Nuclear Projections Research Articles

Vexas Syndrome: A Complex Necessarily Integrated Diagnosis That Can Benefit from the Help of Deep Learning

Introduction At the end of 2020, a novel entity dubbed VEXAS (for vacuoles, E1 enzyme, X-linked, auto-inflammatory, somatic) was described by Beck et al. (NEJM, 2020). This syndrome is defined molecularly by a mutation of the UBA1 gene that codes for the E1 enzyme, a major actor of ubiquitinylation. From a pathophysiological point of view, UBA1 mutations induce the transcription of a deficient enzyme. Affected cells display an altered ubiquitinylation of misfolded proteins and dysregulated autophagy. This leads in fine to an impairment of several pathways of innate immunity, overproduction of a range of pro-inflammatory cytokines and, more generally, systemic inflammation. Clinical manifestations are pleomorphic and patient-dependent, with reported cases of fever, vasculitis, ophthalmic lesions, chondritis, Sweet syndrome or pulmonary interstitial infiltration. From a hematological point of view, thromboses have also been described as well as several cytologic alterations. The latter include cytopenias of any lineage, myeloid hyperplasia with erythroblastic hypoplasia (M/E) and, notably, the presence of vacuoles essentially in granulocytes and erythroblasts precursors. Some cases are associated to myelodysplastic syndrome (MDS). Here, an in-depth morphological examination of VEXAS and non-VEXAS patients was performed, to delineate and quantify several anomalies. These data were then fed to a deep learning algorithm to evaluate the additional help provided by this artificial intelligence (AI) tool in predicting VEXAS syndrome and orienting further analyses towards the identification of the molecular anomaly. Patients, material and methods To identify diagnostic tools for VEXAS syndrome on blood and bone marrow smears, 4 patient cohorts were analyzed :i) patients with a diagnosis of VEXAS syndrome confirmed by genetic analysis (n=6), ii) MDS patients (n=4), iii) patients with an initial clinical suspicion of VEXAS invalidated by molecular analysis (UBA1 WT: n=3) and iv) 4 healthy controls. For each patient, morphological examination of blood and marrow smears was performed independently by two experts in a blind fashion. In order to guide the diagnosis of the syndrome on the blood smears, a deep learning method was trained in a multilabel classification setting to automatically evaluate the percentages of abnormal polymorphonuclears (PMN). The final dataset was therefore composed of PMN from healthy controls (n=5, 519 images) and from VEXAS syndrome (n=4, 938 images) (DI microscope, Cellavision ®). Results Among the 6 patients with VEXAS syndrome, the main clinical manifestations were: asthenia 100%; fever 83.3%; skin involvement 66.7%; thrombosis 66.7%, chondritis 33.3% and interstitial lung disease 33.3%. The most frequent cytopenia was macrocytic anemia in 66.7% of the patients. Upon morphological examination of blood smears, the following abnormalities were statistically associated with the diagnosis of VEXAS : percentage of pseudo-Pelger PMNs (p=0.003), percentage of PMNs with more than 4 nuclear projections (Barr bodies; p=0.0009), percentage of vacuolated PMNs (p=0.01). On bone marrow smears, compared to the MDS and UBA1 WT cohort, patients with VEXAS syndrome had significantly more PMNs with a pseudo-Pelger aspect (p<0.05), more vacuolization of granular (p<0.05) and erythroblastic (p<0.05) precursors. Different deep learning architectures were tested on blood smear images, with the objectives of distinguishing abnormal PMN from others. The trainings were conducted by cross-validation, and then the algorithm was evaluated on new patients. The metrics used to evaluate algorithm performance were precision, recall, F1-score and Hamming loss. These data allowed to establish a standardized computer aided diagnosis tool. Discussion/conclusion The diagnosis of VEXAS syndrome is complex. This analysis identified cytological features on blood smears leading to the development of a deep learning-based diagnosis algorithm. Promising leads are currently investigated to improve the efficiency and robustness of this deep learning algorithm such as the inclusion of other pathologies in order to train a disease agnostic anomaly detection algorithm, or leveraging data from other modalities as prior knowledge.

