Search Results (3,667)

Proteomics has emerged as a powerful tool for advancing our understanding of brain disorders by enabling large-scale characterization of protein expression, post-translational modifications, and interaction networks. Neurological conditions are often characterized by complex and dynamic molecular changes that are not fully captured by traditional diagnostic approaches. Proteomic technologies, particularly mass spectrometry-based and affinity-based methods, offer the ability to identify disease-specific protein signatures and elucidate underlying pathophysiological mechanisms, including neurodegeneration, neurodevelopment and neuroinflammation and alterations happening to the extracellular matrix and body fluid homeostasis. In recent years, artificial intelligence has emerged as a powerful tool to proteomics, enabling improved analysis of complex biological datasets. This integration has significantly enhanced the discovery of biomarkers for early diagnosis, disease stratification, and monitoring of therapeutic responses. Thus, cerebrospinal fluid and blood-based proteomic analyses have revealed promising candidates for neurological diseases. This review summarizes current advances in proteomics across a range of brain disorders, highlighting key molecular pathways, biomarker discovery efforts, and evolving clinical applications. Furthermore, it outlines future directions, including the application of machine learning for improved biomarker identification and precision medicine. Full article

Background: Giant African Land Snails originate from Africa. Although these snails are becoming more popular as exotic pets in Europe, there is a lack of comprehensive information about their diseases and how to treat them. Reported medical issues included failures in husbandry and feeding (often leading to aestivation, calcium deficiency or renal disease), trauma, poison, prolapse, and ecto- and endoparasites, as well as bacterial and fungal infections. Although their reproductive system has been well studied, dystocia has not yet been reported in terrestrial snail species. Patient Presentation: Two cases of dystocia in pet Giant African Land Snails are presented. Case 1 involved a 5.5-year-old Lissachatina fulica with esophageal prolapse and severe chronic dystocia, as indicated by radiographic and computed tomographic findings, ultimately leading to euthanasia. Case 2 involved a 3-year-old Lissachatina albopicta also affected by dystocia, with computed tomography again showing findings consistent with the diagnosis, but subsequently laying most of the pathological clutch with supportive, conservative treatment. Conclusion: Dystocia in Giant African Land Snails is a significant health concern that can lead to severe complications and mortality. Early diagnosis using imaging techniques is crucial for identifying reproductive issues and determining appropriate treatment strategies. However, because these terrestrial snails have an open circulatory system and vascular anatomy remains incompletely characterized, the reproductive tract remains difficult to access surgically. Furthermore, there is currently insufficient evidence to support hormonal induction of oviposition as a therapeutic approach for egg retention in this species. Consequently, conservative management remains the primary supportive therapy. Full article

In forensic toxicology, the analysis of blood and urine is regarded as the so-called “gold standard.” However, when forensic experts are confronted with advanced postmortem changes, it becomes necessary to secure and examine alternative matrices. Suitable specimens in cases of advanced putrefactive decomposition may include: skin appendages (hair and nails), bones, bone marrow, cartilage tissue, teeth, antemortem fingerprints, cerebrospinal fluid, vitreous humor, breast milk, meconium, placenta and umbilical cord tissue, oral fluid, sweat, and other evidentiary materials. These tissues, owing to their structure and anatomical location, are more resistant to putrefactive decomposition than body fluids and soft tissues. However, several limitations complicate the reliable analysis of these matrices. These include incomplete drug incorporation, depending on physicochemical properties, the inability to correlate analyte concentrations with pharmacological effects, low xenobiotic levels, and the need for highly sensitive analytical methods. Collectively, these factors contribute to interpretative challenges during forensic expert evaluation and reporting. To address key forensic questions, epigenetic variability analyses (forensic epigenetics) may also be employed, particularly when standard DNA profiling is uninformative. DNA methylation patterns in specific tissues and in individual subjects can be used, among other purposes, to identify the tissue of origin of a human biological trace, to differentiate monozygotic twins, and to predict the age of an unidentified trace donor. Over the past few years, this approach has gained increasing importance; in the context of forensic trace analysis, it offers both advantages and limitations. The aim of this study is to present current scientific evidence regarding the use of alternative biological matrices as potential sources of information of forensic relevance. The paper discusses the characteristics of individual biological materials, with particular emphasis on their analytical properties, potential applications, limitations, and possible advantages in forensic toxicological investigations. Furthermore, the key aspects associated with the application of epigenetic methods in forensic science are presented, with particular focus on their role in individual identification and the reconstruction of circumstances surrounding forensic events. Alternative biological matrices and modern analytical approaches may constitute valuable complementary tools to conventional evidentiary materials used in forensic medicine and criminalistics. Due to their physicochemical properties, stability, and ability to preserve specific biological information, these matrices may provide significant data that enable substance identification, assessment of exposure to psychoactive compounds, reconstruction of event circumstances, and support for identification procedures. However, their application requires consideration of analytical limitations, the specific characteristics of the examined matrix, and the necessity for standardization and validation of diagnostic procedures Full article

