Cardiovascular disease and thrombosis: Intersections with the immune system, inflammation, and the coagulation system.

The coagulation and immune system, both essential physiological systems in the human body, are intricately interconnected and play a critical role in determining the overall health of patients. These systems collaborate via various shared regulatory pathways, such as the Tissue Factor (TF) Pathway. Immunological cells that express TF and generate pro-inflammatory cytokines have the ability to affect coagulation. Conversely, coagulation factors and processes have a reciprocal effect on immunological responses by stimulating immune cells and regulating their functions. These interconnected pathways play a role in both preserving well-being and contributing to a range of pathological disorders. The close relationship between blood clotting and inflammation in the development of vascular disease has become a central focus of clinical study. This research specifically examines the crucial elements of this interaction within the contexts of cardiovascular disease and acute coronary syndrome. Tissue factor, the primary trigger of the extrinsic coagulation pathway, has a crucial function by inducing a proinflammatory reaction through the activation of coagulation factors. This, in turn, initiates coagulation and subsequent cellular signalling pathways. Protease-activated receptors establish the molecular connection between coagulation and inflammation by interacting with activated clotting factors II, X, and VII. Thrombosis, a condition characterised by the formation of blood clots, is the most dreaded consequence of cardiovascular disorders and a leading cause of death globally. Consequently, it poses a significant challenge to healthcare systems. Antithrombotic treatments efficiently target platelets and the coagulation cascade, but they come with the inherent danger of causing bleeding. Furthermore, antithrombotics are unable to fully eliminate thrombotic events, highlighting a treatment deficiency caused by a third mechanism that has not yet been sufficiently addressed, namely inflammation. Understanding these connections may aid in the development of novel approaches to mitigate the harmful mutual exacerbation of inflammation and coagulation. Gaining a comprehensive understanding of the intricate interaction among these systems is crucial for the management of diseases and the creation of efficacious remedies. Through the examination of these prevalent regulatory systems, we can discover novel therapeutic approaches that specifically target these complex illnesses. This paper provides a thorough examination of the reciprocal relationship between the coagulation and immune systems, emphasising its importance in maintaining health and understanding disease processes. This review examines the interplay between inflammation and thrombosis and its role in the development of thrombotic disorders.

[Fibro-osseous pseudotumor of the digits: An exemple of USP6-related fibroblastic/myofibroblastic tumor]. / La pseudotumeur fibro-osseuse des doigts : une tumeur fibroblastique/myofibroblastique liée à USP6.

Fibro-osseous pseudotumor of the digits is a benign tumour closely related to myositis ossificans. It is a rare lesion seldom reported in the literature. We report the case of a 33-year-old woman with lancinating pain in the first phalanx of the second finger of the right hand, associated with inflammation. The histopathological examination of the surgical excision biopsy of the lesion revealed a spindle-shaped proliferation within a sclerosing, hyaline, and osteoid stroma. In our observation, immunohistochemistry and molecular biology are the main elements that helped to establish the diagnosis and eliminate the various differential diagnoses, despite a non-specific histopathological aspect.

[Neuroepithelial tumor with PATZ1 fusion - case report and focus on an ill-defined entity]. / Tumeur neuroépithéliale avec fusion PATZ1 ­ à propos d'un cas et mise au point sur une entité mal définie.

The neuroepithelial tumor with PATZ1 fusion is a recently described tumor type, at the border between central nervous system and mesenchymal tumors. The histopathological diagnosis of this neoplasm, not recognized by the 2021 WHO classification, is challenging due to its varied and non-specific morphologic features. Most cases are densely cellular with monomorphous nuclei. Perivascular pseudo-rosettes of the ependymal type and astroblastic features are frequent. Blood vessels may be hyalinized. The tumor may display low- or high-grade features. OLIG2 and GFAP are variably expressed. Guided by DNA methylation profiling, a pathologist aware of this tumor type will search for a fusion involving PATZ1 and EWSR1 or MN1. The physiopathology of neuroepithelial tumor with PATZ1 fusion is not fully understood. The prognosis appears to align with that of intermediate-grade tumors but follow-up data are scarce. The therapeutic management is often similar to that of high-grade neoplasms. Nonetheless, PATZ1 fusion is a potential therapeutic avenue that may lead to personalized and less aggressive treatments.

