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[Display omitted] The complex spreading dynamics of blood on paper matrix is likely to be quantitatively altered with variations in the fractional occupancy of red blood cells in the whole blood (haematocrit). Here, we presented an apparently surprising observation that a finite volume blood drop undergoes a universal time-dependent spreading on a filter paper strip that is virtually invariant with its hematocrit level within physiologically healthy regime, though distinctively distinguishable from the spreading laws of blood plasma and water. Our hypothesis was ascertained by performing controlled wicking experiments on filter papers of different grades. Spreading of human blood samples of different haematocrit levels ranging between 15% and 51% and the plasma separated from therein were traced by combined high-speed imaging and microscopy. These experiments were complemented with a semi-analytical theory to decipher the key physics of interest. Our results unveiled the exclusive influence of the obstructing cellular aggregates in the randomly distributed hierarchically structured porous pathways and deciphered the role of the networked structures of the various plasma proteins that induced hindered diffusion. The resulting universal signatures of spontaneous dynamic spreading, delving centrally on the fractional reduction in the interlaced porous passages, provide novel design basis for paper-microfluidic kits in medical diagnostics and beyond. [ABSTRACT FROM AUTHOR]

Many diseases are detected through blood tests. Currently, most blood tests are done on plasma instead of whole blood because of the interference of blood cells on detection results. Here, we developed a laminated microfluidic paper-based analytical device (L-μPAD) for the separation of plasma from whole blood without using plasma separation membrane (PSM). A lateral flow design consisting of a circular sampling zone and rectangular detection zone was patterned on the paper substrate using laser printing technology. The μPAD was then laminated after impregnation with KCl solution. Lamination and electrolyte addition represented synergistic effects on the separation by controlling the pore size of the paper. In addition, by preventing evaporation on one hand and squeezing paper pores on the other hand, lamination caused longer movement of the separated plasma, the longest plasma path reported so far. The separation process was monitored using colorimetric reagent bromocresol green and scanning electron microscopy. The process of separation was completed in less than 90s without significant hemolysis and the separated plasma was far from the interfering effect of red blood cells. We used the device for the determination of serum albumin. However, it represents the potential for point-of-care testing in multi-assay experiments too. [Display omitted] • A laminated microfluidic paper-based analytical device for separation of plasma from whole blood. • No need to use plasma separation membrane. • Lamination represented significant effects on the separation by preventing evaporation. • Lamination caused longer movement of the separated plasma, the longest plasma path reported so far. • We used the device for determination of serum albumin. [ABSTRACT FROM AUTHOR]

In this work, fast isoelectric focusing (IEF) was successfully implemented on an open paper fluidic channel for simultaneous concentration and separation of proteins from complex matrix. With this simple device, IEF can be finished in 10 min with a resolution of 0.03 pH units and concentration factor of 10, as estimated by color model proteins by smartphone-based colorimetric detection. Fast detection of albumin from human serum and glycated hemoglobin (HBA1c) from blood cell was demonstrated. In addition, off-line identification of the model proteins from the IEF fractions with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was also shown. This PAD IEF is potentially useful either for point of care test (POCT) or biomarker analysis as a cost-effective sample pretreatment method. [ABSTRACT FROM AUTHOR]

Interest in developing paper-based devices for point-of-care diagnostics in resource-limited settings has risen remarkably in recent decades. In this paper, we demonstrate what we refer to as “high yield passive rrythrocyte removal” (HYPER) technology, which utilizes capillary forces in a unique cross-flow filtration for the separation of whole blood with performance comparable to centrifuges. As we will demonstrate, state-of-the-art passive blood separation methods implemented in paper-based systems exhibit rapid blood cell clogging on the filtration media or serum outlet and yield only about 10–30% of the total serum present in the sample. Our innovation results from the inclusion of a differentiation pad, which exploits hydrodynamic effects to reduce the formation of a fouling layer on the blood filtration membrane resulting in more than 60% serum yield with undiluted whole blood as direct input. To demonstrate the effectiveness of the HYPER technology we implement it in a lateral flow system and demonstrate the accurate quantification of vitamin A and iron levels in whole blood samples in 15 minutes. [ABSTRACT FROM AUTHOR]

While a number of assays for soluble analytes have been developed using paper-based microfluidic devices, the detection and analysis of blood cells has remained an outstanding challenge. In this Feature, we discuss how the properties of paper determine the performance of paper-based microfluidic devices and permit the design of cellular assays, which can ultimately impact disparities in healthcare that exist in limited-resource settings. [ABSTRACT FROM AUTHOR]

The quantification of blood cells provides critical information about a patient's health status. Sophisticated analytical equipment, such as hematology analyzers, have been developed to perform these measurements, but limited-resource settings often lack the infrastructure required to purchase, operate, and maintain instrumentation. To address these practical challenges, paper-based microfluidic devices have emerged as a platform to develop diagnostic assays specifically for use at the point-of-care. To date, paper-based microfluidic devices have been used broadly in diagnostic assays that apply immunoassay, clinical chemistry, and electrochemistry techniques. The analysis of cells, however, has been largely overlooked. In this communication, we demonstrate a paper-based microfluidic device that enables the controlled transport of red blood cells (RBCs) and the measurement of the hematocrit―the ratio of RBC packed cell volume to total volume of whole blood. The properties of paper, device treatment, and device geometry affect the overall extent and reproducibility of transport of RBCs. Ultimately, we developed an inexpensive (US$0.03 per device) thermometer-styled device where the distance traveled by RBCs is proportional to the hematocrit. These results provide a foundation for the design of paper-based microfluidic devices that enable the separation and detection of cells in limited-resource settings. [ABSTRACT FROM AUTHOR]

Traditional manual blood smear diagnosis methods are time-consuming and prone to errors, often relying heavily on the experience of clinical laboratory analysts for accuracy. As breakthroughs in key technologies such as neural networks and deep learning continue to drive digital transformation in the medical field, image recognition technology is increasingly being leveraged to enhance existing medical processes. In recent years, advancements in computer technology have led to improved efficiency in the identification of blood cells in blood smears through the use of image recognition technology. This paper provides a comprehensive summary of the methods and steps involved in utilizing image recognition algorithms for diagnosing diseases in blood smears, with a focus on malaria and leukemia. Furthermore, it offers a forward-looking research direction for the development of a comprehensive blood cell pathological detection system. [ABSTRACT FROM AUTHOR]

Certain therapies that target CD markers on some blood cells can affect pretransfusion testing. Key examples are anti‐CD38, CD47 monoclonal antibody (mAb) therapies such as daratumumab (DARA) and magrolimab, which have presented a challenge for transfusion medicine laboratories around the globe. Scientists have been faced with not only introducing a protocol to provide safe blood to patients but also investigating the most effective method to remove the pretransfusion pan‐agglutinating interference caused. A number of papers in the last 5 years have reported on various methods to remove pretransfusion interference; however, most of these studies have been conducted only in a few countries. Most recent reviews on this topic have focused on techniques and reagents to remove pretransfusion interference, and dithiothreitol is currently the gold standard for removing DARA interference. However, it was clear from this review that while many laboratories have developed processes for addressing interference in pretransfusion testing, and DARA interference may not be a major issue, there are still laboratories around the world, that may not have adequately addressed this issue. In addition, the impact of mAb interference on widely used techniques such as flow cytometry is unclear. [ABSTRACT FROM AUTHOR]

