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24 pages, 2184 KB  
Article
Preanalytical Quality Evaluation of Low-Volume Citrate Evacuated Blood Collection Tubes—Anticoagulant Solution Volume Accuracy, pH, and Anionic–Cationic Composition
by Nataša Gros and Zala Hriberšek
Molecules 2026, 31(9), 1516; https://doi.org/10.3390/molecules31091516 (registering DOI) - 2 May 2026
Abstract
Blood collection tubes are widely used medical devices. Inaccurate citrate anticoagulant concentration can influence the results of coagulation tests. The producer’s expertise and responsibility are considered the quality safeguards. However, the tubes undergo changes during their lifecycle, partly due to storage conditions, and [...] Read more.
Blood collection tubes are widely used medical devices. Inaccurate citrate anticoagulant concentration can influence the results of coagulation tests. The producer’s expertise and responsibility are considered the quality safeguards. However, the tubes undergo changes during their lifecycle, partly due to storage conditions, and the end user or a third party has no comprehensive insight. A methodology is necessary to reveal the tube’s inherent characteristics. We provide insight into the anionic–cationic composition and pH of anticoagulant solutions in commercial tubes using high-performance ion exchange chromatography on a purified water model, making the anticoagulant volume accuracy assessment possible through a direct dye-dilution method. The results revealed differences between the tubes of two producers, Greiner BIO-ONE (A and A(nr)) and BD (C). Tube C has the most accurate anticoagulant amount. Both brands contain buffered citrate. The method of buffer preparation is not a source of interferant for the spectrometric method of the tubes’ quality evaluation. Acetate, formate, chloride, nitrite, sulfate, oxalate, bromide, and nitrate impurities were determined in anticoagulant solutions, all in tube A and some in the others. Tubes C exhibit the highest contamination with cations. Full article
(This article belongs to the Special Issue Exclusive Feature Papers in Analytical Chemistry)
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20 pages, 6684 KB  
Article
Sustainable Treatment of Fisheries Wastewater Using Azadirachta indica Leaf Biocoagulant: Optimization of Chemical Oxygen Demand and Total Suspended Solid Removal
by Muhammad Fauzul Imron, Rikky Ramadhan Mustofa, Wahid Dianbudiyanto, Eko Prasetyo Kuncoro, Suriya Vathi Subramanian and Setyo Budi Kurniawan
Sustainability 2026, 18(9), 4466; https://doi.org/10.3390/su18094466 - 1 May 2026
Abstract
Fisheries wastewater contains high levels of suspended solids and organic matter, posing significant environmental risks and necessitating effective and sustainable treatment approaches. This study aims to determine the characteristics of the neem (Azadirachta indica) leaf biocoagulant, assess the interactions among research [...] Read more.
Fisheries wastewater contains high levels of suspended solids and organic matter, posing significant environmental risks and necessitating effective and sustainable treatment approaches. This study aims to determine the characteristics of the neem (Azadirachta indica) leaf biocoagulant, assess the interactions among research variables, and optimize its use to reduce total suspended solids (TSS) and chemical oxygen demand (COD) levels in fisheries wastewater. The method used is response surface methodology (RSM), specifically the Box–Behnken Design (BBD), which involves three variables (biocoagulant concentration, fast stirring speed, and sedimentation time) and two responses (TSS and COD removal). Characterization results (Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD), and zeta potential) indicated that the biocoagulant contains functional groups such as hydroxyl, carboxyl, and amine, contributing to coagulation–flocculation through adsorption and polymer bridging mechanisms. Statistical analysis confirmed that the developed quadratic models were significant (p-value < 0.05), with high F-values, non-significant lack of fit, and strong coefficients of determination (R2 = 0.9111 for TSS and 0.9419 for COD), along with low coefficients of variation (CV < 5%), indicating good model reliability. Although the model generally has a significant effect on the response, the fast stirring speed does not, while the other two factors do. The optimal conditions (based on desirability) were determined to be a biocoagulant concentration of 79.8 mg/L, a fast stirring speed of 100 rpm, and a sedimentation time of 27.5 min. Under these conditions, TSS and COD removals of 88.72% and 79.98%, respectively, were achieved. These findings demonstrate the potential of neem leaf biocoagulant as a sustainable, environmentally friendly alternative to conventional chemical coagulation, supporting cleaner production in aquaculture systems. Full article
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14 pages, 3204 KB  
Article
Personalized Interventional Management of Femoral Pseudoaneurysms of Iatrogenic and Traumatic Origin: Technical Aspects, Clinical Outcomes, and Risk-Adapted Treatment Selection
by Antonio Borzelli, Francesco Giurazza, Luigi Basile, Fabio Corvino, Felice D’Antuono, Francesco Pane, Milena Coppola, Alessandro Punzi, Gianluca Cangiano, Antonio Corvino and Raffaella Niola
J. Pers. Med. 2026, 16(5), 239; https://doi.org/10.3390/jpm16050239 - 30 Apr 2026
Viewed by 46
Abstract
Background: Femoral pseudoaneurysms are clinically heterogeneous, with substantial variability in anatomical features and patient-related bleeding risk. Standard treatment algorithms may be inadequate, particularly in patients receiving anticoagulation or presenting with altered coagulation profiles. A personalized, risk-adapted interventional strategy may optimize outcomes while [...] Read more.
