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Objectives: This study examined the impact of injectable plateletrich fibrin (iPRF) and concentrated growth factor on postoperative pain, edema, trismus, and quality of life in impacted mandibular third molar surgery. The primary aim of this study was to minimize common sequelae following third molar surgery by using iPRF and concentrated growth factor. The secondary objective was to compare the postoperative effects of these products. Method and materials: This study represents a single-center, randomized prospective clinical trial conducted at the Ordu University Faculty of Dentistry. It involved patients who underwent third molar surgery for various reasons between July and October 2022. The predictor variables were the use of concentrated growth factor and i-PRF. They were categorized as concentrated growth factor, i-PRF, and control groups. The outcome variables include pain levels and analgesic consumption measured on a visual analog scale, distances between predetermined anatomical points, maximum mouth opening capacity, and data from the postoperative symptom severity (PoSSe) scale. Some statistical tests were performed with a 95% confidence interval, which was considered significant. Results: Total analgesic use was notably lower in the concentrated growth factor group (P = .044). Concentrated growth factor and iPRF outperformed the control group in all edema measurements by postoperative day 7 (tragus–pogonion, lateral canthus–angulus, tragus–commissura; P < .05). Concentrated growth factor significantly reduced trismus on days 2 and 7. Quality of life was notably higher in the concentrated growth factor group than in the control group (P = .026), although iPRF group differences were not significant. Conclusion: The results indicate that concentrated growth factor has a limited impact on postoperative pain, but significantly reduces edema, trismus, and enhances quality of life. The iPRF group experienced positive effects on pain, edema, and trismus, although the statistically significant differences observed with concentrated growth factor highlight its potential for use instead of iPRF after third molar surgery. An increased sample size is essential for more comprehensive results [ABSTRACT FROM AUTHOR]

With the increasing incidence of kidney diseases, there is an urgent need to develop therapeutic strategies to combat post-injury fibrosis. Immune cells, including platelets, play a pivotal role in this repair process, primarily through their released cytokines. However, the specific role of platelets in kidney injury and subsequent repair remains underexplored. Here, the detrimental role of platelets in renal recovery following ischemia/reperfusion injury and its contribution to acute kidney injury  to chronic kidney disease transition is aimed to investigated. In this study, it is shown that depleting platelets accelerates injury resolution and significantly reduces fibrosis. Employing advanced single-cell and spatial transcriptomic techniques, macrophages as the primary mediators modulated by platelet signals is identified. A novel subset of macrophages, termed cycling M2, which exhibit an M2 phenotype combined with enhanced proliferative activity is uncovered. This subset emerges in the injured kidney during the resolution phase and is modulated by platelet-derived thrombospondin 1 (THBS1) signaling, acquiring profibrotic characteristics. Conversely, targeted inhibition of THBS1 markedly downregulates the cycling M2 macrophage, thereby mitigating fibrotic progression. Overall, this findings highlight the adverse role of platelet THBS1-boosted cycling M2 macrophages in renal injury repair and suggest platelet THBS1 as a promising therapeutic target for alleviating inflammation and kidney fibrosis.

The evolution of endovascular therapies, particularly in the field of intracranial aneurysm treatment, has been truly remarkable and is characterized by the development of various stents. However, ischemic complications related to thrombosis or downstream emboli pose a challenge for the broader clinical application of such stents. Despite advancements in surface modification technologies, an ideal coating that fulfills all the desired requirements, including anti-thrombogenicity and swift endothelialization, has not been available. To address these issues, we investigated a new coating comprising 3-aminopropyltriethoxysilane (APTES) with both anti-thrombogenic and cell-adhesion properties. We assessed the anti-thrombogenic property of the coating using an in vitro blood loop model by evaluating the platelet count and the level of the thrombin-antithrombin (TAT) complex, and investigating thrombus formation on the surface using scanning electron microscopy (SEM). We then assessed endothelial cell adhesion on the metal surfaces. In vitro blood tests revealed that, compared to a bare stent, the coating significantly inhibited platelet reduction and thrombus formation; more human serum albumin spontaneously adhered to the coated surface to block thrombogenic activation in the blood. Cell adhesion tests also indicated a significant increase in the number of cells adhering to the APTES-coated surfaces compared to the numbers adhering to either the bare stent or the stent coated with an anti-fouling phospholipid polymer. Finally, we performed an in vivo safety test by implanting coated stents into the internal thoracic arteries and ascending pharyngeal arteries of minipigs, and subsequently assessing the health status and vessel patency of the arteries by angiography over the course of 1 week. We found that there were no adverse effects on the pigs and the vascular lumens of their vessels were well maintained in the group with APTES-coated stents. Therefore, our new coating exhibited both high anti-thrombogenicity and cell-adhesion properties, which fulfill the requirements of an implantable stent.

Patients treated with antineoplastic therapy often develop thrombocytopenia requiring platelet transfusion, which has potential to exacerbate pulmonary injury. This study tested the hypothesis that amotosalen-UVA pathogen-reduced platelet components (PRPCs) do not potentiate pulmonary dysfunction compared with conventional platelet components (CPCs). A prospective, multicenter, open-label, sequential cohort study evaluated the incidence of treatment-emergent assisted mechanical ventilation initiated for pulmonary dysfunction (TEAMV-PD). The first cohort received CPC. After the CPC cohort, each site enrolled a second cohort transfused with PRPC. Other outcomes included clinically significant pulmonary adverse events (CSPAE) and the incidence of treatment-emergent acute respiratory distress syndrome (TEARDS) diagnosed by blinded expert adjudication. The incidence of TEAMV-PD in all patients (1068 PRPC and 1223 CPC) was less for PRPC (1.7 %) than CPC (3.1%) with a treatment difference of -1.5% (95% confidence interval [CI], -2.7 to -0.2). In patients requiring ≥2 PCs, the incidence of TEAMV-PD was reduced for PRPC recipients compared with CPC recipients (treatment difference, -2.4%; 95% CI, -4.2 to -0.6). CSPAE increased with increasing PC exposure but were not significantly different between the cohorts. For patients receiving ≥2 platelet transfusions, TEARDS occurred in 1.3% PRPC and 2.6% CPC recipients (P = .086). Bayesian analysis demonstrated PRPC may be superior in reducing TEAMV-PD and TEARDS for platelet transfusion recipients compared with CPC recipients, with 99.2% and 88.8% probability, respectively. In this study, PRPC compared with CPC demonstrated high probability of reduced severe pulmonary injury requiring assisted mechanical ventilation in patients with hematology disorders dependent on platelet transfusion. This trial was registered at www.ClinicalTrials.gov as #NCT02549222.

The adaptive mechanical properties of soft and fibrous biological materials are relevant to their functionality. The emergence of the macroscopic response of these materials to external stress and intrinsic cell traction from local deformations of their structural components is not well understood. Here, we investigate the nonlinear elastic behavior of blood clots by combining microscopy, rheology, and an elastic network model that incorporates the stretching, bending, and buckling of constituent fibrin fibers. By inhibiting fibrin cross-linking in blood clots, we observe an anomalous softening regime in the macroscopic shear response as well as a reduction in platelet-induced clot contractility. Our model explains these observations from two independent macroscopic measurements in a unified manner, through a single mechanical parameter, the bending stiffness of individual fibers. Supported by experimental evidence, our mechanics-based model provides a framework for predicting and comprehending the nonlinear elastic behavior of blood clots and other active biopolymer networks in general.

BACKGROUND: Pulmonary hypertension (PH) in dogs with myxomatous mitral valve disease (MMVD) is caused by increased pulmonary venous pressure. Thrombosis, vascular remodeling, and vasoconstriction mediated by platelets could exacerbate PH. HYPOTHESIS: Dogs with PH will exhibit a hypercoagulable state, characterized by increased platelet activation, platelet-leukocyte, and platelet-neutrophil aggregate formation. ANIMALS: Eleven dogs (≥3.5 kg) diagnosed with MMVD and PH and 10 dogs with MMVD lacking PH. METHODS: Prospective cohort ex vivo study. All dogs underwent echocardiographic examination, CBC, 3-view thoracic radiographs, and heartworm antigen testing. Severity of PH and MMVD were assessed by echocardiography. Viscoelastic monitoring of coagulation was assessed using thromboelastography (TEG). Platelet activation and platelet-leukocyte/platelet-neutrophil interactions were assessed using flow cytometry. Plasma serotonin concentrations were measured by ELISA. RESULTS: Unstimulated platelets from dogs with MMVD and PH expressed more surface P-selectin than MMVD controls (P = .03). Platelets from dogs with MMVD and PH had persistent activation in response to agonists. The number of platelet-leukocyte aggregates was higher in dogs with MMVD and PH compared with MMVD controls (P = .01). Ex vivo stimulation of whole blood resulted in higher numbers of platelet-neutrophil aggregates in dogs with MMVD and PH (P = .01). Assessment of hypercoagulability based on TEG or plasma serotonin concentrations did not differ between groups. CONCLUSION AND CLINICAL IMPORTANCE: Platelet hyperresponsiveness and increased platelet-neutrophil interaction occur in dogs with MMVD and PH, suggesting that platelets play a role of in the pathogenesis of PH. Clinical benefits of antiplatelet drugs in dogs with MMVD and PH require further investigation.

