Search Results (13,009)

Sleep is a vital physiological process for recovery and health. In people with knee osteoarthritis (OA), disrupted sleep is common and linked to worse clinical outcomes. Commercial sleep trackers provide an accessible option to monitor sleep in this population, but their accuracy for detecting sleep, wake, and sleep stages remains uncertain. This study compared nighttime sleep data from polysomnography (PSG) and Fitbit Sense in individuals with knee OA and insomnia. Data were collected from 53 participants (60.4% women, mean age 51 ± 8.2 years) over 62 nights using simultaneous PSG and Fitbit recording. Fitbit Sense showed high accuracy (85.76%) and sensitivity (95.95%) for detecting sleep but lower specificity (50.96%), indicating difficulty separating quiet wakefulness from sleep. Agreement with PSG was higher on nights with longer total sleep time, higher sleep efficiency, shorter sleep onset, and fewer awakenings, suggesting better performance when sleep is less fragmented. The device showed limited precision in classifying sleep stages, often misclassifying deep and REM sleep as light sleep. Despite these issues, Fitbit Sense may serve as a useful complementary tool for monitoring sleep duration, timing, and regularity in this population. However, sleep stage and fragmentation data should be interpreted cautiously in both clinical and research settings. Full article

Background/Objectives: Diabetic retinopathy is a leading cause of vision impairment worldwide, and the development of reliable automated classification systems is crucial for early diagnosis and clinical decision-making. This study presents a comprehensive comparative evaluation of two state-of-the-art deep learning families for the task of classifying diabetic retinopathy using retinal fundus images. Methods: The models were trained and tested in both binary and multi-class settings. The experimental design involved partitioning the data into training (70%), validation (20%), and testing (10%) sets. Model performance was assessed using standard metrics, including precision, sensitivity, specificity, F1-score, and the area under the receiver operating characteristic curve. Results: In binary classification, the ResNeXt101-64x4d model and RegNetY32GT model demonstrated outstanding performance, each achieving high sensitivity and precision. For multi-class classification, ResNeXt101-32x8d exhibited strong performance in early stages, while RegNetY16GT showed better balance across all stages, particularly in advanced diabetic retinopathy cases. To enhance transparency, SHapley Additive exPlanations were employed to visualize the pixel-level contributions for each model’s predictions. Conclusions: The findings suggest that while ResNeXt models are effective in detecting early signs, RegNet models offer more consistent performance in distinguishing between multiple stages of diabetic retinopathy severity. This dual approach combining quantitative evaluation and model interpretability supports the development of more robust and clinically trustworthy decision support systems for diabetic retinopathy screening. Full article

Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic malignancy defined by the uncontrolled proliferation of lymphoid precursors. Accurate diagnosis and effective therapeutic strategies hinge on a comprehensive understanding of the genetic and molecular landscape of ALL. This review synthesizes the latest updates in cytogenetic and molecular classifications, emphasizing the 2022 World Health Organization (WHO) and International Consensus Classification (ICC) revisions. Key chromosomal alterations such as BCR::ABL1 and ETV6::RUNX1 and emerging subtypes including Ph-like ALL, DUX4, and MEF2D rearrangements are examined for their prognostic significance. Furthermore, we assess novel diagnostic tools, notably next-generation sequencing (NGS) and optical genome mapping (OGM). While NGS excels at identifying point mutations and small indels, OGM offers high-resolution structural variant detection with 100% sensitivity in multiple validation studies. These advancements enhance our grasp of leukemogenesis and pave the way for precision medicine in both B- and T-cell ALL. Ultimately, integrating these innovations into routine diagnostics is crucial for personalized patient management and improving clinical outcomes. Full article

Background and Objectives: Clostridioides difficile infection (CDI) poses a major public health problem worldwide. Materials and Methods: In this retrospective study, we included 274 patients with CDI, who were hospitalized in Internal Medicine Departments in Evangelismos General Hospital in Athens, Greece, during the past decade. Demographic, clinical and laboratory parameters of the patients were recorded. Statistical analysis revealed an association between older age and mortality as well as heart failure and mortality among patients with CDI. Results: Notably, WBC (white blood count), neutrophils, NLR (neutrophil-to-lymphocyte ratio), dNLR (derived NLR), SII (systemic immune–inflammation index) and hs-CRP (high-sensitivity C-reactive protein) demonstrated a positive association with mortality, whereas serum albumin levels and PNR (platelet-to-neutrophil ratio) exhibited an inverse relationship with mortality. We propose that the aforementioned biomarkers may be used as prognostic parameters regarding mortality from CDI. Conclusions: Large scale studies among patients with CDI with the advent of AI (artificial intelligence) may incorporate demographic, clinical and laboratory features into prognostic scores to further characterize the global CDI threat. Full article

