Median Density Values Research Articles

Abstract 4909: An RNA-based model for tertiary lymphoid structure (TLS) prediction and classification in pancreatic adenocarcinoma (PDAC)

Abstract Although TLS status possesses prognostic significance in PDAC and can potentially affect chemotherapy outcomes, there is currently a notable lack of RNA sequencing (RNA-seq) models that specialize in TLS identification and classification in PDAC. Here, we developed a model for predicting TLS status (high or low) based on RNA-seq data. Design: Hematoxylin and eosin (H&E) whole slide images of PDAC samples from The Cancer Genome Atlas (TCGA, n = 118) and Clinical Proteomic Tumor Analysis Consortium (CPTAC, n = 129) were used to detect intratumoral and borderline TLSs followed by TLS density measurements (units/mm2) by an experienced pathologist. The samples were then stratified into TLS-high and TLS-low groups based on median density values. Next, we used deconvolution by Kassandra algorithm to identify cell subtypes enriched in each TLS group based on gene expression (RNA-seq) data. Calculation of ssGSEA scores for gene signatures corresponding to cell subtypes and TLS structures was performed, along with survival analysis. Differential expression analysis between TLS-high and TLS-low samples, followed by functional enrichment (|logFC| > 2; padj < 0.01), was conducted. The LightGBM gradient boosting classifier was then trained on ranked expression data with sequential feature selection to predict TLS-high and TLS-low groups. We trained the model with H&E staining annotations and ranked RNA expression data from TCGA or CPTAC samples (total n = 167). The remaining 80 were designated as hold-out samples. The weighted F1 score was computed as a performance metric. Findings: Median density of detected TLSs in the TCGA and CPTAC samples was 0.012 units/mm2. Kassandra deconvolution revealed B-cell enrichment, but fibroblast and M2 macrophage depletion in the TLS-high group. Our calculated ssGSEA scores of previously described TLS gene signatures, along with those of different B-cell subtypes and follicular dendritic cells, showed significant association with the TLS-high group. Genes associated with B-cell proliferation, differentiation, and signaling (CD19, CD22, CD79A, CD79B, and CR2) were also upregulated in this group. Comparing the performance of our RNA-based model on the validation dataset with manual TLS classification by a pathologist, we obtained an F1 weighted score of 0.72 and ROC-AUC score of 0.77. Thus, the TLS predictions by our model concurred with the TLS classification based on H&E annotations and pathological evaluation. Moreover, patients in the predicted TLS-low group had worse overall survival (OS) compared to the TLS-high group (Log(HR) = 0.76; 95% CI [0.04; 1.48]; p<0.05). We present an RNA-based model that stratifies PDAC samples as TLS-high or TLS-low, with predictions that conform to pathological findings. We also found TLS-low samples to associate with worse OS, thus offering an objective means to predict prognoses of PDAC patients based on TLS status. Citation Format: Alexandra Livanova, Andrey Tyshevich, Andrey Kravets, Stanislav Kurpe, Nadezhda Lukashevich, Dmitry Ivchenkov, Daniil Dymov, Anna Belozerova, Kirill Kryukov, Aleksandr Sarachakov, Viktor Svekolkin, Vladimir Kushnarev. An RNA-based model for tertiary lymphoid structure (TLS) prediction and classification in pancreatic adenocarcinoma (PDAC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4909.

Osseodensification vs. Conventional Osteotomy: A Case Series with Cone Beam Computed Tomography.

Introduction: Osseodensification is a non-extraction technique using specially designed drills to increase bone density while extending an osteotomy, allowing bone to be preserved and condensed by compacting autograft during osteotomy preparation, increasing bone density around implants, and improving mechanical stability. Aim: The objective of this study is to compare conventional osteotomy and osseodensification protocols in implant placement and analyze whether there are differences in bone density. Materials and Methods: Study variables were defined, namely, osseodensification technique, conventional osteotomy technique, bone density, sex, area of location, implant dimensions, implant dimensions, and implant stability. Eligibility and exclusion criteria were defined. A step-by-step surgical protocol was developed. The surgeon and radiologist underwent intra-examiner calibration. A total of 15 patients were selected according to the eligibility criteria, and a total of 41 implants were inserted, 20 implants by conventional osteotomy and 21 by osseodensification. A cone beam computed tomography was performed one year after prosthetic rehabilitation to estimate bone density. Data were collected and recorded, and in the analysis of the association of variables, non-parametric tests were applied. Results: Significant statistical results were found in bone density values, with higher values being obtained with the osseodensification technique, that is, median density values of 1020, and median density values of 732 for the bone drilling technique. The results of the correlation between bone density in both techniques and sex, primary implant stability, implant dimensions and location area were statistically non-significant. Conclusions: Within the limitations of this study, there are differences in bone density between conventional osteotomy and osseodensification protocols. Bone density is increased with osseodensification over a study period of one year.

