Search Results (1,680)

Rapid hemostasis assessment is essential for managing acute coagulopathy, guiding anticoagulant therapy, and monitoring cardiac surgery patients. Although viscoelastic testing provides valuable guidance for early intervention, its widespread adoption is constrained by large blood usage (~2 mL), prolonged turnaround times (several hours), long assay durations (~25–40 min), and high costs. To overcome these limitations, we developed an innovative, all-in-one magnetoelastic (ME) sensing chip that enables systematic coagulation kinetics monitoring using only 46 μL of whole blood within 15 min. Featuring prepackaged lyophilized reagents and pumpless blood loading, this user-friendly chip is highly cost-effective for disposable use. The experimental results demonstrated good reproducibility for on-chip extrinsic coagulation activation, with clotting parameters maintaining coefficients of variation under 10%. Furthermore, clotting parameters derived from heparin monitoring results exhibited a strong linear correlation that compares favorably with the clinical standard (r = 0.986). Finally, sensitivity evaluation toward various blood components validated the sensor’s dual-mode characterization strategy for identifying coagulation factors and fibrin-related coagulopathies. The proposed ME sensing chip holds promise for bedside testing and flexible, on-demand coagulation monitoring across diverse clinical scenarios. Full article

Type 1 diabetes mellitus (DM1) is characterized by autoimmune destruction of pancreatic β-cells, resulting in insulin deficiency and persistent hyperglycemia, which impair bone metabolism and compromise post-extraction alveolar bone healing. Heterologous fibrin biopolymer (HFB) has previously demonstrated biocompatibility, biodegradability, bioactivity, and osteoconductive properties under normoglycemic conditions. Therefore, the study investigated the association of HFB with post-extraction alveolar bone healing in streptozotocin-induced diabetic rats, using the diabetic blood clot as a biological control. Forty-eight adult male Wistar rats were induced to DM1 by a single intraperitoneal injection of streptozotocin (52 mg/kg). Animals were included after confirmation of hyperglycemia (fasting blood glucose ≥ 250 mg/dL) measured seven days after STZ administration: blood clot (BCG; n = 24) or HFB (HFBG; n = 24). Seven days after DM1 induction, the right maxillary incisor was extracted, and the sockets were filled according to group allocation. Animals were euthanized at 7, 14, and 42 days post-extraction. Fasting blood glucose levels were monitored, and pancreatic insulin immunohistochemistry was performed to characterize the diabetic condition. Alveolar bone healing was assessed by micro-CT, histological (HE), histomorphometric, and picrosirius red analyses. The diabetic phenotype was confirmed by persistent fasting hyperglycemia (260–589 mg/dL) and reduced pancreatic insulin immunostaining in β-cells. At 42 days, bone volume (BV) was 31.86% higher in the HFBG than in the BCG (p < 0.05). BCG exhibited higher trabecular number (Tb.N), while HFBG exhibited higher trabecular thickness (Tb.Th) (p < 0.05). Histologically, the HFBG shows a more mature, compact, and organized bone structure, whereas the BCG presents bone tissue with a more trabecular and immature architecture. HFBG showed the lowest percentage of thin fibers at the late stage, whereas BCG maintained similar values from 14 to 42 days (p < 0.05). These findings suggest that HFB was associated with favorable changes in selected late-stage parameters of post-extraction alveolar bone healing in an STZ-induced diabetic model. Full article

