Blood Cell Types Research Articles

Management of Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Cytomegalovirus (CMV) is a type of double-stranded deoxyribonucleic acid virus belonging to the herpesviridae family. Following a primary infection, the virus becomes latent in various types of white blood cells. Cytomegalovirus infection can remain latent or become active, especially in immunocompromised individuals, such as those undergoing hematopoietic stem cell transplantation (HSCT), where CMV reactivation can occur. In this context, CMV infection is common and associated with high rates of morbidity and mortality. Pneumonia is one of the most serious complications, with mortality rates exceeding 50%. Additionally, even in the absence of organ-specific disease, CMV infection is related to increased mortality unrelated to hematologic neoplasm recurrence. Given the frequency and severity of this infection in HSCT patients, it is crucial to implement effective strategies for monitoring, prevention, and treatment. This guideline was developed to identify patient groups that benefit from a systematic approach to CMV infection and to define the most appropriate strategy for each group. Monitoring CMV viral load in peripheral blood is crucial, especially in patients at moderate to high risk of active infection. Primary prophylaxis with letermovir (an antiviral drug) is recommended to reduce the incidence of active infection, especially in high-risk patients. Secondary prophylaxis with valganciclovir (antiviral drug) is recommended after an episode of active infection, while preemptive and disease treatment is based on monitoring viral load and clinical response. The aim of this guideline is to improve the approach to CMV infection in HSCT patients, ensuring an effective and safe preventive and therapeutic approach.

Associations of three differential white blood cell counts, platelet counts, and their derived inflammatory indices with cancer-related fatigue in patients with breast cancer undergoing chemotherapy.

Inflammation is thought to be a vital element in the etiology of cancer-related fatigue (CRF), and circulating blood cell parameters could be important markers of inflammatory response. However, the associations of several major blood cell counts and their derived inflammatory indices with CRF are not well described. The present study aimed to establish whether a relationship exists between the counts of three white blood cell (WBC) types, platelets, and CRF and investigate whether several systemic inflammatory indices were associated with CRF in patients with breast cancer (BC). A cross-sectional survey was conducted with a sample of 824 patients with BC undergoing chemotherapy. The cancer fatigue scale was administered to assess CRF. Hematological indicators, including neutrophils, lymphocytes, monocytes, and platelets, were retrieved from routine blood test. Network analyses were used to examine the associations among them. Among 824 participants, the mean score of CRF was (27 ± 10), ranging from 0 to 57. The results of network models indicated that physical fatigue was negatively linked to lymphocyte counts (weight = - 0.161), and affective fatigue was positively associated with neutrophil counts (weight = 0.070). Additionally, physical fatigue was positively linked to the platelet-to-lymphocyte ratio (PLR) (weight = 0.049). There were preliminary associations of counts of three WBC types, platelet counts, and systemic inflammatory indices, with distinct dimensions of CRF in patients with BC. Findings provide empirical support for the cellular basis of fatigue-associated inflammatory states.

Advancements in the impact of human microbiota and probiotics on leukemia.

The human gut microbiota is a complex ecosystem that plays a crucial role in promoting the interaction between the body and its environment. It has been increasingly recognized that the gut microbiota has diverse physiological functions. Recent studies have shown a close association between the gut microbiota and the development of certain tumors, including leukemia. Leukemia is a malignant clonal disease characterized by the uncontrolled growth of one or more types of blood cells, which is the most common cancer in children. The imbalance of gut microbiota is linked to the pathological mechanisms of leukemia. Probiotics, which are beneficial microorganisms that help maintain the balance of the host microbiome, play a role in regulating gut microbiota. Probiotics have the potential to assist in the treatment of leukemia and improve the clinical prognosis of leukemia patients. This study reviews the relationship between gut microbiota, probiotics, and the progression of leukemia based on current research. In addition, utilizing zebrafish leukemia models in future studies might reveal the specific mechanisms of their interactions, thereby providing new insights into the clinical treatment of leukemia. In conclusion, further investigation is still needed to fully understand the accurate role of microbes in leukemia.