Optical microscopy videos enable experts to analyze the motion of several biological elements. Particularly in blood samples infected with Trypanosoma cruzi (T. cruzi), microscopy videos reveal a dynamic scenario where the parasites' motions are conspicuous. While parasites have self-motion, cells are inert and may assume some displacement under dynamic events, such as fluids and microscope focus adjustments. This paper analyzes the trajectory of T. cruzi and blood cells to discriminate between these elements by identifying the following motion patterns: collateral, fluctuating, and pan–tilt–zoom (PTZ). We consider two approaches: i) classification experiments for discrimination between parasites and cells; and ii) clustering experiments to identify the cell motion. We propose the trajectory step dispersion (TSD) descriptor based on standard deviation to characterize these elements, outperforming state-of-the-art descriptors. Our results confirm motion is valuable in discriminating T. cruzi of the cells. Since the parasites perform the collateral motion, their trajectory steps tend to randomness. The cells may assume fluctuating motion following a homogeneous and directional path or PTZ motion with trajectory steps in a restricted area. Thus, our findings may contribute to developing new computational tools focused on trajectory analysis, which can advance the study and medical diagnosis of Chagas disease. [ABSTRACT FROM AUTHOR]

A platelet (thrombocyte) can be in two states, activated and inactivated. The paper analyzes the interaction of an inactive platelet cell with the wall of a blood vessel. The goal is to analyze and represent the dynamics of platelet cell interaction when a thrombus has not yet formed. The discrete element method (DEM) can be used for the presented model. The paper presents an analysis of the dependence of force and displacement. This test is an introduction to more advanced tests when a blood clot forms. [ABSTRACT FROM AUTHOR]

We propose a new, paper-based analytical device (PAD) for blood typing that allows for the simultaneous determination of ABO and Rh blood groups on the same device. The device was successfully fabricated by using a combination of wax printing and wax dipping methods. A 1:2 blood dilution was used for forward grouping, whereas whole blood could be used for reverse grouping. A 30% cell suspension of A-cells or B-cells was used for haemagglutination on the reverse grouping side. The total assay time was 10 min. The ratio between the distance of red blood cell movement and plasma separation is the criterion for agglutination and indicates the presence of the corresponding antigen or antibody. The proposed PAD has excellent reproducibility in that the same blood groups, namely A, AB, and O, were reported by using different PADs that were fabricated on the same day ( n =10). The accuracy for detecting blood group A ( n =12), B ( n =13), AB ( n =9), O ( n =14), and Rh ( n =48) typing were 92%, 85%, 89%, 93%, and 96%, respectively, in comparison with the conventional slide test method. The haematocrit of the sample affects the accuracy of the results, and appropriate dilution is suggested before typing. In conclusion, this study proposes a novel method that is straightforward, time-saving, and inexpensive for the simultaneous determination of ABO and Rh blood groups, which is promising for use in developing countries. [ABSTRACT FROM AUTHOR]

Gastrointestinal fistula, a complication of gastrointestinal cancer surgery, has a high mortality rate. Detection of both C-reactive protein (CRP) and prealbumin (PAB) is advantageous in the auxiliary diagnosis of postoperative complications. However, traditional detection methods are not capable of on-site rapid detection. In an attempt to overcome these challenges, a multifunctional origami-paper-based device (ePADs) was developed to simultaneously detect CRP and PAB in whole blood. After integration, functionalization, and modification, the electrochemical dual-parameter device was capable of separating blood cells and detecting target analytes. The plasma separation performance revealed a sample diffusion time of 75 s for a whole blood sample volume of 73.3 μL. The efficiency of the device in separating blood cells was 99.91%. Electrochemical results showed that the multifunctional device exhibited linearity between 5 pg mL−1 and 1 μg mL−1 for CRP (R2 = 0.990), and between 10 pg mL−1 and 1 μg mL−1 for PAB (R2 = 0.998). The limits of detection for CRP and PAB were 5 and 10 pg mL−1, respectively (S/N = 3). We also successfully evaluated the accuracy of the dual-parameter device with clinical whole blood samples. Based on these results, the multifunctional device can facilitate clinical detection and provide a new platform for domestic point-of-care testing. [ABSTRACT FROM AUTHOR]

Simple Summary: Oncolytic herpes simplex viruses (oHSVs) employ as natural entry receptors nectin1 or HVEM. In contrast, retargeted oHSVs (ReHVs) employ as an entry receptor a tumor-associated antigen that no longer interacts with nectin1/HVEM and, thus, spares normal cells. Prior to entry, both oHSVs and ReHVs attach to cells by interaction of gC and gB glycoproteins with heparan sulphates and chondroitin sulphates (glycosaminoglycans–GAGs). The systemic delivery of oncolytic viruses would be the ideal route for hard-to-reach or metastatic cancers that constitute unmet clinical needs. In an accompanying paper, we reported that the blood complement and the antiviral neutralizing antibodies represent the major blood factors that inactivate systemically administered ReHVs. Here, we asked whether ReHV adsorption to GAGs acts as a sink and subtracts the virus from circulation. We report that a genetic modification in gC, which reduced its interaction with GAGs, resulted in a longer half-life of circulating ReHV and a higher anticancer efficacy of systemically (but not intratumorally) administered ReHV. The role of the interaction with cell-surface glycosaminoglycans (GAGs) during in vivo HSV infection is currently unknown. The rationale of the current investigation was to improve the anticancer efficacy of systemically administered retargeted oHSVs (ReHVs) by decreasing their binding to GAGs, including those of endothelial cells, blood cells, and off-tumor tissues. As a proof-of-principle approach, we deleted seven amino acids critical for interacting with GAGs from the glycoprotein C (gC) of R-337 ReHV. The modification in the resulting R-399 recombinant prolonged the half-life in the blood of systemically administered R-399 and enhanced its biodistribution to tumor-positive lungs and to the tumor-negative liver. Ultimately, it greatly increased the R-399 efficacy against metastatic-like lung tumors upon IV administration but not against subcutaneous tumors upon IT administration. These results provide evidence that the increased efficacy seen upon R-399 systemic administration correlated with the slower clearance from the circulation. To our knowledge, this is the first in vivo evidence that the partial impairment of the gC interaction with GAGs resulted in a prolonged half-life of circulating ReHV, an increase in the amount of ReHV taken up by tissues and tumors, and, ultimately, an enhanced anticancer efficacy of systemically administered ReHV. [ABSTRACT FROM AUTHOR]