Background: Femoral pseudoaneurysms are clinically heterogeneous, with substantial variability in anatomical features and patient-related bleeding risk. Standard treatment algorithms may be inadequate, particularly in patients receiving anticoagulation or presenting with altered coagulation profiles. A personalized, risk-adapted interventional strategy may optimize outcomes while preserving procedural safety. This study compares ultrasound-guided compression with endovascular and percutaneous therapies and evaluates the safety of minimally invasive approaches across different risk profiles to support individualized management. Methods: This single-center retrospective cohort study included 65 consecutive patients treated for femoral pseudoaneurysms between January 2019 and May 2025. Treatment modalities comprised ultrasound-guided compression, endovascular embolization (coils, covered stents, NBCA–Lipiodol), percutaneous glue injection, and hybrid approaches. Primary endpoints were technical and clinical success. Safety was assessed using pre- and post-procedural INR, platelet count, and hemoglobin levels. High-risk status was defined as ongoing anticoagulation or antiplatelet therapy, INR > 1.5, or platelet count <50 × 109/L. Results: Endovascular and percutaneous approaches achieved significantly higher technical (100% vs. 68.5%, p = 0.006) and clinical success rates (100% vs. 77.8%, p = 0.009) compared with ultrasound-guided compression. In minimally invasive cohorts, INR and platelet counts remained stable after treatment, while hemoglobin showed an expected post-procedural decrease (p < 0.001). High-risk patients demonstrated technical success rates comparable to standard-risk patients, with no significant differences in laboratory trends. Favorable outcomes were observed across different embolic materials. Conclusions: Endovascular and percutaneous therapies provide superior effectiveness compared with ultrasound-guided compression while maintaining a reassuring safety profile, even in patients at increased bleeding risk. These findings support a personalized, patient-tailored interventional approach based on individual anatomical and clinical characteristics. Full article
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21 pages, 1215 KB  
Article
Effect of Somatic Cell Count on Milk Production, Composition, Colour, Coagulation Properties and Cheese-Making Ability Traits in Manchega Dairy Sheep
by Imen Heddi, Javier Caballero-Villalobos, Nicolò Amalfitano, Fernando Martínez, Miguel Ángel Cantarero-Aparicio, Alessio Cecchinato, Manuel Ramón, Ana Garzón and Ramón Arias
Foods 2026, 15(9), 1527; https://doi.org/10.3390/foods15091527 - 28 Apr 2026
Viewed by 404
Abstract
Somatic cell count (SCC) in milk is widely used as an indicator of intramammary infections in dairy sheep and is routinely monitored by the dairy industry as a marker of milk quality. This study aimed to evaluate the effect of SCC levels on [...] Read more.
Somatic cell count (SCC) in milk is widely used as an indicator of intramammary infections in dairy sheep and is routinely monitored by the dairy industry as a marker of milk quality. This study aimed to evaluate the effect of SCC levels on milk production, composition, colour, coagulation properties, and cheese-making ability in Manchega dairy sheep. A total of 752 individual milk samples were analysed. To normalise SCC distribution, the somatic cell score (SCS) was calculated and samples were classified into SCS classes. Increasing SCS significantly reduced daily milk yield and lactose content, increased milk pH, and decreased lightness (L*). Higher SCS was also associated with impaired coagulation properties, including longer rennet clotting time (RCT) and curd firming rate (k20), as well as reduced curd firmness (A30, A60). Similar effects were observed for modelled coagulation parameters, with delayed RCTeq and reduced kCF and CFp. Regarding cheese-making ability, SCS significantly affected curd humidity and protein recovery, whereas no significant effects were detected for dry curd yield or fat recovery. Overall, elevated somatic cell counts were associated with a reduction in the technological quality of Manchega sheep milk, particularly affecting coagulation behaviour and curd characteristics. These results underline the importance of controlling SCC levels in dairy sheep systems for both udder health monitoring and maintaining milk suitability for cheese-making. Full article
(This article belongs to the Section Dairy)
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15 pages, 440 KB  
Article
The Role of Rotational Thromboelastometry in High-Risk-of-Bleeding Endoscopic Procedures in Patients with Decompensated Liver Cirrhosis
by Irina Girleanu, Laura Huiban, Cristina Muzica, Camelia Cojocariu, Cătălin Victor Sfarti, Stefan Chiriac, Sebastian Zenovia, Gheorghe G. Balan, Raluca Avram, Ana Maria Sîngeap, Iulian Buzincu, Ana Maria Trofin, Ioana-Miruna Balmuș, Carol Stanciu and Anca Trifan
Diagnostics 2026, 16(9), 1289; https://doi.org/10.3390/diagnostics16091289 - 25 Apr 2026
Viewed by 142
Abstract
Background/Objectives: This study aimed to evaluate the differences between two blood product transfusion protocols [a standard coagulation (SC) group and a rotational thromboelastometry (ROTEM) group] in patients with decompensated liver cirrhosis (LC) undergoing high-bleeding-risk endoscopic procedures. Methods: Between December 2024 and [...] Read more.