Tissue of origin detection for cancer tumor using low-depth cfDNA samples through combination of tumor-specific methylation atlas and genome-wide methylation density in graph convolutional neural networks

BackgroundCell free DNA (cfDNA)-based assays hold great potential in detecting early cancer signals yet determining the tissue-of-origin (TOO) for cancer signals remains a challenging task. Here, we investigated the contribution of a methylation atlas to TOO detection in low depth cfDNA samples.MethodsWe constructed a tumor-specific methylation atlas (TSMA) using whole-genome bisulfite sequencing (WGBS) data from five types of tumor tissues (breast, colorectal, gastric, liver and lung cancer) and paired white blood cells (WBC). TSMA was used with a non-negative least square matrix factorization (NNLS) deconvolution algorithm to identify the abundance of tumor tissue types in a WGBS sample. We showed that TSMA worked well with tumor tissue but struggled with cfDNA samples due to the overwhelming amount of WBC-derived DNA. To construct a model for TOO, we adopted the multi-modal strategy and used as inputs the combination of deconvolution scores from TSMA with other features of cfDNA.ResultsOur final model comprised of a graph convolutional neural network using deconvolution scores and genome-wide methylation density features, which achieved an accuracy of 69% in a held-out validation dataset of 239 low-depth cfDNA samples.ConclusionsIn conclusion, we have demonstrated that our TSMA in combination with other cfDNA features can improve TOO detection in low-depth cfDNA samples.

The heterogeneity of erythroid cells: insight at the single-cell transcriptome level.

Erythroid cells, the most prevalent cell type in blood, are one of the earliest products and permeate through the entire process of hematopoietic development in the human body, the oxygen-transporting function of which is crucial for maintaining overall health and life support. Previous investigations into erythrocyte differentiation and development have primarily focused on population-level analyses, lacking the single-cell perspective essential for comprehending the intricate pathways of erythroid maturation, differentiation, and the encompassing cellular heterogeneity. The continuous optimization of single-cell transcriptome sequencing technology, or single-cell RNA sequencing (scRNA-seq), provides a powerful tool for life sciences research, which has a particular superiority in the identification of unprecedented cell subgroups, the analyzing of cellular heterogeneity, and the transcriptomic characteristics of individual cells. Over the past decade, remarkable strides have been taken in the realm of single-cell RNA sequencing technology, profoundly enhancing our understanding of erythroid cells. In this review, we systematically summarize the recent developments in single-cell transcriptome sequencing technology and emphasize their substantial impact on the study of erythroid cells, highlighting their contributions, including the exploration of functional heterogeneity within erythroid populations, the identification of novel erythrocyte subgroups, the tracking of different erythroid lineages, and the unveiling of mechanisms governing erythroid fate decisions. These findings not only invigorate erythroid cell research but also offer new perspectives on the management of diseases related to erythroid cells.

Investigate the impact of laser dosages on the regeneration of peripheral blood leukocytes after gamma radiation exposure

This research aims to examine how treatment with lasers affects the regeneration of peripheral blood leukocytes following ionizing radiation exposure. Furthermore, how may laser treatment be administered to people who have inadvertently come into contact with ionizing radiation? After being subjected to one dose of five Gy, non-lethal (1.5 Gy/min) from gamma radiation (cobalt-60), the mice developed radiation-induced sickness, as evidenced by a drop in white blood cell count and hematological symptoms. The mice were subsequently subjected to non-ionizing radiation using a 20 W power laser (Nd: YAG 1064 nm). Within the first two weeks after the application of gamma rays for 30 min, there were a total of five laser treatments. Laser energy yielded a total of 60,000 J/cm2. The energy density in each treatment was 12,000 J/cm2. Based on the peripheral blood examination, the study establishes that the use of lasers had an important influence on the number of lymphocytes two weeks after irradiation. Furthermore, following laser treatment, the lymphocyte lineage of white blood cells recovered more quickly. In gamma-irradiated mice, the study showed that the treatment laser under examination increased the overall counts of several types of white blood cells, indicating an indefinite effect. The investigation's findings may have an impact on how radiation illness is treated for specific patients. The results of this investigation may have a substantial influence on the treatment of radiation sickness in people.