Leukocyte morphological changes in COVID-19, a peripheral smear study and analysis at a tertiary health care centre in India

Context: Coronavirus disease 2019 (COVID-19) as the name depicts, a contagious disease caused by the coronavirus that emerged in the year 2019 December, at the Wuhan province in China. The knowledge on the pathogenesis of the disease at the cellular level to correlate with the clinical severity is still evolving. Various clinicopathological features and nature of the disease were gradually identified from those who were affected by the disease. Apart from the clinical presentation, certain investigations played a major role in diagnosing and assessing the severity of the disease. Morphological impact on blood cells was also caused by the severe acute respiratory syndrome-CoV-2 virus. Aim: Morphological analysis of leukocytes on blood samples of COVID19 patients. Settings and Design: Peripheral smear study of blood samples of COVID19 patients admitted at our tertiary care center. Subjects and Methods: Microscopic peripheral smear examination of leukocyte morphology on study samples. Statistical Analysis Used: All the data were recorded and analyzed statistically using Ms-Excel. Results: Our study demonstrated certain acquired pathogenic abnormalities of the leukocytes, that are acquired neutrophilic nuclear projections (ANNP), plasmacytoid lymphocytes, acquired Pelger-Huet anomaly (APHA), myeloid left shift, neutrophils with toxic granules and cytoplasmic vacuoles, and apoptotic cells. Conclusion: To summarize, in our study we observed similar features that were recorded in few studies earlier, such as APHA and plasmacytoid lymphocytes in convincing percentages among the COVID-19 patients in our population. Adding to these ANNP was one more prominent feature we encountered in majority of COVID-19 cases.

A compact and mobile hybrid C-arm scanner for simultaneous nuclear and fluoroscopic image guidance

PurposeThis study evaluates the performance of a mobile and compact hybrid C-arm scanner (referred to as IXSI) that is capable of simultaneous acquisition of 2D fluoroscopic and nuclear projections and 3D image reconstruction in the intervention room.ResultsThe impact of slightly misaligning the IXSI modalities (in an off-focus geometry) was investigated for the reduction of the fluoroscopic and nuclear interference. The 2D and 3D nuclear image quality of IXSI was compared with a clinical SPECT/CT scanner by determining the spatial resolution and sensitivity of point sources and by performing a quantitative analysis of the reconstructed NEMA image quality phantom. The 2D and 3D fluoroscopic image of IXSI was compared with a clinical CBCT scanner by visualizing the Fluorad A+D image quality phantom and by visualizing a reconstructed liver nodule phantom. Finally, the feasibility of dynamic simultaneous nuclear and fluoroscopic imaging was demonstrated by injecting an anthropomorphic phantom with a mixture of iodinated contrast and 99mTc.ConclusionDue to the divergent innovative hybrid design of IXSI, concessions were made to the nuclear and fluoroscopic image qualities. Nevertheless, IXSI realizes unique image guidance that may be beneficial for several types of procedures.Key Points• IXSI can perform time-resolved planar (2D) simultaneous fluoroscopic and nuclear imaging.• IXSI can perform SPECT/CBCT imaging (3D) inside the intervention room.

Interventional respiratory motion compensation by simultaneous fluoroscopic and nuclear imaging: a phantom study

