Relevance of apparent diffusion coefficient features for a radiomics-based prediction of response to induction chemotherapy in sinonasal cancer.

In this paper, several radiomics-based predictive models of response to induction chemotherapy (IC) in sinonasal cancers (SNCs) are built and tested. Models were built as a combination of radiomic features extracted from three types of MRI images: T1-weighted images, T2-weighted images and apparent diffusion coefficient (ADC) maps. Fifty patients (aged 54 ± 12 years, 41 men) were included in this study. Patients were classified according to their response to IC (25 responders and 25 nonresponders). Not all types of images were acquired for all of the patients: 49 had T1-weighted images, 50 had T2-weighted images and 34 had ADC maps. Only in a subset of 33 patients were all three types of image acquired. Eighty-nine radiomic features were extracted from the MRI images. Dimensionality reduction was performed by using principal component analysis (PCA) and by selecting only the three main components. Different algorithms (trees ensemble, K-nearest neighbors, support vector machine, naïve Bayes) were used to classify the patients as either responders or nonresponders. Several radiomic models (either monomodality or multimodality obtained by a combination of T1-weighted, T2-weighted and ADC images) were developed and the performance was assessed through 100 iterations of train and test split. The area under the curve (AUC) of the models ranged from 0.56 to 0.78. Trees ensemble, support vector machine and naïve Bayes performed similarly, but in all cases ADC-based models performed better. Trees ensemble gave the highest AUC (0.78 for the T1-weighted+T2-weighted+ADC model) and was used for further analyses. For trees ensemble, the models based on ADC features performed better than those models that did not use those features (P < 0.02 for one-tail Hanley test, AUC range 0.68-0.78 vs 0.56-0.69) except the T1-weighted+ADC model (AUC 0.71 vs 0.69, nonsignificant differences). The results suggest the relevance of ADC-based radiomics for prediction of response to IC in SNCs.

New Evidence of Canthariphily: Tilloidea transversalis (Coleoptera: Cleridae) Sequestering Cantharidin From Lydus trimaculatus (Coleoptera: Meloidae).

Cantharidin (CTD) is a defensive compound autogenously and exclusively produced by two phylogenetically related beetle families: Meloidae and Oedemeridae. Although this molecule usually acts as a strong deterrent against potential predators and parasites, some arthropod species, collectively named 'canthariphilous species', are attracted to CTD. Some species can sequester CTD from the CTD-producing species, using it as a chemical defense against enemies. The present paper focuses on the first-ever description of canthariphilous interactions between a checkered beetle species (Coleoptera: Cleridae) and a CTD -producing species. Field observations revealed individuals of the phytophagous beetle Tilloidea transversalis (Charpentier, 1825) (Coleoptera: Cleridae) biting individuals of the blister beetle Lydus trimaculatus (Fabricius, 1775) (Coleoptera: Meloidae). Laboratory behavioral experiments followed to verify if this peculiar behavior of T. transversalis also occurs on other co-occurring species. Moreover, chemical analyses were performed to assess whether T. transversalis can sequester CTD. Our results show that T. transversalis only attacks CTD-producing species. However, while chemical analyses prove that T. transversalis can sequester CTD from the hemolymph of L. trimaculatus, some clues (based on a CTD-baited traps sampling) suggest that this beetle, contrarily to other canthariphilous species, does not appear to show a high attraction to pure synthetic CTD. Thus, other unknown signals, alone or in combination with CTD, could be implicated in triggering the canthariphilous behaviors of T. transversalis.

Diffusion-weighted MRI radiomics of spine bone tumors: feature stability and machine learning-based classification performance.

