Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins.

The loss of vital cells within healthy tissues contributes to the development, progression and treatment outcomes of many human disorders, including neurological and infectious diseases as well as environmental and medical toxicities. Conversely, the abnormal survival and accumulation of damaged or superfluous cells drive prominent human pathologies such as cancers and autoimmune diseases. Apoptosis is an evolutionarily conserved cell death pathway that is responsible for the programmed culling of cells during normal eukaryotic development and maintenance of organismal homeostasis. This pathway is controlled by the BCL-2 family of proteins, which contains both pro-apoptotic and pro-survival members that balance the decision between cellular life and death. Recent insights into the dynamic interactions between BCL-2 family proteins and how they control apoptotic cell death in healthy and diseased cells have uncovered novel opportunities for therapeutic intervention. Importantly, the development of both positive and negative small-molecule modulators of apoptosis is now enabling researchers to translate the discoveries that have been made in the laboratory into clinical practice to positively impact human health.

Stretching the boundaries of extracellular matrix research.

Extracellular matrix (ECM) proteins constitute >1% of the proteome and interact with many modifiers and growth factors to affect most aspects of cellular behaviour during development and normal physiology, as well as in diseases such as fibroses, cancer and many genetic disorders. In addition to biochemical signals provided to cells by ECM proteins, important cell­ECM interactions involve bidirectional mechanotransduction influences, which are dependent on the physical structure and organization of the ECM. These are beginning to be understood using twenty-first-century approaches, including biophysics, nanotechnology, biological engineering and modern microscopy. Articles in this issue of Nature Reviews Molecular Cell Biology review progress in our understanding of the ECM.

LifeTime and improving European healthcare through cell-based interceptive medicine.

Here we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.

Moving Forward on Tumor Pathology Research Reporting: A Guide for Pathologists From the World Health Organization Classification of Tumors Living Evidence Gap Map by Tumour Type Group.

Evidence-based medicine (EBM) can be an unfamiliar territory for those working in tumor pathology research, and there is a great deal of uncertainty about how to undertake an EBM approach to planning and reporting histopathology-based studies. In this article, reviewed and endorsed by the Word Health Organization International Agency for Research on Cancer's International Collaboration for Cancer Classification and Research, we aim to help pathologists and researchers understand the basics of planning an evidence-based tumor pathology research study, as well as our recommendations on how to report the findings from these. We introduce some basic EBM concepts, a framework for research questions, and thoughts on study design and emphasize the concept of reporting standards. There are many study-specific reporting guidelines available, and we provide an overview of these. However, existing reporting guidelines perhaps do not always fit tumor pathology research papers, and hence, here, we collate the key reporting data set together into one generic checklist that we think will simplify the task for pathologists. The article aims to complement our recent hierarchy of evidence for tumor pathology and glossary of evidence (study) types in tumor pathology. Together, these articles should help any researcher get to grips with the basics of EBM for planning and publishing research in tumor pathology, as well as encourage an improved standard of the reports available to us all in the literature.

Centrioles, centrosomes, and cilia in health and disease.

Centrioles are barrel-shaped structures that are essential for the formation of centrosomes, cilia, and flagella. Here we review recent advances in our understanding of the function and biogenesis of these organelles, and we emphasize their connection to human disease. Deregulation of centrosome numbers has long been proposed to contribute to genome instability and tumor formation, whereas mutations in centrosomal proteins have recently been genetically linked to microcephaly and dwarfism. Finally, structural or functional centriole aberrations contribute to ciliopathies, a variety of complex diseases that stem from the absence or dysfunction of cilia.

Trends in authorship in the Journal of Cutaneous Pathology, 1981-2020.

BACKGROUND: The increase in authors per scientific article in many different medical and scientific disciplines has raised concerns over ethical authorship. Trends in authorship in dermatopathology are unknown. METHODS: Cross-sectional study of a random sample of 200 articles from the Journal of Cutaneous Pathology (1981-2020). RESULTS: The number of authors per article increased by an estimated 96% between 1981 and 2020 (2.7-5.3), while the relative citation ratio decreased by an estimated 56% during the same period (1.19-0.52). Higher author counts were not associated with higher relative citation ratios (p = 0.2349) or analytic study designs (p = 0.2987). Higher relative citation ratios were associated with analytic study designs (p = 0.0374). CONCLUSIONS: There has been significant growth in authorship credit at the journal without a corresponding increase in research impact or study rigor. Remedial measures to stem authorship inflation and promote more impactful studies may be necessary.

The virtual dermatopathology mentorship.