Background/Objectives: This study aimed to evaluate the differences between two blood product transfusion protocols [a standard coagulation (SC) group and a rotational thromboelastometry (ROTEM) group] in patients with decompensated liver cirrhosis (LC) undergoing high-bleeding-risk endoscopic procedures. Methods: Between December 2024 and March 2025, we conducted a prospective cohort study including adult decompensated cirrhotic patients who needed prophylactic blood product transfusion before high-bleeding-risk endoscopic procedures. The prophylactic blood product transfusion strategy in the SC group was based on conventional coagulation tests (INR, platelets, and fibrinogen), and in the ROTEM group on viscoelastic parameters. Results: A total of 72 patients were included in this study (36 patients in each group); most were male (63.9%), Child–Pugh B (54.2%), and had LC with a predominance of alcoholic etiology (51.4%). There were no clinically significant differences regarding the baseline characteristics between the study groups. The most frequent endoscopic procedure was polypectomy (76.4%). Postinterventional bleeding occurred after eight procedures in the SC group and after four procedures in the ROTEM group (p = 0.206). Endoscopic hemostasis was effective. Patients from the ROTEM group received fewer FFP transfusions than the SC group (5.6% vs. 69.4%; p < 0.0001). Blood product transfusion was needed less in patients evaluated using ROTEM compared with the SC group (41.2% vs. 100%; p < 0.0001). There were no differences in the length of hospital stay (p = 0.618) or 30-day mortality (p = 0.643) between the two study groups. Conclusions: ROTEM-guided transfusion management was associated with a significant reduction in blood product use compared with standard coagulation test-based management. However, this difference should be interpreted in the context of the distinct transfusion thresholds applied in the two groups, as the standard coagulation arm followed predefined laboratory-based criteria that may have increased the likelihood of prophylactic transfusion. No statistically significant differences were observed in bleeding complications, length of hospital stay, or 30-day mortality. Therefore, these findings reflect differences in transfusion strategies rather than demonstrating clinical superiority of ROTEM-based management and should be considered preliminary. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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21 pages, 5234 KB  
Article
Fibrin Gel as a Versatile Biomaterial Platform in the Biomedical Landscape: Chemical, Physical, and Biological Insights
by Sabrina Caria, Jessica Petiti, Gerardina Ruocco, Lorenzo Mino, Raffaella Romeo, Gabriele Viada, Laura Revel, Federico Picollo, Valeria Chiono and Carla Divieto
Gels 2026, 12(5), 351; https://doi.org/10.3390/gels12050351 - 22 Apr 2026
Viewed by 343
Abstract
Fibrin gel, a protein-based polymer naturally generated during coagulation, has garnered attention in the biomedical field for applications such as fibrin glue, due to its specific physical and biological properties. Despite it, low mechanical strength and rapid degradation limited its utilization for biomedical [...] Read more.
Fibrin gel, a protein-based polymer naturally generated during coagulation, has garnered attention in the biomedical field for applications such as fibrin glue, due to its specific physical and biological properties. Despite it, low mechanical strength and rapid degradation limited its utilization for biomedical applications. This study presents a reproducible protocol for the synthesis of pure fibrin hydrogels, aimed at achieving predictable structural properties through the precise calibration of fibrinogen and thrombin concentrations. By examining the mechanical and morphological characteristics, as well as the relationship between reagent concentrations and structural integrity, this research assesses impacts on swelling behavior, water absorption, and overall stability. Through a comprehensive analytical approach, we identified an optimal formulation, specifically 2.25 mg/mL fibrinogen and 1.375 U/mL thrombin, that effectively balances structural integrity with high cytocompatibility. The results demonstrate that this calibrated approach ensures high procedural reproducibility and a well-defined hydrogel architecture without the need for exogenous chemical cross-linkers. This work provides a robust methodological framework to overcome the common lack of reproducibility in fibrin-based hydrogel studies, positioning these materials as highly reliable candidates for advanced 3D in vitro models and biomedical applications. Full article
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10 pages, 234 KB  
Article
Platelet Function and Morphology in Patients with Sepsis and Septic Shock: A Retrospective Pilot Study
by Piotr F. Czempik
Hemato 2026, 7(2), 13; https://doi.org/10.3390/hemato7020013 - 21 Apr 2026
Viewed by 358
Abstract
Background: Sepsis remains a leading cause of mortality in the intensive care unit (ICU). Platelets (PLTs) are central to coagulation, inflammation, and the maintenance of endothelial integrity. Although thrombocytopenia is an established prognostic marker in sepsis, alterations in PLT function and morphology may [...] Read more.