Purpose. A compact and mobile hybrid c-arm scanner, capable of simultaneously acquiring nuclear and fluoroscopic projections and SPECT/CBCT, was developed to aid fluoroscopy-guided interventional procedures involving the administration of radionuclides (e.g. hepatic radioembolization). However, as in conventional SPECT/CT, the acquired nuclear images may be deteriorated by patient respiratory motion. We propose to perform compensation for respiratory motion by extracting the motion signal from fluoroscopic projections so that the nuclear counts can be gated into motion bins. The purpose of this study is to quantify the performance of this motion compensation technique with phantom experiments. Methods. Anthropomorphic phantom configurations that are representative of distributions obtained during the pre-treatment procedure of hepatic radioembolization were placed on a stage that translated with three different motion patterns. Fluoroscopic projections and nuclear counts were simultaneously acquired under planar and SPECT/CBCT imaging. The planar projections were visually assessed. The SPECT reconstructions were visually assessed and quantitatively assessed by calculating the activity recovery of the spherical inserts in the phantom. Results. The planar nuclear projections of the translating anthropomorphic phantom were blurry when no motion compensation was applied. With motion compensation, the nuclear projections became representative of the stationary phantom nuclear projection. Similar behavior was observed for the visual quality of SPECT reconstructions. The mean error of the activity recovery in the uncompensated SPECT reconstructions was 15.8% ± 0.9% for stable motion, 11.9% ± 0.9% for small variations, and 11.0% ± 0.9% for large variations. When applying motion compensation, the mean error decreased to 1.8% ± 1.6% for stable motion, 2.2% ± 1.5% for small variations, and 5.2% ± 2.5% for large variations. Conclusion. A compact and mobile hybrid c-arm scanner, capable of simultaneously acquiring nuclear and fluoroscopic projections, can perform compensation for respiratory motion. Such motion compensation results in sharper planar nuclear projections and increases the quantitative accuracy of the SPECT reconstructions.

Respiratory motion compensation in interventional liver SPECT using simultaneous fluoroscopic and nuclear imaging.

PurposeQuantitative accuracy of the single photon emission computed tomography (SPECT) reconstruction of the pretreatment procedure of liver radioembolization is crucial for dosimetry; visual quality is important for detecting doses deposited outside the planned treatment volume. Quantitative accuracy is limited by respiratory motion. Conventional gating eliminates motion by count rejection but increases noise, which degrades the visual reconstruction quality. Motion compensation using all counts can be performed if the motion signal and motion vector field over time are known. The measurement of the motion signal of a patient currently requires a device (such as a respiratory belt) attached to the patient, which complicates the acquisition. The motion vector field is generally extracted from a previously acquired four‐dimensional scan and can differ from the motion in the scan performed during the intervention. The simultaneous acquisition of fluoroscopic and nuclear projections can be used to obtain both the motion vector field and the projections of the corresponding (moving) activity distribution. This eliminates the need for devices attached to the patient and provides an accurate motion vector field for SPECT reconstruction. Our approach to motion compensation would primarily be beneficial for interventional SPECT because the time‐critical setting requires fast scans and no inconvenience of an external apparatus. The purpose of this work is to evaluate the performance of the motion compensation approach for interventional liver SPECT by means of simulations.MethodsNuclear and fluoroscopic projections of a realistic digital human phantom with respiratory motion were generated using fast Monte Carlo simulators. Fluoroscopic projections were sampled at 1–5 Hz. Nuclear data were acquired continuously in list mode. The motion signal was extracted from the fluoroscopic projections by calculating the center‐of‐mass, which was then used to assign each photon to a corresponding motion bin. The fluoroscopic projections were reconstructed per bin and coregistered, resulting in a motion vector field that was used in the SPECT reconstruction. The influence of breathing patterns, fluoroscopic imaging dose, sampling rate, number of bins, and scanning time was studied. In addition, the motion compensation method was compared with conventional gating to evaluate the detectability of spheres with varying uptake ratios.ResultsThe liver motion signal was accurately extracted from the fluoroscopic projections, provided the motion was stable in amplitude and the sampling rate was greater than 2 Hz. The minimum total fluoroscopic dose for the proposed method to function in a 5‐min scan was 10 µGy. Although conventional gating improved the quantitative reconstruction accuracy, substantial background noise was observed in the short scans because of the limited counts available. The proposed method similarly improved the quantitative accuracy, but generated reconstructions with higher visual quality. The proposed method provided better visualization of low‐contrast features than when using gating.ConclusionThe proposed motion compensation method has the potential to improve SPECT reconstruction quality. The method eliminates the need for external devices to measure the motion signal and generates an accurate motion vector field for reconstruction. A minimal increase in the fluoroscopic dose is required to substantially improve the results, paving the way for clinical use.

