ReGen-DTI: A novel generative drug target interaction model for predicting potential drug candidates against SARS-COV2.

Covid-19 has caused massive numbers of infections and fatalities globally. In response, there has been a large-scale experimental and computational research effort to study and develop drugs. Towards this, Deep learning techniques are used for the generation of potential novel drug candidates that are proven to be effective against exploring large molecular search spaces. Recent advances in reinforcement learning in conjunction with generative techniques has proven to be a promising field in the area of drug discovery. In this regard, we propose a generative drug discovery approach using reinforcement techniques for sampling novel molecules that bind to the main protease of SARS-COV2. The generative method reported significant validity scores for the generated novel molecules and captured the underlying features of the training molecules. Further, the model is fine-tuned on existing re-purposed molecules which are active towards specific target proteins based on similarity metrics. Upon fine tuning the model generated 92.71% valid, 93.55% unique, and 100% novel molecules. Unlike previous methods which are dependent on docking procedures, we proposed a deep learning based novel drug target interaction (DTI) model to find the binding affinity between candidate molecules and target protease sequence. Finally, the binding affinity of the generated molecules is predicted against the 3CLPro main protease by using the proposed DTI model. Most of the generated molecules have shown binding affinity scores <100 nM (lower the better), which are significantly better compared to the existing commercial drugs including Remdesevir.

Impact of withdrawal time on adenoma detection rate: results from a prospective multicenter trial.

BACKGROUND AND AIMS: Performing a high-quality colonoscopy is critical for optimizing the adenoma detection rate (ADR). Colonoscopy withdrawal time (a surrogate measure) of ≥6 minutes is recommended; however, a threshold of a high-quality withdrawal and its impact on ADR are not known. METHODS: We examined withdrawal time (excluding polyp resection and bowel cleaning time) of subjects undergoing screening and/or surveillance colonoscopy in a prospective, multicenter, randomized controlled trial. We examined the relationship of withdrawal time in 1-minute increments on ADR and reported odds ratio (OR) with 95% confidence intervals. Linear regression analysis was performed to assess the maximal inspection time threshold that impacts the ADR. RESULTS: A total of 1142 subjects (age, 62.3 ± 8.9 years; 80.5% men) underwent screening (45.9%) or surveillance (53.6%) colonoscopy. The screening group had a median withdrawal time of 9.0 minutes (interquartile range [IQR], 3.3) with an ADR of 49.6%, whereas the surveillance group had a median withdrawal time of 9.3 minutes (IQR, 4.3) with an ADR of 63.9%. ADR correspondingly increased for a withdrawal time of 6 minutes to 13 minutes, beyond which ADR did not increase (50.4% vs 76.6%, P < .01). For every 1-minute increase in withdrawal time, there was 6% higher odds of detecting an additional subject with an adenoma (OR, 1.06; 95% confidence interval, 1.02-1.10; P = .004). CONCLUSIONS: Results from this multicenter, randomized controlled trial underscore the importance of a high-quality examination and efforts required to achieve this with an incremental yield in ADR based on withdrawal time. (Clinical trial registration number: NCT03952611.).

Diagnostic performance of volumetric laser endomicroscopy for Barrett's esophagus dysplasia amongst gastroenterology trainees.

BACKGROUND: Volumetric laser endomicroscopy (VLE) is an advanced imaging modality used in Barrett's esophagus (BE) surveillance. VLE image interpretation is challenged by subtle grayscale image variation across a large amount of data. Training in VLE interpretation is not standardized. This study aims to determine if VLE training can be incorporated into a gastroenterology (GI) fellowship curriculum with the use of a self-directed module. METHODS: A standardized, self-directed training module (30 min) was created explaining the background and established VLE criteria for the diagnosis of BE dysplasia. A VLE image dataset was generated from a multicenter VLE database of targeted biopsies. GI trainees were asked to grade each image for the presence or absence of the following criteria (I) increased surface optical frequency domain imaging (OFDI) signal intensity and (II) atypical glands and provide a final diagnosis (dysplastic vs. non-dysplastic). Diagnostic performance was calculated and results compared to VLE expert interpretation using histology as the gold-standard. RESULTS: The dataset included 50 VLE images (10 high-grade dysplasia, 40 non-dysplastic BE). VLE images were reviewed in a randomized and blinded fashion by 5 GI trainees with no prior VLE experience and 5 experienced VLE users. Sensitivity, specificity and accuracy of GI trainees was 83.3% (95% CI: 71.5-91.7%), 59.0% (95% CI: 51.6-66.0%), and 64.8% (95% CI: 58.5-70.7%) compared to 80.0% (95% CI: 67.7-89.2%), 79.5% (95% CI: 73.0-85.0%), and 79.6% (95% CI: 74.1-84.4%) for VLE experts respectively. The difference in specificity and accuracy between the two groups were statistically significant with P<0.001. CONCLUSIONS: A brief training session on VLE is inadequate to reach competency in interpretation of VLE by GI trainees. Additional experience is required to accurately interpret VLE images.

