Demographically explicit scans for barriers to gene flow using gIMble.

Identifying regions of the genome that act as barriers to gene flow between recently diverged taxa has remained challenging given the many evolutionary forces that generate variation in genetic diversity and divergence along the genome, and the stochastic nature of this variation. Progress has been impeded by a conceptual and methodological divide between analyses that infer the demographic history of speciation and genome scans aimed at identifying locally maladaptive alleles i.e. genomic barriers to gene flow. Here we implement genomewide IM blockwise likelihood estimation (gIMble), a composite likelihood approach for the quantification of barriers, that bridges this divide. This analytic framework captures background selection and selection against barriers in a model of isolation with migration (IM) as heterogeneity in effective population size (Ne) and effective migration rate (me), respectively. Variation in both effective demographic parameters is estimated in sliding windows via pre-computed likelihood grids. gIMble includes modules for pre-processing/filtering of genomic data and performing parametric bootstraps using coalescent simulations. To demonstrate the new approach, we analyse data from a well-studied pair of sister species of tropical butterflies with a known history of post-divergence gene flow: Heliconius melpomene and H. cydno. Our analyses uncover both large-effect barrier loci (including well-known wing-pattern genes) and a genome-wide signal of a polygenic barrier architecture.

Transposable Element Insertions Are Associated with Batesian Mimicry in the Pantropical Butterfly Hypolimnas misippus.

Hypolimnas misippus is a Batesian mimic of the toxic African Queen butterfly (Danaus chrysippus). Female H. misippus butterflies use two major wing patterning loci (M and A) to imitate three color morphs of D. chrysippus found in different regions of Africa. In this study, we examine the evolution of the M locus and identify it as an example of adaptive atavism. This phenomenon involves a morphological reversion to an ancestral character that results in an adaptive phenotype. We show that H. misippus has re-evolved an ancestral wing pattern present in other Hypolimnas species, repurposing it for Batesian mimicry of a D. chrysippus morph. Using haplotagging, a linked-read sequencing technology, and our new analytical tool, Wrath, we discover two large transposable element insertions located at the M locus and establish that these insertions are present in the dominant allele responsible for producing mimetic phenotype. By conducting a comparative analysis involving additional Hypolimnas species, we demonstrate that the dominant allele is derived. This suggests that, in the derived allele, the transposable elements disrupt a cis-regulatory element, leading to the reversion to an ancestral phenotype that is then utilized for Batesian mimicry of a distinct model, a different morph of D. chrysippus. Our findings present a compelling instance of convergent evolution and adaptive atavism, in which the same pattern element has independently evolved multiple times in Hypolimnas butterflies, repeatedly playing a role in Batesian mimicry of diverse model species.

Rapid and predictable genome evolution across three hybrid ant populations.

Hybridization is frequent in the wild but it is unclear when admixture events lead to predictable outcomes and if so, at what timescale. We show that selection led to correlated sorting of genetic variation rapidly after admixture in 3 hybrid Formica aquilonia × F. polyctena ant populations. Removal of ancestry from the species with the lowest effective population size happened in all populations, consistent with purging of deleterious load. This process was modulated by recombination rate variation and the density of functional sites. Moreover, haplotypes with signatures of positive selection in either species were more likely to fix in hybrids. These mechanisms led to mosaic genomes with comparable ancestry proportions. Our work demonstrates predictable evolution over short timescales after admixture in nature.

Chromosome Fissions and Fusions Act as Barriers to Gene Flow between Brenthis Fritillary Butterflies.

Chromosome rearrangements are thought to promote reproductive isolation between incipient species. However, it is unclear how often, and under what conditions, fission and fusion rearrangements act as barriers to gene flow. Here we investigate speciation between two largely sympatric fritillary butterflies, Brenthis daphne and Brenthis ino. We use a composite likelihood approach to infer the demographic history of these species from whole-genome sequence data. We then compare chromosome-level genome assemblies of individuals from each species and identify a total of nine chromosome fissions and fusions. Finally, we fit a demographic model where effective population sizes and effective migration rate vary across the genome, allowing us to quantify the effects of chromosome rearrangements on reproductive isolation. We show that chromosomes involved in rearrangements experienced less effective migration since the onset of species divergence and that genomic regions near rearrangement points have a further reduction in effective migration rate. Our results suggest that the evolution of multiple rearrangements in the B. daphne and B. ino populations, including alternative fusions of the same chromosomes, have resulted in a reduction in gene flow. Although fission and fusion of chromosomes are unlikely to be the only processes that have led to speciation between these butterflies, this study shows that these rearrangements can directly promote reproductive isolation and may be involved in speciation when karyotypes evolve quickly.