Background: Accurate fracture interpretation on plain radiographs is critical for both trauma care and medico-legal decision-making, where reproducibility is as important as point accuracy. Although vision language models (VLMs) have shown promising diagnostic performance, their temporal stability in forensic radiography remains unclear. Methods: We analyzed 300 forensic radiographs (150 fracture-positive, 150 fracture-negative) from six long bones, independently evaluated by three emergency medicine physicians, three forensic medicine physicians, and three VLMs (ChatGPT-5.2, Gemini 3 Pro, Claude Sonnet 4.5) using an identical task format. Assessments included fracture presence and structured fracture subtype description (bone, morphology, displacement). VLM evaluations were repeated after one month under identical conditions. Results: Physician accuracy ranged from 79.7% to 98.7%. Emergency physicians reached the higher median sensitivity (92.0% against 76.7%), while specificity among the forensic readers was the more tightly clustered (median 92.0%, range 87.3–100.0%). ChatGPT-5.2 was the most accurate model (83.0%; sensitivity 70.0%, specificity 96.0%), followed by Gemini 3 Pro (77.7%), whereas Claude Sonnet 4.5 reached only 46.3% because of an extreme false-positive tendency (specificity 11.3%). Over one month, accuracy changed by −5.2, −4.1 and +8.6 percentage points, but these net figures concealed considerable case-level movement: within-model agreement ranged from near chance to substantial (mean Cohen κ 0.131 to 0.622), and the F1-score of Claude Sonnet 4.5 fell by 13.1 points despite its higher accuracy. Subtype descriptions were frequently correct once a fracture had been detected, but end-to-end subtype accuracy remained low. Conclusions: Current vision language models demonstrate encouraging diagnostic performance; however, their temporal reproducibility remains inadequate for independent medico-legal fracture interpretation. These findings highlight that reproducibility, in addition to diagnostic accuracy, should be considered a core benchmark when evaluating VLMs for high-stakes clinical and forensic use. Larger multicenter studies using independent external datasets are needed before forensic application is considered. Full article

Soft tissue sarcomas (STSs) are a heterogeneous group of rare mesenchymal malignancies with overlapping morphological and immunohistochemical features, often making definitive diagnosis challenging. Recent advances in next-generation sequencing (NGS) have enabled the identification of recurrent molecular alterations that contribute to tumor classification, prognostic stratification, and precision oncology approaches. This retrospective study aimed to evaluate the diagnostic and clinical impact of molecular profiling in pediatric soft tissue sarcomas using the Oncomine Childhood Cancer Research Assay (OCCRA) panel. Fifty-five frozen tumor samples representing 24 distinct soft tissue sarcoma subtypes were obtained from the Pediatric Oncology Institute -IOP/GRAACC/UNIFESP Biobank (B-053). Molecular analysis was performed using NGS to identify gene fusions, single nucleotide variants (SNVs), copy number variations (CNVs), and insertions/deletions (InDels). Clinically relevant molecular alterations were identified in 70% (37/55) of cases, including 18 fusion transcripts, 13 SNVs, 8 CNVs, and 6 InDels. Recurrent and diagnostically relevant alterations included BCOR::CCNB3, ASPSCR1::TFE3, NFR1::BRAF, FUS::DDIT3, EML4::NTRK3, ETV6::NTRK3, CIC::DUX4, NAB2::STAT6 and SS18::SSX1/2 fusions, as well as amplifications involving PDGFRA, FGFR1, GLI1, CDK4, ERBB3, and KIT. Pathogenic variants affecting genes involved in tumor suppression and chromatin remodeling, including TP53, NF1, DICER1, SMARCA4, PTEN, and PIK3CA, were also detected. Importantly, molecular profiling had significant diagnostic impact in several histologically ambiguous tumors, enabling molecular reclassification and refinement of previously inconclusive or inaccurate pathological diagnoses. In multiple cases, NGS transformed descriptive histopathological interpretations into genetically defined sarcoma entities, including NTRK-rearranged spindle cell neoplasms, CIC-rearranged sarcomas, synovial sarcoma, low-grade fibromyxoid sarcoma, and clear cell sarcoma. Furthermore, the identification of actionable alterations highlighted potential opportunities for targeted therapies and precision medicine approaches. Our findings demonstrate that comprehensive molecular profiling significantly enhances diagnostic accuracy in pediatric soft tissue sarcomas, particularly in morphologically challenging cases. The integration of NGS into routine sarcoma diagnostics enables biologically informed tumor classification and supports personalized therapeutic strategies. Full article

