Whole-Body MRI Screening for Carriers of Germline TP53 Mutations-A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review evaluated whole-body MRI (WB-MRI) as a cancer screening tool for individuals carrying germline TP53 mutations, a population known to be at a significantly elevated risk of malignancy. The primary objective is to assess the diagnostic performance of WB-MRI in detecting cancer in this cohort. METHODS: PubMed, MEDLINE, EMBASE and the Cochrane Central Registry of Controlled Trials were searched until 18 August 2023. Eligible studies were selected based on predefined inclusion criteria. The data extracted included information on study characteristics, patient demographics, and the WB-MRI diagnostic performance. RESULTS: This systematic review identified eight eligible studies, comprising 506 TP53 mutation carriers. The mean age was 34.6 ± 16.3 (range 1-74) years. In total, 321/506 (63.4%) of the patients were female and 185/506 (36.6%) were male. In addition, 267/506 (52.8%) had a previous oncological diagnosis. Thirty-six new cancers were diagnosed with WB-MRI (36/506 (7.1%)). The overall pooled proportion of cancer detected on MRI was 7% (95% confidence interval 5-10). In total, 44 new lesions were picked up, as multiple lesions were found in some patients. CONCLUSION: WB-MRI is an effective cancer screening tool for TP53 mutation carriers. While these findings suggest the potential for WB-MRI to contribute to early cancer detection in this high-risk population, further research and the standardisation of protocols internationally are warranted to optimise its clinical utility.

pipesnake: generalized software for the assembly and analysis of phylogenomic datasets from conserved genomic loci.

MOTIVATION: Phylogenetics has moved into the era of genomics, incorporating enormous volumes of data to study questions at both shallow and deep scales. With this increase in information, phylogeneticists need new tools and skills to manipulate and analyze these data. To facilitate these tasks and encourage reproducibility, the community is increasingly moving toward automated workflows. RESULTS: Here we present pipesnake, a phylogenomics pipeline written in Nextflow for the processing, assembly, and phylogenetic estimation of genomic data from short-read sequences. pipesnake is an easy to use and efficient software package designed for this next era in phylogenetics. AVAILABILITY AND IMPLEMENTATION: pipesnake is publicly available on GitHub at https://github.com/AusARG/pipesnake and accompanied by documentation and a wiki/tutorial.

The role of urology and radiology in prostate biopsy: current trends and future perspectives.

PURPOSE: Prostate biopsy is central to the accurate histological diagnosis of prostate cancer. In current practice, the biopsy procedure can be performed using a transrectal or transperineal route with different technologies available for targeting of lesions within the prostate. Historically, the biopsy procedure was performed solely by urologists, but with the advent of image-guided techniques, the involvement of radiologists in prostate biopsy has become more common. Herein, we discuss the pros, cons and future considerations regarding their ongoing role. METHODS: A narrative review regarding the current evidence was completed. PubMed and Cochrane central register of controlled trials were search until January 2024. All study types were of consideration if published after 2000 and an English language translation was available. RESULTS: There are no published studies that directly compare outcomes of prostate biopsy when performed by a urologist or radiologist. In all published studies regarding the learning curve for prostate biopsy, the procedure was performed by urologists. These studies suggest that the learning curve for prostate biopsy is between 10 and 50 cases to reach proficiency in terms of prostate cancer detection and complications. It is recognised that many urologists are poorly able to accurately interpret multi parametric (mp)-MRI of the prostate. Collaboration between the specialities is of importance with urology offering the advantage of being involved in prior and future care of the patient while radiology has the advantage of being able to expertly interpret preprocedure MRI. CONCLUSION: There is no evidence to suggest that prostate biopsy should be solely performed by a specific specialty. The most important factor remains knowledge of the relevant anatomy and sufficient volume of cases to develop and maintain skills.

Addressing Technical Failures in a Diabetic Retinopathy Screening Program.

