Search Results (251)

A stroke is a critical medical condition and one of the leading causes of death among humans. Segmentation of the lesions of the brain in which the blood flow is impeded because of blood coagulation plays a vital role in drug prescription and medical diagnosis. Computed tomography (CT) scans play a crucial role in detecting abnormal tissue. There are several methods for segmenting medical images that utilize the main images without considering the patient’s privacy information. In this paper, a deep network is proposed that utilizes compressive sensing and ensemble learning to protect patient privacy and segment the dataset efficiently. The compressed version of the input CT images from the ISLES challenge 2018 dataset is applied to the ensemble part of the proposed network, which consists of two multi-resolution modified U-shaped networks. The evaluation metrics of accuracy, specificity, and dice coefficient are 92.43%, 91.3%, and 91.83%, respectively. The comparison to the state-of-the-art methods confirms the efficiency of the proposed compressive sensing-based ensemble net (CS-Ensemble Net). The compressive sensing part provides information privacy, and the parallel ensemble learning produces better results. Full article

Objectives: The increasing use of fetal MRI has increased the diagnosis of posterior fossa malformations, yet the long-term neurodevelopmental outcomes of affected fetuses remain unclear. This study aims to examine the long-term neurodevelopmental outcomes of fetuses with structural posterior fossa malformation diagnosed on fetal MRI. Methods: A historical cohort study was conducted at a single tertiary referral center, including fetuses diagnosed with structural posterior fossa malformations and apparently healthy fetuses who underwent fetal brain MRI between 2011 and 2019. Maternal, pregnancy, and newborn characteristics were compared between groups, alongside long-term neurodevelopmental outcomes using the Vineland Adaptive Behavior Scales II (VABS-II) questionnaire. This included an extensive assessment of malformation types, additional structural, genetic, or neurodevelopmental anomalies, and outcomes. Results: A total of 126 fetuses met the inclusion criteria, of which 70 were apparently healthy fetuses, and 56 had structural posterior fossa malformations. Among the latter, 18 pregnancies were terminated, 4 resulted in neonatal death, and 11 were lost to follow-up. No significant differences were found in the overall neurodevelopmental outcomes between fetuses with structural posterior fossa malformation (93.4 ± 19.0) and apparently healthy fetuses (99.8 ± 13.8). Motor skills scores were lower among fetuses with structural posterior fossa malformations (87.7 ± 16.5 vs. 99.3 ± 17.2, p = 0.01) but remained within the normal range. Conclusion: Fetuses with structural posterior fossa malformations may exhibit normal long-term neurodevelopmental outcomes if no additional anomalies are detected during thorough prenatal screening that includes proper sonographic, biochemical and genetic screening, as well as fetal MRI. Further research with larger cohorts and longer-term assessments is recommended to validate these findings and support clinical decision-making. Full article

Background/Objectives: Brain metastasis (BM) is a common and often early manifestation in lung adenocarcinoma (LUAD), yet its tumor microenvironment remains poorly defined at the time of initial diagnosis. This study aims to characterize early immune microenvironmental alterations in synchronous BM using spatial proteomic profiling. Methods: We performed digital spatial proteomic profiling using the NanoString GeoMx platform on formalin-fixed paraffin-embedded tissues from five treatment-naïve LUAD patients in whom BM was the initial presenting lesion. Paired primary lung and brain metastatic samples were analyzed across tumor and stromal compartments using 68 immune- and tumor-related protein markers. Results: Spatial profiling revealed distinct expression patterns between primary tumors and brain metastases. Immune regulatory proteins—including IDO-1, PD-1, PD-L1, STAT3, PTEN, and CD44—were significantly reduced in brain metastases (p < 0.01), whereas pS6, a marker of activation-induced T-cell death, was significantly upregulated (p < 0.01). These alterations were observed in both tumor and stromal regions, suggesting a more immunosuppressive and apoptotic microenvironment in brain lesions. Conclusions: This study provides one of the first spatially resolved proteomic characterizations of synchronous BM at initial LUAD diagnosis. Our findings highlight early immune escape mechanisms and suggest the need for site-specific immunotherapeutic strategies in patients with brain metastasis. Full article