This study focuses on understanding the transcriptional heterogeneity of activated platelets and its impact on diseases such as sepsis, COVID-19, and systemic lupus erythematosus (SLE). Recognizing the limited knowledge in this area, our research aims to dissect the complex transcriptional profiles of activated platelets to aid in developing targeted therapies for abnormal and pathogenic platelet subtypes. We analyzed single-cell transcriptional profiles from 47,977 platelets derived from 413 samples of patients with these diseases, utilizing Deep Neural Network (DNN) and eXtreme Gradient Boosting (XGB) to distinguish transcriptomic signatures predictive of fatal or survival outcomes. Our approach included source data annotations and platelet markers, along with SingleR and Seurat for comprehensive profiling. Additionally, we employed Uniform Manifold Approximation and Projection (UMAP) for effective dimensionality reduction and visualization, aiding in the identification of various platelet subtypes and their relation to disease severity and patient outcomes. Our results highlighted distinct platelet subpopulations that correlate with disease severity, revealing that changes in platelet transcription patterns can intensify endotheliopathy, increasing the risk of coagulation in fatal cases. Moreover, these changes may impact lymphocyte function, indicating a more extensive role for platelets in inflammatory and immune responses. This study identifies crucial biomarkers of platelet heterogeneity in serious health conditions, paving the way for innovative therapeutic approaches targeting platelet activation, which could improve patient outcomes in diseases characterized by altered platelet function.

Platelets are the terminal progeny of megakaryocytes, primarily produced in the bone marrow, and play critical roles in blood homeostasis, clotting, and wound healing. Traditionally, megakaryocytes and platelets are thought to arise from multipotent hematopoietic stem cells (HSCs) via multiple discrete progenitor populations with successive, lineage-restricting differentiation steps. However, this view has recently been challenged by studies suggesting that (1) some HSC clones are biased and/or restricted to the platelet lineage, (2) not all platelet generation follows the "canonical" megakaryocytic differentiation path of hematopoiesis, and (3) platelet output is the default program of steady-state hematopoiesis. Here, we specifically investigate the evidence that in vivo lineage tracing studies provide for the route(s) of platelet generation and investigate the involvement of various intermediate progenitor cell populations. We further identify the challenges that need to be overcome that are required to determine the presence, role, and kinetics of these possible alternate pathways.

Hierarchical porous alumina ceramics were prepared through hydratable alumina gel-casting method. The matrices were constructed by interlocked alumina platelets. Hollow glass spheres as pore formers participated in the fluorine-catalyzed structure formation process. The samples with 20 wt% hollow spheres added (1000–1300 °C) had volume densities, apparent porosities, linear shrinkages and compression strengths of 0.59–0.90 g/cm3, 81.68 %∼74.20 %, 1.40 %∼14.07 % and 12.64–23.36 MPa, respectively. Changing the fraction of hollow spheres (10–30 wt%, 1100 °C) had effects on tailoring the compression strengths (3.13–13.40 MPa), without apparently affecting the densities (0.58–0.60 g/cm3)/porosities (79.70 %∼82.28 %)/shrinkages (1.47 %∼1.93 %). The pore size distributions demonstrated the interlocking pores built by alumina platelets, the pores that inherited from the gel network, and the large pores provided by hollow spheres. The reheated (1300 °C) samples presented good structure stability with shrinkages of 6.60 %∼18.57 %. The synthesized ceramics with both high porosities and satisfactory strengths could meet the requirements of high temperature gas/liquid filtration or catalyst supporting, etc. [ABSTRACT FROM AUTHOR]

Al 2 O 3 reticulated porous ceramics (ARPCs) are extensively employed in high-temperature catalytic support, molten metal filtration, and porous media combustion because of their high specific surface area and heat resistance. The high specific surface area is usually maintained by high apparent porosity, but unfortunately, the accompanying poor mechanical properties severely compromise the durability of ARPCs. To synergistically improve the mechanical properties and apparent porosity, a new strategy was proposed to prepare ARPCs with textured structures of in situ interlocking Al 2 O 3 platelet integration using vacuum impregnation Na 3 AlF 6 –SiC–Al 2 O 3 slurry technique. The obtained textural structure had a significant strengthening effect on ARPCs, attributed to the increased contact area among non-equiaxed grains, and the compact growth of Al 2 O 3 platelets with high aspect ratios provided the high apparent porosity and specific surface area of ARPCs, resulting in compressive strength as high as 3.93 MPa at an apparent porosity of 85.31 %, as well as the degradation of Congo red up to 75.35 % due to the Al 2 O 3 platelets facilitating the loading of TiO 2. [ABSTRACT FROM AUTHOR]

Introduction Exposure to high doses of ionizing radiation can result in hematopoietic acute radiation syndrome. Currently, there is no radiation medical countermeasure approved by the U.S. FDA which can be used before radiation exposure to protect exposed individuals. Here we aimed to evaluate the therapeutic potential of an aqueous suspension of synthetic genistein nanoparticles (BIO 300) as a radioprotectant in a pilot efficacy study using a nonhuman primate model of total body irradiation. Materials and Methods Eight rhesus macaques were divided into two groups; four received vehicle and four received BIO 300 Injectable Suspension 24 h before 5.8 Gy total-body irradiation. Survival, blood cell counts, blood chemistry, and clinical parameters were monitored over the 60 days of the study. Tissues were collected at necropsy 60 days post-irradiation or from animals that met unscheduled euthanasia criteria and subjected to histopathological analysis. Tissues analyzed included the duodenum, jejunum, ileum, sternum, lung, heart, liver, kidney, spleen, gut-associated lymphoid tissue, and urinary bladder. Results In this pilot study, all BIO 300 Injectable Suspension treated animals survived to day 60, while only 50% of the vehicle-treated animals survived. We found that BIO 300 Injectable Suspension did not mediate an improvement in blood cell counts (e.g. neutrophils, platelets, white blood cells). However, BIO 300 Injectable Suspension treated animals had a lower incidence of fever and febrile neutropenia, were able to better maintain their body weight post radiation exposure, and exhibited less anemia and faster recovery from anemia. Histopathological analysis revealed that BIO 300-treated animals had less irradiation-induced damage to the sternum and other tissues compared to vehicle controls. Conclusions BIO 300's mechanism of action is complex and protection against irradiation is attainable without much improvement in the complete blood count (CBC) profile. BIO 300's mechanism for radioprotection involves multiple biological pathways and systems. [ABSTRACT FROM AUTHOR]

Introduction Thirdhand smoke (THS) is associated with many public health and disease concerns, such as respiratory illness, cancer, lipidemia, and cardiovascular disease (CVD). We have previously shown that a moderate to long-term exposure to THS increases the risk of thrombosis. However, whether short-term exposure to THS would produce any effects remains to be discovered. Therefore, this study investigated the impact of 1-month THS exposure on platelet function, in vivo and in vitro, and on cytokine response, in a sex-dependent manner. Aims and Methods Secondhand smoke or clean air (CA) exposed upholstery materials for 1 week were kept in cages housed with 5–6 mice, and the procedure was repeated for 4 weeks. These THS-exposed mice were evaluated for thrombogenesis and platelet function assays. In addition, cytokines expression was evaluated from pooled serum. Results Compared to the CA group, THS exposure significantly shortened the tail bleeding time and carotid artery thrombus formation. Moreover, the female mice appeared more sensitive to THS exposure than males. Furthermore, platelet aggregation, dense granule secretion, and P-selectin activation markers were significantly elevated due to THS exposure. In addition, high-throughput screening showed at least 30 cytokines differentially modulated by THS in females relative to 26 in male mice. Conclusions Collectively, these results demonstrate that 1 month of THS exposure represents a high health risk, in part, by triggering a prothrombotic phenotype that appears to be more significant in females, who are at a much higher risk for occlusive CVD. Additionally, changes in cytokine levels mediate some of the THS-induced occlusive effects. Implications This study revealed that THS exposure for 1 month is detrimental to the cardiovascular health of both sexes; however, females could be more aggressively affected than males. In addition, interleukins and chemokines could be critical factors for initiating prothrombotic activity due to THS exposure. [ABSTRACT FROM AUTHOR]