The Covid pandemic necessitated changes in traditional mentorship and educational roles. We offer our experience in structuring a virtual dermatopathology mentorship in the midst of the pandemic. Virtual mentorships have many benefits including ease of access, lack of geographic restrictions, and financial savings, though there still remains an important and irreplaceable role for in-person relationships.

#Pathart and cytopathology: Beauty must be shared.

OBJECTIVE: There is beauty in cytopathology. That beauty and art can be transmitted and shared through fun images on social media. METHODS: As social media becomes more popular, pathologists and related professionals have started to share the images that they capture at work on their profiles, tagging them with the hashtag #Pathart. #Pathart hashtag unites two concepts innately related: Pathology and art. RESULTS: When groups of pathologists share concurring ideas, the result is an explosion of creativity that spreads even to new professionals and students. In addition, it attracts the attention of people, dedicated to other subjects such as journalism, who, with their interactions, give visibility to our field. This helps counteract the stereotypes and gives people a better understanding of what we do and why it is important. Therefore, the more pathologists and related professionals meet and interact with each other, the better. CONCLUSIONS: #Pathart images raise great interest among professionals, which contributes to the creation of a united and strong community of pathologists some of whom are dedicated to cytology. Interaction and professional collaboration between these professionals can positively contribute to disseminating scientific content and creating work/research groups. This might have an impact, both direct and indirect, on improving the quality of diagnoses and treatments in our patients.

Peer creation and sharing of mnemonics in collaborative documents for pathology education: a pilot study.

BACKGROUND: Mnemonic techniques are memory aids that could help improve memory encoding, storage, and retrieval. Using the brain's natural propensity for pattern recognition and association, new information is associated with something familiar, such as an image, a structure, or a pattern. This should be particularly useful for learning complex medical information. Collaborative documents have the potential to revolutionize online learning because they could increase the creativity, productivity, and efficiency of learning. The purpose of this study was to investigate the feasibility of combining peer creation and sharing of mnemonics with collaborative online documents to improve pathology education. METHODS: We carried out a prospective, quasi-experimental, pretest-posttest pilot study. The intervention group was trained to create and share mnemonics in collaborative documents for pathological cases, based on histopathological slides. The control group compared analog and digital microscopy. RESULTS: Both groups consisted of 41 students and did not reveal demographic differences. Performance evaluations did not reveal significant differences between the groups' pretest and posttest scores. Our pilot study revealed several pitfalls, especially in instructional design, time on task, and digital literacy, that could have masked possible learning benefits. CONCLUSIONS: There is a gap in evidence-based research, both on mnemonics and on CD in pathology didactics. Even though, the combination of peer creation and sharing of mnemonics is very promising from a cognitive neurobiological standpoint, and collaborative documents have great potential to promote the digital transformation of medical education and increase cooperation, creativity, productivity, and efficiency of learning. However, the incorporation of such innovative techniques requires meticulous instructional design by teachers and additional time for students to become familiar with new learning methods and the application of new digital tools to promote also digital literacy. Future studies should also take into account validated high-stakes testing for more reliable pre-posttest results, a larger cohort of students, and anticipate technical difficulties regarding new digital tools.

Pathology skills lab: use of macroscopic tumor models in pathology teaching.

BACKGROUND: The shortage of pathologists in Germany, coupled with an aging workforce, requires innovative approaches to attract medical students to the field. Medical education must address different learning styles to ensure that all students are successful. METHODS: The pilot project "Practical Pathology" aims to enhance students' understanding of pathology by providing hands-on experience in macroscopic gross analysis through the use of tumor dummies built from scratch. RESULTS: An evaluation survey, completed by 63 participating students provided positive feedback on the course methodology, its relevance to understanding the pathology workflow, and its improvement over traditional teaching methods. The majority of students recognized the importance of hands-on training in medical education. Students with previous work experience rated the impact of the course on knowledge acquisition even more positively. CONCLUSION: The course improved students' understanding of pathological processes and potential sources of clinical-pathological misunderstanding. An increase in motivation for a potential career in the field of pathology was observed in a minority of students, although this exceeded the percentage of pathologists in the total medical workforce.

Interactive Pathology Tutorial in Neoplastic Hematology Disorders for Medical Hematology-Oncology Fellows.

