Search Results (1,752)

Previous studies have shown that plasma amyloid-beta oligomers (AβOs), the toxic form of amyloid-beta (Aβ), are a critical issue in the development or worsening of Alzheimer’s disease (AD) and can be regarded as a blood marker for screening in dementia. We examined plasma AβOs with their related biomarkers in a case–control study to clarify these issues. A total of 16 patients diagnosed with Alzheimer’s dementia (AD) and 16 cognitively normal controls (NCs) were recruited to compare their plasma biomarkers, AβO, Aβ_1-40, and Aβ_1-42, also referring to other parameters like APOE ε4 status, Clinical Dementia Rating^®-Sum of Boxes (CDR^®-SB), and Mini Mental Status Examination (MMSE) scores. In plasma concentrations of Aβ_1-40, Aβ_1-42, and AβO, the mean concentrations were significantly different between the two groups. There is a significant increase in the concentrations of Aβ_1-40 and AβO, while Aβ_1-42 is decreased in individuals with AD compared to NC. AβO was statistically associated with the Aβ_1-40 and Aβ_1-42/Aβ_1-40 ratio. Higher plasma concentrations of AβO were significantly associated with AD compared to non-dementia controls. This suggests that AβOs can be potential plasma biomarkers to screen in AD. However, a study recruiting more individuals is necessary to examine the association, if any. Full article

Glioblastoma, isocitrate dehydrogenase (IDH1/2) wild-type (IDH-wildtype), is one of the most aggressive and malignant tumors of the central nervous system, characterized by rapid growth, pronounced cellular heterogeneity, and an exceptionally poor prognosis. The median survival time for patients with glioblastoma, IDH-wildtype, is approximately 15 months after diagnosis, and current multimodal treatment strategies remain largely ineffective. This review focuses on contemporary pharmacotherapeutic approaches used in the management of glioblastoma, IDH-wildtype, including temozolomide-based chemotherapy, corticosteroids for edema control, and antiangiogenic therapy in recurrent disease, with particular emphasis on their clinical efficacy and limitations. In addition, the review discusses emerging targeted therapeutic strategies developed for IDH-mutant diffuse gliomas, which represent a biologically distinct disease entity. Particular attention is given to ivosidenib, a selective inhibitor of mutant IDH1, currently evaluated for the treatment of astrocytoma, IDH-mutant, grade 4. Its epigenetic mechanism of action, involving inhibition of the oncometabolite 2-hydroxyglutarate (2-HG), is outlined, along with preliminary clinical evidence suggesting potential to delay disease progression. Finally, innovative drug-delivery technologies designed to overcome the blood–brain barrier are briefly discussed as complementary strategies that may enhance the efficacy of both conventional and targeted therapies. Overall, future advances in the treatment of diffuse gliomas will likely depend on the integration of molecularly targeted agents, predictive biomarkers, and advanced delivery platforms aimed at improving patient survival and quality of life. Full article

Background/Objectives: Dizziness is a symptom of many disorders across a wide range of etiologies. If dizzy patients are seen for vestibular evaluation with an audiologist and no vestibular reason for the patient’s dizziness is found, the medical referral pathway can become convoluted. This can leave patients feeling discouraged and unable to manage their symptoms. Clinically symptomatic chronic respiratory alkalosis (CSCRA) is an acid–base disorder that typically presents with dizziness but is unfamiliar to practitioners in vestibular and balance care settings. Methods: In a retrospective chart review deemed exempt by the Mayo Clinic Institutional Review Board, 74 patients at Mayo Clinic Arizona were included. All had consultations with both Audiology and Aerospace Medicine to assess their dizzy symptoms. Results: After completing vestibular testing, arterial blood gas (ABG) testing, and a functional test developed at Mayo Clinic Arizona called the Capnic Challenge test, 40% of patients were found to have CSCRA contributing to their dizzy symptoms. Many of these patients also had common comorbidities of CSCRA, like postural orthostatic tachycardia syndrome (POTS), migraines, and sleep apnea. Fewer than one-fourth of these patients had measurable vestibulopathies causing their dizziness. Half of the patients referred by the vestibular audiologist to Aerospace Medicine had a diagnosis of CSCRA. Conclusions: Assessment for CSCRA should be considered as a next step for patients presenting with dizziness without a vestibular component. Being aware of the prevalence of CSCRA and its comorbidities may help balance providers offer quality interprofessional referrals and improve patient quality of life. Full article