Analysis on the Factors Behind the Changes in Long-term Nuclear Projections

Analysis on the Factors Behind the Changes in Long-term Nuclear Projections

Changes in membrane properties of rat deep cerebellar nuclear projection neurons during acquisition of eyeblink conditioning

Previous studies have shown changes in membrane properties of neurons in rat deep cerebellar nuclei (DCN) as a function of development, but due to technical difficulties in obtaining viable DCN slices from adult animals, it remains unclear whether there are learning-related alterations in the membrane properties of DCN neurons in adult rats. This study was designed to record from identified DCN cells in cerebellar slices from postnatal day 25-26 (P25-26) rats that had a relatively mature sensory nervous system and were able to acquire learning as a result of tone-shock eyeblink conditioning (EBC) and to document resulting changes in electrophysiological properties. After electromyographic electrode implantation at P21 and inoculation with a fluorescent pseudorabies virus (PRV-152) at P22-23, rats received either four sessions of paired delay EBC or unpaired stimulus presentations with a tone conditioned stimulus and a shock unconditioned stimulus or sat in the training chamber without stimulus presentations. Compared with rats given unpaired stimuli or no stimulus presentations, rats given paired EBC showed an increase in conditioned responses across sessions. Whole-cell recordings of both fluorescent and nonfluorescent DCN projection neurons showed that delay EBC induced significant changes in membrane properties of evoked DCN action potentials including a reduced after-hyperpolarization amplitude and shortened latency. Similar findings were obtained in hyperpolarization-induced rebound spikes of DCN neurons. In sum, delay EBC produced significant changes in the membrane properties of juvenile rat DCN projection neurons. These learning-specific changes in DCN excitability have not previously been reported in any species or task.

From difficult past to imagined future: Projective reversal and the transformation of ground zero

In the United States, the term “ground zero” is now inextricably linked with New York City. Originally, however, it referred to the site directly beneath a detonated atomic bomb. The phrase was first used in government documents to identify the epicenters of destruction in the Japanese cities of Hiroshima and Nagasaki, where U.S. forces dropped nuclear weapons in 1945. How did a term whose origins are bound up with acts of American violence come to signify American victimhood? Examining U.S. political and media discourse from 1945–2001, this paper identifies a long history of projective reversal: faced with the prospect of a “difficult past,” American politicians and media outlets often grappled with the realities of a nuclear age by switching the roles of victim and perpetrator, imagining the United States as a future victim of a nuclear attack. After 9/11, the “ground zero” nomenclature naturalized an understanding of lower Manhattan as akin to a post-atomic landscape and, in turn, helped to animate a new series of nuclear projections leading up to the 2003 invasion of Iraq. In tracing the transformation of ground zero, this paper also forges a more robust link between the extensive literature on collective memory and recent efforts to elaborate a sociology of the future, examining how pasts and futures interpenetrate to shape political action in the present.

Aligned electrospun fibers for neural patterning

ObjectivesTo test a 3D approach for neural network formation, alignment, and patterning that is reproducible and sufficiently stable to allow for easy manipulation.ResultsA novel cell culture system was designed by engineering a method for the directional growth of neurons. This uses NG108-15 neuroblastoma x glioma hybrid cells cultured on suspended and aligned electrospun fibers. These fiber networks improved cellular directionality, with alignment angle standard deviations significantly lower on fibers than on regular culture surfaces. Morphological studies found nuclear aspect ratios and cell projection lengths to be unchanged, indicating that cells maintained neural morphology while growing on fibers and forming a 3D network. Furthermore, fibronectin-coated fibers enhanced neurite extensions for all investigated time points. Differentiated neurons exhibited significant increases in average neurite lengths 96 h post plating, and formed neurite extensions parallel to suspended fibers, as visualized through scanning electron microscopy.ConclusionsThe developed model has the potential to serve as the basis for advanced 3D studies, providing an original approach to neural network patterning and setting the groundwork for further investigations into functionality.