A plain language summary of the TROPHY-U-01 study: sacituzumab govitecan use in people with locally advanced or metastatic urothelial cancer.

Sacituzumab govitecan (brand name: TRODELVY®) is a new treatment being studied for people with a type of bladder cancer, called urothelial cancer, that has progressed to a locally advanced or metastatic stage. Locally advanced and metastatic urothelial cancer are usually treated with platinum-based chemotherapy. Metastatic urothelial cancer is also treated with immune checkpoint inhibitors. There are few treatment options for people whose cancer gets worse after receiving these treatments. Sacituzumab govitecan is a suitable treatment option for most people with urothelial cancer because it aims to deliver an anti-cancer drug directly to the cancer in an attempt to limit the potential harmful side effects on healthy cells. This is a summary of a clinical study called TROPHY-U-01, focusing on the first group of participants, referred to as Cohort 1. All participants in Cohort 1 received sacituzumab govitecan. All participants received previous treatments for their metastatic urothelial cancer, including a platinum-based chemotherapy and a checkpoint inhibitor. The tumor in 31 of 113 participants became significantly smaller or could not be seen on scans after sacituzumab govitecan treatment; an effect that lasted for a median of 7.2months. Half of the participants were still alive 5.4months after starting treatment, without their tumor getting bigger or spreading further. Half of them were still alive 10.9months after starting treatment regardless of tumor size changes. Most participants experienced side effects. These side effects included lower levels of certain types of blood cells, sometimes with a fever, and loose or watery stools (diarrhea). Side effects led 7 of 113 participants to stop taking sacituzumab govitecan. The study showed that sacituzumab govitecan had significant anti-cancer activity. Though most participants who received sacituzumab govitecan experienced side effects, these did not usually stop participants from continuing sacituzumab govitecan. Doctors can help control these side effects using treatment guidelines, but these side effects can be serious. Clinical Trial Registration: NCT03547973 (ClinicalTrials.gov) (TROPHY-U-1).

Plain Language Summary of principles for improving the care of people with eosinophil-associated diseases.

Eosinophil-associated diseases (EADs) are a group of conditions in which eosinophils (a type of white blood cell) are thought to play a key role in the disease and how it develops. Some EADs are common, such as atopic dermatitis (also called eczema) and a subtype of asthma called eosinophilic asthma, while others are rare, such as hypereosinophilic syndrome (a condition in which a person has a very high number of eosinophils in both the blood and one or more organs). People with EADs face many problems related to their conditions. Symptoms such as severe abdominal pain, itch, or shortness of breath impact both the patient as well as their friends and family. Patients with EADs also experience delays to diagnosis and treatment as well as financial barriers. Healthcare professionals sometimes fail to recognize the complex set of symptoms that characterize an EAD, and this may cause delays in reaching a correct diagnosis. As a result, it may take longer for a patient to get the best care and the most effective treatments, which may contribute to poor health. The goal of this charter is to describe the key elements of good quality care, which all people with EADs deserve, as well as to present an action plan to improve health and overall well-being for people with EADs. Proposed use of this patient charter: The principles described in this charter (a written guide to achieve an outcome) show the core elements of quality care that people with EADs must receive. They also describe clear steps to reduce the burden on patients and their caregivers and to improve patient health outcomes. We urge healthcare professionals, hospitals, and policymakers around the world to adopt these principles quickly. By doing this, people with EADs will be more likely to receive an accurate and timely diagnosis and have access to quality care and treatment in the right setting.

