Search Results (5,591)

Early diagnosis of Diabetic Retinopathy (DR) is critical for preventing irreversible vision loss, but precise lesion annotation by ophthalmologists is the dominant cost in building any clinical-grade DR detection model. The structural problem in real hospital settings is not labeling cost per se, but expert availability: ophthalmologists’ time is bounded by clinical duties, so the active-learning (AL) cycle can iterate only a handful of times in practice. We frame this constraint explicitly and ask which AL designs work best under a tight expert budget. We propose Virtuous Cycle, a Human-in-the-Loop (HITL) pipeline that integrates (i) a YOLOv8x-based object detector for microaneurysms, hemorrhages, and exudates, (ii) four AL sampling strategies (Average Confidence, Random, Hybrid-Diversity, Monte Carlo Dropout), and (iii) an in-hospital annotation platform (Diavision Studio) in which clinicians refine AI pre-labels rather than draw from scratch. We evaluate Virtuous Cycle on a real-world fundus dataset from the National Medical Center (NMC) across eight AL rounds, expanding the labeled pool from 81 images (R0) to 481 images (R8) within the actual expert-time budget of two ophthalmologists. Across three independent random seeds, random sampling dominates at cold start (mean mAP@50 $0.14\to 0.25$ over R0–R1), whereas Hybrid-Diversity converges to the highest mAP@50, Precision, and Recall by R7 (431 images; mAP@50 $0.40$, Precision $0.55$, Recall $0.41$), with MC Dropout close behind; by R8, the labeled pool is exhausted and all strategies converge to the same final model. A clinician crossover analysis of 36 paired clinical images, controlling for per-clinician speed bias and per-image difficulty bias, shows no statistically significant difference in overall per-image labeling time between AI-assisted and manual annotation ($p=0.52$), but a statistically significant increase in confirmed lesion detections under AI assistance ($p=0.0058$), driven predominantly (84–$100\%$ of the net increase) by microaneurysms, the lesion type most prone to being missed unaided. The results indicate that, under expert-budget constraints, AL strategy choice should be staged: random sampling for cold start, uncertainty-and-diversity sampling once the model has matured, and that AI assistance trades a modest, lesion-burden-dependent time cost for a measurable gain in the sensitivity of microaneurysm detection. Full article

Introduction/Objectives: Wall irregularity is a known risk factor in the evaluation of intracranial aneurysms, but the prognostic value of its subtypes remains unclear. Materials and methods: In this retrospective single-center cross-sectional study (2023–2025), we reviewed consecutive adult patients with intracranial aneurysms. Morphology was classified as daughter sac, multilobulated, or complex irregularity. We compared rupture status and calculated PHASES, ELAPSS, and UIATS scores. Principal Component Analysis (PCA), and logistic and linear regression were applied. Results: A total of 180 patients with 180 index aneurysms were included; mean age was 67.2 ± 12.1 years, and 72.2% were women. Overall, 43.3% of aneurysms were irregular, specifically: daughter sac (25.0%), multilobulated (36.1%), and complex irregularity (11.1%). SAH occurred in 40 patients (22.2%). Ruptured aneurysms had larger maximum diameter, size ratio, and aspect ratio (all p < 0.0001), plus higher 5-year PHASES (p = 0.0091) and ELAPSS growth scores (p < 0.0001). PCA identified three clusters with differing 5-year rupture risks; Cluster 3 had the highest risk (5.71 ± 5.25%) and was characterized by a higher proportion of daughter sac and multilobulated morphology (p = 1.65 × 10⁻⁷ and 8.80 × 10⁻¹⁶). Linear models showed each irregular subtype was associated with significantly larger aneurysm size. Conclusions: Irregular wall patterns were common and associated with larger aneurysm dimensions and higher risk scores. These findings support further investigation of refined morphological descriptors in rupture risk stratification. Full article

