Acquisition Of Sequences Research Articles

Unsupervised clustering analysis-based characterization of spatial profiles of inaccuracy in apparent diffusion coefficient values with varying acquisition plan orientation and diffusion weighting gradient direction – a large multicenter phantom study

This large multicenter study of 37 magnetic resonance imaging scanners aimed at characterizing, for the first time, spatial profiles of inaccuracy (namely, Δ-profiles) in apparent diffusion coefficient (ADC) values with varying acquisition plan orientation and diffusion weighting gradient direction, using a statistical approach exploiting unsupervised clustering analysis. A diffusion-weighted imaging (DWI) protocol (b-value: 0-200-400-600-800-1000 s mm-2) with different combinations of acquisition plan orientation (axial/sagittal/coronal) and diffusion weighting gradient direction (anterior-posterior/left-right/feet-head) was acquired on a standard water phantom. For each acquisition setup, Δ-profiles along the 3 main orthogonal directions were characterized by fitting data with a second order polynomial function (ar2+ br + c). Moreover, for each Δ-profile, the maximum minus minimum of the fitting function (δmax) was calculated. The parametersa,b,c, andδmaxshowed some significant variations between scanner systems by different manufacturers or with different static magnetic field strengths, as well as between different acquisition/estimation setups. Unsupervised clustering analysis showed two evident clusters with significantly different values of parametera(p< 0.0001), which can be grouped by acquisition protocol/Δ-profile direction but not scanner system. The results of ∆-profiles confirm an appreciable inter-scanner variability in ADC measurement and corroborate the importance of guarantying the reliability of ADC estimations in clinical or research studies, considering for each scanner system the specific acquisition sequence in terms of acquisition plan orientation and diffusion weighting gradient direction.

Unbiased Analysis of Knee Cartilage Thickness Change Over Three Years Post-Treatment with Sprifermin vs. Placebo – A Post-Hoc Analysis from the Phase II FORWARD Study

ObjectivePost-treatment cartilage morphometry in the FORWARD study was performed without blinding to MRI acquisition order, involving potential reader bias. Here we obtained unbiased estimates of cartilage change post-treatment, reading year (Y)2 and Y5 MRIs with blinding to time point. We studied whether post-treatment cartilage thickness change differed between sprifermin- and placebo-treated knees. MethodsFORWARD was a 5-year randomized control trial in 549 knee osteoarthritis patients. Here, Y2/Y5 images were analyzed with blinding to relative temporal order and treatment group. Cartilage change during Y2→Y5 was obtained in 337 participants: n=57 treated with placebo intra-articular injections every 6 months (q6M); n=69 with 30μg sprifermin every 12 months (q12M), n=67 with 30μg q6M, n=73 with 100μg q12M, and n=71 with 100μg q6M between baseline (BL) and 18M. Total femorotibial joint (TFTJ) cartilage thickness was the primary analytic focus. ResultsTFTJ cartilage thickness change during Y2→Y5 was -26μm (SD64; 95%CI -32,-19) across the cohort; no statistically significant difference (p=0.80) was observed between treatment or placebo arms (one-way ANOVA). All groups lost cartilage, but the treatment-related difference in cartilage thickness in Sprifermin arms relative to placebo at Y2 was maintained until Y5. Annualized cartilage change in placebo participants was -8.2μm (SD21; 95%CI -14,-2.5) during Y2→Y5 vs. -5.4μm (SD27; 95%CI -13,1.8) during BL→Y2; no significant difference was identified (t-test). ConclusionFORWARD is the first study evaluating post-treatment benefits of a potential disease modifying osteoarthritis drug. Cartilage thickness gained with 100μg sprifermin at Y2 is maintained to Y5 and thus appears viable and sustainable.This is a post-hoc analysis of the FORWARD trial: ClinicalTrials.gov Identifier: NCT01919164

Evaluating the reproducibility of a deep learning algorithm for the prediction of retinal age.

