurotrophic factors (BDNF) and serotonin were decreased in association with increased corticosterone and repressor element-1 silencing transcription factor (REST), regulators involved in neurological disorders. On the contrary, these PCS-induced changes were alleviated by uremic toxin absorbent AST-120. Taken together, PCS administration in mice with nephrectomy contributed to neurological disorders with increased oxidative stress and neuroinflammation, which were alleviated by PCS chelation. It is suggested that PCS may be a therapeutic target for chronic kidney disease-associated CNS diseases.
Alternative splicing has been widely demonstrated to function as pivotal regulation in specifying cellular fates and biological functions. The relative expression or cellular localization of a ...splicing factor constitutes an important mechanism in spatiotemporal programming of cell- and stage-specific splicing profiles. In this study, results of deep RNA-sequencing (RNA-Seq) analyses first revealed the reprogrammed splicing profile and reduced expression of serine/arginine-rich splicing factor protein kinase 1 (SRPK1) throughout the development of brown adipose tissue (BAT). A gradual increase in the exon 10-skipped SRPK1 transcript, a potential target of a nonsense-mediated decay (NMD) mechanism, was noted during brown adipogenesis. Elevated RBM4a constituted the regulatory mechanism that led to skipping of SRPK1 exon 10. Moreover, brown adipogenesis-induced upregulation of microRNA (miR)-485 interfered with SRPK1 expression by targeting its 3′-untranslated region (UTR). Depletion of endogenous SRPK1 enhanced the development of C3H10T1/2 cells toward brown adipocytes. Taking our results together, multiple post-transcriptional regulations reduced SRPK1 expression, which subsequently affected brown adipogenesis.
•Differential splicing profile of SRPK1is noted during brown adipogenesis.•AS-NMD pathway contributes to the reduced SRPK1 expression during BAT development.•RBM4a and PTBP1 exert opposite effect on the selection of SRPK1 exon 10.•Upregulated miR-485 leads to the reduced SRPK1 during brown adipogenesis.•Upregulated SRPK1 is demonstrated a novel repressor to brown adipogenesis.
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