Nuclear Envelope Rupture Is Enhanced by Loss of p53 or Rb.

The mammalian nuclear envelope (NE) forms a stable physical barrier between the nucleus and the cytoplasm, normally breaking down only during mitosis. However, spontaneous transient NE rupture in interphase can occur when NE integrity is compromised, such as when the nucleus experiences mechanical stress. For instance, deficiencies in the nuclear lamins and their associated proteins can cause NE rupture that is promoted by forces exerted by actin filaments. NE rupture can allow cytoplasmic nucleases to access chromatin, potentially compromising genome integrity. Importantly, spontaneous NE rupture was noted in several human cancer cell lines, but the cause of this defect is not known. Here, we investigated the mechanistic contributions of two major tumor suppressors, p53 (TP53) and Rb (RB1), to the repression of NE rupture. NE rupture was induced in normal human epithelial RPE-1 cells upon impairment of either Rb or p53 achieved by shRNA knockdown and CRISPR/Cas9 gene editing. NE rupture did not involve diminished expression of NE components or greater cell motility. However, cells that underwent NE rupture displayed a larger nuclear projection area. In conclusion, the data indicate that NE rupture in cancer cells is likely due to loss of either the Rb or the p53 pathway.Implications: These findings imply that tumor suppression by Rb and p53 includes the ability to prevent NE rupture, thereby protecting against genome alterations. Mol Cancer Res; 15(11); 1579-86. ©2017 AACR.

Serial block face SEM visualization of unusual plant nuclear tubular extensions in a carnivorous plant (Utricularia, Lentibulariaceae).

In Utricularia nelumbifolia , the nuclei of placental nutritive tissue possess unusually shaped projections not known to occur in any other flowering plant. The main aim of the study was to document the morphology and ultrastructure of these unusual nuclei. In addition, the literature was searched to find examples of nuclear tubular projections in other plant groups, and the nuclei of closely related species of Utricularia (i.e. sects Iperua , Orchidioides , Foliosa and Utricularia ) were examined. To visualize the complexity of the nuclear structures, transmission electron microscopy (TEM) was used, and 3-D ultrastructural reconstructions were made using the serial block face scanning electron microscopy (SBEM) technique. The nuclei of 11 Utricularia species, i.e. U. nelumbifolia , U. reniformis , U. cornigera , U. nephrophylla (sect. Iperua ), U. asplundii , U. alpina , U. quelchii (sect. Orchidioides ), U. longifolia (sect. Foliosa ), U. intermedia , U. minor and U. gibba (sect. Utricularia ) were examined. Of the 11 Utricularia species examined, the spindle-like tubular projections (approx. 5 μm long) emanating from resident nuclei located in placental nutritive tissues were observed only in U. nelumbifolia . These tubular nuclear extensions contained chromatin distributed along hexagonally shaped tubules. The apices of the projections extended into the cell plasma membrane, and in many cases also made contact at the two opposing cellular poles, and with plasmodesmata via a short cisterna of the cortical endoplasmic reticulum. Images from the SBEM provide some evidence that the nuclear projections are making contact with those of neighbouring cells. The term chromatubules (chromatin-filled tubules) for the nuclear projections of U. nelumbifolia placental tissue was proposed here. Due to the apparent association with the plasma membrane and plasmodesmata, it was also speculated that chromatubules are involved in nucleus-cell-cell communication. However, further experimental evidence is required before any functional hypothesis can be entertained.

