Search Results (29,421)

Acute Lymphoblastic Leukemia (ALL) is a rapidly progressing blood cancer that demands timely and accurate diagnosis, particularly in pediatric patients. Conventional diagnosis relies on manual examination of peripheral blood smear images by hematologists, which is time-consuming, subjective, and prone to error. Although deep learning approaches have demonstrated high accuracy in medical imaging, many existing models are computationally intensive, limiting their use in resource-constrained clinical settings. To address these challenges, we propose LeukSNN, a lightweight spiking neural network (SNN) for automated ALL detection from peripheral blood smear images. Unlike conventional CNNs, SNNs employ sparse event-driven computations that can substantially reduce computational and energy requirements, making them attractive for deployment in low-resource healthcare environments. The proposed architecture combines depthwise separable convolutions, residual connections, and attention mechanisms within an SNN framework to achieve high classification performance with reduced computational cost. Experiments on three publicly available datasets demonstrate accuracies of 99.91–100%, while requiring only 8% and 28% of the multiplication and addition operations, respectively, of current state-of-the-art efficient methods. These results demonstrate that LeukSNN can achieve highly accurate and computationally efficient ALL classification on benchmark datasets, highlighting the potential of SNN-based approaches for future investigation in resource-constrained healthcare environments. Full article

Tuberculosis (TB) remains a leading cause of death from a single infectious agent, and its outcome is shaped not only by Mycobacterium tuberculosis (Mtb) itself, but also by the host’s metabolic state. This review synthesises current understanding of how Mtb reprograms macrophage immunometabolism and how this reprogramming propagates to a systemic level, culminating in skeletal muscle dysregulation and TB-associated cachexia. We describe the molecular mechanisms by which Mtb subverts phagosomal maturation, the glycolytic (Warburg-like) switch governed by HIF-1α and accumulation of immunomodulatory tricarboxylic acid cycle intermediates, and the M1/M2 polarisation balance that dictates bacterial containment versus persistence. We then trace the cytokine- and metabolite-mediated circuits (TNF-α, IL-6, IL-1β, lactate, ketone bodies, free fatty acids) that link infected macrophages to ubiquitin–proteasome and autophagy–lysosome-driven muscle proteolysis, mitochondrial dysfunction and oxidative stress. Building on these mechanisms, we propose an immunometabolic and muscle-derived biomarker framework that, although still requiring clinical validation, may offer value for diagnosis, host-response stratification and treatment monitoring, and we discuss host-directed therapeutic strategies that target macrophage metabolism and muscle preservation. By integrating immunity, metabolism and systemic pathology at the molecular level, this work highlights translational opportunities relevant to the host immunity, diagnosis and treatment of tuberculosis. Full article

Background/Objectives: Dilated cardiomyopathy is a heterogeneous disorder with a substantial genetic contribution from a variety of pathogenic variants. Hereditary isolated DCM is often caused by variants in genes encoding sarcomere proteins, as well as proteins involved in desmosomes or other cardiac cell functions. Identifying genetic causes improves our understanding of DCM pathophysiology, facilitates prognostic assessment, and enables more personalized disease management. Methods: We retrospectively analyzed genetic data from adult patients with a clinical diagnosis of isolated DCM evaluated at a Lithuanian tertiary university hospital between 2019 and 2024. All patients were tested with a next-generation sequencing cardiovascular gene panel. Results: We gathered 169 patients and initially reached a 16.0% (n = 27) genetic testing diagnostic yield. We performed all genetic variant reanalyses with the most current classification guidelines, and we found an additional eight positive cases. Our final diagnostic yield was 20.7% (n = 35). TTN was the most frequently affected gene (n = 30), whereas variants in BAG3 (n = 2), DSP (n = 1), LMNA (n = 1), and FLNC (n = 1) were rare. In total, 15 variants were novel—not described in the literature or databases. We did not observe significant clinical differences between patients with pathogenic variants and those without pathogenic variants. We expected a different clinical course with variants in genes like BAG3 or LMNA, but there were only a few cases. Conclusions: Genetic testing remains an important tool for confirming complex DCM cases and allows earlier disease management for relatives at risk. Full article