Background: Sepsis remains a leading cause of mortality in the intensive care unit (ICU). Platelets (PLTs) are central to coagulation, inflammation, and the maintenance of endothelial integrity. Although thrombocytopenia is an established prognostic marker in sepsis, alterations in PLT function and morphology may provide additional insight into disease progression. Methods: This retrospective pilot study examined adult ICU patients diagnosed with sepsis or septic shock. Extracted data included demographic characteristics, clinical variables, and laboratory parameters. Platelet function was evaluated using impedance aggregometry and rotational thromboelastometry (ROTEM), while PLT morphology metrics were obtained from complete blood counts. Statistical analyses comprised Spearman’s rank correlation and logistic regression. Results: Twenty patients were included. Platelet aggregation was impaired across ASPI, ADP, and TRAP-6 assays despite normal PLT counts and morphology. ROTEM-derived measure of PLT contribution to clot strength was within normal ranges. No correlations were observed between PLT function and PLT morphology parameters. An inverse correlation was identified between ROTEM-derived PLT contribution to clot strength and SOFA score (r = −0.60, p = 0.03). Neither PLT function nor PLT morphology was associated with ICU mortality. Conclusions: Functional PLT deficits may occur in sepsis in the absence of structural abnormalities. ROTEM-derived PLT contribution to clot strength may inversely reflect sepsis severity. Platelet function parameters appear unlikely to predict short-term mortality in septic patients. Full article
(This article belongs to the Section Plasma Cell Disorders)
14 pages, 1375 KB  
Article
Remodeling of the circRNA Landscape in Myocardial Infarction Integrates Nuclear Regulation, DNA Damage Response, and Cardiomyocyte Structural Pathways
by Rudaynah Alali, Naif Khalid Alqannas, Alawi H. Habara, Mohammed Almansori, Ali Alsaeed, Chittibabu Vatte, Cyril Cyrus, Safi G. Alqatari, Hassan Albisher, Mustafa H. Al-ajwad, Faisal S. Alshahrani, Moyad M. Almuslim, Morten T. Venø, Brendan J. Keating and Amein K. Al-Ali
Biomolecules 2026, 16(4), 578; https://doi.org/10.3390/biom16040578 - 14 Apr 2026
Viewed by 537
Abstract
Plasma circular RNAs (circRNAs) are stable RNA molecules found in blood, which makes them potential noninvasive biomarkers for acute myocardial infarction (MI). The aim of this study was to describe the plasma circRNA profile in patients with acute MI and to identify circRNA [...] Read more.
Plasma circular RNAs (circRNAs) are stable RNA molecules found in blood, which makes them potential noninvasive biomarkers for acute myocardial infarction (MI). The aim of this study was to describe the plasma circRNA profile in patients with acute MI and to identify circRNA markers that may help detect heart injury and reflect the biological processes involved. We compared plasma samples from patients with acute MI and healthy controls using total RNA sequencing with unique molecular identifiers (UMIs). After sequencing, reads were processed through quality control, alignment, duplicate removal, and circRNA detection. Differential expression was analyzed after adjusting for age, sex, smoking, and technical factors. Several circRNAs were significantly different between MI cases and controls and were able to separate the two groups in principal component and receiver operating characteristic analyses. Among the most increased circRNAs were hsa-PASK_0004, hsa-STXBP3_0002, hsa-RCAN3_0002, and hsa-RANBP9_0044, while hsa-HIF1A_0002, hsa-SUZ12_0049, hsa-PNRC1_0001, and hsa-RAB2A_0002 were decreased. Several candidates showed AUC values above 0.7. Pathway analysis linked the host genes of these circRNAs to inflammation, platelet activation, coagulation, and cardiomyocyte stress responses. Overall, these findings suggest that circulating circRNAs may serve as useful blood-based markers of MI and provide insight into the molecular changes that accompany acute MI. Full article
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14 pages, 2446 KB  
Article
Fibrinogen-to-Platelet Ratio and Hematologic Inflammatory Indexes in Spondylarthritis
by Roxana Doina Ungureanu, Cristina Elena Bita, Mirela Nicoleta Voicu, Adina Turcu-Stiolica, Sineta Cristina Firulescu, Mihai Turcu-Stiolica, Andreea Lili Bărbulescu, Stefan Cristian Dinescu and Florentin Ananu Vreju
J. Clin. Med. 2026, 15(8), 2926; https://doi.org/10.3390/jcm15082926 - 12 Apr 2026
Viewed by 349
Abstract
Background/Objectives: Spondylarthritis (SA) is characterized by high clinical heterogeneity, often resulting in a discrepancy between systemic inflammation and patient-reported symptoms. While hematologic indices are emerging as cost-effective biomarkers, their role in phenotypic differentiation remains unclear. We investigated the utility of traditional inflammatory [...] Read more.