Since 1997, a laboratory-based survey on cryptococcosis has been conducted in Colombia. We present the results for the period 2017–2024. A total of 891 surveys were received. The overall incidence was 0.22 cases per 100,000 people. Among those living with HIV, the incidence was 38, and among HIV-negative people, it was 0.08. Cryptococcosis demonstrated a higher prevalence among men than women (3.2:1). Among patients living with Human Immunodeficiency Virus (HIV), the condition primarily affected younger adults (26–40 years). In contrast, among HIV-negative people, it was mostly observed in older adults (≥60 years). HIV infection was the most significant risk factor (63%), but another cause of immunosuppression was identified in 21.2% cases. Neurocryptococcosis was the most common form of presentation (62.2%), followed by disseminated cryptococcosis (31.1%). The diagnosis was confirmed by culture in 99.4% of patients; the most important sample was cerebrospinal fluid (67.3%), followed by blood (35.4%). Cryptococcus neoformans was identified in 93.1% of cases, and Cryptococcus gatti in 6.9%. Predominant molecular patterns were VNI (92.4%) and VGII (45.3%). The epidemiology of cryptococcosis in Colombia is changing, with a progressive decrease in HIV coinfection and an increase in other immunosuppressive conditions in older people. This study highlights the importance of cryptococcosis in Colombia and the need to report it in order to improve knowledge and thereby promote the quality of diagnosis and the opportunity for more effective treatment. Full article

Background: Malaria remains a major public health concern around the world. Microscopic blood smear examination continues to be the gold standard for diagnosis; however, it requires high technical skills and expertise, limiting diagnostic accuracy in resource-poor settings. Artificial intelligence (AI) has emerged as a promising tool to support malaria detection. This systematic review provides an overview of the diagnostic performance of AI-based systems for malaria diagnosis in a clinical setting. Methods: This study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and involved articles within the last 10 years that were collected from PubMed, ScienceDirect, Cochrane, EBSCO, and Wiley Online Library. Original articles that reported AI diagnostic accuracy with external validation were involved. The quality of each study was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Results: Ten studies with 6754 patients were analyzed. Pooled results of sensitivity [87.7% (95% CI: 78.2–93.4)] and specificity [91.4% (95% CI: 77.3–97.1)] revealed how much the AI agrees with each method when that method is used as a gold standard. Additionally, AI achieved a sensitivity of 87.7% and a specificity of 91.4% compared to microscopy examination and a sensitivity of 90.7% and a specificity of 88.3% compared to polymerase chain reaction (PCR). Conclusions: AI-based systems improve malaria diagnosis by providing high accuracy, automation, and lower costs. Showing performance comparable to reference methods such as microscopy and PCR, AI is a promising complementary tool for malaria control. Full article

Glaucoma is a leading cause of irreversible blindness worldwide, with its asymptomatic progression highlighting the urgent need for early, minimally invasive biomarkers. Exosomes derived from the aqueous humor (AH) have emerged as promising candidates, as they carry proteins, nucleic acids, and lipids that reflect the physiological and pathological state of ocular tissues such as the trabecular meshwork and ciliary body. However, their low abundance, nanoscale size, and the limited volume of AH complicate detection and characterization. Conventional methods, including Western blotting, PCR or mass spectrometry, are labor-intensive, time-consuming, and often incompatible with microliter-scale samples. Electrochemical biosensors offer a highly sensitive, rapid, and low-volume alternative, enabling the detection of exosomal surface markers and internal cargos such as microRNAs, proteins, and lipids. Recent advances in nanomaterial-enhanced electrodes, microfluidic integration, enzyme- and nanozyme-mediated signal amplification, and ratiometric detection strategies have significantly improved sensitivity, selectivity, and multiplexing capabilities. While most studies focus on blood or serum, these platforms hold great potential for AH-derived exosome analysis, supporting early-stage glaucoma diagnosis, monitoring of disease progression, and evaluation of therapeutic responses. Continued development of miniaturized, point-of-care electrochemical biosensors could facilitate clinically viable, noninvasive exosome-based diagnostics for glaucoma. Full article

