Appropriateness of ultrasound imaging for thyroid pathology, the standard of radiology reporting on thyroid nodules and the detection rates of thyroid malignancy: a tertiary centre retrospective audit.

BACKGROUND: The incidence of thyroid cancer is increasing worldwide without a simultaneous rise in mortality. It is thought that the incidence of non-clinically significant thyroid cancers are on the rise as a result of more sensitive diagnostic imaging. AIM: To determine the number of inappropriate requests for thyroid ultrasound (US), the quality of radiology reporting for thyroid nodules based on accepted guidelines and the resultant number of thyroid cancers identified because of these investigations. METHODS: Electronic medical records of patients who underwent thyroid US imaging and thereafter referred to the Endocrine Department at Gold Coast University Hospital, Queensland, between July 2014 and July 2017 were reviewed. Data for 251 patients who had thyroid US were analysed and the final 201 patients who were found to have thyroid nodules were evaluated using descriptive statistics. Indications for thyroid US imaging among referring clinicians were assessed and we compared both clinical management and radiology reporting practices of thyroid nodules to the published 2009 and 2015 American Thyroid Association (ATA) guidelines. RESULTS: There were 50.2% of patients with initial thyroid US imaging deemed outside of expert recommendations where 42% of these patients required further surveillance imaging and 25.4% required fine needle aspiration of their thyroid nodules. A definite recommendation whether to evaluate thyroid nodules further was provided in 44.8% of radiology reports. There were no radiology reports that described thyroid nodules findings based on patterns as recommended by the 2015 ATA guidelines. Two cases of thyroid cancer were detected including one patient with prior history of thyroid cancer and a second patient with hypothyroidism. CONCLUSION: Routine use of US thyroid imaging outside expert recommendation is common. There is lack of standardised reporting when assessing thyroid nodules on US. Limiting the initial use of US in cases of palpable neck lumps and the use of systematic reporting according to the 2017 guidelines published by the American College of Radiology Thyroid Imaging Reporting and Data System may reduce unnecessary investigations for thyroid nodules in the future.

Efficacy of Biologics in the Treatment of Primary Sclerosing Cholangitis Associated With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

This is the first systematic review and meta-analysis that aims to address the scarcity of research on the use of biological therapy in primary sclerosing cholangitis-inflammatory bowel disease (PSC-IBD) and the historical inadequacy of therapeutic options. Its purpose is to investigate this matter comprehensively and furnish guidance for clinical practice. Utilizing Embase, PubMed, Medline, and clinicaltrials.gov studies investigating the roles of biologics and antibiotics in PSC-IBD were identified. The systematic literature review encompassed articles published from inception through September 2023. Two independent reviewers assessed the articles, and methodological quality was gauged using Review Manager 5.4.2. Nine studies were included in the systematic review and meta-analysis. However, only four met the criteria for inclusion in the meta-analysis due to variability and availability of data; the remaining studies underwent descriptive analysis. Notably, infliximab, adalimumab, vedolizumab, and tofacitinib showed ineffectiveness in reducing cholestatic markers. This review underscores the limited impact of biological and small-molecule therapies on disease progression in PSC-IBD patients, signifying the need for further exploration and development of treatment modalities in this domain.

The Diagnostic Utility of Biochemical Markers and Intestinal Ultrasound Compared with Endoscopy in Patients with Crohn's Disease and Ulcerative Colitis: A Systemic Review and Meta-Analysis.