Background: In vitro stimulation of whole blood or isolated blood cells with specific antigens is used for several purposes. Immediately following incubation with antigens, samples have to be centrifuged to stop the reactions by remaining cells and the supernatant refrigerated or analysed directly to preserve the analytes of interest, which makes samples difficult to prepare outside laboratories. We have tested whether spotting whole blood on filter paper after activation can be used in one of the tests for Mycobacterium tuberculosis infection (MTI), the QuantiFERON®-TB Gold In Tube test (QFT), where the spotting technique can make it suitable for use in locations without facilities like a centrifuge and a refrigerator. Materials and methods: Samples from 22 individuals undergoing screening for MTI and 10 healthy controls were incubated, centrifuged and IFN-γ measured by Enzyme-linked immunosorbent assay (ELISA), as described in the kit insert. In parallel, activated blood was spotted on filter paper (Schleicher & Schuell) and dried. The dried blood spot samples were analysed for 21 inflammatory markers with an in-house assay based on Luminex technology. Results: Our multiplex measurements of inflammatory markers in samples from suspected MTI patients confirmed the IFN-γ findings in the QFT. IL-2, GM-CSF, IL-5, and IL-1β were also found as useful markers for MTI. We were not able to distinguish between active tuberculosis and latent MTI. Conclusion: Applying blood on filter paper after incubation makes in vitro stimulation tests feasible in locations where heat and electricity is unavailable. [ABSTRACT FROM AUTHOR]

Substantial custodial sentences were handed down from the English Central Criminal Court for organ trafficking. Attempts to exploit vulnerable people for the purposes of organ removal, and for organ, tissue, and cells (OTC) trafficking are ongoing in many jurisdictions. It is also clear from the 2019 EU evaluation of the Union legislation on blood, tissues, and cells that there is increasing commercialization in the procurement of human material for medical use, using global supply chains. Full traceability of all human material, for which there is a shortage to meet global medical needs, is required. The medical profession has drafted the Istanbul Declaration on Organ Trafficking and Transplant Tourism 2008, calling for transplant tourism to be prohibited, and full engagement with transnational law enforcement to address developing transnational organized crime in this area. This paper addresses the global, Council of Europe, EU, and UK provisions in this area. [ABSTRACT FROM AUTHOR]

FLT-3 aberrations that occur as an internal tandem duplication (ITD) or a mutation at the activation-loop position 835, D835, are common in acute promyelocytic leukaemia (APL). We investigated the clinicopathological associations and prognostic impact of FLT-3 aberrations in a cohort of APL patients. FLT-3 exons 11 and 12 were amplified by polymerase chain reaction (PCR), and the lTD was recognized as an increase in the size of the PCR product. FLT-3 exon 17 was amplified, and D835 mutation was identified by loss of an EcoRV site, followed by DNA sequencing. Of 82 patients studied, FLT-3 aberrations were detected in 35 cases (43%) at diagnosis (ITD: 16; D835 mutation: 18; lTD + D835 mutation: 1). FLT-3 ITD, but not D835 mutations, was significantly associated with higher presentation white blood cell count (WBC) and microgranular morphology. Early/induction deaths were related to male sex and high presentation WBC. There was a trend for FLT-3 lTD to be associated with non-remission (P = 0.06). For disease-free survival, high WBC was the only significant adverse factor. Male sex, high WBC and FLT-3 lTD were significant adverse factors for overall survival. These findings have important implications on the possible use of FLT-3 inhibitors in the treatment of APL. [ABSTRACT FROM AUTHOR]

A reduced incidence of graft versus host disease (GvHD) has been documented among Japanese allogeneic bone marrow transplantation (BMT) patients, as the Japanese are genetically more homogeneous than western populations. To clarify whether this ethnic difference affects the results of allogeneic peripheral blood stem cell transplantation (PBSCT), we conducted a nationwide survey to compare clinical outcomes of allogeneic PBSCT (n = 214) and BMT (n = 295) from a human leucocyte antigen- identical-related donor in Japanese patients. The cumulative incidence of grades II-IV acute GvHD was 374% for PBSCT and 320% for BMT. The cumulative incidence of extensive chronic GvHD at 1 year was significantly higher after PBSCT than BMT (42% vs. 27%; P < 001). The organ involvement patterns of GvHD were different between the two groups. By multivariate analyses, the incidence of chronic GvHD was significantly increased in PBSCT, whereas the stem cell source did not affect the incidence of acute GvHD, transplant-related mortality, relapse or survival. We concluded that Japanese PBSCT patients have an increased risk of chronic GvHD compared with BMT patients, but the incidence of acute GvHD was still lower than in western populations. Thus, the choice of haematopoietic stem cell source should be considered based on data for individual ethnic populations. [ABSTRACT FROM AUTHOR]

Cord blood units ( n = 5500) stored at the London Cord Blood Bank, including 59 units transplanted into a high risk and heterogeneous group of patients, were analysed. Transplant outcome data was available for 44 patients with a median clinical follow-up of 14 months (range 3–44 months). Over 40% of the collected units were of ethnic minority origin with a median volume of 79 ml (range 40–240 ml) and a median total nucleated cell (TNC) count of 11·9 × 109/l (range 10·0–24·8 × 109/l). The average patient's weight was 28 kg (range 5–80 kg) and the median age was 8 years (range 0·7–40 years). The median number of nucleated cells infused was 4 × 107/kg (range 1·10–16 × 107/kg). Neutrophil engraftment of 0·5 × 109/l was observed in 33 (74±%) patients with an average time of 28 days (range 11–60). The Kaplan-Meier estimate of acute graft-versus-host disease (grade II >) at day 100 was 37 ± 7% and in 27 (62%) patients, it was grade I or absent. The overall survival and disease-free survival at 2 years was 49 ± 8% and 41 ± 8%, respectively. Two years after transplantation the survival rate was 69% and 54% for patients receiving a 6/6 or 5/6 HLA matched units, respectively. Infection was the main cause of transplanted related mortality in these patients. [ABSTRACT FROM AUTHOR]

Because of its B-cell depleting effect, rituximab has entered clinical trials in several autoimmune conditions. This study assesses the efficacy and safety of rituximab in 57 adults with chronic immune thrombocytopenic purpura (ITP). All patients had platelet counts <30 × 109/l, all had received two or more previous ITP treatments and 31 had undergone splenectomy. Patients received rituximab 375 mg/m2 weekly for 4 weeks. Thirty-one patients (54%) responded, achieving a platelet count >50 × 109/l: 18 achieved a complete response (CR: platelet count >150 × 109/l) and 13 a partial response (PR: platelet count 50–150 × 109/l). Twenty-nine responses occurred within 8 weeks of the first infusion. Sixteen of 18 CR patients (28% overall), including eight who had failed splenectomy, continued in CR after a median of 72·5 weeks; 15 of 16 are >1 year from the first infusion. Only two of 13 maintained a PR. Thirty-three patients experienced grade 1–2 adverse events and one a grade 3 event, but they all completed treatment. Circulating B cells fell to <0·03 × 109/l. No changes in immunoglobulin levels or infectious complications were seen. In summary, rituximab was well tolerated with no immediate complications and induced a lasting, substantial response in 32% of adults with chronic ITP. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis (IA) is a considerable clinical problem in neutropenic patients with haematological malignancies but its diagnosis remains difficult. We prospectively evaluated a LightCyclerTM polymerase chain reaction (PCR) assay, a nested-PCR assay and a galactomannan (GM) enzyme-linked immunosorbent assay (ELISA) to validate their significance in diagnosing IA. During 205 treatment episodes in 165 patients from six centres, a nested-PCR assay and GM testing was performed at regular intervals. Positive nested-PCR results were quantified by a LightCyclerTM PCR assay. Patient episodes were stratified according to the 2002 European Organization for Research and Treatment of Cancer/Mycosis Study Group consensus criteria and the PCR and serology results were correlated with the clinical diagnostic classification. Sensitivity and specificity rates for the nested-PCR assay were up to 63·6% [95% confidence interval (CI): 30·8–89%) and 63·5% (95% CI: 53·4–72·7%) respectively, and 33·3% and 98·9% (95% CI: 7·5–70·1% and 94·2–99·9%) for GM respectively. The LightCyclerTM PCR assay yielded positive results in 21·4%, lacking discrimination by quantification across the different clinical categories. In this prospective comparison, PCR was superior to GM with respect to sensitivity rates. In patients at high risk for IA, positive results for Aspergillus by PCR of blood samples are highly suggestive for IA and contribute to the diagnosis. [ABSTRACT FROM AUTHOR]

