Decoding the epigenetic blueprint behind Toxoplasma (pre)sexual commitment and chronic persistence.

Toxoplasma gondii, a widespread apicomplexan parasite, navigates a complex life cycle in which it switches back and forth between tachyzoites and bradyzoites to balance acute infection and persistence while also undergoing an often-overlooked one-way commitment to the sexual stage. Emerging evidence suggests that Toxoplasma's developmental trajectories are orchestrated by an interconnected network of transcriptional switches and chromatin remodeling mechanisms, acting in concert to ensure robust stage transitions. This review outlines an updated epigenetic framework for stage transitions and highlights the functional synergy between an Imitation SWItch family chromatin remodeler and the MORC/HDAC3 repressor complex, which together modulate chromatin accessibility to maintain or shift developmental states.

Systemic administration of an RNA binding and cell-penetrating antibody targets therapeutic RNA to multiple mouse models of cancer.

There is intense interest in the advancement of RNAs as rationally designed therapeutic agents, especially in oncology, where a major focus is to use RNAs to stimulate pattern recognition receptors to leverage innate immune responses. However, the inability to selectively deliver therapeutic RNAs within target cells after intravenous administration now hinders the development of this type of treatment for cancer and other disorders. Here, we found that a tumor-targeting, cell-penetrating, and RNA binding monoclonal antibody, TMAB3, can form stable, noncovalent antibody/RNA complexes of a discrete size that mediate highly specific and functional delivery of RNAs into tumors.

Anti-ADAMTS13 Antibodies Trajectory is Associated With ADAMTS13 Recovery in Immune-Mediated TTP.

Current triplet regimens associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab have dramatically improved the outcome of immune-mediated thrombotic thrombocytopenic purpura (iTTP). However, nearly half of the patients require extended caplacizumab treatment (i.e.

Cluster analysis identifies three clinical patterns of patients with systemic autoimmune diseases and anti-Ku antibodies.

Objective: To determine distinct patterns of patients with autoimmune diseases harbouring anti-Ku antibodies and their respective prognosis.

Methods: Anti-Ku-positive patients were retrieved through four immunology departments. Clusters were derived from unsupervised multiple correspondence analysis, not including the disease's diagnosis, followed by hierarchical clustering.

Uncovering biomarkers for chronic toxoplasmosis detection highlights alternative pathways shaping parasite dormancy.

Toxoplasma gondii, a neurotropic protozoan, causes toxoplasmosis, a prevalent zoonotic and food-borne infection, posing significant risks to immunocompromised individuals and congenital cases. The chronic phase, characterized by dormant, cyst-forming bradyzoites, is central to disease progression but is poorly understood due to the lack of serological tests to detect bradyzoite-specific antigens. This study identifies the bradyzoite serological marker (BSM) and cyst-associated BCLA as effective biomarkers for chronic toxoplasmosis.

Diet-induced phospholipid remodeling dictates ferroptosis sensitivity and tumorigenesis in the pancreas.

High-fat diet (HFD) intake has been linked to an increased risk of pancreatic ductal adenocarcinoma (PDAC), a lethal and therapy-resistant cancer. However, whether and how specific dietary fats drive cancer development remains unresolved. Leveraging an oncogenic -driven mouse model that closely mimics human PDAC progression, we screened a dozen isocaloric HFDs differing solely in fat source and representing the diversity of human fat consumption.

Large Language Models as Decision-Making Tools in Oncology: Comparing Artificial Intelligence Suggestions and Expert Recommendations.

Purpose: To determine the accuracy of large language models (LLMs) in generating appropriate treatment options for patients with early breast cancer on the basis of their medical records.

Materials And Methods: Retrospective study using anonymized medical records of patients with BC presented during multidisciplinary team meetings (MDTs) between January and April 2024. Three generalist artificial intelligence models (Claude3-Opus, GPT4-Turbo, and LLaMa3-70B) were used to generate treatment suggestions, which were compared with experts' decisions.

SPINK1-COL18A1 Crosstalk Shapes Epigenome and Drives Cancer Stemness in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with an increasing incidence and extremely dismal prognosis. Discovery and mechanistic understanding of the genetic and epigenetic drivers of PDAC is therefore of critical importance. Here, we uncover serine protease inhibitor Kazal type 1 (SPINK1) as a putative determinant of clinical progression and demonstrate that it can have a non-canonical function as a regulator of epigenomic states of PDAC cells and associated extensive changes in gene expression.

[Artificial intelligence in healthcare: A survival guide for internists].