Subtle Introgression Footprints at the End of the Speciation Continuum in a Clade of Heliconius Butterflies.

Quantifying gene flow between lineages at different stages of the speciation continuum is central to understanding speciation. Heliconius butterflies have undergone an adaptive radiation in wing color patterns driven partly by natural selection for local mimicry. Color patterns are also known to be used as assortative mating cues. Therefore, wing pattern divergence is considered to play a role in speciation. A corollary is that mimicry between closely related species may be associated with hybridization and interfere with reproductive isolation. Here, we take a multifaceted approach to explore speciation history, species boundaries, and traits involved in species differentiation between the two closely related species, Heliconius hecale and Heliconius ismenius. We focus on geographic regions where the two species mimic each other and contrast this with geographic regions where they do not mimic each other. To examine population history and patterns of gene flow, we tested and compared a four-population model accounting for linked selection. This model suggests that the two species have remained isolated for a large part of their history, yet with a small amount of gene exchange. Accordingly, signatures of genomic introgression were small except at a major wing pattern allele and chemosensing genes and stronger in the mimetic populations compared with nonmimetic populations. Behavioral assays confirm that visual confusion exists but that short-range cues determine strong sexual isolation. Tests for chemical differentiation between species identified major differences in putative pheromones which likely mediate mate choice and the maintenance of species differences.

Recent Evolution of a Maternally Acting Sex-Determining Supergene in a Fly with Single-Sex Broods.

Sex determination is a key developmental process, yet it is remarkably variable across the tree of life. The dipteran family Sciaridae exhibits one of the most unusual sex determination systems in which mothers control offspring sex through selective elimination of paternal X chromosomes. Whereas in some members of the family females produce mixed-sex broods, others such as the dark-winged fungus gnat Bradysia coprophila are monogenic, with females producing single-sex broods. Female-producing females were previously found to be heterozygous for a large X-linked paracentric inversion (X'), which is maternally inherited and absent from male-producing females. Here, we assembled and characterized the X' sequence. As close sequence homology between the X and X' made identification of the inversion challenging, we developed a k-mer-based approach to bin genomic reads before assembly. We confirmed that the inversion spans most of the X' chromosome (∼55 Mb) and encodes ∼3,500 genes. Analysis of the divergence between the inversion and the homologous region of the X revealed that it originated very recently (<0.5 Ma). Surprisingly, we found that the X' is more complex than previously thought and is likely to have undergone multiple rearrangements that have produced regions of varying ages, resembling a supergene composed of evolutionary strata. We found functional degradation of ∼7.3% of genes within the region of recombination suppression, but no evidence of accumulation of repetitive elements. Our findings provide an indication that sex-linked inversions are driving turnover of the strange sex determination system in this family of flies.

Imaging-based risk stratification of patients with pulmonary embolism based on dual-energy CT-derived radiomics.

BACKGROUND: Technological progress in the acquisition of medical images and the extraction of underlying quantitative imaging data has introduced exciting prospects for the diagnostic assessment of a wide range of conditions. This study aims to investigate the diagnostic utility of a machine learning classifier based on dual-energy computed tomography (DECT) radiomics for classifying pulmonary embolism (PE) severity and assessing the risk for early death. METHODS: Patients who underwent CT pulmonary angiogram (CTPA) between January 2015 and March 2022 were considered for inclusion in this study. Based on DECT imaging, 107 radiomic features were extracted for each patient using standardized image processing. After dividing the dataset into training and test sets, stepwise feature reduction based on reproducibility, variable importance and correlation analyses were performed to select the most relevant features; these were used to train and validate the gradient-boosted tree models. RESULTS: The trained machine learning classifier achieved a classification accuracy of .90 for identifying high-risk PE patients with an area under the receiver operating characteristic curve of .59. This CT-based radiomics signature showed good diagnostic accuracy for risk stratification in individuals presenting with central PE, particularly within higher risk groups. CONCLUSION: Models utilizing DECT-derived radiomics features can accurately stratify patients with pulmonary embolism into established clinical risk scores. This approach holds the potential to enhance patient management and optimize patient flow by assisting in the clinical decision-making process. It also offers the advantage of saving time and resources by leveraging existing imaging to eliminate the necessity for manual clinical scoring.