Empirical validation of Conformal Prediction for trustworthy skin lesions classification

Background and objective:Uncertainty quantification is a pivotal field that contributes to realizing reliable and robust systems. It becomes instrumental in fortifying safe decisions by providing complementary information, particularly within high-risk applications. existing studies have explored various methods that often operate under specific assumptions or necessitate substantial modifications to the network architecture to effectively account for uncertainties. The objective of this paper is to study Conformal Prediction, an emerging distribution-free uncertainty quantification technique, and provide a comprehensive understanding of the advantages and limitations inherent in various methods within the medical imaging field. Methods:In this study, we developed Conformal Prediction, Monte Carlo Dropout, and Evidential Deep Learning approaches to assess uncertainty quantification in deep neural networks. The effectiveness of these methods is evaluated using three public medical imaging datasets focused on detecting pigmented skin lesions and blood cell types. Results:The experimental results demonstrate a significant enhancement in uncertainty quantification with the utilization of the Conformal Prediction method, surpassing the performance of the other two methods. Furthermore, the results present insights into the effectiveness of each uncertainty method in handling Out-of-Distribution samples from domain-shifted datasets. Our code is available at: github.com/jfayyad/ConformalDx. Conclusions:Our conclusion highlights a robust and consistent performance of conformal prediction across diverse testing conditions. This positions it as the preferred choice for decision-making in safety-critical applications.

#2266 Removal of middle size molecules: effects on the modifications of subgroups of white cell types

Abstract Background and Aims In both classical hemodialysis (HD) and its high convective version, the hemodiafiltration (HDF), the unavoidable contact of blood cells with the filters (e.g. polysulfone), may cause the formation of microaggregates and the release of Inflammatory cytokines. Reducing inflammation and thrombus formation is essential, as these may change the cardiovascular risk of patients undergoing chronic HD. To overcome this problem, removing plasma proteins with greater molecular weight, thereby modifying the protein network around blood cells, might be helpful. Method Synthetic dialyzers (FX 80 CorDiax [Fresenius Medical Care], medium-cutoff filter Theranova 400 [Baxter], Elisio 17-H [Nipro], and BG-U 1.6 [Toray]) have been compared regarding their effects on white blood cell types. We designed a retrospective, dual-center clinical study on patients in ESRD needing substitutive therapy. Groups comparable for age, blood pressure, and body weight have been compared. Changes in albumin, Hb, neutrophils, eosinophils, basophils, monocytes, and platelets have been analysed one month after the treatment. Results The Theranova treatment decreased lymphocytes but was also observed to increase neutrophils and MCV. Platelet count was highest with Elisio-H filters, whereas they were comparable among the other groups. Correlation analysis showed a significant association between platelet counts, neutrophils, and monocytes in all groups. Conversely, the correlation between eosinophils and lymphocytes was significant for all groups except for the Theranova filters. Furthermore, the dialyzers inulin (5.2kDa) clearance was negatively linearly correlated to the lymphocyte counts. Conclusion The recent introduction of MCO filters offers the clinician an adjunctive possibility to modify blood composition in terms of plasma composition and different white blood cells. Further studies may use these unique characteristics in new clinical settings.

Treating moderate-to-severe atopic dermatitis with benralizumab: results from the HILLIER study, a plain language summary.

Atopic dermatitis (AD) is a chronic (long-lasting) skin disease that leads to dry, itchy, and swollen red spots, which can also be painful and flare up at any time. Some people with AD have a high number of eosinophils, a type of white blood cell, which are associated with worse disease. Medicated creams and lotions, prescribed by health care providers, are meant to reduce the symptoms of AD. For some people, these creams and lotions do not work. Benralizumab injection is a medication that reduces and removes eosinophils. A clinical trial called HILLER tested benralizumab to see if there was a difference in symptoms of AD after reducing or removing eosinophils. This article explains how benralizumab reduced eosinophils and the effect it had on AD symptoms in the HILLIER study. Benralizumab reduced blood eosinophil numbers. However, benralizumab showed no evidence of treatment benefit on signs, symptoms, or severity of AD, as measured by three skin assessments compared with placebo. Benralizumab was well tolerated and had a safety profile that was consistent with previous studies. The five most commonly reported side effects were COVID-19 infection, upper respiratory tract infection, headache, swelling of the lymph nodes, and pink eye (conjunctivitis) in patients who received either benralizumab or placebo. Benralizumab lowered the number of blood eosinophils without improving AD symptoms and was well tolerated.

Reliable detection of stochastic epigenetic mutations and associations with cardiovascular aging.

