Antimicrobial resistance (AMR) constrains effective treatment and carries implications for infection control, surveillance, and public health. The World Health Organization (WHO) priority bacterial pathogen framework has intensified the need for diagnostic innovation by redefining research priorities around organisms combining high disease burden with complex resistance profiles. Molecular diagnostics have accordingly moved beyond culture-based workflows, integrating rapid pathogen identification, resistance-marker detection, genomic surveillance, and clinical decision support. The present study conducted a bibliometric mapping of the literature on WHO priority pathogens. Rather than addressing resistance at a general level or a single pathogen or technology, it integrates priority pathogens, molecular platforms, and resistance markers within a single framework, tracing their joint thematic and temporal evolution along an explicit pathogen-platform-marker axis. Scopus-indexed articles and reviews (2000-2025) were retrieved, yielding 1746 publications after screening adapted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Analyses used Bibliometrix/Biblioshiny, R, and VOSviewer. The literature expanded markedly after 2018, led by China and the United States. Methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis, Enterococcus faecium, and the Enterobacterales-carbapenemase axis constituted the principal thematic cores, whereas conventional polymerase chain reaction (PCR)/nucleic acid amplification testing (NAAT) and whole-genome sequencing were the dominant platforms. Overall, the field has evolved from pathogen detection into an AMR-centered translational domain encompassing resistance prediction, genomic epidemiology, surveillance, and clinical decision support. Diagnostic development, stewardship, and surveillance depend on hybrid workflows coupling rapid marker-targeted assays with genome-based characterization, delivering actionable resistance within clinically meaningful timeframes, and extending coverage to underrepresented pathogens and platforms.
Journal of forensic and legal medicinePriyanshi Gangwal, Siva Sai Kumar Pulagura, Vikas Meshram, Rohit Singh Jaggi, Sudeep Khera
Hypertrophic obstructive cardiomyopathy (HOCM) is one of the common causes of sudden cardiac death which can be associated with pulmonary vascular remodelling changes also known as Pulmonary Arteriopathy (PA). Pulmonary Arteriopathy (PA) is a condition affecting the pulmonary arteries, characterised by a range of proliferative and obstructive vascular lesions that ultimately result in lumen obstruction. It may manifest under diverse settings, encompassing both acquired and congenital disorders. We present a case of a 52-year male with no previous known history of illness or disease, who was brought to the Emergency department and was pronounced dead upon arrival. During the autopsy, the heart exhibited left ventricular thickness (3 cm thick) and the interventricular septum thickness (2.5 cm thick). Histopathological examination revealed localised myocardial disarray, muscle fibre hypertrophy, and nuclear enlargement, indicative of left heart disease characterised by left ventricular hypertrophy. The histopathological examination of the both lungs revealed that the blood vessels exhibited thickened walls, characterised by medial wall hypertrophy, manifesting as muscularization suggestive of Grade 2 Pulmonary Arteriopathy (PA). This case examines the pathophysiological mechanisms connecting the characteristics of cardiomyopathy, pulmonary arterial hypertension, and pulmonary arteriopathy, thereby emphasising the significance of pulmonary vascular alterations as a consequence of HOCM but also as a sign of disease progression. Other causes of pulmonary arteriopathy along with advanced ageing should be ruled out in such cases.
BACKGROUND: Whole slide imaging (WSI) has emerged as a key component of digital pathology, enabling remote diagnostics and standardized evaluation. However, its diagnostic concordance in thyroid cytopathology, particularly under real-world conditions, remains insufficiently validated. METHODS: In this retrospective pilot study, thirteen thyroid cases were evaluated using both conventional light microscopy and WSI. One pathologist performed glass slide evaluation, while two independent pathologists assessed the corresponding digital slides remotely. All evaluations were conducted in a blinded manner. Diagnostic agreement was analyzed using percentage concordance and Cohen's kappa coefficient. RESULTS: The overall concordance rate between conventional microscopy and WSI was 69.2%. Cohen's kappa values ranged from 0.58 to 0.63, indicating moderate to substantial agreement. Full concordance was observed in 7 cases, predominantly among malignant diagnoses. Partial concordance occurred in 5 cases, mainly involving borderline categories. Complete discordance was identified in 1 case, exclusively within an indeterminate cytological category. No clinically significant misclassification between benign and malignant diagnoses was observed. CONCLUSION: WSI demonstrated moderate diagnostic agreement with conventional microscopy in well-defined thyroid cytopathology categories. However, variability remains more pronounced in indeterminate cases, reflecting inherent diagnostic challenges. These findings support the preliminary feasibility of WSI in real-world and remote diagnostic workflows, although larger, multicenter studies are required to confirm these results.