Intravenous (IV) anti-D and IV immunoglobulin (IVIG) slow the Fc γ receptor (Fc γR)-mediated destruction of antibody-coated platelets in patients with immune thrombocytopenic purpura (ITP). This pilot study explored the mechanism of these immunoglobulin preparations by measuring interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), IL-6 and tumour necrosis factor  α (TNF α), before and after infusion and by assessing the effect of Fc γRIIa and Fc γRIIIa polymorphisms on both cytokine and haematologic responses to anti-D. Following IVIG, only IL-10 was increased at 2 h and MCP-1 on day 7 ( P < 0·05). In contrast, 2 h after anti-D infusion, plasma levels of all four cytokines were increased ( P < 0·01); five of six patients with the highest MCP-1, IL-6 and TNF α levels had chills. Higher IL-10 levels correlated with platelet increases at 24 h and haemoglobin decreases at day 7 ( P < 0·025). Patients with the Fc γRIIa-131HH genotype had significantly higher MCP-1, IL-6 and TNF α levels. Patients with the Fc γRIIIa-158VF genotype had higher platelet increments at day 7 ( P < 0·05). Soluble CD16 (sCD16) was increased 2 h after IV anti-D; day 7 levels correlated with day 7 haemoglobin decreases ( P < 0·01). In conclusion, the relationship of Fc γRIIa and Fc γRIIIa polymorphisms with both cytokine levels and platelet increments implicated these receptors in responses to anti-D and supported different mechanisms of Fc γR interaction to those seen with IVIG. [ABSTRACT FROM AUTHOR]

Irradiation of whole blood and blood components before transfusion is currently the only accepted methodology to prevent transfusion-associated graft-vs.-host disease. In the present work, we developed an automated system for blood bag storage during irradiation, using a teletherapy unit. A device with two thermal compartments was constructed in acrylic and foam, for the storage of blood bags during irradiation. An automatic acquisition system, coupled with an amplifier and a thermal-sensitive probe, were developed to check blood temperature during irradiation. A polystyrene phantom was constructed to simulate the volume of blood routinely irradiated. The dose distribution was measured in the phantom using thermoluminescent dosimeters and represented in terms of isodose curves. The thermal device kept the blood temperature below 6 °C for more than 2 h. Our system allowed the simultaneous irradiation of two different blood components while maintaining a constant temperature. The temperature monitoring system remained invariant (0·2 °C) over the whole irradiation interval. Phantom dosimetric results showed a homogeneous dose distribution when the phantom was irradiated, using rotational fields with a 2 r.p.m. frequency. The methodology developed in the present work provides appropriate storage conditions during irradiation of both red blood cells and platelet blood components using a teletherapy unit. [ABSTRACT FROM AUTHOR]

Simple Summary: Primordial germ cells (PGCs) play a critical role in the preservation of poultry genetic resources and transgenic research, but there are significant efficiency issues with isolating PGCs from chicken embryonic blood, especially from a single embryo. In this study, we developed a simple and rapid method to isolate PGCs from single chicken embryonic blood. This method is based on the characteristics of PGCs found in the study. That is, when co-cultured with chicken embryonic fibroblasts (CEFs) of passages two to three, PGCs can migrate to the lower layer of CEF through pores smaller than their diameter, which is called cell culture inserts/CEF adhesion method. The PGCs isolated using this method retain their stem cell characteristics and migration ability, and exhibit good proliferation efficiency. These cells can be directly utilized for subsequent transgenic experiments or for the preservation of germplasm resources. Primordial germ cells (PGCs) play a crucial role in preserving poultry genetic resources and conducting transgenic research. A system for the rapid isolation of PGCs from single chicken embryonic blood was established in this paper. We found that PGCs can migrate to the lower layer of chicken embryonic fibroblasts (CEFs) through pores smaller than their diameter, while blood cells cannot, when co-cultured with CEFs of passages two to three. Based on the characteristics of PGCs, we developed a new PGC isolation method (cell culture insert/CEF adhesion method) that utilizes a 3 μm cell culture insert and CEFs of passages two to three. Using this method, approximately 700 PGCs can be isolated from the blood of a single chicken embryo at Hamburger and Hamilton (H&H) stage 17 of development. The separation rate achieved was 87.5%, with a separation purity of 95%. The separation rate of this method was 41.4% higher than the common Percoll density gradient centrifugation method and 33.6% higher than lysis with ACK buffer. PGCs isolated from embryonic blood could proliferate 37-fold within 2 weeks when cultured in a feeder-free culture system. They also continued to express the SSEA-1 and DAZL proteins and retained the ability to migrate in vivo. Overall, PGCs separated using cell culture inserts/CEF adhesion method retain their stem cell characteristics and migration ability. PGCs also exhibit good proliferation efficiency, making them suitable for subsequent transgenic experiments or genetic resource preservation. [ABSTRACT FROM AUTHOR]

The pathophysiology of the severe course of COVID-19 is multifactorial and not entirely elucidated. However, it is well known that the hyperinflammatory response and cytokine storm are paramount events leading to further complications. In this paper, we investigated the vascular response in the pathophysiology of severe COVID-19 and aimed to identify novel biomarkers predictive of ICU admission. The study group consisted of 210 patients diagnosed with COVID-19 (age range: 18–93; mean ± SD: 57.78 ± 14.16), while the control group consisted of 80 healthy individuals. We assessed the plasma concentrations of various vascular factors using the Luminex technique. Then, we isolated RNA from blood mononuclear cells and performed a bioinformatics analysis investigating various processes related to vascular response, inflammation and angiogenesis. Our results confirmed that severe COVID-19 is associated with vWF/ADAMTS 13 imbalance. High plasma concentrations of VEGFR and low DPP-IV may be potential predictors of ICU admission. SARS-CoV-2 infection impairs angiogenesis, hinders the generation of nitric oxide, and thus impedes vasodilation. The hypercoagulable state develops mainly in the early stages of the disease, which may contribute to the well-established complications of COVID-19. [ABSTRACT FROM AUTHOR]