Introduction: This prospective, single-arm, crossover pharmacodynamic study assessed the effect of Bayer® low-dose enteric-coated aspirin 81 mg tablets (LD EC-ASA) (Bayer AG, Leverkusen, North Rhine-Westphalia, Germany) compared to Vazalore® low-dose phospholipid-aspirin liquid-filled 81 mg capsules (LD PL-ASA) (PLx Pharma Inc., Sparta, NJ, USA) on platelet reactivity with respect to aspirin reaction units (ARU). Methods: Forty-seven healthy volunteers were recruited. Platelet function was evaluated with the VerifyNow™ ARU assay (Werfen, Bedford, MA, USA) and assessed post-initiation of Bayer® LD EC-ASA daily for 14 days, with a washout period of 28 days, followed by Vazalore® LD PL-ASA daily for 14 days, again followed by ARU testing. Results: Participants on LD EC-ASA had a mean ARU score of 426, with 19.1% of participants having an ARU > 550; patients on LD PL-ASA derived a mean ARU score of 435, with 14.9% achieving an ARU > 550. There were no significant differences in aspirin resistance (ARU > 550) according to the formulation (Bayer® LD EC-ASA vs. Vazalore® LD PL-ASA) used. Aspirin resistance was independent of ethnicity regardless of the formulation used. In addition, there were no significant associations between body surface area (BSA) and Bayer® LD EC-ASA ARU value (p value 0.788) or Vazalore® LD PL-ASA ARU value (p value 0.477). No patients experienced any serious adverse events or treatment-emergent adverse events. Conclusions: There were no significant differences in aspirin resistance between Bayer® LD EC-ASA and Vazalore® LD PL-ASA. This dedicated pharmacodynamic study could potentially be informative and applicable for Trinidadian patients on dual antiplatelet therapy (DAPT). Further studies are required to confirm these exploratory findings. Trial Registration: ClinicalTrials.gov identifier, NCT06228820, prospectively registered 1/18/2024. [ABSTRACT FROM AUTHOR]

Background: Blood clots are composed of aggregated fibrin and platelets, and thrombosis is the body's natural response to repairing injured blood vessels or stopping bleeding. However, when this process is activated abnormally, such as in a mechanical blood pump, it can lead to excessive thrombus formation. Therefore, how to avoid or reduce the probability of thrombus formation is an important indicator of the stable operation of a blood pump. Methods: In this paper, Lagrangian particle tracking trajectories are simulated to study platelet transport in a blood pump. The design of the thrombus blood pump was optimized using an orthogonal design method based on three factors: inlet angle, outlet angle, and blade number. The effect of blood pump pressure, rotational speed, impeller outlet angle, inlet angle, and number of blades on thrombus formation was analysed using Fluent software. The thrombogenic potential was derived by analyzing the trajectory and flow parameters of platelet particles in the blood pump, as well as the statistical parameters of residence time and stress accumulation thrombus in the platelet pump. Results: When the impeller inlet angle is 30°, the outlet angle is 20°, and the number of blades is 6, the probability of thrombus formation is minimized in the orthogonal design method, aligning with the requirements for blood pump performance. Conclusions: These design parameters serve as a numerical guideline for optimizing the geometry of the semi‐open impeller in blood pumps and provide a theoretical foundation for subsequent in vitro experiments. [ABSTRACT FROM AUTHOR]

Variants in the 5′ UTR of ANKRD26 are a common cause of inherited thrombocytopenia (ANKRD26‐RT), and are associated with sustained ANKRD26 expression, which inhibits megakaryocyte maturation and proplatelet formation. ANKRD26 expression is controlled by the binding of a RUNX1/FLI1 complex to the 5′ UTR. To date, all reported ANKRD26‐RD associated variants have been within the RUNX1 binding site and a 22 base pair flanking region. Here, we report a novel variant in the 5′ UTR of ANKRD26, c.‐107C>T. This variant is in the FLI1 binding site, and is predicted to disrupt FLI1 binding due to loss of a hydrogen bond with FLI1. Differentiated PBMCs from affected family members showed impaired megakaryocyte maturation and proplatelet formation and sustained expression of ANKRD26, and platelets from affected family members had higher ANKRD26 expression than control platelets. The variant increased activity of the ANKRD26 promotor in a reporter assay. We also provide evidence that the previously reported c.‐140C>G ANKRD26 5′ UTR variant is benign and not associated with thrombocytopenia. Identification of the c.‐107C>T variant extends the range of the regulatory region in the 5′ UTR of ANKRD26 that is associated with ANKRD26‐RT. [ABSTRACT FROM AUTHOR]

Platelets are essential component of circulation that plays a major role in hemostasis and thrombosis. During activation and its demise, platelets release platelet‐derived microvesicles, with lysophosphatidylcholine (LPC) being a prominent component in their lipid composition. LPC, an oxidized low‐density lipoprotein, is involved in cellular metabolism, but its higher level is implicated in pathologies like atherosclerosis, diabetes, and inflammatory disorders. Despite this, its impact on platelet function remains relatively unexplored. To address this, we studied LPC's effects on washed human platelets. A multimode plate reader was employed to measure reactive oxygen species and intracellular calcium using H2DCF‐DA and Fluo‐4‐AM, respectively. Flow cytometry was utilized to measure phosphatidylserine expression, mitochondrial membrane potential (ΔΨm), and mitochondrial permeability transition pore (mPTP) formation using FITC‐Annexin V, JC‐1, and CoCl2/calcein‐AM, respectively. Additionally, platelet morphology and its ultrastructure were observed via phase contrast and electron microscopy. Sonoclot and light transmission aggregometry were employed to examine fibrin formation and platelet aggregation, respectively. The findings demonstrate that LPC induced oxidative stress and increased intracellular calcium in platelets, resulting in increased phosphatidylserine expression and reduced ΔΨm. LPC triggered caspase‐independent platelet death and mPTP opening via cytosolic and mitochondrial calcium, along with microvesiculation and reduced platelet counts. LPC increased the platelet's size, adopting a balloon‐shaped morphology, causing membrane fragmentation and releasing its cellular contents, while inducing a pro‐coagulant phenotype with increased fibrin formation and reduced integrin αIIbβ3 activation. Conclusively, this study reveals LPC‐induced oxidative stress and calcium‐mediated platelet death, necrotic in nature with pro‐coagulant properties, potentially impacting inflammation and repair mechanisms during vascular injury. [ABSTRACT FROM AUTHOR]

Hypertension (HT) is a common chronic disease that often causes target-organ damage and severe complications, contributing to cardiovascular morbidity and mortality worldwide. Accumulating evidence suggests that inflammation plays a prominent role in the initiation and progression of HT. Multiple inflammatory biomarkers have been proposed to predict HT. Several new hematological parameters can reflect the inflammatory response and platelet activation. The major advantage of hematological parameters over conventional inflammatory markers is that they are relatively inexpensive and easily obtained from routine blood tests. Numerous studies have investigated several hematological parameters for their utility as predictive biomarkers for the diagnosis and prognosis of HT. Among them, the neutrophil to lymphocyte ratio (NLR), monocyte to high density lipoprotein cholesterol ratio (MHR), red cell distribution width (RDW), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV), platelet distribution width (PDW), and systemic immune-inflammation index (SII) have recently received attention. We searched PubMed and Embase databases (up to September 18, 2022) to assess the relationships between hematological parameters and HT. This review discusses the diagnostic and prognostic value of these hematological parameters in HT, providing an important basis for early screening, risk stratification, and optimal management of hypertensive patients. [ABSTRACT FROM AUTHOR]

In-vivo flow cytometry is a noninvasive real-time diagnostic technique that facilitates continuous monitoring of cells without perturbing their natural biological environment, which renders it a valuable tool for both scientific research and clinical applications. However, the conventional approach for improving classification accuracy often involves labeling cells with fluorescence, which can lead to potential phototoxicity. This study proposes a label-free in-vivo flow cytometry technique, called dynamic YOLOv4 (D-YOLOv4), which improves classification accuracy by integrating absorption intensity fluctuation modulation (AIFM) into YOLOv4 to demodulate the temporal features of moving red blood cells (RBCs) and platelets. Using zebrafish as an experimental model, the D-YOLOv4 method achieved average precisions (APs) of 0.90 for RBCs and 0.64 for thrombocytes (similar to platelets in mammals), resulting in an overall AP of 0.77. These scores notably surpass those attained by alternative network models, thereby demonstrating that the combination of physical models with neural networks provides an innovative approach toward developing label-free in-vivo flow cytometry, which holds promise for diverse in-vivo cell classification applications. [ABSTRACT FROM AUTHOR]