Optimizing resource allocation: Cost-effectiveness of specified D-dimer cut-offs in cancer patients with suspected venous thromboembolism.

An accurate diagnosis of venous thromboembolism (VTE) is crucial, given the potential for high mortality in undetected cases. Strategic D-dimer testing may aid in identifying low-risk patients, preventing overdiagnosis and reducing imaging costs. We conducted a retrospective, comparative analysis to assess the potential cost savings that could be achieved by adopting different approaches to determine the most effective D-dimer cut-off value in cancer patients with suspected VTE, compared to the commonly used rule-out cut-off level of 0.5 mg/L. The study included 526 patients (median age 65, IQR 55-75) with a confirmed cancer diagnosis who underwent D-dimer testing. Among these patients, the VTE prevalence was 29% (n = 152). Each diagnostic strategy's sensitivity, specificity, negative likelihood ratio (NLR), as well as positive likelihood ratio (PLR), and the proportion of patients exhibiting a negative D-dimer test result, were calculated. The diagnostic strategy that demonstrated the best balance between specificity, sensitivity, NLR, and PLR, utilized an inverse age-specific cut-off level for D-dimer [0.5 + (66-age) × 0.01 mg/L]. This method yielded a PLR of 2.9 at a very low NLR for the exclusion of VTE. We observed a significant cost reduction of 4.6% and 1.0% for PE and DVT, respectively. The utilization of an age-adjusted cut-off [patient's age × 0.01 mg/L] resulted in the highest cost savings, reaching 8.1% for PE and 3.4% for DVT. Using specified D-dimer cut-offs in the diagnosis of VTE could improve economics, considering the limited occurrence of confirmed cases among patients with suspected VTE.

Does Dual-Energy Computed Tomography Material Decomposition Improve Radiomics Capability to Predict Survival in Head and Neck Squamous Cell Carcinoma Patients? A Preliminary Investigation.

OBJECTIVE: Our study objective was to explore the additional value of dual-energy CT (DECT) material decomposition for squamous cell carcinoma of the head and neck (SCCHN) survival prognostication. METHODS: A group of 50 SCCHN patients (male, 37; female, 13; mean age, 63.6 ± 10.82 years) with baseline head and neck DECT between September 2014 and August 2020 were retrospectively included. Primary tumors were segmented, radiomics features were extracted, and DECT material decomposition was performed. We used independent train and validation datasets with cross-validation and 100 independent iterations to identify prognostic signatures applying elastic net (EN) and random survival forest (RSF). Features were ranked and intercorrelated according to their prognostic importance. We benchmarked the models against clinical parameters. Intraclass correlation coefficients were used to analyze the interreader variation. RESULTS: The exclusively radiomics-trained models achieved similar ( P = 0.947) prognostic performance of area under the curve (AUC) = 0.784 (95% confidence interval [CI], 0.775-0.812) (EN) and AUC = 0.785 (95% CI, 0.759-0.812) (RSF). The additional application of DECT material decomposition did not improve the model's performance (EN, P = 0.594; RSF, P = 0.198). In the clinical benchmark, the top averaged AUC value of 0.643 (95% CI, 0.611-0.675) was inferior to the quantitative imaging-biomarker models ( P < 0.001). A combined imaging and clinical model did not improve the imaging-based models ( P > 0.101). Shape features revealed high prognostic importance. CONCLUSIONS: Radiomics AI applications may be used for SCCHN survival prognostication, but the spectral information of DECT material decomposition did not improve the model's performance in our preliminary investigation.

Comparison of 96-kV and 120-kV cone-beam CT for the assessment of cochlear implants.