Background: Parkinson’s disease (PD) often involves autonomic dysfunction, most notably impaired baroreflex sensitivity (BRS), which disrupts cardiovascular homeostasis and contributes to orthostatic hypotension (OH). Pharmacological and invasive treatments, including deep brain stimulation, have yielded inconsistent benefits and carry procedural risks, highlighting the need for safer, more accessible alternatives. In this systematic review, we evaluated non-invasive interventions—spanning somatosensory stimulation, exercise modalities, thermal therapies, and positional strategies—aimed at improving cardiovascular autonomic function in PD. Methods: We searched PubMed, Embase, MEDLINE (Ovid), Google Scholar, ScienceDirect, and Web of Science for studies published between January 2014 and December 2024. Eight original studies (n = 8) including 205 participants met the inclusion criteria for analyzing cardiac sympathovagal balance. Results: Five studies demonstrated significant post-intervention increases in BRS. Most reported favorable shifts in heart rate variability (HRV) and favorable changes in the low-frequency/high-frequency (LF/HF) ratio. Across modalities, systolic blood pressure (SBP) decreased by an average of 5%, and some interventions produced benefits that persisted up to 24 h. Conclusion: Although sample sizes were small and protocols heterogeneous, the collective findings support the potential of non-invasive neuromodulation to enhance BRS and overall cardiovascular regulation in PD. Future research should focus on standardized, higher-intensity or combined protocols with longer follow-up periods to establish durable, clinically meaningful improvements in autonomic function and quality of life for people living with PD. Full article

Background/Objectives: Acute kidney injury (AKI) is a common and severe complication in patients with acute myocardial infarction (AMI). Very elderly patients are at a heightened risk of developing AKI. Fibrinogen and albumin are well-known biomarkers of inflammation and nutrition, which are highly related to AKI. We aim to explore the predictive value of the fibrinogen-to-albumin ratio (FAR) for AKI in very elderly patients with AMI. Methods: A retrospective cohort of AMI patients ≥ 75 years old hospitalized at the First Affiliated Hospital of Xi’an Jiaotong University between January 2018 and December 2022 was established. Clinical data and medication information were collected through the biospecimen information resource center at the hospital. Univariate and multivariable logistic regression models were used to analyze the association between FAR and the risk of AKI in patients with AMI. FAR was calculated as the ratio of fibrinogen (FIB) to serum albumin (ALB) level (FAR = FIB/ALB). The primary outcome is acute kidney injury, which was diagnosed based on KDIGO 2012 criteria. Results: Among 1236 patients enrolled, 66.8% of them were male, the median age was 80.00 years (77.00–83.00), and acute kidney injury occurred in 18.8% (n = 232) of the cohort. Comparative analysis revealed significant disparities in clinical characteristics between patients with or without AKI. Patients with AKI exhibited a markedly higher prevalence of arrhythmia (51.9% vs. 28.1%, p < 0.001) and lower average systolic blood pressure (115.77 ± 25.96 vs. 122.64 ± 22.65 mmHg, p = 0.013). In addition, after adjusting for age, sex, history of hypertension, left ventricular ejection fraction (LVEF), and other factors, FAR remained an independent risk factor for acute kidney injury (OR = 1.47, 95%CI: 1.36–1.58). ROC analysis shows that FAR predicted stage 2–3 AKI with superior accuracy (AUC 0.94, NPV 98.6%) versus any AKI (AUC 0.79, NPV 93.0%), enabling risk-stratified management. Conclusions: FAR serves as both a high-sensitivity screening tool for any AKI and a high-specificity sentinel for severe AKI, with NPV-driven thresholds guiding resource allocation in the fragile elderly. Full article