Hematology-oncology (HO) fellows receive limited instruction in the process of establishing a diagnosis for hematologic neoplasms, and learning neoplastic hematology often occurs in limited encounters. In the current study, we developed a web-based interactive pathology tutorial in neoplastic hematologic disorders for HO fellows to work up simulated cases and establish the diagnosis. An online system ("Pathology Playground") was utilized to load case materials including microscopic images and ancillary studies. Twelve high-yield simulated cases of common leukemias and lymphoma were included. At the beginning of each case, trainees review the clinical history and slide images, and then, they are given the option to request additional pathology work-up. Based on the results, they can enter their diagnostic impression. If the diagnosis is correct, the user is shown a short educational presentation. If the diagnosis is not correct, the user gets notified by the message "Incorrect." The tutorial was integrated in the educational curriculum of our HO fellowship program, and bimonthly teaching sessions were held to review two cases each time. During the sessions, trainees request ancillary studies to complete the diagnostic work-up using the software and interpret the findings. As the case is being worked up by the trainee, the hematopathologists and HO fellowship program director discuss the findings, the appropriate work-up tools, and the implications on management. All of our six HO fellows attended the sessions, and a survey from the trainees showed high ease of use of the system and they viewed it as a very useful educational tool. A pre-test and post-test were administered for one of the sessions, and the result showed improvement in the average from 62 to 73%. Expanding the use of this online interactive tutorial and incorporating additional cases would enhance its value as a learning resource.

How to use AI in pathology.

AI plays an important role in pathology, both in clinical practice supporting pathologists in their daily work, and in research discovering novel biomarkers for improved patient care. Still, AI is in its starting phase, and many pathology labs still need to transition to a digital workflow to be able to enjoy the benefits of AI. In this perspective, we explain the major benefits of AI in pathology, highlight key requirements that need to be met and example how to use it in a typical workflow.

[Ecology: The blind spot in pathology research]. / Écologie : l'angle mort de la recherche en ACP.

INTRODUCTION: The 2015 Paris Agreement has been the first restrictive agreement in the fight against climate change. The newer generations of pathologists, who feel more anxiety due to environmental problems than their predecessors, are asked to publish research works while they are harder and harder to and in a context of demographical tensions. We wanted to measure the rise of ecology research in pathology since the Paris Agreement. MATERIAL & METHODS: Over a ten years study period (2013-2022), we have identified via PubMed the number of articles in which forty-three terms taken from the sustainable development vocabulary appeared in ten renowned international pathology journals, selected for their SJR index from ScimagoJr and their impact factor, plus the Annales de pathologie, and compared their means of incidence between the 2013-2015 (m1) and 2016-2022 (m2) periods. The same process has been applied for "artificial intelligence", "deep learning" and "digital pathology". RESULTS: A total of 1336 articles have been identified. Only "digital pathology" (fromm1=8,33 to m2=23,29; p=0,010) and "deep learning" (fromm1=0 to m2=10,14; p=0,034) saw their incidence rise significantly. A significant decrease has been observed with "biological" (fromm1=70,00 to m2=56,86; p=0,020). DISCUSSION-CONCLUSIONS: Pathology reacts to trends but research in ecology has remained in the blind spot since 2015. However there seems to be an awakening as editorials, articles and communications in congress have blossomed the last two years.

[Call attention to the overall benefit of digital pathology and promote its development].

The successful operation of the complete digital pathology(CDP) in foreign countries indicates that the full digital pathology process has entered the full implementation stage. Digital pathology in China started late and progressed slowly, so far there has not been a truly meaningful CDP. The pathologist's understanding of digital pathology is not comprehensive enough, and there are still doubts about the time efficiency and cost effectiveness of digital pathology processes. Therefore,a comprehensive analysis of the process, overall advantages and cost-effectiveness of CDP was made by drawing on international successful experience and hands-on practice experience, in order to promote the construction and development of the CDP in our country.

[Scientific, transparent and applicable rankings of Chinese pathological guidelines and consensus published in the medical journals in 2022].

The STAR tool was used to evaluate and analyze the science, transparency, and applicability of Chinese pathology guidelines and consensus published in medical journals in 2022. There were a total of 18 pathology guidelines and consensuses published in 2022, including 1 guideline and 17 consensuses. The results showed that the guideline score was 21.83 points, lower than the overall guideline average (43.4 points). Consensus ratings scored an average of 27.87 points, on par with the overall consensus level (28.3 points). Areas that scored above the overall level were "conflict of interest" and "working groups", while areas that scored below the overall level were "proposals", "funding", "evidence", "consensus approaches" and "accessibility". To sum up, the formulation of pathology guidelines and consensuses in 2022 is not standardized, and the evidence retrieval process, evidence evaluation methods and grading criteria for recommendations on clinical issues are not provided in the formulation process; the process and method for reaching consensus are not provided, the plan is lacking, and registration is not carried out. It is therefore suggested that guidelines/consensus makers in the field of pathology should attach importance to evidence-based medical evidence, strictly follow guideline formulation methods and processes, further improve the scientific, applicable and transparent guidelines/consensuses in the field, and better provide support for clinicians and patients.