Aside from new software the blood cell separator TRIMA (GambroBCT) also received a newly designed separation chamber offering a novel single stage separation technology, called Trima Accel. We evaluated this new system focusing on productivity and donor comfort by comparing it to the previous version (Trima version 4) in collecting single-donor platelet concentrates (SD-PCs) and plasma. Each of 20 donors underwent platelet apheresis using both devices. We compared the collection efficiency (CE), the collections rate (CR), the volume of the collected plasma and the residual leukocytes. Furthermore we compared donor comfort in terms of duration of the donation, flow of citrate back to the donor and platelet and whit blood cell (WBC) loss. While the number of collected platelets and the platelet concentration did not differ significantly between both techniques the time of the procedure was reduced by 15.6% with Trima Accel. This results in an increase of the CR and CE of 25% and 15% respectively when using Trima Accel. Log normal probability plotting of WBC counts showed that both techniques complied with the European and the US leukoreduction guidelines. The mean flow of ACDA to the donor perminute and per litre blood volume was also reduced by 20%. These data show that the Trima Accel represents a further improvement in apheresis platelet production with a better productivity and donor comfort, especially regarding the mean flow of ACDA to the donor. [ABSTRACT FROM AUTHOR]

This paper addresses digital staining and classification of the unstained white blood cell images obtained with a differential contrast microscope. We have data coming from multiple domains that are partially labeled and partially matching across the domains. Using unstained images removes time-consuming staining procedures and could facilitate and automatize comprehensive diagnostics. To this aim, we propose a method that translates unstained images to realistically looking stained images preserving the inter-cellular structures, crucial for the medical experts to perform classification. We achieve better structure preservation by adding auxiliary tasks of segmentation and direct reconstruction. Segmentation enforces that the network learns to generate correct nucleus and cytoplasm shape, while direct reconstruction enforces reliable translation between the matching images across domains. Besides, we build a robust domain agnostic latent space by injecting the target domain label directly to the generator, i.e., bypassing the encoder. It allows the encoder to extract features independently of the target domain and enables an automated domain invariant classification of the white blood cells. We validated our method on a large dataset composed of leukocytes of 24 patients, achieving state-of-the-art performance on both digital staining and classification tasks. [ABSTRACT FROM AUTHOR]

Continuously recording the dynamic changes of circulating tumor cells (CTCs) is crucial for tumor metastasis. This paper creates a continuous magnetic separation microfluidic chip that enables rapid and continuous in vivo cell detection. The chip shows its potential to study tumor cell circulation in the blood, offering a new platform for studying the cellular mechanism of tumor metastasis. [ABSTRACT FROM AUTHOR]

Analysis of white blood cells from blood can help to detect Acute Lymphoblastic Leukemia, a potentially fatal blood cancer if left untreated. The morphological analysis of blood cells images is typically performed manually by an expert; however, this method has numerous drawbacks, including slow analysis, low precision, and the results depend on the operator's skill. We have developed and present here an automated method for the identification and classification of white blood cells using microscopic images of peripheral blood smears. Once the image has been obtained, we propose describing it using brightness, contrast, and micro-contour orientation histograms. Each of these descriptions provides a coding of the image, which in turn provides n parameters. The extracted characteristics are presented to an encoder's input. The encoder generates a high-dimensional binary output vector, which is presented to the input of the neural classifier. This paper presents the performance of one classifier, the Random Threshold Classifier. The classifier's output is the recognized class, which is either a healthy cell or an Acute Lymphoblastic Leukemia-affected cell. As shown below, the proposed neural Random Threshold Classifier achieved a recognition rate of 98.3 % when the data has partitioned on 80 % training set and 20 % testing set for. Our system of image recognition is evaluated using the public dataset of peripheral blood samples from Acute Lymphoblastic Leukemia Image Database. It is important to mention that our system could be implemented as a computational tool for detection of other diseases, where blood cells undergo alterations, such as Covid-19. [ABSTRACT FROM AUTHOR]

This paper proposes an improved target detection algorithm, SDE-YOLO, based on the YOLOv5s framework, to address the low detection accuracy, misdetection, and leakage in blood cell detection caused by existing single-stage and two-stage detection algorithms. Initially, the Swin Transformer is integrated into the back-end of the backbone to extract the features in a better way. Then, the 32 × 32 network layer in the path-aggregation network (PANet) is removed to decrease the number of parameters in the network while increasing its accuracy in detecting small targets. Moreover, PANet substitutes traditional convolution with depth-separable convolution to accurately recognize small targets while maintaining a fast speed. Finally, replacing the complete intersection over union (CIOU) loss function with the Euclidean intersection over union (EIOU) loss function can help address the imbalance of positive and negative samples and speed up the convergence rate. The SDE-YOLO algorithm achieves a mAP of 99.5%, 95.3%, and 93.3% on the BCCD blood cell dataset for white blood cells, red blood cells, and platelets, respectively, which is an improvement over other single-stage and two-stage algorithms such as SSD, YOLOv4, and YOLOv5s. The experiment yields excellent results, and the algorithm detects blood cells very well. The SDE-YOLO algorithm also has advantages in accuracy and real-time blood cell detection performance compared to the YOLOv7 and YOLOv8 technologies. [ABSTRACT FROM AUTHOR]

The combination of a blood cell analyzer and artificial microscopy to detect white blood cells is used in hospitals. Blood cell analyzers not only have large throughput, but they also cannot detect cell morphology; although artificial microscopy has high accuracy, it is inefficient and prone to missed detections. In view of the above problems, a method based on Fourier ptychographic microscopy (FPM) and deep learning to detect peripheral blood leukocytes is proposed in this paper. Firstly, high-resolution and wide-field microscopic images of human peripheral blood cells are obtained using the FPM system, and the cell image data are enhanced with DCGANs (deep convolution generative adversarial networks) to construct datasets for performance evaluation. Then, an improved DETR (detection transformer) algorithm is proposed to improve the detection accuracy of small white blood cell targets; that is, the residual module Conv Block in the feature extraction part of the DETR network is improved to reduce the problem of information loss caused by downsampling. Finally, CIOU (complete intersection over union) is introduced as the bounding box loss function, which avoids the problem that GIOU (generalized intersection over union) is difficult to optimize when the two boxes are far away and the convergence speed is faster. The experimental results show that the mAP of the improved DETR algorithm in the detection of human peripheral white blood cells is 0.936. In addition, this algorithm is compared with other convolutional neural networks in terms of average accuracy, parameters, and number of inference frames per second, which verifies the feasibility of this method in microscopic medical image detection. [ABSTRACT FROM AUTHOR]

In the human body, white blood cells (WBCs) are crucial immune cells that help in the early detection of a variety of illnesses. Determination of the number of WBCs can be used to diagnose conditions such as hematological, immunological, and autoimmune diseases, as well as AIDS and leukemia. However, the conventional method of classifying and counting WBCs is time-consuming, laborious, and potentially erroneous. Therefore, this paper presents a computer-assisted automated method for recognizing and detecting WBC categories from blood images. Initially, the blood cell image is preprocessed and then segmented using an effective deep learning architecture called SegNet. Then, the important features are devised and extracted using the EfficientNet architecture. Finally, the WBCs are categorized into four different types using the XGBoost classifier: neutrophils, eosinophils, monocytes, and lymphocytes. The advantages of SegNet, EfficientNet, and XGBoost make the proposed model more robust and achieve a more efficient classification of the WBCs. The BCCD dataset is used to evaluate the performance of the proposed methodology, and the findings are compared to existing state-of-the-art approaches based on accuracy, precision, sensitivity, specificity, and F1-score. Evaluation results show that the proposed approach has a higher rank-1 accuracy of 99.02% and outperformed other existing techniques. [ABSTRACT FROM AUTHOR]

Present abstracts of research papers presented at the Japan-UK Platelet Conference at Magdalen College in Oxford, England on June 2-3, 2004. Range of topics; Authors; Institutes represented.