BACKGROUND: To compare the diagnostic value of 120-kV with conventional 96-kV Cone-Beam CT (CBCT) of the temporal bone after cochlear implant (CI) surgery. METHODS: This retrospective study included CBCT scans after CI surgery between 06/17 and 01/18. CBCT allowed examinations with 96-kV or 120-kV; other parameters were the same. Two radiologists independently evaluated following criteria on 5-point Likert scales: osseous spiral lamina, inner and outer cochlear wall, semi-circular canals, mastoid trabecular structure, overall image quality, metal and motion artefacts, depiction of intracochlear electrode position and visualisation of single electrode contacts. Effective radiation dose was assessed. RESULTS: Seventy-five patients (females, n = 39 [52.0%], mean age, 55.8 ± 16.5 years) were scanned with 96-kV (n = 32, 42.7%) and 120-kV (n = 43, 57.3%) protocols including CI models from three vendors (vendor A n = 7; vendor B n = 43; vendor C n = 25). Overall image quality, depiction of anatomical structures, and electrode position were rated significantly better in 120-kV images compared to 96-kV (all p < = 0.018). Anatomical structures and electrode position were rated significantly better in 120-kV CBCT for CI models from vendor A and C, while 120-kV did not provide improved image quality in CI models from vendor B. Radiation doses were significantly higher for 120-kV scans compared to 96-kV (0.15 vs. 0.08 mSv, p < 0.001). CONCLUSIONS: 120-kV and 96-kV CBCT provide good diagnostic images for the postoperative CI evaluation. While 120-kV showed improved depiction of temporal bone and CI electrode position compared to 96-kV in most CI models, the 120-kV protocol should be chosen wisely due to a substantially higher radiation exposure.

Overuse injury and affects in competitive sport: A prospective longitudinal study.

Overuse injuries, which have a high prevalence in sport, are suggested to result in different affective responses in comparison to traumatic injuries. Affects may also reciprocally act as risk factors for overuse injury. The aim of this study was to examine the associations between overuse injury and affects within a longitudinal follow-up design. Competitive athletes (N = 149) of various sports and levels of competition completed the Positive and Negative Affect Schedule (PANAS) and the Oslo Sports Trauma Research Centre Overuse injury questionnaire (OSTRC-O) once a week over 10 consecutive weeks. Bivariate unconditional latent curve model analyses with structured residuals were performed to evaluate the associations within and across weeks between OSTRC-O severity score and affects. Results indicated that OSTRC-O severity score and positive affects (PA) had a statistically significant negative within-week relation (r = -24.51, 95% CI = [-33.9, -15.1], p < 0.001). Higher scores of overuse injury were significantly related to lower levels of PA across weeks (ß = -0.02, 95% CI = [-0.04, -0.001], p = 0.044), while the reciprocal effect of PA on overuse injury was not significant (ß = -0.13, 95% CI = [-0.52, 0.26], p = 0.51). No statistically significant association was observed between OSTRC-O severity score and negative affects, neither within nor across weeks. Our findings suggest that overuse injury may have adverse psychological consequences on the long run through lessened PA and address the need for providing sustainable psychological support focusing upon such PA when working with athletes experiencing overuse injury.

From pixels to prognosis: Imaging biomarkers for discrimination and outcome prediction of pulmonary embolism : Original Research Article.

PURPOSE: Recent advancements in medical imaging have transformed diagnostic assessments, offering exciting possibilities for extracting biomarker-based information. This study aims to investigate the capabilities of a machine learning classifier that incorporates dual-energy computed tomography (DECT) radiomics. The primary focus is on discerning and predicting outcomes related to pulmonary embolism (PE). METHODS: The study included 131 participants who underwent pulmonary artery DECT angiography between January 2015 and March 2022. Among them, 104 patients received the final diagnosis of PE and 27 patients served as a control group. A total of 107 radiomic features were extracted for every case based on DECT imaging. The dataset was divided into training and test sets for model development and validation. Stepwise feature reduction identified the most relevant features, which were used to train a gradient-boosted tree model. Receiver operating characteristics analysis and Cox regression tests assessed the association of texture features with overall survival. RESULTS: The trained machine learning classifier achieved a classification accuracy of 0.94 for identifying patients with acute PE with an area under the receiver operating characteristic curve of 0.91. Radiomics features could be valuable for predicting outcomes in patients with PE, demonstrating strong prognostic capabilities in survival prediction (c-index, 0.991 [0.979-1.00], p = 0.0001) with a median follow-up of 130 days (IQR, 38-720). Notably, the inclusion of clinical or DECT parameters did not enhance predictive performance. CONCLUSION: In conclusion, our study underscores the promising potential of leveraging radiomics on DECT imaging for the identification of patients with acute PE and predicting their outcomes. This approach has the potential to improve clinical decision-making and patient management, offering efficiencies in time and resources by utilizing existing DECT imaging without the need for an additional scoring system.