European radiology experimentalDominic Gascho, Marco Palmesino, Michael Josef Thali, Edda Emanuela Guareschi
Postmortem imaging has become an integral component of modern forensic pathology, with postmortem computed tomography (PMCT) and magnetic resonance (PMMR) imaging now routinely supplementing or, in selected cases, partially replacing conventional autopsy. Despite these advances, postmortem imaging remains predominantly static, capturing anatomy and injuries at a single point in time after death. In contrast, clinical radiology has increasingly embraced four-dimensional (4D) imaging approaches that incorporate time as a diagnostic dimension, enabling the assessment of motion, functional change, and dynamic processes. This narrative review with a conceptual perspective explores whether and how 4D concepts can be meaningfully translated into postmortem forensic imaging. By reviewing simulated motion models, multiphase PMCT angiography, ventilated PMCT, serial documentation of postmortem biological and physical processes, fracture mechanics research, and PMMR spectroscopy, it can be argued that time is already an implicit diagnostic dimension in forensic radiology. Although true real-time 4D imaging of the deceased remains technically limited, existing studies demonstrate that temporal reconstruction through controlled simulation and serial acquisition is feasible and forensically relevant. Embracing 4D thinking may allow postmortem imaging to evolve from static documentation toward a more process-oriented tool for reconstructing events and mechanisms leading to death. KEY POINTS: Question Can postmortem imaging provide time-related information that is already present after death? Findings 4D PMMCT and PMMR introduce time as an explicit element, allowing postmortem imaging to capture dynamic and evolving processes. Relevance statement This review highlights the emerging role of time-resolved ("4D") approaches in postmortem imaging, demonstrating how integrating temporal information can enhance reconstruction of injury mechanisms, postmortem processes, and medicolegal interpretation, thereby expanding forensic radiology beyond static documentation toward process-oriented forensic investigation.
Acta neuropathologicaCeleste Laureyssen, Dietmar Rudolf Thal, Kristel Sleegers
Alzheimer's disease (AD) and overlapping pathologies represent a growing worldwide health concern. With the first disease-modifying treatments on the rise, it becomes increasingly important to move research in this area forward. Genetic research is excellent at discovering novel contributors to disease mechanisms, which has been demonstrated by the discovery of over 75 disease loci associated with AD. However, classical large-scale genome-wide association studies (GWAS) use cohorts of individuals that have been assigned a case or a control status based on a clinical diagnosis. For AD, this can result in bias due to the complex nature of the disease profile. More specifically, on the neuropathological level, AD is multifaceted with co-morbid pathological lesions being the norm rather than the exception. Together with the substantial preclinical phase, this can lead to the introduction of type I and type II errors. An alternative to using large-scale clinical cohorts is to shift toward studying individuals where the disease diagnosis has been neuropathologically confirmed, or cohorts where an endophenotype is used which can directly reflect ongoing pathological processes in vivo. Such endophenotypes could entail biofluid or imaging-based biomarkers, but the most undiluted signal is obtained when employing neuropathological data. These data typically represent the presence or absence of a lesion or reflects the semi-quantitative burden of pathological features. Here, we review what this shift toward more detailed phenotypes has already contributed to the field by investigating the genetic background of AD hallmark lesions as well as commonly observed co-pathologies.
International journal of molecular sciencesMaría Orosia Lucha-López
Musculoskeletal disorders are among the leading causes of disability worldwide and represent a major driver of physical therapy needs across the life course [...].
Signal transduction and targeted therapyDing-Kun Ji, Haozhi Lei, Jia Liu, Fangfang Xia, Xiaobo Gao, Yi-Qing Zhou, Ruiying Li, Yongqi Han, Ruowen Wang, Weihong Tan
Nucleic acid aptamers, often referred to as "chemical antibodies," are versatile, specific, and easily modifiable functional nucleic acids. There is a growing focus on new methods for the selection and target validation of aptamers, with the aim of expanding their biomedical applications in molecular diagnostics and therapeutics, which is currently a research hotspot. This review is composed of eight sections. In the first section, we briefly introduce aptamers and review their development in molecular diagnostics and therapeutics. The "Advantages of aptamers in molecular diagnosis and therapeutics" section summarizes and discusses the advantages of aptamers in these fields. The "New methods for screening aptamers" section presents and discusses nucleic acid aptamer screening methods, including both classical and novel approaches. In the "New methods for target validation" section, we explore new methods for target validation, covering aptamer structure validation, target recognition validation, and aptamer-target interaction validation. The "New methods for molecular diagnostics" section summarizes and discusses recent applications of aptamers in molecular diagnostics, particularly focusing on new mechanisms and detection strategies as well as their applications in various diseases. The "New methods for molecular therapeutics" section summarizes and discusses recent applications of aptamers in molecular therapeutics, emphasizing new mechanisms and aptamer-based therapy strategies, along with their therapeutic applications in different diseases. The "Challenges and future perspectives of nucleic acid aptamers" section addresses the challenges and future perspectives of aptamers in disease diagnosis and treatment. Finally, the "Conclusion" section shares our views on the future directions of aptamers in clinical disease molecular diagnostics and therapeutics.