PPred-PCKSM: A multi-layer predictor for identifying promoter and its variants using position based features.

Promoter is a small region of DNA where a protein called RNA polymerase binds thus resulting in initiation of transcription of a specific gene. In bacteria with prokaryotic cell type, the sigma subunit that combines with RNA polymerase helps in identifying promoters. In Escherichia coli (E.coli), the promoters are identified by different sigma factors consisting of different functionalities. There have been various methods used for prediction of different class of promoters. However, these methods need to be improved for better identification and classification of promoters. In this work, we propose a new multi-layer predictor named PPred-PCKSM that uses position-correlation based k-mer scoring matrix (PCKSM), a new feature extraction strategy and an artificial neural network (ANN) for predicting promoters and its six types, namely σ70, σ24, σ28, σ32, σ38 and σ54 in E.coli bacteria. We employ PCKSM technique to extract feature sets from different k-mers. The feature sets obtained from trimers and tetramers are concatenated and then passed through ANN for final prediction. The resultant feature set contained effective features that contributed towards achieving an accuracy of 98.02% and Matthews correlation coefficient (MCC) of 96.04% for promoter prediction task. Our model used 5-fold cross validation on the benchmark dataset and outperformed all the current state-of-art-methods used for prediction of promoters and its different types in E.coli bacteria.

High-Definition Colonoscopy Compared With Cuff- and Cap-Assisted Colonoscopy: Results From a Multicenter, Prospective, Randomized Controlled Trial.

BACKGROUND AND AIMS: Mucosal exposure devices including distal attachments such as the cuff and cap have shown variable results in improving adenoma detection rate (ADR) compared with high-definition white light colonoscopy (HDWLE). METHODS: We performed a prospective, multicenter randomized controlled trial in patients undergoing screening or surveillance colonoscopy comparing HDWLE to 2 different types of distal attachments: cuff (CF) (Endocuff Vision) or cap (CP) (Reveal). The primary outcome was ADR. Secondary outcomes included adenomas per colonoscopy, advanced adenoma and sessile serrated lesion detection rate, right-sided ADR, withdrawal time, and adverse events. Continuous variables were compared using Student's t test and categorical variables were compared using chi-square or Fisher's exact test using statistical software Stata version16. A P value <.05 was considered significant. RESULTS: A total of 1203 subjects were randomized to either HDWLE (n = 384; mean 62 years of age; 81.3% males), CF (n = 379; mean 62.7 years of age; 79.9% males) or CP (n = 379; mean age 62.1 years of age; 80.5% males). No significant differences were found among 3 groups for ADR (57.3%, 59.1%, and 55.7%; P = .6), adenomas per colonoscopy (1.4 ± 1.9, 1.6 ± 2.4, and 1.4 ± 2; P = .3), advanced adenoma (7.6%, 9.2%, and 8.2%; P = .7), sessile serrated lesion (6.8%, 6.3%, and 5.5%; P = .8), or right ADR (48.2%, 49.3%, and 46.2%; P = .7). The number of polyps per colonoscopy were significantly higher in the CF group compared with HDWLE and CP group (2.7 ± 3.4, 2.3 ± 2.5, and 2.2 ± 2.3; P = .013). In a multivariable model, after adjusting for age, sex, body mass index, withdrawal time, and Boston Bowel Preparation Scale score, there was no impact of device type on the primary outcome of ADR (P = .77). In screening patients, CF resulted in more neoplasms per colonoscopy (CF: 1.7 ± 2.6, HDWLE: 1.3 ± 1.7, and CP: 1.2 ± 1.8; P = .047) with a shorter withdrawal time. CONCLUSIONS: Results from this multicenter randomized controlled trial do not show any significant benefit of using either distal attachment devices (CF or CP) over HDWLE, at least in high-detector endoscopists. The Endocuff may have an advantage in the screening population. (ClinicalTrials.gov, Number: NCT03952611).