Background/Objectives: Spondylarthritis (SA) is characterized by high clinical heterogeneity, often resulting in a discrepancy between systemic inflammation and patient-reported symptoms. While hematologic indices are emerging as cost-effective biomarkers, their role in phenotypic differentiation remains unclear. We investigated the utility of traditional inflammatory markers, including the novel fibrinogen-to-platelet ratio (FPR), in differentiating SA subtypes and predicting patient-reported disease activity. Methods: This cross-sectional study included 64 patients with spondylarthritis: axial SA (n = 32), peripheral SA (n = 8), and psoriatic SA (n = 24). Clinical assessments included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Functional Index (BASFI). Systemic inflammation was evaluated via C-reactive protein (CRP), fibrinogen, and calculated ratios (NLR, PLR, MLR, and FPR). Principal Component Analysis (PCA) was employed to map the inflammatory architecture, while Receiver Operating Characteristic (ROC) curves evaluated the predictive power for high disease activity (BASDAI ≥ 4). Results: Significant phenotypic differences were observed with the FPR demonstrating superior discriminative capacity (p = 0.003). Patients with peripheral SA exhibited significantly higher FPR (median 1.88) compared to axial (1.33) and psoriatic (1.32) subtypes, and the dedicated ROC analysis for phenotypic discrimination yielded an AUC of 0.866 (95% CI: 0.745–0.987) (1.36, p = 0.039). HLA-B27 prevalence was low overall (31.3%) and in psoriatic SA (4.2%, p = 0.012). Correlation analysis revealed strong associations between BASDAI and BASFI (ρ = 0.79), NLR and MLR (ρ = 0.78), and CRP and fibrinogen (ρ = 0.66). PCA identified two independent inflammatory dimensions explaining 74.8% of variance: neutrophil-hypercoagulable axis (41.4%, driven by NLR, PLR, and MLR), and an acute-phase/fibrinogen axis (33.4%, driven by CRP, fibrinogen, and FPR). Notably, FPR clustered with acute-phase reactants rather than leukocyte-derived ratios, supporting its role as a marker of systemic inflammatory burden. Although fibrinogen is involved in the coagulation cascade, the absence of direct coagulation markers precludes definitive characterization of this component as hypercoagulable. ROC analysis revealed that fibrinogen showed the highest discriminative ability for disease activity (BASDAI ≥ 4), with an AUC of 0.690 (95% CI: 0.519–0.861), followed by NLR (0.621), MLR (0.592), and FPR (0.583). However, overall discriminative performance remained modest, with most 95% confidence intervals crossing 0.5. Conclusions: FPR emerges as a robust phenotypic biomarker capable of discriminating against SA subtypes, particularly identifying peripheral SA with high accuracy and excellent negative predictive value. In contrast, its ability to predict patient-reported disease activity remains limited, reinforcing the distinction between trait and state biomarkers. Exploratory PCA revealed that FPR clusters with acute-phase reactants rather than leukocyte-derived ratios, supporting its biological link to systemic inflammatory burden. These findings advocate for a dual-purpose biomarker approach in SA: FPR for phenotypic stratification and fibrinogen for activity assessment, while clinical indices remain indispensable for symptom monitoring. Validation in larger, prospective cohorts is warranted. Full article
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13 pages, 799 KB  
Article
Protein C Levels in Human Immunodeficiency Virus-Infected Women with and Without Pre-Eclampsia in South Africa
by Wendy N. Phoswa, Lawrence Chauke, Kabelo Mokgalaboni, Gaynor Balie, Sidney Hanser and Olive P. Khaliq
Biomedicines 2026, 14(4), 866; https://doi.org/10.3390/biomedicines14040866 - 10 Apr 2026
Viewed by 449
Abstract
Background: Pre-eclampsia (PE) is a significant cause of maternal and perinatal morbidity and mortality globally and is characterized by impaired endothelial function and disturbances in coagulation pathways. The effects of Human Immunodeficiency Virus (HIV) on the immune and coagulation systems have been investigated [...] Read more.
