Facial soft tissue thicknesses in Bulgarian adults: relation to sex, body mass index and bilateral asymmetry

Background: The aim of the study is to measure the facial soft tissue thicknesses (STTs) in Bulgarians, to evaluate the relation of the STTs to the nutritional status, sex and bilateral asymmetry, and to examine the correlations between the separate STTs as well as between the STTs and body weight, height, and body mass index (BMI). In the present study, the facial STTs were measured on computed tomography scans of the head of Bulgarian adults. Materials and methods: The STTs were measured at 7 midline and 9 bilateral landmarks. The measurements were performed in the free software InVesalius in the axial and sagittal planes. The mean, standard deviation, minimum and maximum values, median and coefficient of variation were reported for the STT at each landmark according to the sex and BMI category. The BMI, sex and bilateral differences were assessed for statistical significance. Pearson correlation analysis was applied to assess the strength and direction of the relationships between the STTs and body height, weight and BMI, as well as between separate STTs. Results and Conclusions: The facial soft tissues in Bulgarian adults changed in accordance with the nutritional status of the individual and in both sexes all STTs augmented with the increasing BMI. For both normal and overweight BMI categories, males had more soft tissue at the majority of facial points than females, as the only exceptions were observed in the cheek zone, where STTs were thicker in females. Significant bilateral differences were observed in either sex and BMI category. Stronger correlations were established for the STTs in the jaw region and between the cheek and jaw soft tissues. Besides, the correlations between the homologous bilateral landmarks were among the strongest ones

Challenges of diagnostic exome sequencing in an inbred founder population

Exome sequencing was used as a diagnostic tool in a Roma/Gypsy family with three subjects (one deceased) affected by lissencephaly with cerebellar hypoplasia (LCH), a clinically and genetically heterogeneous diagnostic category. Data analysis identified high levels of unreported inbreeding, with multiple rare/novel "deleterious" variants occurring in the homozygous state in the affected individuals. Step‐wise filtering was facilitated by the inclusion of parental samples in the analysis and the availability of ethnically matched control exome data. We identified a novel mutation, p.Asp487Tyr, in the VLDLR gene involved in the Reelin developmental pathway and associated with a rare form of LCH, the Dysequilibrium Syndrome. p.Asp487Tyr is the third reported missense mutation in this gene and the first example of a change affecting directly the functionally crucial β‐propeller domain. An unexpected additional finding was a second unique mutation (p.Asn494His) with high scores of predicted pathogenicity in KCNV2, a gene implicated in a rare eye disorder, retinal cone dystrophy type 3B. This result raised diagnostic and counseling challenges that could be resolved through mutation screening of a large panel of healthy population controls. The strategy and findings of this study may inform the search for new disease mutations in the largest European genetic isolate

Rapid conjugation of antibodies to toxins to select candidates for the development of anticancer Antibody-Drug conjugates (ADcs)

Antibody-Drug Conjugates (ADCs) developed as a targeted treatment approach to deliver toxins directly to cancer cells are one of the fastest growing classes of oncology therapeutics, with eight ADCs and two immunotoxins approved for clinical use. However, selection of an optimum target and payload combination, to achieve maximal therapeutic efficacy without excessive toxicity, presents a significant challenge. We have developed a platform to facilitate rapid and cost-effective screening of antibody and toxin combinations for activity and safety, based on streptavidin-biotin conjugation. For antibody selection, we evaluated internalization by target cells using streptavidin-linked antibodies conjugated to biotinylated saporin, a toxin unable to cross cell membranes. For payload selection, we biotinylated toxins and conjugated them to antibodies linked to streptavidin to evaluate antitumour activity and pre-clinical safety. As proof of principle, we compared trastuzumab conjugated to emtansine via streptavidin-biotin (Trastuzumab-SB-DM1) to the clinically approved trastuzumab emtansine (T-DM1). We showed comparable potency in reduction of breast cancer cell survival in vitro and in growth restriction of orthotopic breast cancer xenografts in vivo. Our findings indicate efficient generation of functionally active ADCs. This approach can facilitate the study of antibody and payload combinations for selection of promising candidates for future ADC development

Acute immune signatures and their legacies in severe acute respiratory syndrome coronavirus-2 infected cancer patients

Given the immune system’s importance for cancer surveillance and treatment, we have investigated how it may be affected by SARS-CoV-2 infection of cancer patients. Across some heterogeneity in tumor type, stage, and treatment, virus-exposed solid cancer patients display a dominant impact of SARS-CoV-2, apparent from the resemblance of their immune signatures to those for COVID-19+ non-cancer patients. This is not the case for hematological malignancies, with virus-exposed patients collectively displaying heterogeneous humoral responses, an exhausted T cell phenotype and a high prevalence of prolonged virus shedding. Furthermore, while recovered solid cancer patients’ immunophenotypes resemble those of nonvirus-exposed cancer patients, recovered hematological cancer patients display distinct, lingering immunological legacies. Thus, while solid cancer patients, including those with advanced disease, seem no more at risk of SARS-CoV-2-associated immune dysregulation than the general population, hematological cancer patients show complex immunological consequences of SARS-CoV-2 exposure that might usefully inform their care