In Memory of Anthony Stevens: A Career Retrospective with Emphasis on His Formative Role in the Archetype Debate.

This paper celebrates the life and legacy of psychiatrist and Jungian author Anthony Stevens, who passed away at age 90 on July 13, 2023. It outlines Stevens's origins as a research fellow in Greece, where his work on infant attachment led to a lifelong dedication to establishing the biological and evolutionary foundation of psychiatry. It details his instrumental role in the debate about the theory of archetypes and describes the current state of the literature including the responses and reactions to Stevens's biological innatist position. The paper concludes with a career retrospective in which Stevens's major works are introduced and briefly described.

Cet article célèbre la vie et l'héritage du psychiatre et auteur jungien Anthony Stevens, décédé à l'âge de 90 ans le 13 juillet 2023. L'article décrit les origines de Stevens en tant que chercheur en Grèce, où ses travaux sur l'attachement du nourrisson l'ont conduit à se consacrer toute sa vie à établir le fondement biologique de la psychiatrie, dans une perspective évolutionniste. L'article détaille son rôle important dans le débat sur la théorie des archétypes et décrit l'état actuel de la littérature, y compris les réponses et réactions à la position biologique innéiste de Stevens. L'article se termine par une rétrospective de sa carrière, dans laquelle les œuvres majeures de Stevens sont présentées et brièvement décrites.

Este artículo celebra la vida y el legado del psiquiatra y autor Junguiano Anthony Stevens, quien falleció a los 90 años el 13 de julio de 2023. Describe los orígenes de Stevens como investigador en Grecia, donde su trabajo sobre el apego infantil lo llevó a una dedicación de por vida para establecer los fundamentos biológicos y evolutivos de la psiquiatría. Detalla su papel instrumental en el debate sobre la teoría de los arquetipos y describe el estado actual del arte, incluyendo las respuestas y reacciones a la posición biológica innatista de Stevens. El artículo concluye con una retrospectiva de su carrera en la que se presentan y describen brevemente las principales obras de Stevens.

[mRNA vaccination, a model of transition from basic biology to medicine]. / Vaccination ARN messager (ARNm), modèle de transition de la biologie fondamentale à la médecine.

Sixty years elapsed between the discovery of messenger RNA (mRNA) and the use of this molecule in an unprecedented global vaccination campaign that brought the Covid-19 pandemic under control. Sixty years of doubts for some and certainties for others about the possibility of using mRNA-an example of synthetic biology-in therapeutic medicine and vaccinology. Years of "translational" research and development have culminated in the success of anti-Covid-19 mRNA vaccines and the promise of more to come against emerging pathogens. A new paradigm in vaccinology, enabling pandemics to be tackled as they emerge. A lesson to be learned: medical progress is less a question of time than of the critical nature of the biological discovery that underpins it. Before leaving us, François Gros, who played a key role in the discovery of mRNA, was able to appreciate the relevance of this obvious fact.

Soixante ans ont séparé la découverte de l'ARN messager (ARNm) et l'utilisation de cette molécule dans une campagne planétaire inédite de vaccination ayant permis le contrôle de la pandémie de Covid-19. Soixante ans de doutes chez certains et de certitudes chez d'autres sur la possibilité d'utiliser l'ARNm ­ un exemple de biologie de synthèse ­ en médecine thérapeutique et en vaccinologie. Des années de recherche et de développement «  translationnels  ¼ pour aboutir au succès de vaccins à ARNm anti-Covid-19 et à la promesse d'autres à venir contre de nouveaux pathogènes émergents. Un nouveau paradigme de la vaccinologie permettant d'attaquer les pandémies dans le temps de leur émergence. Une leçon à tirer, le progrès médical est moins affaire de temps que de la nature décisive de la découverte biologique qui le sous-tend. François Gros, acteur de la découverte de l'ARNm a pu, avant de nous quitter, juger de la pertinence de cette évidence.

[Myelodysplastic syndrome : prognostic factors]. / Facteurs pronostiques des syndromes myélodysplasiques.

