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Highlights: [•] The manuscript describes our view on hemocyte subsets, lineages and compartments. [•] The paper details the plasticity of plasmatocyte/macrophage lineages. [•] One of the main points of the paper is the regulation of the cell mediated immunity. [•] Phenotypic and functional changes upon effector cell differentiation are described. [•] The ontogenesis of the hematopoietic compartments is presented. [ABSTRACT FROM AUTHOR]

A ten-year-old neutered female mixed breed dog was referred for pale mucous membrane and acute onset of right prosencephalic clinical signs. Brainmagnetic resonance imagingwas suggestive for right middle cerebral artery ischemic stroke. Based on cell blood count, serum biochemistry and serologic tests and flow cytometric detection of anti-platelets and anti-red blood cells antibodies, a diagnosis of immunomediated haemolytic anemia associated with thrombocytopenia of suspected immunomediated origin was done. Immunosuppresive therapy with prednisone was started and the dog clinically recovered. Two months later complete normalization of CBC and serum biochemistry was documented. The dog remained stable for 7 months without therapy; then she relapsed. CBC revealed mild regenerative anemia with spherocytosis and thrombocytopenia. A conclusive Evans' syndrome diagnosis was done and prednisone and cyclosporine treatment led to normalization of physical and CBC parameters. The dog is still alive at the time the paper submitted. Possible thrombotic etiopathogenetic mechanisms are illustrated in the paper and the authors suggest introducing Evans' syndrome in the differential diagnosis list for brain ischemic stroke in dogs. [ABSTRACT FROM AUTHOR]

This paper describes the methodology used to develop a consensual glossary for haematopoietic cells within Diagnostics-WP10 of European-LeukemiaNet EU-project. This highly interactive work was made possible through the use of the net, requiring only a single two-day meeting of actual confrontation and debate. It resulted in the production of a freely accessible tool that could be useful for training as well as harmonization of morphological reports in onco-haematology especially, without geographic limitation, not limited to European countries. Moreover, this collective work resulted in the production of a consensus statement, taking into account individual practices, collegial agreement and literature data.

Intense research has been carried out in recent years into methods that aim to harvest fetal genetic material from maternal blood as substitutes to amniocentesis and chorionic villus sampling. Just over 30 years have past since the first fetal cells were separated from maternal blood using flow cytometry highlighting the prospect of non-invasive prenatal diagnosis of fetal abnormalities. The aim of this review paper is to describe the most commonly used cell separation methods with emphasis on the isolation of fetal cells from maternal blood. The most significant breakthroughs and advances in fetal cell separation are reviewed and critically analyzed. Although much has been accomplished using well established techniques, a rapid and inexpensive method to separate fetal cells with great accuracy, sensitivity and efficiency to maximize cell yield is still required. In the past decade MEMS (Micro Electro Mechanical Systems) technologies have enabled the miniaturization of many biological and medical laboratory processes. Lab-on-chip systems have been developed and encompass many modules capable of processing different biological samples. Such chips contain various integrated components such as separation channels, micropumps, mixers, reaction and detection chambers. This article will also explore new emerging MEMS based separation strategies, which hope to overcome the current limitations in fetal cell separation., (2010 Elsevier B.V. All rights reserved.)

This paper proposes a novel and probably the first method, using Attanassov intuitionistic fuzzy set theory to segment blood vessels and also the blood cells in pathological images. This type of segmentation is very important in detecting different types of human diseases, e.g., an increase in the number of vessels may lead to cancer in prostates, mammary, etc. The medical images are not properly illuminated, and segmentation in that case becomes very difficult. A novel image segmentation approach using intuitionistic fuzzy set theory and a new membership function is proposed using restricted equivalence function from automorphisms, for finding the membership values of the pixels of the image. An intuitionistic fuzzy image is constructed using Sugeno type intuitionistic fuzzy generator. Local thresholding is applied to threshold medical images. The results showed a much better performance on poor contrast medical images, where almost all the blood vessels and blood cells are visible properly. There are several fuzzy and intuitionistic fuzzy thresholding methods, but these methods are not related to the medical images. To make a comparison with the proposed method with other thresholding methods, the method is compared with six nonfuzzy, fuzzy, and intuitionistic fuzzy methods.

Interactions between flow and biological cells and tissues are intrinsic to the circulatory, respiratory, digestive and genitourinary systems. In the circulatory system, an understanding of the complex interaction between the arterial wall (a living multi-component organ with anisotropic, nonlinear material properties) and blood (a shear-thinning fluid with 45% by volume consisting of red blood cells, platelets, and white blood cells) is vital to our understanding of the physiology of the human circulation and the etiology and development of arterial diseases, and to the design and development of prosthetic implants and tissue-engineered substitutes. Similarly, an understanding of the complex dynamics of flow past native human heart valves and the effect of that flow on the valvular tissue is necessary to elucidate the etiology of valvular diseases and in the design and development of valve replacements. In this paper we address the influence of biomechanical factors on the arterial circulation. The first part presents our current understanding of the impact of blood flow on the arterial wall at the cellular level and the relationship between flow-induced stresses and the etiology of atherosclerosis. The second part describes recent advances in the application of fluid-structure interaction analysis to arterial flows and the dynamics of heart valves.