PURPOSE: To evaluate stability and machine learning-based classification performance of radiomic features of spine bone tumors using diffusion- and T2-weighted magnetic resonance imaging (MRI). MATERIAL AND METHODS: This retrospective study included 101 patients with histology-proven spine bone tumor (22 benign; 38 primary malignant; 41 metastatic). All tumor volumes were manually segmented on morphologic T2-weighted sequences. The same region of interest (ROI) was used to perform radiomic analysis on ADC map. A total of 1702 radiomic features was considered. Feature stability was assessed through small geometrical transformations of the ROIs mimicking multiple manual delineations. Intraclass correlation coefficient (ICC) quantified feature stability. Feature selection consisted of stability-based (ICC > 0.75) and significance-based selections (ranking features by decreasing Mann-Whitney p-value). Class balancing was performed to oversample the minority (i.e., benign) class. Selected features were used to train and test a support vector machine (SVM) to discriminate benign from malignant spine tumors using tenfold cross-validation. RESULTS: A total of 76.4% radiomic features were stable. The quality metrics for the SVM were evaluated as a function of the number of selected features. The radiomic model with the best performance and the lowest number of features for classifying tumor types included 8 features. The metrics were 78% sensitivity, 68% specificity, 76% accuracy and AUC 0.78. CONCLUSION: SVM classifiers based on radiomic features extracted from T2- and diffusion-weighted imaging with ADC map are promising for classification of spine bone tumors. Radiomic features of spine bone tumors show good reproducibility rates.

Unraveling the role of male reproductive tract and haemolymph in cantharidin-exuding Lydus trimaculatus and Mylabris variabilis (Coleoptera: Meloidae): a comparative transcriptomics approach.

BACKGROUND: Meloidae (blister beetles) are known to synthetize cantharidin (CA), a toxic and defensive terpene mainly stored in male accessory glands (MAG) and emitted outward through reflex-bleeding. Recent progresses in understanding CA biosynthesis and production organ(s) in Meloidae have been made, but the way in which self-protection is achieved from the hazardous accumulation and release of CA in blister beetles has been experimentally neglected. To provide hints on this pending question, a comparative de novo assembly transcriptomic approach was performed by targeting two tissues where CA is largely accumulated and regularly circulates in Meloidae: the male reproductive tract (MRT) and the haemolymph. Differential gene expression profiles in these tissues were examined in two blister beetle species, Lydus trimaculatus (Fabricius, 1775) (tribe Lyttini) and Mylabris variabilis (Pallas, 1781) (tribe Mylabrini). Upregulated transcripts were compared between the two species to identify conserved genes possibly involved in CA detoxification and transport. RESULTS: Based on our results, we hypothesize that, to avoid auto-intoxication, ABC, MFS or other solute transporters might sequester purported glycosylated CA precursors into MAG, and lipocalins could bind CA and mitigate its reactivity when released into the haemolymph during the autohaemorrhaging response. We also found an over-representation in haemolymph of protein-domains related to coagulation and integument repairing mechanisms that likely reflects the need to limit fluid loss during reflex-bleeding. CONCLUSIONS: The de novo assembled transcriptomes of L. trimaculatus and M. variabilis here provided represent valuable genetic resources to further explore the mechanisms employed to cope with toxicity of CA in blister beetle tissues. These, if revealed, might help conceiving safe and effective drug-delivery approaches to enhance the use of CA in medicine.

Prognostic role of pre-treatment magnetic resonance imaging (MRI)-based radiomic analysis in effectively cured head and neck squamous cell carcinoma (HNSCC) patients.