Hemorrhagic pneumonia is a severe and often fatal disease in captive forest musk deer (Moschus berezovskii), but the pathogen remains incompletely understood. Based on incomplete statistics, the estimated incidence in captive populations ranges from 20% to 80%, with the disease occurring mainly in autumn, winter, and early spring. The disease has an acute onset and rapid progression. Due to the species’ strong stress response, affected animals rarely show behavioral changes, making early detection difficult. In this study, we investigated a mortality case presenting with oral bleeding and hematemesis on a forest musk deer farm. Postmortem examination revealed diffuse hemorrhagic pneumonia, and lung tissue samples were collected for histopathology, bacterial isolation, full-length 16S rRNA gene sequencing, and DNA/RNA virome sequencing. Histological examination showed extensive alveolar hemorrhage, fibrinous exudate, and macrophage infiltration. Bacterial culture and 16S rRNA gene sequencing identified Bergeyella zoohelcum as the predominant bacterium, accounting for 100% of the bacterial community in the lung tissue. Virome analysis revealed predominantly DNA bacteriophages (e.g., Cirlivirales, Cremevirales, Microviridae) and no known pathogenic RNA viruses; only seven low-abundance, unclassified RNA viral contigs of low completeness were detected. These results indicate that B. zoohelcum is the likely causative agent of hemorrhagic pneumonia in this case, with no evidence of viral involvement. This study provides the first direct association of B. zoohelcum with hemorrhagic pneumonia in forest musk deer, highlighting its pathogenic potential and the importance of monitoring this bacterium in captive populations. Full article

Whole-genome sequencing (WGS) is central to outbreak response for high-consequence ribonucleic acid (RNA) viruses, but useful genomes depend on workflow design, sample quality, biosafety, diagnostic breadth, infrastructure, and bioinformatics as much as sequencing platform. The 2026 Bundibugyo virus disease outbreak in the Democratic Republic of the Congo and Uganda provides a case example. Bundibugyo virus (BDBV) was already known from the 2007–2008 Uganda and 2012 Democratic Republic of the Congo outbreaks, but sparse historical genome sampling, Ebola virus-centered diagnostic assumptions, non-specific febrile and viral hemorrhagic fever presentations, and difficult field conditions created a need for broad differential diagnosis, rapid species assignment, and representative genome generation. This review compares outbreak WGS strategies by the degree of prior viral sequence knowledge required, distinguishing direct RNA sequencing, random-primed complementary DNA (cDNA) sequencing, sequence-independent amplified cDNA sequencing, background-depleted or particle-enriched cDNA sequencing, probe-based hybrid capture, tiled amplicon sequencing, portable field sequencing, culture-derived sequencing, and associated bioinformatics workflows. For BDBV-like outbreaks, the most defensible strategy is staged and adaptive: broad viral hemorrhagic fever and febrile illness differential testing at recognition; Filoviridae-wide testing when filovirus disease remains plausible; divergence-tolerant first-genome recovery; quantification-cycle-informed sequencing prioritization without BDBV-only diagnostic narrowing; validated amplicon scale-up; and representative sequencing across locations and time. Full article

Background/Objectives: Post-hemorrhagic hydrocephalus (PHH) is a major complication of extreme prematurity associated with significant neurodevelopmental morbidity. Although post-hemorrhagic ventricular dilatation (PHVD) is a recognized consequence of intraventricular hemorrhage (IVH), progression from an apparently low-grade IVH to severe shunt-dependent disease with imaging features suggestive—but not diagnostic—of a non-communicating hydrocephalus pattern is uncommon and presents important diagnostic and management challenges. We report such a case. Case Presentation: A male infant born at 26 weeks’ gestation developed an initially documented Grade II intraventricular hemorrhage that subsequently evolved into progressive post-hemorrhagic ventricular dilatation. Serial cranial ultrasonography demonstrated progressive ventriculomegaly, later confirmed by computed tomography showing marked dilatation of the lateral and third ventricles with severe cortical mantle thinning and a relatively preserved fourth ventricle, raising suspicion of a non-communicating hydrocephalus pattern. Clinical deterioration with progressive macrocephaly and neurological manifestations necessitated temporizing ventricular cerebrospinal fluid drainage, followed by ventriculoperitoneal shunt placement after stabilization and management of secondary complications. Management throughout the clinical course relied on serial neuroimaging, multidisciplinary decision-making, and individualized neurosurgical intervention. Conclusions: This case illustrates that an apparently low-grade neonatal intraventricular hemorrhage may evolve into severe shunt-dependent PHVD and emphasizes the importance of serial neuroimaging surveillance, objective assessment of ventricular progression, and cautious interpretation of imaging findings suggestive—but not diagnostic—of a non-communicating hydrocephalus pattern. It further highlights the diagnostic and therapeutic challenges encountered when atypical radiological evolution complicates the management of PHVD in extremely premature infants. 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