Background: Pre-eclampsia (PE) is a significant cause of maternal and perinatal morbidity and mortality globally and is characterized by impaired endothelial function and disturbances in coagulation pathways. The effects of Human Immunodeficiency Virus (HIV) on the immune and coagulation systems have been investigated during pregnancy, but there are few reports on anticoagulant factors in pregnant women who are infected with HIV and develop PE. This investigation compares plasma protein C levels in pregnant women with pre-eclampsia and those without pre-eclampsia, and compares the results based on their HIV status. Methods: A hospital-based cross-sectional study design was used for the current research, which was carried out at Charlotte Maxeke Johannesburg Academic Hospital, South Africa. A total of 83 pregnant women participated in the study and were categorized into one of four groups: normotensive HIV-negative (n = 36); normotensive HIV-positive (n = 18); pre-eclamptic HIV-negative (n = 21); and pre-eclamptic HIV-positive (n = 8). Data collected included demographic information and clinical characteristics that were abstracted from maternity records. Plasma protein C concentrations were determined by ELISA (enzyme-linked immunosorbent assay). Nonparametric statistical methods were used to compare the mean values of plasma protein C between each of the four groups, and significance was set at p < 0.05. Subgroup analyses, particularly for the pre-eclamptic HIV-positive group (n = 8), were considered exploratory due to small sample sizes. Results: As would be anticipated, both systolic and diastolic blood pressure values were significantly elevated in the pre-eclamptic group when compared to the normotensive control subjects (p < 0.0001). There were no statistically significant differences in plasma protein C concentration between the normotensive and pre-eclamptic groups, nor between the HIV-negative and HIV-positive groups. Similarly, there were no significant differences in plasma protein C concentration when comparing all four study groups (Kruskal–Wallis test p = 0.2295). Conclusions: Plasma protein C concentrations did not vary significantly according to the presence of pre-eclampsia or HIV status in this cohort. These findings suggest that protein C concentrations were not measurably altered between groups within this study population. However, due to the small sample size in key subgroups, these findings should be considered preliminary and interpreted with caution. Larger, adequately powered studies are required to further investigate potential associations between HIV infection, pre-eclampsia, and anticoagulant pathways during pregnancy. Full article
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18 pages, 1977 KB  
Review
Large Animal Models for Preclinical Evaluation of Heart Valve Prostheses, Left Ventricular Assist Devices and Total Artificial Hearts: A Narrative Review
by Oskar Gülcher, Celeste Koster, Jolanda Kluin and Paul Gründeman
Biomimetics 2026, 11(4), 258; https://doi.org/10.3390/biomimetics11040258 - 8 Apr 2026
Viewed by 665
Abstract
Large animal models are a critical component of the preclinical evaluation of mechanical cardiac implants, enabling assessment of safety and performance under physiological conditions that cannot be adequately reproduced in vitro. Choosing a suitable animal model is important for both scientifically valid and [...] Read more.
Large animal models are a critical component of the preclinical evaluation of mechanical cardiac implants, enabling assessment of safety and performance under physiological conditions that cannot be adequately reproduced in vitro. Choosing a suitable animal model is important for both scientifically valid and ethically responsible preclinical evaluation. However, interspecies differences between animal models and humans pose significant challenges for relevant translation of preclinical findings to clinical outcomes. This narrative review provides a comprehensive overview of commonly used large animal models (sheep, goats, pigs, and calves) for the preclinical assessment of mechanical cardiac implants, including prosthetic heart valves, ventricular assist devices, and total artificial hearts. We summarize key anatomical and physiological characteristics that influence device implantation, chronic follow-up, and translational value. Emphasis is placed on three critical outcome domains for preclinical evaluation of mechanical cardiac implants: calcification, thrombogenicity, and hemodynamic performance. Species- and age-dependent differences in calcification are reviewed, identifying juvenile sheep as a worst-case model for early manifestation and detection of graft mineralization. Interspecies differences in coagulation biology are examined, showing attenuated platelet responses in sheep and closer similarity between porcine and human platelet behavior, supporting pigs as the preferred thrombogenicity model. Hemodynamic evaluation strategies in acute and chronic large-animal studies are discussed, with particular emphasis on circulatory demands influenced by somatic growth and on device adaptability under varying loading conditions. Overall, this review provides practical, outcome-driven guidance for large animal model selection and experimental design in mechanical cardiac implant research, while identifying key limitations, knowledge gaps, and the need for standardized reporting to improve the translational reliability of preclinical studies. Based on the findings presented in this review, we conclude that there is no single animal model capable of evaluating all relevant aspects of a device. Instead, different animal models provide distinct advantages depending on the outcomes of interest. Full article
(This article belongs to the Section Development of Biomimetic Methodology)
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14 pages, 2130 KB  
Article
Gasdermin as a Molecular Signature and Predictor of Adult-Type Diffuse Glioma Severity and Grading
by Szymon Kaczor, Klepacki Hubert, Sandra Papuga, Dariusz Pawlak, Babu Harish, Adam Hermanowicz, Małgorzata Kowalska and Justyna Magdalena Hermanowicz
J. Clin. Med. 2026, 15(7), 2706; https://doi.org/10.3390/jcm15072706 - 2 Apr 2026
Viewed by 509
Abstract
Background/Objectives: Gasdermin D (GSDMD) is a critical mediator of pyroptosis—an inflammatory form of programmed cell death increasingly implicated in tumor biology. Our objective was to evaluate the utility of GSDMD as a diagnostic and prognostic biomarker and to investigate its association with [...] Read more.
