Study demonstrates that elicited repetitive daily blindness is a clinical feature in patients with familial hemiplegic migraine 3 because of gain-of-function Nav1.1 variants. Patients in this report responded to sodium channel blocker medications.
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https://doi.org/10.1172/jci.insight.203645 Here, Aaron A.R. Tobian & team use this method to evaluate antibody repertoires in kidney donors with and without HIV, reporting that antibodies against adenovirus infection in kidney donors with HIV may be associated with allograft rejection.
2Department of Pathology, School of Medicine, and.
3Department of Medicine, School of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA.
4Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Pathways that favor the balance of immune cells toward those with healing potential offer therapeutic promise following injury. Here, Lynch at al. show that treatment with IL-4 expands pro-reparative macrophages through proliferation while driving concurrent death of their more inflammatory precursors, resulting in accelerated hepatic repair following acute liver injury.
Background: Atypical carcinoid of the thymus is an exceptionally rare neuroendocrine tumor originating from neuroendocrine cells within the thymus. These tumors often present with no symptoms or with nonspecific clinical signs, making early diagnosis particularly challenging. Despite their rarity, atypical carcinoids are clinically significant due to their aggressive nature and relatively poor prognosis. Early detection and appropriate management are therefore crucial to improving patient outcomes. Results: In this report, we present the case of a 64-year-old patient in whom an atypical carcinoid of the thymus was incidentally discovered following a thoracic computed tomography scan performed for unrelated reasons. Imaging revealed a suspicious anterior mediastinal mass, which was subsequently surgically resected.
Microbiota in clinical cancer immunotherapy.
Gut microbiota research has progressed from mechanistic studies to clinical trials, revealing strong potential to enhance cancer immunotherapy.
Fecal microbiota transplantation, single bacterial strains, and defined microbial consortia are in clinical testing; yet, standardization and implementation remain major challenges.
Donor selection, patient enrollment, microbiota implantation, antibiotic use, safety assessment, and endpoint evaluation each offer distinct opportunities and obstacles.
A ‘4D’ framework, enhancing diversity, diffusion, depth, and delicacy, can guide the optimization of microbiomebased immunotherapy. sciencenewshighlights ScienceMission https://sciencemission.com/microbiota-to-clinical-cancer
Fundamental research has elucidated the indispensable role of gut microbiota in modulating cancer immunotherapy efficacy. Despite promising preclinical findings, few related approaches have reached clinical trials. In this opinion, we provide insights based on current clinical trials using fecal microbiota transplant or specific bacterial strains as adjuvants to enhance immune checkpoint blockade therapy. We also systematically analyze the challenges in trial design, with a focus on donor selection, patient enrollment, implantation procedures, antibiotic use, safety assessment, and endpoint evaluation. Moving forward, we offer a comprehensive ‘4D’ framework (diversity, diffusion, depth, and delicacy) for accelerating the bench-to-bedside translation.
Online now: Lee et al. demonstrate that oxidative stress reprograms astrocytes to produce collagen through glycosylation-dependent mechanisms, driving glial barrier formation and progressive neuronal death after stroke. Targeting this pathway disrupts the glial barrier, prevents neurodegeneration, and improves functional recovery. A drug candidate, KDS12025, shows a potent effect in a non-human primate stroke model.
Studying cognition by averaging data from many people’s brain scans hides how individuals use their brains, new Stanford Medicine research has shown. In particular, children who struggle with goal-oriented tasks show distinct patterns of brain activity when their data is analyzed individually, rather than as part of a group of kids with mixed abilities. The findings, which have implications for understanding how the brain works in such conditions as attention-deficit/hyperactivity disorder, will be published April 27 in Nature Communications.
“Investigating how dynamics unfold within individual brains can provide significant insights into the neuroscience of individual differences and help us tackle questions that cannot be answered using conventional approaches,” said Percy Mistry, Ph.D., a research scholar in psychiatry and behavioral sciences, and a lead author of the study.
Mistry shares lead authorship with Nicholas Branigan, MS, a research data analyst in psychiatry and behavioral sciences. The senior author is Vinod Menon, Ph.D., a professor of psychiatry and behavioral sciences and the Rachael L. and Walter F. Nichols, MD, Professor.
Attention-deficit/hyperactivity disorder (ADHD) affects millions of children, yet many go years without a diagnosis, missing the chance for early support that can change long-term outcomes even when early signs are present. In a new study, Duke Health researchers found that artificial intelligence tools can analyze routine electronic health records to accurately estimate a child’s risk of developing ADHD years before a typical diagnosis. By reviewing patterns in everyday medical data, the approach could help flag children who may benefit from earlier evaluation and follow-up.
The research, published in Nature Mental Health, highlights how powerful insights can come from information already collected during regular health care visits to help support early decision making by primary care providers.
“We have this incredibly rich source of information sitting in electronic health records,” said Elliot Hill, lead author of the study and data scientist in the Department of Biostatistics & Bioinformatics at Duke University School of Medicine.
CAR-T therapy has revolutionized treatments for many hematologic malignancies, but it has shown far less efficacy against solid tumors. One reason for this lower efficacy in solid tumors is increased antigen heterogeneity. This study utilizes a ligand-based CAR-T approach, which allows targeting of multiple receptors by a single ligand. A high expression of the ligand oncostatin M’s (OSM) receptors, oncostatin M receptor (OSMR), and/or leukemic inhibitory factor receptor (LIFR) were noted in osteosarcoma cell lines and patient samples. Osteosarcoma is a bone cancer where treatment options have been stagnant for close to 40 years. Thus, this study explores the therapeutic potential of OSM ligand-based CAR-T cells against osteosarcoma.
Third-generation CAR-T cells expressing human OSM on their surface were created, with the surface expression of OSM confirmed by flow cytometry. Co-incubation of OSM CARs and osteosarcoma in vitro was performed, with cell death assessed via Incucyte and PI detection by flow cytometry. CAR-Ts were injected i.v. into mice with osteosarcoma cell line xenografts, and metastatic osteosarcoma. New patient-derived samples were tested for OSMR and LIFR expression and vulnerability to OSM CAR T cells. A new PDX model (named KKOS) from a patient with metastatic treatment-resistant osteosarcoma was characterized and tested for its susceptibility to OSM CAR T cells. All cytotoxic in vivo experiments were performed with n =3–6 mice per group per experiment.
OSM-CAR-T cells displayed cytotoxicity against osteosarcoma cell lines and patient samples expressing either one of OSM’s receptors in vitro and in vivo. Large increases in cytokine release, specifically IFNγ, were noted in a target-specific manner. One injection of OSM-CAR-T cells intravenously reduced tumor burden in two different mouse xenograft models. A similar anti-tumor effect was also noted in a metastatic model and a mouse model with multiple implanted KKOS tumors.