Thyroid cancer is the most common endocrine malignancy, and preoperative distinction between benign and malignant nodules remains challenging, especially in cytologically indeterminate cases. Circulating microRNAs (miRNAs) have gained interest as non-invasive biomarkers due to their stability and involvement in tumorigenesis. This study aimed to assess the preoperative diagnostic value of circulating miR-146a and miR-221 in patients undergoing thyroidectomy. A total of 56 patients were included, of whom 24 had malignant and 32 had benign thyroid lesions confirmed by histopathology. Preoperative plasma levels of miR-146a and miR-221 were quantified using qRT-PCR, and relative expression was calculated with the 2^−ΔΔCt method. miR-221 expression was significantly higher in malignant cases, with an area under the ROC curve of 1.00, achieving 100% sensitivity and specificity at the optimal threshold. miR-146a showed no significant discriminatory ability. Weak correlations were observed between miRNA expression and clinical parameters such as age, TIRADS score, or thyroid volume. Logistic regression including miR-221 led to perfect separation, indicating strong predictive capacity but precluding multivariate modeling. These findings suggest that circulating miR-221 may serve as a highly accurate biomarker for thyroid malignancy and warrant further validation in larger, prospective cohorts. Full article

Background/Objectives: In recent years, lipids have emerged as critical regulators of different disease processes, being involved in cancer pathogenesis, progression, and outcome. Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) has significantly expanded the technology’s reach, enabling spatially resolved profiling of lipids directly from tissue, including formalin-fixed paraffin-embedded (FFPE) specimens. In this context, MALDI matrix selection is crucial for lipid extraction and ionization, influencing key aspects such as molecular coverage and sensitivity, especially in such specimens with already depleted lipid content. Thus, in this work, we aim to explore the feasibility of mapping lipid species in FFPE clinical samples with MALDI-MSI using 6-aza-2-thiothymine (ATT) as a matrix of choice. Methods: To do so, ATT performances were first compared to those two other matrices commonly used for lipidomic analyses, 2′,5′-dihydroxybenzoic acid (DHB) and Norharmane (NOR), on lipid standards. Results: As a proof-of-concept, we then assessed ATT’s performance for the MALDI-MSI analysis of lipids in FFPE brain sections, both in positive and negative ion modes, comparing results with those obtained from other commonly used dual-polarity matrices. In this context, ATT enabled the putative annotation of 98 lipids while maintaining a well-balanced detection of glycerophospholipids (60.2%) and sphingolipids (32.7%) in positive ion mode. It outperformed both DHB and NOR in the identification of glycolipids (3%) and fatty acids (4%). Additionally, ATT exceeded DHB in terms of total lipid count (62 vs. 21) and class diversity and demonstrated performance comparable to NOR in negative ion mode. Moreover, ATT was applied to a FFPE glioblastoma tissue microarray (TMA) evaluating the ability of this matrix to reveal biologically relevant lipid features capable of distinguishing normal brain tissue from glioblastoma regions. Conclusions: Altogether, the results presented in this work suggest that ATT is a suitable matrix for pathology imaging applications, even at higher lateral resolutions of 20 μm, not only for proteomic but also for lipidomic analysis. This could enable the use of the same matrix type for the analysis of both lipids and peptides on the same tissue section, offering a unique strategic advantage for multi-omics studies, while also supporting acquisition in both positive and negative ionization modes. Full article

Background/Objectives: Feigning spectrum behavior (FSB) is the exaggeration, fabrication, or false imputation of symptoms. It occurs in compensable injury with great cost to society by way of loss of productivity and excessive costs. The aim of this study is to identify feigning by developing cut scores on the long and short forms (SF) of the Orebro Musculoskeletal Pain Screening Questionnaire (OMPSQ and OMPSQ-SF) and the Perceived Stress Scale (PSS and PSS-4). Methods: As part of pre-screening for a support program, 40 injured workers who had been certified unfit for work for more than 2 weeks were screened once with the OMPSQ and PSS by telephone by a mental health professional. A control sample comprised of 40 non-injured community members were screened by a mental health professional on four occasions under different aliases, twice responding genuinely and twice simulating an injury. Results: Differences between the workplace injured people and the community sample were compared using ANCOVA with age and gender as covariates, and then receiver operator characteristics (ROCs) were calculated. The OMPSQ and OMPSQ-SF discriminated (ρ < 0.001) between all conditions. All measures discriminated between the simulation condition and workplace injured people (ρ < 0.001). Intraclass correlation demonstrated the PSS, PSS-4, OMPSQ, and OMPSQ-SF were reliable (ρ < 0.001). Area Under the Curve (AUC) was 0.750 for OMPSQ and 0.835 for OMPSQ-SF for work-injured versus simulators. Conclusions: The measures discriminated between injured and non-injured people and non-injured people instructed to simulate injury. Non-injured simulators produced similar scores when they had multiple exposures to the test materials, showing the uniformity of feigning spectrum behavior on these measures. The OMPSQ-SF has adequate discriminant validity and sensitivity to feigning spectrum behavior, making it optimal for telephone screening in clinical practice. Full article