Extracellular vesicles (EVs) are important for intercellular signalling in multi-cellular organisms. However, the role of mature transfer RNAs (tRNAs) and tRNA fragments in EVs has yet to be characterised. This systematic review aimed to identify up-to-date literature on tRNAs present within human EVs and explores their potential clinical significance in health and disease. A comprehensive and systematic literature search was performed, and the study was conducted in accordance with PRISMA guidelines. Electronic databases MEDLINE and EMBASE were searched up until 1 January 2022. From 685 papers, 60 studies were identified for analysis. The majority of papers reviewed focussed on the role of EV tRNAs in cancers (31.7%), with numerous other conditions represented. Blood and cell lines were the most common EV sources, representing 85.9% of protocols used. EV isolation methods included most known methods, precipitation being the most common (49.3%). The proportion of EV tRNAs was highly variable, ranging between 0.04% to >95% depending on tissue source. EV tRNAs are present in a multitude of sources and show promise as disease markers in breast cancer, gastrointestinal cancers, and other diseases. EV tRNA research is an emerging field, with increasing numbers of papers highlighting novel methodologies for tRNA and tRNA fragment discovery. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cells are a group of heterogeneity cells with the potential to differentiate into various types of mature blood cells. Their basic biological properties include quiescence, self-renewal, multilineage differentiation, and homing ability, with the homing of exogenous hematopoietic stem cells after transplantation becoming a new focus, while the first three properties share some similarity in mechanism due to connectivity. In various complex mechanisms, the role of E3 ubiquitin ligases in hematopoietic homeostasis and malignant transformation is receiving increasing attention. As a unique part, E3 ubiquitin ligases play an important role in physiological regulation mechanism of posttranslational modification. In this review, we focus on the recent progress of the crucial role of E3 ubiquitin ligases that target specific proteins for ubiquitination to regulate biological properties of hematopoietic stem cells. Additionally, this paper deals with E3 ubiquitin ligases that affect the biological properties through aging and summarizes the relevant applications of targeting E3 ligases in hematopoietic malignancies. We present some ideas on the clinical application of E3 ubiquitin ligase to regulate hematopoietic stem cells and also believe that it is meaningful to study the upstream signal of these E3 ubiquitin ligases because hematopoietic stem cell dysfunction is caused by deficiency of some E3 ligases. [ABSTRACT FROM AUTHOR]

The phenomenon of bifurcation in disease transmission models has been observed in a number of epidemiological models. The consequence of bifurcation is that the classical requirement of the reproduction number being less than unity becomes only a necessary, but not sufficient, for disease elimination. This paper addresses the problem of finding the causes of bifurcation in standard deterministic models for the spread of HBV diseases with non-Cytolytic cure processes on infected liver and blood cells. The model contains logistic growth of healthy liver and blood cells and non -Cytolytic cure processes of infected cells. I have got that the model exhibits back ward and forward bifurcations with some conditions. The existence of a backward bifurcation is an interesting artifact since this means that the disease cannot be eradicated by simply reducing the value of the basic reproduction number R 0 below 1.This can have important implications on drug therapy protocols, since it sheds light on possible control mechanisms for disease eradication. [ABSTRACT FROM AUTHOR]

The isolation of a specific lymphocyte subset from blood is the required first step in the manufacturing of many novel cellular immunotherapies. Microfluidic size-based separation methods are poised to significantly simplify this process because they require neither centrifugation nor magnetic or fluorescent labeling to operate. Lymphocytes can be separated from red blood cells (RBCs) and platelets as well as monocytes and granulocytes because their size differs from each of these cell types. However, further separation of a specific lymphocyte subset from other unwanted lymphocytes using size-based methods is impossible because all lymphocytes have approximately the same size and can only be distinguished by surface markers. This paper describes a new approach that made it possible for a size-based separation method to isolate a desired subset of lymphocytes by making unwanted lymphocytes as well as other blood cells artificially larger. The separation was enabled by selectively binding multiple RBCs to each unwanted cell to create 'rosettes' with an effective size significantly larger than the diameter of a typical lymphocyte. The desired lymphocytes remained unaffected by rosetting and were separated from the rosettes by passing the mixture through a microfluidic size-based separation device based on controlled incremental filtration (CIF). This new rosette-enabled size-based (RESIZE) separation approach demonstrated recovery of 80–90% for all lymphocyte subsets tested (CD3+, CD4+, CD56+) which was ∼2.5-fold higher than that for the standard immunodensity method (RBC rosetting followed by density gradient centrifugation). The purity of separation was >90% for CD3+ cells but declined with increasing cell rarity. Unlike the immunodensity approach, RESIZE required neither centrifugation nor cell washing after the separation and was ∼2.5-fold faster when processing the same sample volume. The results of this study suggest that integration of the RESIZE approach for high-yield isolation of lymphocyte subsets from blood could significantly streamline the manufacturing workflow and thus have a potentially transformative impact on the cost and availability of novel cellular immunotherapies. [ABSTRACT FROM AUTHOR]

Alterations in intestinal function play a crucial role in the pathogenesis of sepsis, and the repair of the intestinal barrier is a potential strategy for the treatment of sepsis. Sestrin2 (SESN2), a highly conserved stress-responsive protein, can be induced in response to stress. This paper aimed to explore the role and mechanism of SESN2 in septic intestinal dysfunction. Blood samples were collected from patients with septic intestinal dysfunction, and Caco-2 cells were subjected to lipopolysaccharide (LPS) to construct in vitro models. The expression level of SESN2 was determined in the blood samples and cells. The impacts of SESN2 overexpression on cell inflammation, oxidative stress, barrier integrity, and MAPK/Nrf2 signaling were evaluated. To determine the mediated role of MAPK signaling and ferroptosis, AMPK inhibitor (Compound C) and ferroptosis inducer (erastin) were separately used to treat cells, and the influences on the above aspects in cells were assessed. The expression level of SESN2 was down-regulated in patients with septic intestinal dysfunction and LPS-induced cells. SESN2 overexpression was found to suppress cell inflammation and oxidative stress, maintain barrier integrity, and activate AMPK/Nrf2 signaling. Following the AMPK signaling was inhibited or the ferroptosis was triggered, the effects of SESN2 overexpression on the cells were both reversed. Reduced SESN2 contributed to inflammatory response and barrier dysfunction in septic intestinal dysfunction by promoting ferroptosis via activating the AMPK/Nrf2 signaling pathway. [ABSTRACT FROM AUTHOR]