Background/Objectives: Gasdermin D (GSDMD) is a critical mediator of pyroptosis—an inflammatory form of programmed cell death increasingly implicated in tumor biology. Our objective was to evaluate the utility of GSDMD as a diagnostic and prognostic biomarker and to investigate its association with tumor burden and hematological parameters. Methods: We analyzed GSDMD expression levels in patients with adult-type diffuse gliomas compared to healthy controls and assessed correlations with tumor size, histological grade, hematological markers, and survival outcomes. Data was complemented by transcriptomic analysis from The Cancer Genome Atlas (TCGA). Diagnostic performance was assessed using ROC curve analysis. Results: GSDMD expression was significantly elevated in adult-type diffuse glioma patients and increased with tumor grade, suggesting an association with disease severity. A positive correlation was observed between GSDMD level and tumor size (R = 0.332; p = 0.01). ROC analysis showed moderate classification ability (AUC = 0.657) with high specificity (96%), supporting its diagnostic potential. Survival analysis showed that higher GSDMD expression was associated with reduced disease-specific survival. GSDMD also correlated positively with the erythrocyte parameter mean corpuscular hemoglobin (MCH, R = 0.34, p = 0.016) and negatively with the systemic inflammatory marker C-reactive protein (CRP, R = −0.32; p = 0.042). TCGA data showed no significant sex-related differences in GSDMD expression. Baseline characteristics such as age, BMI, and coagulation parameters were matched between patients and controls. Conclusions: GSDMD is significantly associated with astrocytoma severity, tumor size, and inflammatory status, with elevated expression indicating a worse prognosis. Its correlation with tumor grade, survival and high specificity in distinguishing patients from healthy individuals, underlines its promise as a clinically relevant, non-sex-specific biomarker for diagnosis and monitoring. Full article
(This article belongs to the Section Clinical Neurology)
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14 pages, 432 KB  
Article
A Cross-Sectional Analysis of Clinical and Biological Characteristics of Inpatients with Complicated Acute Pyelonephritis
by Marius-Costin Chițu, Carmen-Marina Pălimariu, Teodor Salmen, Tudor-Petru Nicodin, Delia Reurean-Pintilei, Dan-Arsenie Spînu, Viorel Jinga, Anca Pantea Stoian and Dan Liviu Dorel Mischianu
Antibiotics 2026, 15(4), 363; https://doi.org/10.3390/antibiotics15040363 - 1 Apr 2026
Viewed by 523
Abstract
Background: Complicated acute pyelonephritis (AP) is a severe upper urinary tract infection associated with systemic inflammation, organ dysfunction, and the risk of sepsis. The increasing prevalence of antimicrobial-resistant (AMR) organisms can alter clinical management. This study aimed to characterize the biological profile [...] Read more.
Background: Complicated acute pyelonephritis (AP) is a severe upper urinary tract infection associated with systemic inflammation, organ dysfunction, and the risk of sepsis. The increasing prevalence of antimicrobial-resistant (AMR) organisms can alter clinical management. This study aimed to characterize the biological profile of inpatients with complicated AP and to eventually identify laboratory markers associated with risks of sepsis and AMR infections. Material and Methods: A retrospective observational analysis on 553 adult inpatients diagnosed with complicated AP between 2021 and 2025 was conducted in a tertiary center. Demographic, clinical, and biological parameters were analyzed, including inflammatory markers and renal and hepatic markers. Results: Group characteristics included a mean age of 63.82 ± 15.67 years, and 63% were female. At admission, inflammatory markers were raised, with leukocytosis (15.6 ± 5.8 × 103/µL), neutrophilia (10.1 ± 4.7 × 103/µL), and elevated C-reactive protein (CRP) (median 43.2 mg/dL). Coagulation activation was significant with elevated fibrinogen of 747 ± 145 mg/dL and D-dimer with a median level of 1249 ng/mL, of which 58% exceeded 1000 ng/mL. Mild to moderate renal impairment was frequently observed (creatinine 1.69 ± 0.76 mg/dL). In multivariate analysis, no biological parameter proved to be an independent predictor of AMR status among organisms. Discussion and Conclusions: Inpatients with complicated AP showed a pronounced inflammatory and procoagulant biological profile that did not vary between AMR pathogen and non-AMR pathogen infections. This suggests that the clinical value of biomarkers, such as leukocyte and neutrophile, CRP, D-dimer, fibrinogen, procalcitonin, urea, and creatinine, lies primarily in assessing disease severity rather than predicting antimicrobial resistance. The microbiological profile was dominated by Gram-negative pathogens, particularly Escherichia coli, although a heterogeneous spectrum of microorganisms was identified. Full article
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14 pages, 449 KB  
Systematic Review
Microparticles in Pregnancy Complicated by Intrauterine Growth Restriction: A Systematic Review of Literature
by Nikoleta Aikaterini Xixi, Rozeta Sokou, Fotios Grigoropoulos, Georgia Gkaroutsou, Paraskevi Volaki, Styliani Paliatsiou, Zoi Iliodromiti, Anastasios G. Kriebardis, Nicoletta Iacovidou and Theodora Boutsikou
Medicina 2026, 62(4), 658; https://doi.org/10.3390/medicina62040658 - 30 Mar 2026
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Abstract
Background and Objectives: Intrauterine growth restriction (IUGR) affects 5–10% of pregnancies and is associated with increased perinatal morbidity and long-term complications for the neonate. Extracellular vesicles (EVs), and in particular, microparticles (MPs), have emerged as potential biomarkers of pregnancy complications; however, the [...] Read more.