Chemical-physical characteristics of artificial saliva substitutes: rheological evaluation.

We aimed at evaluating some chemical-physical properties of artificial saliva substitutes easily available on the E.U. market, such as viscosity, pH, buffering capacity, superficial tension, density and spinnbarkeit and to compare the results with human natural saliva bibliographic data. Based on the easy availability on the market, twelve artificial saliva solutions in liquid formulation were analyzed. Kinematic viscosity (cSt) was determined using a micro-Ubbelohde model capillary viscosimeter (ViscoClock, SCHOOT-GERATE Mainz, Germany). Dynamic viscosity (mPas) was determined, through a simple multiplication between density (g/cm3) and kinematic viscosity of each solution. pH analyses were carried out at room temperature using a pH-meter (Mettler Toledo®- Five Easy, Columbus, OH, USA). Spinnbarkeit analysis was performed by a self-owned instrument built for the purpose. The median density value, obtained from the cohort of artificial saliva substitutes, was 1.036 g/cm3. The median value of the kinematic viscosity was 8.984 cSt. The median spinnbarkeit value was 3.2 mm and the median pH value was 6.29. In this study we found an almost linear correlation between the kinematic viscosity and spinnbarkeit values of the artificial saliva substitutes evaluated. Saliva substitutes should be as faithful as possible to the characteristics of human saliva, in order to completely replace its functions in the oral cavity. Nevertheless, despite several R&D efforts, it is difficult to reproduce all the different features that belongs to natural saliva in one device. Therefore, it would be desirable to create more products reproducing saliva with various rheological characteristics in respect of the main salivary functions such as: chewing, speaking and tissue coating.

Contrast enhanced computed tomography assessment of superficial inguinal lymph node metastasis in canine mammary gland tumors.

Mammary gland neoplasms are predominant in dogs. However, sentinel lymph node (SLN) status assessment criteria have not been established for these cases. In this retrospective, secondary analysis, diagnostic case control study, CT images of 65 superficial inguinal SLNs were obtained before and 1, 3, 5, and 10 min after intravenous administration of contrast agent (iopamidol 370mgI/mL). The presence and degree of postcontrast enhancement were assessed, by means of the median absolute density value and the maximum absolute density value at any time point in the center and in the periphery of each SLN measured in Hounsfield units (HU), before and after contrast agent administration. These values were compared with histopathological findings postsurgical excision. Receiver operating characteristic analysis was conducted. The absolute density values ranged widely at each time point and within each group of nodes (negative, positive, control group). At all time points, the median density value in the center and in the periphery was significantly higher in metastatic than in non-metastatic SLNs (P≤.014). Among the parameters tested, the median absolute density value measured in the periphery of the SLN 3min after injection showed the highest sensitivity, specificity, and accuracy (AUC) (87.5%, 82.1%, and 92.1% respectively), with a cutoff value of 50.9HU. The maximum absolute density value at any time point in the center and periphery of the SLNs was also significantly higher in metastatic SLNs compared to non-metastatic (P≤.001). With a cutoff value of 59.5HU, the maximum absolute density value in the periphery of the SLN displayed high sensitivity and specificity (87.5% and 89.3%, respectively). The results of this study support the hypothesis that contrast enhanced CT imaging may aid in the assessment of SLN metastasis in dogs with mammary gland neoplasms.

Evaluation of physiologic pineal gland calcification via computed tomography in the pediatric population

Aim: To determine the area, density and morphology of physiologic pineal gland calcification in the preadolescents and adolescents using computed tomography and to evaluate correlations with age and sex.Material and Methods: This retrospective study evaluated 220 cases (110 males, 110 females) with ages ranging from 7-17 years (mean age: 12±3.17). Cases were divided into two groups according to age of 7-12 years (n=120, preadolescent) and 13-17 years (n=100, adolescent). Morphology (homogeneous-heterogeneous), area (mm2) and density (Hounsfield Units [HU]) of pineal calcifications were investigated on computed tomography. Comparisons were made between age groups and sex in terms of these variables.Results: This study found pineal calcification frequency was 50%, 35% and 67% in all cases, preadolescents, and adolescents, respectively. According to morphology, 60.9% of calcifications were homogeneous and 39.1% were heterogeneous. Median calcification area and density values were 8.50 (6-15) mm2 and 67 (50-109.75) HU, and 7 (4.75-14.25) mm2, and 67 (53.25-87.75) HU, for males and females, respectively, with no significant difference identified between the sexes (p=0.353 and p=0.463, respectively). Median calcification area in the preadolescent and adolescent age groups was 7 (6-12) and 10 (5-18) mm2, with no significant difference identified between the groups (p=0.175). Median density values were 70 (56-109) HU for adolescents and this was high compared to preadolescents (59 [47-78] HU) (p=0.005). Conclusion: Physiologic pineal calcification frequency, area, density and morphology were revealed for preadolescent and adolescents. These values may be used as qualitative and quantitative reference data for differentiation of normal/abnormal pineal calcification in routine practice.

