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Background Delayed diagnosis of inflammatory bowel disease (IBD) is common, there is still no effective imaging system to distinguish Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. Methods This multicenter retrospective study included IBD patients at three centers between January 2012 and May 2022. The intestinal and perianal imagin g signs were evaluated. Visceral fat information from CT images was extracted, including the ratio of visceral to subcutaneous fat volume (VSR), fat distribution, and attenuation values. The valuable indicators were screened out in the derivation cohort by binary logistic regression and receiver working curve (ROC) analysis to construct an imaging report and data system for IBD (IBD-RADS), which was tested in the validation cohort. Results The derivation cohort included 606 patients (365 CD, 241 UC), and the validation cohort included 155 patients (97 CD, 58 UC). Asymmetric enhancement (AE) (OR = 87.75 [28.69, 268.4]; P  < 0.001), perianal fistula (OR = 4.968 [1.807, 13.66]; P  = 0.002) and VSR (OR = 1.571 [1.087, 2.280]; P  = 0.04) were independent predictors of CD. VSR improved the efficiency of imaging signs (AUC: 0.929 vs. 0.901; P  < 0.001), with a threshold greater than 0.97 defined as visceral fat predominance (VFP). In IBD-RADS, AE was the major criterion, VFP and perianal fistula were auxiliary criteria, and intestinal fistula, limited small bowel disease, and skip distribution were special favoring items as their 100% specificity. Grade 3 to 5 correctly classified most CD patients (derivation: 96.5% (352/365), validation: 98.0% (95/97)), and 98% of those were eventually diagnosed with CD (derivation: 97.8% (352/360), validation: 98.0% (95/97)). Conclusions IBD-RADS can help radiologists distinguish between CD and UC in patients with suspected IBD.

ObjectiveThe aim of this study is to evaluate the ability of magnetic resonance enterography global score (MEGS) to diagnose the activity of pediatric Crohn’s disease (CD) and its correlation with endoscopic activity score.Materials and methods70 pediatric CD patients (between the ages of 6 and 17) were enrolled who underwent ileocolonoscopy and magnetic resonance enterography (MRE) within 7 days. The simplified endoscopic activity score for Crohn’s disease (SES-CD) and MEGS were acquired in the terminal ileum. Sensitivity and specificity of MEGS for detection disease activity against SES-CD was compared using the McNemar test. The correlation between MEGS and SES-CD was assessed by Spearman's rank estimation. The diagnostic accuracy of MEGS for active disease defined by SES-CD was calculated. Receiver operating characteristic curves (ROC) were constructed.ResultsFifty-two pediatric CD patients (median age, 12 years old; 28 girls, 24 boys) were included. The incidence of upper gastrointestinal (GI) tract (23%) involvement and perianal lesions (42%) is high in pediatric Crohn’s patients, and most of them suffer from internal hemorrhoids (86.5%). MEGS showed strong correlation to SES-CD (r = 0.70, P < 0.001). With endoscopic as the standard of reference, the MEGS had a high accuracy for the detection of inflammation (area under the ROC curve (AUC) of 0.89, sensitivity 0.95 and specificity 0.82) and for disease activity (AUC of 0.81, sensitivity 0.88 and specificity 0.75) in the terminal ileum.ConclusionPediatric Crohn’s disease is unique. Our study has shown a good correlation between MEGS and endoscopy activity score with equal diagnostic efficacy. MEGS is a promising method to assess disease activity and perhaps be a valuable tool in following therapeutic changes.