Recently, a deep learning algorithm (DLA) has been developed to predict the chronological age from retinal images. The Retinal Age Gap (RAG), a deviation between predicted age from retinal images (Retinal Age, RA) and chronological age, correlates with mortality and age-related diseases. This study evaluated the reliability and accuracy of RA predictions and analyzed various factors that may influence them. We analyzed two groups of participants: Intravisit and Intervisit, both imaged by color fundus photography. RA was predicted using an established algorithm. The Intervisit group comprised 26 subjects, imaged in two sessions. The Intravisit group had 41 subjects, of whom each eye was photographed twice in one session. The mean absolute test-retest difference in predicted RA was 2.39years for Intervisit and 2.13years for Intravisit, with the latter showing higher prediction variability. The chronological age was predicted accurately from fundus photographs. Subsetting image pairs based on differential image quality reduced test-retest discrepancies by up to 50%, but mean image quality was not correlated with retest outcomes. Marked diurnal oscillations in RA predictions were observed, with a significant overestimation in the afternoon compared to the morning in the Intravisit cohort. The order of image acquisition across imaging sessions did not influence RA prediction and subjective age perception did not predict RAG. Inter-eye consistency exceeded 3years. Our study is the first to explore the reliability of RA predictions. Consistent image quality enhances retest outcomes. The observed diurnal variations in RA predictions highlight the need for standardized imaging protocols, but RAG could soon be a reliable metric in clinical investigations.

Spectral Analysis of MRI Sound Signal

Magnetic Resonance Imaging (MRI) is a very versatile diagnostic tool for non-invasive analysis of human organ functions, without use of ionizing radiations. Loud operating sound is the major challenge associated with the MRI technology, reaching up to 130&amp;nbsp;dB. This paper analyses and compares the spectral properties of acoustic noise produced in the examination room of the mobile imaging trailer based 1.5 Tesla MRI system, during different scanning sequences of image acquisition. The analysis is useful in understanding the dynamic behavior of the sound generated inside the examination room to develop the noise reduction strategy.

AI-Powered Biodiversity Assessment: Species Classification via DNA Barcoding and Deep Learning

Only 1.2 million out of an estimated 8.7 million species on Earth have been fully classified through taxonomy. As biodiversity loss accelerates, ecologists are urgently revising conservation strategies, but the “taxonomic impediment” remains a significant barrier, limiting effective access to and understanding of taxonomic data for many researchers. As sequencing technologies advance, short DNA sequence fragments increasingly serve as DNA barcodes for species identification. Rapid acquisition of DNA sequences from diverse organisms is now possible, highlighting the increasing significance of DNA sequence analysis tools in species identification. This study introduces a new approach for species classification with DNA barcodes based on an ensemble of deep neural networks (DNNs). Several techniques are proposed and empirically evaluated for converting raw DNA sequence data into images fed into the DNNs. The best-performing approach is obtained by representing each pair of DNA bases with the value of a related physicochemical property. By utilizing different physicochemical properties, we can create an ensemble of networks. Our proposed ensemble obtains state-of-the-art performance on both simulated and real datasets.

Subliminal priming modulates motor sequence learning.

Sequential behaviour is underpinned by the selection and inhibition of movement at appropriate points in space and time. Sequences embedded among movement patterns must be learnt, yet the contribution of response selection and inhibition to the acquisition of motor sequences remains poorly understood. We addressed this issue by overlaying the serial reaction time task (SRTT) with subliminal masked primes that differentially weighed response tendencies. In Experiment 1, twenty-four healthy young adults, and in Experiment 2, thirty-six participants, performed the SRTT with congruent (same position), incongruent (different position), or neutral (no prime) subliminal masked primes. Each condition featured an embedded eight-digit (Experiment 1) or ten-digit (Experiment 2) second-order sequence, with conditions presented in counterbalanced order during a single session. Sequence specific learning was observed under neutral and congruent prime conditions. Independent of sequence awareness, congruent primes reduced initial response latency and led to greater sequence specific learning compared with neutral primes. However, incongruent primes appeared to attenuate learning (Experiment 1). These results demonstrate that prime congruency modulates sequence specific learning below the threshold of conscious awareness. Congruent primes may elevate the salience of stimulus-response compounds and accentuate learning, but at the cost of increased awareness. Incongruent primes, and the induction of response conflict, attenuate sequence specific learning (Experiment 1) and may prevent the formation of cross-temporal contingencies necessary for implicit motor sequence learning.