American journal of clinical pathologyArthur Vaz Alvares Fernandes
OBJECTIVES: To review clinically important preanalytical variables in surgical pathology and their effects on diagnostic accuracy, ancillary testing, and patient safety. METHODS: A narrative review was developed from selected literature on surgical pathology preanalytics, fixation, specimen handling, histotechnology, immunohistochemistry, molecular testing, tissue contamination, and quality improvement. Emphasis was placed on practical variables that affect routine anatomic pathology workflows. RESULTS: The diagnostic value of a surgical pathology specimen is shaped before microscopic interpretation. Ischemia time, delayed or inadequate fixation, tissue thickness, container and transport problems, labeling discrepancies, poor orientation, grossing variability, histotechnical artifacts, and tissue contamination can compromise morphology, margin assessment, staging, biomarker interpretation, and molecular testing. These effects are especially consequential in small biopsy specimens and precision oncology specimens, in which the same limited tissue may be required for diagnosis, immunohistochemistry, fluorescence in situ hybridization, polymerase chain reaction-based testing, and next-generation sequencing. Gross examination is a particularly important pathology-controlled preanalytical step because block selection determines what can be assessed microscopically. CONCLUSIONS: Preanalytical control should be regarded as a diagnostic quality and patient safety process rather than a technical background activity. Standardized fixation, specimen tracking, communication, grossing protocols, histotechnical quality assurance, and tissue stewardship are essential to reliable surgical pathology practice.
Digital pathology has rapidly expanded over the past decade, driven by advances in whole-slide imaging and increasing demand for remote and data-integrated diagnostic workflows. However, many implementations remain limited to partial digitization, without fundamentally transforming laboratory and diagnostic processes. In this review, we examine digital transformation in pathology as a systems-level redesign encompassing workflow optimization, digital infrastructure, and networked diagnostic services. Using the implementation at International University of Health and Welfare (IUHW) Narita Hospital as an illustrative example, we describe how a digital-first approach can be integrated into routine clinical practice. Key elements include continuous laboratory workflows aligned with slide digitization, comprehensive digital infrastructure enabling seamless access to diagnostic data, and networked systems that support multi-institutional collaboration and subspecialty consultation. We further discuss how digital pathology extends beyond clinical diagnosis to support education and research, transforming traditional slide archives into accessible data resources, and outline practical considerations for implementation, including workflow redesign, user adoption, and institutional coordination. Finally, by comparing the IUHW Narita experience with other large-scale implementations, we discuss generalizable principles for digital transformation in pathology, including workflow-driven design, data integration, interoperability, and network-based diagnostic models.
Cancer cytopathologyK Hasan Bilal, Joanna Gibson, David Kim, Angelique W Levi, Aziza Nassar, Handy Oen, Valentina Robila, Mauro T Saieg, Qiuying Shi, Vanda F Torous, Akkus Zeynett…
Large language models (LLMs) and vision-language models represent a fundamentally different category of artificial intelligence (AI) compared to prior image analysis approaches in digital pathology, which have largely been based on convolutional neural network architectures. This review from the American Society of Cytopathology Clinical Practice Committee examines the current evidence for LLM and vision-language model applications in cytopathology, including structured reporting, diagnostic assistance, quality control, education, and workflow integration. The distinction between applications with preliminary evidence and those that remain hypothetical is described. A detailed assessment of the challenges that must be addressed before clinical deployment, including hallucination risk, limited explainability, bias, data privacy, validation gaps, and infrastructure barriers is discussed. A review of the regulatory landscape in the United States and European Union as it applies to AI-enabled software as a medical device is provided. Recommendations addressing cytopathology-specific benchmarks, multi-institutional validation, transparent governance, and incremental deployment beginning with low-risk applications are suggested. In the current environment, LLMs have the potential to augment cytopathology practice, but responsible adoption requires rigorous validation and sustained collaboration among cytopathologists, AI researchers, and regulatory bodies.
BACKGROUND: Digital pathology supports whole-slide imaging, remote review, and computational analysis. Most pathology AI systems, however, remain restricted to predefined tasks. Agentic architectures coordinate perception models, language-based reasoning, external tools, and feedback-dependent actions, but their clinical evidence is derived mainly from retrospective benchmarks and research prototypes. MAIN BODY: We review agentic systems in computational pathology using an operational taxonomy based on dynamic control flow, inference-time tool selection, and knowledge integration. We assess architectures, enabling technologies, and applications in diagnosis, prognosis, and therapeutic support. Reported gains are difficult to attribute to agentic organization because studies differ in backbones, training data, and inference budgets. We therefore emphasize validation scope, computational cost, workflow integration, hallucination and security risks, regulatory requirements, patient preferences, and the conditions under which specialist non-agentic models remain preferable. CONCLUSIONS: Agentic architectures have established technical feasibility, but not clinical benefit. Translation should prioritize verifiable tasks, matched comparisons, prospective and external validation, lifecycle governance, and interfaces that preserve pathologist oversight.