ObjectivesTo achieve automated quantification of visceral adipose tissue (VAT) distribution in CT images and screen out parameters with discriminative value for inflammatory bowel disease (IBD) subtypes.MethodsThis retrospective multicenter study included Crohn’s disease (CD) and ulcerative colitis (UC) patients from three institutions between 2012 and 2021, with patients with acute appendicitis as controls. An automatic VAT segmentation algorithm was developed using abdominal CT scans. The VAT volume, as well as the coefficient of variation (CV) of areas within the lumbar region, was calculated. Binary logistic regression and receiver operating characteristic analysis was performed to evaluate the potential of indicators to distinguish between IBD subtypes.ResultsThe study included 772 patients (365 CDs, median age [inter-quartile range] = 31.0. (25.0, 42.0) years, 255 males; 241 UCs, 46.0 (34.0, 55.5) years, 138 males; 166 controls, 40.0 (29.0, 53.0) years, 80 males). CD patients had lower VAT volume (CD = 1584.95 ± 1128.31 cm3, UC = 1855.30 ± 1326.12 cm3, controls = 2470.91 ± 1646.42 cm3) but a higher CV (CD = 29.42 ± 15.54 %, p = 0.006 and p ˂ 0.001) compared to UC and controls (25.69 ± 12.61 % vs. 23.42 ± 15.62 %, p = 0.11). Multivariate analysis showed CV was a significant predictor for CD (odds ratio = 6.05 (1.17, 31.12), p = 0.03). The inclusion of CV improved diagnostic efficiency (AUC = 0.811 (0.774, 0.844) vs. 0.803 (0.766, 0.836), p = 0.08).ConclusionCT-based VAT distribution can serve as a potential biomarker for distinguishing IBD subtypes.Critical relevance statementVisceral fat distribution features extracted from CT images using an automated segmentation algorithm (1.14 min) show differences between Crohn’s disease and ulcerative colitis and are promising for practical radiological screening.Key points• Radiological parameters reflecting visceral fat distribution were extracted for the discrimination of Crohn’s disease (CD) and ulcerative colitis (UC).• In CD, visceral fat was concentrated in the lower lumbar vertebrae, and the coefficient of variation was a significant predictor (OR = 6.05 (1.17, 31.12), p = 0.03).• The differences between CD, UC, and controls are promising for practical radiological screening.

The aim of the present study was to evaluate the diagnostic benefit of diffusion-weighted imaging (DWI) in the detection of homogenous isoattenuating insulinoma on biphasic contrast-enhanced computed tomography (CT) preoperatively and to determine which magnetic resonance (MR) sequences exhibited the best diagnostic performance. A total of 44 consecutive patients who underwent biphasic contrast-enhanced CT and conventional MR imaging (MRI), including DWI on a 3T scanner, were identified retrospectively. Apparent diffusion coefficient (ADC) values of insulinomas and the surrounding pancreatic parenchyma were compared using a Wilcoxon signed-rank test. Receiver operating characteristic analysis was used to compare the diagnostic accuracy of four randomized image sets [T2-weighted image (WI), axial T1WI, DWI and T2WI + DWI] for each reader. Axial T1-weighted MRI exhibited the highest relative sensitivity for each reader; DWI alone exhibited the lowest relative sensitivity and the lower inter-reader agreement. There was no significant difference in lesion detection between T2WI and T2WI + DWI image sets for each reader. The ADC values of the insulinoma were significantly lower compared with those of the surrounding parenchyma. In conclusion, DWI does not benefit the detection of homogenous isoattenuating insulinoma. Axial T1WI is the optimal pulse sequence. Quantitative assessment of the tumor ADC values may be a useful tool to characterize identified pancreatic neoplasms.

We investigated the process parameters of the high temperature MOCVD (HT-MOCVD) numerical model for the AlN growth based on CFD simulation using orthogonal test design. It is believed that high temperature growth condition is favorable for improving efficiency and crystallization quality for AlN film, while the flow field in the HT-MOCVD reactor is closely related to the process parameters, which will affect the uniformity of the film. An independently developed conceptual HT-MOCVD reactor was established for the AlN growth to carry out the CFD simulation. To evaluate the role of the parameters systematically and efficiently on the growth uniformity, the process parameters based on CFD simulation were analyzed using orthogonal test design. The advantages of the range, matrix and variance methods were considered and the results were analyzed comprehensively and the optimal process parameters were obtained as follows, susceptor rotational speed 400 rpm, operating pressure 40 Torr, gas flow rate 50 slm, substrate temperature 1550 K.