Functional localization of the human auditory and visual thalamus using a thalamic localizer functional magnetic resonance imaging task

Abstract Functional magnetic resonance imaging (fMRI) of the auditory and visual sensory systems of the human brain is an active area of investigation in the study of human health and disease. The medial geniculate nucleus (MGN) and lateral geniculate nucleus (LGN) are key thalamic nuclei involved in the processing and relay of auditory and visual information, respectively, and are the subject of blood-oxygen-level-dependent (BOLD) fMRI studies of neural activation and functional connectivity in human participants. However, localization of BOLD fMRI signal originating from neural activity in MGN and LGN remains a technical challenge, due, in part, to the poor definition of boundaries of these thalamic nuclei in standard T1-weighted and T2-weighted magnetic resonance imaging sequences. Here, we report the development and evaluation of an auditory and visual sensory thalamic localizer (TL) fMRI task that produces participant-specific functionally-defined regions of interest (fROIs) of both MGN and LGN, using 3 Tesla multiband fMRI and a clustered-sparse temporal acquisition sequence, in less than 16 minutes of scan time. We demonstrate the use of MGN and LGN fROIs obtained from the TL fMRI task in standard resting-state functional connectivity (RSFC) fMRI analyses in the same participants. In RSFC analyses, we validated the specificity of MGN and LGN fROIs for signals obtained from primary auditory and visual cortex, respectively, and benchmarked their performance against alternative atlas- and segmentation-based localization methods. The TL fMRI task and analysis code (written in Presentation and MATLAB, respectively) have been made freely available to the wider research community.

Repeatability of diffusion kurtosis tensor parameters in muscles of the lower legs.

The aim of this study was to provide measurements from and investigate the repeatability of diffusion kurtosis tensor parameters in the muscles of the lower legs. Test-retest acquisition of a kurtosis tensor sequence was performed in 13 healthy volunteers. Quantitative kurtosis tensor parameters were derived, and repeatability of each parameter was evaluated by muscle group and over the whole muscle through intraclass correlation coefficient (ICC) and within-subject coefficient of variation (wsCV). Bland-Altman analysis was also conducted. Differences in parameter values by muscle group were investigated through an analysis of variance. Axial kurtosis and radial kurtosis values from the test data were 0.63 ± 0.04 and 0.70 ± 0.05, respectively. Kurtosis tensor parameters from all muscle groups and over the whole muscle had wsCV below 15%. ICC for the parameters from most muscle groups was above 85%, with the lowest ICC over the whole muscle being 88.39%. The medial gastrocnemius and extensor digitorum longus showed highest repeatability. Mean, axial, and radial diffusivity had higher wsCV despite being lower-order terms than kurtosis. This study sought to examine the repeatability of diffusion kurtosis tensor-derived parameters in the legs and verify that they could potentially be used as longitudinal imaging metrics. wsCV values from test-retest data indicated high repeatability throughout all examined muscle groups. There were minimal differences in kurtosis and diffusivity parameters between muscle groups in this healthy volunteer cohort.