The prognostic evaluation of myelodysplastic syndromes has evolved considerably over time, both due to the evolution of diagnostic classifications and the improvement in the prediction of the outcome. Many prognostic scores that have been developed over time take into account number and depth of blood cytopenias, as well bone marrow blast, cytogenetic, and more recently, molecular mutations. All these variables have been grouped together in IPSS-M score since 2022, which should quickly become a reference for the prognostic evaluation of MDS, as soon as molecular information is available for the patient.

[Next Generation Sequencing (NGS) for beginners]. / Approches diagnostiques basées sur le séquençage à haut débit.

Genetic diagnoses have progressed through the development of Next Generation Sequencing (NGS), which enables improved patient care and more precise genetic counseling. NGS techniques analyze DNA regions of interest in view accurately determining the relevant nucleotide sequence. Different kinds of analysis apply NGS : multigene panel testing, Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS). While regions of interest depend on the type of analysis (multigene panels testing studies the exons of genes implicated in a particular phenotype, WES studies all exons of all genes, and WGS studies all exons and introns), the technical protocol remains similar. Clinical/biological interpretation is based on a body of evidence allowing categorization of variants into five groups (from benign to pathogenic) in accordance with an international classification, which takes into account segregation criteria (variant detected in affected relatives, but absent in healthy relatives), matching phenotype, databases, scientific literature, prediction scores and data drawn from functional studies. Clinical/biological interaction and expertise are essential during this interpretative step. Pathogenic and probably pathogenic variants are returned to the clinician. Variants of unknown significance can likewise be returned, if they are liable to be reclassified through further analysis as pathogenic or benign. Variant classifications may change, as new data emerge suggesting or ruling out pathogenicity.

[Rare tumors: Angiosarcoma]. / Tumeurs rares : angiosarcome.

Angiosarcomas are a rare subtype representing 1-2% of soft tissue sarcomas. Risk factors are rarely elucidated but radiotherapy and lymphedema are the most common ones, usually following local treatment for local breast cancer. Despite the improvement of our knowledge, the prognosis remains poor with 35-40% of 5 year-overall survival. Local treatment when feasible should include a R0 surgery completed with adjuvant radiation. When metastatic, front lines chemotherapies include doxorubicine or weekly paclitaxel. If possible, in oligometastatic patients, metastasectomy should always be considered allowing the best responses. The knowledge of angiosarcoma's biology is rapidly increasing and new biomarkers are emerging. The use of immunotherapy in particular subtypes including head and neck angiosarcomas shows promising results. The model of the angiosarcoma project, a patient-participating study, seems to be an excellent way to study rare tumors. We should focus our efforts on understanding the underlying molecular biology to propose the best precision medicine for those patients.

[Differential diagnostic between hepatocellular carcinoma and hepatoid carcinoma with bone metastasis revelation: What tools can be used?] / Diagnostic différentiel entre un carcinome hépatocellulaire et un carcinome hépatoïde à révélation métastatique osseuse : quels outils sont à disposition ?

Bone metastases of hepatocellular carcinoma (HCC) are rare and disease-revealing bone metastasis are exceptional. Here, we report the case of a 69-year-old man with a cervical vertebral metastasis of hepatocellular carcinoma. Morphological aspect of a metastatic tumor with eosinophilic and polygonal cells raises the question of the differential diagnosis between a localization of a hepatocellular carcinoma or an hepatoid carcinoma, notably when the metastasis is the first clinical manifestation. The morphological aspect by itself does not provide strong enough arguments for diagnosis. Well selected immunohistochemical markers can sometimes help to orientate towards one of the two hypotheses, in particular SALL4 and LIN28 which are in favour of hepatoid carcinoma when both are positive. Finally, as these two entities have different molecular profiles, molecular study can also be helpful to distinguish them. Indeed, HCCs often present TERT promoter, CTNNB1 mutations and IL-6/JAK/STAT pathway activation while hepatoid adenocarcinoma frequently presents chromosome 20 long arm gain. TP53 mutations are found in both entities and are therefore not discriminating. Differential diagnosis is important because the treatment will be that of the primary. Prognostic data for HCC revealed by bone metastasis are scarce, although they seem to be associated with a poor prognosis, with a 1 to 2 months overall survival. There is currently no data for hepatoid adenocarcinoma with bone metastasis.

Recent Developments in Islet Biology: A Review With Patient Perspectives.