Purpose: Diabetic retinopathy (DR) is a preventable cause of blindness detectable through screening using retinal digital photography. The Irish National Diabetic Retina Screening (DRS) programme, Diabetic RetinaScreen, provides free screening services to patients with diabetes from aged 12 years and older. A technical failure (TF) occurs when digital retinal imaging is ungradable, resulting in delays in the diagnosis and treatment of sight-threatening disease. Despite their impact, the causes of TFs, and indeed the utility of interventions to prevent them, have not been extensively examined. Aim: Primary analysis aimed to identify factors associated with TF. Secondary analysis examined a subset of cases, assessing patient data from five time points between 2019 and 2021 to identify photographer/patient factors associated with TF. Methods: Patient data from the DRS database for one provider were extracted for analysis between 2018 and 2022. Information on patient demographics, screening results, and other factors previously associated with TF were analyzed. Primary analysis involved using mixed-effects logistic regression models with nested patient-eye random effects. Secondary analysis reviewed a subset of cases in detail, checking for causes of TF. Results: The primary analysis included a total of 366,528 appointments from 104,407 patients over 5 years. Most patients had Type 2 diabetes (89.2%), and the overall TF rate was 4.9%. Diabetes type and duration, dilate pupil status, and the presence of lens artefacts on the camera were significantly associated with TF. The Secondary analysis identified the primary cause of TF was found to be optically dense cataracts, accounting for over half of the TFs. Conclusion: This study provides insight into the causes of TF within the Irish DRS program, highlighting cataracts as the primary contributing factor. The identification of patient-level factors associated with TF facilitates appropriate interventions that can be put in place to improve patient outcomes and minimize delays in treatment and diagnosis.

Current applications and future potential of ChatGPT in radiology: A systematic review.

This study aimed to comprehensively evaluate the current utilization and future potential of ChatGPT, an AI-based chat model, in the field of radiology. The primary focus is on its role in enhancing decision-making processes, optimizing workflow efficiency, and fostering interdisciplinary collaboration and teaching within healthcare. A systematic search was conducted in PubMed, EMBASE and Web of Science databases. Key aspects, such as its impact on complex decision-making, workflow enhancement and collaboration, were assessed. Limitations and challenges associated with ChatGPT implementation were also examined. Overall, six studies met the inclusion criteria and were included in our analysis. All studies were prospective in nature. A total of 551 chatGPT (version 3.0 to 4.0) assessment events were included in our analysis. Considering the generation of academic papers, ChatGPT was found to output data inaccuracies 80% of the time. When ChatGPT was asked questions regarding common interventional radiology procedures, it contained entirely incorrect information 45% of the time. ChatGPT was seen to better answer US board-style questions when lower order thinking was required (P = 0.002). Improvements were seen between chatGPT 3.5 and 4.0 in regard to imaging questions with accuracy rates of 61 versus 85%(P = 0.009). ChatGPT was observed to have an average translational ability score of 4.27/5 on the Likert scale regarding CT and MRI findings. ChatGPT demonstrates substantial potential to augment decision-making and optimizing workflow. While ChatGPT's promise is evident, thorough evaluation and validation are imperative before widespread adoption in the field of radiology.

Efficacy of embolotherapy for the treatment of pelvic congestion syndrome: A systematic review.

Pelvic congestion syndrome (PCS) poses a significant health, diagnostic, and economic challenges. Transcatheter embolisation has emerged as a promising treatment for PCS. A systematic review was performed in order to assess the safety and efficacy of transcatheter embolisation in the treatment of PCS. A systematic search of electronic databases was performed using 'PubMed', 'Embase', 'Medline (OVID)', and 'Web of Science', for articles pertaining to efficacy of embolotherapy for the treatment of pelvic congestion syndrome. A total of 25 studies were included in this systematic review with a combined total of 2038 patients. All patients included were female with a mean average age of 37.65 (31-51). Of the 25 studies, 18/25 studies reported pre- and post-procedural pelvic pain outcomes using a visual analogue scale (VAS). All studies showed a reduction in VAS post-procedure. Transcatheter embolisation had a high technical success rate (94%) and an overall complication rate of 9.0%, of which 10.4% were major and 89.6% were minor. Fifteen out of 19 (78.9%) major complications required a subsequent intervention. Transcatheter embolisation using various techniques is effective and safe in treating PCS. A low quality of evidence limits the currently available literature; however, embolisation has shown to improve symptoms in the majority of patients with low complication rates and recurrence rates.