SYMPATHIQUE: image-based tracking of symptoms and monitoring of pathogenesis to decompose quantitative disease resistance in the field

BackgroundQuantitative disease resistance (QR) is a complex, dynamic trait that is most reliably quantified in field-grown crops. Traditional disease assessments offer limited potential to disentangle the contributions of different components to overall QR at critical crop developmental stages. Yet, a better functional understanding of QR could greatly support a more targeted, knowledge-based selection for QR and improve predictions of seasonal epidemics. Image-based approaches together with advanced image processing methodologies recently emerged as valuable tools to standardize relevant disease assessments, increase measurement throughput, and describe diseases along multiple dimensions.ResultsWe present a simple, affordable, and easy-to-operate imaging set-up and imaging procedure for in-field acquisition of wheat leaf image sequences. The development of Septoria tritici blotch and leaf rusts was monitored over time via robust methods for symptom detection and segmentation, spatial alignment of images, symptom tracking, and leaf- and symptom characterization. The average accuracy of the spatial alignment of images in a time series was approximately 5 pixels (~ 0.15 mm). Leaf-level symptom counts as well as individual symptom property measurements revealed stable patterns over time that were generally in excellent agreement with visual impressions. This provided strong evidence for the robustness of the methodology to variability typically inherent in field data. Contrasting patterns in the number of lesions resulting from separate infection events and lesion expansion dynamics were observed across wheat genotypes. The number of separate infection events and average lesion size contributed to different degrees to overall disease intensity, possibly indicating distinct and complementary mechanisms of QR.ConclusionsThe proposed methodology enables rapid, non-destructive, and reproducible measurement of several key epidemiological parameters under field conditions. Such data can support decomposition and functional understanding of QR as well as the parameterization, fine-tuning, and validation of epidemiological models. Details of pathogenesis can translate into specific symptom phenotypes resolvable using time series of high-resolution RGB images, which may improve biological understanding of plant-pathogen interactions as well as interactions in disease complexes.

Real-time non-line-of-sight computational imaging using spectrum filtering and motion compensation.

Non-line-of-sight (NLOS) imaging aims at recovering the shape and albedo of hidden objects. Despite recent advances, real-time video of complex and dynamic scenes remains a major challenge owing to the weak signal of multiply scattered light. Here we propose and demonstrate a framework of spectrum filtering and motion compensation to realize high-quality NLOS video for room-sized scenes. Spectrum filtering leverages a wave-based model for denoising and deblurring in the frequency domain, enabling computational image reconstruction with a small number of sampling points. Motion compensation tailored with an interleaved scanning scheme can compute high-resolution live video during the acquisition of low-quality image sequences. Together, we demonstrate live NLOS videos at 4 fps for a variety of dynamic real-life scenes. The results mark a substantial stride toward real-time, large-scale and low-power NLOS imaging and sensing applications.

Oculomotor functional connectivity associated with motor sequence learning.

Acquisition of learned motor sequences involves saccades directed toward the goal to gather visual information prior to reaching. While goal-directed actions involve both eye and hand movements, therole of brain areas controlling saccades during motor sequence learning is still unclear. This study aimed to determine whether resting-state functional connectivity of oculomotor regions is associated with behavioral changes resulting from motor sequence learning. We investigated connectivity between oculomotor control regions and candidate regions involved in oculomotor control and motor sequence learning. Twenty adults had brain scans before 3 days of motor task practice and after a 24-hour retention test, which was used to assess sequence-specific learning. During testing, both saccades and reaches were tracked. Stronger connectivity in multiple oculomotor regions prior to motor task practice correlated with greater sequence-specific learning for both saccades and reaches. A more negative connectivity change involving oculomotor regions from pre- to post-training correlated with greater sequence-specific learning for both saccades and reaches. Overall, oculomotor functional connectivity was associated with themagnitude of behavioral change resulting from motor sequence learning, providing insight into thefunction of the oculomotor system during motor sequence learning.