PloS oneJonathan Williams Ramirez, Dina Zemlyanker, Lucas Deden-Binder, Rogeny Herisse, Erendira Garcia Pallares, Karthik Gopinath, Harshvardhan Gazula, Christopher Mo…
Advances in image registration and machine learning have recently enabled volumetric analysis of postmortem brain tissue from conventional photographs of coronal slabs, which are routinely collected in brain banks and neuropathology laboratories around the world. One caveat of this methodology is the requirement of segmentation of the tissue from the background and out-of-slice tissue in photographs, which currently requires laborious manual intervention. Manual delineation is a bottleneck in this process and poses challenges in scalability, and resources, restricting adoption of these methods. In this article, we present a deep learning model to automate this process. The automatic segmentation tool relies on a U-Net architecture that was trained with a combination of 1,414 manually segmented images of both fixed and fresh tissue, from specimens with varying diagnoses, photographed at two different sites. Automated model predictions on a subset of photographs not seen in training were analyzed to estimate performance compared to manual labels, including both inter- and intra-rater variability. Our model achieved a median Dice score over 0.98, mean surface distance under 0.4 mm, and 95% Hausdorff distance under 1.60 mm, which approaches inter-/intra-rater levels. Our tool is publicly available at surfer.nmr.mgh.harvard.edu/fswiki/PhotoTools and training data is available at https://zenodo.org/records/20647553.
Journal of visualized experiments : JoVEEitan Halper-Stromberg, Suguna Narayan, Vincent Laufer, Melvin Limson, Tracy Busse, Jeremy P Segal, Dara L Aisner, Jennifer J D Morrissette, Helga Thorvaldsdot…
The integrative genomics viewer (IGV) is a pivotal tool in clinical genomics, enabling the visualization and interpretation of complex sequencing data. Bringing clinical knowledge to bear with visual evaluation of sequencing results is the primary means by which molecular pathologists and other professionals assess and finalize cases. A variety of software tools can assist, but their relationship to the underlying data must be understood and applied systematically. This study includes essential background on next-generation sequencing (NGS) data file types (e.g., FASTQ, BAM, VCF) with a discussion of their format and purpose. We then describe features of IGV that derive nuances from these files. We utilize a series of curated practical cases based on clinical vignettes through which the reader will interact with clinical NGS sequencing data using the IGV software to review various types of clinically relevant variants relative to the human reference genome. These clinical vignettes have been curated to describe examples of some of the complexities of interpretation of genomic data, and how utilizing IGV as part of a routine workflow can provide additional interpretive information for variants beyond routine bioinformatic software algorithm variant calls. The visual inspection of genomic variants utilizing the tools within IGV can unmask subtle contextual cues (i.e., variant allele frequency, strand bias, tissue-specific context) that can influence the interpretation of genomic variants. Although this study focuses on using IGV for the detection and interpretation of somatic variants, the provided applications can be extrapolated for use in the germline setting, including analysis of complex variants and detection of mosaicism.
Legal medicine (Tokyo, Japan)Ghadeer M M Abdelaal, Amira A M Said, Sarah E Y Elreffaey, Bothina H F Omran
Accurate determination of wound age is crucial in forensic investigations, aiding in crime scene analysis and establishing the cause of death. However, this remains a challenging task in medicolegal practice. This study aimed to investigate the temporal dynamics of skin incised wound healing in adult male albino rats by employing biochemical, histopathological, and immunohistochemical analyses. Thirty-six adult male albino rats were utilized. Six served as controls, while the remaining thirty were equally divided into five groups. Standardized incisions were inflicted, and the animals were euthanized at predetermined time points (1, 3-, 5-, 7- and 14-days post-wounding). Blood and skin samples were collected for subsequent biochemical, histopathological, and immunohistochemical examinations, including morphometric analysis. Significant elevations in Interleukin-6 (IL-6) and nitric oxide (NO) were observed, peaking at days 1 and 3 post-wounding, respectively. Indicators of the wound repair process were detected 3-, 5- and 7-days post-wounding and a scab covering the wound surface was detected until the 7th day and completely detached at 14 days post-wounding. Collagen fiber deposition demonstrated a significant increase, reaching its peak at day 14 post-wounding. Immunohistochemical analysis revealed a significant upregulation of vascular endothelial growth factor (VEGF), peaking at day 7 post-wounding. The observed temporal changes in biochemical, histological, and immunohistochemical parameters during skin incisional wound healing in rats provide valuable insights that may contribute to the development of more accurate methodologies for wound age estimation in forensic contexts.