NoAS-DS: Neural optimal architecture search for detection of diverse DNA signals.

Neural network architectures are high-performing variable models that can solve many learning tasks. Designing architectures manually require substantial time and also prior knowledge and expertise to develop a high-accuracy model. Most of the architecture search methods are developed over the task of image classification resulting in the building of complex architectures intended for large data inputs such as images. Motivated by the applications of DNA computing in Neural Architecture Search (NAS), we propose NoAS-DS which is specifically built for the architecture search of sequence-based classification tasks. Furthermore, NoAS-DS is applied to the task of predicting binding sites. Unlike other methods that implement only Convolution layers, NoAS-DS, specifically combines Convolution and LSTM layers that helps in the process of automatic architecture building. This hybrid approach helped in achieving high accuracy results on TFBS and RBP datasets which outperformed other models in TF-DNA binding prediction tasks. The best architectures generated by the proposed model can be applied to other DNA datasets of similar nature using transfer learning technique that demonstrates its generalization capability. This greatly reduces the effort required to build new architectures for other prediction tasks.

Explainable deep neural networks for novel viral genome prediction.

Viral infection causes a wide variety of human diseases including cancer and COVID-19. Viruses invade host cells and associate with host molecules, potentially disrupting the normal function of hosts that leads to fatal diseases. Novel viral genome prediction is crucial for understanding the complex viral diseases like AIDS and Ebola. While most existing computational techniques classify viral genomes, the efficiency of the classification depends solely on the structural features extracted. The state-of-the-art DNN models achieved excellent performance by automatic extraction of classification features, but the degree of model explainability is relatively poor. During model training for viral prediction, proposed CNN, CNN-LSTM based methods (EdeepVPP, EdeepVPP-hybrid) automatically extracts features. EdeepVPP also performs model interpretability in order to extract the most important patterns that cause viral genomes through learned filters. It is an interpretable CNN model that extracts vital biologically relevant patterns (features) from feature maps of viral sequences. The EdeepVPP-hybrid predictor outperforms all the existing methods by achieving 0.992 mean AUC-ROC and 0.990 AUC-PR on 19 human metagenomic contig experiment datasets using 10-fold cross-validation. We evaluate the ability of CNN filters to detect patterns across high average activation values. To further asses the robustness of EdeepVPP model, we perform leave-one-experiment-out cross-validation. It can work as a recommendation system to further analyze the raw sequences labeled as 'unknown' by alignment-based methods. We show that our interpretable model can extract patterns that are considered to be the most important features for predicting virus sequences through learned filters.

Comparing accuracy of high-risk features for detecting advanced neoplasia in pancreatic cystic lesions: a systematic review and meta-analysis.

BACKGROUND: The American Gastroenterological Association recommends endoscopic ultrasound (EUS) for evaluating pancreatic cystic lesions (PCL) with ≥2 high-risk features (HRF), whereas the American College of Gastroenterology recommends EUS for ≥1 HRF. This systematic review and meta-analysis compared the diagnostic accuracy of using ≥1 vs. ≥2 HRF for assessing the risk of advanced neoplasia (AN) and performing EUS in PCL. METHODS: An electronic database search was performed for eligible studies. AN was defined as pancreatic adenocarcinoma, intraductal papillary mucinous neoplasm or mucinous cystadenoma with high-grade dysplasia, pancreatic intraepithelial neoplasia and pancreatic neuroendocrine tumors. HRF included cyst size ≥3 cm, solid component, and dilated pancreatic duct ≥5 mm. The primary outcome was the sensitivity and specificity of using ≥1 vs. ≥2 HRF as an indication for EUS to detect AN in PCL. RESULTS: Of 38 studies initially screened, 8 were included in the final analysis. Seven studies assessed the accuracy of ≥2 HRF and 4 studies assessed ≥1 HRF. The pooled sensitivity, specificity, positive and negative predictive values of EUS for detecting AN were 41.7% (95% confidence interval 19.5-67.8%), 90.8% (81.9-95.5%), 30.4% (19.4-44.2%) and 94.3% (89.6-97.0%) with ≥2HRFs, and 77.1% (66.1-85.3%), 72.7% (50.4-87.5%), 17.95% (10.3-29.4%), 98.1% (90.8-99.6%), respectively, with ≥1 HRF. CONCLUSION: Performing EUS for PCL with ≥1 HRF could offer greater sensitivity in detecting AN compared to ≥2 HRF, with a similar negative predictive value.