Autonomous microrobot teams have significant potential for distributed drug delivery, cooperative vascular intervention, and parallelized biomedical diagnostics. However, coordinated control in cardiovascular environments remains challenging due to partial observability, limited communication bandwidth, and hydrodynamically coupled pulsatile blood flow. This paper introduces Decentralized Hemodynamic-Aware Multi-Agent Reinforcement Learning (DH-MARL), a distributed learning and control framework in which individual microrobots learn decentralized policies from local observations while graph-based attention mechanisms model inter-agent interactions during centralized training. The proposed framework integrates turbulence-aware adaptive exploration, reduced-order hydrodynamic interaction modeling, diffusion-based local communication, and hemodynamic-aware counterfactual credit assignment to improve cooperative learning and role specialization in dynamic vascular environments. A scalable Unity-based simulator supporting coupled pulsatile flow for up to 32 agents was developed for training and evaluation. Our experimentalresults cover four therapeutic scenarios: distributed drug delivery, cooperative clot dispersion, stenosis mapping, and vessel bottleneck traversal. For 16-agent teams, DH-MARL reaches an 88.7% team success rate. This performance exceeds independent single-agent controllers and centralized MAPPO baselines, and inter-robot collision rates remain below 4%. The learned policies generalize to unseen team sizes with minimal performance degradation, highlighting the scalability and robustness of the proposed decentralized control strategy. These simulation-level results demonstrate the feasibility of distributed reinforcement learning and graph-based coordination as a control paradigm for future multi-agent microrobot systems in biomedical environments. The results also provide a foundation for the calibration of subsequent microfluidic, ex vivo, and preclinical experiments. Full article

Periodontitis, a chronic inflammatory disease driven by plaque biofilm, is a leading cause of tooth loss in adults worldwide. Effective treatment requires not only infection and inflammation control but, more critically, functional regeneration of the periodontal ligament, cementum, and alveolar bone. Periodontal regeneration, however, is a highly ordered, multi-stage biological cascade involving temporally coordinated phases of blood clot formation, inflammatory regulation, tissue formation, and remodeling. Conventional single-drug or mixed-delivery strategies cannot distinguish the distinct demands of each healing phase and fail to replicate this natural rhythm. Sequential controlled-release systems address this gap by delivering multiple bioactive agents (antimicrobials, immunomodulators, and growth factors) in a programmed order tailored to the healing cascade, enabling precise modulation of the periodontal microenvironment and orderly tissue regeneration. This review systematically summarizes advances in these systems, classifying material platforms into four categories: (1) diffusion-barrier and degradation-kinetics systems, including multilayer films, core–shell fibers, porous microspheres, and microneedle arrays; (2) stimuli-responsive systems triggered by pH, matrix metalloproteinases, reactive oxygen species, or exogenous physical stimuli; (3) cell and extracellular vesicle-based systems exploiting the inflammatory tropism of M2 macrophage-derived exosomes for targeted immune reprogramming; and (4) asymmetric structural designs achieving spatiotemporal coordination of physical and biochemical signals through hierarchical architectures. These systems follow an anti-infection/anti-inflammation first, osteogenesis later therapeutic logic, circumventing temporal antagonism among bioactive factors. However, significant challenges hinder clinical translation, including individualized prediction of release kinetics, long-term biocompatibility of carrier materials, material retention under dynamic oral conditions, translational limitations of animal models, and precise regulation of complex factor networks. Future progress will likely depend on multi-responsive and logic-gated systems, deeper integration of biotechnology and immunomodulation, personalized precision medicine, AI-driven material design, and robust clinical translational research. Full article

A bioengineered version of recombinant tissue plasminogen activator, i.e., tenecteplase (TNK-tPA), was designed to have a longer half-life, resistance to plasminogen activator inhibitor-1, and fibrin-targeted plasminogen activation. By comparison to tPA, clinical trials suggest that TNK-tPA may be less susceptible to the effects of alpha2-antiplasmin (α2AP), the primary inhibitor of thrombus dissolution. However, preclinical studies are limited, and whether α2AP affects TNK-tPA’s fibrinolytic activity or efficacy in experimental ischemic stroke is unknown. We examined the effects of TNK-tPA and α2AP on the dissolution of human plasma clots (in vitro) and experimental ischemic brain injury from stroke induced by transient middle cerebral artery ischemia. TNK-tPA induced a dose-dependent increase in plasma clot dissolution; inhibition of α2AP with a specific monoclonal antibody caused a synergistic increase in TNK-tPA-mediated clot dissolution. In experimental ischemic stroke with ischemia and reperfusion, TNK-tPA treatment of α2AP^−/− mice significantly reduced ischemic infarct volume, brain swelling, brain hemorrhage, and neurobehavioral disability vs. TNK-tPA-treated α2AP^+/+ (C57BL/6 background) mice with normal α2AP levels (p < 0.05 to p < 0.0001). α2AP impairs the dissolution of human clots in vitro by TNK-tPA and significantly exacerbates ischemic brain injury, swelling, hemorrhage, and neurobehavioral disability after experimental stroke, even with reperfusion. Targeting α2AP may improve the efficacy of TNK-tPA and reduce hemorrhagic complications. Full article