Genome sequence of Ophryocystis elektroscirrha, an apicomplexan parasite of monarch butterflies: cryptic diversity and response to host-sequestered plant chemicals.

Apicomplexa are ancient and diverse organisms which have been poorly characterized by modern genomics. To better understand the evolution and diversity of these single-celled eukaryotes, we sequenced the genome of Ophryocystis elektroscirrha, a parasite of monarch butterflies, Danaus plexippus. We contextualize our newly generated resources within apicomplexan genomics before answering longstanding questions specific to this host-parasite system. To start, the genome is miniscule, totaling only 9 million bases and containing fewer than 3,000 genes, half the gene content of two other sequenced invertebrate-infecting apicomplexans, Porospora gigantea and Gregarina niphandrodes. We found that O. elektroscirrha shares different orthologs with each sequenced relative, suggesting the true set of universally conserved apicomplexan genes is very small indeed. Next, we show that sequencing data from other potential host butterflies can be used to diagnose infection status as well as to study diversity of parasite sequences. We recovered a similarly sized parasite genome from another butterfly, Danaus chrysippus, that was highly diverged from the O. elektroscirrha reference, possibly representing a distinct species. Using these two new genomes, we investigated potential evolutionary response by parasites to toxic phytochemicals their hosts ingest and sequester. Monarch butterflies are well-known to tolerate toxic cardenolides thanks to changes in the sequence of their Type II ATPase sodium pumps. We show that Ophryocystis completely lacks Type II or Type 4 sodium pumps, and related proteins PMCA calcium pumps show extreme sequence divergence compared to other Apicomplexa, demonstrating new avenues of research opened by genome sequencing of non-model Apicomplexa.

Dual-Energy CT-based Opportunistic Volumetric Bone Mineral Density Assessment of the Distal Radius.

Background In patients with distal radius fractures (DRFs), low bone mineral density (BMD) is associated with bone substitute use during surgery and bone nonunion, but BMD information is not regularly available. Purpose To evaluate the feasibility of dual-energy CT (DECT)-based BMD assessment from routine examinations in the distal radius and the relationship between the obtained BMD values, the occurrence of DRFs, bone nonunion, and use of surgical bone substitute. Materials and Methods Scans in patients who underwent routine dual-source DECT in the distal radius between January 2016 and December 2021 were retrospectively acquired. Phantomless BMD assessment was performed using the delineated trabecular bone of a nonfractured segment of the distal radius and both DECT image series. CT images and health records were examined to determine fracture severity, surgical management, and the occurrence of bone nonunion. Associations of BMD with the occurrence of DRFs, bone nonunion, and bone substitute use at surgical treatment were examined with generalized additive models and receiver operating characteristic analysis. Results This study included 263 patients (median age, 52 years; IQR, 36-64 years; 132 female patients), of whom 192 were diagnosed with fractures. Mean volumetric BMD was lower in patients who sustained a DRF (93.9 mg/cm3 vs 135.4 mg/cm3; P < .001), required bone substitutes (79.6 mg/cm3 vs 95.5 mg/cm3; P < .001), and developed bone nonunion (71.1 mg/cm3 vs 96.5 mg/cm3; P < .001). Receiver operating characteristic curve analysis identified these patients with an area under the curve of 0.71-0.91 (P < .001). Lower BMD increased the risk to sustain DRFs, develop bone nonunion, and receive bone substitutes at surgery (P < .001). Conclusion DECT-based BMD assessment at routine examinations is feasible and could help predict surgical bone substitute use and the occurrence of bone nonunion in patients with DRFs. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Carrino in this issue.

Do chromosome rearrangements fix by genetic drift or natural selection? Insights from Brenthis butterflies.

Large-scale chromosome rearrangements, such as fissions and fusions, are a common feature of eukaryote evolution. They can have considerable influence on the evolution of populations, yet it remains unclear exactly how rearrangements become established and eventually fix. Rearrangements could fix by genetic drift if they are weakly deleterious or neutral, or they may instead be favoured by positive natural selection. Here, we compare genome assemblies of three closely related Brenthis butterfly species and characterize a complex history of fission and fusion rearrangements. An inferred demographic history of these species suggests that rearrangements became fixed in populations with large long-term effective size (Ne ), consistent with rearrangements being selectively neutral or only very weakly underdominant. Using a recently developed analytic framework for characterizing hard selective sweeps, we find that chromosome fusions are not enriched for evidence of past sweeps compared to other regions of the genome. Nonetheless, we do infer a strong and recent selective sweep around one chromosome fusion in the B. daphne genome. Our results suggest that rearrangements in these species likely have weak absolute fitness effects and fix by genetic drift. However, one putative selective sweep raises the possibility that natural selection may sometimes play a role in the fixation of chromosome fusions.