This paper introduces a novel recovery strategy for endothelial colony forming progenitor cells (ECFCs) from heparinized but otherwise unmanipulated adult human peripheral blood within a mean of 12 days. After large scale expansion >1x10(8) ECFCs can be obtained for further tests. Advantageously by using pHPL the contact of human cells with bovine serum antigens can be excluded. By flow cytometry and immunohistochemistry the isolated cells can be characterized as ECFC and their in vitro functionality to form vascular like structures can be tested in a matrigel assay. Further these cells can be subcutaneously injected in a mouse model to form functional, perfused vessels in vivo. After long term expansion and cryopreservation proliferation, function and genomic stability appear to be preserved. (3,4) This animal-protein free isolation and expansion method is easily applicable to generate a large quantity of ECFCs.

Since most clinical assays are performed on cell-free serum or plasma, micro-analytical systems for blood tests require integrated on-chip microfluidics for the isolation of plasma or serum from crude blood samples. In this paper, we present a crossflow filtration method using novel silicon nano-filters for plasma separation. The microfluidic chip is made of a silicon substrate containing micropillar arrays, feed channels, side channels and nano-gap structures, sealed with a PDMS-glass compound cover. The design of the silicon filtration structures were optimized using numerical analysis and the optimal MEMS fabrication procedures were obtained. The filtration structures including nano-filters were characterized using SEM and subsequently used to isolate plasma from whole blood in a continuous manner. Compared with micro-gap structures in silicon microfluidic channels, the nano-gap structures have been used to separate plasma from whole blood samples with higher selectivity, where a maximum plasma selectivity of 97.7% has been obtained. Common problems of clogging and jamming in filtration applications have seldom been noticed in our device. The presented microfluidic filtration device for plasma isolation could be integrated into microTAS for point-of-care diagnostics in the near future.

This paper presents a microfluidic chip for highly efficient separation of red blood cells (RBCs) from whole blood on the basis of their native magnetic properties. The glass chip was fabricated by photolithography and thermal bonding. It consisted of one inlet and three outlets, and a nickel wire of 69-microm diameter was positioned in the center of a separation channel with 149-microm top width and 73-microm depth by two parallel ridges (about 10 microm high). The two ridges were formed simultaneously during the wet etching of the channels. The nickel wire for generating the magnetic gradient inside the separation channel was introduced from the side of the chip through a guide channel. The external magnetic field was applied by a permanent magnet of 0.3 T placed by the side of the chip and parallel to the main separation channel. The RBCs were separated continuously from the 1:40 (v/v) diluted blood sample at a flow rate in the range 0.12-0.92 microL/min (9-74 mm/min) with the chip, and up to 93.7% of the RBCs were collected in the middle outlet under a flow rate of 0.23 microL/min. The cell sedimentation was alleviated by adjusting the specific density of the supporting media with bovine serum albumin. Quantum dot labeling was introduced for visual fluorescence tracking of the separation process. The uneven distribution phenomenon of the blood cells around the nickel wire was reported and discussed.

The Spanish haematology external quality assessment scheme (EQAS), established in 1984, is run by the Spanish Haematology and Haemotherapy Association (AEHH) [Quality Assurance in Health Care 3 (1991) 75] and functions to evaluate the quality and reproducibility of the assessment of diagnostic samples by clinical laboratories. The Hospital Clinic of the University of Barcelona (HCB) serves as the EQAS Coordination Centre and follows the guidelines established by the International Committee for Standardization in Haematology [Annali dell'Istituto superiore di Sanità 31 (1995) 95; International Journal of Hematology 68 (1998) 45]. During the period 2001-2006, replicates of 25 different blood films were sent to 604 EQAS participants for cell morphology evaluation. Some patient details corresponding to the samples were disclosed, such us age, sex, haemoglobin value and white blood cell count. The participants were asked to select up to four significant morphology features using a coding list, provided by the Coordination Centre, which included significant morphological alterations that appear in haematopoietic cells. For each survey, individual results were assessed against the morphological reference results (MRR) established by the Cytology Group of the AEHH ('true' answers). This paper describes the organization of the 6-year-long study and the evaluation of laboratory performance for blood smear interpretation by the Spanish haematology EQAS. Different performance levels were detected relative to the laboratory category. Laboratories providing services to hospitalized patients showed higher performances compared with laboratories providing services to nonhospitalized patients. Pathological lymphoid cells were the most difficult to identify by the participants. To improve the results in EQAS peripheral blood morphology, the development of specific cytology educational trainings is discussed.

The paper shows limitations of the traditional indices used to evaluate a patient's chemical status and describes methods for assessment of its uniformity, by using nonparametric chi 2 test, identifying patient subgroups, and comparing a few groups. A new procedure is proposed to present cytochemical findings.

In this paper, we present a blood cell recognition method based on wavelet packet analysis and the neural network. The blood cell signals were decomposed, then the discrete wavelet coefficients were reconstructed and energy values were calculated. The energy values together with seven features in time domain were used as the inputs of the BP network. Finally the network was established and trained. The accuracies of recognition on different conditions are discussed too. The experimental results show that the proposed method has a high accuracy of recognition.

MEKOC microscopy complexes have a group of specialized automatic functions for medical analyses of biomaterials integrated with general virtual microscopy accessories. Such functions provide a way of making specialized reference virtual slides (RVS). The latter contain the results of virtual analysis or expert evidence of the automatic analysis results presented in the virtual slide. The use of RVS yields an open system with a step-by-step control of the quality of automatic operations. RVS as realistic preparation models are also used to train staff. The results of step-by-step trials of the MEKOC--2 are presented in the paper.