Background: Inflammatory bowel disease (IBD) consists of Crohn's disease (CD) and Ulcerative colitis (UC). The main goal of treatment is to obtain mucosal healing via endoscopy. More recently, intestinal ultrasounds, along with biochemical markers, have been increasingly popular as point-of-care testing to monitor treatment response. This systemic review and meta-analysis aimed to assess the diagnostic test performance of ultrasonography and biochemical markers (C-reactive protein and fecal calprotectin) compared with endoscopy for detecting inflammation in IBD. Methods: A comprehensive literature search was conducted using PubMed Medline, EMBASE, ScienceDirect, and CINAHL from 1 January 2018 to 1 January 2024. The included studies were prospective and retrospective observational studies, clinical trials, and cross-sectional studies investigating the diagnostic sensitivity and specificity of ultrasonography, biochemical markers, and endoscopy. Studies were selected based on the Preferred Reporting Items for Systematic Review and Meta-analysis Statement (PRISMA). Results: Of the 1035 studies retrieved, 16 met the inclusion criteria, and most of the included studies were prospective observational studies. Diagnostic test accuracy was conducted, and the pooled sensitivity and specificity of all the studies revealed that ultrasonography has the highest pooled sensitivity, at 85% (95% CI, 78 to 91%), and specificity, at 92% (95% CI, 86 to 96%), as compared with biochemical markers and endoscopy. More specifically, biochemical markers had a pooled sensitivity and specificity of 85% (95% CI, 81 to 87%) and 61% (95% CI, 58 to 64%), respectively, and endoscopy had 60% (95% CI, 52 to 68%) and 82% (95% CI, 76 to 87%), respectively. However, the results also show substantial heterogeneity in the studies because of various populations, protocols, and outcomes in the studies included. This was especially noted in the assessment of biochemical markers, in which a metaregression was performed showing a nonsignificant p-value of 0.8856 for the coefficient. Conclusions: IUS was found to have the highest pooled sensitivity and specificity of all the included studies for diagnosing inflammation in patients with CD and UC, and this, coupled with biochemical markers, can improve diagnostic utility.

Putative glycosyltransferases and other plant Golgi apparatus proteins are revealed by LOPIT proteomics.

The Golgi apparatus is the central organelle in the secretory pathway and plays key roles in glycosylation, protein sorting, and secretion in plants. Enzymes involved in the biosynthesis of complex polysaccharides, glycoproteins, and glycolipids are located in this organelle, but the majority of them remain uncharacterized. Here, we studied the Arabidopsis (Arabidopsis thaliana) membrane proteome with a focus on the Golgi apparatus using localization of organelle proteins by isotope tagging. By applying multivariate data analysis to a combined data set of two new and two previously published localization of organelle proteins by isotope tagging experiments, we identified the subcellular localization of 1,110 proteins with high confidence. These include 197 Golgi apparatus proteins, 79 of which have not been localized previously by a high-confidence method, as well as the localization of 304 endoplasmic reticulum and 208 plasma membrane proteins. Comparison of the hydrophobic domains of the localized proteins showed that the single-span transmembrane domains have unique properties in each organelle. Many of the novel Golgi-localized proteins belong to uncharacterized protein families. Structure-based homology analysis identified 12 putative Golgi glycosyltransferase (GT) families that have no functionally characterized members and, therefore, are not yet assigned to a Carbohydrate-Active Enzymes database GT family. The substantial numbers of these putative GTs lead us to estimate that the true number of plant Golgi GTs might be one-third above those currently annotated. Other newly identified proteins are likely to be involved in the transport and interconversion of nucleotide sugar substrates as well as polysaccharide and protein modification.

Application of a Bayesian deconvolution approach for high-resolution (1)H NMR spectra to assessing the metabolic effects of acute phenobarbital exposure in liver tissue.

High-resolution (1)H NMR spectroscopy is frequently used in the field of metabolomics to assess the metabolites found in biofluids or tissue extracts to define a metabolic profile that describes a given biological process. In this study, we aimed to increase the utility of NMR-based metabolomics by using advanced Bayesian modeling of the time-domain high-resolution 1D NMR free induction decay (FID). The improvement over traditional nonparametric binning is twofold and associated with enhanced resolution of the analysis and automation of the signal processing stage. The automation is achieved by using a Bayesian formalism for all parameters of the model including the number of components. The approach is illustrated with a study of early markers of acute exposure to different doses of a well-characterized nongenotoxic hepatocarcinogen, phenobarbital, in rats. The results demonstrate that Bayesian deconvolution produces a better model for the NMR spectra that allows the identification of subtle changes in metabolic concentrations and a decrease in the expected false discovery rate compared with approaches based on "binning". These properties suggest that Bayesian deconvolution could facilitate the biomarker discovery process and improve information extraction from high-resolution NMR spectra.