91 - Different Repo Doses (High vs Standard) for Treatment of Anemia in MDS Patients: A Survey from the Italian MDS Registry

Studies of morphology of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) refer to the definitions produced by the French-American-British (FAB) group and by the World Health Organization expert group. To clarify some points regarding the dysgranulopoiesis that are still unclear we analyzed a series of 98 neutrophils from MDS patients with regard to granularity, nuclear segmentation, the appearance of the chromatin, the presence of giant neutrophils, and the presence of nuclear chromatin extensions. We found that cells with at least 2/3 reduction of the content of granules, Pelger-like neutrophils, dysplastic non-Pelger cells, neutrophils with abnormal clumping of the chromatin, and macropolycytes could be recognized as dysplastic and included in the 10% count recommended by these two classifications. In addition, we suggest that neutrophils with more than 4 nuclear projections could be recognized as a relevant dysplastic feature.

78 - Addition of Lenalidomide to Azacitidine in Higher Risk Myelodysplastic Syndromes. Long-Term Results of a Randomized Phase II Multicenter Study

Studies of morphology of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) refer to the definitions produced by the French-American-British (FAB) group and by the World Health Organization expert group. To clarify some points regarding the dysgranulopoiesis that are still unclear we analyzed a series of 98 neutrophils from MDS patients with regard to granularity, nuclear segmentation, the appearance of the chromatin, the presence of giant neutrophils, and the presence of nuclear chromatin extensions. We found that cells with at least 2/3 reduction of the content of granules, Pelger-like neutrophils, dysplastic non-Pelger cells, neutrophils with abnormal clumping of the chromatin, and macropolycytes could be recognized as dysplastic and included in the 10% count recommended by these two classifications. In addition, we suggest that neutrophils with more than 4 nuclear projections could be recognized as a relevant dysplastic feature.

59 - Prognostic Impact of Mutations in Patients with Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms with Normal Karyotype

Studies of morphology of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) refer to the definitions produced by the French-American-British (FAB) group and by the World Health Organization expert group. To clarify some points regarding the dysgranulopoiesis that are still unclear we analyzed a series of 98 neutrophils from MDS patients with regard to granularity, nuclear segmentation, the appearance of the chromatin, the presence of giant neutrophils, and the presence of nuclear chromatin extensions. We found that cells with at least 2/3 reduction of the content of granules, Pelger-like neutrophils, dysplastic non-Pelger cells, neutrophils with abnormal clumping of the chromatin, and macropolycytes could be recognized as dysplastic and included in the 10% count recommended by these two classifications. In addition, we suggest that neutrophils with more than 4 nuclear projections could be recognized as a relevant dysplastic feature.

GENOTOXICITY AND CYTOTOXICITY OF X-RAYS IN CHILDREN EXPOSED TO PANORAMIC RADIOGRAPHY.

ABSTRACTObjective: To assess the genotoxicity and cytotoxicity produced by X-rays in the epithelium of the oral mucosa of infants exposed to panoramic radiography.Methods: The sample consisted of 30 healthy children, 19 females and 11 males, ranging in age from 4 to 10 years (average of 7 years of age). Oral mucosa cells were collected by liquid-based cytology immediately before and after seven days following the exposure to panoramic radiography. Smears were processed and stained using the modified Feulgen Rossenbeck technique. Bud and broken egg nuclear projections, changes in the form of micronuclei, and genotoxic and cytotoxic changes of pyknosis, karyorrhexis and karyolysis were analyzed and quantified.Results: The frequency of pyknosis, buds and broken eggs was significantly higher after exposure to X-rays (p<0.05), but there was no statistically significant difference regarding gender, as well as in the other changes studied.Conclusions: Exposure to X-rays emitted during submission to panoramic radiography may induce cell death in the epithelium of children’s oral mucosa. No evidence was found for a significant genotoxic effect.