Prostate cancer volume associates with preoperative plasma levels of testosterone that independently predicts high grade tumours which show low densities (quotient testosterone/tumour volume)

ObjectiveTo investigate potential associations of preoperative total testosterone (TT) with tumor volume (TV) and grade of prostate cancer (PCa). MethodsPatients who were under medications impacting on the hypothalamic-pituitary-adrenal-testis-prostate axis were excluded. TT was measured preoperatively at least 1 month after biopsies and TV was calculated on the removed prostate specimen. Other continuous variables included total prostate specific antigen (PSA), percentage of positive cores (P+) and weight (W) of the removed prostate. Patients were categorized according to the pathologic Gleason score (pGS) in 3 groups (pGS 6, 7 and > 7). Invasion of the seminal vesicles was coded as seminal vesicle invasion (SVI). ResultsThe median levels of TT were significantly and increasingly higher from pGS 6 (14.7 nmol/L) to pGS 7 (15.0 nmol/L) and pGS > 7 (18.8 nmol/L). The median values of TV were also detected significantly and increasingly higher from pGS 6 (5.6 mL) to pGS 7 (8.1 mL) and pGS > 7 (14.8 mL). The median preoperative levels of PSA were also increasing from pGS 6 (5.9 μg/L) to pGS 7 (6.2 μg/L) and pGS > 7 (7.7 μg/L). There was a significant and positive correlation of TV to PSA, TT and P+. Multiple linear regression analysis showed that TV was significantly and independently predicted by TT, PSA and P+. High grade PCa (pGS > 7) independently associated with TV, TT, P+ and SVI. The median density values of TT relative to TV (quotient TT/TV) significantly decreased from pGS 6 (2.6 nmol/L/mL) to pGS 7 (1.9 nmol/L/mL) and pGS > 7 (1.4 nmol/L/mL). The median density values of PSA relative to TV (quotient PSA/TV) also significantly decreased from pGS (1.1 μg/L/mL) to pGS 7 (0.7 μg/L/mL) and pGS > 7 (0.6 μg/L/mL). ConclusionThe investigation shows that TT relates to volume and grade of PCa; moreover, the density of TT relative to TV inversely associates with rate of increase of cancer that depends on the grade of the tumour.

Computed tomography and magnetic resonance imaging findings of acquired dacryocystoceles

In this study, radiological findings of acquired dacryocystocele are presented. A total of 13 dacryocystoceles including bilateral in two of the patients, in four patients on the left and in five patients on the right, were determined. Six of the patients had dacryocystocele infection. Average density of the non-infected dacryocystoceles was 11.8±7.8 Haunsfield units (HU), while the median density value of infected ones was 35.0 HU. There was expansion on unilateral nasolacrimal duct in four patients. Acquired dacryocystoceles are rare masses in medial canthal area, and their radiological imaging findings may vary based on etiological factors and presence of infections.

Refilling process in the plasmasphere: a 3-D statistical characterization based on Cluster density observations