Integrating cell lysis and DNA purification process into a micrototal analytical system (microTAS) is one critical step for the analysis of nucleic acids. On-chip cell lysis based on a chemical method is realized by sufficient blend of blood sample and the lyzing reagent. In this paper two mixing models, T-type mixing model and sandwich-type mixing model, are proposed and simulation of those models is conducted. Result of simulation shows that the sandwich-type mixing model with coiled channel performs best and this model is further used to construct the microfluidic biochip for on-line cell lysis and DNA extraction. The result of simulation is further verified by experiments. It asserts that more than 80% mixing of blood sample and lyzing reagent which guarantees that completed cell lysis can be achieved near the inlet location when the cell/buffer velocity ratio is less than 1:5. After cell lysis, DNA extraction by means of a solid-phase method is implemented by using porous silicon matrix which is integrated in the biochip. During continuous flow process in the microchip, rapid cell lysis and PCR-amplifiable genomic DNA purification can be achieved within 20 min. The potential of this microfluidic biochip is illustrated by pretreating a whole blood sample, which shows the possibility of integration of sample preparation, PCR, and separation on a single device to work as portable point-of-care medical diagnostic system.

This paper reports on the comparison analysis of four main types of silicon-based microfilter for isolation of white blood cells (WBCs) from red blood cells (RBCs) in a given whole blood. The microfilter designs, namely, weir, pillar, crossflow, and membrane, all impose the same cut-off size of 3.5 mum to selectively trap WBCs. Using human whole blood, the microfilters have been characterized and compared for their blood handling capacity, WBCs trapping efficiency and RBCs passing efficiency. Based on the experimental results, the crossflow microfilter is superior and can be integrated with downstream components for on-chip genomic analysis.

This paper reports a lens-integrated liquid crystal display (LCD)-based optoelectronic tweezers (OET) system for interactive manipulation of polystyrene microspheres and blood cells by optically induced dielectrophoretic force. When a dynamic image pattern is projected into a specific area of a photoconductive layer in an OET, virtual electrodes are generated by spatially resolved illumination of the photoconductive layer, resulting in dielectrophoresis of microparticles suspended in the liquid layer under nonuniform electric field. In this study, the simple-structured OET system has been easily constructed with an OET device, an LCD and a condenser lens integrated in a conventional microscope. By using a condenser lens, both stronger dielectrophoretic forces and higher virtual electrode resolution than previously reported lens-less LCD-based OET platform are obtained. The effects of blurred LCD image and liquid chamber height on the performances of optoelectronic particle manipulation are investigated by measuring the bead velocities according to their sizes. An interactive control program for OET-based microparticle manipulation is also developed by Flash language. The integrated system is successfully applied to the parallel and interactive manipulation of red and white blood cells. Due to its simple structures, cheap manufacturing costs, and high performances, this new LCD-based OET platform may be a widely usable integrated system for optoelectronic manipulation of microparticles including living cells.

Segmentation of vessels in biomedical images is important as it can provide insight into analysis of vascular morphology, topology and is required for kinetic analysis of flow velocity and vessel permeability. Intravital microscopy is a powerful tool as it enables in vivo imaging of both vasculature and circulating cells. However, the analysis of vasculature in those images is difficult due to the presence of cells and their image gradient. In this paper, we provide a novel method of segmenting vessels with a high level of cell related clutter. A set of virtual point pairs ("vessel probes") are moved reacting to forces including Vessel Vector Flow (VVF) and Vessel Boundary Vector Flow (VBVF) forces. Incorporating the cell detection, the VVF force attracts the probes toward the vessel, while the VBVF force attracts the virtual points of the probes to localize the vessel boundary without being distracted by the image features of the cells. The vessel probes are moved according to Newtonian Physics reacting to the net of forces applied on them. We demonstrate the results on a set of five real in vivo images of liver vasculature cluttered by white blood cells. When compared against the ground truth prepared by the technician, the Root Mean Squared Error (RMSE) of segmentation with VVF and VBVF was 55% lower than the method without VVF and VBVF.

In this paper we study automatic classification of working areas in peripheral blood smears using image analysis and recognition methods. Such automatic classification can provide objective and reproducible quality control for the evaluation of smears and smear maker devices. However, research in this filed has drawn little attention. Existing methods either can not differentiate correctly different cell distributions or rely on the extraction of the central pallor zones in cells for counting, which are not always observable. In contrast, we do not rely on the pallor zone extraction thus on more general basis. We introduce two generic parameters to measure the goodness of working areas, one for the degree of overlap, and the other for the spatial occupancy. We also propose a cascading classification network for the classification of different areas. The effectiveness of our method has been tested on over 150 labeled images acquired from three malaria-infected Giemsa-stained blood smears using an oil immersion 100 x objective.

Ultrastructural characteristics of erythrocytes, heterophils, eosinophils, lymphocytes, monocytes and thrombocytes of the loggerhead sea turtle (Caretta caretta) were evaluated, using blood samples from 15 healthy juvenile animals. Except for the eosinophils, the rest of the white blood cells from loggerhead turtles had similar ultrastructural characteristics compared with blood cells from other sea turtle species. Eosinophils from loggerhead turtles were homogeneous in size, and no crystalline structures were observed within the granules. This paper provides an ultrastructural characterization of blood cells of loggerhead sea turtles, as a reference for future haematological studies of this species.