MASTERING SWIMMING AND TECHNICAL SKILLS IN THE FRAMEWORK OF INITIAL WATER POLO TRAINING

The purpose of the article is to consider the content and sequence of acquisition of swimming and technical skills by children and adolescents as part of initial water polo training, to provide relevant methodological recommendations to children’s coaches. Methods applied: analysis of scientific sources, pedagogical observation, generalization of coaching experience, synthesis of empirical information, classification and typology, and comparison. The article describes water polo swimming styles and some specific techniques of initial swimming training, including Head-Up Freestyle and Head-Up Backstroke, Trudgen and Sidestroke, swimming in place and walking in the water using various techniques such as Eggbeater Kick, Sculling or Breaststroke Kick, lifting and holding the body above the water and jumping out of the water, start for performing a dash, stopping, turning, and lunging. After mastering swimming skills, the initial training focuses on the technique of working with the ball. It is necessary to study the technical elements of water polo in compliance with the basic didactic principles, in a clear sequence of learning techniques from easier to more difficult. The author recommends switching to technical training no earlier than 10 years of age and devoting 2-3 years to mastering technical techniques. In the process of technical training, young water polo players consistently learn the techniques of picking up the ball from the water in different ways, dribbling the ball, catching it, transferring the ball from one hand to other, different types of Shooting for passing. Exercises for mastering the technical skills of water polo should be selected and used methodically competently. It is desirable to perform some of them first on land, and only then in water, first without movement, and only then in motion, so that the conditions for performing the exercises gradually approach those of the game. To make water polo training more interesting and attractive for children, the author recommends using Splashball as a modified version of water polo for beginners.

Prevalence of cardiomyopathies and myocardial scar in patients with non-complicated premature ventricular beats: a CMR study

Abstract Introduction Frequent or symptomatic premature ventricular beats (PVBs) in subjects with no personal or family history of cardiac disease or sudden death is a recurrent motive for cardiac magnetic resonance (CMR) prescriptions. This represents a significant burden on healthcare services, given the low availability of CMR technique. If CMR is a recommended imaging modality in patients with history of cardiac arrest due to ventricular arrhythmia, sustained ventricular arrhythmias or when first-line tests are abnormal, its diagnostic value in this specific setting has not been evaluated. Purpose To determine the prevalence of significant CMR abnormalities (myocardial fibrosis, arrhythmogenic cardiomyopathies) in patients with no personal nor family history of cardiac disease and non-complicated PVBs. Methods Between September 2010 and July 2021, 416 healthy adults with no personal nor family cardiac disease history underwent CMR at our institution to explore non complicated PVBs, and were retrospectively included (Figure 1). Right and left ventricular (RV/LV) function and dimensions were systematically evaluated on CMR, as the presence of myocardial late gadolinium enhancement (LGE). Criteria for cardiomyopathies (hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), ARVD), the presence and location of myocardial fibrosis were looked after. Results A total of 605 patients were referred for CMR to explore frequent PVBs, representing 14% of all tests performed during this period. Among them, 12 patients (3%) presented significant myocardial abnormalities possibly related to PVBs: 2 patients had sequelae of myocardial infarction and 3 of myocarditis, 1 patient had criteria of HCM and 1 of ARVD, finally 5 presented non-specific myocardial fibrosis (septal mid-wall LGE). In addition, after a mean follow-up of 5 years, there was no death in patients with abnormal CMR, and only 2 patients underwent transcatheter ablation for focal non complicated but symptomatic PVBs. There was no hospitalization for heart failure. Conclusion In patients with non-complicated PVBs and no history of cardiac disease, the rate of cardiomyopathy pattern or myocardial scar on CMR is very low (3%). In this specific population, events were very rare: frequent isolated PVBs, even when associated with myocardial abnormalities, were a benign condition in our study. Given the high volume of patients referred for this indication in daily practice (14% of total CMRs in our center), the limited availability and high costs of CMR, and the difficulties of CMR sequences acquisition in the context of frequent PVBs (possibly leading to misdiagnosis), these data suggest that we should refine the selection of patients undergoing CMR for PVBs exploration.