OBJECTIVES: To identify and validate baseline magnetic resonance imaging (b-MRI) radiomic features (RFs) as predictors of disease outcomes in effectively cured head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS AND METHODS: Training set (TS) and validation set (VS) were retrieved from preexisting datasets (HETeCo and BD2Decide trials, respectively). Only patients with both pre- and post-contrast enhancement T1 and T2-weighted b-MRI and at least 2 years of follow-up (FUP) were selected. The combination of the best extracted RFs was used to classify low risk (LR) vs. high risk (HR) of disease recurrence. Sensitivity, specificity, and area under the curve (AUC) of the radiomic model were computed on both TS and VS. Overall survival (OS) and 5-year disease-free survival (DFS) Kaplan-Meier (KM) curves were compared for LR vs. HR. The radiomic-based risk class was used in a multivariate Cox model, including well-established clinical prognostic factors (TNM, sub-site, human papillomavirus [HPV]). RESULTS: In total, 57 patients of TS and 137 of VS were included. Three RFs were selected for the signature. Sensitivity of recurrence risk classifier was 0.82 and 0.77, specificity 0.78 and 0.81, AUC 0.83 and 0.78 for TS and VS, respectively. VS KM curves for LR vs. HR groups significantly differed both for 5-year DFS (p<.0001) and OS (p=.0004). A combined model of RFs plus TNM improved prognostic performance as compared to TNM alone, both for VS 5-year DFS (C-index: 0.76 vs. 0.60) and OS (C-index: 0.74 vs. 0.64). CONCLUSIONS: Radiomics of b-MRI can help to predict recurrence and survival outcomes in HNSCC.

Phylogeny, biogeography and systematics of the hyper-diverse blister beetle genus Hycleus (Coleoptera: Meloidae).

Hycleus is a hyper-diverse genus of blister beetles including ~500 species widely distributed in the Old World, currently divided into three "sections" and into 45 "phenetic" species groups according to morphological characters. Recently the monophyly of Hycleus was questioned pointing out its paraphyly with respect to the genera Ceroctis and Paractenodia. In this study, we built a time-calibrated phylogenetic tree based on DNA sequence data from mitochondrial and nuclear genes obtained from 125 species, to understand the phylogenetic relationships among the species of this genus, to infer the biogeographic processes behind their diversification, and to assess their taxonomy and classification. Our results identified four main lineages one of which included the species belonging to Ceroctis and Paractenodia; therefore, both taxa are now referred to Hycleus as new synonyms. The three described sections of Hycleus resulted polyphyletic and are rejected, whereas several species groups represented well supported clades. Hycleus likely originated in Africa during the Early Miocene (~20 Mya), and subsequently spread in Europe and western Asia. Later, in the Late Miocene (~6 Mya) a Saharo-Sindian group branched off from the Palaearctic lineage, whereas the Oriental Region was colonized following a dispersal event through the Arabian Peninsula from the Afrotropical Region (~5 Mya).

Phylogenetic systematics of Mylabris blister beetles (Coleoptera, Meloidae): a molecular assessment using species trees and total evidence.

Mylabris is a diverse genus of Meloidae and includes over 170 species throughout the Palaearctic region, classified into 14 subgenera. The current classification is largely built on taxonomic works pre-dating the application of cladistic methods and based on a few morphological characters. In the present study, we use molecular data from mitochondrial and nuclear loci sampled across Mylabrini to assess the monophyly of Mylabris and its subgenera, and to identify which diagnostic morphological characters used for taxa delimitation represent synapomorphic features. We obtain a robust phylogeny which is consistent across datasets (3-, 4- and 5-gene datasets), methods (Bayesian vs. Maximum Parsimony), and approaches (species tree vs. total evidence). The genus Mylabris is monophyletic provided that Pseudabris is included and Ammabris is excluded. Most of the morphology-based subgenera are recovered as well-supported phylogenetic clades. Although previous classifications based on number and shape of antennomeres were confounded by convergent evolution of these traits, mesosternal and male genitalia features provided unambiguous apomorphies of Mylabrini genera and subgenera. We integrate these insights into an updated phylogenetic systematics of Mylabris and Mylabrini blister beetles, and we provide the description of two new subgenera, Dvorabris and Pardabris.

Assessment of Stability and Discrimination Capacity of Radiomic Features on Apparent Diffusion Coefficient Images.