Background: Despite the survival benefit of ICDs in patients with HFrEF, most recipients do not receive appropriate therapy during follow-up. Existing risk models based on echocardiographic and clinical parameters show limited predictive accuracy for arrhythmic events. This study aimed to assess whether ECG-derived markers outperform conventional measures in predicting appropriate ICD shocks. Methods: This retrospective observational study included 375 patients with HFrEF who underwent ICD implantation for primary prevention at least six months before study enrollment. Twelve-lead surface ECGs were analyzed for a QTc interval, Tp-e/QT ratio, frontal QRS-T angle, and maximum deflection index (MDI). Clinical, echocardiographic, and arrhythmic event data obtained from device interrogations were evaluated. Receiver operating characteristic (ROC) curve analysis and multivariate logistic regression were performed to identify independent predictors of appropriate ICD shocks. Results: Patients who experienced appropriate ICD shocks had significantly higher rates of a complete bundle branch block, digoxin use, QRS duration, QTc, Tp-e/QT ratio, frontal QRS-T angle, MDI, and right-ventricular pacing ratio. Conversely, beta-blocker use was significantly lower in this group. In multivariate analysis, independent predictors of appropriate shocks included the patient’s digoxin use (OR = 2.931, p = 0.003), beta-blocker use (OR = 0.275, p = 0.002), frontal QRS-T angle (OR = 1.009, p < 0.001), QTc interval (OR = 1.020, p < 0.001), and Tp-e/QT ratio (OR = 4.882, p = 0.050). The frontal QRS-T angle had a cutoff value of 105.5° for predicting appropriate ICD shocks (sensitivity: 73.6%, specificity: 85.2%, AUC = 0.758, p < 0.001). Conclusions: Electrocardiographic markers, particularly the frontal QRS-T angle, QTc interval, and Tp-e/QT ratio, demonstrated superior predictive power for appropriate ICD shocks compared to conventional echocardiographic and clinical measures. These easily obtainable, non-invasive ECG parameters may improve current risk stratification models and support more individualized ICD implantation strategies. Full article

The treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has transformed significantly with the advent of triplet therapy involving androgen deprivation therapy (ADT), docetaxel, and androgen receptor signalling inhibitors (ARSIs). While clinical guidelines increasingly support early intensification, real-world practice remains challenged by patient heterogeneity, evolving evidence, and limited consensus on treatment sequencing. This narrative review integrates evidence from landmark trials, clinical guidelines, and expert insights from oncologists managing mHSPC in India. Findings affirm that triplet therapy, particularly with darolutamide, improves survival in high-volume disease and underscores the need for personalized treatment based on disease burden, comorbidities, and genomic profiles. The review also highlights gaps in real-world data, sequencing strategies, and biomarker-driven therapy, reinforcing the need for precision medicine and locally relevant evidence to guide treatment. Ultimately, optimizing mHSPC management requires harmonizing guideline-based approaches with individualized, real-world decision making to improve patient outcomes. Full article

Cancer remains a major global health challenge requiring the development of diagnostic and therapeutic strategies. Liquid biopsy is considered a promising minimally invasive tool for cancer screening, prognosis and treatment monitoring. Recent studies suggest that neutrophil extracellular traps (NETs) may also be potential liquid biopsy markers. NETs are web-like chromatin structures released by neutrophils in response to various stimuli to trap and neutralize pathogens. However, excessive or dysregulated NET formation has been implicated in tumor progression and metastasis. Elevated levels of NETs have been observed in patients with various types of cancer and correlate with disease stage and prognosis. The presence of NET markers such as citrullinated histone H3 (H3Cit), neutrophil elastase (NE) and myeloperoxidase (MPO) has been associated with higher tumor burden and poorer clinical outcomes. Several studies have shown a positive correlation between NET markers and circulating free DNA (cfDNA) levels, suggesting that NETs may increase the sensitivity of liquid biopsy in detecting and monitoring cancer progression. This review examines the role of NETs in the tumor microenvironment, their contribution to cancer progression and metastasis, and their potential use in liquid biopsy and cancer therapy. Full article