Free-breathing accelerated whole-body MRI using an automated workflow: Comparison with conventional breath-hold sequences.

Whole-body magnetic resonance imaging (MRI) has become increasingly popular in oncology. However, the long acquisition time might hamper its widespread application. We sought to assess and compare free-breathing sequences with conventional breath-hold examinations in whole-body MRI using an automated workflow process. This prospective study consisted of 20 volunteers and six patients with a variety of pathologies who had undergone whole-body 1.5-T MRI that included T1-weighted radial and Dixon volumetric interpolated breath-hold examination sequences. Free-breathing sequences were operated by using an automated user interface. Image quality, diagnostic confidence, and image noise were evaluated by two experienced radiologists. Additionally, signal-to-noise ratio was measured. Diagnostic performance for the overall detection of pathologies was assessed using the area under the receiver operating characteristics curve (AUC). Study participants were asked to rate their examination experiences in a satisfaction survey. MR free-breathing scans were rated as at least equivalent to conventional MR scans in more than 92% of cases, showing high overall diagnostic accuracy (95% [95% CI 92-100]) and performance (AUC 0.971, 95% CI 0.942-0.988; p < 0.0001) for the assessment of pathologies at simultaneously reduced examination times (25 ± 2 vs. 32 ± 3 min; p < 0.0001). Interrater agreement was excellent for both free-breathing (Ï° = 0.96 [95% CI 0.88-1.00]) and conventional scans (Ï° = 0.93 [95% CI 0.84-1.00]). Qualitative and quantitative assessment for image quality, image noise, and diagnostic confidence did not differ between the two types of MR image acquisition (all p > 0.05). Scores for patient satisfaction were significantly better for free-breathing compared with breath-hold examinations (p = 0.0145), including significant correlations for the grade of noise (r = 0.79, p < 0.0001), tightness (r = 0.71, p < 0.0001), and physical fatigue (r = 0.52, p = 0.0065). In summary, free-breathing whole-body MRI in tandem with an automated user interface yielded similar diagnostic performance at equivalent image quality and shorter acquisition times compared to conventional breath-hold sequences.

Advanced biomedical imaging for accurate discrimination and prognostication of mediastinal masses.

BACKGROUND: To investigate the potential of radiomic features and dual-source dual-energy CT (DECT) parameters in differentiating between benign and malignant mediastinal masses and predicting patient outcomes. METHODS: In this retrospective study, we analysed data from 90 patients (38 females, mean age 51 ± 25 years) with confirmed mediastinal masses who underwent contrast-enhanced DECT. Attenuation, radiomic features and DECT-derived imaging parameters were evaluated by two experienced readers. We performed analysis of variance (ANOVA) and Chi-square statistic tests for data comparison. Receiver operating characteristic curve analysis and Cox regression tests were used to differentiate between mediastinal masses. RESULTS: Of the 90 mediastinal masses, 49 (54%) were benign, including cases of thymic hyperplasia/thymic rebound (n = 10), mediastinitis (n = 16) and thymoma (n = 23). The remaining 41 (46%) lesions were classified as malignant, consisting of lymphoma (n = 28), mediastinal tumour (n = 4) and thymic carcinoma (n = 9). Significant differences were observed between benign and malignant mediastinal masses in all DECT-derived parameters (p ≤ .001) and 38 radiomic features (p ≤ .044) obtained from contrast-enhanced DECT. The combination of these methods achieved an area under the curve of .98 (95% CI, .893-1.000; p < .001) to differentiate between benign and malignant masses, with 100% sensitivity and 91% specificity. Throughout a follow-up of 1800 days, a multiparametric model incorporating radiomic features, DECT parameters and gender showed promising prognostic power in predicting all-cause mortality (c-index = .8 [95% CI, .702-.890], p < .001). CONCLUSIONS: A multiparametric approach combining radiomic features and DECT-derived imaging biomarkers allows for accurate and noninvasive differentiation between benign and malignant masses in the anterior mediastinum.