Viscous shear stress and Reynolds stress are often used to predict hemolysis and thrombosis due to flow-induced stress on blood elements in cardiovascular devices. These macroscopic stresses are distinct from the true stress on an individual cell, which is determined by the local microscale flow field. In this paper the flow-induced stress on blood cells is calculated for laminar and turbulent flow, using simplified models for cells and for turbulent eddies. The model is applied to estimate shear stress on red blood cells in flow through a prosthetic heart valve, using the energy spectral density measured by Liu et al. [J. Biomech. Eng. 122:118-124, 2000]. Results show that in laminar flow, the maximum stress on a cell is approximately equal to the macroscopic viscous shear stress. In turbulent flow through a prosthetic heart valve, the estimated root mean square of flow-induced stress on a cell is at least an order of magnitude less than the Reynolds stress. The results support the hypothesis that smaller turbulent eddies cause higher stress on cells. However, the stress due to an eddy depends on the velocity scale of the eddy as well as its length scale. For the heart valve flow investigated, turbulence contributes to flow-induced stress on cells almost equally across a broad range of the frequency spectrum. The model suggests that Reynolds stress alone is not an adequate predictor of cell damage in turbulent flow, and highlights the importance of the energy spectral density.

Autofocusing is a fundamental procedure towards automated microscopic evaluation of blood smear and pap smear samples for clinical diagnosis. This paper presents comparison results of 16 selected focus algorithms based on 8000 static bright-field images and 1600 dynamic autofocusing trials using 10 blood smear and pap smear samples. Besides static behaviour, dynamic autofocusing performance is introduced for ranking the 16 focus algorithms. The Fibonacci search algorithm is employed for controlling the z-motor of the microscope to reach the focus position that is determined by focus objective functions. Experimental results demonstrate that the variance algorithm provides the best overall performance. Together with our previously reported findings, it is demonstrated that the variance algorithm or the normalized variance algorithm is the optimal focus algorithm for non-fluorescence microscopy applications including pap smear and blood smear imaging.

The paper describes the design of a cell that allows one by the chemiluminescence technique to assess the interaction of whole blood cells with the macroscopic hard surface of various materials, as well as procedures for its handling. The cell ensures thermostatting, mixing, supply of a blood microvolume with nutrients and additional reagents, and cell vital activity maintenance within several hours.

L-Arginine is a precursor of polyamine, nitric oxide (NO), creatine, and agmatine and is essential for the differentiation and proliferation of blood cells, although the precise biological role of L-arginine is unclear. We have recently reported that the depletion of L-arginine in cultured medium prevented both proliferation and differentiation of blood cells (Shima et al., Blood First Edition Paper, October 6, 2005; DOI 10.1182). Since one of metabolic products of L-arginine in the cells is polyamine that associates with cell differentiation and proliferation, the effects of L-arginine on the human K562 cell line and human cord blood-derived CD34 positive cells were investigated by focusing on polyamines such as putrescine, spermidine, and spermine in the present study. When polyamines were added to the culture medium in the absence of L-arginine, the cells did not grow or differentiate well. However, when intracellular polyamines were depleted using ornithine decarboxylase inhibitor, alpha-difluoromethylornithine (DFMO), the proliferation and differentiation of K562 cells to erythrocytes were reduced even in the presence of L-arginine. Moreover, in the presence of DFMO, cell differentiation and proliferation were recovered by the addition of putrescine or spermidine in the presence of L-arginine. Accordingly, it was demonstrated that polyamines are essential for the proliferation and differentiation of the blood cells as the metabolites of L-arginine and the externally added polyamines are also effective by being taken up through polyamine transporter.

This paper examines the service-wide costs to the English NHS that are associated with a Hospital Trust expanding the utilisation of cell salvage techniques as an alternative to using donated blood collected from volunteer donors. Costs in the respective NHS organisations should not be viewed in isolation. Significant savings can be realised by adopting a collaborative approach to expand the use of cell salvage techniques. In time, the associated increase in cell salvage utilisation will generate cost savings at the National Blood Service, with more immediate realisable savings arising within Hospital Trust budgets.

Simple Summary: This paper proposes a hybrid generative adversarial networks model—WGAN-GP-AC—to generate synthetic microscopic cell images. We generate the synthetic data for the cell types containing fewer data to obtain a balanced dataset. A balanced dataset would help enhance the classification accuracy of each cell type and help with an easy and quick diagnosis that is critical for leukemia patients. In this work, we combine images from three datasets to form a single concrete dataset with variations of multiple microscopic cell images. We provide experimental results that prove the correlation between the original and our synthetically generated data. We also deliver classification results to showcase that the generated synthetic data can be used for real-life experiments and the advancement of the medical domain. Every year approximately 1.24 million people are diagnosed with blood cancer. While the rate increases each year, the availability of data for each kind of blood cancer remains scarce. It is essential to produce enough data for each blood cell type obtained from bone marrow aspirate smears to diagnose rare types of cancer. Generating data would help easy and quick diagnosis, which are the most critical factors in cancer. Generative adversarial networks (GAN) are the latest emerging framework for generating synthetic images and time-series data. This paper takes microscopic cell images, preprocesses them, and uses a hybrid GAN architecture to generate synthetic images of the cell types containing fewer data. We prepared a single dataset with expert intervention by combining images from three different sources. The final dataset consists of 12 cell types and has 33,177 microscopic cell images. We use the discriminator architecture of auxiliary classifier GAN (AC-GAN) and combine it with the Wasserstein GAN with gradient penalty model (WGAN-GP). We name our model as WGAN-GP-AC. The discriminator in our proposed model works to identify real and generated images and classify every image with a cell type. We provide experimental results demonstrating that our proposed model performs better than existing individual and hybrid GAN models in generating microscopic cell images. We use the generated synthetic data with classification models, and the results prove that the classification rate increases significantly. Classification models achieved 0.95 precision and 0.96 recall value for synthetic data, which is higher than the original, augmented, or combined datasets. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), still remains a severe threat. At the time of writing this paper, the second infectious wave has caused more than 280,000 deaths all over the world. Italy was one of the first countries involved, with more than 200,000 people reported as infected and 30,000 deaths. There are no specific treatments for COVID-19 and the vaccine still remains somehow inconclusive. The world health community is trying to define and share therapeutic protocols in early and advanced clinical stages. However, numbers remain critical with a serious disease rate of 14%, ending with sepsis, acute respiratory distress syndrome (ARDS), multiple organ failure (MOF) and vascular and thromboembolic findings. The mortality rate was estimated within 2–3%, and more than double that for individuals over 65 years old; almost one patient in three dies in the Intensive Care Unit (ICU). Efforts for effective solutions are underway with multiple lines of investigations, and health authorities have reported success treating infected patients with donated plasma from survivors of the illness, the proposed benefit being protective antibodies formed by the survivors. Plasma transfusion, blood and stem cells, either autologous or allograft transplantation, are not novel therapies, and in this short paper, we propose therapeutic autologous plasma and peripheral blood stem cells as a possible treatment for fulminant COVID-19 infection. [ABSTRACT FROM AUTHOR]