Do Water-aided Techniques Improve Serrated Polyp Detection Rate During Colonoscopy?: A Systematic Review With Meta-Analysis.

BACKGROUND AND STUDY AIMS: The utility of water-aided techniques (WT): water exchange (WE) and water immersion (WI) have been studied extensively in the literature for improving colonoscopy outcome metrics such as adenoma detection rate. Serrated polyps owing to their location and appearance have a high miss rate. The authors performed a systematic review and meta-analysis of studies comparing WT with the standard gas-assisted (GA) method to determine if there was any impact on serrated polyp detection rate (SPDR) and sessile serrated polyp detection rate. METHODS: The following databases were queried for this systematic review: Medline, EMBASE, Cochrane Library, CINAHL, and Web of Sciences. The authors only included randomized controlled trials (RCTs). The primary outcome was SPDR and secondary outcomes were sessile serrated polyp detection rate and cecal intubation rate. Risk ratios (RRs) were calculated for each outcome. A P-value <0.05 was considered to be statistically significant. RESULTS: A total of 4 RCTs (5 arms) with 5306 patients (2571 in the GA group and 2735 in the WT group) were included. The SPDR was significantly increased for the WT group compared with GA (6.1% vs. 3.8%; RR, 1.63; 95% confidence interval, 1.24-2.13; P<0.001; I2=22.7%). A subgroup analysis for WE technique also demonstrated improved SPDR compared with the GA method (4.9% vs. 3.2%; RR, 1.57; 95% confidence interval, 1.15-2.14; P=0.004; I2=6.1%). CONCLUSIONS: WT, particularly, the WE method results in improved SPDR. This technique should be encouraged in a clinical setting to detect these polyps to prevent interval colorectal cancer.

Does timing of endoscopy affect outcomes in patients with upper gastrointestinal bleeding: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The timing of esophagogastroduodenoscopy (EGD) for the management of upper gastrointestinal bleeding (UGIB) remains controversial. Early EGD (E-EGD) (within 24 h of presentation) has been compared to late EGD (L-EGD) (after 24 h) in numerous studies with conflicting results. The previous systematic review included three randomized controlled trials (RCTs); however, the cutoff time for performing EGD was arbitrary. We performed an updated systematic review and meta-analysis of the studies comparing the outcomes of E-EGD and L-EGD group. METHODS: A comprehensive search of PubMed, EMBASE, Cochrane Library, and Web of Science was undertaken to include both RCTs and cohort studies. Primary outcomes including overall mortality and secondary outcomes (recurrent bleeding, need for transfusion, and length of stay) were compared. Risk ratios and standardized mean difference (SMD) with 95% confidence interval (CI) were calculated. RESULTS: A total of 13 observational studies (with over 1.8 million patients) were included in the final analysis. No significant difference in overall mortality (risk ratio: 0.97; CI, 0.74-1.27), recurrent bleeding (risk ratio: 1.12; CI, 0.62-2.00), and length of stay (SMD: -0.07, CI, -0.31 to 0.18) was observed for E-EGD group compared to L-EGD group. The possibility of endoscopic intervention was higher in E-EGD group (risk ratio: 1.70, CI, 1.28-2.27). Consistent results were obtained for subgroup analysis of studies with 100% nonvariceal bleed (NVB) patient (risk ratio: 1.12; CI, 0.84-1.50). CONCLUSION: Given the outcomes and limitations, our meta-analysis did not demonstrate clear benefit of performing EGD within 24 h of presentation for UGIB (particularly NVB).

A Comparative Study of 22G versus 19G Needles for EUS-Guided Biopsies for Parenchymal Liver Disease: Are Thinner Needles Better?