Stochastic epigenetic mutations (SEMs) have been proposed as novel aging biomarkers to capture heterogeneity in age-related DNA methylation changes. SEMs are defined as outlier methylation patterns at cytosine-guanine dinucleotide sites, categorized as hypermethylated (hyperSEM) or hypomethylated (hypoSEM) relative to a reference. Because SEMs are defined by their outlier status, it is critical to differentiate extreme values due to technical noise or data artifacts from those due to real biology. Using technical replicate data, we found SEM detection is not reliable: across 3 datasets, 24 to 39% of hypoSEM and 46 to 67% of hyperSEM are not shared between replicates. We identified factors influencing SEM reliability-including blood cell type composition, probe beta-value statistics, genomic location, and presence of SNPs. We used these factors in a training dataset to build a machine learning-based filter that removes unreliable SEMs, and found this filter enhances reliability in two independent validation datasets. We assessed associations between SEM loads and aging phenotypes in the Framingham Heart Study and discovered that associations with aging outcomes were in large part driven by hypoSEMs at baseline methylated probes and hyperSEMs at baseline unmethylated probes, which are the same subsets that demonstrate highest technical reliability. These aging associations were preserved after filtering out unreliable SEMs and were enhanced after adjusting for blood cell composition. Finally, we utilized these insights to formulate best practices for SEM detection and introduce a novel R package, SEMdetectR, which uses parallel programming for efficient SEM detection with comprehensive options for detection, filtering, and analysis.

Whole-genome sequences reveal zygotic composition in chimeric twins

While most dizygotic twins have a dichorionic placenta, rare cases of dizygotic twins with monochorionic placenta have been reported. The monochorionic placenta in dizygotic twins allows in utero exchange of embryonic cells, resulting in chimerism in the twins. In practice, this chimerism is incidentally identified on mixed ABO blood types or in the presence of cells with a discordant sex chromosome. Here, we applied whole-genome sequencing to one triplet and one twin families to precisely understand their zygotic compositions, using millions of genomic variants as barcodes of zygotic origins. Peripheral blood showed asymmetrical contributions from two sister zygotes, where one of the zygotes was the major clone in both twins. Single-cell RNA sequencing of peripheral blood tissues further showed differential contributions from the two sister zygotes across blood cell types. In contrast, buccal tissues were pure in genetic composition, suggesting that in utero cellular exchanges were confined to the blood tissues. Our study illustrates the cellular history of twinning during human development, which is critical for managing the health of chimeric individuals in the era of genomic medicine.

Comparative Study of Men and Knock-in Mice Expressing Red Cell Glycophorin B-A-B hybrid Protein Identifies Physiological Functions of SLC4A1 (band 3)

GP.Mur is a common Southeast Asian red blood cell (RBC) type, with 4.7% prevalence in Taiwan (compared to 5.8% AB blood type). In people with the GP.Mur (glycophorin B-A-B hybrid) type, their expression of Cl−/HCO3− anion exchanger-1 (AE1; SLC4A1; band 3) on the RBC membrane is increased. Glycophorin A, as well as this glycophorin B-A-B variant, are chaperone proteins that promote SLC4A1 folding and protein formation by 10% or more. Healthy people with the GP.Mur blood type exhibit two unique physiological features: (1) slightly higher blood pressure, and (2) more effcient CO2 excretion. Human and mouse lacking SLC4A1 cannot survive postnatally. As the physiological impacts and mechanisms of SLC4A1 are unclear, we created a knock-in mouse model of human GYP.Mur. To verify whether these physiological features could indeed be the direct consequences of GYP.Mur expression, we tested the knock-in mice by (1) blood pressure measurements with antihypertensive drug challenges, and (2) whole-body plethysmorgraphy (WBP)-respiration measurements. We found that GYP.Mur knock-in mice also expressed more SLC4A1 on the RBC membrane. The knock-in mice exhibited significantly higher mean arterial pressure (MAP) than age-matched control C57BL/6J mice, with differential antihypertensive sensitivities. In WBP measurements on freely-moving mice, GYP.Mur knock-in and the control mice also showed differential respiratory patterns, which were diminished with acetazolamide pretreatments. Thus, GYP.Mur knock-in mice recapitulates the major phenotypes of people carrying the GP.Mur blood type. Taiwan Ministry of Science & Technology (MOST 108-2628-B-195-001; 109-2628-B-195-001; 110-2628-B-195-001); Taiwan MacKay Memorial Hospital. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

OGT and OGA gene-edited human induced pluripotent stem cells for dissecting the functional roles of O-GlcNAcylation in hematopoiesis.