Abstract. The Cluster mission offers an excellent opportunity to investigate the evolution of the plasma population in a large part of the inner magnetosphere, explored near its orbit's perigee, over a complete solar cycle. The WHISPER sounder, on board each satellite of the mission, is particularly suitable to study the electron density in this region, between 0.2 and 80 cm−3. Compiling WHISPER observations during 1339 perigee passes distributed over more than three years of the Cluster mission, we present first results of a statistical analysis dedicated to the study of the electron density morphology and dynamics along and across magnetic field lines between L = 2 and L = 10. In this study, we examine a specific topic: the refilling of the plasmasphere and trough regions during extended periods of quiet magnetic conditions. To do so, we survey the evolution of the ap index during the days preceding each perigee crossing and sort out electron density profiles along the orbit according to three classes, namely after respectively less than 2 days, between 2 and 4 days, and more than 4 days of quiet magnetic conditions (ap ≤ 15 nT) following an active episode (ap > 15 nT). This leads to three independent data subsets. Comparisons between density distributions in the 3-D plasmasphere and trough regions at the three stages of quiet magnetosphere provide novel views about the distribution of matter inside the inner magnetosphere during several days of low activity. Clear signatures of a refilling process inside an expended plasmasphere in formation are noted. A plasmapause-like boundary, at L ~ 6 for all MLT sectors, is formed after 3 to 4 days and expends somewhat further after that. In the outer part of the plasmasphere (L ~ 8), latitudinal profiles of median density values vary essentially according to the MLT sector considered rather than according to the refilling duration. The shape of these density profiles indicates that magnetic flux tubes are not fully replenished after 6 days of quiet conditions. In addition, the outer plasmasphere in the night and dawn sectors (22:00 to 10:00 MLT range) maintains an overall clear deficit of ionospheric population, when compared to the situation in the noon and dusk sectors (10:00 to 22:00 MLT range).

Solar cycle dependence of bulk ion composition at geosynchronous orbit

[1] While the average ion mass M (normalized to amu) of bulk plasma at geosynchronous orbit has been calculated at solar maximum (during the era of the Combined Release and Radiation Effects Satellite (CRRES)), the solar cycle dependence of bulk ion composition at geosynchronous orbit is not known. Here, we use measurements of mass density ρm from Alfven wave frequencies measured by the Geostationary Operational Environmental Satellites and ion density measurements by the Magnetospheric Particle Analyzer (MPA) on Los Alamos National Laboratory (LANL) spacecraft to establish the solar cycle dependence of bulk ion composition. We show that there is a strong correlation between the yearly median value of ρm, ρm,yr−med, and the yearly average of the solar EUV flux F10.7, F10.7,yr−av; log10(ρm,yr−med) ≃ 0.5089 + 0.003607F10.7,yr−av (for ρm values adjusted to a magnetic latitude MLAT of 8°). We calibrate the measurements of the MPA instrument on one spacecraft to those from another by using yearly median density values. Then, using close conjunctions of LANL spacecraft with CRRES (for which we have inferred values of ρm and ne), we calibrate the ideal theoretical value of MPA ion density nMPA−th (the value that MPA would measure if it measured all the ions) to the observed values directly measured by the instrument, nMPA−obs. We find that nMPA−th is approximately 1.47 times the value of nMPA−obs measured by the LANL 1994 spacecraft. Using the yearly median values of ρm as a function of F10.7, the yearly median values of nMPA−th from the MPA instruments, and a model for the concentration of He+, we are able to calculate the solar cycle dependence of the average ion mass M and the O+ concentration ηO+ ≡ nO+/ne. We find that M is typically ∼3.8 at solar maximum and near unity at solar minimum. Typical values of ηO+ vary by 2 orders of magnitude over the solar cycle, from about 0.2 at solar maximum to ∼2 × 10−3 at solar minimum. Furthermore, our results also demonstrate that the typical concentration of He+ must also be very low at solar minimum. Since the median yearly values of density are low, characteristic of the plasma trough, our results are most applicable to that region. Considering, however, that the plasmasphere and plume typically have a low concentration of O+, the concentration of O+ at geosynchronous orbit at solar minimum is likely to be low for all conditions (with the possible exception of very low densities for which the high-energy component might dominate).

Characterization of N-methyl- d-aspartate receptors in the hyperammonemic Sparse fur mouse

The N-methyl- d-aspartate (NMDA) receptor, a glutamate receptor subtype, is a ligand-gated ion channel. Overstimulation of NMDA receptors may increase intracellular Ca 2+ concentrations to lethal levels in neurodegenerative disorders affecting the basal ganglia. Such excitotoxicity may also contribute to the loss of medium spiny neurons in the striata of the hyperammonemic sparse fur ( spf/Y) mouse, a model of the X-linked disorder of the urea cycle, ornithine carbamoyltransferase deficiency (OCTD). Levels of quinolinic acid (QA), a potent NMDA agonist, are elevated in the brains of spf/Y mice. Further, direct injection of QA into the striatum produces selective degeneration of medium spiny neurons. Microglia, an endogenous source of QA in the brain, are abundant in spf/Y mice during the period of neuronal degeneration. The location and density of NMDA receptors was visualized by gold labelled immunocytochemistry with a polyclonal antibody to the NMDAR1 receptor subtype and their distribution quantified. A 58% reduction was found in the median density value in the layer V pyramidal neurons in fronto-parietal cortex ( p<0.001), but no significant change was observed in the striatum. NMDA receptor binding was examined using [ 3 H ]dizocilpine ([ 3 H ]MK-801). Receptor density ( B max) in the striata of clinically stable spf/Y mice and +/Y littermates was unchanged, but was decreased 15% ( p<0.01) in the fronto-parietal cortices in clinically stable spf/Y mice compared with +/Y littermate controls.