Development of an oligosaccharide library to characterise the structural variation in glucuronoarabinoxylan in the cell walls of vegetative tissues in grasses.

BACKGROUND: Grass glucuronoarabinoxylan (GAX) substitutions can inhibit enzymatic degradation and are involved in the interaction of xylan with cell wall cellulose and lignin, factors which contribute to the recalcitrance of biomass to saccharification. Therefore, identification of xylan characteristics central to biomass biorefining improvement is essential. However, the task of assessing biomass quality is complicated and is often hindered by the lack of a reference for a given crop. RESULTS: In this study, we created a reference library, expressed in glucose units, of Miscanthus sinensis GAX stem and leaf oligosaccharides, using DNA sequencer-Assisted Saccharide analysis in high throughput (DASH), supported by liquid chromatography (LC), nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Our analysis of a number of grass species highlighted variations in substitution type and frequency of stem and leaf GAX. In miscanthus, for example, the ß-Xylp-(1 → 2)-α-Araf-(1 → 3) side chain is more abundant in leaf than stem. CONCLUSIONS: The reference library allows fast identification and comparison of GAX structures from different plants and tissues. Ultimately, this reference library can be used in directing biomass selection and improving biorefining.

Comparison of DIGE and post-stained gel electrophoresis with both traditional and SameSpots analysis for quantitative proteomics.

2-DE is an important tool in quantitative proteomics. Here, we compare the deep purple (DP) system with DIGE using both a traditional and the SameSpots approach to gel analysis. Missing values in the traditional approach were found to be a significant issue for both systems. SameSpots attempts to address the missing value problem. SameSpots was found to increase the proportion of low volume data for DP but not for DIGE. For all the analysis methods applied in this study, the assumptions of parametric tests were met. Analysis of the same images gave significantly lower noise with SameSpots (over traditional) for DP, but no difference for DIGE. We propose that SameSpots gave lower noise with DP due to the stabilisation of the spot area by the common spot outline, but this was not seen with DIGE due to the co-detection process which stabilises the area selected. For studies where measurement of small abundance changes is required, a cost-benefit analysis highlights that DIGE was significantly cheaper regardless of the analysis methods. For studies analysing large changes, DP with SameSpots could be an effective alternative to DIGE but this will be dependent on the biological noise of the system under investigation.

Time-domain Bayesian detection and estimation of noisy damped sinusoidal signals applied to NMR spectroscopy.

The problem of model detection and parameter estimation for noisy signals arises in different areas of science and engineering including audio processing, seismology, electrical engineering, and NMR spectroscopy. We have adopted the Bayesian modeling framework to jointly detect and estimate signal resonances. This considers a model of the time-domain complex free induction decay (FID) signal as a sum of exponentially damped sinusoidal components. The number of model components and component parameters are considered unknown random variables to be estimated. A Reversible Jump Markov Chain Monte Carlo technique is used to draw samples from the joint posterior distribution on the subspaces of different dimensions. The proposed algorithm has been tested on synthetic data, the (1)H NMR FID of a standard of L-glutamic acid and a blood plasma sample. The detection and estimation performance is compared with Akaike information criterion (AIC), minimum description length (MDL) and the matrix pencil method. The results show the Bayesian algorithm superior in performance especially in difficult cases of detecting low-amplitude and strongly overlapping resonances in noisy signals.

B chromosomes of the Podisma sapporensis Shir. (Orthoptera, Acrididae) analysed by chromosome microdissection and FISH.