BACKGROUND AND AIMS: Data on comparative efficacy of various available endoscopic ultrasound-guided liver biopsy (EUS-LB) needles are limited. We sought to compare the performance of a novel Franseen-tip 22G fine-needle biopsy (FNB) device to that of 19G needle platforms for liver parenchyma. METHODS: Consecutive patients referred for EUS and suspected to have hepatic parenchymal disease underwent EUS-LB using different EUS needles and were included in this retrospective study. Two blinded expert liver pathologists independently reviewed and reported on: total number of tissue fragments, length of longest fragment, number of complete and incomplete portal tracts (CPT and IPT), and specimen adequacy. RESULTS: A 22G Franseen-tip needle (A) was used in 30 patients; 19G Tru-Cut needle (B) in 50 patients; 19G reverse beveled non-Tru-Cut needle (C) in 27 patients; and a 19G flexible non-Tru-Cut needle (D) in 28 patients. In the order of needles, A, B, C and D, > 10 tissue fragments were obtained in 100%, 6%, 82%, and 96% samples, the mean number of CPTs was 6.9; 3.0; 7.3; and 16.9, length of longest fragment was 3.8, 4. 7, 3.9, and 8.4 mm, and specimen adequacy was 66.7%, 46%, 82.1%, and 81.5%, respectively. A positive correlation was obtained between number of CPTs and length of longest fragment in samples accrued by 19G needles. CONCLUSION: EUS-LB specimens using 22G Franseen-tip needle appear highly fragmented, leading to inferior specimen adequacy compared to 19G non-Tru-Cut needles. We also report on using length of longest fragment as an additional criterion for specimen adequacy as it positively correlates with number of CPTs standard.

Second-generation distal attachment cuff improves adenoma detection rate: meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Multiple randomized controlled trials (RCTs) using the second-generation distal attachment cuff device (Endocuff Vision; Olympus America, Center Valley, Pa, USA) have reported conflicting results in improving adenoma detection rate (ADR) compared with standard high-definition colonoscopy without the distal attachment. We conducted a systematic review and meta-analysis of RCTs to compare outcomes between second-generation cuff colonoscopy (CC) versus colonoscopy without the distal attachment (standard colonoscopy [SC]). METHODS: An electronic literature search was performed using PubMed, Google Scholar, Embase, and Cochrane Library through May 2020. The primary outcome was reporting of ADR, and secondary outcomes were polyp detection rate (PDR), mean withdrawal time, mean adenomas per colonoscopy (APC), sessile serrated lesion detection rate, and adverse events. Pooled rates and risk ratios (RRs) with 95% confidence intervals were reported. RESULTS: Eight RCTs with 5695 patients were included in the final analysis, with 2862 patients (mean age, 62.8 years; 52.9% men) in the CC group and 2833 patients (mean age, 62.6 years; 54.2% men) in the SC group. Compared with SC, use of CC was associated with a significant improvement in ADR (49.8% vs 45.6%, respectively; RR, 1.12; P = .02), PDR (58.1% vs 53%, respectively; RR, 1.12; P = .009), and APC (P < .01). Furthermore, use of CC had a .93-minute lower mean withdrawal time (P < .01) when compared with SC. The difference in ADR was larger in the screening/surveillance population (6.5%, P = .02) and when used by endoscopists with ADRs <30% (9.4%, P = .03). CONCLUSIONS: The results of this meta-analysis of randomized trials show a significant improvement in ADR and APC with shorter withdrawal times using the second-generation cuff device compared with SC.

Diagnostic accuracy of a novel third generation esophageal capsule as a non-invasive detection method for Barrett's esophagus: A pilot study.

BACKGROUND AND AIM: Previous two generations of esophageal capsule did not show adequate detection rates for Barrett's esophagus (BE). We assessed the diagnostic accuracy of a novel third generation capsule with an improved frame rate of 35 frames per second for the detection of BE in a pilot study. METHODS: This was a blinded prospective pilot study conducted at a tertiary medical center. Patients with known BE (at least C0M > 1) who presented for endoscopic surveillance (May to October 2017) were included. All patients underwent novel esophageal capsule (PillCam™ UGI; Medtronic) ingestion using the simplified ingestion protocol followed by standard high-definition upper endoscopy (esophagogastroduodenoscopy [EGD]). Capsule endoscopy findings were interpreted by examiners blinded to endoscopy results and compared with endoscopic findings (gold standard). Following completion of both tests, a subjective questionnaire was provided to all patients regarding their experience. RESULTS: Twenty patients (95%males, mean age 66.3 [±7.9] years) with BE undergoing surveillance EGD were eligible. The mean BE length was 3.5 (±2.7) cm. Novel esophageal capsule detected BE in 75% patients when images were compared with endoscopy. Novel capsule detected BE in 82% patients when the BE length was ≥2 cm. The mean esophageal transit time was 0.59 s. On a subjective questionnaire, all 20 patients reported novel capsule as being more convenient compared with EGD. CONCLUSIONS: In this pilot, single-center study, novel esophageal capsule was shown to be not ready for population screening of BE. Studies integrating artificial intelligence into improved quality novel esophageal capsule should be performed for BE screening.