Radiomics; Contemporary Applications in the Management of Anal Cancer; A Systematic Review.

INTRODUCTION: The management of anal cancer relies on clinical and histopathological features for treatment decisions. In recent years, the field of radiomics, which involves the extraction and analysis of quantitative imaging features, has shown promise in improving management of pelvic cancers. The aim of this study was to evaluate the current application of radiomics in the management of anal cancer. METHODS: A systematic search was conducted in Medline, EMBASE, and Web of Science databases. Inclusion criteria encompassed randomized and non-randomized trials investigating the use of radiomics to predict post-operative recurrence in anal cancer. Study quality was assessed using the QUADAS-2 and Radiomics Quality Score tools. RESULTS: The systematic review identified a total of nine studies, with 589 patients examined. There were three main outcomes assessed in included studies: recurrence (6 studies), progression-free survival (2 studies), and prediction of human papillomavirus (HPV) status (1 study). Radiomics-based risk stratification models were found to provide valuable insights into treatment response and patient outcomes, with all developed signatures demonstrating at least modest accuracy (range: .68-1.0) in predicting their primary outcome. CONCLUSION: Radiomics has emerged as a promising tool in the management of anal cancer. It offers the potential for improved risk stratification, treatment planning, and response assessment, thereby guiding personalized therapeutic approaches.

Tracheoesophageal fistula development following radiotherapy and tyrosine kinase inhibitors in a patient with advanced follicular thyroid carcinoma: a case-based review.

INTRODUCTION: Tracheoesophageal fistulas (TEF) are a rare complication that can occur in patients with radioactive iodine refractory metastatic follicular thyroid carcinoma (FTC) following treatment with radiotherapy (RT) and tyrosine kinase inhibitors (TKI). METHODS: We describe the case of a TEF development in a 69-year-old male who underwent targeted therapy TKIs and adjuvant RT for radioactive iodine refractory FTC. RESULTS: In the case, staging investigations revealed a metastatic, poorly differentiated FTC refractory to radioactive iodine. After 2 years of disease control on Lenvatinib, the patient's condition progressed, necessitating a switch to Cabozantinib. Soon after, they presented with haemoptysis secondary to invasion of the primary thyroid tumour into the trachea. Radical radiotherapy (45 Gy/30 fractions) was also administered to the thyroid gland, ultimately complicated by radiation necrosis. Four months post-completion of RT and recommencing TKI, the patient presented with haemoptysis and hoarseness secondary to recurrent laryngeal nerve compression and tracheal invasion, as well as dysphagia secondary to oesophageal compression. Following an acute presentation with intractable throat pain, investigations revealed a TEF. Surgical and endoscopic management was deemed inappropriate given the patient's rapid deterioration and anatomical position of the TEF, and therefore a palliative approach was taken. CONCLUSION: This case report highlights a rare cause of TEF development in a patient having TKI therapy post-RT for advanced FTC. It highlights the importance of monitoring TEF development in this cohort of patients. It demonstrates the importance of patient counselling and education regarding treatment options and the rare side effects of treatments.

Populating a Continent: Phylogenomics Reveal the Timing of Australian Frog Diversification.