Global population aging has emerged as a major driver of the growing burden of neurological diseases, highlighting the urgent demand for advances in early diagnosis, prevention, and rehabilitation. These conditions are typically characterized by insidious onset and irreversible progression, yet their clinical management remains critically compromised by substantial diagnostic delays, representing an intractable bottleneck for existing detection technologies. Therefore, the development of precise, early-stage detection technologies is crucial for expanding the therapeutic window and improving long-term clinical outcomes, addressing a critical unmet clinical need. Herein, we review and compare precision detection strategies for neurological diseases, focusing on the types and mechanisms of mainstream biosensing platforms. Based on the classification of detection substrates and signal transduction mechanisms, four major bio-detection branches are analyzed, including liquid, exosomal, imaging, and digital biomarker detection, with representative studies demonstrating detection limits reaching femtomolar concentrations, clinical diagnostic sensitivities exceeding 90%, and classification accuracies comparable to or surpassing conventional imaging modalities. The inherent advantages and limitations of each biosensing technology are also comprehensively discussed. This review underscores that future research on neurological biomarker sensing is trending toward multimodal integration, which enables the construction of more robust early warning and prognostic assessment systems. This work aims to provide valuable theoretical insights for clinical translation of relevant sensing technologies and integrated diagnostic and treatment strategies, thereby facilitating the progress of early intervention and rehabilitation for common neurological diseases. Full article

Medical image segmentation is critical for clinical diagnosis, yet existing methods face a persistent trade-off: CNN-based approaches are constrained by local receptive fields, while Transformer-based methods suffer from semantic dilution when modeling global context. To address these limitations, we propose SCAGC-UNet, a region-aware graph convolutional network that bridges local detail extraction and global dependency modeling through structured region-level reasoning. The architecture features a dual-layer residual encoder for hierarchical feature extraction and a Spatial-Channel Graph Convolution (SC-GCN) module at the bottleneck, which simultaneously captures inter-region spatial topology and intra-region channel semantics via dual-branch graph inference. Feature refinement in the decoder is further enhanced by Context-Corrected Modules and Backward-Aided Modules to reduce the semantic gap across skip connections. We validate SCAGC-UNet on three public benchmarks covering distinct imaging challenges. On Kvasir-SEG, the model achieves a Dice score of 92.28% and MIOU of 92.41%, surpassing the strongest CNN-based baseline CCBANet by 0.73% in DSC and outperforming TransUNet by 11.76% in DSC. On BUSI, it attains an IOU of 78.10% and MIOU of 87.68%, outperforming UNet by 2.82% in IOU and TransUNet by 6.91% in DSC. On COVID-19 CT, it achieves a DSC of 82.51%, surpassing UNet by 4.99% and TransUNet by 7.47%, demonstrating robust performance on irregular lesion morphologies. These results confirm that SCAGC-UNet achieves consistent and robust segmentation performance across three public benchmark datasets spanning distinct imaging modalities, suggesting its potential clinical relevance. Full article

Neuroinvasive free-living amoebae (FLA), particularly Naegleria fowleri and Acanthamoeba spp., are responsible for rare but devastating infections of the central nervous system (CNS). Approximately 480 cases of primary amoebic meningoencephalitis (PAM) and fewer than 200 well-documented cases of Acanthamoeba-associated granulomatous amoebic encephalitis (GAE) have been reported worldwide. Mortality rates frequently exceed 90%. PAM typically develops following exposure to warm freshwater contaminated with N. fowleri and progresses rapidly in otherwise healthy individuals. In contrast, GAE usually follows a more indolent course and occurs predominantly in immunocompromised hosts. Despite their distinct clinical courses, both infections are characterized by CNS invasion, amoeba-mediated tissue destruction, blood–brain barrier (BBB) disruption, and host inflammatory responses. These processes drive neuroinflammation, neuronal injury, and neurological deterioration. Early diagnosis remains challenging because clinical manifestations are nonspecific and disease progression can be either fulminant or initially subtle. Therapeutic management is hindered by poor CNS drug penetration, limited efficacy of currently available therapies, treatment-related toxicity, and the absence of standardized treatment protocols or controlled clinical trials. This narrative review critically synthesizes current evidence on CNS invasion, neuroinflammation, neuropathology, diagnostic challenges, and therapeutic strategies in neuroinvasive FLA infections. It also highlights key translational priorities, including earlier diagnosis, standardized treatment protocols, stronger clinical evidence, and improved CNS-targeted drug delivery. Full article