Therapeutic neutralization of Oncostatin M (OSM) causes mechanism‐driven anemia and thrombocytopenia, which narrows the therapeutic window complicating the selection of doses (and dosing intervals) that optimize efficacy and safety. We utilized clinical data from studies of an anti‐OSM monoclonal antibody (GSK2330811) in healthy volunteers (n = 49) and systemic sclerosis patients (n = 35), to quantitatively determine the link between OSM and alterations in red blood cell (RBC) and platelet production. Longitudinal changes in hematopoietic variables (including RBCs, reticulocytes, platelets, erythropoietin, and thrombopoietin) were linked in a physiology‐based model, to capture the long‐term effects and variability of therapeutic OSM neutralization on human hematopoiesis. Free serum OSM stimulated precursor cell production through sigmoidal relations, with higher maximum suppression (Imax) and OSM concentration for 50% suppression (IC50) for platelets (89.1% [95% confidence interval: 83.4–93.0], 6.03 pg/mL [4.41–8.26]) than RBCs (57.0% [49.7–64.0], 2.93 pg/mL [2.55–3.36]). Reduction in hemoglobin and platelets increased erythro‐ and thrombopoietin, respectively, prompting reticulocytosis and (partially) alleviating OSM‐restricted hematopoiesis. The physiology‐based model was substantiated by preclinical data and utilized in exploration of once‐weekly or every other week dosing regimens. Predictions revealed an (for the indication) unacceptable occurrence of grade 2 (67% [58–76], 29% [20–38]) and grade 3 (17% [10–25], 3% [0–7]) anemias, with limited thrombocytopenia. Individual extent of RBC precursor modulation was moderately correlated to skin mRNA gene expression changes. The physiological basis and consideration of interplay among hematopoietic variables makes the model generalizable to other drug and nondrug scenarios, with adaptations for patient populations, diseases, and therapeutics that modulate hematopoiesis or exhibit risk of anemia and/or thrombocytopenia. [ABSTRACT FROM AUTHOR]

Anisotropic Nd-Fe-B magnets have been fabricated by the hot forward-extrusion method and exhibit the same heterogeneous microstructure characteristics as conventional die-upsetting magnets. It has been found that the magnetic properties on both sides of the magnetic sheet are better than that of the middle zone, and that the magnetic properties of the intermediate zone in the extrusion direction are better than those of the top zone (close to the extrusion die and the latest extruded zone) and the bottom zone (the earliest extruded zone) in the extrusion direction. With the decrease of extrusion speed, the process by which Nd2Fe14B grains become flat platelets with their c-axes parallel to the stress axis by grain rotating and diffusion slip have been more fully completed, while the texture, remanence, and maximum magnetic energy product (BH)max of the forward-extruded magnetic sheet monotonically increased. With the increase of hot-pressing and hot-extrusion temperatures, the texture, remanence, and (BH)max of the hot-extruded magnetic sheet initially increased and then decreased. The magnetic sheet hot-pressed at 550°C and hot-extruded at 850°C with an extrusion speed of 0.05 mm s−1 had the best magnetic properties, its (BH)max being 40.3 MGOe, Br 13.5 kGs, and Hcj 9.8 kOe. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease (COVID-19) induces inflammation, coagulopathy following platelet and monocyte activation, and fibrinolysis, resulting in elevated D-dimer levels. Activated platelets and monocytes produce microvesicles (MVs). We analyzed the differences in platelet and monocyte MV counts in mild, moderate, and severe COVID-19, as well as their correlation with D-dimer levels. Methods: In this cross-sectional study, blood specimens were collected from 90 COVID-19 patients and analyzed for D-dimers using SYSMEX CS-2500. Platelet MVs (PMVs; PMVCD42b+ and PMVCD41a+), monocyte MVs (MMVs; MMVCD14+), and phosphatidylserinebinding annexin V (PS, AnnV+) were analyzed using a BD FACSCalibur instrument. Results: PMV and MMV counts were significantly increased in COVID-19 patients. AnnV+ PMVCD42b+ and AnnV+ PMVCD41a+ cell counts were higher in patients with severe COVID-19 than in those with moderate clinical symptoms. The median (range) of AnnV+ PMVCD42b+ (MV/μL) in mild, moderate, and severe COVID-19 was 1,118.3 (328.1-1,910.5), 937.4 (311.4-2,909.5), and 1,298.8 (458.2-9,703.5), respectively (P =0.009). The median (range) for AnnV+ PMVCD41a+ (MV/μL) in mild, moderate, and severe disease was 885.5 (346.3-1,682.7), 663.5 (233.8-2,081.5), and 1,146.3 (333.3-10,296.6), respectively (P =0.007). D-dimer levels (ng/mL) weak correlated with AnnV+ PMVCD41a+ (P =0.047, r=0.258). Conclusions: PMV PMVCD42b+ and PMVCD41a+ counts were significantly increased in patients with severe clinical symptoms, and PMVCD41a+ counts correlated with D-dimer levels. Therefore, MV counts can be used as a potential biomarker of COVID-19 severity. [ABSTRACT FROM AUTHOR]

Platelets play a key role in physiological hemostasis and pathological thrombosis. Based on the limitations of current antiplatelet drugs, it's important to elucidate the mechanisms of regulating platelet activation. In addition to dissolving lipid nutrients, bile acids (BAs) can regulate platelet function. However, the specific mechanisms underlying BAs‐mediated effects on platelet activation and thrombotic diseases remain unknown. Therefore, the effects of BAs on platelets and intracellular regulatory mechanisms are explored. It is showed that the inhibitory effect of secondary BAs is more significant than that of primary BAs; lithocholic acid (LCA) shows the highest inhibitory effect. In the process of platelet activation, BAs suppress platelet activation via the spleen tyrosine kinase (SYK), protein kinase B (Akt), and extracellular signal‐regulated kinase1/2 (Erk1/2) pathways. Nck adaptor proteins (NCK1) deficiency significantly suppress the activity of platelets and arterial thrombosis. Phosphorylated proteomics reveal that LCA inhibited phosphorylation of syntaxin‐11 at S80/81 in platelets. Additional LCA supplementation attenuated atherosclerotic plaque development and reduced the inflammation in mice. In conclusion, BAs play key roles in platelet activation via Syk, Akt, ERK1/2, and syntaxin‐11 pathways, which are associated with NCK1. The anti‐platelet effects of BAs provide a theoretical basis for the prevention and therapy of thrombotic diseases. [ABSTRACT FROM AUTHOR]

Platelet lysate (PL) is investigated as a potential replacement for fetal bovine serum (FBS) in cell culture. However, there is limited research on its impact on the immune profile of equine mesenchymal stromal cells (eMSCs). This study aimed to evaluate the effects of different PL formulations on the proliferative capacity, multipotentiality, and immune profile of equine adipose tissue-derived MSCs (eAD-MSCs). In vitro growth kinetics and trilineage differentiation of eAD-MSCs (n = 7) were assessed under three culture conditions: mediumconcentration PL (MPL), high-concentration PL (HPL), and FBS as a control. The immune profile was evaluated by studying the expression of immunogenic receptors such as MHC I, MHC II, and immunomodulatory molecules IL-6, IL-10, and TNF-α, determined by gene expression, surface marker expression, and cytokine quantification. Both PL formulations, pooled from 5 donors, exhibited 3.3 and 6.5-fold higher platelet counts than baseline plasma for MPL and HPL, respectively. Higher concentrations of TGF-β and PDGF were found in both PL formulations compared to baseline. Furthermore, MPL and HPL subcultures demonstrated proliferative, clonogenic, and multipotent capacities similar to FBS. The immune profile of PL-cultured cells exhibited gene expression levels related to immunogenicity and immunomodulation similar to the reference condition, and the surface antigen presence of MHC II was also similar. However, HPL media exhibited higher IL-6, IL-10, and TNF-α concentrations in the culture supernatant. In conclusion, both PL media contained higher concentrations of growth factors compared to FBS, supporting the in vitro culture of eAD-MSCs with proliferative, clonogenic, and multipotent capacity similar to the reference medium. Nonetheless, PL usage led to a variation in the immunomodulatory cytokine microenvironment, with higher concentrations of IL-6, IL-10, and TNF-α in HPL media compared to MPL and FBS. [ABSTRACT FROM AUTHOR]

Background Objectives Animals Methods Results Conclusions and Clinical Importance Immune thrombocytopenia (ITP) is a common cause of severe thrombocytopenia in dogs. The pathogenesis of nonassociative, primary ITP (pITP) appears complex, with ill‐defined thrombopoietic response.Develop an immunoassay to measure plasma canine thrombopoietin (TPO) concentration and characterize TPO concentrations in dogs with pITP.Forty‐one healthy dogs, 8 dogs in an induced ITP model (3 control, 5 ITP), and 58 pITP dogs.Recombinant canine TPO (rcTPO) was purchased and its identity confirmed by mass spectrometry. Monoclonal antibodies were raised to rcTPO and used to configure a sandwich ELISA using streptavidin‐biotin detection. Assay performance, coefficients of variability, and healthy dog plasma TPO reference interval (RI) were determined, followed by assay of ITP samples.Assay dynamic range was 15 pg/mL (lower limit of detection) to 1000 pg/mL TPO, with limit of quantitation of 62 pg/mL. Plasma TPO RI was 0 to 158 pg/mL, with plasma TPO <62 pg/mL for 35/41 healthy dogs. All dogs with induced ITP developed marked increases in plasma TPO concentration. Peak values ranged from 515 to >6000 pg/mL. In contrast, only 2/58 pITP dogs had TPO values above RI.Plasma TPO concentration is paradoxically low at diagnosis for most dogs with pITP. This finding suggests that ineffective thrombopoiesis contributes to thrombocytopenia in pITP dogs and supports evaluating TPO receptor agonist treatment as used for pITP in humans. The TPO assay provides a new tool to study thrombopoiesis in pITP and other thrombocytopenic syndromes in dogs. [ABSTRACT FROM AUTHOR]