Embodied Semantics: Early Simultaneous Motor Grounding in First and Second Languages.

Although the embodiment of action-related language is well-established in the mother tongue (L1), less is known about the embodiment of a second language (L2) acquired later in life through formal instruction. We used the high temporal resolution of ERPs and topographic ERP analyses to compare embodiment in L1 and L2 and to investigate whether L1 and L2 are embodied with different strengths at different stages of linguistic processing. Subjects were presented with action-related and non-action-related verbs in a silent reading task. Subjects were late French-German and German-French bilinguals, respectively, and we could therefore collapse across languages to avoid common confounding between language (French and German) and order of acquisition (L1, L2). We could show distinct effects of embodiment and language. Embodiment affected only the sensory and lexical stages of processing with increased strength and power of the N1 component for motor vs. non-motor verbs, and language affected the lexical and semantic stages of processing with stronger P2/N400 components for L2 than for L1. Non-motor verbs elicited a stronger P1 component in L2. Our results suggest that processing words in L2 requires more effortful processing. Importantly, L1 and L2 are not embodied differently, and embodiment affects early and similar stages of processing in L1 and L2, possibly integrating other process of action-language interaction.

Is Bilinguality an Illusive Concept?

Background and Objective: In an effort to study bilinguality, researchers in this field have often compared bilinguals with monolinguals, generally considering each group to be a homogeneous, monolithic body with no discernable within-group individual differences. This approach overlooks the various levels of proficiency among bilinguals, the age and order of acquisition of each of their languages, as well as their language history, and daily usage. Although monolinguals may not be conversant, some may still at least partially comprehend a second language. By failing to actively consider and collect more details about a variety of participant language attributes, researcher assumptions can lead to conclusions that are not a true reflection of the similarities and differences between monolinguals and bilinguals. A number of studies have found bilingual advantage in health-related outcomes as well as performance on cognitive tasks. All these reported findings are based on the performance of participants who may or may not be true bilinguals consequently impacting the results of this research [9,11]. Recommendations: The impact of considering a wide variable of participant characteristics in bilinguality research, including age and order of acquisition, daily usage, and fluency is examined. In addition, a recently proposed psychometric model that evaluates the above variables is discussed. Finally, recommendations are made on how to further improve the standards of research in bilinguality, including performing objective fluency testing, and asking detailed questions about participants’ complete language history.

Functional Localization of the Human Auditory and Visual Thalamus Using a Thalamic Localizer Functional Magnetic Resonance Imaging Task.

Functional magnetic resonance imaging (fMRI) of the auditory and visual sensory systems of the human brain is an active area of investigation in the study of human health and disease. The medial geniculate nucleus (MGN) and lateral geniculate nucleus (LGN) are key thalamic nuclei involved in the processing and relay of auditory and visual information, respectively, and are the subject of blood-oxygen-level-dependent (BOLD) fMRI studies of neural activation and functional connectivity in human participants. However, localization of BOLD fMRI signal originating from neural activity in MGN and LGN remains a technical challenge, due in part to the poor definition of boundaries of these thalamic nuclei in standard T1-weighted and T2-weighted magnetic resonance imaging sequences. Here, we report the development and evaluation of an auditory and visual sensory thalamic localizer (TL) fMRI task that produces participant-specific functionally-defined regions of interest (fROIs) of both MGN and LGN, using 3 Tesla multiband fMRI and a clustered-sparse temporal acquisition sequence, in less than 16 minutes of scan time. We demonstrate the use of MGN and LGN fROIs obtained from the TL fMRI task in standard resting-state functional connectivity (RSFC) fMRI analyses in the same participants. In RSFC analyses, we validated the specificity of MGN and LGN fROIs for signals obtained from primary auditory and visual cortex, respectively, and benchmark their performance against alternative atlas- and segmentation-based localization methods. The TL fMRI task and analysis code (written in Presentation and MATLAB, respectively) have been made freely available to the wider research community.