Artificial intelligence (AI) is experiencing considerable growth in medicine, driven by the explosion of available biomedical data and the emergence of new algorithmic architectures. Applications are rapidly multiplying, from diagnostic assistance to disease progression prediction, paving the way for more personalized medicine. The recent advent of large language models, such as ChatGPT, has particularly interested the medical community, thanks to their ease of use, but also raised questions about their reliability in medical contexts.

Neurological manifestations in patients with VEXAS syndrome.

Background: VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a recently described syndrome linked to somatic mutations in the UBA1 gene, causing systemic autoinflammatory manifestations. To date, few data are available concerning neurological manifestations. The aim of this study was to describe their prevalence, clinical spectrum and outcome under treatment.

The evolving role of liver biopsy: Current applications and future prospects.

Histopathologic evaluation of liver biopsy has played a longstanding role in the diagnosis and management of liver disease. However, the utility of liver biopsy has been questioned by some, given the improved imaging modalities, increased availability of noninvasive serologic tests, and development of artificial intelligence over the past several years. In this review, we discuss the current and future role of liver biopsy in both non-neoplastic and neoplastic liver diseases in the era of improved noninvasive laboratory, radiologic, and digital technologies.

Fumagillin Shortage: How to Treat Microsporidiosis in Solid Organ Transplant Recipients in 2024?

Unlabelled: Intestinal microsporidiosis caused by is an opportunistic infection that especially affects solid organ transplant (SOT) recipients. Management revolves around tapering the immunosuppressive regimen and/or using a specific anti-microsporidia treatment, but only fumagillin has demonstrated efficacy for treatment of this infection. Since fumagillin has been commercially discontinued, nitazoxanide is increasingly being used in this indication.

Contribution of major histocompatibility complex class II immunostaining in distinguishing idiopathic inflammatory myopathy subgroups: A histopathological cohort study.

Idiopathic inflammatory myopathies (IIM) are rare, acquired muscle diseases; their diagnosis of is based on clinical, serological, and histological criteria. MHC-I-positive immunostaining, although non-specific, is used as a marker for IIM diagnosis; however, the significance of major histocompatibility complex (MHC)-II immunostaining in IIM remains debated. We investigated patterns of MHC-II immunostaining in myofibers and capillaries in muscle biopsies from 103 patients with dermatomyositis ([DM], n = 31), inclusion body myositis ([IBM], n = 24), anti-synthetase syndrome ([ASyS], n = 10), immune-mediated necrotizing myopathy ([IMNM], n = 18), or overlap myositis ([OM], n = 20).

Parent-led Communication Therapy for Young Bilingual Autistic Children: A Scoping Review.

A scoping review of the literature was undertaken using JBI guidelines to map the evidence of parent-led therapy (PLT) for young autistic children (≤ 6 years) raised in bilingual environments. Reviewers used Covidence to screen located sources. Sixteen papers met inclusion criteria.

[IL-17A and IL-17F: from discovery to target of biologics - an illustrative example of translational research].

Interleukin (IL)-17A and then IL-17F have been discovered through their roles in chronic inflammatory diseases. These cytokines share 50% of sequence homology and bind to the same receptor made of the IL-17RA et IL-17RC chains. While they have rather similar pro-inflammatory effects, slight differences exist depending on the cell type considered or whether there is TNF or not.

Assessing hand and global disability in a cohort of Algerian patients with systemic sclerosis: Construct validities of the Arab Hand Function Index and the Arabic Health Assessment Questionnaire.

Objective: The study aimed to assess the construct validity of the Arab Hand Function Index and the Arabic Health Assessment Questionnaire in Algerian patients with systemic sclerosis.

Methods: Consecutive Algerian patients who fulfilled the American College of Rheumatology/European League Against Rheumatism criteria for systemic sclerosis were included. In addition to disease characteristics, global disability and hand disability were assessed using the Arabic Health Assessment Questionnaire and the Arab Hand Function Index, respectively.

Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer: A Nonrandomized Controlled Trial.

Importance: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant tumor, and durable disease control is rare with the current standard of care, even for patients who undergo surgical resection.

Objective: To assess whether neoadjuvant modified 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFIRINOX) leads to early control of micrometastasis and improves survival.

Design, Setting, And Participants: This open-label, single-arm, phase 2 nonrandomized controlled trial for resectable PDAC was conducted at the Yale Smilow Cancer Hospital from April 3, 2014, to August 16, 2021.

[Adherence to endocrine therapy: A major issue in breast cancer management].

Endocrine therapy plays a crucial role in the treatment of women with hormone receptor-positive breast cancer. However, non-adherence remains a frequent issue known to negatively impact survival. Based on a comprehensive literature review, this article explores the terminologies employed to describe adherence and methods used for its assessment, the adherence data reported with adjuvant endocrine therapy with targeted therapies, the determinants of adherence or non-adherence, and finally, tested solutions to address it.