The objectives of the study are to develop a new way to assess stability and discrimination capacity of radiomic features without the need of test-retest or multiple delineations and to use information obtained to perform a preliminary feature selection. Apparent diffusion coefficient (ADC) maps were computed from diffusion-weighted magnetic resonance images (DW-MRI) of two groups of patients: 18 with soft tissue sarcomas (STS) and 18 with oropharyngeal cancers (OPC). Sixty-nine radiomic features were computed, using three different histogram discretizations (16, 32, and 64 bins). Geometrical transformations (translations) of increasing entity were applied to the regions of interest (ROIs), and the intra-class correlation coefficient (ICC) was used to compare the features computed on the original and modified ROIs. The distribution of ICC values for minimal and maximal entity translations (ICC10 and ICC100, respectively) was used to adjust thresholds of ICC (ICCmin and ICCmax) used to discriminate between good, unstable (ICC10 < ICCmin), and non-discriminative features (ICC100 > ICCmax). Fifty-four and 59 radiomic features passed the stability-based selection for all the three histogram discretizations for the OPC and STS datasets, respectively. The excluded features were similar across the different histogram discretizations (Jaccard's index 0.77 ± 0.13 and 0.9 ± 0.1 for OPC and STS, respectively) but different between datasets (Jaccard's index 0.19 ± 0.02). The results suggest that the observed radiomic features are mainly stable and discriminative, but the stability depends on the region of the body under observation. The method provides a way to assess stability without the need of test-retest or multiple delineations.

Taxonomy, bionomics and faunistics of the nominate subgenus of Mylabris Fabricius, 1775, with the description of five new species (Coleoptera: Meloidae: Mylabrini).

The nominate subgenus of the mylabrine genus Mylabris is revised: five new species, M. (M.) alpicola sp.n., M. (M.) cernyi sp.n., M. (M.) mediorientalis sp.n., and M. (M.) pseudoemiliae sp.n., are described and figured; M. (M.) apiceguttata sp.n., is provisionally refered to the nominate subgenus. M. (M.) rishwani Makhan, 2012 is synonymized with M. (M.) quadripunctata (Linnaeus, 1767). The other 20 species are characterized by short descriptions and figures, and a key to the species is provided. Tentatively, M. barezensis  and M. batnensis are placed in the nominate subgenus. The bionomics of the species is summarized in tables including information on phenology, elevation, habitat preference, host plants, larval biology, and host insects. Zoogeographic analysis of the subgenus was carried out on the basis of all available faunistic records from literature and collections which are summarized in Appendix.

Comparative genomics provides insights into molecular adaptation to hypermetamorphosis and cantharidin metabolism in blister beetles (Coleoptera: Meloidae).

Blister beetles (Coleoptera: Meloidae) are currently subdivided into three subfamilies: Eleticinae (a basal group), Nemognathinae, and Meloinae. These are all characterized by the endogenous production of the defensive terpene cantharidin (CA), whereas the two most derived subfamilies show a hypermetamorphic larval development. Here, we provide novel draft genome assemblies of five species sampled across the three blister beetle subfamilies (Iselma pallidipennis, Stenodera caucasica, Zonitis immaculata, Lydus trimaculatus, and Mylabris variabilis) and performed a comparative analysis with other available Meloidae genomes and the closely-related canthariphilous species (Pyrochroa serraticornis) to disclose adaptations at a molecular level. Our results highlighted the expansion and selection of genes potentially responsible for CA production and metabolism, as well as its mobilization and vesicular compartmentalization. Furthermore, we observed adaptive selection patterns and gain of genes devoted to epigenetic regulation, development, and morphogenesis, possibly related to hypermetamorphosis. We hypothesize that most genetic adaptations occurred to support both CA biosynthesis and hypermetamorphosis, two crucial aspects of Meloidae biology that likely contributed to their evolutionary success.

Larval features of the Italian endemic Pyrochroa serraticornis kiesenwetteri Fairmaire, 1849 (Coleoptera: Pyrochroidae: Pyrochroinae) solve taxonomic uncertainties.