Background: Endothelial dysfunction is a central pathophysiological hallmark of preeclampsia. Laboratory and clinical features of preeclampsia can rapidly deteriorate and evidence on appropriate surveillance strategies is scarce. We aimed to evaluate the prognostic value of longitudinal changes in the “Endothelial Activation and Stress Index” (EASIX) for adverse outcomes in patients with preeclampsia. Methods: Patients with preeclampsia who delivered at Heidelberg University Hospital between 2017 and 2022 were included in this retrospective analysis. We assessed EASIX, derived from lactate dehydrogenase, creatinine and platelets, longitudinally between first admission and diagnosis of an adverse outcome. Composite adverse outcomes included pulmonary edema, HELLP syndrome, kidney injury, eclampsia, postpartum hemorrhage and death. We applied logistic and mixed linear regression modeling adjusted for age, gestational age and body mass index. Results: In total, 1733 EASIX measurements of 443 patients were included in the analysis, of which 81 patients experienced an adverse outcome. Both the first EASIX (aOR 2.81 [1.86;4.37]) and the absolute change per day (aOR 4.35 [1.77; 12.05]) were independently associated with adverse outcomes. Addition of the absolute change in EASIX to the model including the first EASIX (AUC 0.74 [0.68–0.81]) did not substantially improve the discriminatory performance (AUC 0.76 [0.70; 0.82]). Linear mixed regression modeling demonstrated that patients with adverse outcomes had a steeper rise in EASIX compared to patients without adverse outcomes (β = 0.024 [0.013, 0.034]). Conclusions: In patients with preeclampsia, EASIX diverged over time with steeper slopes in patients who developed adverse maternal outcomes. Our findings suggest that longitudinal EASIX monitoring may correlate with endothelial dysfunction and capture individual disease dynamics that are not apparent from a single measurement. Full article

Background/Objectives: The optimal anesthetic strategy during mechanical thrombectomy (MT) for acute ischemic stroke (AIS) remains debated. Although randomized trials suggest broadly comparable outcomes between general anesthesia (GA) and conscious sedation (CS), real-world data may be influenced by baseline severity, airway management, and postprocedural complications. We evaluated associations between anesthetic strategy, functional outcomes, mortality, and infectious and hemorrhagic complications after MT. Methods: This retrospective observational study included 257 consecutive adults with AIS treated with MT at a single comprehensive stroke center. Patients were managed under CS or GA according to clinical and procedural considerations. Outcomes, mortality, infectious and hemorrhagic complications were compared between groups. Multivariable logistic regression assessed associations with 90-day functional independence and mortality, adjusting for baseline and procedural factors. In an exploratory GA subgroup analysis, outcomes were compared according to extubation timing, defined as early (≤6 h) or delayed (>6 h). Results: Of 257 patients, 155 (60.3%) underwent MT under CS and 102 (39.7%) under GA. GA-treated patients had higher baseline NIHSS scores and worse unadjusted functional outcomes throughout follow-up. After adjustment, GA remained associated with higher 90-day mortality (OR 4.39, 95% CI 1.50–12.84; p = 0.007) and lower odds of 90-day functional independence (OR 0.29, 95% CI 0.10–0.82; p = 0.020). Pneumonia was more frequent with GA (49.0% vs. 26.5%; p < 0.001), although attenuated in adjusted analyses. Delayed extubation was associated with worse outcomes, higher pneumonia rates, and more frequent symptomatic intracranial hemorrhage. Conclusions: GA was associated with worse functional outcomes and higher mortality after MT, but residual confounding and differences in baseline stroke severity likely contributed to these associations. Pneumonia and hemorrhagic complications may identify patients at increased risk of poor outcome, especially when extubation is delayed. Findings require prospective confirmation. Full article