Background and Objectives: Intrauterine growth restriction (IUGR) affects 5–10% of pregnancies and is associated with increased perinatal morbidity and long-term complications for the neonate. Extracellular vesicles (EVs), and in particular, microparticles (MPs), have emerged as potential biomarkers of pregnancy complications; however, the literature on their role in neonates remains limited. To investigate the functional characteristics, concertation in maternal blood and potential role of MPs in IUGR. Materials and Methods: PubMed, Scopus and preprint servers were systematically searched for studies on MPs in correlation with IUGR from 1 August until 18 September 2025. Data on MP characteristics and concentration in maternal blood samples in the context of IUGR were collected. The systematic review is registered in PROSPERO (CRD420251156939). Results: A total of 12 studies fulfilled the inclusion criteria and were included in the review. In IUGR-complicated pregnancies, circulating MPs exhibited preserved procoagulant activity despite minimal quantitative differences compared to controls. Platelet-, endothelial-, and placenta-derived MPs were most frequently studied. Clinically, elevated AV+ placenta-derived MPs were associated with increased risk of IUGR, whereas MPs from isolated IUGR pregnancies showed limited predictive value. Conclusions: MPs play a crucial role in the pathophysiology of IUGR through their interplay in coagulation, inflammation, and vascular dysfunction. They show potential as predictive biomarkers, particularly in cases of preeclampsia-associated IUGR, reflecting systemic maternal endothelial and inflammatory changes. However, their utility in isolated IUGR appears limited, likely due to the predominantly local placental origin of the pathology. Full article
(This article belongs to the Section Pediatrics)
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14 pages, 2875 KB  
Article
Tumor-Specific Pro-Thrombotic Gene Expression in Head and Neck Squamous Cell Carcinoma: A Multi-Cohort Transcriptomic Analysis
by Kiranya E. Arnold, Nadia Debick, John Brognard and Auyon J. Ghosh
Cancers 2026, 18(7), 1055; https://doi.org/10.3390/cancers18071055 - 25 Mar 2026
Viewed by 501
Abstract
Objectives: Head and neck tumors have been associated with varying risks for venous thromboembolism (VTE). Through a cross-tumor comparison, we assessed site-specific coagulation-related gene expression changes in head and neck squamous cell carcinoma (HNSCC) compared to squamous cell tumors in the esophagus [...] Read more.
Objectives: Head and neck tumors have been associated with varying risks for venous thromboembolism (VTE). Through a cross-tumor comparison, we assessed site-specific coagulation-related gene expression changes in head and neck squamous cell carcinoma (HNSCC) compared to squamous cell tumors in the esophagus (ESCCa) and lung (LUSC). Further, we assessed the relationship between clinicopathologic features of HNSCC and coagulome gene expression. Methods: RNA-sequencing data from primary tumor tissues of HNSCCa, ESCCa, and LUSC were obtained from The Cancer Genome Atlas (TCGA). Three previously identified pro-thrombotic genes (F3, SERPINE1, and SERPINB2) were analyzed and, for pan-cancer comparisons, gene expression was Z-standardized and summarized as a composite coagulome score. For HNSCCa-specific analyses, gene expression was compared using log2 RSEM counts, contrasting between HPV status, primary tumor site, tumor stage, grade, and demographic characteristics. Results: HNSCCa demonstrated the highest composite coagulome activation (mean Z-score = 0.29, 95% CI: 0.23–0.35) compared with LUSC and ESCCa (mean Z-scores = −0.27 and −0.16, respectively; p < 0.001). Among 487 HNSCCa tumors, HPV-negative tumors exhibited significantly higher composite coagulome expression than HPV-positive tumors (mean ± SD, 11.25 ± 1.39 vs. 10.14 ± 1.30; p < 0.001). Oral cavity tumors demonstrated the highest coagulome expression, while oropharyngeal tumors were most suppressed. Higher histologic grade was inversely associated with coagulome expression (p < 0.001). Patient age, sex, and race were not significantly associated with coagulome expression. Conclusions: HNSCCa exhibits a tumor-specific pro-thrombotic expression profile with substantial heterogeneity driven by HPV status and primary tumor site. Despite elevated tumor-specific pro-coagulant signaling, these findings reflect tumor-specific pro-thrombotic potential rather than clinical VTE risk in HNSCCa, which likely remains context-dependent and may require additional inflammatory or treatment-related triggers to clinically manifest. Full article
(This article belongs to the Special Issue The Genetics of Head and Neck Squamous Cell Carcinoma)
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