This paper reports a polyelectrolytic salt bridge-based electrode (PSBE), which is a key embedded unit in a microchip device that can size-selectively count microparticles and measure their velocities. The construction of salt bridges at specific locations within a microfluidic chip enables dc-driven electrical detection to be performed successfully. This is expected to be a competitive alternative to the optical methods currently used in conventional cell sorters. The PSBEs were fabricated by irradiating ultraviolet light over a patterned mask on the parts of interest, which were filled with an aqueous monomer solution containing diallyldimethylammonium chloride. A pair of such PSBEs was easily formed at the two lateral branches perpendicular to the main microchannel and was found to be very useful for dc impedometry. The human blood cells as well as the fluorescent microbeads passing between the two PSBEs produced impedance signals in proportional to their size. The information about the velocity of a microparticle was extracted from a doublet of the dc impedance signals, which were generated when cells or microbeads sequentially passed through two PSBE pairs separated from each other by a fixed distance. The plot of peak amplitude versus velocity of the moving microbeads and cells indicated only a slight correlation between the size and the velocity, which means that the peak amplitude of the dc impedance signals alone can provide information about the size of the cells in a mixture. The experimental results showed a screening rate of over 1000 cells s(-1) and a velocity of the cells of over 100 mm s(-1). Compared with the previously suggested electrical detection system based on metal electrodes, the sensitivity and selectivity in cell detection were remarkably improved. In addition, the detection unit including the operating circuit became innovatively simple and the whole device could be miniaturized.

Neurodegenerative diseases as well as acute center nervous system (CNS) injuries remains a problematic and frustrating area of medicine in terms of treatments and cures, which is mostly due to the complex circuitry of the CNS along with our limited knowledge. Therapeutically, the last two and a half decades have offered new hope for those suffering from neurodegenerative diseases or injuries with advent of new drug discoveries and cellular therapies. Cell transplantation is a compelling and potential treatment for certain neurological and neurodegenerative diseases as well as for acute injuries to the spinal cord and brain. The hematopoietic system offers an alternative source of cells that is easily obtainable, abundant, and reliable when compared to cells obtained from fetal or embryonic origins. Human umbilical cord blood (HUCB) cells have been used clinically for over ten years to treat both malignant and non-malignant diseases. With in the last five years these cells have been used pre-clinically in animal models of brain and spinal cord injuries, in which functional recovery have been shown. This paper reviews the advantages, utilization, and progress of HUCB cells in the field of cellular transplantation and repair.

Potentialities of analyzing the health condition of human organism and of its separate systems, i.e. digestive, respiratory, cardiovascular, etc., by the peripheral-blood parameters and with the help of the suggested AKS-ENOFIT analytical system are demonstrated in the paper.

The support vector machine (SVM) is a new learning technique based on the statistical learning theory. It was originally developed for two-class classification. In this paper, the SVM approach is extended to multi-class classification problems, a hierarchical SVM is applied to classify blood cells in different maturation stages from bone marrow. Based on stepwise decomposition, a hierarchical clustering method is presented to construct the architecture of the hierarchical (tree-like) SVM, then the optimal control parameters of SVM are determined by some criterion for each discriminant step. To verify the performances of classifiers, the SVM method is compared with three classical classifiers using 3-fold cross validation. The preliminary results indicate that the proposed method avoids the curse of dimensionality and has greater generalization. Thus, the method can improve the classification correctness for blood cells from bone marrow.

This paper describes a system on a chip (SoC) that makes use of nanoscale cellular adhesion mechanisms in an integrated electronic microsystem to filter infected cells from blood or lymph. An example of a human immunodeficiency virus-specific SoC is explored in depth. Such systems work in vivo, and blood and lymph are filtered on a continuous basis. With the intelligence on the chip, captured cells can be identified and lyzed, expelled, or otherwise acted upon. These types of systems transfer the burden of research from traditional chemotherapy to bioengineering and system design.