Reliability of neutrophilic nuclear appendages in morphological sex differentiation

Background: The inactive X-chromosome in neutrophils appears in one of the three forms. They are drumsticks, racquet forms, and sessile nodules. Objective: A correlative study based on the presence of “drumstick and other nuclear appendages” in polymorphonuclear neutrophils to determine the morphological sex. Materials and Methods: Sixty-eight randomly selected blood smears (34 males and 34 females) were stained with Leishman’s stain. One hundred well-stained neutrophils were double-blindly studied in the tail-end of the smears and classified into four groups based on Kosenow’s formula as drumstick (Form A), sessile nodule (Form B), and other pedunculated nuclear projections such as tag and hooks (Form C). Results: Significant correlation of neutrophilic nuclear appendage of Form A (P = 0.00001) and Form C (P = 0.00016) was obtained for females and males, respectively. Difference of A-C gives a positive value in females and a negative value in males. Conclusion: Neutrophilic nuclear appendages which include true drumsticks, sessile nodules, and racket structures form a useful tool for morphological sex differentiation.

Simultaneous fluoroscopic and nuclear imaging: impact of collimator choice on nuclear image quality.

X-ray-guided oncological interventions could benefit from the availability of simultaneously acquired nuclear images during the procedure. To this end, a real-time, hybrid fluoroscopic and nuclear imaging device, consisting of an X-ray c-arm combined with gamma imaging capability, is currently being developed (Beijst C, Elschot M, Viergever MA, de Jong HW. Radiol. 2015;278:232-238). The setup comprises four gamma cameras placed adjacent to the X-ray tube. The four camera views are used to reconstruct an intermediate three-dimensional image, which is subsequently converted to a virtual nuclear projection image that overlaps with the X-ray image. The purpose of the present simulation study is to evaluate the impact of gamma camera collimator choice (parallel hole versus pinhole) on the quality of the virtual nuclear image. Simulation studies were performed with a digital image quality phantom including realistic noise and resolution effects, with a dynamic frame acquisition time of 1 s and a total activity of 150 MBq. Projections were simulated for 3, 5, and 7 mm pinholes and for three parallel hole collimators (low-energy all-purpose (LEAP), low-energy high-resolution (LEHR) and low-energy ultra-high-resolution (LEUHR)). Intermediate reconstruction was performed with maximum likelihood expectation-maximization (MLEM) with point spread function (PSF) modeling. In the virtual projection derived therefrom, contrast, noise level, and detectability were determined and compared with the ideal projection, that is, as if a gamma camera were located at the position of the X-ray detector. Furthermore, image deformations and spatial resolution were quantified. Additionally, simultaneous fluoroscopic and nuclear images of a sphere phantom were acquired with a physical prototype system and compared with the simulations. For small hot spots, contrast is comparable for all simulated collimators. Noise levels are, however, 3 to 8 times higher in pinhole geometries than in parallel hole geometries. This results in higher contrast-to-noise ratios for parallel hole geometries. Smaller spheres can thus be detected with parallel hole collimators than with pinhole collimators (17 mm vs 28 mm). Pinhole geometries show larger image deformations than parallel hole geometries. Spatial resolution varied between 1.25 cm for the 3 mm pinhole and 4 cm for the LEAP collimator. The simulation method was successfully validated by the experiments with the physical prototype. A real-time hybrid fluoroscopic and nuclear imaging device is currently being developed. Image quality of nuclear images obtained with different collimators was compared in terms of contrast, noise, and detectability. Parallel hole collimators showed lower noise and better detectability than pinhole collimators.

Peptidergic modulation of cerebellar nuclear neurons in promoting motor coordination