Legal medicine (Tokyo, Japan)Rossana Cecchi, Jessika Camatti, Maria Laura Schirripa, Jacopo Marani, Nicoletta Campanini, Anna Laura Santunione
Traumatic brain injury (TBI) is characterized by complex secondary injury mechanisms, including microvascular dysfunction and platelet/endothelial activation. The formation of microthrombi within the cerebral microcirculation has been proposed as a contributing factor to secondary brain damage, but its characterization in human post-mortem tissue remains limited. This retrospective study included 30 cases of fatal TBI resulting from road traffic accidents and 13 non-traumatic controls without evidence of cranial or parenchymal brain pathology. Brain samples were collected during medico-legal autopsy and analyzed using immunohistochemistry for P-selectin (CD62P). Microthrombi were evaluated using a semi-quantitative approach based on 12 non-overlapping microscopic fields per section. Cases were grouped according to survival intervals. P-selectin-positive microthrombi were detectable at early stages after trauma, including within the first hour. Their number increased in the early post-traumatic period, with the highest values observed within 4-48 h, followed by a progressive decline at longer survival intervals. Morphological analysis showed a transition from P-selectin-positive aggregates compatible with early platelet/endothelial activation to thrombotic formations with an increasing cellular component morphologically compatible with leukocytes over time. Control cases showed minimal or absent P-selectin expression, with significantly lower counts than TBI cases. P-selectin-positive microthrombi can be identified in human post-mortem brain tissue following TBI and show a time-related distribution, supporting the involvement of platelet/endothelial activation and thromboinflammatory microvascular alterations in secondary brain injury. Further studies are needed to validate these findings and to better define their specificity, temporal significance, and forensic applicability.
Pediatric central nervous system tumors remain a leading cause of cancer-related mortality in children, while their diagnosis, risk stratification, and therapeutic management increasingly depend on integrated molecular characterization. However, representative tumor tissue is often difficult to obtain because of tumor location, surgical risk, limited biopsy material, and the impracticality of repeated sampling during disease evolution. Cerebrospinal fluid (CSF) has therefore emerged as a particularly informative liquid biopsy compartment for many CNS malignancies, enriched in tumor-derived cell-free DNA and, for tumors in contact with the CSF spaces, more directly reflective of intracranial tumor biology than plasma; its yield nonetheless varies with tumor biology and anatomical proximity to CSF pathways. Here, we review the evidence supporting CSF cell-free DNA sequencing as an emerging extension of molecular neuropathology in pediatric CNS tumors. Targeted next-generation sequencing, low-pass whole-genome sequencing, methylation-based classifiers, and nanopore sequencing now enable complementary assessment of somatic mutations, copy number alterations, epigenetic tumor class, and longitudinal tumor burden from low-input pediatric CSF samples. Recent studies have moved the field beyond analytical proof of concept towards defined clinical scenarios, including molecular diagnosis when biopsy is infeasible, molecular staging of high-CSF-shedding tumors, minimal residual disease monitoring in medulloblastoma and other embryonal tumors, and clarification of ambiguous radiological progression. CSF-based sequencing does not replace tissue neuropathology, but provides a liquid molecular layer that can complement, extend, or in selected situations partially substitute tissue-based diagnosis. Its broader adoption now depends on workflow standardization, assay-specific reporting standards, external quality assurance, and prospective evidence that CSF-guided decisions improve patient outcomes.
American journal of clinical pathologyRiley Jepkema, Meredith Herman, Sanjay Gadasalli, Sean Hacking, Julia Kochanowski, Casey Schukow, Kamran Mirza
OBJECTIVES: The use of #pathology and #pathologist is increasing on TikTok, a short-form video platform with over 1 billion users. As of July 2024, #pathology had over 21 000 posts and 468 million views, while #pathologist had over 3000 posts. It could be a useful tool for education and recruitment if the content is accurate and engaging. METHODS: To assess the accuracy, engagement, and educational value of this growing content, we conducted a cross-sectional study analyzing 105 English-language TikTok videos identified using these keywords over a 72-hour period. Videos were evaluated using the Patient Education Assessment Tool for audiovisual material (PEMAT-AV) for audiovisual quality, the Global Quality Scale (GQS) for overall content quality, and a modified JAMA benchmark score for information accountability. Additionally, a harm-benefit score categorized educational impact. RESULTS: Statistical analysis revealed that educational content demonstrated significantly higher quality scores on GQS (P = .0001) and PEMAT-AV (P = .0007) than other content types. In contrast, medical profile type was associated with higher PEMAT-AV (P = .0147), JAMA (P = .0332), and harm-benefit (P = .0004) scores. CONCLUSIONS: While the volume of pathology-specific content is currently limited, the high average engagement metrics-298 100 followers, 1.5 million views, and 67 884 likes per video-indicate substantial user interest. The higher-quality scores for educational and medical content suggest that pathology content creators are generally knowledgeable and accurately represent the field on TikTok, highlighting TikTok's potential as a valuable platform for disseminating reliable pathology-related information.
Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDGCornelia S L Müller, Torsten Hansen
Digital pathology has become an increasingly established component of routine diagnostic practice in recent years. Whole-slide imaging enables the complete digitization of histological slides and allows for primary diagnosis using digital images. This development offers new opportunities for diagnostics, consultations, archiving, education, and quality assurance. In dermatology and dermatopathology, digital pathology is particularly relevant for the evaluation of inflammatory skin diseases, melanocytic lesions, epithelial skin tumors, and immunohistochemical analyses. This article provides an overview of the technical principles of digital pathology, describes workflow integration and implementation in clinical routine, and outlines requirements for quality assurance and validation. Key applications in dermatology as well as advantages and limitations of digital diagnosis are discussed. A dedicated section addresses the role of artificial intelligence as an assistive tool in dermatopathological diagnostics. The aim of this CME article is to provide dermatologists and pathologists with a comprehensive basis for evaluating and applying digital pathology systems in clinical practice and to place current developments into a realistic clinical context.