Acute deep vein thrombosis (DVT) continues to represent a significant global contributor to morbidity and mortality. Although multiple international societies have published evidence-based clinical practice guidelines, important differences persist. This structured narrative review compares contemporary international guidance to identify areas of consensus, methodological divergence, evidence gaps, and priorities for future research. Recommendations were compared across diagnostic evaluation, anticoagulant selection, treatment duration, outpatient management, compression therapy, endovascular intervention, and special populations. Broad agreement was identified regarding clinical pretest probability assessment, D-dimer testing, compression ultrasonography, and direct oral anticoagulants as first-line therapy for most eligible patients with acute DVT. Clinically important differences remain, however, in the management of isolated distal DVT, anticoagulation duration, catheter-directed interventions, compression therapy, and selected high-risk populations. These discrepancies primarily reflect differences in publication timing, methodological frameworks, interpretation of emerging evidence, and healthcare-system context rather than fundamentally conflicting evidence. Contemporary international guidance therefore demonstrates substantial convergence on the core principles of acute DVT management while continuing to differ in areas supported by limited or evolving evidence. Future harmonization will require high-quality randomized trials, broader international collaboration, and the integration of precision medicine, validated risk-prediction models, biomarkers, and emerging anticoagulant strategies into guideline development. Full article

Both genetics and the environment affect the phenotypes of polycystic kidney diseases (PKD), such as autosomal dominant (AD) PKD, autosomal recessive (AR) PKD and nephronophthisis (NPH). Variable phenotypes, pleiotropy, divergent severity and progression, even in family members who inherited the same disease-causing mutation(s), signal the involvement of networked genes and modifiers. Several PKD-linked genes function in development and renal tubule morphogenesis. Cystic renal tissues feature metabolic remodeling, functional reprogramming and dysregulation of several shared factors and pathways. ADPKD, ARPKD and NPH partially phenocopy each other. Understanding the developmental arc of cystic kidney disease and its complex phenotypes would improve diagnostics and help develop effective personalized treatments. However, this is challenging to study in vertebrate systems due to genetic redundancy, functional overlap, and a dearth of genetic tools. Underused in this context, Drosophila melanogaster offers high genomic and pathway conservation, a wealth of genetic tools, and rapid generation times, making it a reliable and sustainable model for mechanistic, genome-wide, and precision medicine studies. Here, we surveyed ADPKD, ARPKD, and NPH, compared renal and extrarenal phenotypes, and examined the network of shared and unique contributors, their healthy and diseased functions and conservation from the perspective of mechanistic whole-animal modeling. Full article

Background: Traditional osteopathic manipulative medicine (OMM) instruction relies on laboratory sessions constrained by scheduling, faculty availability, and practice partner variability. Virtual reality (VR) may address these limitations by providing on-demand access to standardized training scenarios. This pilot feasibility and acceptability study evaluated first-year osteopathic medical students’ motivational responses and perceptions of a novel VR training module focused on thoracic spine assessment techniques. Methods: This pilot single-arm observational study enrolled 45 first-year students at the New York Institute of Technology College of Osteopathic Medicine to assess the feasibility and acceptability of VR-based OMM instruction. A VR training module developed using Unity 3D and deployed on Oculus Quest headsets included 40 interactive assessment items covering thoracic diagnostic techniques. Participants received one-week access to the program then completed the Reduced Instructional Materials Motivation Survey (RIMMS) based on the Attention, Relevance, Confidence, and Satisfaction (ARCS) model and a custom 10-item feedback survey. Session duration and assessment scores were automatically recorded. Descriptive statistics and Pearson correlation analysis were performed. Results: The Relevance domain achieved the highest RIMMS composite mean (3.98), while Attention demonstrated the greatest opportunity for enhancement (3.49). The overall RIMMS composite score was 3.81, indicating favorable motivational reception. Feedback survey results showed that 89.2 percent of participants endorsed the VR experience as educationally positive, and 81.1 percent supported expansion to additional OMM procedures. Performance analysis revealed minimal correlation between session duration and assessment scores (R² = 0.0169). Conclusions: First-year osteopathic medical students demonstrated positive motivational responses and favorable perceptions toward VR-based OMM training. Based on student perception and feasibility, these findings suggest VR is well-received and perceived by students as a potentially viable supplement to traditional OMM instruction, though attention-capturing elements and interface usability warrant refinement. This pilot study did not measure learning outcomes or skill acquisition. Full article