Cannabis hyperemesis syndrome: an update on the pathophysiology and management.

Cannabis hyperemesis syndrome (CHS) is a form of functional gut-brain axis disorder characterized by bouts of episodic nausea and vomiting worsened by cannabis intake. It is considered as a variant of cyclical vomiting syndrome seen in cannabis users especially characterized by compulsive hot bathing/showers to relieve the symptoms. CHS was reported for the first time in 2004, and since then, an increasing number of cases have been reported. With cannabis use increasing throughout the world as the threshold for legalization becomes lower, its user numbers are expected to rise over time. Despite this trend, a strict criterion for the diagnosis of CHS is lacking. Early recognition of CHS is essential to prevent complications related to severe volume depletion. The recent body of research recognizes that patients with CHS impose a burden on the healthcare systems. Understanding the pathophysiology of the endocannabinoid system (ECS) remains central in explaining the clinical features and potential drug targets for the treatment of CHS. The frequency and prevalence of CHS change in accordance with the doses of tetrahydrocannabinol and other cannabinoids in various formulations of cannabis. CHS is unique in presentation, because of the cannabis's biphasic effect as anti-emetic at low doses and pro-emetic at higher doses, and the association with pathological hot water bathing. In this narrative review, we elaborate on the role of the ECS, its management, and the identification of gaps in our current knowledge of CHS to further enhance its understanding in the future.

Proton pump inhibitors do not increase the risk of dementia: a systematic review and meta-analysis of prospective studies.

Published studies have reported variable results on the association between duration of proton pump inhibitor (PPI) use and the risk of dementia. An extensive literature search was performed in PubMed, Embase, Google Scholar, and Cochrane for studies examining the risk of cognitive decline and dementia among PPI users versus non-PPI users in prospective studies. Retrospective database linkage studies, case reports, case series, editorials, uncontrolled cohort studies, cross-sectional studies, and review articles were excluded. Primary outcome was pooled hazard rate (HR) of any dementia among PPI users compared with non-PPI users. Secondary outcomes were pooled HR of Alzheimer's dementia (AD) and risk with long-term PPI follow-up (more than 5 years) studies. Meta-analysis outcomes, heterogeneity (I2), and meta-regression (for the effect of covariates) were derived by statistical software R and Open meta-analyst. A total of six studies (one RCT and five prospective) with 308249 subjects, average age of 75.8 ± 5.2 years, and follow-up of 5 (range 1.5-11) years were included in the analysis. Pooled HR of any dementia was 1.16 (n = 6, 95% confidence interval (CI) = 0.86-1.47). Results remained unchanged when only studies with long-term PPI use (more than 5 years) were analyzed (n = 4, pooled HR 1.10, 95% CI 0.66-1.53). Finally, the pooled HR for AD was 1.06 (n = 3, 95% CI 0.70-1.41). There was substantial heterogeneity among inclusion studies (I2 = 93%). Meta-regression did not demonstrate a significant role of age at study start (P = 0.1) or duration of PPI use (P = 0.62) to incident dementia. The results of this systematic review and meta-analysis do not show a significant relationship between PPI use and dementia in prospective studies with at least a 5-year follow-up.

Comparative analysis of protein synthesis rate in COVID-19 with other human coronaviruses.