The Malaysian journal of pathologyN R Abdul Rahman, N H Othman, E S Ch'ng
The transition from traditional microscopy-based diagnostic workflows to digital pathology for primary diagnosis necessitates a robust understanding of the applicable legal and regulatory frameworks. This review synthesises the multi-layered regulatory landscape governing digital pathology adoption in Malaysia. Key statutory and professional requirements are examined, including the Medical Device Act 2012 for system registration; MS ISO 15189 and STR 2.2 for laboratory accreditation and clinical validation; and the Malaysian Medical Council's 2024 Telemedicine Guideline for its implications on telepathology practice. In addition, the integration of digitised slides into formal medical records is considered under the Private Healthcare Facilities and Services Regulations 2006, alongside data privacy obligations under the Personal Data Protection Act 2010 and evidentiary admissibility requirements under the Evidence Act 1950 Malaysia. This review underscores that safe and legally compliant implementation of digital pathology requires rigorous system validation, strict data security protocols, appropriate institutional credentialing, and comprehensive audit trail maintenance.
The Japanese General Rules of Clinical and Pathological Reporting of Cancers (Kiyaku) are unique standardized systems for cancer handling and documentation used by professionals involved in cancer care in Japan. The Japanese Society of Pathology (JSP) conducted a questionnaire survey among practicing pathologists regarding the utilization and awareness of Kiyaku. We analyzed 1083 valid responses, representing 22.4% of the JSP members and 33.8% of the board-certified pathologists. Kiyaku, with > 90% latest-edition ownership, covered approximately 90% of all cancers in Japan. The timing of the implementation of the new editions varied not only across institutions but also among individuals in each institution. Among department directors, 46.1% reported implementing new editions at their discretion without prior notice. Item-level responses were collected for the stomach, lung, and breast as representative Kiyaku; histological classification and descriptive symbols were widely considered useful and frequently used across the three cancers, whereas biopsy-related items in the lung and breast were used less frequently. In conclusion, Kiyaku is broadly embedded in daily practice and facilitates standardized cancer documentation in Japan, although several challenges remain. The JSP should clearly articulate the purpose of Kiyaku and promote coordinated adoption to standardize its use in pathology practice.
International journal of molecular sciencesAngelo Montana
Forensic pathology and forensic toxicology are experiencing one of the most significant scientific transformations since the introduction of molecular biology into biomedical research [...].
Journal of Zhejiang University. Science. BXiang Li, Honglin Chen, Xu Wang, Yuhe Hu, Zhaofei Yang, Min Wei
Parkinson's disease (PD) is the second most common neurodegenerative disorder, and continues to present significant challenges in early diagnosis, precise subtyping, and prognosis assessment. In recent years, the field of biomarker research has undergone a profound paradigm shift from static concentration measurements to functional activity detection. The most revolutionary breakthrough is the α-synuclein seed amplification assay (α-Syn-SAA), which enables ultrasensitive and specific detection of pathological α-Syn in both clinical and prodromal stages, thus providing an unprecedented window for early intervention. Substantial progress has also been made in the development of biomarkers such as neurofilament light chain (NfL), Alzheimer's disease-related biomarkers, and genetic biomarkers, as well as in detection technologies based on peripheral samples. The integrated application of cutting-edge technologies, such as real-time quaking-induced conversion (RT-QuIC), high-resolution mass spectrometry, and high-field magnetic resonance imaging (MRI), is advancing the field into a new stage characterized by a focus on pathological activity, multi-omics integration, and non- or minimally invasive approaches. In this review, we explore recent advances in PD biomarkers, focusing on core pathophysiological markers. We examine the potential of multi-omics and artificial intelligence (AI) to enhance diagnostic, subtyping, and prognostic accuracy, while also outlining the pivotal role and future directions of biomarkers in advancing precision medicine for PD.
Alzheimer's & dementia : the journal of the Alzheimer's AssociationBrittany N Dugger, Melanie N Luu, Viharkumar Patel, Charles DeCarli, Lee-Way Jin, Paola Gilsanz, Dan Mungas, Claudia Kawas, Maria M Corrada, Rachel A Whitmer
INTRODUCTION: Studies of the oldest-old show great neuropathologic heterogeneity; little is known in diverse populations after age 90. METHODS: LifeAfter90 is a lifecourse cohort study of individuals aged ≥ 90 years evaluated every 6 months with optional brain donation; this study presents initial neuropathological findings. RESULTS: A total of 124 decedents (mean age 96, 49.2% White, 12.1% Black, 16.9% Asian, 18.5% Latino individuals) came to autopsy. At last evaluation, 35% had dementia, 23% cognitive impairment, and 41% normal cognition. 35.5% had intermediate AD, 8.1% had high AD neuropathologic changes, 73% had moderate/severe arteriolosclerosis, 23% one or more microinfarcts, 32% Lewy bodies, 24% TDP-43 deposits, and 4% hippocampal sclerosis. There was a high degree of mixed neuropathology, with 69% having three or more pathologies. Cognitive impairment was most strongly associated with AD pathology. DISCUSSION: Multiple pathologies were common, and many individuals maintained normal cognition indicating substantial neuropathologic burden may be present in the absence of overt cognitive impairment, especially in the oldest-old.