Myotonic dystrophy type 1 (DM1) is caused by an expansion of CTG repeats in the DMPK gene. In a proportion of patients, the expanded allele contains variant repeats, which have been associated with later disease onset and different clinical presentation, although their full impact remains incompletely defined. We compared sociodemographic, neuromuscular, and multisystem clinical features between DM1 patients with pure CTG expansions (n = 66) and those with variant repeats (n = 9), who formed a consecutive cohort of unrelated index cases evaluated at the age of diagnosis in routine clinical practice. Patients with variant repeats were nine years older at diagnosis than patients with pure repeat expansions (p = 0.025), had more years of formal education (p = 0.024), and showed reduced muscle strength in proximal lower limbs (p = 0.049). No childhood or juvenile forms were observed among patients with variant repeats. Sex, disease duration, and most other clinical parameters, including multisystem involvement, did not differ between groups. The results of our exploratory study support variant repeats as disease modifiers in both age at onset and pattern of muscle involvement, and imply a two-sequential-component hypothesis in DM1 pathogenesis. Full article

Background: Vulvar cancer is a rare gynecologic malignancy comprising 1–3% of all cases. No established standard exists for advanced disease, and treatment is often extrapolated from cervical cancer. Although HER2 overexpression is well defined in breast cancer and recognized across multiple solid tumors, its prevalence and significance in vulvar cancer remain unclear. Recent activity of HER2-directed antibody–drug conjugate Trastuzumab deruxtecan in solid tumors with an objective response rate (ORR) of around 37% highlights the need to better characterize HER2 expression in vulvar cancer. Methods: We performed a systematic search of Medline, Embase, and the Cochrane Library up to May 2025. Eligible studies included ≥10 vulvar cancer cases, predominantly vulvar squamous cell carcinoma (VSCC), excluding vulvar Paget’s disease, with available HER2 assessment by immunohistochemistry and/or in situ hybridization. Two reviewers independently screened the studies. A random-effects model was used to estimate pooled HER2 positivity. Heterogeneity was assessed using Cochrane’s Q and Higgins’s I². Results: Of 506 records, nine retrospective studies including 769 patients with predominantly squamous cell carcinoma histology (98%, n = 752) met inclusion criteria. A total of 50 HER2-positive cases were observed. Median age at diagnosis of vulvar cancer was between 55 and 78, reported in three studies. Molecular profiling was limited. Among three studies with known TP53 status (n = 206), 59% of the tumors expressed TP53 (n = 122), and among two studies with known human papilloma virus (HPV) status (n = 128), 21% (n = 27) were HPV-positive. Six studies used American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 testing guidelines in breast cancer. Pooled HER2-positive expression across ASCO/CAP-based studies was 2% (95% CI: 1%, 3%) and for non-ASCO/CAP-based studies was 21% (95% CI: 2%, 52%). Exploratory pooled estimated proportion of HER2-positive expression was 5% (95% CI: 0.4%, 14%). There was substantial heterogeneity across studies, I² value of 91.1% [95% CI: 85.4%; 94.6%], and no significant publication bias was observed (Egger’s test p = 0.364). This study could not assess prognostic value of HER2 overexpression in VSCC. Conclusions: HER2 positivity in VSCC appears uncommon but it remains to be fully explored. Standardized assessment using contemporary ASCO/CAP breast, endometrial-specific and/or gastric criteria are needed to clarify the prevalence of HER2-positive versus HER2-low/ultralow disease to inform potential use of HER2-targeted therapy. Full article