Background/Objectives: Traumatic brain injury is one of the leading causes of death and disability. When traumatic brain injury is repeated over time, it can lead to the development of Chronic Traumatic Encephalopathy, a chronic neurodegenerative disease commonly observed in individuals who engage in contact sports or military personnel involved in activities with a high risk of repeated head trauma. At autopsy, the examination of the brain reveals regional atrophy, corresponding to high concentrations of glutamate receptors. Microscopically, the primary findings are the deposition of neurofibrillary tangles and neuropil threads. The aim of this study is to highlight the clinical and histopathological characteristics of Chronic Traumatic Encephalopathy, providing diagnostic support to forensic pathologists. Additionally, it seeks to aid in the differential diagnosis of similar conditions. Methods: A review of literature was conducted following the PRISMA criteria. Of 274 articles, 7 were selected. Results: According to these papers, most patients were male and exhibited neurological symptoms and neuropsychiatric impairments, and a proportion of them committed suicide or had aggressive behavior. Conclusions: Chronic Traumatic Encephalopathy remains largely underdiagnosed during life. The definitive diagnosis of Chronic Traumatic Encephalopathy is established post-mortem through the identification of pathognomonic tauopathy lesions. Early and accurate antemortem recognition, particularly in at-risk individuals, is highly valuable for its differentiation from other neurodegenerative conditions, thereby enabling appropriate clinical management and potential interventions. Full article

Kernicterus spectrum disorder is the permanent and highly disabling neurologic sequel of neonatal exposure to hyperbilirubinemia, presenting, among other symptoms, variable and untreatable motor disabilities. To search for potential biomolecular explanations, we used a Gunn rat colony exhibiting spontaneous hyperbilirubinemia and a large variability of motor deficits on a beam-walking test. Histological and microscopic analyses confirmed worsening damage in the cerebellum (Cll; hypoplasia, increased death of neurons, and disrupted astroglial structures) and parietal motor cortex (hCtx; increased cell sufferance and astrogliosis). Clustering and network analyses of transcriptomic data reveal rearrangement of the physiological expression patterns and signaling pathways associated with bilirubin neurotoxicity. Bilirubin content among hyperbilirubinemic (jj) animals is overlapped, which suggests that the amount of bilirubin challenge does not fully explain the tissue, transcriptomic, proteomic, and neurobehavioral alterations. The expression of nine genes involved in key postnatal brain development processes is permanently altered in a phenotype-dependent manner. Among them, Grm1, a metabotropic glutamatergic receptor involved in glutamate neurotoxicity, is consistently downregulated in both brain regions both at the transcriptomic and proteomic levels. Our results support the role of Grm1 and glutamate as biomolecular markers of ongoing bilirubin neurotoxicity, suggesting the possibility to improve diagnosis by ¹H-MR spectroscopy. Full article

Background/Objectives: Nutritional support in neurosurgical patients is challenging due to severe brain injury, neurological disease, or post-surgical complications. This study aimed to assess outcomes of long-term enteral nutrition via endoscopic gastrostomy (PEG) in these patients over a 22-year period. Methods: A single-center retrospective (2001–2023) study was conducted on patients referred for PEG. Included patients presented severe traumatic brain injury (TBI), stroke, brain tumor, or other neurosurgical conditions. Demographic, anthropometric, and clinical data were collected. Results: A total of 196 patients were included (105 men); 57% were under 65 years. The main diagnoses were stroke (41.8%), TBI (35.2%), and brain tumors (19.9%). The median time from diagnosis to PEG was 94 days. At the time of PEG, only 38.5% were underweight. Outcomes: A total of 132 deaths (75.4%) occurred, while 21 patients resumed oral feeding (10.7%), 22 patients remained PEG-fed (12.6%), and 21 patients were lost to follow-up (10.7%). Most surviving PEG-fed patients had experienced stroke (77%). Median post-PEG survival was 11.5 months and 88% survived >1 month. Higher albumin, transferrin, and cholesterol levels at the time of PEG were associated with longer survival. Albumin (p < 0.001) and transferrin (p < 0.01) were significantly associated with reduced short-term mortality. Conclusions: Despite limited overall survival, reflecting the clinical severity of the diseases, most patients were adequate survivors, and PEG-feeding proved to be appropriate and useful for neurosurgical patients. While most patients had normal-to-high BMI, low serum biomarkers reflected acute illness. Higher serum albumin level was associated with better outcomes, supporting its potential prognostic value. Full article