Glioblastoma multiforme (GBM) is the most common brain tumor in the adult population, and it is characterized by poor prognosis; thus, new treatment strategies are strongly needed. Precision medicine is a rapidly growing field in oncology that identifies specific molecular features of tumor cells and allows theranostic strategies (combining diagnosis and therapy). In nuclear medicine, prostate-specific membrane antigen (PSMA) represents an interesting molecular target in theranostics, considering its involvement in the neoangiogenesis of many kinds of tumors, including GBM. In this narrative review, we performed a web-based literature search to explore the current evidence regarding PSMA-targeted nuclear medicine theranostics in GBM, highlighting diagnostic applications, therapeutic potential, and future clinical perspectives. Full article

Anatomical pathology is a fundamental component of diagnostic medicine, relying on the combined expertise of physicians and technical scientific professionals to ensure accurate, reliable, and reproducible results. In veterinary medicine, the quality of pathological diagnosis directly influences clinical decision-making, treatment outcomes, and overall health management. Veterinary pathology, in particular, plays a crucial role in contemporary clinical practice. This review aims to highlight the essential role of pathology technicians within the veterinary medicine field. It explores their contributions across multiple domains, including biosafety, diagnostic workflows, quality control, research support, academic training and the challenges associated with veterinary pathology. In addition, emerging areas such as molecular pathology, digital pathology, and biobanking are discussed to illustrate the increasing scope of technical responsibilities. Full article

Microbiota has emerged as a potential regulator of female reproductive health through immunological, metabolic, and endocrine networks. Growing evidence suggests that the composition and stability of the vaginal, uterine, and gut microbiota are associated with fertility outcomes. Disruptions in reproductive tract homeostasis have been linked to infertility, implantation failure, pregnancy loss, and diminished success in assisted reproductive technologies. Beyond local interactions, maternal gut microbiota may influence systemic immunity and metabolic pathways related to vaginal and endometrial microbiota. While these findings highlight the microbiome-based signatures’ potential as predictive and prognostic biomarkers, their clinical applicability remains unconfirmed. Evidence is limited by small cohort sizes, methodological and analytical heterogeneity, and lack of standardization, limiting clinical translation. This narrative review summarizes the current knowledge regarding the microbiome’s role in female reproductive health, highlighting its potential impact on pathophysiology, diagnostics, and therapeutic strategies. While this approach allows for a broad conceptual overview, we explicitly note that it is not systematic. As a result, this review is limited by the absence of a standardized search protocol, which may introduce selection bias. Finally, we review advances in microbial engineering and synthetic biology, highlighting engineered living biotherapeutics as promising strategies to improve microbiome-based reproductive medicine. Full article

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of clinically aggressive mature T-cell and natural killer (NK)-cell neoplasms that account for approximately 10–15% of all non-Hodgkin lymphomas in Western countries . The most common subtypes include extranodal NK/T-cell lymphoma (ENKTL), nodal T-follicular helper cell lymphomas, peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma (ALK-positive and ALK-negative), and T-cell lymphoblastic lymphoma. Non-coding RNAs (ncRNAs) constitute the majority of the human transcriptome and play critical roles in regulating gene expression, cellular proliferation, differentiation, migration, and apoptosis. Among these, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have emerged as key regulators of lymphomagenesis and disease progression in PTCLs. These molecules modulate diverse oncogenic pathways through chromatin remodeling, transcriptional regulation, competing endogenous RNA activity, and interactions with RNA-binding proteins, thereby influencing proliferation, immune evasion, treatment resistance, and clinical outcomes. Representative examples include the lncRNA TCLlnc1, which promotes PTCL progression through activation of transforming growth factor-β (TGF-β) signaling, and the circRNAs circKIF4A, circADARB1, and circ-LAMP1, which regulate miRNA-dependent signaling networks involving PDK1/BCL11A, STAT3, and DDR2, respectively. In this review, we summarize the current understanding of the biological and clinical roles of lncRNAs and circRNAs in PTCL and related T-cell and NK-cell neoplasms and highlight their potential as diagnostic and prognostic biomarkers as well as therapeutic targets. We also discuss recent advances and future directions for integrating ncRNA-based approaches into precision medicine for T-cell lymphoma. Full article