Newcastle disease (ND), a highly contagious poultry disease caused by NDV, primarily triggers gastrointestinal lesions. Microecological preparations, novel biological additives for restoring intestinal microbiota diversity, improve nutrient absorption, reinforce intestinal barrier function, and modulate host immune responses. This study investigated the effects of a compound microecological preparation on intestinal pathogenicity in chickens infected with genotype VII Newcastle disease virus (NDV). SPF chickens were allocated to four dietary groups with or without a compound microecological preparation, followed by NDV challenge in two groups. Survival, intestinal morphology, and transcriptomic responses were assessed. The results showed that chickens fed with the compound microecological preparation exhibited improved intestinal development. Following NDV infection, these chickens displayed milder cecal lesions without obvious hemorrhage and a higher survival rate. Furthermore, differential gene transcription analysis revealed that supplementation with the compound microecological preparation regulated the expression of genes associated with metabolic processes, biological regulation, immune response, and growth and development pathways, consistent with the clinical findings. In conclusion, we demonstrated that the compound microecological preparation promotes intestinal development in chickens, delays disease progression following NDV infection, and alleviates pathological damage. Transcriptomic analysis further indicated that the preparation enhances intestinal mucosal immunity by stimulating IgA production and strengthening the immune response against genotype VII NDV. These findings provide a scientific basis for the application of compound microecological preparations in regulating the intestinal immune system and in the prevention of Newcastle disease. Full article

Background/Objectives: As population aging increases the prevalence of atrial fibrillation (AF), the use of direct oral anticoagulants (DOACs) has expanded for thromboembolism prevention. Although DOACs offer advantages over vitamin K antagonists (VKAs), gastrointestinal bleeding (GIB) remains the most common extracranial adverse event. Current guidelines address global bleeding risk but provide limited guidance on site-specific gastrointestinal risk assessment and prevention. This narrative review aims to summarize current evidence on the mechanisms, etiologies, and risk factors for DOAC-associated gastrointestinal bleeding and to propose a pragmatic, risk-based framework to support clinicians in individualized bleeding prevention. Methods: A narrative review of studies published between 2004 and 2025 was conducted, including randomized clinical trials, real-world evidence, meta-analyses, and major society guidelines. Evidence addressing DOAC safety profiles, gastrointestinal bleeding etiologies, patient-level risk factors, medication interactions, and preventive strategies was analyzed. Results: Gastrointestinal bleeding in patients treated with DOAC is strongly influenced by underlying gastrointestinal pathology, comorbid conditions, and concomitant medications. Established risk factors include prior gastrointestinal hemorrhage, Helicobacter pylori infection, gastrointestinal malignancy, diverticulosis, and angiodysplasia, as well as the use of nonsteroidal anti-inflammatory drugs (NSAIDs), antiplatelet therapy, or selective serotonin reuptake inhibitors (SSRIs). DOACs differ in gastrointestinal safety: apixaban consistently demonstrates the most favorable profile, whereas rivaroxaban and high-dose dabigatran show higher GIB rates. Preventive strategies such as H. pylori testing and eradication, proton pump inhibitor use in high-risk individuals, avoidance of NSAIDs and unnecessary antiplatelet therapy, and individualized DOAC selection may help reduce bleeding risk. Conclusions: Gastrointestinal bleeding risk in patients receiving DOAC therapy should be assessed using a site-specific and dynamic approach. A structured strategy integrating baseline risk evaluation, correction of modifiable factors, tailored anticoagulant selection, and risk-adapted follow-up may improve the safety of anticoagulation. The proposed framework may provide a pragmatic approach to individualized bleeding risk mitigation while preserving the benefits of DOAC therapy; however, prospective validation is required before its routine implementation can be recommended. Full article