Recent findings rearranged the taxonomy of the European species of the genus Pyrochroa Geoffroy (Coleoptera: Pyrochroidae), and to date three species are recognized: P. bifoveata Molfini et al., 2022 and P. coccinea (Linnaeus, 1761) with cryptic adults and distinctive larvae, and the polytypic P. serraticornis (Scopoli, 1763), including the subspecies kiesenwetteri Fairmaire, 1849. Incongruences between molecular and morphological analyses questioned the recognition of P. s. serraticornis and P. s. kiesenwetteri as taxa of the same species. In the present paper, observations of larval characters of P. s. kiesenwetteri confirm this taxon as a subspecies of P. serraticornis. Moreover, new characters of P. s. serraticornis larvae are offered by analysing specimens from a new European locality.

The cranial apparatus glands of the canthariphilous Pyrochroa coccinea (Coleoptera: Pyrochroidae: Pyrochroinae), and their implications in sexual behaviour.

Some Pyrochroidae species are known as "canthariphilous" for their attraction to cantharidin (CTD), a toxic terpene with anti-predatory effects, produced in nature by only two beetle families (Meloidae and Oedemeridae). It has been demonstrated that males of Neopyrochroa flabellata ingesting CTD are positively selected by females. Indeed, the compound is re-emitted from a glandular cranial apparatus as secretions that are licked up by females during courtship behaviour, inducing copulation. Herein, we provide the first description of the glands associated to the cranial apparatus of male Pyrochroinae using the European species Pyrochroa coccinea as a model. Morphological analyses show that the cranial apparatus consists of a concave pit lined with short setae retaining secretions emitted through numerous glandular pores. Ultrastructural investigations reveal the presence of two different class 3 glands (Gl.A and Gl.B), intermixed at the level of the pit but exhibiting distinct features. Gl.A are mainly characterised by short conducting canals, rounded nuclei and electrondense vesicles while Gl.B are characterised by long conducting canals, irregular nuclei, vesicles containing a particulate substance and a multifolded plasma membrane. Observations of sexual behaviour are also reported for P. coccinea and compared to N. flabellata, confirming the involvement of cranial apparatus secretions in courtship behaviour.

Blister Beetle Dermatitis Outbreaks in Mali.

INTRODUCTION: Meloidae are distributed in temperate and arid regions but are also common in subtropical and tropical savannahs. These insects contain cantharidin, a vesicant substance that can cause poisoning by ingestion and dermatitis by direct contact. MATERIAL AND METHODS: We describe recurrent Meloidae-related dermatitis outbreaks and their health impact by analyzing medical consultation records and meteorological data. RESULTS: Between 2015 and 2019, dermatitis outbreaks took place at a French military base at the end of the rainy season, from July to August, with 100 cases reported in 2015, 74 in 2017, 100 in 2018, and 36 in 2019. In 2017, the incidence rate was 4.4% for the base's population. Initial medical consultations represented 31.5% of total medical care activity. Meloidae were identified as Cyaneolytta fryi. CONCLUSIONS: These outbreaks of burn-like lesions, although clinically benign, can place a considerable burden on the medical activity of health care facilities. The diagnosis of Meloidae dermatitis is exclusively anamnestic and clinical and requires reported contact with the insect. The treatment protocol is that of standard burn care, and the best preventive measure is to avoid bright white lights. Military personnel, foreign workers, and travelers venturing into the Sahel should be warned of the risks associated with these beetles.

Repeatability and reproducibility of MRI-radiomic features: A phantom experiment on a 1.5 T scanner.