Navigating the coronavirus disease-2019 (COVID-19, now COVID) pandemic has required resilience and creativity worldwide. Despite early challenges to productivity, more than 2,000 peer-reviewed articles on islet biology were published in 2021. Herein, we highlight noteworthy advances in islet research between January 2021 and April 2022, focussing on 5 areas. First, we discuss new insights into the role of glucokinase, mitogen-activated protein kinase-kinase/extracellular signal-regulated kinase and mitochondrial function on insulin secretion from the pancreatic ß cell, provided by new genetically modified mouse models and live imaging. We then discuss a new connection between lipid handling and improved insulin secretion in the context of glucotoxicity, focussing on fatty acid-binding protein 4 and fetuin-A. Advances in high-throughput "omic" analysis evolved to where one can generate more finely tuned genetic and molecular profiles within broad classifications of type 1 diabetes and type 2 diabetes. Next, we highlight breakthroughs in diabetes treatment using stem cell-derived ß cells and innovative strategies to improve islet survival posttransplantation. Last, we update our understanding of the impact of severe acute respiratory syndrome-coronavirus-2 infection on pancreatic islet function and discuss current evidence regarding proposed links between COVID and new-onset diabetes. We address these breakthroughs in 2 settings: one for a scientific audience and the other for the public, particularly those living with or affected by diabetes. Bridging biomedical research in diabetes to the community living with or affected by diabetes, our partners living with type 1 diabetes or type 2 diabetes also provide their perspectives on these latest advances in islet biology.

Macleod Before Banting.

John James Rickard Macleod provided the facilities and support that enabled Frederick Banting and Charles Best to perform the experimental work that resulted in the discovery of insulin. This review considers Macleod's intellectual contribution to the initial discovery in light of his previously expressed opinions on glucose metabolism. He acknowledged the likely existence of an internal secretion from the pancreas and was aware of previous work in the area; however, seeking it was not among his research priorities. His advice in the immediate aftermath of the discovery does not appear to have made any essential contribution to the project, although he made its ultimate success possible. Instead, he gave Banting the chance he needed, gave him full credit for what he achieved, and promoted insulin tirelessly as a gift to the world.

Résumé. John James Rickard Macleod fournit les installations et le soutien qui ont permirent à Frederick Banting et Charles Best de découvrir l'insuline. Il contribua aussi intellectuellement au projet. Ce texte étudie cette contribution en analysant les idées de Macleod sur le métabolisme des glucides. Bien au fait des travaux antérieurs, le chercheur admettait l'existence probable d'une sécrétion interne du pancréas, mais l'étudier ne faisait pas partie de ses priorités de recherche. Si les conseils qu'il prodigua immédiatement après cette découverte ne semblent pas avoir été essentiels, ils contribuèrent néanmoins au succès du projet. En fait, Macleod offrit à Banting l'opportunité dont il avait besoin, lui attribua pleinement le mérite de la découverte et fit ensuite sans relâche la promotion des bienfaits de l'insuline.

Proceedings of the Dual Use Research of Concern Panel Discussion: challenges and perspectives.

To address real and perceived emerging risks originating from the ever-accelerating breakthroughs in life science research, the Dual Use Research of Concern (DURC) Panel Discussion, organized by Synbio Canada and the Alberta RNA Research and Training Institute (ARRTI), took place on June 23rd, 2021. It brought together six stakeholders from different levels of academic research, administration, governance, and science publishing to explore the current and future challenges in addressing DURC. Technological advancements within the life sciences, especially within the field of omics technology, make it difficult to apply a simple checklist for dual-use assessment and require continuous and integrated effort. Bottom-up approaches from within the scientific community are suggested by all stakeholders to enable efficient governance and address the true risks resulting from DURC, not just the alleged risks. To address such alleged risks, open and broadscale communication of DURC and its oversight policies may be required. At the same time, any form of open communication also contains the risk of information hazards, defined as potentially creating public fear or informing malicious actors. Here, an overview of the DURC panel and its outcomes is provided.

[From an optimal management of bone tissue samples to a quality patients' care in 2022 : A new paradigm]. / D'une gestion optimale des échantillons osseux à une prise en charge de qualité des malades en 2022 : un nouveau paradigme.