The Australian continent's size and isolation make it an ideal place for studying the accumulation and evolution of biodiversity. Long separated from the ancient supercontinent Gondwana, most of Australia's plants and animals are unique and endemic, including the continent's frogs. Australian frogs comprise a remarkable ecological and morphological diversity categorized into a small number of distantly related radiations. We present a phylogenomic hypothesis based on an exon-capture dataset that spans the main clades of Australian myobatrachoid, pelodryadid hyloid, and microhylid frogs. Our time-calibrated phylogenomic-scale phylogeny identifies great disparity in the relative ages of these groups which vary from Gondwanan relics to recent immigrants from Asia and include arguably the continent's oldest living vertebrate radiation. This age stratification provides insight into the colonization of⁠, and diversification on, the Australian continent through deep time, during periods of dramatic climatic and community changes. Contemporary Australian frog diversity highlights the adaptive capacity of anurans, particularly in response to heat and aridity, and explains why they are one of the continent's most visible faunas.

Evolutionary models demonstrate rapid and adaptive diversification of Australo-Papuan pythons.

Lineages may diversify when they encounter available ecological niches. Adaptive divergence by ecological opportunity often appears to follow the invasion of a new environment with open ecological space. This evolutionary process is hypothesized to explain the explosive diversification of numerous Australian vertebrate groups following the collision of the Eurasian and Australian plates 25 Mya. One of these groups is the pythons, which demonstrate their greatest phenotypic and ecological diversity in Australo-Papua (Australia and New Guinea). Here, using an updated and near complete time-calibrated phylogenomic hypothesis of the group, we show that following invasion of this region, pythons experienced a sudden burst of speciation rates coupled with multiple instances of accelerated phenotypic evolution in head and body shape and body size. These results are consistent with adaptive radiation theory with an initial rapid niche-filling phase and later slow-down approaching niche saturation. We discuss these findings in the context of other Australo-Papuan adaptive radiations and the importance of incorporating adaptive diversification systems that are not extraordinarily species-rich but ecomorphologically diverse to understand how biodiversity is generated.

Prevalence, nature and trajectory of dysphagia postoesophageal cancer surgery: a prospective longitudinal study protocol.

INTRODUCTION: Dysphagia is a common problem following oesophagectomy, and is associated with aspiration pneumonia, malnutrition, weight loss, prolonged enteral feeding tube dependence, in addition to an extended in-hospital stay and compromised quality of life (QOL). To date, the prevalence, nature and trajectory of post-oesophagectomy dysphagia has not been systematically studied in a prospective longitudinal design. The study aims (1) to evaluate the prevalence, nature and trajectory of dysphagia for participants undergoing an oesophagectomy as part of curative treatment, (2) to determine the risk factors for, and post-operative complications of dysphagia in this population and (3) to examine the impact of oropharyngeal dysphagia on health-related QOL across time points. METHODS AND ANALYSIS: A videofluoroscopy will be completed and analysed on both post-operative day (POD) 4 or 5 and at 6-months post-surgery. Other swallow evaluations will be completed preoperatively, POD 4 or 5, 1-month and 6-month time points will include a swallowing screening test, tongue pressure measurement, cough reflex testing and an oral hygiene evaluation. Nutritional measurements will include the Functional Oral Intake Scale to measure feeding tube reliance, Malnutrition Screening Tool and the Strength, Assistance With Walking, Rise From a Chair, Climb Stairs and Falls questionnaire. The Reflux Symptom Index will be administered to investigate aerodigestive symptoms commonly experienced by adults post-oesophagectomy. Swallowing-related QOL outcome measures will be determined using the European Organisation for Research and Treatment of Cancer QLQ-18, MD Anderson Dysphagia Inventory and the Swallowing Quality of Life Questionnaire. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Tallaght University Hospital/St. James' Hospital Research Ethics Committee (JREC), Dublin, Ireland (Ref. No. 2021-Jul-310). The study results will be published in peer-reviewed journals and presented at national and international scientific conferences.

Competition and geography underlie speciation and morphological evolution in Indo-Australasian monitor lizards.