Hematopoiesis continues throughout life to produce all types of blood cells from hematopoietic stem cells (HSCs). Metabolic state is a known regulator of HSC self-renewal and differentiation, but whether and how metabolic sensor O-GlcNAcylation, which can be modulated via an inhibition of its cycling enzymes O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT), contributes to hematopoiesis remains largely unknown. Herein, isogenic, single-cell clones of OGA-depleted (OGAi) and OGT-depleted (OGTi) human induced pluripotent stem cells (hiPSCs) were successfully generated from the master hiPSC line MUSIi012-A, which were reprogrammed from CD34+ hematopoietic stem/progenitor cells (HSPCs) containing epigenetic memory. The established OGAi and OGTi hiPSCs exhibiting an increase or decrease in cellular O-GlcNAcylation concomitant with their loss of OGA and OGT, respectively, appeared normal in phenotype and karyotype, and retained pluripotency, although they may favor differentiation toward certain germ lineages. Upon hematopoietic differentiation through mesoderm induction and endothelial-to-hematopoietic transition, we found that OGA inhibition accelerates hiPSC commitment toward HSPCs and that disruption of O-GlcNAc homeostasis affects their commitment toward erythroid lineage. The differentiated HSPCs from all groups were capable of giving rise to all hematopoietic progenitors, thus confirming their functional characteristics. Altogether, the established single-cell clones of OGTi and OGAi hiPSCs represent a valuable platform for further dissecting the roles of O-GlcNAcylation in blood cell development at various stages and lineages of blood cells. The incomplete knockout of OGA and OGT in these hiPSCs makes them susceptible to additional manipulation, i.e., by small molecules, allowing the molecular dynamics studies of O-GlcNAcylation.

Acoustic Enrichment of Heterogeneous Circulating Tumor Cells and Clusters from Metastatic Prostate Cancer Patients.

There are important unmet clinical needs to develop cell enrichment technologies to enable unbiased label-free isolation of both single cell and clusters of circulating tumor cells (CTCs) manifesting heterogeneous lineage specificity. Here, we report a pilot study based on the microfluidic acoustophoresis enrichment of CTCs using the CellSearch CTC assay as a reference modality. Acoustophoresis uses an ultrasonic standing wave field to separate cells based on biomechanical properties (size, density, and compressibility), resulting in inherently label-free and epitope-independent cell enrichment. Following red blood cell lysis and paraformaldehyde fixation, 6 mL of whole blood from 12 patients with metastatic prostate cancer and 20 healthy controls were processed with acoustophoresis and subsequent image cytometry. Acoustophoresis enabled enrichment and characterization of phenotypic CTCs (EpCAM+, Cytokeratin+, DAPI+, CD45-/CD66b-) in all patients with metastatic prostate cancer and detected CTC-clusters composed of only CTCs or heterogeneous aggregates of CTCs clustered with various types of white blood cells in 9 out of 12 patients. By contrast, CellSearch did not detect any CTC clusters, but detected comparable numbers of phenotypic CTCs as acoustophoresis, with trends of finding a higher number of CTCs using acoustophoresis. Our preliminary data indicate that acoustophoresis provides excellent possibilities to detect and characterize CTC clusters as a putative marker of metastatic disease and outcomes. Moreover, acoustophoresis enables the sensitive label-free enrichment of cells with epithelial phenotypes in blood and offers opportunities to detect and characterize CTCs undergoing epithelial-to-mesenchymal transitioning and lineage plasticity.

Epigenetic age oscillates during the day.