Background: Obesity is a worldwide public health problem, affecting organs and systems. It is also a cardiovascular risk factor, which facilitates the development of diseases, such as arterial hypertension, dyslipidemia, and diabetes, which are used as criteria for the diagnosis of metabolically unhealthy obesity. Objective: To analyze the association between blood pressure and metabolic health factors, stress level, and nutrient intake in overweight and obese university students through mediation analysis. Methods: A quantitative, non-experimental, cross-sectional, correlational, and quantitative study was conducted in a sample of 230 obese/overweight university students selected by a multistage mass random sampling method. To evaluate habitual dietary intakes, a CFCA food frequency questionnaire was applied; a DASS-21 scale was used to evaluate stress; blood pressure and anthropometric data were collected; insulin levels, lipid profile, and glucose were determined using fasting blood samples. Statistical analysis was performed using univariate methods (frequencies, trend, and dispersion measures) and a mediational model. Results: The majority were young people aged 18 years (18.7%), with morning and afternoon shifts (60%), overweight (76.1%), and obese (23.9%). Not all obese people have arterial hypertension; however, an increase in BMI increases the risk of suffering from this disease. Model 1 showed that certain types of stress and sex at birth have an important relationship with diastolic blood pressure, mediated in some cases by weight. In Model 2, weight is a significant mediator in the relationship between moderate stress and systolic BP, and between sex at birth and systolic BP, thus allowing us to contribute to the understanding of how these variables are interrelated. Conclusions: This suggests that severe stress and sex at birth not only affect BP directly, but also do so through their effect on weight. Thus, both pathways contribute to understanding the relationship between stress, sex at birth, and diastolic and systolic blood pressure. Nevertheless, the results of this study provide empirical knowledge to design evidence-based prevention and treatment strategies. Full article

Background/Objectives: Active surveillance (AS) has become the standard of care for many men with localised prostate cancer, aiming to avoid the overtreatment of indolent disease while maintaining oncological safety. Despite improvements in diagnostic techniques, misclassification at diagnosis and the limited ability to predict disease progression remain major challenges in AS. Novel molecular and genetic biomarkers, assessed through liquid biopsy approaches, offer the potential to refine patient selection and support risk-adapted monitoring in AS. Methods: We conducted a narrative review of biomarkers in the context of AS for prostate cancer, framing the discussion in terms of the challenges in AS and how biomarkers may address these. PubMed and Embase were searched for English-language peer-reviewed studies published between 2000 and 2025. International guidelines (AUA, EAU, NCCN, NICE) and reference lists were reviewed manually. Priority was given to large prospective cohorts, meta-analyses, and high-impact publications. Results: Blood-based assays such as PHI and the 4K score, urinary tests including ExoDx and SelectMDx, and the Prostate Urine Risk (PUR) signatures have all shown associations with disease progression or decisions to undergo earlier treatment. However, studies are often small, use surrogate endpoints, and lack validation in MRI-integrated cohorts. Biomarkers appear most informative in men with Gleason Grade 1 (GG1) disease, while evidence in GG2 cohorts is limited. Cost-effectiveness, heterogeneity of endpoints, and uncertainty in managing discordant biomarker and MRI results remain barriers to clinical adoption. Conclusions: Molecular and genetic biomarkers show promise for improving AS by reducing diagnostic misclassification and enhancing prediction of progression. Future research should define clinically relevant cut-offs, clarify integration with MRI, and evaluate longitudinal use. Demonstrating utility in contemporary cohorts could enable the development of biomarker-guided, personalised AS that maintains safety while minimising harm. Full article