Background/Objectives: Cognitive impairment is one of the most common and debilitating clinical features of Multiple Sclerosis (MS). Neuropsychological assessment, however, is time-consuming and requires personal resources, so, due to limited resources in daily clinical practice, information on cognitive profiles is often lacking, despite its high prognostic relevance. Time-saving and effective tools are required to bridge this gap. This study evaluates the sensitivity and specificity of a revised version of TRACK-MS (TRACK-MS-R), a recently published screening tool to identify cognitive impairment in MS in a fast and reliable way, offering a balance between efficiency and diagnostic yield for the individual patient. Methods: In this prospective cross-sectional study, 102 MS patients and 94 age-, sex-, and education-matched healthy controls (HC) completed an extensive neuropsychological assessment, including TRACK-MS-R, to test for cognitive processing speed (Symbol Digit Modalities Test, SDMT) and verbal fluency (Regensburger Word Fluency Test, RWT). Sensitivity of TRACK-MS-R was assessed by using the BICAMS-M battery as a reference, and specificity was determined by comparing MS patients to HC. Results: TRACK-MS-R demonstrated high sensitivity (97.44%) when compared to the gold standard as represented by BICAMS-M for early and accurately detecting cognitive impairment in MS patients. Additionally, as a potential cognitive marker, TRACK-MS-R showed a specificity of 82.98% in distinguishing MS patients from healthy controls. Conclusions: TRACK-MS-R proves to be a highly sensitive and time-efficient screening tool for detecting cognitive impairment in patients with MS, while demonstrating good specificity compared to HC. Whereas high sensitivity is a prerequisite for a valid screening tool, its relatively modest specificity compared to BICAMS-M (62.9%) calls for caution in interpreting standalone results but instead indicates more extensive neuropsychological testing. Its briefness and diagnostic accuracy support its implementation in routine clinical practice, particularly in time-constrained settings. Full article

The global spread of Mpox virus (MPXV) underscores the urgent need for rapid, field-deployable diagnostic tools, especially in low-resource settings. We evaluated a loop-mediated isothermal amplification (LAMP) assay, termed LAMPOX, developed by Coris BioConcept. The assay was tested in three formats—two liquid versions and a dried, ready-to-use version—targeting only the ORF F3L (Liquid V1) or both the ORF F3L and N4R (Liquid V2 and dried) genomic regions. Analytical sensitivity and specificity were assessed using 60 clinical samples from confirmed MPXV-positive patients. Sensitivity on clinical samples was 81.7% for Liquid V1 and 88.3% for Liquid V2. The dried LAMPOX assay demonstrated a sensitivity of 88.3% and a specificity of 100% in a panel of 112 negative controls, with most positive samples detected in under 7 min. Additionally, a simplified sample lysis protocol was developed to facilitate point-of-care use. While this method showed slightly reduced sensitivity compared to standard DNA extraction, it proved effective for samples with higher viral loads. The dried format offers key advantages, including ambient-temperature stability and minimal equipment needs, making it suitable for point-of-care testing. These findings support LAMPOX as a promising tool for rapid MPXV detection during outbreaks, especially in resource-limited settings where traditional PCR is impractical. Full article

Human cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is a complex parasitic disease marked by dynamic host–parasite interactions and immunomodulation. Extracellular vesicles (EV) derived from immune cells have emerged as key mediators of intercellular communication and potential biomarkers in infectious diseases. In this study, we combined a modified lymphocyte proliferation assay with nano-flow cytometry to quantify and phenotype EV released by CD4⁺, CD8⁺, and CD14⁺ cells in PBMC cultures from CL patients at different clinical stages: before treatment (PBT), during treatment (PDT), and post-treatment (PET) with antimonial. Healthy individuals (HI) were included as physiological controls. Upon stimulation with L. (V.) braziliensis antigens, we observed a distinct modulation of EV subsets. In the PBT group, CD4⁺ and CD14⁺ EV were significantly reduced, while CD8⁺ EV remained elevated. During PDT and PET, EV concentrations were restored across all subsets. These findings suggest that L. (V.) braziliensis selectively modulates the release of immune cell–derived EV, possibly as an immune evasion mechanism. The restoration of EV release following antimonial therapy highlights their potential as sensitive biomarkers for disease activity and treatment monitoring. This study offers novel insights into the immunoregulatory roles of EV in CL and underscores their relevance in host–parasite interactions. Full article