[Developing pathology guidelines and consensus: methods and considerations].

Pathological diagnosis is vital in medicine. Developing and implementing high-quality pathology guidelines and consensus can enhance disease diagnosis accuracy and reduce unnecessary misdiagnosis and missed diagnoses. This article will cover the current status of pathology guidelines and consensus, methods for high-quality development, and the distinctions between them. Additionally, it will provide thoughts and suggestions for promoting their development in China.

Revolutionizing Digital Pathology With the Power of Generative Artificial Intelligence and Foundation Models.

Digital pathology has transformed the traditional pathology practice of analyzing tissue under a microscope into a computer vision workflow. Whole-slide imaging allows pathologists to view and analyze microscopic images on a computer monitor, enabling computational pathology. By leveraging artificial intelligence (AI) and machine learning (ML), computational pathology has emerged as a promising field in recent years. Recently, task-specific AI/ML (eg, convolutional neural networks) has risen to the forefront, achieving above-human performance in many image-processing and computer vision tasks. The performance of task-specific AI/ML models depends on the availability of many annotated training datasets, which presents a rate-limiting factor for AI/ML development in pathology. Task-specific AI/ML models cannot benefit from multimodal data and lack generalization, eg, the AI models often struggle to generalize to new datasets or unseen variations in image acquisition, staining techniques, or tissue types. The 2020s are witnessing the rise of foundation models and generative AI. A foundation model is a large AI model trained using sizable data, which is later adapted (or fine-tuned) to perform different tasks using a modest amount of task-specific annotated data. These AI models provide in-context learning, can self-correct mistakes, and promptly adjust to user feedback. In this review, we provide a brief overview of recent advances in computational pathology enabled by task-specific AI, their challenges and limitations, and then introduce various foundation models. We propose to create a pathology-specific generative AI based on multimodal foundation models and present its potentially transformative role in digital pathology. We describe different use cases, delineating how it could serve as an expert companion of pathologists and help them efficiently and objectively perform routine laboratory tasks, including quantifying image analysis, generating pathology reports, diagnosis, and prognosis. We also outline the potential role that foundation models and generative AI can play in standardizing the pathology laboratory workflow, education, and training.

Teaching Infectious Disease Pathology and Taking it To Africa.

With the advent of increasing emerging infectious diseases, rising antibiotic resistance, and the growing number of immunocompromised patients, there is increasing demand for infectious disease (ID) pathology expertise and microbiology testing. Currently, ID pathology training and emerging molecular microbiology techniques (eg, metagenomic next-generation sequencing and whole genome sequencing) are not included in the most American Council of Graduate Medical Education medical microbiology fellowship curricula, and not surprisingly, many institutions lack anatomical pathologists with expertise in ID pathology and advanced molecular diagnostics. In this article, we describe the curriculum and structure of the Franz von Lichtenberg Fellowship in Infectious Disease and Molecular Microbiology at Brigham and Women's Hospital in Boston, MA. We emphasize the value of a training model that strives to integrate anatomical pathology, clinical pathology, and molecular pathology by providing examples in a case-based format and presenting selected metrics of the potential effect of such integrative ID pathology service and briefly describing opportunities and challenges of our global health efforts in Rwanda.

Expansion microscopy: A revolution in diagnostic pathology.

Expansion microscopy (ExM) is a recent discovery in diagnostic pathology and microbiology that promotes a physical magnification of the tissue specimen instead of optical magnification. It not only improves the resolution of the specimen but also enhances the diagnostic precision, and permits nanoscale imaging of the specimen. Optical microscopy is routinely used in histopathology and microbiology for ages. Due to its simplicity, compatibility with different types of specimens, and ease of operation it is accepted by pathologists. ExM and its variants have been widely tested in different types of tissue specimens and microbiological specimens and yielded brilliant results.

Evolutionary Changes in Pathology and Our Understanding of Disease.

The history of pathology involves human dissections, autopsies, microscopy, as well as the development of histopathological, immunohistochemical, and molecular techniques. Through these methods, our understanding of anatomy and disease improved, and models of pathogenesis were gradually refined over time. This review discusses key milestones in the development of pathology as a branch of medical science, from ancient civilizations to the modern day.