Canonical signal peptides (SPs) are short N-terminal sequences that direct nascent proteins into the secretory pathway, but their role extends far beyond protein targeting. Advances in sequencing and computational tools have enabled their systematic identification across proteomes, highlighting SPs as critical regulators of protein biogenesis, including endoplasmic reticulum (ER) targeting, translocation, folding, and proteostasis. Clinically, mutations affecting SP function underlie a distinct group of human disorders, while SP-derived fragments are emerging as diagnostic biomarkers and therapeutic targets. In biotechnology, SPs are engineered to enhance recombinant protein production and serve as molecular tags for intracellular delivery. Together, these developments position SPs at the intersection of fundamental cell biology, medicine, and biotechnology. While this review primarily focuses on canonical SPs, it also considers selected non-canonical targeting and topogenic sequences whose dysfunction contributes to protein misfolding, impaired ER translocation, disrupted degradation pathways, and altered intracellular trafficking in neurodegenerative diseases. Aberrations involving both conventional SPs and alternative targeting/topogenic elements contribute to pathological protein aggregation, a hallmark of major neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington Disease (HD), prion diseases, and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD); in multiple sclerosis (MS) is primarily an inflammatory demyelinating disease, where abnormal protein exposure, potentially linked to misprocessed SPs, can activate immune responses. By synthesizing current knowledge, the review explores how alterations in targeting determinants influence key proteostasis pathways, acting as upstream modulators of disease-relevant molecular cascades. It further discusses the emerging concept that SP-derived fragments may participate in intercellular communication, adding an additional layer of regulatory complexity. Full article

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide despite substantial advances in screening, surgical techniques, systemic therapies, and multidisciplinary care. The increasing implementation of precision oncology has fundamentally transformed CRC management by enabling molecularly guided therapeutic strategies based on tumor-specific genetic alterations. In recent years, the molecular landscape of CRC has expanded considerably beyond traditional histopathological classification, incorporating a growing number of clinically actionable biomarkers with prognostic, predictive, and therapeutic significance. This review provides a comprehensive and up-to-date overview of the genetic landscape of CRC, focusing on established biomarkers currently integrated into clinical practice, including microsatellite instability/mismatch repair deficiency (MSI/dMMR), KRAS, NRAS, BRAF, HER2, and NTRK alterations. In addition, emerging biomarkers such as tumor mutational burden (TMB), POLE/POLD1 mutations, circulating tumor DNA (ctDNA), DNA damage repair (DDR) alterations, transcriptomic signatures, and artificial intelligence-based molecular prediction models are critically discussed. Particular emphasis is placed on their biological significance, diagnostic methodologies, prognostic and predictive value, and potential role in treatment selection. A structured, database-informed narrative review identified 140 relevant publications, primarily published between January 2020 and June 2026, supplemented by earlier seminal studies and major clinical guidelines. Based on the available evidence, we propose a Clinical Actionability Framework for CRC, categorizing biomarkers into three hierarchical tiers according to their level of clinical validation and therapeutic relevance: established standard-of-care biomarkers, emerging clinical biomarkers, and future precision oncology biomarkers. Collectively, current evidence supports a progressive transition from single-gene testing toward integrated multi-omics precision medicine. Advances in comprehensive genomic profiling, liquid biopsy technologies, transcriptomics, radiogenomics, and artificial intelligence are expected to further refine patient stratification, optimize therapeutic decision-making, and facilitate the development of adaptive precision oncology models. Understanding the evolving genetic landscape of CRC is therefore essential for maximizing treatment efficacy and improving patient outcomes in the era of personalized cancer care. Full article

We present a microfluidic platform for real-time, label-free cytometry and sorting of single cells based on intrinsic biophysical properties. The system integrates impedance-based electrokinetic sensing with a constriction microchannel architecture to induce controlled deformation during cell transit. Electrical signals captured via lock-in amplification are processed through a parallel software pipeline incorporating deep learning algorithms for event detection and feature extraction. A biomechanical model enables conversion of raw signal features into cell size and whole-cell elasticity, validated against imaging measurements. Experimental results demonstrate accurate phenotyping and sorting of live and dead MCF-7 cells, achieving sorting accuracy of 84%. This approach offers a cost-effective and scalable solution for biophysical analysis, with potential applications in liquid biopsy, disease diagnostics, and personalized medicine. Full article