Betulin and betulinic acid, plant-derived triterpenoid compounds, have been described to possess anti-inflammatory activity. In this paper, we examine the ability of both compounds to induce and modulate cytokine production in human whole blood cell cultures. The results indicate that betulin is a modest TNF-alpha inducer and also an enhancer of mitogen-induced TNF-alpha production. In contrast to betulin, betulinic acid is a modulator of cytokine production by Th1/Th2 cell subpopulations which slightly enhances IL-10 formation and inhibits IFN-gamma production, reducing IFN-gamma/IL-10 ratio from 3.6 to 2.6.

The paper presents a technique to automatically detect the working area of peripheral blood smears stained with May-Grünwuald Giemsa. The optimal area is defined as the well spread part of the smear. This zone starts when the erythrocytes stop overlapping (on the body film side) and finishes when the erythrocytes start losing their clear central zone (on the feather edge side). The approach yields a quick detection of this area in images scanned under low magnifying power (immersion objective x 25 or x 16). The algorithm consists of two stages. First, an image analysis procedure using mathematical morphology is applied for extracting the erythrocytes, the centers of erythrocytes and the erythrocytes with center. Second, the number of connected components from the three kinds of particles is counted and the coefficient of spreading rho(s) and the coefficient of overlapping rho(o) are calculated. The data from fourteen smears illustrate how the technique is used and its performance. Colour figures can be viewed on http://www.esacp.org/acp/2003/25-1/angulo.htm.

Axial flow blood pumps provide additional energy to blood for heart failure patients, but its implanting destroys the environment of blood cells; the direct consequence is hemolysis. According to energy conservation theorem, the severity of pump hemolysis depends on the energy utilization ratio of it. This is a new train of thought in this field. In the light of it, it is necessary to clear up how much energy is used to pump blood, and so a portion of the remaining energy is the energy leading to hemolysis. At present, a complete hemolysis model of axial blood pump remains unknown. Based on the analysis of factors leading to hemolysis, this paper calculates the driving energy of blood pump from the angle of energy conservation, deduces the power for hemolysis, and then establishes a universally applicable hemolytic model of axial blood pump in normal operation conditions. Results: The relevant coefficients of it are derived from the in vivo experimental data. The setting up of mathematic model plays very important role in forecasting the hemolysis and improve the blood compatibility. This paper proposes a novel idea for hemolysis predicting of axial blood pump, which provides vital guidance for the design and improving of pumps control system and establishes a basis for follow-up work. [ABSTRACT FROM AUTHOR]

Since the start of the SARS-CoV-2 vaccination campaign, our knowledge of the effects of vaccines in people with inflammatory rheumatic diseases has remained incomplete. In particular, the effects of immunomodulatory therapies on vaccine success are poorly understood. Three notable papers from the past year have helped to fill these knowledge gaps. Key advances: Although SARS-CoV-2 vaccination seroconversion rates are lower in individuals with inflammatory rheumatic diseases under immunomodulatory therapy, the neutralizing capacity of anti-SARS-CoV-2 antibodies does not differ between affected and non-affected individuals7. In contrast to the humoral immune response, the cellular immune response to SARS-CoV-2 vaccination in patients receiving rituximab is maintained8. After rituximab therapy, determination of peripheral blood B cells may be a means to facilitate successful immunization, as the threshold for a successful immune response is 10 B cells per microlitre of peripheral blood9. [ABSTRACT FROM AUTHOR]

Vasculogenic mimicry (VM) refers to the ability of malignant cells to form microvascular channels, having nature of blood vessels but are not endothelium lined. These channels contain blood cells & plasma and provide sufficient nutrient supply to the cancerous cells to meet their metabolic demands. VM can be seen in various tumors and is associated with their malignant phenotype, high tumor grade, invasion, metastasis and poor clinical outcome. In this paper, we made an attempt to explain the mechanism, visualisation and prognostic significance of vasculogenic mimicry. [ABSTRACT FROM AUTHOR]

The contribution gives a survey about the problematics of surface tension in biomedical sciences. The paper presents results of a study devoted to the cerebrospinal fluid. The distribution of the surface tension values of this liquid in healthy individuals is presented (n = 33), and further, statistically significant correlations between the cerebrospinal fluid surface tension value and 1. concentration of total proteins expressed by Spearman's coefficient p(s) = (-0.995) and 2. number of cell elements expressed through Spearman's coefficient p(s) = (-0.965) in cerebrospinal fluid are described.