PURPOSE: Aim of this study is to assess the repeatability of radiomic features on magnetic resonance images (MRI) and their stability to variations in time of repetition (TR), time of echo (TE), slice thickness (ST), and pixel spacing (PS) using vegetable phantoms. METHODS: The organic phantom was realized using two cucumbers placed inside a cylindrical container, and the analysis was performed using T1-weighted (T1w), T2-weighted (T2w), and diffusion-weighted images. One dataset was used to test the repeatability of the radiomic features, whereas other four datasets were used to test the sensitivity of the different MRI sequences to image acquisition parameters (TR, TE, ST, and PS). Four regions of interest (ROIs) were segmented: two for the central part of each cucumber and two for the external parts. Radiomic features were extracted from each ROI using Pyradiomics. To assess the effect of preprocessing on the reduction of variability, features were extracted both before and after the preprocessing. The coefficient of variation (CV) and intra-class correlation coefficient (ICC) were used to evaluate variability. RESULTS: The use of intensity standardization increased the stability for the first-order statistics features. Shape and size features were always stable for all the analyses. Textural features were particularly sensitive to changes in ST and PS, although some increase in stability could be obtained by voxel size resampling. When images underwent image preprocessing, the number of stable features (ICC > 0.75 and mean absolute CV < 0.3) was 33 for apparent diffusion coefficient (ADC), 52 for T1w, and 73 for T2w. CONCLUSIONS: The most critical source of variability is related to changes in voxel size (either caused by changes in ST or PS). Preprocessing increases features stability to both test-retest and variation of the image acquisition parameters for all the types of analyzed MRI (T1w, T2w, and ADC), except for ST.

Artificial Intelligence Applied to Chest X-ray: A Reliable Tool to Assess the Differential Diagnosis of Lung Pneumonia in the Emergency Department.

BACKGROUND: Considering the large number of patients with pulmonary symptoms admitted to the emergency department daily, it is essential to diagnose them correctly. It is necessary to quickly solve the differential diagnosis between COVID-19 and typical bacterial pneumonia to address them with the best management possible. In this setting, an artificial intelligence (AI) system can help radiologists detect pneumonia more quickly. METHODS: We aimed to test the diagnostic performance of an AI system in detecting COVID-19 pneumonia and typical bacterial pneumonia in patients who underwent a chest X-ray (CXR) and were admitted to the emergency department. The final dataset was composed of three sub-datasets: the first included all patients positive for COVID-19 pneumonia (n = 1140, namely "COVID-19+"), the second one included all patients with typical bacterial pneumonia (n = 500, "pneumonia+"), and the third one was composed of healthy subjects (n = 1000). Two radiologists were blinded to demographic, clinical, and laboratory data. The developed AI system was used to evaluate all CXRs randomly and was asked to classify them into three classes. Cohen's κ was used for interrater reliability analysis. The AI system's diagnostic accuracy was evaluated using a confusion matrix, and 95%CIs were reported as appropriate. RESULTS: The interrater reliability analysis between the most experienced radiologist and the AI system reported an almost perfect agreement for COVID-19+ (κ = 0.822) and pneumonia+ (κ = 0.913). We found 96% sensitivity (95% CIs = 94.9-96.9) and 79.8% specificity (76.4-82.9) for the radiologist and 94.7% sensitivity (93.4-95.8) and 80.2% specificity (76.9-83.2) for the AI system in the detection of COVID-19+. Moreover, we found 97.9% sensitivity (98-99.3) and 88% specificity (83.5-91.7) for the radiologist and 97.5% sensitivity (96.5-98.3) and 83.9% specificity (79-87.9) for the AI system in the detection of pneumonia+ patients. Finally, the AI system reached an accuracy of 93.8%, with a misclassification rate of 6.2% and weighted-F1 of 93.8% in detecting COVID+, pneumonia+, and healthy subjects. CONCLUSIONS: The AI system demonstrated excellent diagnostic performance in identifying COVID-19 and typical bacterial pneumonia in CXRs acquired in the emergency setting.

Postoperative atrial fibrillation in mitral valve surgery is not benign.