Polar cap electron densities from DE 1 plasma wave observations

Electric field spectrum measurements from the plasma wave instrument on the Dynamics Explorer 1 spacecraft are used to study the local electron density at high altitudes in the northern polar cap region. The electron density is determined from the upper cutoff of whistler mode radiation at the electron plasma frequency. Median density values over the polar cap at L greater than 10 are found to vary from 35.2±8.5 cm−3 at 2.1 RE to 0.99±0.51 cm−3 at 4.66 RE. The steady state radial outflow model is examined for consistency with the observed density profile. A power law fit to the radial variation of the electron density yields an exponent of −3.85±0.32, which for the radial outflow model implies a flow velocity increasing nearly linearly with increasing radial distance. Comparison of the observed electron densities with theoretical polar wind densities yields consistent results up to 2.8 RE. A comparison of the observed electron densities with low‐altitude density profiles from the Alouette II and ISIS 1 spacecraft illustrate transitions in the slope of the profile at 1.16 RE and between 1.55 and 2.0 RE. The changes in the density profile suggest that changes occur in the basic radial transport processes at these altitudes.

The Differential Fragmentation of Rabbit Skeletal-Muscle Membrane Systems during Homogenization

sedimentation (Fig. lb). These studies indicate that the density distribution patterns of basal ATPase and Ca2+-dependent ATPase activities are different. Table 1 indicates the median density values of basal ATPase, Ca2+-dependent ATPase and cholesterol. The rate-sedimentation studies indicate that the basal-ATPase-associated vcsicles are larger than Ca2+-dependent-ATPase-associated vesicles. Consideration of the rate and isopycnic separations illustrates that basal-ATPase-associated vesicles are lighter but larger than Ca2+-dependent-ATPase-associated vesicles. Sodium dodecyl sulphatepolyacrylamide-gel electrophoresis (Barrett & Headon, 1975~) of the separated membranes indicated distinct differences between the two types of vesicles. It has been indicated that cholesterol is associated with the vesicles of muscle microsoma1 preparationscontaining basal ATPase activity (O’Flaherty C I al., 1975). However, consideration of the ratio of cholesterol (pgiml) to basal ATPase activity (pnol of PJmin per ml) in two regions of the isopycnic gradient separations described here (i.e. density range 1.08-1.14,cholesteroI/basal ATPaseratio 1.4; densityrange 1.14-1.17, cholesterol/ basal ATPase ratio 1 .O) indicates that cholesterol, though associated with basal ATPase activity, is also associated with other membranes in rabbit skeletal muscle. This interpretation is confirmed by results obtained in homogenization studies by Barrett & Headon (197%).

Topology and growth of the intracytoplasmic membrane system of Rhodopseudomonas spheroides: protein, chlorophyll, and phospholipid insertion into steady-state anaerobic cells.

An equilibrium density gradient centrifugation study involving the separation of "old" and "new" membranes has been developed to determine the manner in which protein, lipid, and chlorophyll are incorporated into growing intracytoplasmic membranes (chromatophores) of Rhodopseudomonas spheroides. Chromatophores derived from cells grown in an H(2)O-medium had a density of 1.175 to 1.180 g/cm(3) and were readily separable from chromatophores having a density of 1.220 to 1.230 isolated from cells grown in a 70% D(2)O-medium. After a shift from "D(2)O-" to "H(2)O"-based media, only hybrid chromatophores derived from a combination of "heavy" (old) and "light" (new) chromatophore material could be detected. The experimentally determined, median density values for the growing intracytoplasmic membrane system followed a theoretically determined profile which was calculated from the density of full "heavy" and full "light" material assuming random, homogeneous incorporation of new material into old membrane. The distribution of the radioactive labels for protein (leucine) and chlorophyll (delta-aminolevulinic acid) were identical and showed a reproducible displacement of the "old" material to the heavy side of the optical density at 365 nm (OD(365)) absorbance and a displacement of the "new" material to the light side of the OD(365) absorbance profile. Specific phospholipid growth showed no displacement for either the "old" or "new" material from the median absorbance profile.