Bone tissue can be involved by primitive or metastatic tumors and requires a specific processing both at the department of pathology and during multidisciplinary meetings. The development of fine-needle percutaneous biopsies and of molecular techniques in bone tumor pathology requires a specific management. Moreover, decalcification of samples is crucial but can be deleterious if not controlled or not appropriate. The aim of this review is to provide recommendations for management and decalcification of bone tumor samples.

[From neuroendocrinology to cell biology: Andrée Tixier-Vidal]. / De la neuroendocrinologie à la biologie cellulaire : Andrée Tixier-Vidal (1923­2021).

This article relates the life, career and main scientific achievements of a pioneer in neuroendocrinology and French cell biology research, Mrs Andrée Tixier-Vidal, who passed away in December 2021. After her first works on hypophyseal-thyroid neuroendocrine axis, in birds then in mammals, Andrée Tixier-Vidal devoted herself then her group at the College of France to the histophysiological study of adenohypophysis and namely of prolactin (PRL) cells. Using in vitro models of organotypic cultures and cultures of GH3 cells, she described up to ultrastructural level the secretory process of PRL and its regulation by TRH. Furthermore, she extended her study to the TRH neurons themselves thanks to original models of in vitro cultures of hypothalamic neurons. Her fundamental and methodological achievements have largely contributed to major knowledge advances in cell biology of the secretion during the last century.

Title: De la neuroendocrinologie à la biologie cellulaire : Andrée Tixier-Vidal (1923­2021). Abstract: Cet article relate la vie, la carrière et l'œuvre scientifique de Mme Andrée Tixier-Vidal, disparue en décembre 2021. Il montre comment, après avoir développé une approche histophysiologique originale de la neuroendocrinologie et tout particulièrement de l'axe hypophyso-thyroïdien, elle a réalisé des travaux pionniers qui ont complètement renouvelé les connaissances sur les neurones hypothalamiques à thyréolibérine (TRH) qui interviennent dans la régulation des cellules à thyréostimuline (TSH), mais également de celles à prolactine (PRL). Le fil conducteur de ses recherches a été la biologie cellulaire de la sécrétion abordée par les techniques morphologiques et cytochimiques sur des modèles originaux de cultures organotypiques d'hypophyse mais aussi de cellules tumorales GH3 et enfin de neurones hypothalamiques. Le rayonnement scientifique de Mme Tixier-Vidal et de son équipe se prolonge encore à travers les multiples générations de chercheurs qui ont eu le privilège de profiter de son dynamisme intellectuel et de son enthousiasme pour la recherche en biologie.

Radiation guidelines for gliomas.

Gliomas are the most frequent primary brain tumour. The proximity of organs at risk, the infiltrating nature, and the radioresistance of gliomas have to be taken into account in the choice of prescribed dose and technique of radiotherapy. The management of glioma patients is based on clinical factors (age, KPS) and tumour characteristics (histology, molecular biology, tumour location), and strongly depends on available and associated treatments, such as surgery, radiation therapy, and chemotherapy. The knowledge of molecular biomarkers is currently essential, they are increasingly evolving as additional factors that facilitate diagnostics and therapeutic decision-making. We present the update of the recommendations of the French society for radiation oncology on the indications and the technical procedures for performing radiation therapy in patients with gliomas.

[POCT-management during the first wave of Covid-19 in France. Results of a national survey leaded by the SFBC-POCT Working Group]. / Gestion de la biologie délocalisée lors de la première vague de Covid-19 en France. Résultats de l'enquête nationale menée par le groupe de travail des EBMD de la SFBC.

During the first wave of Covid-19 in France, in spring 2020, healthcare institution's laboratory had to adapt itself quickly to the growing demand for emergency biology, in particular by reorganizing their POCT analyzers: redeployment of analyzers and/or new installations. In order to analyze this management, a subgroup of 15 hospital biologists from the SFBC Working Group "Biochemical markers of Covid-19" sent, in fall 2020, an on-line survey to French hospital laboratories using POCT. Answers analysis (n = 86) shows a territorial disparity related to the severity of the first wave: increased activity essentially in red zones, management of unexpected situations, training of additional nursing staff for 40 % of the laboratories... The survey also showed simplification of aspects related to accreditation those periods of health crisis. An additional survey, carried out in the spring of 2021, showed good overall satisfaction of the healthcare services (n = 139) concerning the services provided by biology in the POCT sector. Because of their great adaptation capacity, the laboratories and their POCT-teams have played a key role in the management of the first wave of Covid-19 in France. However, the success of these organizations requires an essential collaboration between laboratories and healthcare services. The results of this survey are fundamental in the context of the prolongation of the pandemia throughout the world with a POCT sector appearing to be growing.