Application of the deblurring technique and segmentation on medical computed tomography (CT) images for improved visualization of the cranial sutures

Introduction: The investigation of the cranial suture morphology and the changes occurring during the oblit­eration is an important precondition for understanding suture maturation and its relation to ageing. The μCT-imaging of dry skulls with known age-at-death is a powerful tool in this direction, but this technology is still ex­pensive, difficult to access and entirely inapplicable on living individuals. On the other hand, the diagnostic im­aging of patients accumulates large amount of volumetric images, which could be used for scientific researches. In medical imaging, the generated data is typically artificially blurred for denoising purposes. The standard Gauss­ian blur assigns a weighted average value for the gray-scale intensity of each pixel, based on the initial intensities of the pixel and its neighbors. Unfortunately, together with the noise reduction, such a procedure decreases the contrast on image contours and significantly complicates the study of cranial sutures.Aim: This study aims to apply theoretical and experimental scientific techniques for optimal extraction of useful data for the degree of suture obliteration, from medical tomographic images.Materials: Volumetric images obtained from diagnostic imaging of patients with multislice CT system Toshiba Aquillion64 were used.Methods: We developed a deblurring technique, based on the penalized total variation optimization. We also segmented the output image, using an appropriate threshold in order to separate the suture (region of interest) from the background.Results: After processing the images, the contact between the adjacent cranial bones is clearer and the degree of suture closure could be interpreted more accurately.Acknowledgements: This study was supported by the Bulgarian National Science Fund, grant DN01/15- 20.12.2016

Assessment of sex differences in size and shape of foramen magnum on CT scans of Bulgarian adults

The aim of the study is to assess the sex differences in size and shape of the foramen magnum, to develop discrim­inant functions based on the measurements of the foramen magnum and to establish the most reliable variables for sex determination in Bulgarian adults.Computed tomography scans of the heads of 120 Bulgarian adults (52 males and 68 females) were used in the study. The segmentation of the skulls was performed with the software InVesalius. The length, breadth, and cir­cumference of the foramen were measured digitally based on the 3D coordinates of definite landmarks and semi­landmarks. The area of the foramen magnum was calculated using the Radinsky and Teixeria formulae, based on the dimensions of the foramen length and breadth. The shape of foramen magnum was classified as narrow, medium wide or wide on the basis of the breadth/length index values. The significance of the sex differences in the measurements and shape of foramen magnum was assessed by independent sample t-test and chi-square test. Univariate and multivariate discriminate function analyses were conducted. The leave-one-out classification method was used as a cross-validation procedure.The results demonstrated statistically significant sex differences in the size and shape of the foramen magnum. The area of the foramen magnum is the best discriminating parameter. Generally, the results from the univariate and multivariate discriminant function analysis showed that the measurements of the foramen magnum did not provide high predicting rates for sex estimation among the Bulgarian population.Acknowledgements: The study was supported by the Bulgarian National Science Fund, grant DN01/15-20.12.2016

Transversal, sagittal and dorsal anatomical MRI study of the rabbit liver

Magnetic resonance imaging (MRI) is an applicable method for the contemporary anatomical visualization of small mammals` abdominal organs. The anatomical object studied is separated into voxel units, depending on the magnetic field. The anatomical objects are obtained on thin scan levels. We studied the liver of ten sexually mature, clinically healthy New Zealand white rabbits in T2- and T1-weight­ed sequence.On a transversal plane, T2-weighted sequence, the anatomical boundary between the left and right liver lobes was not defined. The left medial lobe of the liver was hyperintense compared to the left lateral lobe. The gallbladder demonstrated a hypersignal. Medial to the quadrate lobe was the gallbladder. The cystic duct demonstrated hy­persignal to the parenchyma. The right, left medial and left lateral lobes of the liver had dark grey tissue contrast.On sagittal T2 of the abdominal region at the level of the plane, 10 mm to the left, the left medial lobe of the liver was hypointense. Caudal to the left medial lobe was the lateral one. In the sagittal plane, 20 mm to the left, the me­dial and left lateral lobes and papillary process were hyposignal anatomical findings. In the sagittal plane, at 10 mm to the right, the right lobe was cranial to the fundus and body of the stomach. The papillary process touched the fundus of the stomach. The caudate process reached the right adipose capsule of the kidney. In the sagittal plane, 20 mm to the right, the left medial and quadrate lobes were caudal to the right lobe. The caudate lobe was dorsal.In the dorsal plane (T1-weighted sequence), 15 mm ventral to the spine, the right lobe was cranial to the other lobes. Left to the median plane was the left lobe. In the dorsal plane, 30 mm to the spine, the right lobe was cov­ered by the caudate lobe. The left medial lobe covered the left one. In the plane, 45 mm ventral to the spine, the right and left lobes were hyposignal findings in the same anatomical plane