Since their introduction, epigenetic clocks have been extensively used in aging, human disease, and rejuvenation studies. In this article, we report an intriguing pattern: epigenetic age predictions display a 24-h periodicity. We tested a circadian blood sample collection using 17 epigenetic clocks addressing different aspects of aging. Thirteen clocks exhibited significant oscillations with the youngest and oldest age estimates around midnight and noon, respectively. In addition, daily oscillations were consistent with the changes of epigenetic age across different times of day observed in an independant populational dataset. While these oscillations can in part be attributed to variations in white blood cell type composition, cell count correction methods might not fully resolve the issue. Furthermore, some epigenetic clocks exhibited 24-h periodicity even in the purified fraction of neutrophils pointing at plausible contributions of intracellular epigenomic oscillations. Evidence for circadian variation in epigenetic clocks emphasizes the importance of the time-of-day for obtaining accurate estimates of epigenetic age.

A double‐edged sword: The complex interplay between engineered nanoparticles and platelets

AbstractNanoparticles (NP) play a crucial role in nanomedicine, serving as carriers for localized therapeutics to allow for precise drug delivery to specific disease sites and conditions. When injected systemically, NP can directly interact with various blood cell types, most critically with circulating platelets. Hence, the potential activation/inhibition of platelets following NP exposure must be evaluated a priori due to possible debilitating outcomes. In recent years, various studies have helped resolve the physicochemical parameters that influence platelet‐NP interactions, and either emphasize nanoparticles' therapeutic role such as to augment hemostasis or to inhibit thrombus formation, or conversely map their potential undesired side effects upon injection. In the present review, we discuss some of the main effects of several key NP types including polymeric, ceramic, silica, dendrimers and metallic NPs on platelets, with a focus on the physicochemical parameters that can dictate these effects and modulate the therapeutic potential of the NP. Despite the scientific and clinical significance of understanding Platelet‐NP interactions, there is a significant knowledge gap in the field and a critical need for further investigation. Moreover, improved guidelines and research methodologies need to be developed and implemented. Our outlook includes the use of biomimetic in vitro models to investigate these complex interactions under both healthy physiological and disease conditions.

Comprehensive data analysis of white blood cells with classification and segmentation by using deep learning approaches.

Deep learning approaches have frequently been used in the classification and segmentation of human peripheral blood cells. The common feature of previous studies was that they used more than one dataset, but used them separately. No study has been found that combines more than two datasets to use together. In classification, five types of white blood cells were identified by using a mixture of four different datasets. In segmentation, four types of white blood cells were determined, and three different neural networks, including CNN (Convolutional Neural Network), UNet and SegNet, were applied. The classification results of the presented study were compared with those of related studies. The balanced accuracy was 98.03%, and the test accuracy of the train-independent dataset was determined to be 97.27%. For segmentation, accuracy rates of 98.9% for train-dependent dataset and 92.82% for train-independent dataset for the proposed CNN were obtained in both nucleus and cytoplasm detection. In the presented study, the proposed method showed that it could detect white blood cells from a train-independent dataset with high accuracy. Additionally, it is promising as a diagnostic tool that can be used in the clinical field, with successful results in classification and segmentation.

Blood Cell Types and Abnormalities in Free Ranging Hermann’s Tortoise (Testudo hermanni) Populations from Different Habitats

Testudo hermanni is considered near threatened globally in the wild. In this study differential leukocyte percentages, nuclear abnormalities, and erythrocyte morphology abnormalities of Testudo hermanni populations from two different habitat types in the Thrace Region were determined to whether habitats have a potential effect on blood cells. A total of 37 tortoises, 18 from an open habitat in Kırklareli/Karakoç, and 19 from an isolated habitat in Edirne/Keşan were studied. According to the results obtained from the Micronucleus Test, which detects genotoxic damage, there was no statistically significant difference between the two habitats. There were statistically significant differences in erythrocyte morphology abnormalities and differential leukocyte count between two populations, such as frequencies of anucleated erythrocyte, nuclear shift, elliptical shape distortion, monocyte and eosinophile percentages. This is the first study examined nuclear abnormalities of Testudo hermanni in Türkiye.