Background: Platelet concentrates are widely used in regenerative dentistry and maxillofacial surgery; however, the lack of protocol standardization and selection criteria results in contradictory clinical outcomes. This study aimed to perform a comparative analysis of the biological activity of various platelet concentrates obtained via different fractionation and activation procedures under uniform in vitro experimental conditions. Methods: Rat adipose-derived stem cells (ADSCs) and human EA.hy926 endothelial cells were used to evaluate four platelet concentrate types via tube formation, wound healing (scratch), and cell proliferation assays. Results: Platelet concentrates obtained by the single-centrifugation protocol (L-PRP-1) exhibited maximal retained platelet potential, corresponding to a peak 5-fold increase in cell migration. Chemical activation of plasma-based concentrates (L-PRP, P-PRP) with calcium/thrombin was critically required to trigger angiogenesis and accelerate endothelial chemotaxis. Conversely, plasma-free platelet concentrate (PFPC) exhibited a unique capacity for spontaneous activation and clot formation without exogenous inducers, triggering rapid angiogenesis and sustaining ADSC proliferation. Conclusions: Within the framework of our in vitro model, activated plasma-based forms are biologically justified for accelerated soft tissue healing and socket preservation, whereas the complete removal of plasma proteins suggests the potential utility of PFPC as a biomimetic matrix-carrier for maxillofacial tissue engineering. Full article

Trap–neuter–return (TNR) programs are the leading non-lethal approach to managing free-roaming cat populations. When cats are anesthetized for surgical sterilization, veterinarians have a brief opportunity to obtain blood samples for pre-surgical screening, infectious-disease surveillance, and contribution to population-level reference-interval research. Field conditions, however, make collecting good-quality blood samples difficult: cats are often dehydrated and stressed, the procedure is kept brief, and their medical history is unknown. This narrative review draws on the American Society for Veterinary Clinical Pathology (ASVCP) reference-interval guidelines, feline anesthesia and the blood-collection literature, and operational experience from Portuguese TNR programs to describe seven points in the sampling workflow at which technique most often fails: anesthetic depth verification, controlled aspiration speed, immediate EDTA-tube mixing, post-venipuncture hemostasis, hemolysis recognition, precise FIV/FeLV point-of-care test timing, and adherence to a maximum-attempts limit. Three recurrent failure modes—collapsed veins from excessive aspiration, clotted EDTA samples from inadequate mixing, and hematoma formation from insufficient hemostasis—account for the majority of poor samples observed in routine practice. The framework presented here is intended to support reproducible, welfare-compliant sample collection during TNR operations, giving veterinary teams a single, structured reference that supports both animal welfare and the diagnostic value of the samples they collect. Full article

Exuding wounds require dressings that combine effective exudate management, hemostatic activity, and bioactive therapeutic effects. Curcumin possesses antioxidant and anti-inflammatory properties, but its clinical application is limited by poor bioavailability and uncertain effects on coagulation. This study aimed to develop an alginate-based dressing incorporating liposomal curcumin and evaluate its physicochemical and in vitro hemostatic properties. Alginate dressings containing 0–0.5% liposomal curcumin were prepared and characterized. The selected 0.2% liposomal curcumin (D_0.2) formulations were evaluated for swelling behavior, dimensional stability, water vapor transmission rate, optical properties, calcium and polyphenol release, prothrombin time, fibrin morphology, and fibrin secondary structure in simulated serous, inflammatory, and infected wound exudates. D_0.2 exhibited favorable macroscopic integrity and flexibility, enhanced swelling capacity, improved exudate management, and favorable moisture-vapor permeability. The dressing showed controlled release of Ca²⁺ and polyphenols, producing a biphasic hemostatic response characterized by transient early coagulation delay followed by accelerated clot formation. Fibrin analysis revealed improved network organization and preservation of ordered protein conformations, particularly under inflammatory and infected conditions. Liposomal curcumin-modified alginate dressings combine effective fluid handling with adaptive hemostatic performance and enhanced fibrin stabilization, demonstrating promising potential for the management of serous, inflammatory, and infected wounds. Full article