How biotic and abiotic factors act together to shape biological diversity is a major question in evolutionary biology. The recent availability of large datasets and development of new methodological approaches provide new tools to evaluate the predicted effects of ecological interactions and geography on lineage diversification and phenotypic evolution. Here, we use a near complete phylogenomic-scale phylogeny and a comprehensive morphological dataset comprising more than a thousand specimens to assess the role of biotic and abiotic processes in the diversification of monitor lizards (Varanidae). This charismatic group of lizards shows striking variation in species richness among its clades and multiple instances of endemic radiation in Indo-Australasia (i.e., the Indo-Australian Archipelago and Australia), one of Earth's most biogeographically complex regions. We found heterogeneity in diversification dynamics across the family. Idiosyncratic biotic and geographic conditions appear to have driven diversification and morphological evolution in three endemic Indo-Australasian radiations. Furthermore, incumbency effects partially explain patterns in the biotic exchange between Australia and New Guinea. Our results offer insight into the dynamic history of Indo-Australasia, the evolutionary significance of competition, and the long-term consequences of incumbency effects.

Differential Circulating MicroRNA Expression in Age-Related Macular Degeneration.

This study explored the expression of several miRNAs reported to be deregulated in age-related macular degeneration (AMD). Total RNA was isolated from sera from patients with dry AMD (n = 12), wet AMD (n = 14), and controls (n = 10). Forty-two previously investigated miRNAs were selected based on published data and their role in AMD pathogenesis, such as angiogenic and inflammatory effects, and were co-analysed using a miRCURY LNA miRNA SYBR® Green PCR kit via quantitative real-time polymerase chain reaction (qRT-PCR) to validate their presence. Unsupervised hierarchical clustering indicated that AMD serum specimens have a different miRNA profile to healthy controls. We successfully validated the differentially regulated miRNAs in serum from AMD patients versus controls. Eight miRNAs (hsa-let-7a-5p, hsa-let-7d-5p, hsa-miR-23a-3p, hsa-miR-301a-3p, hsa-miR-361-5p, hsa-miR-27b-3p, hsa-miR-874-3p, hsa-miR-19b-1-5p) showed higher expression in the serum of dry AMD patients than wet AMD patients and compared with healthy controls. Increased quantities of certain miRNAs in the serum of AMD patients indicate that these miRNAs could potentially serve as diagnostic AMD biomarkers and might be used as future AMD treatment targets. The discovery of significant serum miRNA biomarkers in AMD patients would provide an easy screening tool for at-risk populations.

Ecomorphometric Analysis of Diversity in Cranial Shape of Pygopodid Geckos.

Pygopodids are elongate, functionally limbless geckos found throughout Australia. The clade presents low taxonomic diversity (∼45 spp.), but a variety of cranial morphologies, habitat use, and locomotor abilities that vary between and within genera. In order to assess potential relationships between cranial morphology and ecology, computed tomography scans of 29 species were used for 3D geometric morphometric analysis. A combination of 24 static landmarks and 20 sliding semi-landmarks were subjected to Generalized Procrustes Alignment. Disparity in cranial shape was visualized through Principal Component Analysis, and a multivariate analysis of variance (MANOVA) was used to test for an association between shape, habitat, and diet. A subset of 27 species with well-resolved phylogenetic relationships was used to generate a phylomorphospace and conduct phylogeny-corrected MANOVA. Similar analyses were done solely on Aprasia taxa to explore species-level variation. Most of the variation across pygopodids was described by principal component (PC) 1(54%: cranial roof width, parabasisphenoid, and occipital length), PC2 (12%: snout elongation and braincase width), and PC3 (6%: elongation and shape of the palate and rostrum). Without phylogenetic correction, both habitat and diet were significant influencers of variation in cranial morphology. However, in the phylogeny-corrected MANOVA, habitat remained weakly significant, but not diet, which can be explained by generic-level differences in ecology rather than among species. Our results demonstrate that at higher levels, phylogeny has a strong effect on morphology, but that influence may be due to small sample size when comparing genera. However, because some closely related taxa occupy distant regions of morphospace, diverging diets, and use of fossorial habitats may contribute to variation seen in these geckos.