Emerging regulatory challenges of next-generation synthetic biology.

Cell-free synthetic biology is a rapidly developing biotechnology with the potential to solve the world's biggest problems; however, this promise also has implications for global biosecurity and biosafety. Given the current situation of COVID-19 and its economic impact, capitalizing on the potential of cell-free synthetic biology from an economic, biosafety, and biosecurity perspective contributes to our preparedness for the next pandemic, and urges the development of appropriate policies and regulations, together with the necessary mitigation technologies. Proactive involvement from scientists is necessary to avoid misconceptions and assist in the policymaking process.

Global population structure of Haemophilus influenzae serotype a (Hia) and emergence of invasive Hia disease: capsule switching or capsule replacement?

The population structure of Haemophilus influenzae serotype a (Hia) was examined by interrogation of the H. influenzae MLST website. There were 196 entries of Hia with 55 sequence types (STs) identified (as of 3 September 2020). BURST analysis clustered related STs into four complexes with ST-23, ST-4, ST-21, and ST-62 identified as their ancestral STs. The majority of Hia entries (73.4%) and STs (65.5%) were identified as clonal division I (ST-23 and ST-4 complexes). Only 43 (21.9%) entries and 14 STs (25.5%) were identified as clonal division II (ST-62 and ST-21 complexes). Current data suggest that most invasive Hia belonged to clonal division I and the ST-23 complex, while most clonal division II Hia were respiratory isolates, with the exception of ST-62 which was common among invasive Hia in the US southwest. Comparison of the capsule bexABCD genes from clonal divisions I and II strains showed sequence diversity with variations following the pattern of clonal divisions. Evidence from the literature and the current study suggests that the recent emergence of invasive Hia might be related to capsule replacement subsequent to the implementation of the Hib conjugate vaccine and possibly exacerbated by other conjugate vaccines that may have altered the microbial flora of the human respiratory tract.

Advancing undergraduate synthetic biology education: insights from a Canadian iGEM student perspective.

The last two decades have seen vigorous activity in synthetic biology research and the ever-increasing applications of these technologies. However, pedagogical research pertaining to teaching synthetic biology is scarce, especially when compared to other science and engineering disciplines. Within Canada, there are only three universities that offer synthetic biology programs, two of which are at the undergraduate level. Rather than taking place in formal academic settings, many Canadian undergraduate students are introduced to synthetic biology through participation in the annual International Genetically Engineered Machine (iGEM) competition. Although the iGEM competition has had a transformative impact on synthetic biology training in other nations, its impact in Canada has been relatively modest. Consequently, the iGEM competition remains a major setting for synthetic biology education in Canada. To promote further development of synthetic biology education, we surveyed undergraduate students from the Canadian iGEM design teams of 2019. We extracted insights from these data using qualitative analysis to provide recommendations for best teaching practices in synthetic biology undergraduate education, which we describe through our proposed Framework for Transdisciplinary Synthetic Biology Education (FTSBE).

[NSCLC and new oncogenic mutations: Diagnosis and perspectives]. / Carcinome bronchique non à petites cellules : nouvelles addictions oncogéniques, diagnostic et perspectives.

The development of new targeted therapies in non-small cell lung carcinoma (NSCLC) depends on a better understanding of the molecular basis of carcinogenesis, a knowledge of the role of molecular aberrations in disease progression and the development of molecular biology platforms with the capacity to identify new biomarkers. In the current article, we review the techniques routinely used in cancer molecular biology platforms as well as new techniques under development. These new NSCLC biomarkers have been made available to clinicians and biologists in parallel with the development of targeted drugs. New molecular abnormalities of EGFR exon 20, HER2, MET, RET, BRAF, ROS1 and NTRK have been identified and there have been clinical trials of the most innovative targeted drugs.