The analysis of the distribution of repetitive DNA of the B chromosomes of Podisma sapporensis in the A and B chromosomes of the natural populations and in A chromosomes of three other species of the Podismini grasshoppers were made. DNA-libraries of the B chromosome and the euchromatic segment of the A chromosome of P. sapporensis were generated by meiotic chromosome microdissection followed by degenerated oligonucleotide primed polymerase chain reaction (DOP-PCR). Paints based on these DNA-libraries were used for FISH analysis to detect localization of homologous sequences in A and B chromosomes of P. sapporensis from different natural populations. On the basis of the FISH analysis the authors suggest that evolution of the B chromosomes in Podisma sapporensis was associated mainly with the insertions of "alien DNA sequences" into ancestral A chromosome and their further amplification. The number of initial sites of amplifications differed in the different Bs, the distance between these sites also varying. Karyotype evolution in P. sapporensis was associated partly with the insertion of "alien DNA sequences" into pericentromeric chromosomal regions. Insertion into the small short arms of the acrocentric chromosomes followed, with the DNA amplification leading to the formation of the additional C-heterochromatic arms or euchromatic-like regions of different size.

Development and application of a high throughput carbohydrate profiling technique for analyzing plant cell wall polysaccharides and carbohydrate active enzymes.

BACKGROUND: Plant cell wall polysaccharide composition varies substantially between species, organs and genotypes. Knowledge of the structure and composition of these polysaccharides, accompanied by a suite of well characterised glycosyl hydrolases will be important for the success of lignocellulosic biofuels. Current methods used to characterise enzymatically released plant oligosaccharides are relatively slow. RESULTS: A method and software was developed allowing the use of a DNA sequencer to profile oligosaccharides derived from plant cell wall polysaccharides (DNA sequencer-Assisted Saccharide analysis in High throughput, DASH). An ABI 3730xl, which can analyse 96 samples simultaneously by capillary electrophoresis, was used to separate fluorophore derivatised reducing mono- and oligo-saccharides from plant cell walls. Using electrophoresis mobility markers, oligosaccharide mobilities were standardised between experiments to enable reproducible oligosaccharide identification. These mobility markers can be flexibly designed to span the mobilities of oligosaccharides under investigation, and they have a fluorescence emission that is distinct from that of the saccharide labelling. Methods for relative and absolute quantitation of oligosaccharides are described. Analysis of a large number of samples is facilitated by the DASHboard software which was developed in parallel. Use of this method was exemplified by comparing xylan structure and content in Arabidopsis thaliana mutants affected in xylan synthesis. The product profiles of specific xylanases were also compared in order to identify enzymes with unusual oligosaccharide products. CONCLUSIONS: The DASH method and DASHboard software can be used to carry out large-scale analyses of the compositional variation of plant cell walls and biomass, to compare plants with mutations in plant cell wall synthesis pathways, and to characterise novel carbohydrate active enzymes.

A combined metabolomic and proteomic investigation of the effects of a failure to express dystrophin in the mouse heart.

Muscle degeneration in the heart of 1-9 month-old mdx mice (a model for Duchenne muscular dystrophy) has been monitored using metabolomic and proteomic approaches. In both data sets, a pronounced aging trend was detected in control and mdx mice, and this trend was separate from the disease process. In addition, the characteristic increase in taurine associated with dystrophic tissue is correlated with proteins associated with oxidative phosphorylation and mitochondrial metabolism.

DNA content of the B chromosomes in grasshopper Podisma kanoi Storozh. (Orthoptera, Acrididae).

A DNA library derived from the B chromosome of Podisma kanoi was obtained by chromosome microdissection. A total of 153 DNA clones were isolated from the microdissected DNA library. Twenty of them were sequenced. A comparison of B chromosome DNA sequences with sequences of other species from the DDBJ/GenBank/EMBL database ( http://www.ddbj.nig.ac.jp/ ) was performed. Different patterns of signals were observed after FISH with labeled cloned DNA fragments. FISH signals with cloned DNA fragments painted either whole Bs or their different regions. Some clones also gave signals in pericentromeric regions of A chromosomes. Other cloned DNA fragments gave only background-like signals on A and B chromosomes. Comparative FISH analysis of B chromosomes in Podisma kanoi and P. sapporensis with DNA probes derived from the Bs of these species revealed homologous DNA that was confined within pericentromeric and telemetric regions of the B chromosome in P. kanoi. In contrast to the B chromosomes in P. sapporensis containing large regions enriched with rDNA, only a small cluster of rDNA was detected in one of the examined B chromosomes in P. kanoi. The data strongly suggest an independent origin of B chromosomes in two closely related Podisma species.