Objectives: The aim of the study was to compare CBCT (Cone Beam Computed Tomography)-derived radiographic hard tissue gain after hydraulic transcrestal sinus floor elevation performed with versus without cross-linked hyaluronic acid (HA) and to assess associated clinical, radiographic, and patient-reported outcomes. Materials and Methods: This single-center, prospective clinical study enrolled 58 patients with 2–6 mm residual bone height in the posterior maxilla, assigned in a non-randomized parallel-group design to HA (n = 29) or No Graft (n = 29). The primary endpoint was CBCT-based 3D CBCT-derived radiographic hard-tissue volume gain at 12 months; secondary endpoints included vertical bone gain, marginal bone loss (MBL) at 12 and 24 months, implant stability quotient (ISQ), implant survival/success, complications, and patient-reported outcomes (VAS pain, OHIP-14). Analyses used ANCOVA and appropriate comparative statistics. Results: At 12 months, mean CBCT-derived radiographic hard-tissue volume gain was higher with HA (1210 +/− 610 mm³) than with No Graft (858 +/− 605 mm³; adjusted difference +352 mm³, 95% CI: 140–564; p = 0.002). ISQ at 12 months was greater with HA (p = 0.028), while MBL at 12/24 months did not differ significantly. Twenty-four-month implant survival was 98.1% (HA) vs. 94.3% (No Graft; p = 0.041). Complication rates were low and comparable; VAS pain at 72 h was modestly lower with HA. Conclusions: In this non-randomized prospective clinical study, cross-linked hyaluronic acid was associated with greater CBCT-derived radiographic hard-tissue volume gain and vertical radiographic gain after hydraulic transcrestal sinus floor elevation compared with clot stabilization alone. Clinical outcomes were favorable in both groups during the 24-month observation period. These findings support the interpretation of cross-linked hyaluronic acid as a potential space-maintaining adjunct in posterior maxillary sites with limited residual bone height; however, because no histological or histomorphometric assessment was performed, they should not be interpreted as proof of vital mature bone regeneration or superior bone quality. Full article

Sepsis-induced coagulopathy (SIC) represents an early, predominantly prothrombotic disturbance that is difficult to detect using conventional coagulation tests. This review aims to evaluate whether rotational thromboelastometry (ROTEM) provides added value in the diagnosis and phenotyping of SIC compared with standard laboratory parameters. We summarize current evidence on SIC pathophysiology and its relationship to disseminated intravascular coagulation (DIC), with particular focus on mechanisms driving hypercoagulability and fibrinolytic shutdown. The limitations of routine tests, platelet count, PT/INR, fibrinogen, and fibrin-related markers are examined, especially their inability to capture early dynamic changes in coagulation. We then outline the principles of ROTEM and review clinical studies assessing its application in sepsis. Available data consistently demonstrate increased clot firmness, frequently driven by elevated fibrinogen, along with impaired fibrinolysis. These patterns often precede overt SIC or DIC and are associated with worse clinical outcomes, including organ dysfunction and mortality. Finally, we discuss the implications of these findings for clinical management. While routine anticoagulation in unselected septic patients remains unsupported, integrating SIC criteria with ROTEM profiles may improve risk stratification and help identify prothrombotic phenotypes that could benefit from targeted therapies. Overall, ROTEM appears to be a valuable adjunct to conventional testing, with potential to refine diagnostic accuracy and guide future interventional strategies in septic coagulopathy. Full article