(1) Hematological malignancies are characterized by an immortalization, uncontrolled proliferation of blood cells and their differentiation block, followed by the loss of function. The primary goal in the treatment of leukemias is the elimination of rapidly proliferating leukemic cells (named blasts). However, chemotherapy, which removes proliferating blasts, also prevents the remaining immune cells from being activated. Acute leukemias affect elderly people, who are often not fit to survive aggressive chemotherapy. Therefore, there is a need of milder treatment, named differentiation therapy, which might simulate the immune system of the patient. 1,25-Dihydroxyvitamin D, or low-calcemic analogs of this compound, were proposed as supporting therapy in acute leukemias. (2) Bone marrow blasts from patients with hematological malignancies, and leukocytes from healthy volunteers were ex vivo exposed to 1,25-dihydroxyvitamin D, and then their genomes and transcriptomes were investigated. (3) Our analysis indicates that 1,25-dihydroxyvitamin D regulates in blood cells predominantly genes involved in immune response, such as CAMP (cathelicidin antimicrobial peptide), CP (ceruloplasmin), CXCL9 (C-X-C motif chemokine ligand 9), CD14 (CD14 molecule) or VMO1 (vitelline membrane outer layer 1 homolog). This concerns blood cells from healthy people, as well as blasts from patients with hematological malignancies. In addition, in one patient, 1,25-dihydroxyvitamin D significantly downregulated transcription of genes responsible for cell division and immortalization. (4) In conclusion, the data presented in this paper suggest that addition of 1,25-dihydroxyvitamin D to the currently available treatments would stimulate immune system, inhibit proliferation and reduce immortal potential of blasts. [ABSTRACT FROM AUTHOR]

Inertial microfluidics is a high‐throughput and high‐efficiency cell separation approach to which attention has been progressively paid in recent years. However, research on the influencing factors that compromise the efficiency of cell separation is still lacking. Therefore, the aim of this study was to evaluate the cell separation efficiency by changing the influencing factors. A four‐ring inertial focusing spiral microchannel was designed to separate two kinds of circulating tumor cells (CTCs) from blood. Human breast cancer (MCF‐7) cells and human epithelial cervical cancer (HeLa) cells enter the four‐ring inertial focusing spiral microchannel together with blood cells, and cancer cells and blood cells were separated from each other at the outlet of the channel by inertial force. The cell separation efficiency at the inlet flow rate in the Reynolds number range of 40–52 was studied by changing the influencing factors such as the cross‐sectional shape of the microchannel, the average thickness of the cross‐section, and the trapezoidal inclination angle. The results showed that the reduction of the channel thickness and the increase of a certain trapezoidal inclination enhanced the cell separation efficiency to a certain extent, the study showed that when the channel inclination was 6 ° and the average channel thickness was 160 μm. The two kinds of CTC cells could be completely separated from the blood and the efficiency could reached 100%. Significance statement: In this study, a helical inertial focusing microchannel was designed by summarizing the previous experiences. Based on the previous studies, the influences of the channel factors on the separation efficiency and focusing range of two circulating tumor cells (CTCs) in blood cells were studied. In this paper, three important influencing factors, namely channel Reynolds number, channel inclination and average channel thickness, were systematically summarized, the changes of these three influencing factors, the separation efficiency of CTCs, and the focus range were drawn in detail, and the channel itself factors which were most suitable for the separation of two CTCs in blood were summarized. This will lay a foundation for subsequent research on the influence of channel factors on the focusing effect and separation efficiency of particles in the channel [ABSTRACT FROM AUTHOR]

We introduce a new spatial statistic, the weighted pair correlation function (wPCF). The wPCF extends the existing pair correlation function (PCF) and cross-PCF to describe spatial relationships between points marked with combinations of discrete and continuous labels. We validate its use through application to a new agent-based model (ABM) which simulates interactions between macrophages and tumour cells. These interactions are influenced by the spatial positions of the cells and by macrophage phenotype, a continuous variable that ranges from anti-tumour to pro-tumour. By varying model parameters that regulate macrophage phenotype, we show that the ABM exhibits behaviours which resemble the 'three Es of cancer immunoediting': Equilibrium, Escape, and Elimination. We use the wPCF to analyse synthetic images generated by the ABM. We show that the wPCF generates a 'human readable' statistical summary of where macrophages with different phenotypes are located relative to both blood vessels and tumour cells. We also define a distinct 'PCF signature' that characterises each of the three Es of immunoediting, by combining wPCF measurements with the cross-PCF describing interactions between vessels and tumour cells. By applying dimension reduction techniques to this signature, we identify its key features and train a support vector machine classifier to distinguish between simulation outputs based on their PCF signature. This proof-of-concept study shows how multiple spatial statistics can be combined to analyse the complex spatial features that the ABM generates, and to partition them into interpretable groups. The intricate spatial features produced by the ABM are similar to those generated by state-of-the-art multiplex imaging techniques which distinguish the spatial distribution and intensity of multiple biomarkers in biological tissue regions. Applying methods such as the wPCF to multiplex imaging data would exploit the continuous variation in biomarker intensities and generate more detailed characterisation of the spatial and phenotypic heterogeneity in tissue samples. Author summary: Multiplex images provide exquisitely detailed information about the spatial distribution and intensity of up to 40 biomarkers within two-dimensional tissue regions, creating challenges and opportunities for quantitative analysis. Although stain intensities are measured on a continuous scale, they are typically converted into discrete labels to simplify subsequent spatial analysis. In this paper we propose a new spatial statistic, the weighted pair correlation function (wPCF), which exploits, rather than neglects, the continuous variation in stain intensity contained in multiplex images, and can characterise both spatial and phenotypic heterogeneity. As proof-of-principle, we apply the wPCF to synthetic data that resemble multiplex images of solid tumours. We generate data from an agent-based model (ABM) that simulates macrophage-tumour interactions. The wPCF shows how the continuous label describing macrophage phenotype is spatially related to categorical labels associated with tumour cells and blood vessels. We demonstrate that correlation functions can categorise spatial relationships in a manner which is interpretable and quantitative. The methods we present can be used to analyse both ABM simulations and multiplex imaging data, with applications that go beyond macrophage phenotype to include other biological processes that exhibit continuous variation (e.g., cancer cell stemness, biomarkers for T-cell exhaustion, and levels of oxygenation). [ABSTRACT FROM AUTHOR]

The journal Blood Cells was initiated in 1975 by Marcel Bessis, a French hematologist and cell biologist, as a vehicle for the publication of papers and discussions presented at an international blood club meeting he convened at L' Institut de Pathologie Cellulaire on the campus of Hôpital Bicétre in Kremlin Bicétre, France, a commune on the southern border of Paris. The group met at the Institute for the first time in October 1972. After the first meeting, Bessis published the articles describing the presentations in the Nouvelle Revue d'Hématologie Française , France's principal journal for articles on the science and practice of hematology of which he was the editor. The refusal of the Nouvelle Revue d'Hématologie Française to continue publishing the papers from the meeting of the blood club in English prompted Bessis to start a new journal, Blood Cells , in 1975. Blood Cells , also, began to accept individual submitted papers unrelated to the blood club meeting and, thus, it evolved into a standard journal. A decade later, when Bessis became ill, he asked Brian Bull, a hematopathologist and professor at Loma Linda University School of Medicine in California to assume the position as the second editor-in-chief. He and Bessis had become scientific collaborators and good friends in the preceding years. In 1995, Ernest Beutler, Chair of Molecular and Experimental Medicine at Scripps Research Institute, assumed the editor-in-chief position and transformed the Journal by making three consequential changes. He expanded its title to Blood Cells, Molecules and Diseases , converted its editorial board to past presidents of the American Society of Hematology plus a few additional experimental hematologists of note, a few from abroad, and he converted the Journal to a digital format, hosted on the Scripps Research Institute server. The Journal was the first published solely in a digital format. It, subsequently, was bought by Academic Press, then Harcourt and, then, by Elsevier. The next three editors-in-chief were (i) Marshall A. Lichtman, then Professor of Medicine (Hematology) and of Biochemistry and Biophysics and former Dean of the School of Medicine and Dentistry at the University of Rochester Medical Center, editor from 2000 to 2013, (ii) Mohandas Narla, then Vice President for Research and Director of The Laboratory of Red Cell Physiology at the New York Blood Center, editor from 2014 to 2021 and (iii) Lionel Blanc, Professor of Molecular Medicine and Pediatrics, Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research and the Les Nelkin Professor of Pediatric Oncology Donald and Barbara Zucker School of Medicine at Hofstra-Northwell from 2022 to the present. Although the Journal publishes papers on any aspect of hematology, it has developed a focus on disorders of red cells, erythropoiesis and hematopoiesis. In October 2024, it celebrates its 50th anniversary as a vehicle for the publication of papers in the discipline of hematology. [ABSTRACT FROM AUTHOR]