Lymphatic vessels are essential for preventing the accumulation of harmful components within peripheral tissues, including the artery wall. Various endogenous mechanisms maintain adequate lymphatic function throughout life, with platelets being essential for preserving lymphatic vessel integrity. However, since lymph lacks platelets, their impact on the lymphatic system has long been viewed as restricted to areas where lymphatics intersect with blood vessels. Nevertheless, platelets can also exert long range effects through the release of extracellular vesicles (EVs) upon activation. We observed that platelet EVs (PEVs) are present in lymph, a compartment to which they could transfer regulatory effects of platelets. Here, we report that PEVs in lymph exhibit a distinct signature enabling them to interact with lymphatic endothelial cells (LECs). In vitro experiments show that the internalization of PEVs by LECs maintains their functional integrity. Treatment with PEVs improves lymphatic contraction capacity in atherosclerosis-prone mice. We suggest that boosting lymphatic pumping with exogenous PEVs offers a novel therapeutic approach for chronic inflammatory diseases characterized by defective lymphatics. This work shows that platelet extracellular vesicles play a role in regulating lymphatic endothelial cell integrity and improving lymphatic function. [ABSTRACT FROM AUTHOR]

Background: To assess the association between various systemic lupus erythematosus (SLE) disease manifestations, SLE disease activity index 2000 (SLEDAI-2K), systemic lupus international collaborating clinics/American College of Rheumatology Damage Index (SLICC/ACR- SDI) and serum levels of Slit2 in SLE patients. Results: The mean age of SLE patients was 31.12 ± 8.68 years while the age at onset was 26.05 ± 7.60 years. Female: male was 9 vs 1. The mean serum levels of Slit2 in SLE patients were significantly higher than the controls (0.55 ± 0.25 vs 0.42 ± 0.15) (P = 0.013). There was no significant difference in Slit2 levels between patients with active vs inactive SLE (P = 0.353) or between patients with and without lupus nephritis (P = 0.900). An insignificant difference in Slit2 levels was found among SLE patients using SDI (P = 0.982). No significant correlations were observed between the serum Slit2 and SLE patients' demographics, laboratory data, SLEDAI-2K, and SDI except for a positive correlation with platelets and a negative correlation with serum albumin. ROC curve analysis showed that at a cutoff value of 0.44, the area under the curve was 0.677 (95% CI 0.538–0.816, P = 0.013) with a sensitivity of 74%, specificity of 56%, and accuracy of 68%. Conclusion: While we observed elevated serum Slit2 levels in SLE patients, there was no significant correlation observed between serum Slit2 levels and SLE clinical manifestations, disease activity, or damage index. Trial registration: NCT05105217. Registered 3 November 2021 [ABSTRACT FROM AUTHOR]

Accurate real-time detection of platelets and white blood cells (WBCs) is crucial to the diagnosis of clinical disease and blood cell classification. This paper proposes a lightweight and advanced feature fusion single shot multibox detector (LAFSSD) model to enhance the multi-scale detection capability of platelets and WBCs. To generate a more effective multi-scale feature fusion module composed of depthwise separable convolution, the model first substitutes VGG16, the basic backbone of the FSSD model, with a lightweight MobileNet network. Afterward, the K-means clustering algorithm is used to modify the aspect ratio and size of the default box. The CBAM attention modules in the multi-scale feature map of LAFSSD's structure are added to further enhance the detection of platelets and WBCs. Finally, the RMSProp gradient descent algorithm is used to decrease the irregular oscillations of the loss function. The experimental outcomes demonstrate that the mAP of the LAFSSD model is 98.4%, a rise of 24.7% from before the enhancement. Our model can precisely and in real-time detect platelets and WBCs at multiple scales of different sizes and shapes in human peripheral blood smear images. [ABSTRACT FROM AUTHOR]

Background: Proper control of the lineage bias of megakaryocytic and erythroid progenitor cells (MEPs) is of significant importance, the disorder of which will lead to abnormalities in the number and function of platelets and erythrocytes. Unfortunately, the signaling pathways regulating MEP differentiation largely remain to be elucidated. This study aimed to analyze the role and the underlying molecular mechanism of miR-1915-3p in megakaryocytic and erythroid differentiation. Methods: We utilized miRNA mimics and miRNA sponge to alter the expression of miR-1915-3p in megakaryocytic and/or erythroid potential cells; siRNA and overexpression plasmid to change the expression of SOCS4, a potential target of miR-1915-3p. The expression of relevant surface markers was detected by flow cytometry. We scanned for miR-1915-3p target genes by mRNA expression profiling and bioinformatic analysis, and confirmed the targeting by dual-luciferase reporter assay, western blot and gain- and lost-of-function studies. One-way ANOVA and t-test were used to analyze the statistical significance. Results: In this study, overexpression or knockdown of miR-1915-3p inhibited or promoted erythroid differentiation, respectively. Accordingly, we scanned for miR-1915-3p target genes and confirmed that SOCS4 is one of the direct targets of miR-1915-3p. An attentive examination of the endogenous expression of SOCS4 during megakaryocytic and erythroid differentiation suggested the involvement of SOCS4 in erythroid/megakaryocytic lineage determination. SOCS4 knockdown lessened erythroid surface markers expression, as well as improved megakaryocytic differentiation, similar to the effects of miR-1915-3p overexpression. While SOCS4 overexpression resulted in reversed effects. SOCS4 overexpression in miR-1915-3p upregulated cells rescued the effect of miR-1915-3p. Conclusions: miR-1915-3p acts as a negative regulator of erythropoiesis, and positively in thrombopoiesis. SOCS4 is one of the key mediators of miR-1915-3p during the differentiation of MEPs. [ABSTRACT FROM AUTHOR]

Summary Patient characteristics and platelet responses at romiplostim initiation according to the duration of immune thrombocytopenia (ITP) are poorly understood. Amongst romiplostim‐exposed adults with ITP lasting ≥6 months during 2009–2018 in Denmark, Sweden, and Norway, we examined characteristics at romiplostim initiation, romiplostim dosage, and durable platelet response (≥75% of measurements ≥50 × 109/L at 14–24 weeks) for subcohorts with newly diagnosed (duration <3 months), persistent (3–12 months), or chronic (>12 months) ITP initiating romiplostim. The 285 romiplostim initiators comprised 81 (28%) with newly diagnosed, 47 (16%) with persistent, and 157 (55%) with chronic ITP. More patients with newly diagnosed ITP than longer ITP duration, had low comorbidity levels, two or more prior ITP therapies, and previous bleeding requiring hospitalisation. The median romiplostim doses were similar across subcohorts. During treatment, median platelet counts were similar across subcohorts (75–76 × 109/L), and the durable platelet response was 64.6%, 52.9%, and 52.7% for newly diagnosed, persistent, and chronic ITP, respectively. After treatment cessation, the median platelet count was 138 × 109/L, 68 × 109/L, and 71 × 109/L, respectively. In conclusion, newly diagnosed patients, compared with romiplostim initiators with longer disease duration, had more severe ITP, higher frequency of durable platelet response, and higher median platelet count after cessation. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the potential of readily available laboratory parameters, specifically the alanine aminotransferase to platelet ratio (ALT/PLT) and other novel hematological ratios, as diagnostic predictors of mild intrahepatic cholestasis of pregnancy (ICP), particularly in settings where bile acid testing poses a financial or logistical barrier. Methods: A retrospective analysis was conducted on data from 83 pregnant women with pruritus at a single center in Türkiye. They were categorized into two groups: 40 diagnosed with mild ICP and 43 with non-pathological pruritus as a control group. The laboratory parameters on admission and the perinatal outcomes of the patients in the two groups were compared. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of the ratios. Results: The ICP group showed significantly higher levels of ALT/PLT, aspartate aminotransferase (AST) to platelet ratio, and ALT to total bile acid (TBA) ratio compared to the control group, while PLT/TBA was significantly lower. ALT/PLT demonstrated promising results with 82.5% sensitivity and 88.37% specificity for diagnosing mild ICP. Additionally, PLT/TBA ratio exhibited exceptional performance, achieving 97.5% sensitivity and 97.67% specificity. Conclusion: This study suggests that the ALT/PLT ratio may serve as valuable and cost-effective tool for diagnosing mild ICP, especially in resource-limited settings where traditional total bile acid testing is challenging. The integration of AST/PLT, ALT/PLT, and PLT/TBA ratios into diagnostic algorithms contributes to the more accessible and cost-effective identification of mild ICP in pregnant women with pruritus. [ABSTRACT FROM AUTHOR]