Background/Objectives: Regional citrate anticoagulation (RCA) is guideline-preferred for continuous renal replacement therapy (CRRT), yet implementation requires expertise, calcium protocols, and reliable monitoring. Evidence for standardized low-molecular-weight heparin strategies without routine anti-Xa monitoring remains limited. Methods: We retrospectively analyzed adult ICU patients receiving protocolized divided-dose enoxaparin during CRRT from January 2020 to December 2024. Enoxaparin 1.5 mg/kg/24 h was divided into six equal prefilter doses every 4 h. The primary outcome was circuit clotting; death and hemodynamic instability were treated as competing termination events. Safety endpoints were ISTH major bleeding, clinically relevant non-major bleeding (CRNMB), minor bleeding, thrombosis, and suspected heparin-induced thrombocytopenia (HIT). Results: The cohort included 200 patients and 223 CRRT runs, contributing 8829.8 CRRT-hours. Median run duration was 35.0 h (IQR, 27.2–52.1). Circuit clotting occurred in 31 runs (13.9%; 95% CI, 9.6–19.1), equivalent to 0.35 events per 100 CRRT-hours. Kaplan–Meier clotting-free survival at 48 h was 89.8% (95% CI, 84.3–95.2), and the competing-risk cumulative incidence of clotting was 9.0%. Any classified bleeding occurred in 10 runs (4.5%; 95% CI, 2.2–8.1), including one ISTH major bleeding event and one CRNMB event. No thrombotic or HIT events were identified. In a prespecified four-variable Cox model with patient-level cluster-robust standard errors, no predictor was significantly associated with clotting. Conclusions: In a citrate-unavailable or citrate-not-routinely-implemented ICU setting, this standardized divided-dose enoxaparin protocol showed low observed major/clinically relevant bleeding rates and acceptable clotting-free circuit performance. Prospective comparative evaluation is warranted. Full article

Background: Same-day or post-admission cancellation of elective surgery is associated with inefficient operating room utilization, patient distress, and disruption of coordinated perioperative care. Functional neurosurgery is particularly vulnerable to late-stage cancellation because procedural readiness depends on parallel clinical, anatomical, medication-related, device-related, and systemic considerations. Objective: This paper aims to describe the implementation of a structured preoperative review framework for functional neurosurgery and to evaluate its association with late-stage surgical cancellation after patient admission. Methods: We performed a retrospective single-center before-and-after study of consecutive functional neurosurgical procedures scheduled at Sheba Medical Center between January 2020 and December 2025. The ABCDE framework was introduced in 2023 as a structured workflow model organized around five domains: Anatomy, Bacteria, Clotting, Devices, and Elsewhere. Included procedures were deep brain stimulation, vagus nerve stimulation, focused ultrasound, intrathecal pump implantation or replacement, implantable pulse generator replacement, spinal cord stimulation, peripheral nerve stimulation, and other palliative neuromodulation procedures. The primary endpoint was late-stage cancellation, defined as cancellation after hospital admission and initiation of operative preparation. The primary comparison was between 2020–2022 and 2023–2025. A sensitivity analysis excluded 2020 because of pandemic-era disruption. Results: A total of 867 procedures were scheduled. Late-stage cancellation occurred in 16 of 407 pre-implementation procedures and 5 of 460 post-implementation procedures, corresponding to rates of 3.9% and 1.1%, respectively. The absolute risk difference was −2.8 percentage points (95% CI, −5.2 to −0.8), and the relative risk for cancellation after implementation was 0.28 (95% CI, 0.10 to 0.75). A two-sided Fisher’s exact test comparing cancellation versus non-cancellation across the pre-implementation and post-implementation periods was statistically significant (16/407 vs. 5/460; p = 0.0074). After excluding 2020, the direction of effect remained similar, but the difference was not statistically significant: 8 of 302 procedures in 2021–2022 were canceled compared with 5 of 460 in 2023–2025 (2.6% vs. 1.1%; p = 0.15). Detailed source-level attribution was incomplete for 10 of 21 cancellation events, and domain-level analyses should therefore be interpreted descriptively. Conclusions: Implementation of the ABCDE framework was associated with fewer late-stage surgical cancellations in this single-center before-and-after study. Because the design is observational, the number of events is small, and the study period overlaps with pandemic-era disruption and post-pandemic service stabilization, the findings should be interpreted as hypothesis-generating rather than causal. The framework may provide a practical structure for standardizing preoperative review in functional neurosurgery, but prospective studies with formal adherence tracking and procedure-specific analyses are needed. Full article