Highly efficient image navigator based 3D whole-heart cardiac MRA at 0.55T.

To develop and evaluate a highly efficient free-breathing and contrast-agent-free three-dimensional (3D) whole-heart Cardiac Magnetic Resonance Angiography (CMRA) sequence at 0.55T. Free-breathing whole-heart CMRA has been previously proposed at 1.5 and 3T. Direct application of this sequence to 0.55T is not possible due to changes in the magnetic properties of the tissues. To enable free-breathing CMRA at 0.55T, pulse sequence design and acquisition parameters of a previously proposed whole-heart CMRA framework are optimized via Bloch simulations. Image navigators (iNAVs) are used to enable nonrigid respiratory motion-correction and 100% respiratory scan efficiency. Patch-based low-rank denoising is employed to accelerate the scan and account for the reduced signal-to-noise ratio at 0.55T. The proposed approach was evaluated on 11 healthy subjects. Image quality was assessed by a clinical expert (1: poor to 5: excellent) for all intrapericardiac structures. Quantitative evaluation was performed by assessing the vessel sharpness of the proximal right coronary artery (RCA). Optimization resulted in an imaging flip angle of , fat saturation flip angle of , and six k-space lines for iNAV encoding. The relevant cardiac structures and main coronary arteries were visible in all subjects, with excellent image quality (mean ) and minimal artifacts (mean ), with RCA vessel sharpness ( ) comparable to previous studies at 1.5T. The proposed approach enables 3D whole-heart CMRA at 0.55T in a 6-min scan ( ), providing excellent image quality, minimal artifacts, and comparable vessel sharpness to previous 1.5T studies. Future work will include the evaluation of the proposed approach in patients with cardiovascular disease.

Myeloid neoplasm with concurrent BCR::ABL1 translocation, and JAK2 and SF3B1 co-mutations with severe fibrosis: a case report

Abstract Introduction/Objective Myeloproliferative neoplasms (MPNs) arise from hematopoietic stem cells with somatically altered tyrosine kinase signaling. Classification of MPNs is based on hematologic, histopathologic and molecular characteristics including the presence of BCR::ABL1 and JAK2 V617F. Methods/Case Report We present a 72-year-old male with a myeloid neoplasm and severe fibrosis, with concurrent BCR::ABL1 translocation, and co-mutations in JAK2 and SF3B1. Initially, the patient was diagnosed with anemia, thrombocytosis and folic acid deficiency and was prescribed supplemental folic acid. At follow up, normocytic anemia and thrombocytosis were seen. Bone marrow biopsy showed overtly fibrotic marrow with maturing trilineage hematopoiesis, markedly increased megakaryopoiesis and ring sideroblasts. Chromosome analysis and sequential GTG-fluorescence in situ hybridization (FISH) of metaphases using the dual-fusion three color probe BCR/ABL1- ASS1 revealed abnormal results. A t(9;22)(q34;q11.2) was detected along with an atypical FISH signal pattern with a single BCR::ABL1 fusion on the derivative chromosome 22 instead of the typical two fusions, resulting in loss of one BCR::ABL1 fusion signal including loss of the ASS1 on the derivative chromosome 9. Next-generation sequencing (NGS) analysis detected double driver mutations, JAK2 p. Val617Phe and SF3B1 p. Lys700Glu in the patient. JAK2 V617F mutation was further confirmed by real-time quantitative PCR (qPCR) with variant allele frequencies of 39.7%. Additionally, the patient was positive for BCR::ABL1 p190 fusion transcript (10%). The presence of JAK2 and SF3B1 co-mutations along with ring sideroblasts and the patient’s clinical presentation suggests the diagnosis of myelodysplastic/myeloproliferative neoplasm with thrombocytosis and SF3B1 mutation. Results (if a Case Study enter NA) NA Conclusion Although, the detection of t(9;22) by chromosome analysis is a diagnostic feature of chronic myeloid leukemia (CML), our case adds to the limited information on co-existence of BCR::ABL1 and JAK2 V617F with SF3B1 mutations in severe fibrosis. The frequency of co-occurrence, the temporal order of acquisition and clonal relationship of these alterations is poorly understood, and it is also unclear for this case since there is no prior bone marrow biopsy or diagnostic work up. Literature search of these rare cases show that some patients with similar findings progress to myelofibrosis as in this patient. It is possible that the presence of two mutated tyrosine kinase genes accelerates disease progression.