Cancer patients with venous thromboembolism: Diagnostic and prognostic value of elevated D-dimers.

BACKGROUND: D-dimer testing is known to have a high sensitivity at simultaneously low specificity, resulting in nonspecific elevations in a variety of conditions. METHODS: This retrospective study sought to assess diagnostic and prognostic features of D-dimers in cancer patients referred to the emergency department for suspected pulmonary embolism (PE) and deep vein thrombosis (DVT). In total, 526 patients with a final adjudicated diagnosis of PE (n = 83) and DVT (n = 69) were enrolled, whereas 374 patients served as the comparative group, in which venous thromboembolism (VTE) has been excluded. RESULTS: For the identification of VTE, D-dimers yielded the highest positive predictive value of 96% (95% confidence interval (CI), 85-99) at concentrations of 9.9 mg/L and a negative predictive value of 100% at .6 mg/L (95% CI, 97-100). At the established rule-out cut-off level of .5 mg/L, D-dimers were found to be very sensitive (100%) at a moderate specificity of nearly 65%. Using an optimised cut-off value of 4.9 mg/L increased the specificity to 95% for the detection of life-threatening VTE at the cost of moderate sensitivities (64%). During a median follow-up of 30 months, D-dimers positively correlated with the reoccurrence of VTE (p = .0299) and mortality in both cancer patients with VTE (p < .0001) and without VTE (p = .0008). CONCLUSIONS: Although D-dimer testing in cancer patients is discouraged by current guidelines, very high concentrations above the 10-fold upper reference limit contain diagnostic and prognostic information and might be helpful in risk assessment, while low concentrations remain useful for ruling out VTE.

Unveiling the diagnostic enigma of D-dimer testing in cancer patients: Current evidence and areas of application.

BACKGROUND: Cancer is a well-known risk factor for venous thromboembolism (VTE). A combined strategy of D-dimer testing and clinical pre-test probability is usually used to exclude VTE. However, its effectiveness is diminished in cancer patients due to reduced specificity, ultimately leading to a decreased clinical utility. This review article seeks to provide a comprehensive summary of how to interpret D-dimer testing in cancer patients. METHODS: In accordance with PRISMA standards, literature pertaining to the diagnostic and prognostic significance of D-dimer testing in cancer patients was carefully chosen from reputable sources such as PubMed and the Cochrane databases. RESULTS: D-dimers have not only a diagnostic value in ruling out VTE but can also serve as an aid for rule-in if their values exceed 10-times the upper limit of normal. This threshold allows a diagnosis of VTE in cancer patients with a positive predictive value of more than 80%. Moreover, elevated D-dimers carry important prognostic information and are associated with VTE reoccurrence. A gradual increase in risk for all-cause death suggests that VTE is also an indicator of biologically more aggressive cancer types and advanced cancer stages. Considering the lack of standardization for D-dimer assays, it is essential for clinicians to carefully consider the variations in assay performance and the specific test characteristics of their institution. CONCLUSIONS: Standardizing D-dimer assays and developing modified pretest probability models specifically for cancer patients, along with adjusted cut-off values for D-dimer testing, could significantly enhance the accuracy and effectiveness of VTE diagnosis in this population.

Selective sweeps on novel and introgressed variation shape mimicry loci in a butterfly adaptive radiation.

Natural selection leaves distinct signatures in the genome that can reveal the targets and history of adaptive evolution. By analysing high-coverage genome sequence data from 4 major colour pattern loci sampled from nearly 600 individuals in 53 populations, we show pervasive selection on wing patterns in the Heliconius adaptive radiation. The strongest signatures correspond to loci with the greatest phenotypic effects, consistent with visual selection by predators, and are found in colour patterns with geographically restricted distributions. These recent sweeps are similar between co-mimics and indicate colour pattern turn-over events despite strong stabilising selection. Using simulations, we compare sweep signatures expected under classic hard sweeps with those resulting from adaptive introgression, an important aspect of mimicry evolution in Heliconius butterflies. Simulated recipient populations show a distinct 'volcano' pattern with peaks of increased genetic diversity around the selected target, characteristic of sweeps of introgressed variation and consistent with diversity patterns found in some populations. Our genomic data reveal a surprisingly dynamic history of colour pattern selection and co-evolution in this adaptive radiation.