The blood protein Von Willebrand factor (VWF) is critical in facilitating arterial thrombosis. At pathologically high shear rates, the protein unfolds and binds to the arterial wall, enabling the rapid deposition of platelets from the blood. We present a novel continuum model for VWF dynamics in flow based on a modified viscoelastic fluid model that incorporates a single constitutive relation to describe the propensity of VWF to unfold as a function of the scalar shear rate. Using experimental data of VWF unfolding in pure shear flow, we fix the parameters for VWF's unfolding propensity and the maximum VWF length, so that the protein is half unfolded at a shear rate of approximately 5000 s - 1 . We then use the theoretical model to predict VWF's behaviour in two complex flows where experimental data are challenging to obtain: pure elongational flow and stenotic arterial flow. In pure elongational flow, our model predicts that VWF is 50% unfolded at approximately 2000 s - 1 , matching the established hypothesis that VWF unfolds at lower shear rates in elongational flow than in shear flow. We demonstrate the sensitivity of this elongational flow prediction to the value of maximum VWF length used in the model, which varies significantly across experimental studies, predicting that VWF can unfold between 2000 and 3200 s - 1 depending on the selected value. Finally, we examine VWF dynamics in a range of idealised arterial stenoses, predicting the relative extension of VWF in elongational flow structures in the centre of the artery compared to high shear regions near the arterial walls. [ABSTRACT FROM AUTHOR]

Introduction: Necrotizing enterocolitis (NEC) is a severe gastrointestinal problem that predominantly affects premature babies. The aim of this retrospective study was to evaluate patients who underwent surgical treatment for NEC and newborns who initially recovered with medical treatment but later developed a stricture and required surgery. Materials and Methods: We analyzed patients diagnosed with NEC between January 2009 and December 2021. Our study included patients who developed strictures after initially receiving medical treatment for NEC and subsequently underwent surgery. Demographic findings, mother's age, gestational weeks, birth weight, type of birth, postnatal age at NEC diagnosis, pH, first C-reactive protein (CRP) after onset of symptoms, leukocytes, hemoglobin and thrombocytes at the onset of NEC, echocardiography results, age at surgery, blood values before surgery, surgery technique, and outcomes were retrospectively analyzed. Results: Out of 40 patients who underwent primary surgery for NEC during the newborn period, 6 patients underwent surgery after initially receiving medical treatment. The female-to-male ratio was 15/31, and the median gestational age was 29 weeks. The median mother's age was 30 years, and the median birth weight was 1097g. The median postnatal age at NEC onset was 6 days (range 2-39). Echocardiography was performed in 43 patients, with 6 showing normal results and 28 having congenital cardiac anomalies. The median surgery day for patients who underwent primary surgery for NEC was 19 days (range 2-90). Ileostomy was performed in 26 patients, colostomy in 8 patients, and ileostomy plus colostomy in 1 patient. Surgery was conducted in 6 out of 392 patients who developed post- NEC strictures after initial medical treatment. Comparison between post-NEC stricture patients and those who underwent surgery for NEC revealed significant differences only in the age at surgery (p=0.024). Conclusion: Patients who clinically experience NEC should be considered for the development of strictures, especially in cases of prolonged feeding intolerance, distention, gastric residual, and rectal bleeding. Therefore, close follow-up and multidisciplinary approaches are crucial, and contrast barium radiography should be the initial diagnostic step. [ABSTRACT FROM AUTHOR]

Background and Objectives: Blood safety measures used by blood establishments to increase blood component safety can be validated using Transfusion‐Relevant Bacterial Reference Strains (TRBRS). Ultra‐cold storage conditions and manual preparation of the current TRBRS may restrict their practical use. To address this issue, the ISBT Transfusion‐Transmitted Infectious Diseases Working Party's Bacterial Subgroup organized an international study to validate TRBRS in a user‐friendly, lyophilised format. Materials and Methods: Two bacterial strains Klebsiella pneumoniae PEI‐B‐P‐08 and Staphylococcus aureus PEI‐B‐P‐63 were manufactured as lyophilised material. The lyophilised bacteria were distributed to 11 different labs worldwide to assess the robustness for enumeration, identification and determination of growth kinetics in platelet concentrates (PCs). Results: Production of lyophilised TRBRS had no impact on the growth properties compared with the traditional format. The new format allows a direct low‐quantity spiking of approximately 30 bacteria in PCs for transfusion‐relevant experiments. In addition, the lyophilised bacteria exhibit long‐term stability across a broad temperature range and can even be directly rehydrated in PCs without losing viability. Interlaboratory comparative study demonstrated the robustness of the new format as 100% of spiked PC exhibited growth. Conclusion: Lyophilised TRBRS provide a user‐friendly material for transfusion‐related studies. TRBRS in the new format have improved features that may lead to a more frequent use in the quality control of transfusion‐related safety measures in the future. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the effects of darbepoetin on platelet population and reactivity in healthy cats (HCs) and azotemic cats with remnant kidney (RK) model-induced chronic kidney disease. ANIMALS: 12 purpose-bred domestic shorthair cats (n = 6 HCs and n = 6 RK). METHODS: In this pilot study, all cats received darbepoetin (1 µg/kg, SC) on days 0, 7, and 14. Blood was sampled at baseline and on days 3, 10, 15, 17, 20, and 21. At each time point, a CBC was performed, platelet aggregometry was assessed by impedance and optical methods, and platelet P-selectin (CD62P) was quantified before and after thrombin stimulation. Additionally, reticulated platelets were quantified using both thiazole orange staining and proprietary analysis by the CBC analyzer. For RK cats, systemic blood pressure (BP) was serially measured. RESULTS: No adverse effects of darbepoetin were seen. There was no statistically significant change in platelet count between or within groups at any time point. Hematocrit increased significantly over time in the RK but not the HC group. RBC reticulocyte numbers in both groups increased over time. Reticulated platelet percentage did not increase in either group. Differences in platelet reactivity within or between groups were not seen in the aggregometry or flow cytometric assessments. In RK cats, indirect BP did not significantly change during the study. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the effect of daily 5 mg tadalafil on the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR) in patients with erectile dysfunction (ED). Patients and methods: 30 subjects with ED were given tadalafil as well as 30 subjects with ED who were not receiving tadalafil were recruited. 30 healthy individuals served as controls. Results: Receiver operating characteristic curve (ROC) showed that the best cut off point of pre-treatment and post treatment NLR in the ED treatment group was found <1.51, <1.51, sensitivity of 68.3%, 58.3%, specificity of 53.3%, 53.3%, lower bound of 0.558, 0.517, upper bound of 0.789, 0.757, total accuracy of 67.4%, 63.7% and p 0.003, 0.0025, respectively. Additionally, the best cut off point of pre-treatment and post treatment PLR in the ED treatment group was found <5.89, <5.99, sensitivity of 65%, 63.3%, specificity of 63.3%, 53.3%, lower bound of 0.515, 0.435, upper bound of 0.755, 0.687, total accuracy of 63.5%, 56.1% and p 0.027, 0.341, respectively. Conclusion: Daily 5 mg Tadalafil supplementation significantly improves erectile function through decreasing these markers as well as depression and anxiety. [ABSTRACT FROM AUTHOR]

Background: Cutibacterium acnes, a common anaerobic platelet concentrate (PC) contaminant, has been associated with rare mild adverse transfusion reactions and is often considered a harmless commensal. Notably, C. acnes can cause chronic infections and has been shown to induce the release of proinflammatory cytokines by immune cells. Since elevated concentrations of proinflammatory factors in PCs have been linked to noninfectious adverse reactions, this study aimed to assess whether C. acnes could elicit the release and accumulation of proinflammatory factors during PC storage, thereby enhancing the risk of such reactions. Study Design/Methods: Four ABO‐matched buffy coat PCs were pooled and split into six units, each were inoculated with either saline (negative control), a Staphylococcus aureus isolate (positive control, 30 colony forming units [CFU]/unit), or four C. acnes PC isolates (10 CFU/mL) and stored at 20–24°C with agitation. Bacterial counts, platelet activation, and concentration of proinflammatory factors were assessed on days 0, 3, and 5. N = 3. Results: C. acnes counts remained stable, while S. aureus proliferated reaching 108CFU/mL by the end of PC storage. By day 5, no significant differences in platelet activation or proinflammatory cytokine profiles were observed in C. acnes‐contaminated PCs compared to the negative control (p >.05), while there was a significant increase (p ≤.05) in sCD40L concentration (day 3), and platelet activation and IL‐8 concentration (day 5) in S. aureus‐contaminated units. Discussion: C. acnes contamination does not promote the accumulation of proinflammatory factors in the absence of proliferation during storage and may not enhance the risk of inflammatory reactions when transfused to patients. [ABSTRACT FROM AUTHOR]