The development of predictive appearance models for organic tissues is a challenging task due to the inherent complexity of these materials. In this paper, we closely examine the biophysical processes responsible for the appearance attributes of whole blood, one the most fundamental of these materials. We describe a new appearance model that simulates the mechanisms of light propagation and absorption within the cellular and fluid portions of this specialized tissue. The proposed model employs a comprehensive, and yet flexible first principles approach based on the morphological, optical and biochemical properties of blood cells. This approach allows for environment driven changes in the cells' anatomy and orientation to be appropriately included into the light transport simulations. The correctness and predictive capabilities of the proposed model are quantitatively and qualitatively evaluated through comparisons of modeled results with actual measured data and experimental observations reported in the scientific literature. Its incorporation into rendering systems is illustrated through images of blood samples depicting appearance variations controlled by physiologically meaningful parameters. Besides the contributions to the modeling of material appearance, the research presented in this paper is also expected to have applications in a wide range of biomedical areas, from optical diagnostics to the visualization and noninvasive imaging of blood-perfused tissues. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a devastating traumatic injury that causes persistent, severe motor and sensory dysfunction. Immune responses are involved in functional recovery after SCI. Mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) has been shown to regulate the survival and differentiation of immune cells and to play a critical role in many diseases, but its function in lesion recovery after SCI remains unclear. In this paper, we generated KI (knock in) mice with a point mutation (C472G) in the active center of MALT1 and found that the KI mice exhibited improved functional recovery after SCI. Fewer macrophages were recruited to the injury site in KI mice and these macrophages differentiated into anti-inflammatory macrophages. Moreover, macrophages from KI mice exhibited reduced phosphorylation of p65, which in turn resulted in decreased SOCS3 expression and increased pSTAT6 levels. Similar results were obtained upon inhibition of MALT1 paracaspase with the small molecule inhibitor "MI-2" or the more specific inhibitor "MLT-827". In patients with SCI, peripheral blood mononuclear cells (PBMC) displayed increased MALT1 paracaspase. Human macrophages showed reduced pro-inflammatory and increased anti-inflammatory characteristics following the inhibition of MALT1 paracaspase. These findings suggest that inhibition of MALT1 paracaspase activity in the clinic may improve lesion recovery in subjects with SCI. [ABSTRACT FROM AUTHOR]

Following protein adsorption/activation which is the first step after the contact of material surfaces and whole blood (part 2), fibrinogen is converted to fibrin and platelets become activated and assembled in the form of a thrombus. This thrombus formation is the key feature that needs to be minimized in the creation of materials with low thrombogenicity. Further aspects of blood compatibility that are important on their own are complement and leukocyte activation which are also important drivers of thrombus formation. Hence this review summarizes the state of knowledge on all of these cascades and cells and their interactions. For each cascade or cell type, the chapter distinguishes statements which are in widespread agreement from statements where there is less of a consensus. This paper is part 3 of a series of 4 reviews discussing the problem of biomaterial associated thrombogenicity. The objective was to highlight features of broad agreement and provide commentary on those aspects of the problem that were subject to dispute. We hope that future investigators will update these reviews as new scholarship resolves the uncertainties of today. [ABSTRACT FROM AUTHOR]

The subset of pro-inflammatory B cells, called late memory, tissue-like or double negative (DN), accumulates in the blood of elderly individuals. Here we show that DN B cells do not proliferate and do not make antibodies to influenza antigens, but they secrete antibodies with autoimmune reactivity, in agreement with their membrane phenotype (CD95+CD21-CD11c+) and their spontaneous expression of the transcription factor T-bet. These cells also increase in the blood of individuals with obesity and autoimmune diseases, but causative mechanisms and signaling pathways involved are known only in part. In the present paper we compare frequencies and metabolic requirements of these cells in the blood of healthy individuals of different ages and in the blood and the subcutaneous adipose tissue (SAT) of individuals with obesity. Results show that DN B cells from young individuals have minimal metabolic requirements, DN B cells from elderly and obese individuals utilize higher amounts of glucose to perform autoimmune antibody production and enroll in aerobic glycolysis to support their function. DN B cells from the SAT have the highest metabolic requirements as they activate oxidative phosphorylation, aerobic glycolysis and fatty acid oxidation. DN B cells from the SAT also show the highest levels of ROS and the highest levels of phosphorylated AMPK (5’-AMP activated kinase) and Sestrin 1, both able to mitigate stress and cell death. This metabolic advantage drives DN B cell survival and function (secretion of autoimmune antibodies). [ABSTRACT FROM AUTHOR]

The paper presents experimental material on the composition of students' blood with insufficient oxygen content in atmospheric air. The impact of the mountain climate contributed to a significant increase in the values characterizing red blood and neutrophils, to a drop in the values of monocytes and to insignificant changes on both sides of other blood parameters. So, the growth of red blood cells and hemoglobin in boys in the middle mountains was 0.8 million in mm3 and 23 g / l, and in their peers - 0.9 and 26, respectively. In the blood of the girls of the second experimental group, there was 10.6% more neutrophils than controls. The concentration of monocytes is lower by 2,6% in young men from middle mountains. [ABSTRACT FROM AUTHOR]

Microscopic evaluation of peripheral blood smear analysis is a commonly used laboratory procedure to diagnose various diseases such as anemia, malaria, leukemia, etc. Manual microscopic evaluation is laborious and hence many research groups have attempted to automate smear analysis. Variations in staining procedure and smear preparation introduces color shade variations into peripheral blood smear images. Illumination provided by point source bulb introduces brightness variations across the smear which affects the performance of an automated method. In this paper we present an image processing algorithm for detection of nuclei of white blood cells which is robust to color and brightness variations. In the proposed method we used two different datasets and also five datasets which were derived from original images by introducing brightness variations. We also compared the results of the proposed method with four state-of-the-art methods. The results demonstrate that the proposed method detects nuclei accurately with an average accuracy of 0.99 and Dice coefficient of 0.965. [ABSTRACT FROM AUTHOR]

Hematological disorders refer to the diseases caused with the changes in blood cells or blood system such as Leukemia, Anemia, Malaria and Azotemia. Preprocessing of blood cell images is very important step in the detection of these disorders. Hence after image acquis ion from hematologists and oncologists denoising and edge detection are to be done to enhance the image for segmentation of blood cell images and leukocytes, erythrocytes and thrombocytes. Because leukemia can be detected from leukocytes and malarial parasites can be detected from erythrocytes. In this paper we have applied few techniques such as Gabor filter, Gaussian filter, Prewitt filter, Sobel and Canny edge operators for the preprocessing purpose. We have compared the performance of these techniques based on their accuracy and resolution. [ABSTRACT FROM AUTHOR]