Objectives: To analyze factors associated with prolonged mechanical ventilation (MV) after patent ductus arteriosus (PDA) ligation in preterm infants and identify high-risk patients. Methods: A retrospective analysis (2021–2025) was conducted on preterm infants (≤32 weeks) who underwent PDA ligation. Demographic, preoperative and postoperative data were analyzed; machine learning and SHAP analysis identified associated factors. Results: A total of 271 infants (152 males, 119 females; median gestational age 27 weeks [23–32 weeks], median birth weight 920 g [470–2220 g]) were included. Based on postoperative MV duration ≤6 days or >6 days, 150 cases were assigned to the short MV group and 121 to the prolonged MV group. Significant differences were found between groups in terms of gestational age, birth weight, weight at surgery, PDA diameter, postoperative slowest heart rate, Respiratory Severity Score (RSS), rate of bidirectional PDA shunting, preoperative high-frequency ventilation use, post-ligation cardiac syndrome incidence, and rate of preoperative pulmonary hemorrhage/atelectasis (p < 0.05). RSS was identified as the most central predictor of prolonged postoperative MV duration. RSS > 4.5 was associated with a markedly elevated risk of MV >6 days (AUC = 0.865, sensitivity = 80.2%, specificity = 82.5%). In contrast, birth weight > 1500 g or post-ligation heart rate >135 bpm was correlated with shorter MV duration. Conclusions: High RSS, low birth weight, and slow postoperative heart rate are associated with prolonged postoperative MV. This may aid in identifying infants requiring closer perioperative monitoring. Full article

Background: Hemorrhagic wounds pose significant clinical challenges, with approximately 20% associated with surgical site infections and an increased mortality risk. Despite growing interest in natural product-based medicines, the molecular targets and bioactive phytochemicals of Musa acuminata peel relevant to hemorrhagic wound healing are insufficiently established. Methods: This study employed an integrative in silico approach to identify bioactive phytochemicals from the ethyl acetate extract of Musa acuminata peel as potential wound healing agents. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) profiling was performed for phytochemical characterization, followed by drug-likeness and toxicity screening via OSIRIS DataWarrior. Network pharmacology, molecular docking, molecular dynamics (MD), binding free energy calculation, pharmacokinetic properties prediction, and density functional theory (DFT) analysis were subsequently conducted. Results: LC–HRMS profiling identified 211 compounds across 21 chemical classes, of which 18 met drug-likeness criteria. Network pharmacology revealed five key protein targets. Molecular docking demonstrated that Compound 16 (−9.34 kcal/mol) and Compound 17 (−9.26 kcal/mol) exhibited stronger binding affinity toward VEGFR2 than Axitinib (−9.15 kcal/mol), with key interactions at glutamic acid-917 (GLU917) and cysteine-919 (CYS919). MD simulations over 100 ns confirmed complex stability, with BP16 showing superior binding stability and favorable MM/PBSA free energy. Pharmacokinetics and DFT analysis further supported BP16 as the most promising lead compound, exhibiting favorable pharmacokinetic properties, low predicted toxicity, and enhanced electronic stability. Conclusions: BP16 and BP17 are identified as potential VEGFR2-targeting candidates, providing a rational mechanistic foundation for future experimental validation as natural hemorrhagic wound healing therapeutics. Full article

Background: Early-onset neonatal listeriosis is a rare, life-threatening infection of vertical origin caused by Listeria monocytogenes. First-line therapy is intravenous ampicillin combined with an aminoglycoside; acquired β-lactam resistance is exceptionally uncommon. Case Presentation: A 34-week preterm female neonate (birth weight 1990 g, appropriate for gestational age) was born to a febrile primigravida with fetid greenish amniotic fluid at a regional secondary maternity and transferred at 30 h of life to our tertiary NICU with respiratory failure requiring mechanical ventilation. L. monocytogenes was recovered from blood, gastric aspirate, pharyngeal exudate, ocular secretion, and skin swab. Gradient strip susceptibility testing reported ampicillin and trimethoprim–sulfamethoxazole non-susceptibility, although confirmatory broth microdilution was unavailable. Broad-spectrum empirical therapy was revised on Day 5 to include ampicillin–sulbactam, with piperacillin–tazobactam and gentamicin continued. A follow-up blood culture on Day 9 remained sterile through 7 days. The hospital course was complicated by thrombocytopenia, transiently elevated aminotransferases, and a Grade I subependymal hemorrhage; tertiary NICU length of stay was 25 days. Conclusions: Recovery under a multi-agent regimen precludes attribution of effect to any single component. Discordant gradient strip susceptibility results in L. monocytogenes should be confirmed by broth microdilution before any therapeutic change; survivors of severe early-onset listeriosis require structured multidisciplinary follow-up. Full article