Assessment of the stability of inflammatory parameters in bovine blood samples is important because it enables evaluation of the impact of preanalytical factors on biomarker preservation, standardization of sample processing and storage conditions, as well as reliable and consistent interpretation of results in diagnostic and research studies. The aim of the work was to evaluate the stability of the most common inflammatory markers in the blood of cows in early lactation. The influence of the serum–clot contacts duration and the storage of the separated serum in 24 cows, at 25 °C and 4 °C, in intervals of 0–24 h, was examined. Concentrations of interleukin 1 and 6 (IL-1, IL-6), tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), haptoglobin (Hp), serum amyloid A (SAA) and extracellular heat shock protein 70 (eHsp70) were determined by ELISA method, stability was assessed by ANOVA analysis and maximum permissible instability method. Stability was determined over a range of 2–15 h for IL-1, 8–24 h for IL-6, 9–13 h for TNF-α, 10–20 h for IFN-γ, 20–24 h for Hp, 15–24 h for SAA, and 9–12 h for eHsp70. The stability was strongly dependent on temperature and sample type, with storage at 4 °C providing the highest stability in most cases, while differences between serum and serum–clot samples were analyte-specific and less consistent compared to the effect of temperature. Full article

Factor Xa (FXa) remains a clinically validated and chemically tractable anticoagulant target despite the therapeutic role of direct oral FXa inhibitors. Contemporary FXa inhibitor literature, however, is heterogeneous in scaffold design, endpoint reporting, assay consistency, translational depth, and suitability for computer-aided drug design (CADD). This review evaluates published series of small-molecule FXa inhibitors through a framework that combines translational structure–activity relationships (SARs), assay-aware data quality, and QSAR-readiness. A structured narrative synthesis focused mainly on post-2014 studies reporting discrete small-molecule or semisynthetic FXa inhibitors. Eligible series were classified as fully synthetic or natural-product-derived/semisynthetic chemotypes, and extraction covered scaffold architecture, potency endpoints, assay context, selectivity, clotting or antithrombotic readouts, PK/ADME, structural clarity, translational context, and extraction confidence. QSAR-readiness was assessed using analog density, congenericity, endpoint quality, assay comparability, activity range, structural interpretability, and curation burden. Fully synthetic chemotypes, particularly anthranilamide-derived and related scaffolds, provided the most coherent and modellable FXa datasets, whereas natural-product-derived and semisynthetic series expanded structural diversity. Many exploratory series, however, were limited by small analog sets, heterogeneous endpoints, incomplete translational characterization, narrow activity ranges, or higher curation burden. The practical value of published FXa inhibitor series, therefore, depends not only on potency but also on whether chemical and biological information can be reconstructed with confidence for reproducible SAR interpretation, local QSAR modeling, AI/ML-enabled CADD reuse, and clinical benchmark-aware prioritization. The QSAR-readiness framework is a critical triage tool, not a substitute for formal validation, distinguishing datasets suitable for curated local modeling from those better suited to qualitative SAR, scaffold inspiration, or translational hypotheses. Full article

This current research is a narrative review that seeks to establish the occasions under which thrombophilia can result in complications regarding bleeding and thrombosis during pregnancy. Under such circumstances, the influence of vitamin K deficiency is considered, since vitamin K plays an important role in activating the coagulation system. This occurs directly, via the activation of coagulation factors, as well as indirectly, through the activation of proteins S and C. Both proteins play an important role in the hemostatic mechanism of thrombosis and bleeding. However, the risk associated with the relationship between thrombosis and bleeding changes during pregnancy and is heightened by the natural tendency towards hypercoagulability during pregnancy. This paper presents a narrative review of the literature concerning the links between vitamin K, protein C, and protein S in relation to thrombophilia from the perspectives of both biochemistry and medicine, with a special focus on pregnancy. The study examined factors that could be useful to define the balance between hemorrhagic and thrombotic tendency, comparing conventional methods of studying hemostasis with other possible tests that can help better understand the interplay between hemorrhage and thrombosis. Collectively, disorders within the processes associated with vitamin K-mediated blood clotting may have a considerable effect on the woman’s thrombotic risk, especially for women who suffer from thrombophilia. This study confirms the need for monitoring and personalized treatment options to avoid thrombotic and hemorrhagic complications during pregnancy. Full article