Creutzfeldt–Jakob disease (CJD) is a rare but devastating neurodegenerative disorder characterized by the pathological misfolding of the cellular prion protein (PrP^C) into the pathogenic isoform-scrapie prion protein (PrP^Sc), ultimately leading to fatal outcomes. Cerebrospinal fluid (CSF) biomarkers play a pivotal role in early diagnosis, longitudinal monitoring, and prognostic assessment, thereby enhancing the clinical management of this challenging disease. This review summarizes the established CSF biomarkers, 14-3-3 protein, tau protein (total tau), phosphorylated tau isoforms, α-synuclein, neurofilament light chain (Nfl), S100B, neuron-specific enolase (NSE), and phosphorylated neurofilament heavy chain (pNFH), highlighting typical sensitivity ranges (14-3-3 ~70–85%; RT-QuIC > 90%) and subtype-dependent performance variation. We further dissect limitations related to assay variability, inter-laboratory cut-off inconsistencies, and reduced specificity in non-prion dementias. Looking ahead, we discuss emerging multi-omics discovery, integration of CSF with blood-based biomarkers and imaging signatures, and AI-enabled diagnostic modeling. We propose a three-tier biomarker framework combining Real-Time Quaking-Induced Conversion (RT-QuIC) as a confirmatory assay, tau/NfL/pNFH as injury-severity indicators, and multi-omics-derived signatures for early detection and prognosis stratification. Full article

A promising application of smart materials based on natural polymers is the potential to solve problems related to hemostasis in cases of severe bleeding caused by injury or surgery. This can be a life-threatening situation. Cellulose and its modified derivatives represent one of the most promising sources for creating effective hemostatic systems, as well as for various sensing applications related to disease detection, infection diagnosis, chronic condition monitoring, and blood analysis. The aim of this review was to identify key criteria for the efficiency of cellulose-based gels with hemostatic activity. Experimental studies aimed at evaluating new hemostatic devices were analyzed based on international sources using the PRISMA methodology. A total of 111 publications were identified. Following the identification and screening stages, 20 articles were selected for the final qualitative synthesis. The analyzed publications include experimental studies focused on the development and analysis of highly porous cellulose-based scaffolds in the form of aerogels and cryogels. The type and origin of cellulose, as well as the influence of additional components and synthesis conditions on gel formation, were investigated. Three major groups of key criteria that should be considered when developing new cellulose-based highly porous scaffolds with hemostatic functionality were identified: (I) physicochemical and mechanical properties (pore size distribution, compressive strength, and presence of functional groups); (II) in vitro tests (blood clotting index, red blood cell adhesion rate, hemolysis, cytocompatibility, and antibacterial activity); (III) in vivo hemostatic efficiency (hemostasis time and blood loss) in compliance with the 3Rs policy (replacement, reduction, refinement). The prospects for the development of highly porous cellulose-based scaffolds are not only focused on their hemostatic properties, but also on the development of smart platforms. Full article

Background: We aimed to investigate the diagnostic performance between the oral glucose tolerance test (OGTT) and HbA1c in diagnosing prediabetes and diabetes among obese individuals, and to evaluate the diagnostic performance of HbA1c for detecting OGTT-defined diabetes in obese individuals referred for evaluation of suspected prediabetes. Methods: Individuals with prediabetes were included between 1 January 2020 and 31 December 2022. Participants were categorized as mildly, moderately, morbidly, or super obese based on body mass index (BMI). According to the 75 g OGTT results, patients were classified into three groups: isolated impaired fasting glucose (IFG), combined IFG + impaired glucose tolerance (IGT), and overt type 2 diabetes mellitus (T2DM). The threshold HbA1c value for T2DM diagnosis in obese patients was determined based on OGTT outcomes. Results: Of the 139 prediabetic obese patients included, 115 (82.7%) were female, with a mean age of 45.18 ± 11.74 years. Based on BMI, 34 patients (24.5%) were mildly obese, 41 (29.5%) moderately obese, 49 (35.3%) morbidly obese, and 15 (10.8%) super obese. According to the 75 g OGTT results, 37.4% (n = 52) had isolated IFG, 45.3% (n = 63) had combined IFG + IGT, and 17.3% (n = 24) had overt T2DM. A weak–moderate positive correlation was observed between HbA1c and fasting blood glucose (Spearman’s rho = 0.263, p = 0.002). ROC–AUC analysis showed that HbA1c had significant discriminatory power in detecting T2DM diagnosed by the 75 g OGTT (AUC = 0.881, 95% CI: 0.816–0.946, p < 0.001). The optimal HbA1c cut-off was 6.15%, with 83.3% sensitivity and 80% specificity. The positive predictive value was 46.1%, and the negative predictive value was 95.8%. Conclusions: An HbA1c threshold of 6.15% demonstrated optimal performance for detecting OGTT-defined diabetes in obese individuals with suspected prediabetes. This value should not be interpreted as a population-wide diagnostic threshold. These findings indicate that HbA1c may serve as a useful screening tool to identify obese individuals who warrant confirmatory OGTT testing, rather than as a stand-alone diagnostic criterion. Further large-scale studies are warranted to confirm these results and support future clinical guidelines. Full article