Validity. The paper describes the results of a study aimed at the investigation of the influence of electrolyzed alkaline water (catholyte) on the tumor development in hamsters. At present there are no much data about the effect of catholyte on the tumor growth and hematological parameters of experimental animals. Goal: The goal of the present work is to investigate biological effects of the catholyte on the tumor growth, hematological biomarkers and morphology of the blood cells from tumor-bearing hamsters. Methods: Graffitumor was transplanted subcutaneously in the back of the experimental group of Golden Syrian hamsters. Tumor appearance and growth were registered every day. Blood parameters were measured from blood smears on the 10th and 25th day after transplantation. Results: Hamsters treated with catholyte developed tumor with some delay. Also, the tumor growth was slow and the survival rate was increased. The analysis of blood parameters and cell morphology has shown significant differences in the value of some hematometric parameters and morphological changes of some blood cells. Conclusion: The obtained results suggest about the beneficial influence of catholyte as well as the possible use of it as a supporting non-invasive therapy of cancer diseases. [ABSTRACT FROM AUTHOR]

Microscopic examination of peripheral blood plays an important role in the field of diagnosis and control of major diseases. Peripheral leukocyte recognition by manual requires medical technicians to observe blood smears through light microscopy, using their experience and expertise to discriminate and analyze different cells, which is time-consuming, labor-intensive and subjective. The traditional systems based on feature engineering often need to ensure successful segmentation and then manually extract certain quantitative and qualitative features for recognition but still remaining a limitation of poor robustness. The classification pipeline based on convolutional neural network is of automatic feature extraction and free of segmentation but hard to deal with multiple object recognition. In this paper, we take leukocyte recognition as object detection task and apply two remarkable object detection approaches, Single Shot Multibox Detector and An Incremental Improvement Version of You Only Look Once. To improve recognition performance, some key factors involving these object detection approaches are explored and the detection models are generated using the train set of 14,700 annotated images. Finally, we evaluate these detection models on test sets consisting of 1,120 annotated images and 7,868 labeled single object images corresponding to 11 categories of peripheral leukocytes, respectively. A best mean average precision of 93.10% and mean accuracy of 90.09% are achieved while the inference time is 53 ms per image on a NVIDIA GTX1080Ti GPU. [ABSTRACT FROM AUTHOR]

Many mRNA-based vaccines have been investigated for their specific potential to activate dendritic cells (DCs), the highly-specialized antigen-presenting cells of the immune system that play a key role in inducing effective CD4+ and CD8+ T-cell responses. In this paper we report a new vaccine/gene delivery platform that demonstrates the benefits of using a self-amplifying (“replicon”) mRNA that is protected in a viral-protein capsid. Purified capsid protein from the plant virus Cowpea Chlorotic Mottle Virus (CCMV) is used to in vitro assemble monodisperse virus-like particles (VLPs) containing reporter proteins (e.g., Luciferase or eYFP) or the tandem-repeat model antigen SIINFEKL in RNA gene form, coupled to the RNA-dependent RNA polymerase from the Nodamura insect virus. Incubation of immature DCs with these VLPs results in increased activation of maturation markers – CD80, CD86 and MHC-II – and enhanced RNA replication levels, relative to incubation with unpackaged replicon mRNA. Higher RNA uptake/replication and enhanced DC activation were detected in a dose-dependent manner when the CCMV-VLPs were pre-incubated with anti-CCMV antibodies. In all experiments the expression of maturation markers correlates with the RNA levels of the DCs. Overall, these studies demonstrate that: VLP protection enhances mRNA uptake by DCs; coupling replicons to the gene of interest increases RNA and protein levels in the cell; and the presence of anti-VLP antibodies enhances mRNA levels and activation of DCs in vitro. Finally, preliminary in vivo experiments involving mouse vaccinations with SIINFEKL-replicon VLPs indicate a small but significant increase in antigen-specific T cells that are doubly positive for IFN and TFN induction. [ABSTRACT FROM AUTHOR]

Blood counting is one of the most commonly ordered clinical assays, and is often part of the basis for initial diagnosis and screening for disease. While substantial prior research has shown the ability of portable instruments to accurately produce blood counts through image- or flow-based cytometry, these methods require complex sample preparation using either costly commercial imaging chambers or complicated reagents. To address these issues, in this paper we developed a method to prepare trace volumes of whole blood aimed at portable blood counting. The strategy is based on pre-storing dry-form reagents and fabricating a specifically designed cell counter. In order to obtain total cell counts for red blood cells, platelets, and 3-part differentials of white blood cells, two parallel counting chambers with different depths are made from cost- and environmentally friendly materials using soft lithography. As little as 1 μl of whole blood is prepared with pre-stored reagents in centrifuge vials, whereas red blood cells are sphered and white blood cells are stained at the same time. Driven by the capillary force, prepared blood samples enter the hydrophilic chambers automatically. Monolayers of cells are formed when the blood dilution factors and the chamber depths are co-optimized. Combined with our previous custom-built instrument and automated analysis algorithm, the sample preparation strategy allows producing counting results with excellent agreement to a gold-standard clinical hematology instrument. The success of this preparation method may further advance applications of our technology for global use in low-resource settings where central hematology laboratories are not accessible. [ABSTRACT FROM AUTHOR]