Background: Critical shortages in the national blood supply have led to a re‐evaluation of previously overlooked donor sources for blood products. As a part of that effort, red blood cells collected from therapeutic phlebotomy of donors on testosterone replacement therapy (TRT) have been conditionally approved for transfusion. However, platelets from TRT donors are not currently approved for use due to limited data on effects of supraphysiologic testosterone on recipient safety and platelet function. The objective of this study was to provide a comprehensive profile of phenotype and function in platelets from TRT and control donors. Study Design and Methods: Platelets in plasma were collected from TRT and control donors (N = 10 per group; age‐ and sex‐matched) and stored at room temperature for 7 days. On storage Day 1 (D1) and Day 7 (D7), platelet products were analyzed for platelet count, metabolic parameters (i.e., glucose, lactate, mitochondrial function), surface receptor expression, aggregation, thrombin generation, and thrombus formation under physiological flow conditions. Results: TRT donor platelets were not significantly different than control donor platelets in terms of count, surface phenotype, metabolic function, ability to aggregate, thrombin generation, or ability to form occlusive thrombus under arterial flow regimes. Both groups were similar to each other by D7, but had significantly lost hemostatic function compared to D1. Discussion: Platelets derived from donors undergoing TRT have similar phenotypic and functional profiles compared to those derived from control donors. This suggests that therapeutic phlebotomy of TRT donors may provide a useful source for platelet products. [ABSTRACT FROM AUTHOR]

Background and Objectives: Regulatory requirement of fixed holding time (6 h) of whole blood (WB) at room temperature, that is, 22–24°C (RT) results in sub‐optimal component separation. The aim was to evaluate the platelet concentrates (PC) prepared by both platelet rich plasma (PRP) and buffy coat (BC) methods after overnight hold (18–24 h) at RT. Materials and Methods: A prospective experimental study was performed. A total of 48 WB units collected were divided into four groups (12 each) control‐1 (C1) and test‐1 (T1) for PRP and control‐2 (C2) and test‐2 (T2) for the BC method. Control groups were processed within 6 h, and in test groups, components were prepared after overnight hold, followed by evaluation of quality parameters. Results: Irrespective of the method used, all PCs had similar volume, platelet yield, swirling, no bacterial contamination, RBC contamination, PaO2 and PaCO2 levels. PCs in the T1 group had significant differences in glucose and MPV values on d1, which were resolved by d5 of storage. PCs in T2 has significant differences in pH, glucose, and MPV levels throughout storage. PRBC in test and control groups had similar quality parameters till d42 of storage. FFPs in all tests were noninferior to the concurrent control groups till 3 months of storage. Conclusion: Overnight holding of WB had no lasting deleterious changes. Though a few biochemical parameters in the test groups were significantly different, they can be accepted to improve the logistics of component separation. Overall PRP method seemed to have a better result than the BC method after an overnight hold. [ABSTRACT FROM AUTHOR]

Myeloproliferative neoplasms (MPN) are hematological diseases associated with genetic driver mutations in the JAK2, CALR, and MPL genes and exacerbated oncoinflammatory status. Analyzing public microarray data from polycythemia vera (n = 41), essential thrombocythemia (n = 21), and primary myelofibrosis (n = 9) patients' peripheral blood by in silico approaches, we found that pro-inflammatory and monocyte-related genes were differentially expressed in MPN patients' transcriptome. Genes related to cell activation, secretion of pro-inflammatory and pro-angiogenic mediators, activation of neutrophils and platelets, coagulation, and interferon pathway were upregulated in monocytes compared to controls. Together, our results suggest that molecular alterations in monocytes may contribute to oncoinflammation in MPN. [ABSTRACT FROM AUTHOR]

In this paper, the simple refined plate theory (S-RPT) is extended for the analysis of the bending and buckling behaviours of functionally graded graphene platelets reinforced composite (FG-GPLRC) plates supported by local elastic foundations under different boundaries. For the first time, an analytical method for determining the location of the local elastic foundation distribution by simple integration is extended to the analysis of the bending and buckling behaviour of plates. The method avoids complex calculations compared to previous methods for determining the position of the elastic foundation. Compared with other simplified plate theories, the displacement pattern of S-RPT is able to reflect the interrelationship between the gradient material properties and the displacement distribution along plate's thickness. The material properties of FG-GPLRC plates are affected by temperature. Using the static equilibrium method, the plate equilibrium equations are derived by directly integrating the three-dimensional elastic equations along the plate cross section. Galerkin's method is used to solve the governing equations. The accuracy of S-RPT under different boundary conditions and the accuracy of the analytical method for determining the location of the elastic foundation are verified by comparing the numerical results with the existing literature. Finally, the effects of different distribution patterns, weight fractions of GPLs, thickness ratios, aspect ratios, boundary conditions, temperature, elastic foundation distribution patterns, and elastic foundation parameters were investigated in detail. [ABSTRACT FROM AUTHOR]

The present work focuses on the detection of dengue virus using a proposed copper (Cu) and black phosphorus (BP)–based SPR sensor. This proposed sensor is capable of detecting normal and infected blood samples containing plasma, platelets and hemoglobin. We studied the performance parameter at optimized Cu layer thickness of the proposed sensor by calculating that the maximum sensitivity is 150.55°/RIU, 226.73°/RIU and 295.58°/RIU at Rmin values with 57 nm, 57 nm and 51 nm thickness of Cu layer for the detection of plasma, platelet and hemoglobin in the blood sample of dengue malaria. The properties of BP combined with the unique plasmonic properties of SPR sensors can result in enhanced interactions between surface plasmons and incident light. These results are intended for improved sensitivity and remarkable figure of merit (FoM). We also calculated the electric field and penetration depth (PD) for the same sample. In this study, the normal and infected blood samples are successfully examined for the performance parameters for the plasma, platelets and hemoglobin. [ABSTRACT FROM AUTHOR]

Kawasaki disease, a systemic vasculitis that affects young children and can result in coronary artery aneurysms, is the leading cause of acquired heart disease among children. A hallmark of Kawasaki disease is increased blood platelet counts and platelet activation, which is associated with an increased risk of developing resistance to intravenous immunoglobulin and coronary artery aneurysms. Platelets and their releasate, including granules, microparticles, microRNAs and transcription factors, can influence innate immunity, enhance inflammation and contribute to vascular remodelling. Growing evidence indicates that platelets also interact with immune and non-immune cells to regulate inflammation. Platelets boost NLRP3 inflammasome activation and IL-1β production by human immune cells by releasing soluble mediators. Activated platelets form aggregates with leukocytes, such as monocytes and neutrophils, enhancing numerous functions of these cells and promoting thrombosis and inflammation. Leukocyte–platelet aggregates are increased in children with Kawasaki disease during the acute phase of the disease and can be used as biomarkers for disease severity. Here we review the role of platelets in Kawasaki disease and discuss progress in understanding the immune-effector role of platelets in amplifying inflammation related to Kawasaki disease vasculitis and therapeutic strategies targeting platelets or platelet-derived molecules. This Review outlines the role of platelets in Kawasaki disease and the immune-effector role of platelets in amplifying inflammation related to Kawasaki disease vasculitis and highlights therapeutic strategies that target platelets or platelet-derived molecules. Key points: Platelets are essential for haemostasis and thrombosis; however, platelets also have multifaceted roles in regulating immune responses and contributing to the pathogenesis of inflammatory diseases. Thrombocytosis is usually reported in Kawasaki disease, a systemic paediatric vasculitis, and has been associated with increased risk of developing coronary artery aneurysms. Levels of monocyte–platelet aggregates (MPAs) and neutrophil–platelet aggregates (NPAs) increase during Kawasaki disease; these leukocyte–platelet aggregates (LPAs) might amplify Kawasaki disease pathogenesis through their pro-inflammatory and thrombotic functions and have been related to the development of coronary artery aneurysms in Kawasaki disease. Although aspirin therapy does not reduce MPA formation, studies suggest that targeting the P-selectin–PSGL1 axis or inhibiting the P2Y12 receptor might attenuate platelet-induced monocyte activation. Platelets are active participants and mediators of cardiovascular inflammation during Kawasaki disease vasculitis, not innocent bystanders. Hence, platelets might be promising therapeutic targets for Kawasaki disease vasculitis. [ABSTRACT FROM AUTHOR]