OBJECTIVE: Postoperative atrial fibrillation (POAF) is common after cardiac surgery and is often considered to be benign despite recent data suggesting worse outcomes. There are no guidelines for the amount of POAF that triggers anticoagulation or for postoperative surveillance. We examined the rate of POAF, incidence of neurologic events, development of permanent atrial fibrillation, and mortality in patients undergoing isolated mitral valve surgery at a Mitral Foundation reference center. METHODS: This is a retrospective cohort study of 922 adult patients from 2011 to 2022 with no preoperative history of arrhythmias. Multivariable logistic regression was used to identify independent risk factors for the primary outcomes. Kaplan-Meier analysis and Cox proportional-hazards model were used to characterize long-term survival. RESULTS: The incidence of POAF was 39%. Median follow-up was 4.9 months (interquartile range, 1.1-42.6 months). Diabetes (odds ratio [OR], 2.2; 95% CI, 1.2-4.1; P = .01) and increasing age (OR, 1.1; 95% CI, 1.0-1.1; P < .001) were risk factors for POAF, whereas New York Heart Association functional class was not. POAF was a risk factor for the development of permanent atrial fibrillation (OR, 3.2; 95% CI 1.9-5.4; P < .001), which was associated with increased risk of neurologic events (OR, 3.8; 95% CI, 1.5-9.7; P = .004). Ultimately, patients with POAF had worse unadjusted (P < .001) and adjusted long-term mortality (hazard ratio, 1.8; 95% CI, 1.1-3.1; P = .03). CONCLUSIONS: POAF is associated with an increased rate of neurologic events, portends development of permanent atrial fibrillation, and is associated with worse long-term survival. POAF is not benign and carries a long-term mortality implication.

Prognostic radiomic signature for head and neck cancer: Development and validation on a multi-centric MRI dataset.

BACKGROUND AND PURPOSE: Prognosis in locally advanced head and neck cancer (HNC) is currently based on TNM staging system and tumor subsite. However, quantitative imaging features (i.e., radiomic features) from magnetic resonance imaging (MRI) may provide additional prognostic info. The aim of this work is to develop and validate an MRI-based prognostic radiomic signature for locally advanced HNC. MATERIALS AND METHODS: Radiomic features were extracted from T1- and T2-weighted MRI (T1w and T2w) using the segmentation of the primary tumor as mask. In total 1072 features (536 per image type) were extracted for each tumor. A retrospective multi-centric dataset (n = 285) was used for features selection and model training. The selected features were used to fit a Cox proportional hazard regression model for overall survival (OS) that outputs the radiomic signature. The signature was then validated on a prospective multi-centric dataset (n = 234). Prognostic performance for OS and disease-free survival (DFS) was evaluated using C-index. Additional prognostic value of the radiomic signature was explored. RESULTS: The radiomic signature had C-index = 0.64 for OS and C-index = 0.60 for DFS in the validation set. The addition of the radiomic signature to other clinical features (TNM staging and tumor subsite) increased prognostic ability for both OS (HPV- C-index 0.63 to 0.65; HPV+ C-index 0.75 to 0.80) and DFS (HPV- C-index 0.58 to 0.61; HPV+ C-index 0.64 to 0.65). CONCLUSION: An MRI-based prognostic radiomic signature was developed and prospectively validated. Such signature can successfully integrate clinical factors in both HPV+ and HPV- tumors.

Coronary artery plaque rupture and erosion: Role of wall shear stress profiling and biological patterns in acute coronary syndromes.