International review of neurobiologyPriya, Radhika Mittal, Jyotirmoy Banerjee, Aparna Dixit
Alzheimer's (AD) and Parkinson's disease (PD) represent a major class of neurodegenerative disorders characterized by different proteinopathies with amyloid-β plaques and tau tangles in AD, while α-synuclein containing Lewy bodies in PD, specific molecular signatures. Alongside this central mechanism, they share pathological cascades including axonal degeneration, synaptic dysfunction, glial activation and neuroinflammation. The emergence of blood-based biomarkers, represents a paradigm shift in the field of diagnosis and therapeutics by addressing these core pathological mechanism of central nervous system. This chapter highlights a overview of blood-based biomarkers emerging in the field of AD and PD, exploring the clinical utility of core pathology markers (Aβ42/40, p-tau species, and α-synuclein), alongside other neurodegenerative markers such as neurofilament light chain and glial activation markers like GFAP. Beyond the diagnosis, we emphasize on the potential role of blood-based biomarkers as a surrogate and pharmacodynamic endpoint in disease modifying clinical trial development, facilitating dose optimization and target engagement. Future prospects empathize on the use of multimodal approach integration, trajectory modeling and novel target discovery. Collectively, these blood-based biomarkers enable transition of neurodegenerative disorders treatment from symptom-based classification to towards a mechanism targeted therapeutic framework.
An updated version of the generally accepted forensic classification of motor vehicle injuries is proposed. The general principle of the current classification, based on the relationship between the circumstances, phase, and mechanism (type of traumatic impact) of injury formation, is retained. The proposed classification takes into account the modern design diversity of automobiles and the variety of conditions under which the victim comes into contact with parts of a moving vehicle.
Sudebno-meditsinskaia ekspertizaO S Lavrukova, E L Kazakova, V L Popov, N G Panov
OBJECTIVE: Analysis and comparison of impedance parameters of cadaveric tissues and their dynamics depending on the number of accumulated degree-days. Materials and methods: the experiment was carried out on model objects - pig cadavers (skin flap, cartilage, tendon) under two conditions: standardized (+4 °C, humidity around 40%, condition I) and natural biocenosis (average temperature around +18.5 °C, condition II). The impedance modulus and phase shift angle θ were measured at five frequencies f (100 Hz, 120 Hz, 1 kHz, 10 kHz, 100 kHz) at different times of the postmortem interval; a Keysight U1733 device was used. Various coefficients were calculated for dispersion analysis, and time referencing was carried out by calculating the number of accumulated degree-days. Measurements were also carried out on embalmed anatomical preparations. RESULTS: The study demonstrates that calculating accumulated degree-days allows for the reconciliation and quantitative comparison of changes in the impedance characteristics of cadaveric tissues obtained under various environmental conditions. An important result is that similar values of accumulated degree-days (~300 degree-days) correspond to similar qualitative changes in tissues under standardized and natural conditions, and the θ-lgf trend equations for similar values of accumulated degree-days coincide or are close in coefficients. CONCLUSION: This confirms the predictive value of calculating the number of accumulated degree-days when interpreting impedance measurements to clarify the duration of the postmortem period and the possibility of extrapolating results obtained under certain temperature conditions to other environmental conditions. However, further research is needed to explore the mechanisms of postmortem biophysics, expand the sample size (including human cadavers), examine the influence of entomological and other factors, and validate the methodology for practical use in forensic practice.
Sudebno-meditsinskaia ekspertizaV L Popov, S N Lyabzina
Drowning represents one of the most frequent causes of accidental death; however, many submerged remains remain unrecovered or unidentified due to the challenges associated with aquatic decomposition. This process differs substantially from decomposition on land and is influenced by a complex array of factors, including temperature, oxygen availability, depth, and the presence of necrophagous organisms. In aquatic environments, decomposition follows a nonlinear trajectory and can be either slowed - under hypoxic conditions or at low temperatures - or accelerated by the activity of scavenging organisms. In marine ecosystems, key contributors to soft tissue degradation include crustaceans (such as crabs, shrimp, and lobsters), fish, and other invertebrates (e.g., polychaete worms and mollusks). Their activity leads to rapid skeletonization. Subsequently, the remains are colonized by fouling organisms (including barnacles and bivalves) and undergo bioerosion by specialized species such as the bone-devouring worms of the genus Osedax. In freshwater environments, the main participants in the process are leeches, flatworms, insects, and crustaceans. Their sequential succession ensures complete recycling of organic material. The rate of decomposition is highly variable, ranging from several days to several months, complicating the estimation of the postmortem submersion interval. Biological indicators, such as the developmental stage of barnacles, are used to address this challenge.