A return-on-investment approach for prioritization of rigorous taxonomic research needed to inform responses to the biodiversity crisis.

Global biodiversity loss is a profound consequence of human activity. Disturbingly, biodiversity loss is greater than realized because of the unknown number of undocumented species. Conservation fundamentally relies on taxonomic recognition of species, but only a fraction of biodiversity is described. Here, we provide a new quantitative approach for prioritizing rigorous taxonomic research for conservation. We implement this approach in a highly diverse vertebrate group-Australian lizards and snakes. Of 870 species assessed, we identified 282 (32.4%) with taxonomic uncertainty, of which 17.6% likely comprise undescribed species of conservation concern. We identify 24 species in need of immediate taxonomic attention to facilitate conservation. Using a broadly applicable return-on-investment framework, we demonstrate the importance of prioritizing the fundamental work of identifying species before they are lost.

A Comprehensive Approach to Detect Hybridization Sheds Light on the Evolution of Earth's Largest Lizards.

Hybridization between species occurs more frequently in vertebrates than traditionally thought, but distinguishing ancient hybridization from other phenomena that generate similar evolutionary patterns remains challenging. Here, we used a comprehensive workflow to discover evidence of ancient hybridization between the Komodo dragon (Varanus komodoensis) from Indonesia and a common ancestor of an Australian group of monitor lizards known colloquially as sand monitors. Our data comprise $>$300 nuclear loci, mitochondrial genomes, phenotypic data, fossil and contemporary records, and past/present climatic data. We show that the four sand monitor species share more nuclear alleles with $V$. komodoensis than expected given a bifurcating phylogeny, likely as a result of hybridization between the latter species and a common ancestor of sand monitors. Sand monitors display phenotypes that are intermediate between their closest relatives and $V$. komodoensis. Biogeographic analyses suggest that $V$. komodoensis and ancestral sand monitors co-occurred in northern Australia. In agreement with the fossil record, this provides further evidence that the Komodo dragon once inhabited the Australian continent. Our study shows how different sources of evidence can be used to thoroughly characterize evolutionary histories that deviate from a treelike pattern, that hybridization can have long-lasting effects on phenotypes, and that detecting hybridization can improve our understanding of evolutionary and biogeographic patterns.[Biogeography; introgression; Komodo dragon; phylogenetic networks; phylogenomics; reticulation; Varanus.].

Phylogenomics of Monitor Lizards and the Role of Competition in Dictating Body Size Disparity.

Organismal interactions drive the accumulation of diversity by influencing species ranges, morphology, and behavior. Interactions vary from agonistic to cooperative and should result in predictable patterns in trait and range evolution. However, despite a conceptual understanding of these processes, they have been difficult to model, particularly on macroevolutionary timescales and across broad geographic spaces. Here, we investigate the influence of biotic interactions on trait evolution and community assembly in monitor lizards (Varanus). Monitors are an iconic radiation with a cosmopolitan distribution and the greatest size disparity of any living terrestrial vertebrate genus. Between the colossal Komodo dragon Varanus komodoensis and the smallest Australian dwarf goannas, Varanus length and mass vary by multiple orders of magnitude. To test the hypothesis that size variation in this genus was driven by character displacement, we extended existing phylogenetic comparative methods which consider lineage interactions to account for dynamic biogeographic history and apply these methods to Australian monitors and marsupial predators. Incorporating both exon-capture molecular and morphological data sets we use a combined evidence approach to estimate the relationships among living and extinct varaniform lizards. Our results suggest that communities of Australian Varanus show high functional diversity as a result of continent-wide interspecific competition among monitors but not with faunivorous marsupials. We demonstrate that patterns of trait evolution resulting from character displacement on continental scales are recoverable from comparative data and highlight that these macroevolutionary patterns may develop in parallel across widely distributed sympatric groups.[Character displacement; comparative methods; phylogenetics; trait evolution; Varanus.].