AIMS: Wall shear stress (WSS) is involved in coronary artery plaque pathological mechanisms and modulation of gene expression. This study aims to provide a comprehensive haemodynamic and biological description of unstable (intact-fibrous-cap, IFC, and ruptured-fibrous-cap, RFC) and stable (chronic coronary syndrome, CCS) plaques and investigate any correlation between WSS and molecular pathways. METHODS AND RESULTS: We enrolled 24 CCS and 25 Non-ST Elevation Myocardial Infarction-ACS patients with IFC (n = 11) and RFC (n = 14) culprit lesions according to optical coherence tomography analysis. A real-time PCR primer array was performed on peripheral blood mononuclear cells for 17 different molecules whose expression is linked to WSS. Computational fluid dynamics simulations were performed in high-fidelity 3D-coronary artery anatomical models for three patients per group. A total of nine genes were significantly overexpressed in the unstable patients as compared to CCS patients, with no differences between IFC and RFC groups (GPX1, MMP1, MMP9, NOS3, PLA2G7, PI16, SOD1, TIMP1, and TFRC) while four displayed different levels between IFC and RFC groups (TNFα, ADAMTS13, EDN1, and LGALS8). A significantly higher WSS was observed in the RFC group (p < 0.001) compared to the two other groups. A significant correlation was observed between TNFα (p < 0.001), EDN1 (p = 0.036), and MMP9 (p = 0.005) and WSS values in the RFC group. CONCLUSIONS: Our data demonstrate that IFC and RFC plaques are subject to different WSS conditions and gene expressions, suggesting that WSS profiling may play an essential role in the plaque instability characterization with relevant diagnostic and therapeutic implications in the era of precision medicine.

Refining Tumor Treatment in Sinonasal Cancer Using Delta Radiomics of Multi-Parametric MRI after the First Cycle of Induction Chemotherapy.

BACKGROUND: Response to induction chemotherapy (IC) has been predicted in patients with sinonasal cancer using early delta radiomics obtained from T1- and T2-weighted images and apparent diffusion coefficient (ADC) maps, comparing results with early radiological evaluation by RECIST. METHODS: Fifty patients were included in the study. For each image (at baseline and after the first IC cycle), 536 radiomic features were extracted as follows: semi-supervised principal component analysis components, explaining 97% of the variance, were used together with a support vector machine (SVM) to develop a radiomic signature. One signature was developed for each sequence (T1-, T2-weighted and ADC). A multiagent decision-making algorithm was used to merge multiple signatures into one score. RESULTS: The area under the curve (AUC) for mono-modality signatures was 0.79 (CI: 0.65-0.88), 0.76 (CI: 0.62-0.87) and 0.93 (CI: 0.75-1) using T1-, T2-weighted and ADC images, respectively. The fuse signature improved the AUC when an ADC-based signature was added. Radiological prediction using RECIST criteria reached an accuracy of 0.78. CONCLUSIONS: These results suggest the importance of early delta radiomics and of ADC maps to predict the response to IC in sinonasal cancers.

Male Accessory Glands of Blister Beetles and Cantharidin Release: A Comparative Ultrastructural Analysis.

Members of the family Meloidae are known to produce cantharidin, a highly toxic monoterpene found in their hemolymph and exuded as droplets capable of deterring many predators. As a nuptial gift, males transfer large amounts of cantharidin to females via a spermatophore, which is formed by specific accessory glands containing high concentrations of this terpene. Using light, electron and ion beam microscopy, the ultrastructural features of the three pairs of male accessory glands as well as the glandular part of the vasa deferentia were comparatively investigated in seven species of blister beetles belonging to five different tribes and two subfamilies. All gland pairs examined share common features such as mesodermal derivation, the presence of muscle sheath, a developed rough endoplasmic reticulum, abundant mitochondria, secretory vesicles, and microvillated apical membranes. Within the same species, glands exhibit distinctive features, suggesting that each pair is responsible for the formation of a specific substance. The vasa deferentia, while showing many similarities within the family, often exhibit features unique to each of the individual species investigated, whereas the accessory glands of the first and second pairs display the highest degree of ultrastructural variability. A comparison across the species shows an interesting constancy limited to ultrastructural features in the third pair of accessory glands. The similarities and differences among the species are discussed in the light of the available literature and in relation to the potential role that blister beetles' male accessory glands could play in the storage and management of cantharidin.