Background: Cerebral aneurysms and aneurysmal subarachnoid hemorrhage (aSAH) may induce cardiac electrical instability through autonomic dysregulation and an exaggerated neurohumoral stress response. Electrocardiographic (ECG) abnormalities, including QT/QTc prolongation, QTc dispersion, and P-wave dispersion, are recognized markers of ventricular repolarization heterogeneity and atrial conduction abnormalities associated with arrhythmogenic risk. However, data regarding the reversibility of these electrophysiological alterations following definitive aneurysm treatment remain limited. Methods: This retrospective, single-center study included 39 patients with cerebral aneurysms who underwent microsurgical clipping between January 2025 and May 2026 and 35 age- and sex-matched healthy controls. Standard 12-lead ECGs were evaluated at baseline (preoperative) and one month after surgery in the aneurysm group. QT interval, corrected QT (QTc) interval, QTc dispersion, and P-wave dispersion were assessed using standardized methods. Baseline transthoracic echocardiographic parameters, including left ventricular ejection fraction and left atrial diameter, were evaluated to minimize potential confounding related to structural cardiac abnormalities. Between-group and within-group comparisons were performed using appropriate statistical analyses. Results: Baseline demographic and echocardiographic characteristics were comparable between the aneurysm and control groups. Patients with cerebral aneurysms demonstrated significantly higher baseline QT interval, QTc interval, QTc dispersion, and P-wave dispersion compared with healthy controls. Following microsurgical treatment, significant reductions in QT interval, QTc interval, QTc dispersion, and P-wave dispersion were observed at one month compared with preoperative values, whereas PR interval and QRS duration remained unchanged. These findings suggest a partial normalization of cardiac electrical heterogeneity after definitive aneurysm treatment. Conclusions: Cerebral aneurysms are associated with increased ventricular repolarization and atrial conduction heterogeneity, reflecting autonomic-mediated cardiac electrical instability. The significant reduction in QTc dispersion and P-wave dispersion following microsurgical treatment suggests that these electrophysiological abnormalities may be at least partially reversible after aneurysm repair. ECG-derived markers such as QTc dispersion and P-wave dispersion may represent practical and non-invasive tools for monitoring cardiac electrical instability and recovery in patients with cerebral aneurysms. Full article

Background/Objectives: Ischemic stroke remains a major global health challenge, yet therapeutic options are severely restricted by narrow treatment windows and the risk of hemorrhagic transformation. Natural small molecules represent a valuable reservoir for discovering novel neuroprotective leads with favorable safety profiles. Cinchonidine, a natural quinoline alkaloid, has shown anti-inflammatory and cytoprotective properties, but its potential in treating ischemic stroke is largely unexplored. This study aimed to evaluate the neurovascular protective effects and hemostatic safety of cinchonidine in preclinical stroke models. Methods: We evaluated cinchonidine using a mouse model of middle cerebral artery occlusion (MCAO) and in vitro oxygen–glucose deprivation (OGD) models in cerebral endothelial cells (CECs) and Neuro2A cells. Infarct volume, brain edema, and neurological recovery were assessed. Blood–brain barrier (BBB) integrity was measured via Evans blue extravasation. Mechanistic markers, including microglial activation, pro-inflammatory mediators (iNOS, COX-2), and apoptosis-related signaling, were examined. Additionally, cinchonidine’s effect on platelet aggregation was also tested. Results: Cinchonidine significantly reduced infarct volume and brain edema while improving neurological functional recovery. It effectively preserved BBB integrity and enhanced cell viability under OGD conditions. Furthermore, cinchonidine suppressed microglial activation and decreased the expression of pro-inflammatory mediators. These protective effects were associated with the modulation of apoptotic signaling pathways. These protective effects were accompanied by reduced p53-associated stress signaling in endothelial cells and ischemic brain tissue. Importantly, cinchonidine did not significantly interfere with platelet aggregation, suggesting a potentially favorable hemostatic profile. Conclusions: Cinchonidine attenuates ischemic brain injury and is associated with endothelial protection, preservation of BBB integrity, and modulation of inflammatory and apoptotic responses. As a natural lead compound that does not compromise hemostasis, cinchonidine represents a promising lead compound for further development as a neurovascular protective strategy in ischemic stroke. Full article