Prostate cancer (PCa) is a common malignancy in men worldwide, with incidence projected to rise in the coming years. Traditional screening and diagnostic methods, such as prostate-specific antigen (PSA) testing and biopsy, face limitations in specificity and invasiveness. Circulating microRNAs (miRNAs) have emerged as stable, non-invasive biomarkers obtainable via liquid biopsies (blood, urine, semen) that could transform PCa management. These small regulatory RNAs reflect underlying tumor biology and are detectable at early disease stages, enabling improved early detection when used alongside or in place of PSA. Distinct miRNA expression patterns correlate with tumor aggressiveness. For example, miR-141 and miR-375 are elevated in metastatic cases, whereas let-7 family members and miR-326 are upregulated in aggressive disease, highlighting their prognostic value. Moreover, dynamic changes in reported miRNAs during therapy provide real-time insights into treatment response. In androgen-deprivation therapy (ADT), oncogenic miRNAs, such as miR-21 and miR-125b, increase upon resistance, whereas a decline in tumor-suppressive miRNAs, such as miR-23b/-27b, flags the transition to castration-resistant PCa (CRPC). Similarly, baseline levels of miRNAs (e.g., miR-200b/c, miR-20a) can predict chemotherapy outcomes. Integrating multi-miRNA panels has demonstrated superior accuracy for risk stratification and monitoring, paving the way for personalized treatment. Although promising, clinical implementation of miRNA-based assays requires further validation, standardization of protocols, and large-scale prospective studies. Harnessing circulating miRNAs could usher in a new era of precision oncology for PCa, improving early diagnosis, prognostication, and real-time therapeutic guidance. Full article

Non-coding RNAs have emerged as central regulators of gene expression in neurodegenerative diseases, offering new opportunities for diagnosis and therapy. This review synthesizes current knowledge on microRNAs, long non-coding RNAs, and circular RNAs in Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, emphasizing their roles in synaptic function, proteostasis, mitochondrial biology, and neuroinflammation. We evaluate evidence supporting non-coding RNAs as circulating and tissue-based biomarkers for early detection, disease monitoring, and patient stratification, and we compare analytical platforms and biofluid sources. Mechanistic insights reveal how non-coding RNAs modulate pathogenic protein aggregation, neuronal excitability, immune cell crosstalk, and blood–brain barrier integrity. Translational efforts toward RNA-targeted interventions are reviewed, including antisense oligonucleotides, small interfering RNAs, miRNA mimics and inhibitors, circular RNA decoys, and extracellular vesicle-mediated delivery systems. We discuss pharmacological modulation, delivery challenges, safety concerns, and strategies to enhance specificity and CNS penetration. Finally, we outline emerging computational and multi-omics approaches to prioritize therapeutic targets and propose a roadmap for advancing non-coding RNA research from preclinical models to clinical trials. Addressing biological heterogeneity and delivery barriers will be pivotal to realizing the diagnostic and therapeutic promise of the non-coding transcriptome in neurodegenerative disease. Collaboration across disciplines and rigorous clinical validation are urgently needed. Full article