Automated medical diagnosis is an important topic, especially in detection and classification of diseases. Malaria is one of the most widespread diseases, with more than 200 million cases, according to the 2016 WHO report. Malaria is usually diagnosed using thin and thick blood smears under a microscope. However, proper diagnosis is difficult, especially in poor countries where the disease is most widespread. Therefore, automatic diagnostics helps in identifying the disease through images of red blood cells, with the use of machine learning techniques and digital image processing. This paper presents an accurate model using a Deep Convolutional Neural Network build from scratch. The paper also proposed three CNN models each one trained on the Malaria RBC dataset with different architectures for handling the classification tasks. Furthermore, disadvantage of the traditional method of using transfer learning, and how to control model complexity to achieve better performance was discussed. The dropout regularization technique was used to avoid overfitting problems and minimize validation loss. Applying Data Augmentation technique to avoid the problem of small data in training of proposed models, which is a very common problem in medical dataset. Finally, removing noise in Malaria images using a Median blur filter, and studying how effects of that on training CNN models. According to the classification results, the proposed model achieved better classification results at accuracy 99.22 on the original Malaria RBCs dataset, and it has the best performance comparing with related work. [ABSTRACT FROM AUTHOR]

Background/Aim. Measles is a contagious disease with a good prognosis; however, severe complications may sometimes develop. C-reactive protein (CRP) and blood cells count-derived inflammatory indices -- granulocytelymphocyte ratio (GLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), mean platelet volume (MPV)/platelet count ratio (MPR), red blood cell distribution width (RDW), and MPV are the indicators related to the clinical outcome in various inflammatory diseases. The aim of the study was to analyze the values of CRP, blood cell count, GLR, PLR, MLR, MPR, RDW, and MPV in measles-affected children compared to healthy controls and between measles-affected children with complicated and severely complicated measles form. A particular aim of the paper was to assess the suitability of inflammatory-derived markers for predicting the severity of the disease. Methods. The study included 55 measlesaffected children who developed complications (examination group), while the control group included 30 healthy children. The first peripheral blood count, obtained on the first hospitalization day (before treatment), was used for further analyses. Results. The white blood cells, lymphocytes, monocytes, and platelets count were significantly lower, while GLR, PLR, MPR, and CRP were significantly higher in measles-affected children (p < 0.05). In severely complicated measles form, significantly higher values of granulocytes, CRP, GLR, and PLR were documented, including lower lymphocytes (p < 0.05). A linear regression analysis showed that CRP was the only indicator with predictive significance for the severity of the course of measles. Conclusion. The blood cell count-derived inflammatory indices should not be crucial in assessing the severity of measles in children. CRP was the most valuable predictive factor for the development of the severe course of measles in measles-affected children. [ABSTRACT FROM AUTHOR]

Micro-ribonucleic acids are control gene expression in cells. They represent the changed cellular states that occur can be employed as biomarkers. Red blood cells alter biochemically and morphologically while they are being stored, which could be detrimental to transfusion. The effect of storage on the erythrocyte transcriptome is not mostly investigated. Because adult erythrocytes lack a nucleus, it has long been assumed that they lack deoxyribonucleic acid and ribonucleic acid. On the other hand, erythrocytes contain a diverse range of ribonucleic acids, of which micro-ribonucleic acids are key component. Changes in this micro-ribonucleic acid protect cells from death and adenine triphosphate depletion, and they are linked to specific storage lesions. As a result, changes in micro-ribonucleic acid in stored erythrocytes may be used as a marker to assess the quality and safety of stored erythrocytes. Therefore, this review ams to review the role of microRNA in stored packed red blood cells as quality indicator. Google Scholar, PubMed, Scopus, and Z-libraries are used for searching articles and books. The article included in this paper was written in the English language and had the full article. During long storage of RBCs, miR-16-2-3p, miR-1260a, miR-1260b, miR-4443, miR-4695-3p, miR-5100, let-7b, miR-16, miRNA-1246, MiR-31-5p, miR-203a, miR-654-3p, miR-769-3p, miR-4454, miR-451a and miR-125b- 5p are up regulated. However, miR-96, miR-150, miR-196a, miR-197, miR-381 and miR-1245a are down regulated after long storage of RBCs. The changes of this microRNAs are linked to red blood cell lesions. Therefore, micro-ribonucleic acids are the potential quality indicator in stored packed red blood cells in the blood bank. Particularly, micro-ribonucleic acid-96 is the most suitable biomarker for monitoring red blood cell quality in stored packed red blood units. [ABSTRACT FROM AUTHOR]

Blood platelets are crucial to prevent excessive bleeding following injury to blood vessels. Platelets are crucial for the formation of clots and for clot strength. Platelet activation involves aggregation, attachment to fibrin and clot retraction. Most assays that address platelet function measure platelet aggregation, not clot retraction. Here, we describe a 96-well-based clot retraction assay that requires a relatively short runtime and small sample volume. The assay involves continuous optical density monitoring of platelet-rich plasma that is activated with thrombin. The data can be analyzed using time-series analytical tools to generate quantitative information about different phases of clot formation and clot retraction. The assay demonstrated good repeatability and reproducibility and was robust to different calcium concentrations. Impairment of platelet bioenergetics, actin polymerization, fibrin interaction, and signaling significantly affected clot retraction and was detected and showed good agreement with light transmission aggregometry, suggesting that clot retraction is predictive of platelet function. Using this microplate clot retraction assay, we showed a significant difference in platelets stored in autologous plasma compared with platelet additive solution after 7 days of room temperature storage. Platelets are cell fragments in the blood that are necessary for clot formation. They are crucial to preventing excessive bleeding following trauma. To form clots, platelets clump (aggregate) and attach to fibrin protein and cells inside the blood vessels to form strong web-like structures. Platelets also contract to pull the edges of the wound close. Most measurements of platelet function involve aggregation. This paper focuses on platelet contraction. Here, we describe a new assay to measure platelets contraction that is repeatable and reproducible. The assay uses standard and common laboratory equipment and can be performed by most laboratory personnel and has the potential to detect clinical pathologies of clot formation. The assay could be developed for bedside patient care where platelet function could be assessed rapidly and assist in the diagnosis of coagulation and platelet disorders. [ABSTRACT FROM AUTHOR]