Glioblastoma (GBM) is the most aggressive and challenging brain cancer, in terms of diagnosis and therapy. The highly infiltrative glioblastoma stem cells (GSCs) are difficult to visualize and surgically remove with the current diagnostic tools, which often lead to misdiagnosis and false-positive results. In this study, we focused on a groundbreaking tool for specifically visualizing and removing GSCs. We exploited the specific binding of A40s aptamer to EphA2 for the selective delivery of Near-Infrared Dyes (NIR-Dyes), like IR700DX and ICG, both in vitro and in vivo. The A40s aptamer, engineered through the NIR-Dye conjugation, did not affect aptamer binding ability; indeed, A40s-NIR-Dye conjugates bound GLI261 stem-like cells and patient-derived GSCs in vitro; moreover, they induced cell death upon photodynamic therapy treatment (PDT). Additionally, when systemically administrated, the A40s-NIR-Dye conjugates allowed GSC visualization and accumulated in tumor mass. This allows GSCs detection and treatment. Our findings demonstrate the potential use of A40s aptamer as a targeted therapeutic approach and imaging tool in vivo for GSCs, paving the way for improved, more effective, and less invasive GBM management. Full article

: Alzheimer’s disease (AD) is a neurodegenerative disorder closely associated with aging, and its pathogenesis involves the interaction of multidimensional pathophysiologic processes. This review outlines the core mechanisms linking aging and AD. The amyloid cascade hypothesis emphasizes that abnormal deposition of amyloid-β (Aβ) triggers neuronal damage and synaptic dysfunction, which is exacerbated by aging-associated declines in protein clearance. Neuroinflammation, a synergistic pathogenetic factor in AD, is mediated by microglia activation, creating a vicious cycle with Aβ and tau pathology. The cholinergic hypothesis states that the degeneration of cholinergic neurons in the basal forebrain can lead to acetylcholine deficiency, which is directly associated with cognitive decline. Endothelial disorders promote neuroinflammation and metabolic waste accumulation through blood–brain barrier dysfunction and cerebral vascular abnormalities. In addition, glutamate-mediated excitotoxicity and mitochondrial dysfunction (e.g., oxidative stress and energy metabolism imbalance) further lead to neuronal death, and aging-associated declines in mitochondrial autophagy exacerbate such damage. This review also explores the application of animal models that mimic AD and aging in studying these mechanisms and summarizes therapeutic strategies targeting these pathways. Future studies need to integrate multi-targeted therapies and focus on the role of the aging microenvironment in regulating AD pathology in order to develop more effective early diagnosis and treatment options. Full article

The thyroid is a vital endocrine organ that regulates metabolism, heart rate, respiration, digestion, body temperature, brain development, skin and bone maintenance, and reproduction and fertility. Thyroid cancer (TC) is the most common endocrine malignancy, with an estimate of 44,020 new cases in 2025. Incidence has been increasing, most notably at 4–5% per year in young adults. Papillary thyroid cancer (PTC), the most common TC subtype, accounts for approximately 80% of newly diagnosed TC cases. Furthermore, 2290 deaths are expected from the disease in 2025, with survival at over 98% with treatment. However, as PTC occurs most frequently in young women, recurrences are frequent and the 10-year disease-specific survival rate for advanced PTC is less than 50%. This narrative review aims to describe the current understanding of the thyroid gland, the incidence and subtypes of thyroid cancer, and specifically the diagnosis, prognosis, treatment, and recurrence of PTC. This is supplemented by the role of molecular pathways and biomarkers in PTC. Full article

Background and Objectives: Despite the latest advancements in interventional procedures and pharmacological therapy, the incidence of heart failure and death rate following an acute myocardial remain unacceptably high. This study was designed in response to the limited and conflicting literature data regarding the diagnostic and prognostic role of modern inflammatory biomarkers in patients with coronary artery disease. Materials and Methods: We conducted a case–control, prospective observational study. A total of 145 patients were analyzed, of whom 105 patients had an acute coronary syndrome diagnosis and represented the study group, while 40 patients with a chronic coronary syndrome diagnosis represented the control group. This study investigates the diagnostic and prognostic role of the interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10), Growth differentiation factor 15 (GDF-15), and classic biomarkers in patients with ischemic coronary heart disease. Results: IL-1β exhibited a prognostic role, being significantly correlated with a left ventricular ejection fraction below 30%. GDF-15 plays a dual role, as a cardio-inflammatory biomarker, being significantly correlated with both N-terminal pro-brain natriuretic peptide (NT-proBNP), and IL-1β, IL-6, and CRP. At the same time, GDF-15 represents a surrogate marker for renal dysfunction. According to the ROC analysis, patients at high mortality risk can be identified with adequate accuracy by cardiac troponin, GDF-15, and IL-10, in addition to NT-proBNP. Logistic regression models confirmed NT-proBNP and IL-10 as mortality predictors. Conclusions: IL-1β stands out for its significant prognostic role, while IL-6 did not demonstrate a diagnostic or prognostic role in acute myocardial infarction patients. IL-10 demonstrated superior predictive value in terms of fatal prognosis compared with the other modern biomarkers. GDF-15 is representative of a multivalent biomarker involved in inflammation, heart failure, and renal dysfunction. Full article