New specimens of Bunaia woodwardi Clarke, 1919 (Euchelicerata): a new member of Offacolidae providing insight supporting the Arachnomorpha.

The rapid early diversification of arthropods has made understanding internal relationships within the group fiendish. Particularly unresolved is the origin of Euchelicerata, a clade consisting of the Prosomapoda (comprising the extant Xiphosura and Arachnida and the extinct Chasmataspidida, Eurypterida and synziphosurines) and the extinct Offacolidae. Here we describe new material of the Silurian 'synziphosurine' Bunaia woodwardi Clarke, 1919 that reveals previously unknown features of its ventral anatomy: a pair of elongated chelicerae in the prosoma, followed posteriorly by five pairs of biramous appendages, a first pre-abdomen somite bearing a pair of paddle-like uniramous appendages (exopods) and a ventral pretelsonic process. Phylogenetic analyses retrieve B. woodwardi as a member of Offacolidae closely related to Setapedites abundantis from the Early Ordovician Fezouata Biota. An anatomical comparison of the pretelsonic process of B. woodwardi, also present in Setapedites, with the posterior trunk morphologies of other Offacolidae, Habeliida and Vicissicaudata, suggests a possible homologous appendicular origin. This proposed apomorphic character supports a monophyletic Arachnomorpha, formed of Vicissicaudata, Habeliida and Euchelicerata. The establishment of this new homology could help to clarify the highly enigmatic phylogeny at the base of the euchelicerates as well as the sequence of character acquisition during their early evolution.

Quantifying the effects of the mitochondrial genome on milk production traits in dairy cows: empirical results and modelling challenges

Significant advances in livestock traits have been achieved primarily through selection strategies targeting variation in the nuclear genome, with little attention given to mitogenome variation. We analyzed the influence of the mitogenome on milk production traits of Holstein cattle in Croatia based on strategically generated next-generation sequencing data for 109 cows pedigree-linked to 7115 milk production records (milk, fat and protein yield) from 3006 cows (first 5 lactations). Since little is known about the biology of the relationship between mitogenome variation and production traits, our quantitative genetic modeling was complex. Thus, the proportion of total variance explained by mitogenome inheritance was estimated using 5 different models: (1) cytoplasmic model with maternal lineages (CYTO), (2) haplotypic model with mitogenome sequences (HAPLO), (3) amino acid model with unique amino acid sequences (AMINO), (4) evolutionary model based on a phylogenetic analysis using Bayesian Evolutionary Analysis Sampling Trees phylogenetic analysis (EVOL), and (5) mitogenome SNP model (SNPmt). The polygenic autosomal and X chromosome additive genetic effects based on pedigree were modeled, together with the effects of herd-year-season interaction, permanent environment, location, and age at first calving. The estimated proportions of phenotypic variance explained by mitogenome in 4 different models (CYTO, HAPLO, AMINO, and SNPmt) were found to be substantial given the size of mitogenome, ranging from 5% to 7% for all 3 milk traits. At the same time, a negligible proportion of the phenotypic variance was explained by mitogenome with the EVOL model. Similarly, in all models, no proportion of phenotypic variance was explained by the X chromosome. Although our results should be confirmed in other dairy cattle populations, including a large number of sequenced mitogenomes and nuclear genomes, the potential of utilizing mitogenome information in animal breeding is promising, especially as the acquisition of complete genome sequences becomes cost-effective.