Background: The financial burden of diagnostic testing for obstructive sleep apnea (OSA) represents a substantial barrier to treatment initiation, with cost-related access disparities disproportionately affecting the low-income and underinsured population. Home sleep testing (HST) offers a cost-effective diagnostic alternative, yet economic patterns across provider types remain unclear. This study assessed whether board-certified sleep medicine provider (BCSMP) status is associated with differences in provider-billed HST charges and evaluated how organizational and payment contexts influence these charges. Methods: A retrospective cross-sectional analysis was conducted using 2019 data from Optum’s de-identified Clinformatics^® Data Mart Database (N = 61,531 adult HST claims). The main exposure was provider status (BCSMP vs. non-BCSMP). The outcome was total provider-requested charge per HST procedure. Generalized Linear Models with a gamma distribution estimated adjusted charge differences, controlling for organizational context, place of service, and payer type. Results: BCSMP encounters had significantly lower adjusted mean HST charges than non-BCSMPs (mean difference: −$78.04; 95% CI: −$89.06 to −$67.02; p < 0.001). Individual practitioners charged $168.48 less than hospital-affiliated providers, while group practices and other facilities charged more (all p < 0.001). Fee-for-service arrangements were associated with lower charges than commercial and Medicare Advantage plans (p < 0.001). Conclusions: Board-certified sleep medicine providers and individual practice settings were associated with lower billed charges for home sleep testing; however, these findings do not necessarily reflect actual cost reduction. To translate these baseline charge differences into equitable clinical protocols and healthcare policies, future research must analyze negotiated reimbursement rates, billing structures, and practice environments to determine how these cost parameters impact the overall cost of an OSA diagnosis. Full article

Background: Genetic testing is increasingly part of the diagnostic pathway of congenital hearing loss (CHL), clarifying etiology and supporting clinical management. However, its psychosocial impact, especially differences between syndromic and non-syndromic conditions, remains underexplored. Objectives: This study evaluated the differential psychological impact of genetic diagnosis in syndromic versus non-syndromic pediatric patients, its relationship with clinical and rehabilitative variables, and the role of post-diagnostic psychological assessment. Methods: A cross-sectional post-diagnosis survey was conducted in families of children with genetically confirmed syndromic (Usher syndrome, n = 21) and non-syndromic (GJB2-related, n = 21) CHL; a total of 37 families responded. Parental empowerment was assessed using an Italian translated version of the Genetic Counseling Outcome Scale (GCOS-24). In an exploratory analysis, GCOS-24 items were grouped into three author-derived domains (understanding/awareness, emotional experience, and informational support) based on semantic content, not validated psychometrically. Results: No significant differences in GCOS-24 scores emerged between groups, nor in relation to clinical variables like hearing loss severity, auditory outcomes, or rehabilitative interventions. Genetic diagnosis occurred later in the syndromic group. Qualitative observations suggested parental empowerment varied with timing of diagnosis, clarity of information, and therapeutic alliance quality. Conclusions: Overall, these results highlight the importance of integrating psychological support and structured communication into clinical pathways to support families and patients in understanding and adapting to the diagnosis over time. Further longitudinal studies are needed to clarify the evolving psychosocial impact of genetic diagnosis in CHL. Full article