Background: Real-world data provide insights into populations underrepresented in clinical trials such as non-small-cell cancer (NSCLC) patients with brain metastases (BMs). Despite global survival improvement due to novel drug employment, their impact in resource-limited settings like Serbia remains underexplored. This study analyzes the overall survival (OS) of NSCLC patients with BMs treated in routine clinical practice, considering patient-, disease- and treatment-related factors amid restricted access to novel drugs. Methods: We retrospectively analyzed 267 NSCLC patients diagnosed with BMs from 2018 to 2022 at a single Serbian clinical center. Inclusion required histologically confirmed NSCLC, radiologically verified BMs and complete clinical data. OS was defined as the time from BM verification to death or last follow-up. Kaplan–Meier curves and Cox regression were used for survival analysis. Results: Median OS (mOS) was 5.0 months. Univariate analysis linked age < 65 years, female gender, single BM, asymptomatic BMs, ECOG PS 0–1, BM verification at diagnosis and combined systemic and local therapy to better OS. Combined therapy offered the best survival rates (mOS: 9.0 months), while best supportive care and local-only therapy both resulted in a poor mOS of 2.0 months. Immunotherapy and targeted therapy were associated with the highest mOS, outperforming chemotherapy alone (13.0 vs. 7.0 months, p < 0.001). Multivariate analysis confirmed younger age, single BM, early BM verification and combined therapy as independent predictors of improved survival. Conclusions: limited access to novel therapies remains associated with poor patient survival, highlighting the need for better global availability. Full article

Background/Objectives: Human glioblastoma (GBM) is the most aggressive brain cancer in adults and a highly treatment-refractory malignancy. The overall prognosis for the GBM is extremely poor, with a median survival of 12–14 months after initial diagnosis. Many GBM patients initially respond to the DNA alkylating agent temozolomide (TMZ), but patients often become therapy-resistant, and tumors recur. We previously reported that treatment with PFI-3, which is a small molecule inhibitor of the bromodomain of the BRG1 subunit of the SW1/SNF chromatin remodeling complex, enhanced the sensitivity of GBM cells to TMZ in vitro and in vivo GBM animal models. Our general objective was to perform an SAR study of new diphenyl PFI-3 analogs. Methods: New structural analogs of PFI-3 were developed, synthesized, and tested for their ability to enhance TMZ-induced GBM cell death by ELISA. Results: Following on the enhanced activity of compounds 2a and 2b, new diphenyl PFI-3 analogs with specific structural adjustments were made to better understand the structural requirements to optimize function. Additionally, several new structurally different candidates (e.g., 4a, 4b, and 5) showed much better efficacy in sensitizing GBM cells to TMZ-induced GBM cell death. Conclusions: Four series of PFI-3 analogs (2, 3, 4, and 5) were designed, synthesized, and tested for the ability to sensitize GBM cells to TMZ-induced cell death. Series 2 optimized the A-ring and R-isomer chirality. Series 3 used a 5-membered linker with weak activity. Series 4’s di-phenyl urea compounds showed better bromodomain inhibition. Series 5’s methoxyphenyl-B-ring analogs were exceptionally strong inhibitors. Full article

Background: Traumatic brain injury (TBI) is one of the main causes of death in trauma pathology, especially among the youngest victims. After having evaluated the causality relationship between damage to the brain tissue and death, pathologists should try to estimate the duration between the TBI and death. Immunohistochemistry could be used in this field as a personalized medico-legal approach. This study aims to evaluate the possible role of vimentin and p53 as TBI markers to assess vitality and date the TBI. Methods: Twelve cases of TBI deaths were selected (two women and ten men, with a mean age of 46.83 years). In seven cases, death occurred immediately after the trauma, while in the others, death occurred after some days. An immunohistological study of brain samples using anti-p53 and anti-vimentin antibodies was performed. A semi-quantitative scale was adopted to grade the immunohistochemical reaction. Results: Our results showed a strong relationship between the p53 immunoreaction grade and TBI (X-squared value 10.971, p-value < 0.01), suggesting that p53 expression is enhanced in TBI cases. Vimentin is more expressed when the PTI is longer. Vimentin-immunoreaction was weaker than p53-immunoreaction (+0.75 vs. +1.83 mean values, respectively) in a group predominantly including short post-traumatic interval cases. Conclusions: The present research is limited by the small sample size; however, the molecules tested, vimentin and p53, have shown great potential to be used, in addition to others, as biological markers for the diagnosis and timing of TBI. Full article