Sudebno-meditsinskaia ekspertizaA L Shkutenko, A V Fedotov, O L Antonova, D N Uslontsev
The purpose of the work is to establish and compare the morphological characteristics of damage caused by shots from a hunting rifle MC 21-12, using factory-made and self-loaded cartridges at various distances, with the possibility of further use of the results in expert practice. The aim is to determine the morphological features of the resulting damage and the nature of the deposition of the products of the shot. As a result of the study, the composition and maximum distances of the spread of the products of the shot with cartridges from such a gun were established. The features of the experimental damage of white biazi targets, struck from different distances, were identified.
Sudebno-meditsinskaia ekspertizaS V Leonov, P V Pinchuk, A I Sakharov
The article presents a method for hair examination using an electronic scanning microscope Hitachi FlexSem1000 II (Japan) and describes sample preparation method. As part of the experimental study, damage was caused by blades with varying degrees of bluntness: sharp (up to 2-25 microns), medium sharp (up to 26-40 microns), blunt (up to 41-50 microns) and severely blunt (over 51-60 microns). According to the results of the research, specific signs characteristic of each sharpness level of the traumatic object have been established, which is illustrated by microphotographs. A subgroup of ideally sharp objects with a sharpness of 1-3 microns has been identified, which form a rather specific morphological picture of the cut. It differs from other sharp objects, and an algorithm for determining the level of sharpness of the trace-forming object has been developed.
Sudebno-meditsinskaia ekspertizaO V Sokolova, V L Popov
OBJECTIVE: Forensic histological assessment and analysis of pathomorphological changes in internal organs during generalized viral infection in infants in the first year of life. MATERIAL AND METHODS: 65 forensic medical examinations performed at the Bureau of Forensic Medical Examination from 2012 to 2024; cytological examination of smears-prints stained according to Pavlovsky's method and histological examination of microspore slides of internal organs stained with hematoxylin and eosin and MSB Zerbino staining technique. RESULTS AND CONCLUSION: Generalization of the infectious process is an important stage in the course of a viral disease in infants in the first year of life. Generalized viral infection is accompanied by pronounced, deep structural changes in the vascular-stromal and parenchymal components of internal organs, accompanied by severe circulatory disorders in the form of extensive hemorrhages, erythrocyte stasis with sludge phenomenon and clot formation in the microcirculatory bed of internal organs. When conducting forensic medical examinations, a combination of results of the cytological and histological research methods allows us to determine viral lesions of internal organs and to assess the severity and prevalence of pathomorphological changes in internal organs that developed as a result of infectious lesions. The complete forensic histological diagnosis is based on clinical data (if available), results of virological testing and severity of pathomorphological changes that have developed in the internal organs during the generalization of the viral infection.
Sudebno-meditsinskaia ekspertizaA Yu Chudakov, I A Tolmachev, V V Gaivoronskaya
This study focuses on an important aspect of forensic medical diagnostics: the identification and interpretation of tissue discoloration around subcutaneous veins that occurs during general hypothermia. We delve into the morphological manifestations of this phenomenon, its mechanisms of development, and its role in differential diagnosis. We particularly emphasize how this feature helps to establish the fact and extent of low-temperature exposure on the body, as well as to rule out other possible causes of death. Drawing on the analysis of scientific literature and our own practical experience, we assess the reliability and boundaries of applicability of this diagnostic criterion. The main objective of our work is to comprehensively analyze the forensic significance of this staining in cases of death from hypothermia, determine its informational value, and its place in the complex of diagnostic methods.
The length of the wound channel of a stab wound is a morphological feature that can serve as a criterion for assessing the degree of force of a knife strike. A study of 412 stab wounds to the chest and abdomen in 252 homicide cases showed that clothing, bone-cartilaginous structures and the density of internal organs did not affect the depth of immersion of the knife blade in the wound. The wound channel of non-penetrating wounds with a length of less than 6 cm indicates an impact of «moderate» force. The length of the wound channel of penetrating wounds from 6 to 15 cm corresponds to an impact of «middle» force, and over 15 cm corresponds to an impact inflicted with «considerable» force.
Methods in molecular biology (Clifton, N.J.)Cong Cong, Antonio Di Ieva, Sidong Liu
Federated learning (FL) has emerged as a powerful paradigm for privacy-preserving, collaborative training of machine learning models, particularly valuable in fields like digital pathology, where data sharing is constrained by institutional policies and regulatory concerns. This chapter presents a reproducible computational pipeline for whole-slide image (WSI) classification in digital neuropathology using a federated learning framework. In addition to outlining the end-to-end implementation, including preprocessing, model training, and deployment, we highlight key challenges specific to applying FL in WSI analysis, such as data heterogeneity and communication efficiency. Detailed code snippets, implementation guidance, and deployment recommendations are provided to support real-world adoption. We hope this chapter serves as a valuable resource for neuropathologists, researchers, and machine learning practitioners aiming to bridge technology and medical science in the evolving landscape of digital neuropathology.