Clinical prediction rules often suffer from a translation gap, balancing high-dimensional statistical accuracy against practical bedside interpretability. This study presents the Surgical Complication Risk Index (S-CRI), an explainable, data-decoupled risk-stratification framework designed to predict post-operative complications using multi-center electronic health registry records (N = 19,965). To ensure strict validation integrity, data partitioning (70% development, n = 13,975; 30% independent holdout testing, n = 5990) was executed before any engineering or risk-tier group isolation. A parsimonious multivariate logistic regression model was fitted within the development cohort, utilizing five predictors: length of stay (LOS) accrued up to the morning of assessment, two institutional categorical groupings, and two historical entry-diagnosis empirical risk tiers. To bridge the translational gap, all fractional regression coefficients were scaled by the baseline anchor and rounded to the nearest whole integer, yielding a simple bedside scorecard where 1 point = 1 inpatient day. On the completely blinded independent holdout cohort, the whole-integer S-CRI demonstrated robust discriminative performance with an Area Under the Receiver Operating Characteristic curve (AUC) of 0.8741 (95% CI: 0.864–0.884) and a Precision–Recall AUC of 0.5785. Setting a baseline operational threshold ≥ 0 yielded an accuracy of 88.18%, a specificity of 96.43%, and a sensitivity of 35.43%, while an optimized integer screening cutoff score of ≥−4 maximized screening capacity (sensitivity: 63.95%; specificity: 91.68%). By enforcing strict temporal landmark constraints to eliminate reverse causality and removing all out-of-sample data leakage, the S-CRI provides an objective, transparent, and interpretable clinical decision support mechanism for early inpatient risk stratification, designed as a supplementary clinical decision-support aid, rather than as a definitive diagnostic replacement for independent clinical judgment. Full article

Background: Cracked teeth may present with variable and atypical symptoms, sometimes mimicking non-odontogenic orofacial pain conditions, making diagnosis challenging, particularly when cracks appear limited to enamel. Case presentation: A 36-year-old woman presented with intermittent pain in a mandibular molar radiating to the ipsilateral temporal region. Clinical examination identified a crack line on the lingual surface of the mandibular first molar. Pulp sensibility testing (cold test and electric pulp test), occlusal loading tests, and cone-beam computed tomography (CBCT) were performed. CBCT was used primarily to exclude vertical root fracture and periapical pathology, and no radiographic abnormalities were identified. Differential diagnosis was conducted using structured diagnostic frameworks, including the International Classification of Orofacial Pain and the International Classification of Headache Disorders (3rd edition). Diagnostic local anaesthesia eliminated both biting pain and referred pain, supporting an odontogenic source. Collectively, the findings suggested that the enamel crack was the most likely source of odontogenic pain, although a definitive causal relationship could not be established. Because pulp sensibility remained normal, conservative management was selected. Crack sealing with a methyl methacrylate-based adhesive resin resulted in complete symptom resolution that was maintained throughout a 3-year follow-up period without the need for root canal treatment. Conclusions: Although the diagnosis remained probabilistic, the structured diagnostic approach, together with the favourable clinical response after crack sealing, supported the enamel crack as the most likely source of odontogenic pain. Full article

Background/Objectives: Catatonia is a severe transdiagnostic neuropsychiatric syndrome for which accessible biological correlates remain insufficiently characterized. This study explored whether complete blood count (CBC)-derived inflammatory indices differ between psychiatric inpatients with catatonia and matched psychiatric controls without catatonia. Methods: This retrospective matched case–control study included 46 patients with catatonia and 46 psychiatric controls selected from the same clinical setting and study period. Controls were frequency-matched by sex, age distribution, and broad psychiatric diagnosis. CBC parameters obtained within the first 24 h of admission were used to calculate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune–inflammation index (SII), and systemic inflammation response index (SIRI). Group comparisons, adjusted log–linear regression models, Spearman correlations with documented catatonic signs, and exploratory receiver operating characteristic analyses were performed. Results: SII was higher in patients with catatonia than in controls and remained significant after Bonferroni correction (median 584 [IQR 468–823] vs. 476 [IQR 339–619], Bonferroni-adjusted p = 0.032). In secondary adjusted models, catatonia was associated with higher SII and SIRI after adjustment for body mass index, smoking, antipsychotic exposure, diabetes mellitus, and arterial hypertension. No inflammatory index correlated significantly with the number of documented catatonic signs after correction. Exploratory discrimination was poor to fair, with SII showing the highest AUC (0.665, 95% CI 0.550–0.773). Conclusions: CBC-derived indices, particularly SII, may reflect systemic inflammatory or physiological stress burden in catatonia, but they should be interpreted as exploratory markers rather than diagnostic biomarkers. Full article