Event Abstract Back to Event Peptidergic modulation of cerebellar nuclear neurons in promoting motor coordination Jing-Ning Zhu1* and Jian-Jun Wang1* 1 Nanjing University, State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology, School of Life Sciences, China The cerebellar circuitry receives not only classic glutamatergic mossy fibers and climbing fibers but also fibers containing various peptides, such as orexin and corticotropin-releasing factor (CRF). Both the orexinergic afferent inputs from the hypothalamus and the CRFergic climbing fiber-like afferent inputs from the inferior olive directly excite projection neurons rather than interneurons in the cerebellar interposed nucleus (IN), one of the final outputs of the spinocerebellum. In addition, orexin receptors and CRF receptors are selectively expressed on projection neurons in the IN. Na+-Ca2+ exchangers and inward rectifier K+ channels co-mediate the orexin-induced inward currents on IN projection neurons, whereas HCN channels and inward rectifier K+ channels contribute to the excitation induced by CRF. Furthermore, microinjection of orexin or CRF into bilateral cerebellar INs significantly promotes motor balance and coordination. Intriguingly, blocking orexinergic afferent inputs in IN does not influence routine movements but remarkably attenuates motor performances during motor challenges, whereas interfering CRFergic climbing fiber-like inputs directly leads to an ataxia-like motor incoordination. Therefore, through direct modulations on cerebellar nuclear projection neurons, peptidergic inputs may play important roles in the cerebellar circuitry, and actively promote cerebellar motor control. Acknowledgements Supported by NSFC grants 31330033, 91332124, 31471112, 31461163001, and SRFDP/RGC ERG grant 20130091140003. Keywords: Cerebellar circuitry, Cerebellar nucleus, CRF, orexin, motor control Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Symposium 1: Motor Control and Sensorimotor Integration: Circuitry and Plasticity Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Zhu J and Wang J (2016). Peptidergic modulation of cerebellar nuclear neurons in promoting motor coordination. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00005 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 26 Jul 2016; Published Online: 11 Aug 2016. * Correspondence: Prof. Jing-Ning Zhu, Nanjing University, State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology, School of Life Sciences, Nanjing, Jiangsu, China, jnzhu@nju.edu.cn Prof. Jian-Jun Wang, Nanjing University, State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology, School of Life Sciences, Nanjing, Jiangsu, China, jjwang@nju.edu.cn Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jing-Ning Zhu Jian-Jun Wang Google Jing-Ning Zhu Jian-Jun Wang Google Scholar Jing-Ning Zhu Jian-Jun Wang PubMed Jing-Ning Zhu Jian-Jun Wang Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Diagnosis of MDS: morphology, chromosome abnormalities and genetic mutations

Myelodysplastic syndromes (MDS) are a group of hematological neoplasms associated with ineffective hematopoiesis and that can transform into acute leukemia. The clinical classification of MDS which is defined by cytopenia, the rate of blasts in peripheral blood and bone marrow, dysplasia, and chromosomal abnormalities, has undergone continuous revision. To increase the accuracy of dysplastic evaluation, IWGM-MDS and the Research Committee for Idiopathic Hematopoietic Disorders, Ministry of Health, Labour and Welfare, Japan have proposed a quantitative and qualitative definition of dysplasia. Recently, refining the definition of dysgranulopoiesis was proposed by IWGM-MDS. Neutrophils with abnormal clumping of chromatin, and harboring more than 4 nuclear projections, were recognized as dysplastic features. At present, karyotypic abnormalities are detected in approximately 50% of de novo MDS and these remain the most critical prognostic factor. In the new cytogenetic scoring system, cytogenetic abnormalities were classified into five prognostic subgroups. This new classification was adopted by the revised IPSS. Approximately 80% to 90% of MDS patients have detectable mutations by whole-exon sequencing or whole genome sequencing. Many genetic mutations had biological and prognostic significance. It is important to further understand the utility of this factor in determining prognosis and in selecting among therapeutic options.

Aberrant “Barbed-Wire” Nuclear Projections of Neutrophils in Trisomy 18 (Edwards Syndrome)

We discuss the significance of neutrophils with increased, aberrant nuclear projections mimicking “barbed-wire” in a newborn child with trisomy 18 (T18). Increased, aberrant nuclear projections have been previously reported in trisomy of the D group of chromosomes (chromosomes 13, 14, and 15), and we report similar findings in a patient with T18. The peripheral blood smear showed relative neutrophilia with the majority (37%) of neutrophils showing two or more thin, rod-shaped or spike-shaped, and often pedunculated aberrant nuclear projections. The number of projections ranged from 2 to 6 per cell, averaged 2 per affected neutrophil, and ranged in length from 0.22 μm to 0.83 μm. This case confirms that the morphologic finding described is not restricted to trisomy of one of the chromosomes in group D, as implied in the literature.