Background/Objectives: No prior studies have attempted to identify a biomarker for initial brain metastasis velocity (iBMV), with limited studies attempting to correlate genomic data with the development of brain metastases. Methods: Patients with non-small-cell lung cancer (NSCLC) who underwent next-generation sequencing (NGS) were identified in our departmental database. iBMV was calculated by dividing the number of BMs by the interval of time between primary cancer and BM diagnosis. Two-sample t-testing was used to identify mutations statistically associated with iBMV (p < 0.1). A value of +1 was assigned to each mutation with a positive association (“deleterious genes”), and a value of −1 to each with an inverse association (“protective genes”). The sum of these values was calculated to define iBMV risk scores of −1, 0 and 1. Pearson correlation test was used to determine the association between iBMV risk score and calculated iBMV, and a competing risk analysis assessed for death as a competing risk to the development of BMs. Results: A total of 312 patients were included in the analysis, 218 of whom (70%) developed brain metastases. “Deleterious genes” included ARID1A, BRAF, CDK4, GNAQ, MLH1, MSH6, PALB2, RAD51D, RB1 and TSC1; “protective genes” included ARAF, IDH1, MYC, and PTPN11. iBMV risk scores of 1, 0 and −1, predicted an 88%, 61% and 65% likelihood of developing a BM (p < 0.01). A competing risk analysis found a significant association between iBMV risk scores of 1 vs. 0 and 1 vs. −1, and the likelihood of developing a BM using death as a competing risk. Overall survival (OS) at 1 and 2 years for patients with iBMV risk scores of 1, 0 and −1 was 72% vs. 84% vs. 85% and 46% vs. 69% vs. 70% (p < 0.02). Conclusions: Development of a genomic signature for iBMV via non-invasive liquid biopsy appears feasible in NSCLC patients. Patients with a positive iBMV risk score were more likely to develop brain metastases. Validation of this signature could lead to a biomarker with the potential to guide treatment recommendations and surveillance schedules. Full article

Background/Objectives: Breast cancer is the most common malignancy in women and the second leading cause of cancer-related deaths globally. It is also the second most frequent source of brain metastases (BMs), contributing to 5–20% of cases. Despite this, routine brain imaging for screening is not recommended and is only conducted when clinical symptoms or physical findings suggest metastasis. This study aims to identify clinical predictors associated with overall survival (OS) and the timing of BM development in breast cancer patients. Methods: We performed a retrospective review of medical records for 113 patients diagnosed with BMs secondary to breast cancer at our institution between 2000 and 2020. Baseline demographic data and clinical characteristics related to BMs were collected. To identify factors associated with OS and time to BM development after breast cancer diagnosis, we conducted univariate analysis using Kaplan–Meier curves, bivariate analysis with the log-rank test, and multivariate analysis via the Cox Proportional Hazard model. Results: An early diagnosis of BMs was identified as a significant predictor of prolonged OS (aHR = 0.22; 95% CI: 0.049–0.98, p = 0.05). Post-menopausal status at breast cancer diagnosis (aHR = 1.69; 95% CI: 1.13–2.53, p = 0.01), Asian ethnicity (aHR = 2.30; 95% CI: 1.03–5.16, p = 0.04), and the ER+/HER2+ subtype (aHR = 2.06; 95% CI: 1.14–3.71, p = 0.02) were significantly associated with a shorter time to BM diagnosis. A subgroup analysis of patients with ER+ breast tumors revealed that Hispanic or Arabic ethnicity (aHR = 3.63; 95% CI: 1.34–9.81, p = 0.01) and stage IV diagnosis (aHR = 2.09; 95% CI: 1.16–3.76, p = 0.01) were significantly associated with shorter intervals to BM diagnosis. Conclusions: Breast cancer remains a significant global health burden for women, yet clear guidelines for routine BMs screening are still lacking. Early detection of BMs has been shown to notably improve long-term survival outcomes. Additionally, post-menopausal status, Hispanic or Arabic ethnicity, and the HER2+ tumor subtype are associated with shorter time to BM development, highlighting these factors as potential indicators for central nervous system screening. Full article