The genetic code contains information that impacts the efficiency and rate of translation. Translation elongation plays a crucial role in determining the composition of the proteome, errors within a protein contributes towards disease processes. It is important to analyze the novel coronavirus (2019-nCoV) at the codon level to find similarities and variations in hosts to compare with other human coronavirus (CoVs). This requires a comparative and comprehensive study of various human and zoonotic nature CoVs relating to codon usage bias, relative synonymous codon usage (RSCU), proportions of slow codons, and slow di-codons, the effective number of codons (ENC), mutation bias, codon adaptation index (CAI), and codon frequencies. In this work, seven different CoVs were analyzed to determine the protein synthesis rate and the adaptation of these viruses to the host cell. The result reveals that the proportions of slow codons and slow di-codons in human host of 2019-nCoV and SARS-CoV found to be similar and very less compared to the other five coronavirus types, which suggest that the 2019-nCoV and SARS-CoV have faster protein synthesis rate. Zoonotic CoVs have high RSCU and codon adaptation index than human CoVs which implies the high translation rate in zoonotic viruses. All CoVs have more AT% than GC% in genetic codon compositions. The average ENC values of seven CoVs ranged between 38.36 and 49.55, which implies the CoVs are highly conserved and are easily adapted to host cells. The mutation rate of 2019-nCoV is comparatively less than MERS-CoV and NL63 that shows an evidence for genetic diversity. Host-specific codon composition analysis portrays the relation between viral host sequences and the capability of novel virus replication in host cells. Moreover, the analysis provides useful measures for evaluating a virus-host adaptation, transmission potential of novel viruses, and thus contributes to the strategies of anti-viral drug design.

Intralesional steroids and endoscopic dilation for anastomotic strictures after esophagectomy: systematic review and meta-analysis.

BACKGROUND: Post-esophagectomy anastomotic strictures are difficult to treat. The impact of adding local steroid injection to endoscopic dilation for the treatment of post-esophagectomy anastomotic strictures is unclear. We conducted a systematic review and meta-analysis to assess the efficacy of performing steroid injection in addition to dilation. METHODS: A search was conducted in MEDLINE, Cochrane Library, EMBASE, and Web of Science from inception to January 2019. Randomized controlled trials (RCTs) comparing the efficacy of endoscopic dilation plus either local steroid injection (steroid group) or saline injection (placebo group) were included in the analysis. RESULTS: Three RCTs were eligible for the final analysis: 72 patients (mean age 61.3 years, 74 % male) in the steroid group and 72 patients (mean age 59.6 years, 71 % male) in the placebo group. The mean number of dilations required to resolve the stricture was significantly lower in the steroid group compared with the placebo group, with a mean weighted difference of -1.62 (95 % confidence interval [CI] -2.73 to -0.50; P = 0.004). After 6 months of follow-up, there was a trend toward more patients in the steroid group remaining dysphagia free compared with the placebo group, with a pooled odds ratio of 2.36 (95 %CI 0.94 to 5.91; P = 0.07, I2  = 24 %). CONCLUSION: This meta-analysis showed that the addition of local steroid injection at the time of dilation for benign anastomotic strictures led to a significant decrease in the number of procedures required to resolve the stricture and may well reduce dysphagia symptoms during follow-up.

Effectiveness and safety of EUS-guided choledochoduodenostomy using lumen-apposing metal stents (LAMS): a systematic review and meta-analysis.

BACKGROUND: Endoscopic ultrasound-guided choledochoduodenostomy (CDD) is emerging as an alternative technique for biliary drainage in patients who fail conventional endoscopic retrograde cholangiopancreatography (ERCP). The lumen-apposing metal stents (LAMS) are being increasingly used for CDD. We performed a systematic review and meta-analysis to evaluate the effectiveness and safety of CDD using LAMS. METHODS: We performed a systematic search of multiple databases through May 2019 to identify studies on CDD using covered self-expanding metal stents. Pooled rates of technical success, clinical success, adverse events, and recurrent jaundice associated with CDD using LAMS were estimated. A subgroup analysis was performed based on use of LAMS with electrocautery-enhanced delivery system (EC-LAMS). RESULTS: Seven studies on CDD using LAMS (with 284 patients) were included in the meta-analysis. Pooled rates of technical and clinical success (per-protocol analysis) were 95.7% (95% CI 93.2-98.1) and 95.9% (95% CI 92.8-98.9), respectively. Pooled rate of post-procedure adverse events was 5.2% (95% CI 2.6-7.9). Pooled rate of recurrent jaundice was 8.7% (95% CI 4.5-12.8). On subgroup analysis of CDD using EC-LAMS (5 studies with 201 patients), the pooled rates of technical and clinical success (per-protocol analysis) were 93.8% (95% CI 90.4-97.1) and 95.9% (95% CI 91.9-99.9), respectively. Pooled rate of post-procedure adverse events was 5.6% (95% CI 1.7-9.5). Pooled rate of recurrent jaundice was 11.3% (95% CI 6.9-15.7). Heterogeneity (I2) was low to moderate in the analyses. CONCLUSION: CDD using LAMS/EC-LAMS is an effective and safe technique for biliary decompression in patients who failed ERCP. Further studies are needed to assess CDD using LAMS as primary treatment modality for biliary obstruction.

