Artificial intelligence-powered early identification of refractory constipation in children.

Background: Children experiencing refractory constipation, resistant to conventional pharmacological approaches, develop severe symptoms that persist into adulthood, leading to a substantial decline in their quality of life. Early identification of refractory constipation may improve their management. We aimed to describe the characteristics of colonic anatomy in children with different types of constipation and develop a supervised machine-learning model for early identification. Methods: In this retrospective study, patient characteristics and standardized colon size (SCS) ratios by barium enema (BE) were studied in patients with functional constipation (n=77), refractory constipation (n=63), and non-constipation (n=65). Statistical analyses were performed and a supervised machine learning (ML) model was developed based on these data for the classification of the three groups. Results: Significant differences in rectum diameter, sigmoid diameter, descending diameter, transverse diameter, and rectosigmoid length were found in the three groups. A linear support vector machine was utilized to build the early detection model. Using five features (SCS ratios of sigmoid colon, descending colon, transverse colon, rectum, and rectosigmoid), the model demonstrated an accuracy of 81% [95% confidence interval (CI): 79.17% to 83.19%]. Conclusions: The application of using a supervised ML strategy obtained an accuracy of 81% in distinguishing children with refractory constipation. The combination of BE and ML model can be used for practical implications, which is important for guiding management in children with refractory constipation.

Efficacy and safety of different modes of exercise-based cardiac rehabilitation delivery for patients with heart failure: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: The prevalence of heart failure (HF) is increasing. Exercise-based cardiac rehabilitation (CR) reduces mortality and further improves the prognosis of patients with HF. However, the effect of different modes of CR delivery on HF remains unclear. Thus, the purpose of this study is to find out the relative efficacy and safety of different modes of CR delivery for individuals with HF using a network meta-analysis. METHODS AND ANALYSIS: We will perform a systematic review and network meta-analysis of randomised controlled trials which compare different modes of exercise-based CR delivery for patients with HF. Databases including Embase, Medline, the Cochrane Central Register of Controlled Trials and Web of Science will be searched up to May 2022. The primary outcomes will focus on the functional capacity and the health-related quality of life (hr-QOL). Functional capacity will be evaluated by peak oxygen consumption (mL/kg/min) and 6 min walking test (metres). The Minnesota Living with Heart Failure questionnaire, Short Form-36, Psychometric properties of the Kansas City cardiomyopathy questionnaire and EuroQol five dimensions questionnaire will serve as measures of hr-QOL. As secondary outcomes, we will assess hospital admissions (all-cause and cardiac) and all-cause mortality, which required a minimum follow-up of 6 months, as well as adverse events during exercise training. The risk of bias for individual studies will be evaluated according to the Cochrane Handbook. The quality of evidence will be assessed by the Grading of Recommendations, Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: This study does not require ethics approval as it is based on published trials. Results of this systematic review and network meta-analysis will be submitted to a peer-reviewed journal for future publication. TRIAL REGISTRATION NUMBER: CRD42021278351.

Aptamer Sandwich Lateral Flow Assay (AptaFlow) for Antibody-Free SARS-CoV-2 Detection.

The COVID-19 pandemic is among the greatest health and socioeconomic crises in recent history. Although COVID-19 vaccines are being distributed, there remains a need for rapid testing to limit viral spread from infected individuals. We previously identified the SARS-CoV-2 spike protein N-terminal domain (NTD) binding DNA aptamer 1 (SNAP1) for detection of SARS-CoV-2 virus by aptamer-antibody sandwich enzyme-linked immunoassay (ELISA) and lateral flow assay (LFA). In this work, we identify a new aptamer that also binds at the NTD, named SARS-CoV-2 spike protein NTD-binding DNA aptamer 4 (SNAP4). SNAP4 binds with high affinity (<30 nM) for the SARS-CoV-2 spike protein, a 2-fold improvement over SNAP1. Furthermore, we utilized both SNAP1 and SNAP4 in an aptamer sandwich LFA (AptaFlow), which detected SARS-CoV-2 UV-inactivated virus at concentrations as low as 106 copies/mL. AptaFlow costs <$1 per test to produce, provides results in <1 h, and detects SARS-CoV-2 at concentrations that indicate higher viral loads and a high probability of contagious transmission. AptaFlow is a potential approach for a low-cost, convenient antigen test to aid the control of the COVID-19 pandemic.

Highly sensitive and specific real-time PCR by employing serial invasive reaction as a sequence identifier for quantifying EGFR mutation abundance in cfDNA.

Detection of EGFR mutations in circulating cell-free DNA (cfDNA) is beneficial to monitor the therapeutic effect, tumor progression, and drug resistance in real time. However, it requires that the mutation detection method has the ability to quantify the mutation abundance accurately. Although the next-generation sequencing (NGS) and digital PCR showed high sensitivity for quantifying mutations in cfDNA, the use of expensive equipment and the high-cost hampered their applications in the clinic. Herein, we propose a highly sensitive and specific real-time PCR by employing serial invasive reaction as a sequence identifier for quantifying EGFR mutation abundance in cfDNA (termed as qPCR-Invader). The mutation abundance can be quantified by using the difference of Ct values between mutant and wild-type targets without the need of making a standard curve. The method can quantify a mutation level as lower as 0.1% (10 copies/tube). Thirty-six tissue samples from non-small-cell lung cancer (NSCLC) patients were detected by our method and 14/36 tissues gave EGFR L858R mutation-positive results, whereas ARMS-PCR just identified 12 of L858R mutant samples. The two inconsistent samples were confirmed as L858R mutant by pyrophosphorolysis-activated polymerization method, indicating that qPCR-Invader is more sensitive than ARMS-PCR for mutation detection. The L858R mutation abundances of 19 cfDNA samples detected by qPCR-Invader were close to that from NGS, indicating our method can precisely quantify mutation abundance in cfDNA. The qPCR-Invader just needs a common real-time PCR device to accomplish quantification of EGFR mutations, and the fluorescence probes are universal for any target detection. Therefore, it could be used in most laboratories to analyze mutations in cfDNA. Graphical abstract ᅟ.

FXR deletion in hepatocytes does not affect the severity of alcoholic liver disease in mice.

Emerging evidence has shown that FXR activation ameliorates the development of alcoholic liver diseases (ALD) while whole-body deficiency of FXR in mice leads to more severe ALD. However, it's unknown whether the enhanced susceptibility to ALD development in FXR-/- mice is due to deficiency of hepatic FXR or increased toxicity secondary to increased bile acid (BA) levels. Hepatocyte-specific FXR knockout mice (FXRhep-/-) present similar BA levels compared to wild-type mice, and are therefore a useful model to study a direct role of hepatic FXR in ALD development. FXRhep-/- mice were subject to an ALD model with chronic plus binge drinking of alcohol to determine the effects of hepatic FXR deficiency on ALD development. The FXRhep-/- mice showed an altered expression of genes involved in BA and lipid homeostasis with alcohol treatment. Despite a slightly increased trend in hepatic lipid deposition and collagen accumulation in FXRhep-/- mice, there were no significant differences in the severity of steatosis, inflammation, or fibrosis between WT and FXRhep-/- mice. Therefore, these findings indicate that FXR deficiency in hepatocytes might only play a minor role in ALD development. Deficiency of FXR in other non-hepatic tissues and/or increased BA levels resultant from whole-body FXR deficiency might be responsible for more severe ALD development.