Long non-coding RNAs (lncRNAs), HOTAIR has been reported to be upregulated in cervical cancer development and progression. However, SNPs (single nucleotide polymorphisms) in the lncRNAs and their associations with cervical cancer susceptibility have not been reported. In the current study, we hypothesized that SNPs within the lncRNA HOTAIR may influence the risk of cervical cancer. We performed a case-control study including 510 cervical cancer patients (cases) and 713 cancer-free individuals (controls) to investigate the association between three haplotype-tagging SNPs (rs920778, rs1899663 and rs4759314) in the lncRNA HOTAIR and the risk of cervical cancer. We found a strong association between the SNP rs920778 in the intronic enhancer of the HOTAIR and cervical cancer (P<10-4). Moreover, the cervical cancer patients with homozygous TT genotype were significantly associated with tumor-node-metastasis (TNM) stage. In vitro assays with allele-specific reporter constructs indicated that the reporter constructs bearing rs920778T allele conferred elevated reporter gene transcriptional activity when compared to the reporter constructs containing rs920778C allele. Furthermore, HOTAIR expression was higher in cervical cancer tissues than that in corresponding normal tissues, and the high expression was associated with the risk-associated allele T. In summary, our studies provide strong functional evidence that functional SNP rs920778 regulates HOTAIR expression, and may ultimately influence the predisposition for cervical cancer.

Objectives IDegLira is a novel fixed-ratio soluble combination of insulin degludec and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide approved for type 2 diabetes (T2D) patients. Individual trials have assessed the clinical profile of IDegLira vs different comparators. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of IDegLira for T2D. Methods PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched from inception to August 15, 2023. The primary outcomes included change from baseline in haemoglobin A1c (HbA1c) and body weight. Risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) were calculated to evaluate the outcomes. Results This meta-analysis identified 1044 citations, and included 13 eligible trials, enroling 7773 patients. Compared with the control groups, IDegLira was optimal in change in HbA1c, percentage of patients achieving HbA1c < 7%, percentage of patients achieving HbA1c < 6.5%, HbA1c < 7.0% without weight gain and without severe or blood glucose (BG)-confirmed hypoglycaemia episodes, HbA1c < 6.5% without weight gain and without severe or BG-confirmed hypoglycaemia episodes, change in fasting plasma glucose, change in self-measured plasma glucose, change in systolic pressure, and total daily insulin dose. No difference was found between the IDegLira and control groups in terms of change in body weight, change in diastolic pressure, severe or BG-confirmed symptomatic hypoglycaemia, nocturnal severe or BG-confirmed symptomatic hypoglycaemia, adverse events or serious adverse events. Conclusions In patients with T2D, IDegLira improved glycaemic control whilst balancing out risk for hypoglycaemia and gastrointestinal side effects.

Animal models of COVID-19 facilitate the development of vaccines and antivirals against SARS-CoV-2. The efficacy of antivirals or vaccines may differ in different animal models with varied degrees of disease. Here, we introduce a mouse model expressing human angiotensin-converting enzyme 2 (ACE2). In this model, with the human cytokeratin 18 promoter was knocked into the Hipp11 locus of C57BL/6J mouse by CRISPR - Cas9 (K18-hACE2 KI). Upon intranasal inoculation with high (3 × 10 PFU) or low (2.5 × 10 PFU) dose of SARS-CoV-2 wildtype (WT), Delta, Omicron BA.1, or Omicron BA.2 variants, all mice showed obvious infection symptoms, including weight loss, high viral loads in the lung, and interstitial pneumonia. 100% lethality was observed in K18-hACE2 KI mice infected by variants with a delay of endpoint for Delta and BA.1, and a significantly attenuated pathogenicity was observed for BA.2. The pneumonia of infected mice was accompanied by the infiltration of neutrophils and pulmonary fibrosis in the lung. Compared with K18-hACE2 Tg mice and HFH4-hACE2 Tg mice, K18-hACE2 KI mice are more susceptible to SARS-CoV-2. In the antivirals test, REGN10933 and Remdesivir had limited antiviral efficacies in K18-hACE2 KI mice upon the challenge of SARS-CoV-2 infections, while Nirmatrelvir, monoclonal antibody 4G4, and mRNA vaccines potently protected the mice from death. Our results suggest that the K18-hACE2 KI mouse model is lethal and stable for SARS-CoV-2 infection, and is practicable and stringent to antiviral development.

Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralizing public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron-specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes a potential immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidence to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity. Convergence of heavy or light chains in antibodies recognising pathogens could drive mutations in these pathogens. Here the authors examine antibodies against SARS-CoV-2 and find that a conserved VL6-57 light chain recognising a conserved motif in the spike protein is associated with virus mutations and could drive changes in SARS-CoV-2 omicron variants.