Vγ9Vδ2 T cells are an attractive cell platform for the off-the-shelf cancer immunotherapy as the result of their lack of alloreactivity and inherent multi-pronged cytotoxicity, which could be further amplified with chimeric antigen receptors (CARs). In this study, we sought to enhance the in vivo longevity of CAR-Vδ2 T cells by modulating ex vivo manufacturing conditions and selecting an optimal CAR costimulatory domain. Specifically, we compared the anti-tumor activity of Vδ2 T cells expressing anti-CD19 CARs with costimulatory endodomains derived from CD28, 4-1BB or CD27 and generated in either standard fetal bovine serum (FBS)- or human platelet lysate (HPL)-supplemented medium. We found that HPL supported greater expansion of CAR-Vδ2 T cells with comparable in vitro cytotoxicity and cytokine secretion to FBS-expanded CAR-Vδ2 T cells. HPL-expanded CAR-Vδ2 T cells showed enhanced in vivo anti-tumor activity with longer T-cell persistence compared with FBS counterparts, with 4-1BB costimulated CAR showing the greatest activity. Mechanistically, HPL-expanded CAR Vδ2 T cells exhibited reduced apoptosis and senescence transcriptional pathways compared to FBS-expanded CAR-Vδ2 T cells and increased telomerase activity. This study supports enhancement of therapeutic potency of CAR-Vδ2 T cells through a manufacturing improvement. [ABSTRACT FROM AUTHOR]

Thermal buckling analysis of a simply supported sandwich cylindrical microshell with piezoelectric layers reinforced with graphene platelets is presented in the current study. The motion equations of the piezoelectric microshell are derived in reference to the first-order shear deformation hypothesis alongside the modified couple stress theory. The critical buckling temperature difference of piezoelectric graphene platelets reinforced cylindrical microshells is derived from adopting Navier's approach and the meshless method. The material properties of every layer for microcomposite shell layers reinforced by graphene platelets are estimated using Halpin–Tsai model. The comparison study is conducted to verify upcoming results. The goal is to investigate the effects of the applied voltage, the thickness of the piezoelectric layers, the distribution pattern, the weight fraction, the material length scale parameter, the length to radius ratio, and the thickness to radius ratio on the buckling of piezoelectric graphene platelets cylindrical microshell. [ABSTRACT FROM AUTHOR]

The surgical management of macular holes is undergoing continuous evolution, with recent focus on the utilization of platelet concentrates as a promising adjunctive intervention. Currently, they present a valid surgical approach for achieving anatomical and functional success with a non-inferiority comparably to the alternative surgical techniques. Nonetheless, the utilization of varied platelet concentrates terminologies, coupled with the lack of standardization in their preparation methodologies, engenders both lexical confusion and challenges in comparing scientific studies published up until now. In this review, we summarized the published evidence concerning the application of platelet concentrates in macular holes surgery, aiming to clarify the terminology and methodologies employed and to establish a common consensus facilitating further development and diffusion of this promising technique. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to assess the platelet parameters and their prognostic value for perinatal outcomes in pregnant women with systemic lupus erythematosus (SLE). Methods: This retrospective study involved 180 participants, 90 pregnant women with SLE and 90 healthy pregnant women. Clinical and demographic variables including routine first-trimester neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and platelet parameters such as platelet distribution width (PDW), mean platelet volume (MPV), plateletcrit (PCT) were compared between the groups. The perinatal outcomes of the whole study group were also compared. Results: SLE patients had lower leukocyte (p = 0.001), lymphocyte (p = 0.001) and platelet counts (p = 0.018), higher PDW (p = 0.002), MPV (p = 0.001), NLR (p = 0.008) and PLR (p = 0.015) and lower PCT (p = 0.015) than the control group. The groups had no significant difference in hemoglobin levels (p = 0.936). SLE patients had higher rates of cesarean section (p = 0.002), small for gestational age (SGA) (p = 0.019) and stillbirth (p = 0.017) and lower birth weight (p = 0.001) than the control group. PCT was a significant predictor of stillbirth with a cut-off value of 0.21, sensitivity of 64.3% and specificity of 83.3% (AUC: 0.843, p < 0.001). Conclusion: Pregnant women with SLE have altered platelet parameters and increased inflammatory markers compared to healthy pregnant women. PCT is a simple and useful marker for predicting stillbirth risk in SLE pregnancies. [ABSTRACT FROM AUTHOR]

Aims: To examine whether nursing diagnoses were associated with delirium in patients with sepsis. Background: Nursing diagnosis is a nurse's clinical judgement about clients' current or potential health conditions. Delirium is regarded as an important nurse‐sensitive outcome. Nonetheless, nursing diagnoses associated with delirium have not yet been identified. Design: Retrospective correlational study. Methods: This study was carried out from December 2021 to January 2023. We analysed electronic health records of patients with sepsis admitted to the intensive care units (ICUs) of a tertiary hospital in Seoul, South Korea. Delirium was defined based on the Intensive Care Delirium Screening Checklist score. Nursing diagnoses established within 24 h of admission to the ICU were included and were based on the North American Nursing Diagnosis Association diagnostic classification. The data were analysed using logistic regression. Demographics, comorbidities, procedures and physiological measures were adjusted. Regression model was evaluated via receiver operating characteristic curve, Nagelkerke R2, accuracy and F1 score. Results: The prevalence of delirium in patients with sepsis was 51.8%. Ineffective breathing patterns, decreased cardiac output and impaired skin integrity were significant nursing diagnoses related to delirium. Age ≥ 65 years, Acute Physiology and Chronic Health Evaluation II score, mechanical ventilation, continuous renal replacement therapy, physical restraint and comatose state were also associated with delirium in patients with sepsis. The area under the receiver operating characteristic curve was 0.806. Conclusion: Ineffective breathing patterns, decreased cardiac output and impaired skin integrity could manifest as prodromal symptoms of delirium among patients with sepsis. Impact: The prodromal symptoms of delirium revealed through nursing diagnoses can be efficiently used to identify high‐risk groups for delirium. The use of nursing diagnosis system should be recommended in clinical practice caring for sepsis patients. Reporting Methods: STROBE checklist. Patient or Public Contribution: No patient or public involvement. [ABSTRACT FROM AUTHOR]

Brachial artery trauma is a rare but potentially devastating injury. There is little data regarding risk factors for reintervention and amputation prevention in this population, as well as anticoagulant (AC) and antiplatelet (AP) regimens and outcomes after discharge in trauma patients with vascular injuries requiring repair. This study aims to identify in-hospital risk factors for reintervention and amputation and stratify outcomes of follow-up by discharge AC or AP regimen. The AAST Prospective Observational Vascular Injury Trial database was queried for all patients who underwent traumatic brachial arterial repair from 2013 to 2022. Patients were evaluated by need for reintervention, amputation, and outcomes at follow-up by AC or AP regimen. Three hundred and eleven patients required brachial repair, 28 (9%) required reoperation, and 8 (2.6%) required amputation. High injury severity score and an increased number of packed red blood cells and platelets showed a significant increase for reoperation and amputation. Damage control and shunt use were significant for the need to reoperate. Seventy-four percent (221/298) of patients were discharged with postoperative AC or AP regimens. There was no significant difference of short-term follow-up by type of AC or AP regimen. Damage control and temporary shunt may lead to additional operations but not an increase in amputations. However, anticoagulation intraoperatively and postoperatively does not appear to play a significant role in reducing reintervention. It also suggests that there is no increase in short-term follow-up complications with or without AC or AP therapy. [ABSTRACT FROM AUTHOR]

Previous literature suggests that sphingolipids may impact systemic coagulation and platelet aggregation, thus modulating the risks of thrombotic events. The goal of this investigation was to evaluate the role of serum sphingolipids on intrinsic platelet function to assess whether pharmacologic manipulation of sphingolipid metabolites would impact platelet aggregability. C57BL/6J mice were injected with either normal saline, 1 mg/kg FTY720 (synthetic sphingosine-1-phosphate [S1P] receptor analog), or 5 mg/kg SLM6031434 (sphingosine kinase two inhibitor). Mice were sacrificed at 6 h and whole blood (WB) was collected for impedance aggregometry assessing platelet responsiveness to arachidonic acid or adenosine diphosphate. Ex vivo studies utilized WB or platelet-rich plasma that was pretreated with S1P, FTY720, amitriptyline, or d-sphingosine then analyzed by aggregability and flow cytometry for platelet and platelet-derived microvesicle characteristics. FTY720 and SLM6031434 pretreated induced similar arachidonic acid and adenosine diphosphate–mediated platelet aggregation as controls. Ex vivo WB and platelet-rich plasma treatment with S1P, FTY720, amitriptyline and d-sphingosine did not impact platelet aggregation. The percentages of CD41+, CD62P+ and CD41+/ceramide+, CD62P+/ceramide + platelets, and platelet-derived microvesicle were not significantly different between amitriptyline-treated and normal saline-treated cohorts. Sphingolipid modulating agents, such as FTY720, SLM6031434, S1P, amitriptyline, ceramide, and d-sphingosine do not appear to independently impact platelet aggregation in murine models. [ABSTRACT FROM AUTHOR]