Improving serrated adenoma detection rate in the colon by electronic chromoendoscopy and distal attachment: systematic review and meta-analysis.

BACKGROUND AND AIMS: The evidence for modification of conventional colonoscopy using either "distal attachments" (DAs; endocap, endocuff, and endoring) or "electronic chromoendoscopy" (EC; narrow-band imaging [NBI], iScan, blue-light imaging, autofluorescence imaging, and linked-color imaging) to improve the detection of serrated adenomas during colonoscopy has shown conflicting results. METHODS: A comprehensive literature search was performed using Medline, Google Scholar, Embase, and Cochrane Library based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized controlled trials (RCTs) comparing any DA or EC with high-definition white-light colonoscopy for detection of serrated adenomas (sessile serrated adenoma/polyp and traditional serrated adenoma) were included. The primary outcome was serrated adenoma detection rate (SADR) defined as the number of patients with at least 1 serrated adenoma of total patients in that group. The secondary outcome was the number of serrated adenomas per subject. Pooled rates were reported using risk ratio (RR) with 95% confidence interval. RESULTS: Seventeen studies with 13,631 patients (56% men; age range, 50-66 years) met the inclusion criteria. The use of DAs (RR, 1.21; P = .45) and EC (RR, 1.29; P = .09) during colonoscopy did not show a significant improvement in SADR. The SADR using EC was 6.9% (4 studies) and that with NBI alone was 3.7% (3 studies). CONCLUSIONS: The results indicate that, except for NBI, the use of DAs or EC during colonoscopy does not improve detection of serrated adenomas in the colon. More RCTs evaluating NBI are needed to explore the effect.

Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm: a systematic review and pooled-analysis.

BACKGROUND AND AIMS: Hot snare polypectomy and EMR are the standard of care in resecting colorectal polyps ≥10 mm. To avoid the risk of electrocautery-induced damage, there is recent evidence about using cold snare polypectomy and cold EMR for such lesions. The aim of this pooled analysis is to report outcomes of cold snare resection for polyps ≥10 mm. METHODS: PubMed/Medline, Embase, Google Scholar, and Cochrane databases were searched up to July 2018 to identify studies that performed cold snare resection for colorectal polyps ≥10 mm. Primary outcomes were adverse events (bleeding, perforation, and postpolypectomy abdominal pain), and secondary outcomes were the rates of complete resection, overall residual polyp rates, and rates for adenomas versus sessile serrated polyps (SSPs). Subgroup analysis was performed focusing on lesion size, location, and resection technique. RESULTS: Eight studies were included in the final analysis that included 522 colorectal polyps with a mean polyp size of 17.5 mm (range, 10-60). The overall adverse event rate was 1.1% (95% confidence interval, CI, 0.2%-2.0%; I2 = 0%). Intra- and postprocedural bleeding rates were .7% (95% CI, 0%-1.4%) and .5% (95% CI, .1%-1.2%), respectively, with abdominal pain rate being .6% (95% CI, .1%-1.3%). Polyps ≥20 mm had a higher intraprocedural bleeding rate of 1.3% (95% CI, .7%-3.3%) and abdominal pain rate of 1.2% (95% CI, .7%-3.0%) but no delayed bleedings. No perforations were reported. The complete resection rate was 99.3% (95% CI, 98.6%-100%). Overall pooled residual rates of polyps of any histology, adenomas, and SSPs were 4.1% (95% CI, .2%-8.4%), 11.1% (95% CI, 4.1%-18.1%), and 1.0% (95% CI, .4%-2.4%), respectively, during a follow-up period ranging from 154 to 258 days. CONCLUSIONS: The results of this systematic review and pooled analysis were excellent with cold snare resection of colorectal polyps >10 mm in terms of postpolypectomy bleeding, complete resection, and residual polyp rates. Randomized controlled trials comparing cold snare resection with hot snare resections of polyps ≥10 mm are required for further investigation.