Background: Persistent low-grade inflammation has been proposed as part of the biological mechanisms underlying post-COVID condition (PCC), which can result in laboratory tests abnormalities. However, the accuracy of routine laboratory tests for the diagnosis and follow-up of PCC is still under discussion. Methods: Patients with SARS-CoV-2 infection enrolled in the prospective, multinational ORCHESTRA cohort study, which included both European and non-European countries, were followed up for 18 months after acute infection. Blood test results were collected at acute infection and at 6, 12, and 18 months. A multivariable analysis was performed to estimate the relationship between the alterations of biochemical markers and the presence of four distinct PCC phenotypes, identified previously through a principal component analysis—respiratory (RESc), chronic pain (CPc), chronic fatigue (CFc), and neurosensorial (NSc)—during follow-up. Furthermore, this study investigated the correlation between biochemical parameters measured during the acute phase and the subsequent development of PCC. Finally, the relationship between the severity of the acute infection and biochemical abnormalities observed during follow-up was assessed. Results: The cohort included 4587 patients, 58% male, with a mean age of 58.7 (±15.5) years. A robust multivariable analysis demonstrated that, compared to controls, patients with PCC, and in particular those in the RESc cluster, presented higher mean C-reactive protein (CRP) levels at the 12- and 18-month follow-up (p-value = 0.01). In each follow-up, CRP values in patients with PCC and RESc were above 3 mg/L, corresponding to those observed in low-grade inflammation (3–10 mg/L). The severity of COVID-19 acute infection was associated with increased levels of CRP, ferritin and LDH during follow-up (p < 0.001). Biochemistry abnormalities detected during the early stages of acute COVID-19 did not correlate with an increased risk of developing PCC and its phenotypes. Conclusions: In patients with the RESc PCC phenotype, identified through a principal component analysis, blood test abnormalities consistent with prolonged and sustained low-grade inflammation can be detected up to 18 months after acute infection, supporting its role in the pathogenesis of PCC. Based on these results, trials on anti-inflammatory drugs, together with symptom-tailored interventions for patients with RESc, should be planned to prove their effectiveness in managing PCC and improving patient outcomes. Full article

Introduction: Prompt diagnosis and differentiation between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) are essential in the treatment of bladder cancer. Inflammation-based biomarkers have recently emerged as potential tools for improving cancer diagnostics and prognostication. This study aims to evaluate the potential value of the Systemic Inflammation Index (SII), Systemic Inflammation Response Index (SIRI), Pan-immune Inflammation Value (PIV), and Platelet-to-Lymphocyte Ratio (PLR) as predictors of muscle-invasive disease. Materials and methods: Analyzed data included 310 bladder tumors. The SII, SIRI, PIV, and PLR were calculated from pre-TURBT complete blood-count results. Differences in inflammatory markers between pathological stages (pTa–pT4) were examined using ANOVA with Tukey’s post hoc testing. Optimal cutoff values for distinguishing NMIBC from MIBC were identified using ROC curve analysis and Youden’s J statistic. Logistic regression models incorporating age, sex, the number of recurrences, and each inflammatory index were developed to evaluate their predictive performance in patients treated with curative intent. Results: All investigated inflammation indices significantly differed across tumor stages (p < 0.001), with lower values observed in pTa tumors compared with muscle-invasive disease. Determined cutoff values for muscle-invasive disease were 865.63 for SII, 2.02 for SIRI, 579.28 for PIV, and 166.35 for PLR. Logistic regression models demonstrated promising diagnostic performance, achieving AUC values of 0.812 (SII), 0.816 (SIRI), 0.821 (PIV), and 0.795 (PLR); sensitivity and specificity were 76% and 75% for SII, 79% and 77% for SIRI, 80% and 72% for PIV, and 88% and 59% for PLR. Discussion: The presented results indicate that inflammation-based indices vary meaningfully between bladder cancer stages and may be utilized in early identification of muscle-invasive disease. As inexpensive and widely available biomarkers, they offer potential value in the evaluation of suspected MIBC before the final pathology report and could enhance the diagnostic process. Full article