Laryngeal paralysis is an uncommon but potentially life-threatening condition in cats due to upper airway obstruction. Surgical arytenoid lateralization is generally considered the treatment of choice; however, complication rates in cats appear higher than in dogs, and alternative techniques may be desirable, particularly in emergency situations. The aim of this study was to evaluate the clinical outcome of transoral partial arytenoidectomy for the treatment of laryngeal paralysis in cats. Eight client-owned cats diagnosed with laryngeal paralysis underwent transoral partial arytenoidectomy. Diagnosis was confirmed by direct visualization of laryngeal motion under light anesthesia. Clinical signs, perioperative findings, complications, and follow-up outcomes were retrospectively reviewed. All cats presented with severe dyspnea and inspiratory stridor and failed to respond to medical stabilization, thereby requiring emergency surgical intervention. No intraoperative complications occurred. No catastrophic or major complications were recorded. All patients showed immediate improvement in respiratory function, with resolution of dyspnea and stridor maintained throughout the follow-up period. Transoral partial arytenoidectomy appears to be a simple, minimally invasive, and effective surgical option for the management of laryngeal paralysis in cats, particularly in emergency settings. Larger prospective studies are warranted to confirm long-term safety and efficacy. Full article

Background/Objectives: The clinical utility of renal ultrasound after pediatric urinary tract infection (UTI) remains controversial, particularly because not all ultrasonographic abnormalities have the same prognostic significance. This study aimed to determine whether nephrourological malformations identify the phenotype associated with greater subsequent clinical burden among children hospitalized with presumed UTI and interpretable renal ultrasound findings, and to differentiate this phenotype from non-malformative ultrasound abnormalities. Methods: A retrospective single-center hospital-based cohort study was conducted in children aged 2 months to 17 years hospitalized with a clinical diagnosis of UTI at a general hospital of the Mexican Social Security Institute between 2020 and 2025. The cohort included both microbiologically confirmed UTI cases and probable clinical/microbiologically unconfirmed UTI cases. Of 182 registered patients, 130 with interpretable renal ultrasound were included. The primary exposure was the presence of adjudicated nephrourological malformation. As a secondary exposure, within the subgroup without malformation, abnormal non-malformative ultrasound findings were compared with normal ultrasound findings. Outcomes included outpatient follow-up, subspecialty referral, and hospital readmission. Crude associations were expressed as relative risks (RR), and adjusted analyses were estimated using modified Poisson regression with HC3 robust errors. Results: Twenty-nine of 130 patients (22.31%) were classified as having nephrourological malformations, and 31 (23.85%) had abnormal non-malformative ultrasound findings. Malformations were associated with higher outpatient follow-up (79.31% vs. 44.55%; RR 1.78, 95% CI 1.34–2.37), greater subspecialty referral (79.31% vs. 49.50%; RR 1.60, 95% CI 1.22–2.10), and increased readmission (44.83% vs. 13.86%; RR 3.23, 95% CI 1.72–6.08). In adjusted models, malformations remained associated with follow-up (aRR 1.72, 95% CI 1.25–2.37), referral (aRR 1.59, 95% CI 1.17–2.16), and readmission (aRR 3.38, 95% CI 1.58–7.23). In contrast, abnormal non-malformative ultrasound findings showed no significant adjusted associations. Microbiologically confirmed UTI was present in 47/130 patients (36.15%), and malformations were more frequent in this subgroup than in probable/non-confirmed clinical UTI (34.04% vs. 15.66%; p = 0.027). Conclusions: In this single-center hospital-based cohort, subsequent clinical burden was concentrated in the nephrourological malformation phenotype rather than in the broader category of “abnormal ultrasound”. These findings suggest that renal ultrasound may serve as a useful prognostic stratification tool beyond its role as a nonspecific detector of abnormalities following pediatric UTI. Given the observational design, these associations should be confirmed in larger prospective studies. Full article